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Association of serum α-tocopherol, β-carotene and retinol with subsequent liver cancer incidence and chronic liver disease mortality in the ATBC Study

Gabriel Y. Lai1,2, Stephanie J. Weinstein1, Demetrius Albanes1, Philip R. Taylor1, Jarmo Virtamo3, Katherine A. McGlynn1, Neal D. Freedman1;
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD; 2Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD; 3Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

Introduction: Antioxidant micronutrients may influence the development or progression of liver cancer and liver disease. We evaluated the association of serum α-tocopherol, β-carotene, and retinol with incident liver cancer and chronic liver disease mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a prospective cohort of middle-aged Finnish male smokers. Methods: Baseline and 3-year follow-up serum were available from 29,046 and 22,805 men, respectively. After up to 24 years of follow-up, 208 men were diagnosed with liver cancer and 237 died from chronic liver disease. Relative risks (RR) and 95% confidence intervals (CIs) were calculated from multivariate Cox proportional hazards models. Results: High serum β-carotene (RR=0.35, 95% CI: 0.22-0.55 for highest vs. lowest quartile; p-trend<0.0001) and retinol (RR=0.58, 95%CI: 0.39-0.85; p-trend=0.0009) were associated with reduced risk of developing liver cancer. Similarly, serum β-carotene (RR=0.47, 95% CI: 0.30-0.75; p-trend=0.001) and retinol (RR=0.55, 95% CI: 0.38-0.78; p-trend=0.0007) were inversely associated with chronic liver disease mortality. We also observed a borderline statistically significant inverse association for serum α-tocopherol and chronic liver disease mortality, (RR=0.63, 95% CI: 0.40-0.99; p-trend=0.06), but none for incident liver cancer (RR=1.06, 95%CI: 0.64-1.74; p-trend=0.77). Associations remained largely similar after removing the first 2, 5 or 10 years of follow-up. Participants with high levels of β-carotene and retinol, but not α-tocopherol, at both baseline and 3-year follow-up had a lower risk for incident liver cancer and chronic liver disease mortality than those with low levels at both times. Conclusion: Men with higher pre-diagnostic β-carotene and retinol had a lower risk of incident liver cancer and chronic liver disease mortality suggesting that higher concentrations of these micronutrients may protect against these diseases.


The following people have nothing to disclose: Gabriel Y. Lai, Stephanie J. Weinstein, Demetrius Albanes, Philip R. Taylor, Jarmo Virtamo, Katherine A. McGlynn, Neal D. Freedman


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Tracing HBV genetic history of Native Americans: Paleovirology can be used to study human prehistory

Dimitrios Paraskevis1, Gkikas Magiorkinis1,2, Simon Y. Ho3, Jean-Pierre Allain4, Angelos Hatzakis1;
1Department of Hygiene Epidemiology and Medical Statistics, Medical School University of Athens, Athens, Greece; 2Department of Zoology, University of Oxford, Oxford, United Kingdom; 3School of Biological Sciences, University of Sydney, Sydney, ACT, Australia; 4Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom

The ancestry of Native American population in the Arctic is debated. Crucially, we have shown recently that HBV has been co-expanding and co-migrating with human populations for the last 40,000 years1. Our objective was to date the origin and estimate the dispersal of HBV types exclusively circulating in

indigenous Arctic populations in the Americas in order to reconstruct Native American history from the virus perceptive (subgenotypes B6, D3/D6 and D4). We calibrated the molecular clock of HBV using estimated divergence times of different indigenous human populations based on archaeological and genetic evidence1. The analysis included global HBV B6, D3/D6 and D4 sampling. Our analysis suggested that peopling of the Americas occurred through at least three separate migration events from Asia. These correspond to the First Americans (distributed across the continent) infected with ancestral HBV genotypes F/H and to two additional events to distinct indigenous Arctic populations such as the Inuit, Yupic Eskimos (subgenotype B6) and the Na-Dene speaking populations (subgenotypes D3/D6, D4). Phylogeographic analyses showed that HBV D4 has followed a long dispersal through Qinghai-Tibet in Central Asia and then two distinct routes in Remote Oceania and North Eastern Asia from where it migrated to the Americas. Similarly, HBV D3/D6 spread through Asia to Near Oceania but also in North Eastern Asia, where it is currently detected among the natives in Chukot region in Siberia. Molecular clock analysis suggested that the origin of the global D4 subgenotype was 7,646 years ago [95% Higher posterior density (HPD): 2,972–13,395)]. The origin of HBV D4 in Na-Dene speaking populations was 3,873 years ago (95%HPD: 1,341–6,817) and for D3 3,247 years ago (95%HPD: 940–6,073). Our study provides date estimates for the origins of Native Americans and lends support to previous hypotheses based on human genetic and linguistic studies that Native Americans descend from at least three migration events from Asia. HBV is probably the only virus with a global spread dating back to the early human migrations. Our study supports that although recent human migrations have changed the molecular epidemiology, HBV in carefully selected samples and populations can be used as a complementary tool of human genetics to study human prehistory. References 1 Dating the origin and dispersal of hepatitis B virus infection in humans and primates. Paraskevis D, Magiorkinis G, Magiorkinis E, Ho SY, Belshaw R, Allain JP, Hatzakis A. Hepatology. 2013 Mar;57(3):908–16.


Jean-Pierre Allain - Advisory Committees or Review Panels: MacoPharma; Consulting: Diagnostic for the Real World; Speaking and Teaching: Novartis

The following people have nothing to disclose: Dimitrios Paraskevis, Gkikas Magiorkinis, Simon Y. Ho, Angelos Hatzakis


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Changes in Hepatitis B (HBV) Vaccination Rates and Differences in Various General Demographics across National Health and Nutrition Examination Surveys (NHANES) from 1999–2010

Pardha Devaki1, Long H. Nguyen2, Robert Wong4, Sidhartha Sinha4, Vidyasagargoud Marupakula1, Sharad Nangia3, Ivo C. Ditah5, Murray N. Ehrinpreis3, Mindie H. Nguyen4;
1Department of Internal Medicine, Detroit Medical Center/Wayne State University, Detroit, MI; 2Division of Medicine, Stanford University School of Medicine, Stanford, CA; 3Division of Gastroenterology, Detroit Medical Center/Wayne State University, Detroit, MI; 4Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA; 5Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN

Background: Due to rising incidence of HBV cases, a national strategy was adopted in 1991 to administer vaccine to all infants, adolescents and certain high-risk populations to improve immunity in the general population. The purpose of this study is to examine the changes in HBV vaccination rates with time among various demographic groups in a nationally representative sample. Methods: Data from 1999–2010 NHANES were analyzed. Vaccination status was identified through self-reporting at patient interviews. Prevalence estimates were weighted to represent the national population. The prevalence among various demographic parameters was compared across the study cycles. Results: A total of 62,160 participants from NHANES were included: 21,004 (1999–2002), 20,470 (2003–2006) and 20,686 (2007–2010). HBV vaccination rates significantly increased from 31.2% (95% CI 29.8–32.7) in 1999–2002, to 42.2% (40.8–43.6) in 2003–2006 and to 45.8% (44.1–47.4) in 2007–2010 (Table 1). Significant increases in vaccination rates were seen among all demographic subgroups from 1999–2002 to 2003–2006 except in patients aged <5 years (p=0.60). Significant increases in vaccination were also seen among all demographic subgroups from 1999–2002 to 2007–2010. When survey participants in 2003–2006 were compared to participants in 2007–2010, statistically significant increases in vaccination rates were seen regardless of gender, in age group 20–39 years, in Non-Hispanic whites and Hispanics, US citizens, high school graduates, those with some college education, participants who were married/living together and individuals with a poverty-income ratio of 1 or above. Conclusion: HBV vaccination rates have improved to 70–80% range in populations younger than 20 years of age in the most recent cycle, but overall rate remains low at less than 50%. Given the public health implications, better implementation of vaccination recommendations in all target groups is warranted.

Vaccination Rates in all patients surveyed from 1999 to 2010

 Sample size (N)Prevalence of VaccinationSample Size (N)Prevalence of Vaccination99–02 vs 03–0699–02 vs 07–1003–06 vs 07–10
Deographic variables         
Age ≤5 years 6–19 years 20–39 years 40–59 years 60+ years3702 7257 3620 2965 370269.7(67.1–72.4) 65.1(61.4–68.8) 25.4(23.6–27.2) 15.0(13.2–16.8) 5.20(3.90–6.60)3680 6770 3665 2884 347172.7(69.9–75.6) 86.2(84.2–88.2) 39.5(37.1–41.9) 24.2(22.2–26.1) 8.60(6.90–10.2)3437 5096 3993 3933 422778.3(73.1–77.4) 88.4(86.9–90.0) 48.9(45.9–51.8) 25.3(22.7–27.9) 12.0(10.2–13.7)0.60 <0.001 <0.001 <0.001 0.0020.01 <0.001 <0.001 <0.001 <0.0010.05 0.10 <0.001 0.47 0.01
Gender Female Male10790 1021431.4(29.8–33.1) 30.7(29.2–32.3)10420 1005043.9(42.1–45.7) 40.4(39.0–41.9)10365 1032153.1(51.1–55.0) 55.5(53.7–57.3)<0.001 <0.001<0.001 <0.00100.01 0.001
Race Non-HispanicWhite Non-Hispanic Black Hispanic Other-Multiracial7973 4909 7275 84528.8(27 3–30 4)36.8(34.0–39.5) 35.1(32.8–37.4) 35.7(30.9–40.4)8061 5373 6056 98038.8(3.71–40.5) 48.7(46.0–51.5) 49.5(46.5–51.6) 54.0(32.4–37.8)8535 4068 6875 110842.1(40.2–44.0) 52.1(18.2–55.9) 55.0(53.0–57.0) 49.5(45.3–53.7)<0.001 <0.001 <0.001 <0.001<0.001 <0.001 <0.001 <0.0010.01 0.16 <0.001 0.18
Country of Birth US Non–US17477 350532.6(30.9–34.2) 20.9(18.8–23.0)17464 299943.1(41.6–44.7) 35.1(32.4–37.8)16038 373547.3(45.3–49.4) 35.8(33.0–38.6)<0.001 <0.001<0.001 <0.0010.001 0.72
Length of stay in US (if born outside US) <5 years 5–10 years ≥10 years982 632 181728.0(23.1–32.9) 23.0(16.9–29.2) 17.5(15.1–19.8)792 558 158144.4(37.2–51.6) 42.4(34.2–50.8) 29.8(26.4–33.2)561 642 233047.9(40.2–55.5) 40.3(34.3–46.2) 31.6(28.9–34.2)<0.001 <0.001 <0.001<0.001 <0.001 <0.0010.50 0.67 0.42
Education level (>20years) Did not complete Hs HS complete Some college or AA College graduate3563 2362 2449 18729.98(7.65–12.3) 13.8(11.7–15.9)21.2(18.8–23.7) 21.0(18.1–24.0)2881 2450 2773 189317.8(15.4–20.3) 19.6(17.7–21.5) 31.4(28.6–34.3) 32.3(29.1–35.4)3637 2888 3247 235921.2(18.7–23.6) 25.3(22.3–27.9) 36.0(33.3–38.6) 35.6(32.2–39.1)<0.0011 <0.001 <0.001 <0.001<0.001 <0.001 <0.001 <0.0010.06 0.001 0.02 0.14
Marital status(>20 years) Married/Living together Single6135 718116.1(14.4–17.8) 19.1(16.9–21.4)6245 721023.6(22.3–25.1) 30.6(28.3–32.9)7186 495928.1(261–30.2) 34.5(31.4–37.5)<0.001 <0.001<0.001 <0.0010.001 0.04
Poverty Income Retio(PIR) <1 ≥15074 1365335.9(33.6–38.3) 30.7(29.2–32.3)5075 1427452.3(49.5–55.0) 41.0(39.6–42.4)5106 1369054.7(51.9–57.6) 44.1(42.3–46.0)<0.001 <0.001<0.001 <0.0010.20 0.01


Mindie H. Nguyen - Consulting: Gilead Sciences, Inc., Bristol-Myers Squibb, Bayer AG; Grant/Research Support: Gilead Sciences, Inc., Bristol-Myers Squibb, Novartis Pharmaceuticals, Roche Pharma AG

The following people have nothing to disclose: Pardha Devaki, Long H. Nguyen, Robert Wong, Sidhartha Sinha, Vidyasagargoud Marupakula, Sharad Nangia, Ivo C. Ditah, Murray N. Ehrinpreis


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Hepatitis B Vaccine Response among Infants Born to Hepatitis B Surface Antigen–Positive Women

Stephen C. Ko, Sarah F. Schillie, Noele Nelson, Steven L. Veselsky, Trudy V. Murphy;
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA

PURPOSE: Annually, an estimated 25,000 infants are born to hepatitis B surface antigen (HBsAg)-positive women in the United States. Hepatitis B (HepB) vaccine and hepatitis B immune globulin (HBIG) are recommended at birth, followed by completion of the 3 or 4 dose HepB vaccine series. Post-vaccination serologic testing (PVST) response is defined by antibody to hepatitis B surface antigen (anti-HBs) ≥10 mIU/mL after the final dose, typically performed at age 9–18 months. In a large cohort of infants born to HBsAg-positive women, factors influencing vaccine response were evaluated. METHODS: Data were analyzed from HBsAg-negative infants born to HBsAg-positive women enrolled in the Enhanced Perinatal Hepatitis B Prevention (EPHBP) Program from 2008-2012. Vaccine non-responders were defined as infants with anti-HBs <10 mIU/mL. Factors associated with non-response were identified in bivariate analyses. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from multivariable analyses after inclusion of statistically significant predictor variables (<0.2). RESULTS: 16,704 infants were born to HBsAg-positive mothers. Median maternal age was 30.1 years and 64.6% were Asian/Pacific Islander. 8,654 infants with at least 3 doses of vaccine received PVST for anti-HBs and 8,199 (94.7%) responded to the initial vaccination series. Factors associated with anti-HBs <10mIU/mL included gestational age <37 weeks, vaccine birth dose >12 hours after birth, timing of last vaccine dose <6 months after birth, receipt of 3 vs. 4 vaccine doses, and PVST interval >6 months from final vaccination dose. After assessing for interaction and confounding, PVST interval >6 months from last vaccination dose (OR=2.7, CI=2.0, 3.6) was significantly associated with anti-HBs <10mIU/mL, while receipt of a 4th dose slightly improved the response rate (OR=0.5, CI=0.3, 0.8). The proportion of infants with anti-HBs <10mIU/mL increased from 2% at 1-2 months PVST to 13.3% at 11-12 months PVST. CONCLUSIONS: Ninety-five percent of all infants born to HBsAg-positive mothers responded to a primary HepB vaccine series. The small proportion of infants with anti-HBs <10mIU/mL increased with longer interval between the final vaccine dose and PVST. Although their anti-HBs levels were <1 0mIU/mL at the time of PVST, some infants might have been protected if their initial anti-HBs was ≥10 mIU/mL. To avoid unnecessary revaccination, optimal timing of PVST is within 6 months of final vaccination.


The following people have nothing to disclose: Stephen C. Ko, Sarah F. Schillie, Noele Nelson, Steven L. Veselsky, Trudy V. Murphy


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Is isolated anti-HBc positivity a risk for reactivation in rituximab-treated patients?

Marcus Robertson1, Christopher Li Wai Suen1, Kushani Jayasinghe1, Andrew Chong3, William Sievert1,2;
1Department of Gas-troenterology and Hepatology, Monash Health, Melbourne, VIC, Australia; 2Centre for Inflammatory Disease, Monash University, Melbourne, VIC, Australia; 3Pharmacy Department, Monash Health, Melbourne, VIC, Australia

Reactivation of hepatitis B virus (HBV) replication in patients receiving rituximab (RTX) is well described. International guidelines, including the American Association for the Study of Liver Diseases and American Society of Clinical Oncology, endorse HBV screening (HBV surface antigen (HBsAg) and core antibody (anti-HBc) prior to RTX therapy and recommend prophylactic antiviral therapy in patients with detectable HBsAg. Discordant recommendations exist for patients with serological evidence of prior infection (HBsAg negative and anti-HBc positive) Aim: To investigate adherence to HBV screening guidelines and clinical outcomes in RTX-treated patients with evidence of current or past HBV infection. Methods: All patients receiving RTX at a tertiary referral centre over a 60-month period from 2008 to 2012 were identified via pharmacy dispensing records. Medical records were reviewed to determine the timing and type of HBV screening. HBV flares (ALT >5 X ULN) and reactivation (detectable viraemia) were identified and correlated with clinical outcomes. Results: 586 patients received RTX for haematological (75%), rheumatological (10.4%), renal (12.4%) or other (2.2%) indications. Mean patient age was 60 years (range 4-96) and 58% were male. 361(62%) patients received pre-RTX HBV screening which was more likely to occur in patients with renal (92%) compared with haematological (61%, p<0.001) or rheumatological (28%, p<0.001) indications. Of screened patients, 344 (95.6%) were tested for HBsAg with 4 (1.2%) detected, 133 (36.8%) for anti-HBc with 25 (18.8%) detected and 91 (25.3%) for anti-HBs with 37 (40.7%) detected. Only 119 (33% of those tested and 20.3% of total cohort) had recommended screening with HBsAg and anti-HBc. All HBsAg positive patients received prophylactic antiviral treatment. 15 (60%) patients with only anti-HBc detected received antiviral therapy. Three (12%) patients had HBV reactivation during or within six months of RTX therapy (two patients had only anti-HBc detectable at screening); two were associated with severe ALT flares and one with reappearance of HBsAg and HBeAg. Two reactivations occurred in patients who had pre-RTX screening however results were not reviewed by the treating team. No patients died from viral reactivation. Conclusions: Screening for HBsAg occurred in 58% of patients prior to RTX therapy but only 20% were screened with both HBsAg and anti-HBc as recommended by international guidelines. Severe HBV reactivation occurred in patients whose only serological marker was anti-HBc, re-enforcing the importance of screening patients and commencing appropriate antiviral therapy.


William Sievert-Advisory Committees or Review Panels: Merck, Janssen, AbbVie, Gilead; Speaking and Teaching: Bristol-Myers Squibb, Merck

The following people have nothing to disclose: Marcus Robertson, Christopher Li Wai Suen, Kushani Jayasinghe, Andrew Chong


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Trends in Incident Hepatitis B Virus (HBV) infection from 1985-2012 in Men who have sex with Men

Oluwaseun Falade-Nwulia1, Eric C. Seaberg2, Charles Rinaldo3, John Phair4, Mallory Witt5, Chloe L. Thio1;
1Department of Medicine, Johns Hopkins University, Baltimore, MD; 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; 3Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA; 4Department of Medicine, Northwestern University Medical School, Chicago, IL; 5 Department of Medicine, Harbor-UCLA Medical Center, Torrence, CA

Background: Men who have sex with men (MSM) are at high risk for hepatitis B infection. It is unknown whether the incidence of hepatitis B has changed in HIV-infected or-uninfected MSM over time. An understanding of trends in and factors associated with incident HBV is important to re-focus prevention. Methods: MSM in the Multicenter AIDS Cohort Study, without serologic evidence of prior infection with HBV (HBsAg & anti-HBc negative at study entry) were prospectively-followed from 1985 to 2012 for incident HBV. Incident HBV was determined by serial anti-HBc & HBsAg testing. Hepatitis B sero-conversion (SC) was considered to be the mid-point between the last negative and first positive anti-HBc/HBsAg test. Men whose SC point could not be narrowed to < a 5 year window were censored at their last negative test. Poisson regression was used to estimate incidence rates (IR) for HBV and to determine factors associated with incident HBV infection. Results: 2260 MSM with a median age of 32.5 (range 1 8-68) years at study entry had 22327 person years (PYs) of follow up. There were 245 incident HBV infections (IR 10.9/1000 PYs, 95% CI 9.7-12.5). The incidence in HIV+ was higher than in HIV- men (IR 18.0/1000 PYs, 95% CI 14.8-22.0 vs. IR 8.8/1000 PYs, 95% CI 7.5 -10.3, P< .001). Among the HIV- men, the rate of incident HBV in the pre-and post-HAART eras were similar (8.8/1000 PYs, 95% CI 7.4-10.5 vs. 8.4/1000 PYs, 95% CI 5.4-12.8, P= .73). Interestingly, among the HIV+ men, the rate of incident HBV in the pre-HAART era (22.1 /1000 PYs, 95% CI 1 7.7-27.5) was significantly higher than that in the HAART era (10.1 /1000 PYs, 95% CI 6.4-16.0), P=0.005. In multivariable analysis, incident HBV in HIV- men was associated with having >2 male sexual partners in the preceding 6 months (incidence rate ratio (IRR) 3.5, 95% CI 2.5-4.9) and younger age (IRR 2.1/10 year decrease in age, 95% CI 1.7-2.5). In the HIV+ men, a similar association was seen between incident HBV and >2 male sexual partners (IRR 2.7, 95% CI 1.8-4.2) and younger age (IRR 1.6/1 0 year decrease in age, 95% CI 1.2-2.1). In addition, in the HIV+ men, incident HBV risk was significantly reduced with use of an HBV active drug as part of ART compared with no HBV active drug (IRR 0.32 95% CI 0.2-0.6). Conclusion: Despite HBV vaccination efforts in MSM, rates of incident HBV have remained constant amongst HIV— MSM enrolled in the MACS comparing pre- and post- HAART periods suggesting that exposure risk has not changed. However, in the HIV+ MSM, the reduction in HBV IRs in MSM receiving an anti-HBV drug as part of ART suggests a role for HBV-active drugs in prevention of incident HBV infection amongst HIV+ men.


The following people have nothing to disclose: Oluwaseun Falade-Nwulia, Eric C. Seaberg, Charles Rinaldo, John Phair, Mallory Witt, Chloe L. Thio


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Successful implementation of a universal screening program to prevent hepatitis B reactivation in a large cancer center

Mary K. Sammons, Dhruv Patel, Kent Sepkowitz, Eric J. Sherman, Robin B. Mendelsohn, Andrew D. Zelenetz, Emmy Ludwig;
Memorial Sloan-Kettering Cancer Center, New York, NY

Background: Reactivation of hepatitis B virus (HBV) infection is a complication of immunosuppressive therapy (IST) and can lead to severe morbidity and mortality. Published data have shown that screening for HBV followed by anti-viral prophylaxis (ppx) in appropriate patients (pts) results in better clinical outcomes than treatment of HBV reactivation (HBVr). We hypothesized that a simple, standardized approach to HBV screening would result in increased compliance and a decreased incidence of HBVr in pts appropriately ppx'd. Methods: A committee at Memorial Sloan-Kettering Cancer Center (MSKCC) began mandatory HBV screening 3/1/2009 as a quality improvement initiative to prevent HBVr. We devised a simple algorithm made available on MSKCC's intranet which indicated required tests for screening and included result-specific flowcharts to guide appropriate administration of anti-viral ppx when indicated. Lectures on HBVr (risk factors, incidence, and severity) were given to providers at our weekly Grand Rounds. Guidance on the algorithm by specified members of the gas-troenterology and infectious disease services was made available to oncologists at any time. A pop-up window prompting HBV screening was programmed into the electronic ordering system to appear before IST orders were entered. Prospective data collection on overall and service-specific compliance, and testing results began 5/1/2009. Testing consisted of HB surface antigen (HBsAg) and core antibody (HBcAb) with reflexive PCR for HBV DNA when either test was positive. Results:

Between 5/1/2009 and 5/31/2013, 14809/19677 pts (75.3%) who met criteria for screening were screened prior to initiation of IST. In 5/2013 our screening compliance rate reached 86.5%. Pre-IST screening found 85 HBsAg+ pts (0.6%) and 1239 HBsAg-/HBcAb+ pts (8.4%). ZERO cases of HBVr occurred in the group of pts screened and ppx'ed per algorithm. An additional 9 pts tested positive for HBsAg and HBcAb after initiation of IST. 17 cases of HBVr occurred after institution of our algorithm, secondary to non-compliance with algorithm (9 pts), inappropriate discontinuation of anti-viral ppx (4) or rare serologic or clinical scenario not guided by algorithm (4). Conclusion: By using simple, widely available information technology, physician education, and consultative support, a universal screening program for HBV with appropriate anti-viral ppx can be successfully implemented in a large cancer institution and can prevent HBVr when utilized correctly. Compliance increases over time. Given their efficacy, screening programs to identify and ppx against HBVr should be widely implemented.


Eric J. Sherman - Advisory Committees or Review Panels: Bayer, BMS Robin B. Mendelsohn - Advisory Committees or Review Panels: NPS Andrew D. Zelenetz - Advisory Committees or Review Panels: Gilead

The following people have nothing to disclose: Mary K. Sammons, Dhruv Patel, Kent Sepkowitz, Emmy Ludwig


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Screening for Chronic Hepatitis B Infection Among African-American Veterans

Bryan L. Love1,2, James W. Hardin3,2, S. Scott Sutton1,2, Steedman A. Sarbah2;
1Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, Columbia, SC; 2WJB Dorn Veterans Affairs Medical Center, Columbia, SC; 3Epidemiology and Biosta-tistics, University of South Carolina, Columbia, SC

PURPOSE: The objective of this study was to compare screening results for chronic hepatitis B (CHB) infection between African-American (AA) and Caucasian (CA) patients within the Department of Veterans Affairs (VA). METHODS: Data from all AA and CA veterans who received care within the VA Veterans Integrated Network (VISN) 7 from 1999 through 2011 with HBV screening were included. The Centers for Disease Control (CDC) 2012 case definition was used to determine chronic hepatitis B status: patients with at least 2 positive HBV screening tests (HBsAg, HBeAg, or HBV DNA) at least 6 months apart were classified as confirmed CHB. The Veteran Population Model (VetPop2011) was utilized to estimate the veteran population for VISN 7. All data were stored and analyzed using the VA Informatics and Computing Infrastructure (VINCI) resources. SAS 9.3 and Stata 12.0 were utilized for data analysis. A P-value of <0.05 was used to determine statistical significance. RESULTS: Using VetPop201 1, it is estimated that there are 1.624 million veterans who receive care within VISN 7. Approximately 70.5% are Caucasian (not Hispanic) and 25.7% are AA (not Hispanic). During the period of 1999 to 2011, 6.72% (28,011) of AA and 2.93% (33,600) of CA patients underwent screening for CHB infection. A total of 154,952 HBV diagnostic labs were evaluated using the CDC case definition for CHB. During this time period, 33,600 CA patients were tested and 7.95% (2672) had at least one positive HBV screening test. By comparison, 28,017 AA patients were tested with 13.03% (3652) having at least one positive HBV screening test. A total of 1,985 patients met the criteria for CHB infection and are summarized in Table 1. AA veterans with CHB are younger, have a higher percentage of HbeAg positivity, and are more likely to be co-infected with HIV. CONCLUSIONS: Compared with CA veterans, AA veterans were more likely to receive screening for CHB infection, and were more likely to meet CDC case definition for CHB. This difference may be related to differences in risk factors for acquiring HBV.

Table 1. Clinical Characteristics of Veterans with Confirmed Chronic Hepatitis B
Age (mean)56.150.6<0.00l
Male sex94.5%88.9%<0.00l
ALT (mean)74.762.7<0.001
HBV DNA15,200,00023,400,0000.303
HIV positive0.04%4.5%<0.00l
HBeAg positive10.2%15%<0.00l


Bryan L. Love - Grant/Research Support: Bristol-Myers-Squibb

S. Scott Sutton - Grant/Research Support: Gilead, Sanofi, Bristol Myers

The following people have nothing to disclose: James W. Hardin, Steedman A. Sarbah


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Updated evaluation of the prognostic impact of Hepatitis B and C infections in kidney recipients

Hélène Fontaine1,2, Laurent Alric3,10, Julia Salleron4, Corinne Antoine5, Christophe M. Legendre6, Marc Hazan7, Nassim Kamar8,11, Stanislas Pol1,2, Alain Duhamel4, Philippe Mathurin9;
1Hepatology Unit, Cochin Hospital, Paris, France; 2U1016, INSERM, Paris, France; 3Department of digestive disease, CHU Toulouse, Toulouse, France; 4Department of Biostatistic EA 2694, Univ Lille 2, Lille, France; 5Pôle Stratégie Greffe, Direction Médicale et Scientifique, Agence de Biomédecine, Saint-Denis, France; 6Nephrology and kidney transplantation Unit, Necker Hospital, Paris, France; 7Nephrology and kidney transplantation Unit, Claude Huriez Hospital, Lille, France; 8Nephrology and kidney transplantation Unit, CHU Toulouse, Toulouse, France; 9Hepatology Unit, Claude Huriez Hospital, Lille, France; 10UMR152, IRD Paul Sabatier University, Toulouse, France; 11U1043, INSERM, Toulouse, France

Introduction: Previous studies performed in the era without available antiviral therapy showed that hepatitis B (HBV) and C (HCV) lead to reduced patient and graft survival after renal transplantation. However, it is necessary to update the evaluation of the prognostic impact of HBV and HCV when considering the wide use of nucleostides analogs (NA) in patients with end-stage renal disease in the last 15 years. Patients and methods: Patient and graft survival were analyzed according to viral status in a French prospective database ("Cristal") of kidney recipients who were recorded between 1995 and 2012. Results: 25830 patients were prospectively included in the "Cristal database": 449 (1.7%) with positive HBs-Ag, 983 (3.8 %) with positive HCV antibodies, 76 (0.3 %) co-infected patients (positive HBs Ag and HCV antibodies) and 24322 (94.2 %) non infected patients. HCV and HBV-HCV kidney recipients had significantly lower patient and graft survival than HBV and non infected patients (p < 0.0001 for both comparisons) without significant in these 2 latter groups (table). The confusion factors included in the multivariate analysis were sex, age, alcohol consumption of the donor, the incompatibility HLA DR and B. After adjustment on the confounding factors, HCV and co-infection were independent predictors of patient survival, with HR of 1.8[1.6;2.2] and 3.2[1.9;5.2] (p <0.0001 for both); for HBV, HR was 1.1[0.9;1 .5] (p = 0.8). HCV and coinfection were independently associated with graft survival after adjustment with HR of 1.3[1.2;1.6] (p<0.0001) and 1.8[1.2;2.7] (p < 0.01); for HBV, HR was 1.0[0.8;1 .3] (p = 0.9). Conclusion: This huge prospective database showed that HBV has no more deleterious impact on patient and graft survival thanks to the wide use of NA. In contrast, due to the lack of efficient therapeutic options, HCV still has a deleterious impact on patient and graft survival with the worse outcome observed in co-infected patients.

 Patient survival (%)Graft survival (%)
 1 year5 years10 years15 years1 year5 years10 years15 years
HBV patients9793807395887558
HCV patients9585726494847053
Co-infected patients9683595990796054
Non infected patients9791837395887766


Hélène Fontaine - Independent Contractor: gilead, BMS, MSD, Roche

Stanislas Pol - Board Membership: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/Research Support: Glaxo Smith Kline, Gilead, Roche, MSD; Speaking and Teaching: Sanofi, Bristol-Myers-Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis

Philippe Mathurin - Board Membership: Schering-Plough, Janssen-Cilag, BMS, Gilead; Consulting: Roche, Bayer, Boehringer

The following people have nothing to disclose: Laurent Alric, Julia Salleron, Corinne Antoine, Christophe M. Legendre, Marc Hazan, Nassim Kamar, Alain Duhamel


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Prognostic value of combined use of liver stiffness measurement using transient elastography and FibroTest in patients with chronic hepatitis B

Mi Sung Park1, Beom Kyung Kim1,2, Seung Up Kim1,2, Jun Yong Park1,2, Do Young Kim1,2, Sang HoonAhn1,3, Kwang-Hyub Han1,3;
1Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 3Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea

Background: Liver stiffness (LS) measurement using transient elastography (TE) and FibroTest (FT) have been validated as alternatives to a liver biopsy (LB) for assessing liver fibrosis in patients with chronic hepatitis B (CHB). We investigated the prognostic value of the combined use of LS and FT in predicting liver-related events (LREs) in patients with CHB. Methods: Consecutive patients with CHB who underwent LB, along with LS and FT measurement on the same day from January 2007 to December 201 0 were recruited prospectively. Liver fibrosis was evaluated using the Batts and Ludwig scoring system. LRE was defined as hepatic decompensation, hepatocellular carcinoma (HCC), or liver-related deaths. Results: The study analyzed 154 patients (88 males, 66 females). Their median age was 48 years. During the follow-up period (median 50.9 months), 1 8 (1 1.7%) patients experienced LREs (decompensation in 3 and HCC in 15 patients). The median time to LRE was 25.1 (range5.9-85.2) months. The area under the receiver operating characteristic curve (AUROC) of LS, FT, LS+FT, LSxFT, and histological fibrosis staging for predicting a LRE at the 5-year follow-up was 0.740 (95% confidence interval [CI]0.625-0.856), 0.628 (95% CI0.516-0.740), 0.739 (95% CI0.624-0.855), 0.731 (95% CI0.608-0.853), and 0.661 (95% CI0.538-0.785), respectively. After adjusting for age and clinically diagnosed liver cirrhosis, which were significant in the univariate analyses (P<0.05), LS, LS+FT, and LSxFT independently predicted LRE (P=0.009, hazard ratio (HR) 1.050, 95% CI 1.012-1.090; P=0.009, HR 1.051, 95% CI 1.012-1.091; P=0.011, HR 1.084, 95% CI 1.019-1.153, respectively), whereas FT was not significant (P=0.094). Conclusion: LS had a prognostic value similar to LS+FT and LSxFT, and was even better than FT and histological fibrosis staging for predicting LRE in patients with CHB. The addition of FT does not seem to improve the prognostic value of LS.


The following people have nothing to disclose: Mi Sung Park, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han


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Suboptimal Vaccination Rates for Hepatitis B Virus (HBV) among U.S. Adults at High Risk for HBV Infection in National Health and Nutrition Examination Survey (NHANES) from 2001-2010

Pardha Devaki1, Robert Wong2, Long H. Nguyen3, Sharad Nangia4, Sidhartha Sinha2, Vidyasagargoud Marupakula1, Ivo C. Ditah5, Murray N. Ehrinpreis4, Mindie H. Nguyen2;
1Department of Internal Medicine, Detroit Medical Center/Wayne State University, Detroit, MI; 2Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA; 3Division of Medicine, Stanford University School of Medicine, Stanford, CA; 4Division of Gastroenterology, Detroit Medical Center/Wayne State University, Detroit, MI; 5Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN

Background: National strategies aimed at vaccination of adults at high risk for HBV infection have not yielded satisfactory results. Our goal is to estimate the prevalence of adults at high risk for HBV infection, their self-reported vaccination rates and predictors of vaccination. Methods: Data from 2001-2010 NHANES were analyzed. High risk populations for HBV were defined as men who have sex with men (MSM), intravenous drug users (IVDU), individuals positive for antibody to hepatitis C virus (HCV), individuals with multiple sexual partners, patients with sexually transmitted diseases (STD) and patients on dialysis. Sampling weights were used to obtain prevalence estimates for the nationally representative population. Results: The study included 2716 participants, comprising 17% of survey participants aged 20-59 years. The self-reported vaccination rate among the high risk population group was 34.6% (95% CI 32.2%-37.0%) ranging from approximately 24% to 60% in various subgroups (Figure) . On multivariate analysis, positive independent predictors for vaccination were higher education levels and non-white ethnicity. Non-Hispanic blacks and Hispanics were more likely to receive vaccination compared to non-Hispanic whites (OR=1.45, 95% CI=1 .17-1.80, p=0.001 and OR=1.58, 95% CI=1. 12-2.2 1,p=0.01, respectively). Negative independent predictors for vaccination were age older than 29 (age 30-39: OR=0.46, 95% CI=0.34-0.62, p<0.001; age 40-49: OR=0.30, 95% CI=0.23-0.40, p<0.001; age 50-59: OR=0.27, 95% CI=0.19-0.39, p<0.001), male gender (OR=0.61, 95% CI=0.49-0.74, p<0.001), and lack of insurance (OR=0.66, 95% CI=0.52-0.85, p<0.001). Conclusions: Among the high-risk populations identified, only one-third self-reported prior hepatitis B vaccination. Aggressive strategies should be implemented to improve vaccination rates especially in older, uninsured, less educated and non-Hispanic white high-risk populations. Vaccination rates in population at high risk for hepatitis B virus infection

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Mindie H. Nguyen - Consulting: Gilead Sciences, Inc., Bristol-Myers Squibb, Bayer AG; Grant/Research Support: Gilead Sciences, Inc., Bristol-Myers Squibb, Novartis Pharmaceuticals, Roche Pharma AG

The following people have nothing to disclose: Pardha Devaki, Robert Wong, Long H. Nguyen, Sharad Nangia, Sidhartha Sinha, Vidyasagargoud Marupakula, Ivo C. Ditah, Murray N. Ehrinpreis


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Shifting scales: comparing viral hepatitis and HIV/AIDS mortality data 1990-2010 in the Global Burden of Disease Study 2010

Benjamin C. Cowie1,2, Jennifer H. MacLachlan1,2;
1WHO Regional Reference Laboratory for Hepatitis B, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia; 2Department of Medicine, University of Melbourne, Melbourne, VIC, Australia

Methods: The Global Burden of Disease Study 2010 (GBD 2010) collated estimates of 67 risk factors, 291 diseases and injuries, and 1,160 sequelae for 1 87 countries and 21 regions to identify the determinants of death and disability throughout the world. Using country-level and regional causes of death data, we analysed mortality attributed to hepatitis B and hepatitis C (cirrhosis, liver cancer and acute infections) and HIV/AIDS, both globally and specifically in the USA, Western Europe, India, China and Australia. Results: Globally, deaths from both viral hepatitis and HIV increased from 1 990 to 201 0 to be leading causes of human mortality, with HIV ranking 6th (1.47 million deaths in 201 0) and viral hepatitis B and C combined ranking 9th, with 1.29 million deaths in 201 0. Whereas HIV related deaths in China and India increased over this time period, in the USA, Western Europe and Australia, deaths attributable to HIV/AIDS fell by approximately half following the introduction of highly active antiretroviral therapy from the late 1990s. As a result of declining HIV deaths but increasing viral hepatitis deaths, it was estimated that in 2010, in the USA there were approximately 3 times as many hepatitis attributable deaths as there were HIV attributable deaths. In Australia and Western Europe, an estimated 10 times as many people died as a result of viral hepatitis than from HIV/AIDS. Conclusions: These results from the GBD 201 0 suggest that while HIV/AIDS undeniably remains a key global health priority, mortality from viral hepatitis is higher than that of HIV/AIDS in a number of regions. Although the analysis presented here is drawn from a single study, and needs to be considered together with other available data, the release of the GBD 201 0 results provides a unique opportunity to set global and local priorities for health, and address previous imbalances in addressing the major preventable causes of human death, among which hepatitis B and C must clearly now be counted.


The following people have nothing to disclose: Benjamin C. Cowie, Jennifer H. MacLachlan


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Association Between Insulin Resistance and Hepatic Fibrosis in Patients with Combined Chronic Hepatitis B and Steatosis

Hwi Young Kim1, Sae Kyung Joo1, Ja Young Jung1, Yong Jin Jung1, Donghee Kim2, Won Kim1;
1Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea;2Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea

Background and Aim: Hepatic steatosis and insulin resistance are associated with severity of fibrosis in non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C. However, clinical significance of steatosis and insulin resistance on fibrosis in chronic hepatitis B (CHB) is not well established. The aim was to investigate the relationship between insulin resistance, hepatic steatosis, and fibrosis in patients with CHB. Methods: This study included a total of 85 consecutive CHB patients without significant alcohol consumption or other known liver diseases, who showed evidences of hepatic steatosis on ultrasonography. We evaluated the relationships among the followings: 1) noninvasive markers of hepatic steatosis and fibrosis, including NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index, aspartate aminotransferase-to-alanine aminotransferase ratio, FIB-4 score, cirrhosis discriminant score, platelet-to-spleen ratio, hepatic steatosis index; 2) insulin resistance determined by the homeostasis model assessment (HOMA-IR); 3) liver stiffness (LS) measured by acoustic radiation force impulse (ARFI) imaging. Results: Median age of patients was 45 years, and 50 (58.8%) were male. Baseline HBeAg was negative in 54 patients (63.5%), and median serum HBV DNA level was 5350 IU/mL. Median body mass index was 25.8 kg/m2, and median HOMA-IR was 2.61. Median LS was 1.17 m/s. Significant correlations were observed between LS and the followings: HOMA-IR (P=0.002); hepatic steatosis index (HIS (Digestive and Liver Disease 42 (2010) 503-508); P=0.018); serum triglyceride (P=0.043). No significant correlation was found with viral factors or other noninvasive fibrosis markers. HOMA-IR (coefficient(B)=0.371; P=0.01) and HSI (coefficient(B)=0.510; P=0.036) were significant factors associated with LS in multiple logistic regression analysis. Conclusion: In patient with combined CHB and NAFLD, severity of fibrosis might be associated with the degree of insulin resistance.


The following people have nothing to disclose: Hwi Young Kim, Sae Kyung Joo, Ja Young Jung, Yong Jin Jung, Donghee Kim, Won Kim


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Innate And Adaptive Immune Responses Correlate to Antibody Recall Responses to Hepatitis B Booster Vaccination

Jens M. Werner, Adil Abdalla, Naveen Gara, Marc G. Ghany, Barbara Rehermann;
Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, MD

BACKGROUND: Hepatitis B virus (HBV) infection can be prevented by vaccination using hepatitis B surface antigen (HBs). Anti-HBs levels decline over time and may become undetectable, but booster vaccination typically induces protective antibody levels within 2-4 weeks. The rapid booster response suggests the existence of immunological memory, the characteristics of which remain poorly defined. AIM: To identify immune parameters that may contribute to successful antibody recall response in subjects who have lost anti-HBs levels after primary vaccination. METHODS: 32 of 158 (20%) healthy volunteers who where vaccinated >1 0 years ago had anti-HBs levels <12 mIU/ml and received a booster vaccination were studied. Anti-HBs responses, NK cell responses and T cell responses were assessed by EIA, multicolor flow cytometry and ELISPOT, respectively, prior to and 1, 7 and 21 days after booster vaccination. RESULTS: Among 30/32 of vaccines who had tested anti-HBs negative >1 0 years after primary vaccination, 53% tested anti-HBs-positive within a week, and 94% tested anti-HBs-positive within 3 weeks after the boost. There was a strong, positive correlation between the baseline HBs-specific T cell response (p=0.0002, rho=0.62), and the frequency of HBs-specific poly-functional IFNγ+ TNFα+ CD4 T cells (p=0.0087, rho=0.57) with the anti-HBs titer three weeks after booster vaccination. The size of this CD4 T cell subset increased from baseline to day 7 after booster vaccination (0.012+0.008 % at baseline vs. 0.031+0.013% at day 7, p=0.009), and again, correlated to the week 3 anti-HBs titer (p=0.008, rho=0.58). In a linear regression analysis both the baseline HBs-specific T cell response (p=0.031) and the HBs-specific poly-functional IFNγ+ TNFα+ CD4 T cell response (p=0.039) were significant predictors for the week 3 anti-HBs titer. Booster vaccination also resulted in activation of innate immune cells.The frequency of CD57+ mature NK cells (52.3+2.4% vs. 55.2+2.1%, p=0.0015) and the expression of CD122 which is part of the activatory IL-2 receptor (MFI 514+20 vs. 558+31, p=0.026) increased from baseline to day 7 after booster vaccination. IFNγ production of CD56Bright NK cells increased in parallel (87.9+1.9% vs. 91.4+1.7%, p=0.03) but correlated inversely to the amount of the secreted Th2 cytokine IL-10 (p=0.002, Rho=-0.66) and to the week 3 anti-HBs titer (p=0.039, Rho=-0.46) CONCLUSIONS: Humoral and cellular recall responses are maintained for decades after vaccination even in those who have lost their anti-HBs titer. The presence of poly-functional memory CD4 T cell response against HBsAg may be used as a predictor of successful booster vaccination.


The following people have nothing to disclose: Jens M. Werner, Adil Abdalla, Naveen Gara, Marc G. Ghany, Barbara Rehermann


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Estimated impact of screening and antiviral treatment on prevention of HBV reactivation associated with cancer chemotherapy

Roshani J. Desai, Mark A. Schnitzler, Adrian M. Di Bisceglie;
Gastroenterology—SLUCOR, St. Louis University Hospital, St. Louis, MO

Background: The need for routine screening for hepatitis B prior to cancer chemotherapy is not universally accepted. Aims: 1 )To estimate the number of pts undergoing chemotherapy requiring testing for HBsAg and treatment to prevent HBV reactivation and its consequences 2)To estimate the national impact of HBV reactivation with chemotherapy. Methods: We based estimates of frequency of HBV reactivation, liver failure and death among pts with HBsAg, treated(T) and untreated(Un) on a meta-analy-sis(Ann Intern Med 2008; 1 48:51 9) corrected for the frequency of HBsAg, in the general population(0.42%, Am J Pub Health 1 999;89:1 4)and among the Asian population, estimated at 8.0%. We calculated the Number Needed to Screen (NNS) and Number Needed to Treat (NNT) based on similar assumptions and estimates of the number of pts receiving chemotherapy on estimates of 1,596,670 new diagnoses of cancer and cancer deaths 571,950. (CA. 2011 ;61:213). Results: Screening for HBsAg and use of antiviral therapy is associated with an approximate 1 0X decrease in risk of HBV reactivation and a 3X decrease in risk of death. The number of cases of chemotherapy-associated HBV reactivation is the US each year is estimated to be 770 to 2,310, liver failure 270 to 810 and the number of preventable deaths annually due to HBV reactivation is between 70 and 210. Conclusions: Among the U.S. population undergoing chemotherapy, 721 must be tested to prevent 1 reactivation and 6,61 1 to prevent 1 death. However, treatment is required in only 3.0 to prevent 1 reactivation and 27.8 to prevent one death. The NNT to prevent 1 death for this strategy is far superior to most common therapeutic interventions in the US, for example statin therapy(NNT to prevent 1 death in high risk cases is ~200 and is likely greater than 1000 in the general population). The relative rarity of reactivation and clinical consequences in the U.S. population may contribute to perceptions among some that this is not an important problem. However, screening and treating decreases reactivation and clinically important consequences, which is even more prominent in the Asian population. These estimates do not account for HBV reactivation among HBsAg-/antiHBc+ pts and among those receiving other forms of immunosuppressive therapy.

 General (HBsAg 0.42%)Asian (HBsAg 8.0%)NNSNNT
 Frequency#/1,0001 per#/1,000GeneralAsianAll
Reactivation (Un)1/6461.541/3429.4721373.0
Reactivation (T)1/6,3300.151/3333.0
Liver Failure (Un)1/1,8350.541/9610.41,830967.7
Liver Failure (T)N/AN/AN/AN/A
Death (Un)1/4,3450.221/2284.36,61134627.8
Death (T)1/12,3760.036501.5


Mark A. Schnitzler - Management Position: Xynthisis, LLC, XynManagement, LLC; Stock Shareholder: Xynthisis, LLC, XynManagement, LLC

Adrian M. Di Bisceglie - Advisory Committees or Review Panels: Genentech, Vertex, Janssen, BMS, Salix; Consulting: Vertex; Grant/Research Support: Genentech, Gilead, Idenix, Vertex, Abbott, Janssen, GlobeImmune

The following people have nothing to disclose: Roshani J. Desai


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Novel community-based hepatitis B and C screening program among African immigrants with linkage to care by a culturally-targeted patient navigator

Hari Shankar1,2, Demetri A. Blanas1,2, Mulusew Bekele2, Kian Bichoupan1, Ellie Carmody3, Valerie Martel-Laferriere1, Kim E. Nichols2, Douglas T. Dieterich1, Ponni Perumalswami1;
1Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY;2African Services Committee, New York, NY; 3Division of Infectious Diseases and Immunology, NYU School of Medicine, New York, NY

Background: Over 5 million people in the United States are chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), of whom more than 1.3 million are foreign-born. Our objectives were to estimate the prevalence of HBV and HCV among African-born NYC residents, to determine the role of known risk factors and identify new ones, and to test the effectiveness of a community-based screening and linkage-to-care program that relies on culturally-targeted patient navigators (PN). Methods: Between October 201 1 and May 2013, our research team offered a series of community based screenings targeting African-born persons. After written informed consent, participants completed a written questionnaire assessing demographics and viral hepatitis risk factors and underwent serological testing for hepatitis B and C. Patients identified as HBV positive (HBsAg+) or HCV positive (HCV Ab+) in screening were informed, counseled and linked to care at Mount Sinai Hospital and partnering federally qualified health centers (FQHC) via a PN. Results: A total of 858 African-born participants underwent screening, and originated from numerous countries, including Senegal (37%), Mali (10.2%), Ghana (8.8%), Togo (8.8%) and Burkina Faso (8%), among others. Overall prevalence of HBsAg in African-born persons was 10.7% (n=858). Several countries were highly represented in the HBsAg-positive group, including Senegal (34.7%), Benin (9.8%), Burkina Faso (9.8%), Mali (7.6%) and Togo (6.5%). Men were more likely to be HBsAg positive than women (12.8% vs 4.4%, p=0.0002), and were also significantly more likely to have been exposed to HBV (HBcAb+) compared to women (60.4% vs. 48.9%, p=0.0001). Body piercings (p=0.01 7) and tattoos (p=0.032) were the only significant risk factors for HBV exposure. In this study sample, 20.5% (n=1 76) were eligible for vaccination. Overall prevalence of HCV Ab was 1.74%. Men were more likely to be HCV Ab positive than women (93.3% vs 6.6%, p = 0.134). All 107 positive patients were successfully informed of their results by a culturally-targeted PN and 77 (72.6%) attended a follow-up visit at Mount Sinai Hospital. Of nine participants who were recommended for treatment, seven were successfully navigated to a partnering FQHC and have begun treatment. Conclusions: The high chronic HBV prevalence among African immigrants underscores a need for further outreach and screening in this at-risk population. This study also identified a significant opportunity for HBV vaccination in this population. Overall, this study demonstrates the effectiveness of culturally targeted patient navigation in linking at-risk African persons to access hepatitis care.


Douglas T. Dieterich - Advisory Committees or Review Panels: Gilead, Genentech, Janssen, achillion, idenix, Merck, Tobira, Boehringer Ingelheim, TIbotec, Inhibitex, Roche, Vertex

The following people have nothing to disclose: Hari Shankar, Demetri A. Blanas, Mulusew Bekele, Kian Bichoupan, Ellie Carmody, Valerie Martel-Laferriere, Kim E. Nichols, Ponni Perumalswami


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The efficacy of lamivudine use in the second vs. third trimester of pregnancy in preventing vertical transmission of HBV in highly viremic mothers

Wei Yi1, Min Liu1, Angel Chen2, Calvin Pan3;
1Beijing Ditan Hospital, Beijing, China; 2Charles B Wang Community Health Center, Flushing, NY; 3Division of Gastroenterology and Hepatology, NYU Langone Medical Center, NYU School of Medicine, Flushing, NY

Backgrounds: Despite the use of timely immunoprophylaxis, vertical transmission (VT) occurs in 10% infants born to highly viremic mothers with chronic hepatitis B. We evaluated if lamivudine use in the 2nd trimester (2T) vs. 3rd trimester (3T) improves the VT rate in treatment naïve HBeAg+ mothers with HBV DNA > 6 log10copies/mL. Methods: HBV mono-infected mothers with lamivudine use (100 mg/day) at the 2T or 3T during 5/2008-1/2013 were retrospectively enrolled and compared to cases with similar maternal baseline from untreated mothers. All infants received appropriate immunoprophylaxis. Infants' HBsAg and HBV DNA status at 28 weeks was used to determine VT rate. Results: 155 consecutive mothers treated with lamivudine (2T/3T=61/94) and 89 match cases selected from untreated mothers were enrolled with comparable maternal baseline values (Table 1). Prior to delivery, maternal HBV DNA mean (SD) levels were 4.15 (0.98), 4.68 (0.90), 7.16 (0.52) log10 copies/mL in the 2T, 3T and control group, respectively (F=327.207, p< 0.001). At birth, HBsAg positivity from venous blood was found in 21.31% (13/61), 31.91% (30/94), and 32.58% (29/89) [p=0.268] of newborns in the 2T, 3T and control group, respectively. At the age of 28 weeks, infants with HBsAg+ or detectable HBV DNA were 0% (0/61 and 0/94) in the 2T and 3T groups vs. 5.62% (5/89) in the control group (p=0.012); all infants in lamivudine-treated groups seroconverted to anti-HBs with undetectable DNA (< 500 copies/mL). There was no significantly difference in VT rates between the groups of lamivudine initiated in the 2T and 3T. 126 lamivudine-treated mothers discontinued therapy at week 4 postpartum. ALT flares during pregnancy (5 x ULN) were observed 6.45% (10/155) and 1.12% (1/89) in lamivudine and control arms respectively (p=0.054), but severe hepatitis exacerbation (ALT>10XULN) was uncommon (lamivudine:control=1/126:5/45, p=0.001). No lamivudine discontinuations from adverse events or genotypic resistance were reported. No differences of infants' complications or adverse events occurred in the three groups. Conclusions: In highly viremic HBsAg+ mothers, significant reduction of VT was achieved with similar efficacy when the lamivudine was initiated in the 2T or 3T. In order to minimize fetal exposure, lamivudine may be deferred to the 3rd trimester for preventing vertical transmission in high risk mothers

Table 2. Maternal and Infant Characteristics
Mothers(mean ±SD)Control(n=89)2T(n=94)3T(n=61)F/X2PInfants( mean ±SD)Control(n=89)2T (n=94)3T(n=61F/X2P
Age (years)27.16±4.1927.39±3.4827.57+4.570.2010.818Birth weight(Kg)3.38±0.383.40±0.423.53±0.412.9280.055
ALT (UNL=40)36.36±39.7127.99±35.3844.80±94.141.5850.2071 minute Apgar score9.91±0.369.94±0.329.95±0.280.3050.737
Log HBV DNA (baseline)7.33±0.477.28±0.487.29±0.610.2470.781HBV DNA detectable at birth11(12.4%)0020.062<0.001
Log HBV DNA (delivery)7.16±0.524.70±0.884.15±0.98327.207<0.001HBsAg+ at birth29(32.6%)30(31.9%)13(21.3%)2.6370.268


Calvin Pan - Advisory Committees or Review Panels: BMS, Gilead; Consulting: BMS, Gilead; Grant/Research Support: BMS, Gilead, Genentech; Speaking and Teaching: BMS, Gilead, Genentech, Onyx, Vertex

The following people have nothing to disclose: Wei Yi, Min Liu, Angel Chen


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Hepatitis B Virus Screening and Prevalence among US Veterans in Department of Veterans Affairs Care

Lisa I. Backus1,2, Pamela S. Belperio1,3, Timothy P. Loomis1, James P. Halloran1, Steven-Huy B. Han3,4, Larry A. Mole1;
1Population Health Group/Office of Public Health, Palo Alto VA, Palo Alto, CA; 2Department of Medicine, Veterans Health Administration Palo Alto, Palo Alto, CA; 3Veterans Health Administration Greater Los Angeles, Los Angeles, CA; 4Pfleger Liver Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA

Background: Little information exists about hepatitis B virus (HBV) screening rates and infection prevalence in a national population-based United States cohort. We assessed the extent to which Veterans in Department of Veterans Affairs (VA) care were screened for HBV and estimated the prevalence in this large, racially diverse national population. Methods: We used VA's Corporate Data Warehouse to identify birth dates, sex, race/ethnicity and VA laboratory tests for all Veterans with at least one VA outpatient visit in 2012. For these individuals, we determined if VA HBV testing occurred at any time from October 1999 through December 2012. We accepted HBV surface antigen (HBsAg), surface antibody (anti-HBs), e antigen (HBeAg), e antibody (anti-HBe), core antibody (anti-HBc), and

HBV DNA tests as evidence of "any" HBV screening. "Recommended" screening required a HBsAg and anti-HBs test. Additionally, individuals with a negative anti-HBc test were considered to have met "alternative" screening according to the American Association for the Study of Liver Disease guidelines. For patients who were HBsAg+, suggested supplementary testing included anti-HBe, HBeAg and HBV DNA. We calculated HBV screening rates, supplementary HBV testing rates, and HBV infection prevalence. Results: Among 5,500,392 Veterans in care in 2012, 28.5% had VA HBV screening with any HBV-related laboratory test, 18.5% had recommended HBV screening, and an additional 2.3% had alternative screening. In the 1,425,376 Veterans with HBsAg testing, HBV infection prevalence was 1.0%. HBV screening and prevalence by race/ethnicity are shown in the table. Among HBsAg+ individuals (n=1 3,949), supplementary testing for anti-HBe, HBeAg and HBV DNA occurred in 59.3%, 65.8% and 63.9%, respectively; rates of positivity were 71.4%, 31.1% and 70.6%, respectively. Conclusions: Among Veterans in VA care, HBV screening rates were generally low and varied by race/ethnicity. Although overall prevalence was low, it is double what has been estimated by NHANES report. Enhanced screening efforts, including supplementary testing, are needed to accurately characterize and address the burden of HBV among Veterans and in the United States.

GroupVeterans in care (#)Recommended or alternative HBV screeningHBsAg tested (#)HBsAg+ prevalence
All patients5,500,39220.8%1,425,3761.0%
African American823,40632.6%319,8021.8%
American Indian/ Alaska Native38,58623.3%12,0500.7%
Native Hawaiian/ Pacific Islander36,75321.5%9,9311.7%


Steven-Huy B. Han - Advisory Committees or Review Panels: Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb; Grant/Research Support: Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb; Speaking and Teaching: Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb, Gilead, Bristol-Myers Squibb

The following people have nothing to disclose: Lisa I. Backus, Pamela S. Belperio, Timothy P. Loomis, James P. Halloran, Larry A. Mole


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Slow regression of liver fibrosis presumed by repeated biomarkers despite long-term virological response in patients with chronic hepatitis B (CHB)

Thierry Poynard1, Julien Vergniol2, Yen Ngo3, Juliette Foucher2, Mona Munteanu3, Wassil Merrouche2, Vincent Thibault1, Olivier Deckmyn3, Pascal Lebray1, Dominique Thabut1, Vlad Ratziu1, Victor de Ledinghen2;
1Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 2Bordeaux University, Bordeaux, France; 3BioPredictive, Paris, France

Background and aim In CHB treated 5 years (yrs) by tenofovir, regression of fibrosis using paired biopsies, was observed in 51% of patients (pts), including 74% pts with regression of baseline cirrhosis (Marcellin 2012). Fibrosis biomarkers such as FibroTest (FT) have been validated for staging and predicting mortality at five-yr in HBV chronic careers in 2 prospective cohorts (Ngo 2008, de Ledinghen 2013). The aim was to assess retrospectively the 10-yr impact of treatments on the fibrosis progression using repeated FT. Patients and methods We pooled the updated individual data of the 2 cohorts. Pts were included if at least 2 FT and viral load (VL) were performed. The last and first FT permitted to estimate the fibrosis regression rate (FRR) and the fibrosis progression rate (FPR) using cumulative hazard rates and to identify the risk factors by Cox model. The main endpoint was the prevalence of cirrhosis (F4) at the end of follow-up (FU) vs baseline prevalence. Fibrosis increase or decrease was defined as change of at least 0.20 in FT, equivalent to 1 METAVIR stage. Results A total of 741 pts were included; advanced fibrosis in 41%, 14% F4, men 69%, Caucasian 33%, SubSaharan 39%, Asian 20%; 42 yrs old, HBeAg 1 9%; CHB in 52% and inactive chronic career 48%; 3% >50g alcohol/day, and 23% BMI >27kg/M2. During the 7 yrs median-follow-up 403 CHB were treated mostly continuously by either lamivudine 31 %, adefovir 1 9%, tenofovir 29%, entecavir 16%, or PEG 5%; 309 (42%) were responders (R) with undetectable or <2000 HBV-DNA, 93 (12%) non-responders (NR) and 339 (46%) NT. The results were disappointing, without reduction of the net number of F4 and a remaining morbidity (5% HCC) and mortality in R (Table). A net reduction of F4 cases (from 15 to 11) was only observed in the 1 14 pts treated with tenofovir. In treated pts (107 stage F2F3 and 55 F4) the independent factors associated with FRR were: treatment by tenofovir [Risk Ratio (RR)= 8.2 (1.01-66) p=0.04], lamivudine [RR=8.2(1.3-65) P=0.05] with 2 adjusting factors: last VL [RR=1.6(1.2-2.8) P=0.0009] and baseline FT [RR= 157(26-939) P=0.0001). alcohol consumption, HIV, and metabolic factors were not associated with FRR. Conclusion: Despite the limitations of such retrospective analyses, the impact of long-term HBV treatment seemed disappointing, as the fibrosis regression was slow and responders still at risk of severe complications (5% HCC).

Status(n)Fibrosis Regression RateFibrosis Progression RateOverall survival (S)S without liver deathS without liver complicationsS without HCCCirrhois
 n [hazard rate (95%CI)]n[% (95%CI)]   n Baselinen End
Responders (309)18 [0.14(0.05-0.23)]45 [0.39(0.24-0.54)]16 [94 (90-97)]7 [97 (95-99)]17 [93 (89-96)]13 [95%(92-98)]4853
Non-rcspondcrs (93)6 [0.11(0.01-0.21)]13 [0.46(0.10-0.81)]5 [94 (89-99)]5 [94 (90-99)]2 [97 (94-100)]1 [99%(96-100)]78
Not Treated (339)10 [0.06(0.02-0.11)]39 [0.91(0.18-1.64)]5 [97 (95-100)]1 [99 (98-100)]3 [95 (89-100)]1 [98%(94-100)]1517


Thierry Poynard -Advisory Committees or Review Panels: Merck; Grant/Research Support: BMS, Gilead; Stock Shareholder: Biopredictive

Yen Ngo - Employment: BioPredictive

Juliette Foucher- Board Membership: roche; Speaking and Teaching: BMS, MSD, Gilead

Mona Munteanu - Employment: Biopredictive

Olivier Deckmyn - Management Position: BioPredictive; Stock Shareholder: Bio-Predictive

Pascal Lebray - Grant/Research Support: Schering Plough; Speaking and Teaching: Janssen, MSD, Gilead

Vlad Ratziu - Advisory Committees or Review Panels: GalMed, Abbott, Genfit, Enterome, Gilead; Consulting: Astellas, Axcan, Pfizer, Sanofi-Synthelabo, Genen-tech, Nycomed

Victor de Ledinghen - Advisory Committees or Review Panels: Merck, Janssen, Gilead, Echosens, Boehringer Ingelheim, Abbvie; Grant/Research Support: Roche, Gilead, Janssen; Speaking and Teaching: Roche, Echosens

The following people have nothing to disclose: Julien Vergniol, Wassil Merrouche, Vincent Thibault, Dominique Thabut


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Randomized controlled trial of home-based self-administered dried blood spot testing versus written advice for community screening of hepatitis B contacts

Gayatri Chakrabarty1, Phil Rice2, Daniel M. Forton1;
1Gastroen-terology and Hepatology, St Georges University of London, London, United Kingdom; 2Virology, St Georges Hospitals NHS Trust, London, United Kingdom

Screening and vaccination of contacts of HBV infected individuals are desirable but often do not occur, due to barriers to access testing and poor uptake. In our practice, chronic hepatitis B (CHB) cases are given either verbal or written advice for their contacts to seek testing. The uptake of the written advice has been poor as noted in a prior study. Dried blood spot testing (DBS) for HBsAg and HBcAb can be used successfully to facilitate screening. Self-administered home DBS (sDBS) is a novel approach to community HBV screening. Aim To determine whether contact screening by postal sDBS was superior to written advice to attend the general practitioner (GP) for screening. Methods Adult sexual or household contacts of CHB patients identified in an urban hepatitis clinic were randomised to be sent either an advice letter to seek testing via the GP or an sDBS pack with clear instructions for self administration. The response was assessed by either the receipt of the completed sDBS back at the hospital or a note of GP attendance. Results Out of 254 CHB patients interviewed, 61 patients reported 81 sexual or household contacts who may not have been tested for HBV infection. Patients were randomly allocated to sDBS (31) and letter (30) groups. sDBS Group: 31 CHB patients reported 41 unscreened adult contacts (17 sexual, 24 household, mean age 41 ± 14, 17 female). 39 contacts received the sDBS pack (38 via the index case and 1 by post). 22 (56%) contacts agreed to take part in the study, 8 (20%) refused, 9 could not be contacted. 20 (51%) returned the completed sDBS card by post; 2 were not received by us. Two case (1 1 %) of new CHB infection and five cases of previous exposure (28%) were identified and 11 negative cases were referred to their GP for vaccination. 11 participants completed an acceptability questionnaire and reported a preference for home sDBS over GP testing. Letter group: 30 CHB patients reported 40 unscreened adult contacts (23 sexual, 1 7 household, mean age 39 ±13, 22 females). 40 contacts received the advice letter via the index case. 14 (35%) response slips were returned by the participants with information about their HBV status and willingness to see their GP. However only 4 (10%) responses were received from the GP about their attendance. Significantly more contacts engaged with services via the sDBS (51%) than GP visits (10%) for HBV testing (p=0.007, chi-square) Conclusion Postal sDBS appears to be a good option for patient engagement to improve the uptake of contact screening service for HBV infection. Tailoring of sDBS to specific populations and demographic groups, with clear instructions may further increase uptake.


Daniel M. Forton - Advisory Committees or Review Panels: Merck, Janssen, Abb-vie; Grant/Research Support: Roche, Boehringer Infelheim, Gilead; Speaking and Teaching: BMS

The following people have nothing to disclose: Gayatri Chakrabarty, Phil Rice


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Ten-year prognostic performances of FibroTest (FT) and transient elastography (TE) in HBV chronic carriers (HBV-CC)

Thierry Poynard1, Julien Vergniol2, Yen Ngo3, Juliette Foucher2, Mona Munteanu3, Wassil Merrouche2, Vincent Thibault1, Olivier Deckmyn3, Dominique Thabut1, Vlad Ratziu1, Victor de Led-inghen2;
1APHP UPMC Groupe Hospitalier Pitié-Salpêtrière, Paris, France; 2Bordeaux University, Bordeaux, France; 3BioPredictive, Paris, France

Background and aim Five-year prognostic performances of baseline FT and TE have been validated in HBV-CC in two prospective cohorts, the Paris cohort (Ngo 2008) and the Bordeaux cohort (de Ledinghen 2013) for survival [overall survival (OS), and survival without liver related complications (S-LRC)]. The long-term prognostic values of FT and TE on each LRC are unknown due to the limited sample size and limited follow-up. Patients and methods To increase the power, we pooled the updated individual data of 2 cohorts at 10 years. Patients were included if at least 1 FT was performed at baseline, and excluded if they had other cause of liver disease. The main end-points were survivals (S) without transplantation (LT), without liver related death (LRD), liver complications (C), primary liver cancer (HCC), ascites (A), jaundice (J), encephalopathy (SE), and variceal bleeding (VB). Results A total of 1295 HBV-CC with interpretable FT were included; men 68%, Caucasian 38%, SubSaharan 36%, Asian 17%; at baseline 42 years old, HBeAg 17%; active 47% and inactive 53%, 6% declared >50g alcohol/day, 24% BMI >27kg/M2. During the 10 years follow-up 598(46%) were treated (14% non-responders >2000 HBV-DNA); 76 [7.2% (95%CI 4.5-8.9)] died, 12 patients (pts) [1.2%(95%CI 0.5-1.8)] have been transplanted, 47 died from LRD [4.0%(2.8-5.2)]; the incidence of C occurring at least 6 months after FT were observed in 29 pts [Kaplan-Meir 4.5%(1.7-5.2)]: 22 HCC [4.5%(1.7-5.2)], 20 A [3.0%(1.5-4.4)], 11 J [1.3%(0.5-2.1)], 9 E [1.0%(0.3-1 .7)], 5 VB [0.8%(0.0-1.5)]. A total of 792 pts had reliable baseline TE, including 657 with contemporaneous FT, which permitted direct performances comparisons. FT had significant independent prognostic values for all S and C; TE had significant prognostic values for all S with lower performances than FT except for survival without any C (Table); too few events occurred in pts with TE for estimating performances concerning A, E and VB. Conclusion: In HBV chronic careers, FT was predictive at 10 years for each liver complications and survivals. TE had significant prognostic performance but lower than those of FT except for survival without complications.

Survival EndpointFibroTest n= 1295TE n=792FibroTest vs TE n=657
 Risk Ratio (95%CI) Adjusted (Cox) on treatment, baseline viral load, HBeAg, inactive carrier status, age and gender P-value% AUROC P-value
Overall61 (20-186) .000110 (3.6-28) .000183(74-89) vs 71(57-81) .02
Without LT493 (28-1000) .000113 (5.0-32) .000185 (77-90) vs 72 (59-81) .003
Without liver related death279 (54-1000) .000115 (6.0-34) .000190 (81-95) vs 79 (60-90) .03
Without liver complications73 (20-1000) .000118 (8.4-40) .000194 (85-97) vs 87 (67-96) .20
Without HCC58 (5.9-558) .0005Two few events: <593 (88-96) vs 77 (63-86) .001
Without ascites159 (14-1000) .0001Two few events: <5Two few events: <5
Without encephalopathy42 (1.8-977) .02Two few events: <5Two few events: <5
Without bleeding626 (1.1-1000) .04Two few events: <5Two few events: <5


Thierry Poynard - Advisory Committees or Review Panels: Merck; Grant/Research Support: BMS, Gilead; Stock Shareholder: Biopredictive

Yen Ngo - Employment: BioPredictive

Juliette Foucher- Board Membership: roche; Speaking and Teaching: BMS, MSD, Gilead

Mona Munteanu - Employment: Biopredictive

Olivier Deckmyn - Management Position: BioPredictive; Stock Shareholder: Bio-Predictive

Vlad Ratziu - Advisory Committees or Review Panels: GalMed, Abbott, Genfit, Enterome, Gilead; Consulting: Astellas, Axcan, Pfizer, Sanofi-Synthelabo, Genen-tech, Nycomed

Victor de Ledinghen - Advisory Committees or Review Panels: Merck, Janssen, Gilead, Echosens, Boehringer Ingelheim, Abbvie; Grant/Research Support: Roche, Gilead, Janssen; Speaking and Teaching: Roche, Echosens

The following people have nothing to disclose: Julien Vergniol, Wassil Merrouche, Vincent Thibault, Dominique Thabut


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Statewide Screening Patterns of Hepatitis B in Hawaii Over a Decade

Chuong T. Tran1, Krista Kiyosaki1, Linda L. Wong1,2;
1Surgery, University of Hawaii John A. Burns School of Medicine, Honolulu, HI; 2University of Hawaii Cancer Center, Honolulu, HI

Purpose: Hawaii has the highest incidence of liver cancer in the US due to many immigrants from areas where Hepatitis B (HBV) is endemic. HBV screening in high-risk populations is a CDC recommendation, thus we examined physician HBV screening patterns in Hawaii. Methods: We retrospectively analyzed billing claims from 1999-2009 to identify all patients (>18 years) enrolled in a large health plan in Hawaii (65% of market share) who underwent HBV screening based on CPT codes. We collected data on age, gender and physician specialty ordering the test: primary care (internal or family medicine, and pediatrics), Ob/Gyn, GI, non-GI specialties, and non-physician providers. Results: Of an estimated 700,000 covered lives, there were 100,711 unique patients with 125,576 HBV screening tests from 1 999-2009. To examine temporal trends, we stratified tests into two eras: 1999-2004 (N=52245) and 2005-2009 (N=73331). 44651 of the tests were men and 80925 were women, with a mean age of 41.9 years. In the first era, 30975 women (59.3%) underwent testing, compared to 49950 women (69.1%) in the second era. Using US census data, the odds ratio for women being screened over the 10-year period was 1.83 (95% CI 1.80 - 1.85, p = .001). There was an overall increase in screening tests performed annually, but the proportion done by primary care MDs decreased from 55.6 to 44.9%. Ob/Gyn's screened 15.6% in the early era and 26.9% in late era. Conclusion: HBV screening among physicians in Hawaii has increased, nearly doubling in the last 5 years, likely due to changing guidelines and increased attention to preventative care. There was an increase in young women screened in the recent era, likely due to prenatal screening by Ob/Gyn physicians. Ob/Gyn physicians play an important role in HBV screening, therefore education on HBV vaccination/treatment or appropriate referral should be directed toward this group as well as primary care physicians.

HBV Screening Patterns in Hawaii: Comparing 2 Eras

Age 18-4046.1%53.7%0.008 (vs. age 41-64)
Age 41-6447.5%38.6% 
Age 65+6.4%7.7% 
Primary Care MD55.6%44.9%<0.0001 (vs. OB/GYN)
Non-GI Specialist9.8%10.0% 
Surgical specialist0.9%1.3% 
Non-MD provider1.3%2.8% 


Linda L. Wong - Speaking and Teaching: Bayer, Bayer

The following people have nothing to disclose: Chuong T. Tran, Krista Kiyosaki


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Risk Factors for Long-term Persistence of Serum Hepatitis B Surface Antigen Following Acute Hepatitis B Virus Infection in Japanese Adults

Kiyoaki Ito1,18, Hiroshi Yotsuyanagi2, Hiroshi Yatsuhashi3, Yoshiyasu Karino4, Yasuhiro Takikawa5, Takafumi Saito6, Yasuji Arase7, Fumio Imazeki8, Masayuki Kurosaki9, Takeji Umemura10, Takafumi Ichida11, Hidenori Toyoda12, Masashi Yoneda1, Eiji Mita13, Kazuhide Yamamoto14, Kojiro Michitaka15, Tatsuji Maeshiro16, Junko Tanuma18, Yasuhito Tanaka17, Masaya Sugiyama18, Kazumoto Murata18, Naohiko Masaki18, Masashi Mizokami18;
1Aichi Medical University School of Medicine, Nagakute, Japan; 2University of Tokyo, Tokyo, Japan; 3NHO Nagasaki Medical Center, Nagasaki, Japan; 4Sapporo Kosei General Hospital, Sapporo, Japan; 5Iwate Medical University, Morioka, Japan; 6Yamagata University School, Yamagata, Japan; 7Toranomon Hospital, Tokyo, Japan; 8Chiba University, Chiba, Japan; 9Musashino Red Cross Hospital, Tokyo, Japan; 10Shinshu University School of Medicine, Matsumoto, Japan; 1 1Juntendo University Shizuoka Hospital, Shizuoka, Japan; 12Ogaki Municipal Hospital, Ogaki, Japan; 13National Hospital Organization Osaka National Hospital, Osaka, Japan; 14Okayama University Graduate School of Medicine, Okayama, Japan; 15Ehime university Graduate School of Medicine, Toon, Japan; 16University of Ryuku, Naha, Japan; 17Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 18National Center for Global Health and Medicine, Tokyo, Japan

Background and Aims: The proportion of patients who progress to chronicity following acute hepatitis B (AHB) widely varies worldwide. Moreover, the association between viral persistence after AHB and hepatitis B virus (HBV) genotypes in adults remains unclear. Many lines of evidence have revealed among the Japanese an increase in acute infection with HBV genotype A following sexual transmission. A multicenter cohort study was conducted throughout Japan with AHB. The aim of this cohort study was to assess the influence of clinical and virological factors, including HBV genotypes and treatment with nucleotide analogues (NAs), on AHB patients who became persistently infected. Patients and Methods: From 2005 through 2010, the study participants were recruited from 38 liver centers throughout Japan. The cohort included patients who were admitted to the hospitals because of AHB and who visited the hospitals every month after being discharged. For comparing factors between AHB patients with viral persistence and those with self-limited infection, 212 AHB patients without co-infection of HIV were observed until serum hepatitis B surface antigen (HBsAg) disappeared or a minimum of 6 months in cases where HBsAg persisted. Results: The time to disappearance of HBsAg was significantly longer for genotype A patients than that of patients infected with non-A genotypes (6.7 ± 8.5 months vs. 3.4 ± 6.5, P < 0.0001). When chronicity was defined as the persistence of HBsAg positivity for more than 6 or 12 months, rate of progression to chronicity was higher in patients with genotype A, although many cases caused by genotype A were prolonged cases of AHB, rather than chronic infection. Multivariate logistic regression analysis revealed only genotype A was independently associated with viral persistence following AHB (Odds Ratio: 5.501, 95% CI: 2.561-11.815, P < 0.001). A higher peak level of HBV DNA (6.7 ± 8.5 vs. 3.4 ± 6.5 log copies/mL, P < 0.0001) and a lower peak of alanine amino-transferase (ALT) levels (1210 ± 646 vs. 2225 ± 2851 IU/L, P= 0.045) were characteristics of AHB caused by genotype A. Treatment with nucleotide analogues (NAs) did not prevent progression to chronic infection following AHB overall. Subanaly-sis suggested early NA initiation (<8 weeks from presentation) appeared to enhance viral clearance across genotypes. Conclusion: Genotype A was an independent risk factor for progression to chronic infection following AHB. Our data will be useful in elucidating the association between viral persistence after AHB, host genetic factors, and treatment with NAs in future studies.


Kazuhide Yamamoto - Advisory Committees or Review Panels: Shionogi Pharmaceutical Co; Grant/Research Support: Tanabe Mitsubishi Co, MSD, Chugai Pharmaceutical Co, Esai Co

Yasuhito Tanaka - Advisory Committees or Review Panels: Nippon Boehringer Ingelheim Co ., Ltd.; Grant/Research Support: Chugai Pharmaceutical CO., LTD., MSD, Mitsubishi Tanabe Pharma Corporation, Dainippon Sumitomo Pharma Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Bristol-Myers Squibb

The following people have nothing to disclose: Kiyoaki Ito, Hiroshi Yotsuyanagi, Hiroshi Yatsuhashi, Yoshiyasu Karino, Yasuhiro Takikawa, Takafumi Saito, Yasuji Arase, Fumio Imazeki, Masayuki Kurosaki, Takeji Umemura, Takafumi Ichida, Hidenori Toyoda, Masashi Yoneda, Eiji Mita, Kojiro Michitaka, Tatsuji Maeshiro, Junko Tanuma, Masaya Sugiyama, Kazumoto Murata, Naohiko Masaki, Masashi Mizokami


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Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma undergoing anti-cancer therapy

Young Woon Kim, Sung Won Lee, Jung Hyun Kwon, Chan Ran You, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Kyu Won Chung, Jeong Won Jang;
Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea

Background: Resolved or occult hepatitis B virus (HBV) infection have been associated with HBV reactivation in HBsAg-negative patients, particularly in settings of rituximab-containing chemotherapy or hematopoietic stem cell transplantation. HBV reactivation in HBsAg-negative patients with hepatocellular carcinoma (HCC) has not been reported explicitly. This study aimed to determine the incidence and risk factors of HBV reactivation during therapy in HBsAg-negative HCC patients. Methods: Between 2007 and 2012, HBsAg-negative patients with HCC were consecutively recruited for the study. Anti-cancer therapies for HCC were divided into three treatments according to intensity: transarterial mono-therapy (doxorubicin; n=78), combination-ECF chemotherapy (epirubicin-cisplatin-5-FU; n=17), or combined chemo-radiotherapy (ECF+RT; n=14). With serial monitoring of HBV DNA and serologic markers, patients with HCC were observed for HBV reactivation (defined as reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with controls consisting of those with HBsAg-negative cirrhosis (n=16) and HBsAg loss (n=46). Results: During the study, HBV reactivation occurred in 1 1 (10.1%) and 1 (1.6%) patients in the treated and control groups, respectively. The estimated probabilities of reactivation at 1 and 2 years were 7.7% and 15.9% in patients with HCC, while the corresponding probabilities were 0% and 2.0% in the control group (P=0.006). Overall, four (36.4%) and one (9.1%) of them experienced hepatitis and hepatic decompensation due to HBV reactivation during therapy, respectively. Among the 12 reactivated patients, 8 (66.7%) had confirmed evidence of prior chronic hepatitis B (CHB) or occult infection. Anti-cancer therapy was significantly correlated with a higher incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment (P=0.005). On multivariate analysis, treatment intensity and a prior history of CHB or occult HBV infection remained independently predictive of HBV reactivation. Conclusions: Anti-cancer treatment can reactivate HBV in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. HBsAg-negative patients with HCC, especially those with a prior history of CHB or occult HBV infection undergoing intensive treatment, should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.


The following people have nothing to disclose: Young Woon Kim, Sung Won Lee, Jung Hyun Kwon, Chan Ran You, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon, Kyu Won Chung, Jeong Won Jang


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Developing national estimates of chronic hepatitis B prevalence, treatment uptake, and outcomes by local health area

Jennifer H. MacLachlan1,2, Nicole Allard1,2, Vanessa Towell3, Benjamin C. Cowie1,2;
1WHO Regional Reference Laboratory for Hepatitis B, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia; 2Department of Medicine, University of Melbourne, Melbourne, VIC, Australia; 3National Policy and Education Division, Australasian Society for HIV Medicine, Sydney, NSW, Australia

Purpose: To identify priority populations and target Australian public health and clinical interventions for chronic hepatitis B (CHB) through mapping of disease burden, complications and treatment uptake at a national, regional and local level. Methods: The prevalence of CHB by area was derived using country of birth and risk group seroprevalence estimates applied to national census population data, as well as for local health jurisdictional areas (average size approximately 356,000 residents). HBV antiviral treatment by area was obtained from national health insurance drug treatment data. Where available, these estimates were augmented with routinely recorded data such as CHB surveillance notifications and liver cancer incidence. Results: Approximately 55% of Australians currently living with CHB were born overseas, predominantly in the Asia Pacific region (38.1% of all Australians with CHB). Other priority populations include Indigenous Australians (9.3%), people who inject drugs (5.7%), and men who have sex with men (4.4%). The national prevalence of CHB in Australia is estimated to be 1.0% (21 8,000 people), of whom only 55% have been diagnosed, and 3% are receiving antiviral therapy. However this prevalence and the priority populations affected are not consistent across Australia. More than one-third of Australian local health areas have now been profiled in depth, and analysis of community profiles reveals significant local diversity, with prevalence of CHB by local area ranging from 0.55% to 1.67%, and treatment uptake from <1% to 7.8%. People living with CHB born overseas are often concentrated in a small number of local health areas; 32% of Chinese-born Australians living with CHB are resident in just 3 areas, and 40% of Vietnamese-born Australians with CHB reside in just 2 areas. Where data were available, a strong correlation between CHB prevalence and HCC incidence was noted. Conclusions: The methodology described could be applied to any population where reliable census data are available and where the predominant burden of CHB is experienced by people born overseas. This study presents a robust method for deriving estimates of CHB prevalence, liver cancer incidence, and treatment uptake at a national, state, and local level. It is informing the development of targeted programs to address CHB in the highest prevalence parts of the country, and will allow the monitoring of treatment uptake over time. In this way the study will both guide and evaluate the impact of interventions to increase access to antiviral therapy for CHB at a population level.


The following people have nothing to disclose: Jennifer H. MacLachlan, Nicole Allard, Vanessa Towell, Benjamin C. Cowie


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CR-HepB: A New Registry System for Documenting and Analyzing the Demography, Virology and Medicine Treatments of Hepatitis B in China

Jidong Jia, Jinlin Hou, Tao Han, Xiaoguang Dou, Yuexin Zhang, Wen Xie, Qing Xie, Hong Ren, Huiguo Ding, Hong Tang, Xiaoyuan Xu, Youqing Xu, Xiaoqing Liu, Junqi Niu, Hong You, Jie Li, Hui Zhuang, Lai Wei;
CR-HepB study group, Beijing, China

Background & Aims: Hepatitis B (HBV) is a common disease in China and associated territories. The last previous national survey showed that the incidence of HBV HBsAg-positivity is 7.18% within the general population in China. We set up a new national registry system to document and analyze unclear information in the demography, virologic status, the treatment and disease progress. Methods & Materials: A national wide registry system named China Registry of Hepatitis B (CR-HepB), involving 15 tertiary hospitals in mainland China, was launched in July 2012. The main criteria for patients registration within the system was HBsAg-positivity over a continuous six months. There were 1 3,493 cases retrospectively registered from the year 2000, and these patients received followed-up visits every three to six months. Up to now totally 83,222 visits, 6.2 times per patients on average, have been recorded. Results: (1) Of the patients registered 72.9% were male and 27.1% were female. The age of onset was 43.8 years on average, with 50.7% being between 30-50 years old. (2) Maternal-neonatal transmission was involved in 12.6% of cases, while the other 51.3% were unclear in origin. For the cases in which we knew their family histories, 41.5% were chronic hepatitis B and 5.3% were of hepatic cellular cancer (HCC). (3) Approximately 80.7% were initially diagnosed as chronic hepatitis B, 16.3% as cirrhosis and 3.0% as HCC. Among the patients 60.7% were detectable by HBV DNA, 56.7% were positive for HBeAg. (4) The biopsies of 1,21 8 patients indicated the rate of G0-G4 (inflammation grade) were 3.3%, 28.2%, 29.1%, 32.5%, 6.9%, and S0-S4 (fibrosis stage) were 1 1.5%, 33.3%, 30.4%, 19.4%, 5.4%. (5) As to the anti-HBV medicines, inter-feron-alfha was used in 9.6% and nucleos(t)ide analogues were used in up to 67.8%. Nearly 21.5% patients were treated with combinations of two types of nucleos(t)ide analogues. The frequency of each nucleos(t)ide analogues used were as follows: adefovir 33.3%, entecavir 29.0%, lamivudine 27.6%, telbivu-dine 9.7% and tenofovir (not commercially available in Mainland China) 0.4%. Conclusion: This CR-HepB Registry includes both the most HBV patients and the most follow-up visits. In this first year report of the registry, middle-age males were the main HBV-infected group. About half were HBeAg positive. Nucleos(t)ide analogues were the most commonly used treatment. Being the most extensive HBV registry, over time it will provide patient outcome information not only for China, but also for the world.


Jidong Jia - Consulting: BMS, MSD, Novartis, Roche; Speaking and Teaching: GSK

Jinlin Hou -Consulting: Roche, Novartis, GSK, BMS, Roche, Novartis, GSK, BMS; Grant/Research Support: Roche, Novartis, GSK, Roche, Novartis, GSK

Xiaoguang Dou - Speaking and Teaching: BMS, GSK, Novartis, Roche

Lai Wei - Consulting: Gilead; Grant/Research Support: BMS, Roche, Novartis; Speaking and Teaching: Gilead

The following people have nothing to disclose: Tao Han, Yuexin Zhang, Wen Xie, Qing Xie, Hong Ren, Huiguo Ding, Hong Tang, Xiaoyuan Xu, Youqing Xu, Xiaoqing Liu, Junqi Niu, Hong You, Jie Li, Hui Zhuang


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High dose Hepatitis B and A vaccination schedules in cirrhotic patients; do they work ?

Alan J. Wigg1, Rachel Wundke1, Rosemary J. McCormick1, Richard J. Woodman2;
1Hepatology and Liver Transplant Medicine Unit, Flinders Medical Centre, Adelaide, SA, Australia; 2Division of General Practice, School of Medicine, Flinders University of South Australia, Adelaide, SA, Australia

INTRODUCTION: Hepatitis B and A vaccination (HBV, HAV) are important preventative measures in cirrhotic patients but are hindered by lower immune response rates. Limited literature surrounds the use of high dose, rapid vaccination regimens in cirrhotic patients. The aims of this study were to; assess the efficacy of high dose, rapid vs. standard dose HBV and HAV regimens in a mixed cirrhotic population and to determine associations with response to vaccination. METHODS: Prospective, non-randomized controlled trial. High dose HBV schedule was; 40 μg at 0, 1 and 2 months with the schedule repeated as a booster if non-immune after 3 doses. High dose HAV schedule was; 1440 μg at 0, 1 and 2 months with the schedule repeated as a booster if non-immune after 3 doses. Differences in response rates were compared using Fishers exact or chi-square test. Variables (age, gender, aetiology, MELD score, Child Pugh score, INR, albumin, creatinine, bilirubin, smoking status, drinking status, presence of renal dysfunction) were tested for association with response using stepwise logistic regression. RESULTS: For HBV schedules 81 and 48 patients received standard and high dose regimens, respectively. The overall clinical characteristics of this population were; mean age 58 years, 65% male, 56% hepatitis C, mean MELD 11.1 with similar clinical characteristics for both groups. The response rates were 60.5 % and 70.8 % for standard and high dose regimens, respectively (p=0.24). Independent associations with response included; female gender (OR 3.1, 95%C1 1.04-9.15, p=0.042) and non-alcoholic fatty liver disease vs. hepatitis C as etiology (OR 0.13, 95%C1 0.03-0.56, p=0.006). For HAV schedules 62 and 37 patients received standard and high dose regimens, respectively. The overall clinical characteristics of this population were; mean age 56 years, male 63%, alcohol liver disease 46%, mean MELD 1 0.2, with similar clinical characteristics for both groups. The response rates were 87.1 % and 97.3 % for standard and high dose regimens, respectively (p=0.15). The only independent association with response was age (OR 0.94, 95%C1 0.88-1.0, p=0.005). The mean increase in per patient cost was A$ 44 and A$ 50 for high dose hepatitis B and A vaccination, respectively. CONCLUSIONS: In cirrhotic patients a 10% improvement in HBV and HAV responses can be obtained using high dose, rapid vaccination regimens. The improved, rapid response rates observed may be clinically useful and are inexpensive. In cirrhotic patients both male gender and non-alcoholic fatty liver disease (for HBV) and older age (for HAV) and predictors for non-response.


The following people have nothing to disclose: Alan J. Wigg, Rachel Wundke, Rosemary J. McCormick, Richard J. Woodman


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Comparison of Demographic and Serological Characteristics of Hispanic and Asian Patients with Chronic Hepatitis B Infection in Los Angeles

Joyce Limurti, Saro Khemichian, Yong W. Cho, Takeshi Saito, Jeffrey Kahn, Allan Redeker, Tse-Ling Fong;
University of Southern California, Los Angeles, CA

Introduction: Among different ethnicities in the U.S., Asians have the highest prevalence of chronic hepatitis B infection (CHB). Prevalence of CHB among Hispanics in the U.S. is 0.27%. There is little data regarding the demographic and serologic characteristics of CHB among Hispanic-Americans. Aim: To compare characteristics of CHB infection among Asian-and Hispanic-American patients (pts) in Los Angeles. Patients and Methods: Medical records of consecutive CHB pts seen between Aug 2012-March 201 3 at the Hepatitis Clinic at Los Angeles County-USC medical center were reviewed. 342 Asian and 54 Hispanic pts were identified. Demographic, baseline serologic and clinical data were obtained and analyzed. Results: The mean ages and preponderance of females were similar in the two groups. 95% of Hispanic and 99.7% of Asian CHB pts were foreign-born. Compared to Asian pts, Hispanic pts were more likely to report sexual transmission and transfusion as a risk factor for CHB. In contrast, maternal-infant transmission or unknown risk factors were more likely to be reported by Asian pts. Family history of CHB was reported in 7% of Hispanic compared to 34% of Asian pts (p<0.001). Five out of fifty four (9%) Hispanic pts were HBeAg(+)/anti-HBe(-), all of whom had active disease (elevated ALT/HBV DNA > 2000 IU/mL). Among Asian pts, 61 of 342 (19%) were HBeAg(+)/anti-HBe(-) of whom 41/61 had active disease. Among HBeAg(-)/anti-HBe(+) pts with abnormal ALT, Hispanic pts were less likely to have HBV DNA ≥ 2000 IU/ml (Hispanics 17% vs. Asians 33%, p=0.031). The proportion of Hispanic pts with HBeAg(-)/anti-HBe(+), normal ALT, and HBV DNA<2000 IU/ml (11%) was not significantly different from Asian pts (13%) (p=0.534). Fifty two percent of Hispanic pts compared to 28% of Asian pts were HBeAg(-)/anti-HBe(+) with HBV DNA<2000 IU/ml and abnormal ALT (p<0.001 ). Among CHB pts who met treatment guidelines, 1 00% of Hispanic and 96% of Asian pts were started on anti-HBV therapy. Conclusions: There are different risk factors for CHB between Hispanic and Asian pts. A lesser proportion of active CHB was seen in Hispanic compared to Asian pts.

CharacteristicsHispanic n=54Asian n=342p value
Female Sex (%)6558NS
Mean Age, range (years)50,(26-71)53, (22-78)NS
Family History (%)734<0.001
Baseline Serologies (%)
Normal ALT/HBV DNA <2000 IU/ml Normal ALT/HBV DNA ≥2000 IU/ml Abnormal ALT/HBV DNA <2000 IU/ml Abnormal ALT/HBV DNA ≥2000 IU/ml00091 23 13NS NS NS NS
Normal ALT/HBV DNA <2000 IU/ml Normal ALT/HBV DNA ≥2000 IU/ml Abnormal ALT/HBV DNA <2000 IU/ml Abnormal ALT/HBV DNA ≥2000 IU/ml11 4 52 1713 7 28 33NSNS <0.001 0.031


Saro Khemichian - Speaking and Teaching: Merck, Salix

Jeffrey Kahn - Speaking and Teaching: Bayer

Tse-Ling Fong - Grant/Research Support: Gilead Sciences; Speaking and Teaching: BMS, Vertex

The following people have nothing to disclose: Joyce Limurti, Yong W. Cho, Takeshi Saito, Allan Redeker


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Liver cancer is the fastest increasing cause of cancer death in Australia

Jennifer H. MacLachlan1,2, KylieCarville1,2, Benjamin C. Cowie1,2;
1WHO Regional Reference Laboratory for Hepatitis B, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia; 2Department of Medicine, University of Melbourne, Melbourne, VIC, Australia

Purpose: This purpose of this study was to examine national trends of liver cancer mortality in Australia, and to extend this analysis through investigation of primary liver cancer in Victoria, Australia since 1982, examining incidence, survival, and geographic and temporal trends. Methods: National cancer mortality trends were derived from Australian Institute of Health and Welfare data. For the Victorian liver cancer analysis, de-identified data on cancer diagnoses in the ICDO-3 range 8170/3 to 8180/3 in Victorian residents from 1st January 1982 to 31st December 2007 were obtained from the Victorian Cancer Registry. Temporal trends, geographic distribution, age and country of birth information were analysed. Results: The mortality rate from liver cancer in Australia more than doubled during the period 1 982-2007, from 2.3 to 4.9 deaths per 1 00,000, increasing more rapidly than any other malignancy and contrasting with a 16% decrease in all-cancer mortality over the same period. Liver cancer is now the 9th most common cause of cancer death in Australians. These trends were reflected in primary liver cancer incidence in the state of Victoria, where the number of HCC cases increased by 5.2% per year in metropolitan areas and 6.2% per year in rural areas. Half of those diagnosed with HCC were born overseas, predominantly in the European region (60% of those born overseas, mainly Italy, England and Greece) and the Asia-Pacific (28% of those born overseas, mainly China and Vietnam), and higher rates of liver cancer were observed in areas of the state with greater migration from areas endemic for hepatitis B and hepatitis C. HCC survival did improve over the study period but overall remained low; between 1999-2007, one-third of patients with HCC died within 30 days of their diagnosis, and five-year survival was among the lowest of all cancer sites, at 1 9%. Conclusions: Liver cancer incidence and mortality continue to rise in Australia, despite the downward trend in overall cancer mortality and the success of prevention and screening initiatives for many other malignancies. The preventable nature of many of these cancers, and evidence of late diagnosis and poor survival, mean liver cancer attributable to viral hepatitis is now recognised as a national cancer prevention priority in Australia. The geographic and temporal analysis presented here demonstrates the capacity for targeting interventions where the burden of liver cancer is greatest.


The following people have nothing to disclose: Jennifer H. MacLachlan, Kylie Carville, Benjamin C. Cowie


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Trends in the Seroprevalence of Hepatitis B and C in a Large Cohort of Patients Attending at a Reference Medical Area in Spain over the Last Five-Years

Alvaro Mena1, Luz Moldes2, Héctor Meijide3, Angelina Cañizares2, Angeles Castro1, José D. Pedreira1, Germán Bou2, Eva Poveda1;
1Division of Clinical Virology, INIBIC-Complejo Hos-pitalario Universitario A Coruña, A Coruña, Spain; 2Service of Microbiology, INIBIC-Complejo Hospitalario Universitario A Coruña, A Coruña, Spain; 3Service of Internal Medicine, Hospital Chiron, A Coruña, Spain

Background: Hepatitis B and C virus infections (HBV & HCV) remain a public health problem representing a significant burden of liver disease worldwide. HBV vaccination, the use of effective anti-HBV agents and the advent of new potent active drugs against HCV infection might be modifying the seroepi-demiology of both infections in our population. Herein, we assessed the trends in the seroprevalence of HBV and HCV in a large cohort of individuals attending a reference medical area in Spain during the last 5 years. Methods: All results entries for HBV and HCV serological markers at our reference lab ordered from primary care and specialized physicians between 2008 and 2012 were recorded. Our center covers a medical care area of 501,526 citizens. Demographic (age, sex and year of birth) and laboratory parameters were also documented. Results: A total of 1 31,544 HBsAg results were generated within the last 5 years, being the overall HBsAg prevalence 1.6%. It remained stable throughout the study period: 1.6% (2008), 1.7% (2009), 1.6% (2010), 1.6% (2011), and 1.5% (2012). HBsAg+ individuals were mostly (61.5%) male with a mean age of 45±17 years; 12.5% were HBeAg+. Among HBsAg-neg individuals, total anti-HBcore was detected in 12.4%. This figure remained stable during the last 5 years. A total of 92,143 anti-HCV-Ab results were generated during the study period, being 8.6% the overall anti-HCV+ rate. The yearly rate has remained stable during the last 5 years: 8.2% (2008), 7.4% (2009), 7.8% (2010), 8% (2011), and 10.1% (2012). The prevalence of anti-HCV-Ab+ vary by year of birth with the highest rates before 1 940 and between 1 960-1975. This is in contrast with data found in the USA, where there is a disproportionate high rate of anti-HCV+ in persons born between 1945 and 1965. Our anti-HCV-Ab+ individuals were male (51.7%), mean age 45±18 years, and 56.3% viremic. The HCV genotype distribution was as follows: 59.7% G1, 5.4% G2, 22.7% G3, and 12.2% G4. Conclusions: The prevalence of HBsAg and anti-HCV in persons requiring medical care in Northern Spain is relatively high (1.6% and 8.6%, respectively). In contrast with the USA there was no evidence of increased HCV exposure in subjects born between 1945 and 1965. Different historical and social circumstances might explain it, including the huge iv drug use epidemic in the eighties in Spain and the large immigration flow HBV and HCV endemic areas in the nineties. Thus, pro-active HBV and HCV screening policies should be expanded in Spain, as antiviral therapy has become very effective and preclude development of clinical complications in most cases.


The following people have nothing to disclose: Alvaro Mena, Luz Moldes, Héctor Meijide, Angelina Cañizares, Angeles Castro, José D. Pedreira, Germán Bou, Eva Poveda


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Reactivation of hepatitis B after hematopoietic stem cell transplantation for hematological malignancy

Shingo Nakamoto, Tatsuo Kanda, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Fumio Imazeki, Hiroshi Shirasawa, Chiaki Nakaseko, Osamu Yokosuka;
Graduate School of Medicine, Chiba University, Chiba, Japan

Hepatitis B virus (HBV) reactivation can occur during the treatment of hematological malignancies even in patients who had cleared hepatitis B surface antigen (HBsAg) before. We analyzed the incidence of HBV reactivation (ALT elevation accompanied with HBV DNA or HBsAg positivity) in patients who had undergone hematopoietic stem cell transplantations (SCT) at our institution. Two hundred forty-six patients who underwent SCT between 1986 and 2006 (mean age, 37 years; male, 63%; mean observation period, 6.7 years) were retrospectively analyzed for the occurrence of HBV reactivation. They were diagnosed either as acute myeloid leukemia (27%), acute lym-phoblastic leukemia (17%), non-Hodgkin lymphoma (15%), chronic myeloid lymphoma (13%), or others (28%). After SCT, immunosuppressants such as cyclosporine and tacrolimus were administered. Overall, HBV reactivation was observed in 12 (5%) out of 244 patients. Before 2000, nucleic acid analogs (NAs) were not available at our hospital. During this period, SCT were performed in 120 patients without screening for the presence of hepatitis B core and/or s antibody (anti-HBc/s). HBV reactivation occurred in 1 (1 00%) of one patient who had HBsAg before SCT and 5 of 1 19 (4%) patients who did not. The patient who had HBsAg before SCT experienced hepatitis B reactivation 1 year after SCT. After the availability of NA, The patient was successfully treated with lamivudine. In remaining 5 patients, the median period between SCT and HBsAg positivity were 1.5 years. No one died from HBV reactivation. After 2000, SCT were performed in 126 patients; 2 had HBsAg and 124 did not. One of 2 patients who had HBsAg was pretreated with NA, which could prevent HBV reactivation. In another patient, HBV reactivation occurred 2 months after SCT. But lamivudine effectively suppressed the reactivated virus. As for 124 HBsAg negative patients, HBV reactivation occurred in 3 (8%) of 36 patients who had anti-HBc/s, in 1 (5%) of 1 9 whose anti-HBc/s status is unknown, and in none of 69 (0%) not having anti-HBc/s. In these patients, HBV reactivation occurred 2.5 to 7 years after SCT. NA treatments were effective in all 4 patients and one patient cleared HBsAg after the withdrawal of NA. Conclusion: Prevention use as well as early administration of NAs is useful for the treatment against HBV for reactivation in the course of SCT. To prevent and treat HBV reactivation successfully, attention should be paid to the HBs status and/or HBV DNA in patients who have history of HBV infection.


Tatsuo Kanda - Speaking and Teaching: MSD K.K., AJINOMOTO PHARMACEUTICALS CO., LTD, CHUGAI PHARMACEUTICAL CO., LTD, GlaxoSmithKlein, BMS; Stock Shareholder: Mitsubishi Tanabe Pharma

The following people have nothing to disclose: Shingo Nakamoto, Shuang Wu, Xia Jiang, Tatsuo Miyamura, Fumio Imazeki, Hiroshi Shirasawa, Chiaki Nakaseko, Osamu Yokosuka


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Differences between Hepatocellular Carcinoma and Hepatitis B Virus Infection in Patients with and without Cirrhosis

Jong Man Kim1, Geum Youn Gwak2, Choon Hyuck D. Kwon1, Joon Hyeok Lee2, Seung Woon Paik2, Jae Won Joh1;
1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

Background: In patients with hepatitis B virus (HBV) infections, differences in hepatocellular carcinoma (HCC) between those with liver cirrhosis and those without cirrhosis have not been elucidated. The aim of this study was to compare clinicopatho-logical characteristics and survival between non-cirrhotic and cirrhotic patients with HBV. Furthermore, we aimed to determine prognostic factors for tumor recurrence after hepatectomy in patients with HBV and HCC. Methods: Between 2005 and 201 0, 441 curative hepatectomies for HCC in patients with cirrhosis and 454 for HCC in patients without cirrhosis were performed. The clinicopathologic characteristics and survival between the two groups were compared and prognostic factors for tumor recurrence were identified by univariate and multi-variate analysis. Results: Cirrhotic patients had lower platelet counts, PIVKA levels, and tumor size than non-cirrhotic patients. Serum ALP, HBV DNA, and ICG levels, as well as the incidence of positive HBeAg in cirrhotic patients, were higher than in non-cirrhotic patients. HCC differentiation in non-cirrhotic patients was poorer than in cirrhotic patients. The 1-year, 3-year and 5-year disease-free survival rates were 72.0%, 61.0% and 55.7% in non-cirrhotic patients, and 68.6%, 51.5% and 45.9% in cirrhotic patients, respectively (P=0.013). However, The 1-year, 3-year and 5-year overall survival rates were 92.4%, 81.7% and 74.8% in non-cirrhotic patients, and 91.9%, 82.4% and 78.7% in cirrhotic patients, respectively (P=0.683). Risk factors for tumor recurrence in each group varied in multivariate analyses. Increased age, high platelet counts, microvascular invasion, serosal invasion, and intrahep-atic metastasis predisposed to tumor recurrence in non-cirrhotic patients, but elevated PIVKA-II and ALP levels, low serum albumin levels, portal vein invasion, intrahepatic metastasis, and tumor size were predisposing factors for recurrence in cirrhotic patients. Conclusions: The clinicopathologic characteristics and risk factors for tumor recurrence in cirrhotic and non-cirrhotic HCC patients with HBV infection differ.


Choon Hyuck D. Kwon - Consulting: Covidien, Novartis

The following people have nothing to disclose: Jong Man Kim, Geum Youn Gwak, Joon Hyeok Lee, Seung Woon Paik, Jae Won Joh


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Hepatitis B screening prior to initiation of chemotherapy in haematology and oncology patients in a large teaching hospital: a clinical challenge

Hassan M. Bholah, Mark Aldersley, Rebecca Jones;
Hepatology, St James University Hospital, Leeds, United Kingdom

Purpose Hepatitis B reactivation in patients receiving chemotherapy is well recognised. Consequences include cessation of treatment, severe hepatitis, hospitalisation or death. The St James's Institute of Oncology chemotherapy service treats over 5000 patients per year and is part of one of the largest cancer centres in the United Kingdom. The aim of this clinical audit was to assess current practice in hepatitis B screening among local oncologists and haematologists prior to initiation of chemotherapy. Methods We conducted a retrospective review of consecutive patients started on chemotherapy in December 2012 and January 2013 using our cancer database and electronic patient records. The Centers for Disease Control and Prevention (CDC) as well as the American Society of Clinical Oncology (ASCO) recommendations were used to compare screening practice locally. Chronic hepatitis B testing using Hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) was evaluated. Results 1 22 patients received chemotherapy over a 2-month period, of whom 85 were female and 37 were male. The majority (91%) were treated fora non-haematological malignancy with breast and gynaecological tumours accounting for 49% of cases (n=60). 121 patients had baseline liver function tests measured (>99%). Only ten patients were tested for HBsAg (8%) and all returned a negative test. 30% of those patients had concomitant anti-HBc testing which was also negative. Seven patients had an unexplained elevated ALT (defined as >40 iU/L using local laboratory values) prior to chemotherapy and were not tested for HBsAg or anti-HBc. Only one out of 1 0 patients considered to be at high risk for chronic HBV on the basis of ethnicity/country of origin (prevalence >2%) was tested for HBV. The only patient in our series who received rituximab had not been tested for chronic HBV prior to initiation of treatment. Conclusion Routine screening for HBV using HBsAg and anti-HBc was very low (8% of patients) in patients undergoing chemotherapy. Barriers for this may include the non-committal nature of the ASCO guidance when compared to the guidance from the CDC, our own regional liver network, and the National Institute for Health and Care Excellence (NICE) draft guidance. Reactivation may not only lead to avoidable death from liver failure, but also avoidable death from cancer due to compromised treatment. There is a need to raise awareness among local oncologists and haematologists about this issue. Local hepatology, oncology and haematology teams should work together to optimise HBV testing prior to starting cytotoxic or immunosup-pressive treatment.


The following people have nothing to disclose: Hassan M. Bholah, Mark Alders-ley, Rebecca Jones


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Hepatitis B Research Network (HBRN): Maternal Knowledge of Children's Hepatitis B Infection and Vaccination Status

Tram T. Tran1, Natalie H. Bzowej2, Ruosha Li3, Colina Yim4, Man-dana Khalili5, Norah Terrault5, Coleman Smith6, Naoky Tsai 7, Daryl Lau8;
1Cedars-Sinai Medical Center, Los Angeles, CA; 2Oschner Medical Center, New Orleans, LA; 3University of Pittsburgh, Pitttsburg, PA;4 University of Toronto, Toronto, ON, Canada; 5UCSF, San Francisco, CA; 6University of Minnesota, Plymouth, MN; 7University of Hawaii, Honolulu, HI; 8Beth Israel Deaconess, Boston, MA

Background: Hepatitis B virus (HBV) transmission persists despite effective perinatal measures including the use of HBIG and HBV vaccination (VAC) to prevent HBV transmission from HBsAg + mothers to their infants. Maternal knowledge may play a role in prevention of perinatal transmission. We aimed to assess maternal knowledge of HBV testing and diagnosis in their children as well as rates of HBV vaccination (VAC) and HBIG within the NIDDK-funded Hepatitis B Research Network. Methods: Adult women with chronic HBV who reported being previously pregnant completed an additional survey assessing their knowledge of the testing or diagnosis of HBV and the administration of VAC and/or HBIG to their biological and adopted children. Results: From 1/1/2011 to 3/18/2013, 787 women were enrolled into the HBRN adult cohort. 539 were previously pregnant and 482 reported at least 1 live birth (total of 1 1 06 children). Median age of the 482 women was 45 (19-75) years; 10% White, 13% Black, 74% Asian, and 4% other; The presumed mode of HBV infection was available for 354: 62% vertical, 37% horizontal and 1% other; 14% of women did not know the HBV status of their child. Maternal age, race, income, education or place of birth did not affect knowledge of child's HBV infection. Women with known mode of transmission of HBV more often knew the HBV status of their child compared to those with unknown mode (88% vs. 78% p=0.01). Administration of perinatal HBIG to the child was unknown by the mother in 27% while VAC administration was unknown in 1 3%. Multiple logistic regression models suggest that lack of VAC knowledge was associated with lower levels of education (high school or less) (OR=1.9 CI 1.1-3.3 p=0.02) and age>40 years (OR=3.1 CI 1.6-6.1 p=0.001). If presumed mode of transmission was unknown for the women (vs. known), it was more likely that VAC status of the child was also unknown (OR=1.9 CI 1.1-3.4 p=0.02). HBIG knowledge reflected similar differences by educational status, maternal age, and knowledge of mode of transmission. No differences in VAC/HBIG knowledge were noted between maternal race or maternal continent of birth. Conclusions: Fourteen percent of North American women with HBV did not know whether their children were infected with HBV. HBV vaccination status was unknown to the mother in 13% of children and HBIG administration was unknown in 27%. Knowledge disparities by educational attainment and age show opportunities in patient based educational programs.


Tram T. Tran - Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb, Vertex; Consulting: Gilead; Grant/Research Support: Bristol Myers Squibb; Speaking and Teaching: Bristol Myers Squibb, Gilead, Vertex

Natalie H. Bzowej - Advisory Committees or Review Panels: Vertex; Grant/Research Support: Genentech, Merck, Gilead Sciences, Vertex, Bristol Myer Squibb, Pharmasset; Speaking and Teaching: Gilead Sciences, Vertex

Colina Yim - Advisory Committees or Review Panels: Merck Canada, Vertex, Roche Canada, Gilead, Janssen; Speaking and Teaching: Merck

Mandana Khalili - Advisory Committees or Review Panels: Gilead Inc.; Grant/Research Support: Gilead Inc., BMS Inc, BMS Inc

Norah Terrault-Advisory Committees or Review Panels: Eisai, Biotest; Consulting: BMS; Grant/Research Support: Eisai, Biotest, Vertex, Gilead, AbbVie, Novartis

Coleman Smith - Advisory Committees or Review Panels: Vertex, Gilead, Janssen; Grant/Research Support: Gilead, Abbvie, Janssen, Salix, BMS; Speaking and Teaching: Merck, Vetex, Gilead, Bayer/Onyx, BMS

Naoky Tsai -Advisory Committees or Review Panels: Gilead, Vertex; Consulting: BMS, Gilead, Merck; Grant/Research Support: BMS, Gilead, Genentech, Vertex, Novartis, GSK, Bayer, Abbvie; Speaking and Teaching: BMS, Gilead, Genentech, Vertex, Merck, Salix, Bayer

Daryl Lau - Advisory Committees or Review Panels: Gilead, BMS; Consulting: Roche; Grant/Research Support: Gilead, Merck

The following people have nothing to disclose: Ruosha Li


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Elevated prevalence of hepatitis B chronic infection and exposure in users of United States Veterans Medical Centers

Michael F. Chang1,2, Jason A. Dominitz3,4, George N. Ioannou3, Christopher W. Forsberg6, Edward J. Boyko7,8, Jennifer L. Sporleder5,6, Nicholas L. Smith6,8;
1Gastroenterology & Hepatol-ogy, OHSU / PVAMC, Portland, OR; 2Northwest Hepatitis C Resource Center, Portland VA Medical Center, Portland, OR; 3Divi-sion of Gastroenterology, Department of Medicine, VA Puget Sound Health Care System, Seattle, WA; 4National Program Director for Gastroenterology, VA Puget Sound Health Care System, Seattle, WA; 5Northwest Hepatitis C Resource Center, VA Puget Sound Health Care System, Seattle, WA; 6Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, WA; 7Department of Medicine, VA Puget Sound Health Care System, Seattle, WA; 8Department of Epidemiology, University of Washington, Seattle, WA

Purpose: To estimate the prevalence of active hepatitis B virus (HBV) infection and exposure and to evaluate factors associated with exposure among Veteran users of the United States Department of Veterans Affairs (VA) medical centers. Background: The prevalence of HBV infection and exposure in the general US population has been reported by the National Health and Nutrition Evaluation Survey (NHANES) from 1999-2008. The prevalence of HBV infection and exposure in men was reported as 0.38% (95%CI, 0.25%-0.50%) and 5.3% (95%CI, 4.7%-5.9%), respectively. The prevalence of HBV infection and exposure among Veteran users of the VA has not been previously reported from a large cross-sectional study. Methods: Study participants for the original VA Hepatitis C Prevalence Study (CSP #488) were randomly chosen from lists of all Veterans who received healthcare at least one time in a 3 year period amongst 20 randomly selected VA facilities (weighting based on size). 1,288 of 3,863 participants completed a survey and underwent phlebotomy; of this original cohort, 1,157 had sera available for evaluation. Administrative and clinical data were used to adjust the prevalence estimate for non-participation. HBV infection was defined by the presence of serum HBV surface antigen and exposure by the presence of HBV core antibody without surface antigen. Results: The participants were predominantly male (96.5%) and middle aged (3.5% were <35yo, 26.8% were 35-54yo, 50.2% were 55-74, and 1 9.4% were >75yo). Most participants were white (78.7% white, 10.6% black, 2.2% Asian/Pacific Islander, 6.3% other, 2.3% unknown) . The unadjusted prevalence of HBV infection and exposure was 0.6% (95% CI, 0.2 - 1.1%) and 1 3.1 % (95% CI, 1 1.1 %- 15.0%), respectively. After adjusting for non-response to study participation, the prevalence of HBV infection and exposure was 0.8% (95% CI, 0.1% - 1.4%) and 13.9% (95% CI, 1 1.6%- 16.3%), respectively. Significant predictors for HBV exposure included demographic factors (e.g. age, race), period of military service, prior diagnoses (e.g. cirrhosis), health care use, and lifestyle factors (e.g. drug use, number of sexual partners). Multivariate analysis adjusting for injection drug use and number of sexual partners showed being stationed in the US or Southern Europe was inversely associated with HBV exposure. Ever being in jail for at least 48 hours, being a health care worker, and military combat exposure were marginally associated with increased odds for HBV exposure. Conclusion: Compared to NHANES data from 1 999-2008, HBV infection and exposure among Veterans who have used VA facilities is more than twice the national prevalence.


Jason A. Dominitz- Employment: Department of Veterans Affairs; Grant/Research Support: Gilead Pharmaceuticals

The following people have nothing to disclose: Michael F. Chang, George N. Ioannou, Christopher W. Forsberg, Edward J. Boyko, Jennifer L. Sporleder, Nicholas L. Smith


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Safety of Tenofovir Disoproxil Fumarate (TDF) treatment for the entire pregnancy in mothers with active chronic hepatitis B or cirrhosis

Calvin Pan1, Min Liu2, Haodong Cai2, Wei Yi2;
1Division of Gas-troenterology and Hepatology, NYU Langone Medical Center, NYU School of Medicine, Flushing, NY; 2Ditan Hospital, Beijing, China

Background: Antiviral therapy may be used during pregnancy to control maternal disease. Data are lacking on TDF treatment throughout pregnancy in mothers with active chronic hepatitis B (CHB). We evaluate the safety and efficacy of TDF therapy in such mothers and their infant outcomes. Methods: We retrospectively enrolled CHB mothers who received TDF (300 mg/day) throughout their pregnancy between 1/2011-5/2013 and assessed mother-infant outcomes. All infants received appropriate immunoprophylaxis. Results: Among 48 mothers enrolled, 43 initiated TDF prior to pregnancy, and 5 were switched from nucleoside at the first trimester; 28 mother delivered 29 newborns (mean TDF fetal exposure 37.6±3.0 weeks), 3 experienced fetal loss at the first trimester (1 got pregnant again on TDF), and 1 8 had not reached full term yet. All subjects had active CHB (1 cirrhosis). The mean age was 30.7±3.2 years; 87.5% mothers were HBeAg positive, 93.8% mothers were nucleoside experience (39 lamivudine resistance; 3 telbivudine resistance). TDF was well tolerated with no viral rebound/breakthrough or alanine aminotransferase (ALT) flare during treatment. Three mothers (6.1%) had spontaneous abortion at the first trimester. Maternal and fetal adverse events are shown on Table 1. Most adverse events were mild in severity and considered unrelated to TDF. A higher percentage of mothers achieved HBV DNA <500 c/mL at delivery compared with those at the first trimester (96.4% [27/28] vs. 71.4% [20/28], respectively; p=0.578); the percentage of mothers with normal ALT also increased between the above two time points (100% [28/28] vs. 71.4% [20/28], respectively; p=0.514). None of the infants were born with obstetric complication or birth defects; however, one infant was diagnosed with a genetic mitochondrial respiratory chain enzyme compound 1 defect at the age of 5 months. Among the 28 infants (1 8 cesarean section), 14 were male, mean (SD) body weight 3237.6±374.2 g, mean (SD) height 49.9±1.5cm, all infants including 1 preterm had one minute Apgar score >9. Among the 19 infants that have since reached the age of 7 months, 1 8 were tested and all were HBsAg(-). Conclusions: TDF treatment for the entire pregnancy period is safe and well-tolerated in pregnant women with active CHB. A majority of mothers in this study maintained complete virological response with normalized ALT and none had antiviral resistance or signs of disease progression. There were no congenital abnormalities related to TDF nor HBV infection among their infants for up to 7 months of follow up.

Maternal adverse eventsn(%)Maternal complicationsn(%)Fetal adverse eventsn(%)
Nausea/vomiting Cough and fever Back pain Anemia3(10.7%) 1(3.6%) 1(3.6%) 5(17.9%)Hyperglycemia Arrhythmia Vaginitis Hypertension Postpartum hemorrhage3(10.7%) 3(10.7%) 3(10.7%) 1(3.6%) 1(3.6%)Pre-term labor Prolonged laboring Anterior placenta Meconiurn- stained II-III1(3.6%) 1(3.6%) 1(3.6%) 1(3.6%)


Calvin Pan - Advisory Committees or Review Panels: BMS, Gilead; Consulting: BMS, Gilead; Grant/Research Support: BMS, Gilead, Genentech; Speaking and Teaching: BMS, Gilead, Genentech, Onyx, Vertex

The following people have nothing to disclose: Min Liu, Haodong Cai, Wei Yi


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Comorbidity Burden of Chronic Hepatitis B in a Commercially-insured Population in the United States

Timothy Juday2, Stephen S. Johnston1, Kathleen Wilson1, Syed Quadri2;
1Truven Health Analytics, Bethesda, MD; 2Bristol-Myers Squibb, Plainsboro, NJ

Background: Published information on the prevalence of comor-bidities in chronic hepatitis B (CHB) patients is limited, but could inform development of optimal patient management strategies. This is the first study to systematically examine the prevalence rates of comorbidities (including CHB sequelae) among CHB patients and to examine how these rates differ from a matched cohort of patients without hepatitis B virus (HBV) infection. Methods: Retrospective, observational study using a large U.S. commercial insurance claims database. CHB patients met all of these criteria: continuous insurance enrollment in 2010 and 2011; aged 1 8-64 years as of 1 /1 /201 0; >1 medical claim with a diagnosis of CHB (ICD-9-CM 070.22, 070.23, 070.32 or 070.33) in 2010 or 201 1. A comparator cohort of patients without HBV diagnoses or treatment (oral antivirals, interferonα, and/or pegylated interferon-α) was matched directly (1:1 ratio) to the CHB patients on: age in years; sex; geographic region. The prevalence rates of comorbidities (including CHB sequelae) in 201 0 and 201 1 were measured using the Agency for Healthcare Research and Quality Clinical Classifications Software (CCS), which classifies the ICD-9-CM into 285 mutually-exclusive clinical categories (CCS conditions). Chi-squared tests were used to test for differences in the prevalence rates of CCS conditions between the CHB patients and comparators. Results: Study included 12,049 CHB patients and 12,049 comparators; mean age 45 years; 57.8% male. The 5 most prevalent CCS conditions among CHB patients were: disorders of lipid metabolism (27.1% among CHB patients), other connective tissue disease (26.9%), essential hypertension (25.9%), other and unspecified liver disorders (25.4%), and abdominal pain (23.3%). The CCS conditions that were associated with the largest differences between CHB patients and comparators were: cirrhosis of liver without mention of alcohol (7.2% among CHB patients, 0.2% among comparators; Odds Ratio=37.52, p<0.001), other and unspecified liver disorders (25.4% vs. 3.4%; OR=9.71, p<0.001), anemia [unspecified] (6.4% vs. 2.9%; OR=2.26, p<0.001), hemorrhoids (9.7% vs. 4.8%; OR=2.14, p<0.001) and abdominal pain (23.3% vs. 12.7%; OR=2.10, p<0.001). The prevalence rates of most CCS conditions increased substantially with age. The prevalence rates of many CCS conditions also varied significantly by whether or not patients had received CHB treatment. Conclusions: This large sample of commercially-insured CHB patients was characterized by a substantial comorbidity burden. Awareness and appropriate treatment of these conditions is critical to the optimal management of CHB patients.


Timothy Juday - Employment: Bristol-Myers Squibb; Stock Shareholder: Bristol-Myers Squibb

Stephen S. Johnston - Employment: Truven Health Analytics Kathleen Wilson - Employment: Truven Health Analytics

Syed Quadri - Employment: Bristol-Myers Squibb; Stock Shareholder: Bristol-Myers Squibb


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Reactivation of HBV infection in patients HBsAg nega-tive/HBcAb positive treated with chemotherapy containing or not Rituximab for lymphoma

Filomena Morisco1, Novella Pugliese2, Maria Guarino1, Matilde Rea1, Anna Vitiello1, Silvia Camera1, Marta Raimondo2, Nicola Caporaso1, Fabrizio Pane2, Marco Picardi2;
1Department of Clinical Medicine and Surgery, Gastroenterology Unit, Federico II University of Naples, Naples, Italy; 2Department of Clinical Medicine and Surgery, Haematology Unit, Federico II University of Naples, Naples, Italy

BACKGROUND and AIM: Hepatitis B reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases, with a high frequency of hepatic failure. Routine antiviral prophylaxis with Lamivudine is recommended for HBsAg+ subjects, while for patients showing HBsAg-/HBcAb+ virological pattern a definite consensus was not reached. Recent guidelines suggest a strict surveillance of transaminasis, HBsAg and HBV-DNA, especially during schedule of therapy containing monoclonal antibody (i.e., Rituximab). We conducted a study to evaluate the effects of cytotoxic chemotherapy containing or not Rituximab in patients HBsAg negative/HBcAb positive with Non Hodgkin Lymphoma (NHL) or Hodgkin Lymphoma (HL). METHODS: This is a retrospective observational study, including all consecutive patients with NHL and HL who attended an Italian tertiary referral hospital. A total of 123 patients were consecutively enrolled, 21 with NHL treated with R-CHOP or CHOP (R-CHOP/CHOP: 11/10) and 102 with HL treated with ABVD. We evaluated systematically serum HBV markers. HBV reactivation was defined as occurrence of HBsAg and HBV-DNA, with or without ALT elevation, during therapy and 6 months after. RESULTS: A total of 46 (37%) HBsAg negative patients (M/F 24/22, median age 49 yrs, range 21-74 yrs), 33 with isolated anti-HBc and 1 3 with anti-HBs/anti-HBc positivity, were observed at the University of Naples "Federico II". Six/46 were treated with therapeutic cytotoxic schedule containing Rituximab. Of them, 5/6 received successfully prophylaxis with Lamivudine (3 with isolated anti-HBc+ and 2 with positivity for anti-HBs/anti-HBc). HBV reactivation was observed in the only patient (anti-HBc+/anti-HBs+) treated with R-CHOP without Lamivudine prophylaxis. No one of the other 40 patients treated with cytotoxic chemotherapy without Rituximab (ABVD/CHOP: 32/8) and without receiving prophylaxis with Lamivudine, showed HBV reactivation. CONCLUSIONS: HBsAg negative/HBcAb positive patients (i.e., with a potential occult HBV infection) receiving chemotherapy containing Rituximab for lymphoma without antiviral prophylaxis are at risk of HBV reactivation. On the contrary, there is no risk of reactivation in patients undergoing Rituximab-free schedule, especially ABVD and CHOP regimens. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.


The following people have nothing to disclose: Filomena Morisco, Novella Pugliese, Maria Guarino, Matilde Rea, Anna Vitiello, Silvia Camera, Marta Raimondo, Nicola Caporaso, Fabrizio Pane, Marco Picardi


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Efficacy and safety of tenofovir in pregnancy to prevent Mother to Baby transmission of HBV

Astrid-Jane Greenup1, Pok Kern Tan1, Vi Nguyen1, Anne L. Glass1, Heidi L. Lord1, Ushmi Chatterjee2, Scott Davison1, Louise E. Smith1, Susan Holdaway3, Dev Samarasinghe3, Stephen Locarnini4, Miriam Levy1,2;
1Gastroenterology, Liverpool Hospital, Sydney, NSW, Australia; 2University of New South Wales, Sydney, NSW, Australia; 3Gastroenterology, Westmead Hospital, Sydney, NSW, Australia; 4Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia

Background:Oral antiviral use in pregnancy reduces perinatal transmission of Hepatitis B Virus(HBV)in mothers with high viral load.We have previously reported that lamivudine has lower potency and emergence of resistance even after short term therapy. Tenofovir may be more favourable,though data regarding use for HBV in pregnancy is limited.Concerns about tenofovir include impact on infant growth parameters from animal stud-ies.Aims of this study were to examine efficacy of tenofovir in reducing HBV maternal viral load compared to lamivudine, the effectiveness of tenofovir in reducing HBV perinatal transmission and maternal and fetal safety of tenofovir. Methods:In this multi-centre,prospective real life study,pregnant women with high viral load (>7 log IU/ml) were offered tenofovir,commencing at 32 weeks gestation.Virological responses,safety in pregnancy and neonatal data were collected.Perinatal transmission was assessed at 9 months of age.Data from 60 women commencing tenofovir was compared to an historical cohort of lamivudine treated(21 women)and untreated(9 women, including four in current study)mothers. Results:Median baseline viral load was 8.1 log IU/mL (+/- 0.23). 18 women had prior antiviral therapy (1 0 during prior pregnancies; 8 short duration therapy).Median baseline ALT was 27 U/L (range 6 -51 7).4 developed marked gastrointestinal intolerance within one week and were switched to lamivudine.Median duration of treatment prior to birth was 57 days. Median birth viral load (tested in 54 women) was 4.56 log IU/mL (+/- 0.31), a 3.6 log IU/mL drop.This was one log greater reduction than lamivudine.Viral load remained >7 log IU/mL at birth in 2 pregnancies,despite 3 log viral load reduction.This 4%(2/54)failure rate is significantly lower than observed lamivudine rate of 19% in our previously reported cohort (p=0.01; Fisher exact).All 61(2 consecutive pregnancies for one woman) tenofovir exposed babies were born alive.One delivered prematurely at 34 weeks.One had unilateral deafness considered unrelated.There were no other congenital abnormalities.Mean birth weight, length and head circumference were no different to historical controls.All 34 tested babies are HBsAg negative at 9 months;3 babies lost to follow up;one unable to be bled;one mother unwilling to consent and the remaining 21 babies younger than nine months. Conclusion:Tenofovir in this setting achieved better viral suppression than lamivudine.Rate of gastrointestinal intolerance was surprising.No perinatal transmission suggests efficacy of tenofovir when compared to expected rate in this high risk population.Infant growth parameters and congenital abnormality data were reassuring.


Stephen Locarnini - Consulting: Gilead, Bristol-Myers Squibb, Merck Sharpe and Dohme; Employment: Melbourne Health

Miriam Levy - Grant/Research Support: Gilead

The following people have nothing to disclose: Astrid-Jane Greenup, Pok Kern Tan, Vi Nguyen, Anne L. Glass, Heidi L. Lord, Ushmi Chatterjee, Scott Davison, Louise E. Smith, Susan Holdaway, Dev Samarasinghe


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HBeAg Status, Race and DNA levels in Women with Chronic Hepatitis B Infection

Tram T. Tran1, Stuart C. Gordon2, Scott Fung3, Phillip Dinh4, Leland J. Yee4, Eduardo B. Martins4, Maria Buti5, Patrick Marcellin6;
1Cedars-Sinai Medical Center, Los Angeles, CA; 2Henry Ford Health System, Detroit, MI; 3University of Toronto, Toronto, ON, Canada; 4Gilead Sciences, Foster City, CA; 5Hospital General Uni-versitari Vall d'Hebron, Barcelona, Spain; 6Hôpital Beaujon, University of Paris, Paris, France

Background: High mother-to-child-transmission of hepatitis B (HBV) has been associated with HBeAg positivity and high HBV DNA levels. The relationship of age, genotype and HBV DNA and HBeAg status has not been fully elucidated. Methods: Subjects screened for tenofovir disoproxil fumarate (TDF) pivotal studies GS-US-174-01 02 and GS-US-174-0103 were assessed for gender, race (Asian vs. non-Asian), age, ALT, and HBeAg status. Standard descriptive statistics and logistic regression were used to explore the association of race, age, HBV DNA with HBeAg status. Results: Overall, 355 female subjects were included in this analysis using data available at screening. The average age was 41 years old, median ALT was 69 U/L (range 8 to 806), average HBV DNA was 7.0 log10 copies/mL (range 2.2 to 10.2), 44.4% of the subjects were HBeAg+, 40.0% were Asians and 49.6% were Caucasians. HBV genotypes were available on 167/355 subjects: 21 (12.6%) A, 21 (12.6%)B, 39 (23.4%) C, 82 (49.1%) D, 3 (1.8%) E, and 1 (0.6%) H. Women 35 and under are more likely to be HBeAg+ than HBeAg- (odds ratio (OR) = 4.2, 95% confidence interval (CI): 2.7 - 6.6, p < 0.001) and to have HBV DNA >= 9 log copies/mL than < 9 log copies/mL (OR = 6.0, CI: 3.1 - 11.8, p < 0.001). Asian women are more likely to be HBeAg+ than HBeAg-(OR = 2.8, CI: 1.8-4.4, p< 0.001). Among women <= 35 years old (N = 135), Asians are also more likely to be HBeAg+ than HBeAg-(OR = 3.9, CI: 1.7-9.1, p = 0.001). Compared to genotype B/C, women with genotype A/D were more likely to be HBeAg negative (OR=4.2, CI: 2.1 - 8.2; p < 0.001). No difference in ALT was observed. Conclusions: In this large cohort of HBV patients, women under 35 had a significantly higher likelihood of HBeAg positivity and high HBV viral load. Asian women and those with genotypes B/C are also more likely to be HBeAg+ compared to non-Asians and those with genotypes A/D, respectively. These results suggest higher risk of HBV perinatal transmission in these groups.

Table 3. Logistic regression analysis of associations between age <=35 years vs > 35 years and characteristics among female subjects.
CharacteristicMultivariate OR* (95% C.I.)p-value
  1. *Multivariable regression model uses a forward selection model with selection criteria of 0.10.

ALT at screening <= 2x ULN vs > 2x ULN1.21(0.75-1.95)0.4449
HBV DNA at screening >= 91og cp/mL vs <9 log cp/mL3.46(1.66-7.19)0.0009
HBeAg at screening positive vs. negative3.21 (1.95-5.26)<0.0001


Tram T. Tran - Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb, Vertex; Consulting: Gilead; Grant/Research Support: Bristol Myers Squibb; Speaking and Teaching: Bristol Myers Squibb, Gilead, Vertex

Stuart C. Gordon - Advisory Committees or Review Panels: Tibotec; Consulting: Merck, CVS Caremark, Gilead Sciences, BMS; Grant/Research Support: Roche/Genentech, Merck, Vertex Pharmaceuticals, Gilead Sciences, BMS, Abbott, Intercept Pharmaceuticals, Exalenz Sciences, Inc.

Scott Fung - Advisory Committees or Review Panels: Gilead Sciences, Vertex; Grant/Research Support: Merck, Roche; Speaking and Teaching: BMS, Gilead

Phillip Dinh - Employment: Gilead Sciences

Leland J. Yee - Employment: Gilead Science

Eduardo B. Martins - Employment: Gilead Sciences, Inc.; Stock Shareholder: Gilead Sciences, Inc.

Maria Buti - Advisory Committees or Review Panels: Gilead, Janssen, Vertex; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead, Janssen, Vertex, Novartis

Patrick Marcellin - Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen-Tibotec, MSD, Boehringer, Pfizer, Abbott, Alios BioPharma; Grant/Research Support: Roche, Gilead, BMS, Novartis, Janssen-Tibotec, MSD, Alios BioPharma; Speaking and Teaching: Roche, Gilead, BMS, Vertex, Novartis, Janssen-Tibotec, MSD, Abbott