The cascade of care for patients with chronic hepatitis delta in Southern Stockholm, Sweden for the past 30 years

Previous studies have shown suboptimal screening for hepatitis D virus (HDV) among patients with chronic hepatitis B (CHB). This study presents the cascade of care for HDV infection in a major secondary referral centre in Southern Stockholm, Sweden.


| INTRODUC TI ON
The World Health Organization (WHO) aims by 2030 for a 90% reduction of new viral hepatitis infections and a 65% reduction of mortality from baseline 2015. 1 These goals are set by the WHO to eliminate chronic viral hepatitis; a public health burden afflicting more than 350 million persons. 1 Barriers in the viral hepatitis cascade of care are one of the important challenges to reaching this elimination goal. 1 Hepatitis D virus (HDV) discovered in 1977, 2 causes a rare form of viral hepatitis; chronic hepatitis D (CHD) which is associated, with more severe disease with accelerated progression to cirrhosis and higher risks for hepatocellular carcinoma (HCC). 3patitis D virus (HDV) requires hepatitis B virus (HBV) surface proteins for packing, release and transmission. 4Recently, new estimates have shown that the prevalence of HDV is around 12.0 (95% confidence interval CI 8.7-18.7) million infected persons worldwide, with remaining uncertainty about these numbers. 5is is due to fragmented primary data, lack of standardized HDV RNA tests and underdiagnosis of CHD among persons with chronic hepatitis B (CHB) due to deficient awareness by many physicians. 6The international recommendations are convergent regarding whom to screen for HDV.The European Association for the Study of the Liver (EASL) and the Asian-Pacific Association for the Study of the Liver (APASL) recommend screening all HBsAgpositive individuals for HDV. 7,8In contrast, the American-and Canadian Associations for the Study of Liver Diseases (AASLD and CASL) recommend to target HDV screening to those HBsAgpositive persons which are at 'high risk' of infection, which involves further inquiries about area of origin, social and medical history. 9,10[13] Sweden is a low-endemic country for CHB or CHD, with an estimated prevalence of 0.37% and 0.01%, respectively. 14The majority of persons with CHB are currently immigrants from high-endemic countries, which is a shift from previous risk groups that consisted of people who inject drugs (PWIDs). 15As linkage to care and access to treatment considerably vary across countries, it is important to assess the efforts and barriers to screening in different settings to fulfil the WHO viral hepatitis elimination plan. 1 Therefore, we aimed to analyse the cascade of care and presentation of persons with CHD at Karolinska University Hospital (KUH), Sweden during the last three decades, that is from the 1990s to the 2020s.This is a major secondary referral facility in the Southern Stockholm region for diagnosed patients with CHB/CHD.We evaluated the risk factors associated with deficient HDV screening, the time to HDV screening, treatment uptake and if these factors had an association with liver-related outcomes.

| Patient cohort
This is a retrospective cohort study of all patients with the diagnosis of HBsAg-positive CHB, who have attended the Department of Infectious Diseases, Karolinska University Hospital (KUH), Sweden since 1992.This department is the Nordic countries' largest outpatient clinic for patients with infectious diseases, with viral hepatitis being one of the most common diagnoses.This is a secondary referral centre for all patients diagnosed with HBsAg positivity in Southern Stockholm of Sweden, with referrals from primary care and other healthcare units.It is estimated that 26.3% of all patients with HBV diagnoses and 53.3% of those with HDV diagnoses in Sweden are notified in the Stockholm region, according to our calculation based on publicly available data from the Public Health Agency of Sweden (data not shown). 14database of all HBsAg-positive patients at this department was set up in the year 1992 (n = 199), in conjunction with moving the department from Roslagstull Hospital to KUH that year.All patients with positive HBsAg attending this department since then have been consecutively included in this cohort, through the collection of records to a database, since 2008 to the quality and research register of InfCare Hepatitis.This register has nationwide coverage of data from patients with viral hepatitis, and the records of the mentioned database were transferred to this register in 2008.16 This present cohort includes patients with CHB diagnosis from 1970s until 31 October 2022.

| Data collection and follow-up
We collected data from the InfCare Hepatitis register and completed data if needed from the patient's medical records.Patients'

Key points
We studied the cascade of care for hepatitis D virus (HDV) infection at Karolinska University Hospital in Sweden, for the last 30 years.This showed that 90.4% of 4095 persons with chronic hepatitis B received an anti-HDV test, and 64.0% of patients received a screening test in <1 year.
• Patients with HIV co-infection were more likely to experience a delay in screening than patients with HBV mono-infection.
• Delayed screening for anti-HDV tests might be associated with a liver-related outcome in persons with positive HDV RNA.demographics at HBV diagnosis (baseline) included age, sex and region of origin categorized as Europe, Africa, Asia (Southeast and Western Pacific), Eastern Mediterranean and South/North Americas per WHO regional nomenclature. 17Detailed methods of data collection and parameters are in the supplement.
Liver-related outcomes were defined as the occurrence of HCC, any decompensation event, liver transplantation and/or liver-related death from baseline to the end of the study designated to October 31st, 2022.

| Assessing cascade of care
We assessed if an anti-HDV screening test has been performed in patients with positive HBsAg, and if a subsequent HDV RNA measurement was performed if the anti-HDV test was positive.
The time duration from the diagnosis of HBsAg positivity to an anti-HDV test was also analysed.The baseline refers to the time of the first positive HBsAg date.Baseline data were collected at the date of positive HBsAg positivity or within 6 months from this date.In persons with anti-HDV positivity having an anti-HDV test >6 months after the HBsAg test, data were collected at the date of the anti-HDV positive test or within 6 months from this date.
Assessment of liver fibrosis stage was performed, using metaanalysis of histological data in viral hepatitis (METAVIR) score in patients with available liver biopsy and/or liver stiffness measurement with transient elastography (Fibroscan) with the collection of the median values in measurements having an IQR <30% and success rate ≥60%.Significant fibrosis ≥F2 was defined as METAVIR fibrosis stage ≥2 at liver biopsy or a median liver stiffness value ≥7.2 kPa.Cirrhosis was defined as either METAVIR F4 in liver biopsy, liver stiffness ≥12.5 kPa, or per the discretion of the treating physician at the healthcare visit due to clinical signs of liver cirrhosis and/or radiological signs of cirrhosis.We then assessed the percentage of HDV RNA-positive patients who had received antiviral therapy against HDV, that is interferon (IFN) therapy and whether they have achieved a maintained virological response (MVR) defined as a negative HDV RNA test at least 6 months after treatment ends and at the last follow-up visit.

| Analyses of virological parameters
Anti-HDV-, anti-HCV-and anti-HIV antibodies were detected by commercial enzyme immunoassays at the laboratory of KUH.For the detection of HDV RNA, before 1996 hybridization assays were used at KUH.The quantitative nested in-house polymerase chain reaction (PCR) method replaced this method with the lower limit of detection (LLoD) of 2-log 10 copies/mL in 1996.Since 2017, most samples were quantified by quantitative real-time PCR (qPCR) using the RoboGene quantification kit 2.0 (AnalytikJena) with LLoD of 6 IU/mL.Logistic regression analysis generating odds ratio (OR) with 95% confidence intervals (CI) was used to test the association of variables such as age, sex, area of origin (Asian vs. non-Asian), HCV, HIV co-infection, any known route of transmission, virological (HBeAg positive/negative, low or undetected HBV DNA defined as <2000 IU/ mL), cirrhosis diagnosis and the time of receiving an HBV diagnosis as well as the speed of receiving a screening test (<2 years vs.

| Statistical analysis
2-5 years, ≥5 years).The choice of a minimum of 2 years as cut-off was due to prior studies describing the fast progression to cirrhosis and liver-related complications as early as 2 years in persons with positive anti-HDV. 18The mentioned parameters were examined in association with receiving an HDV screening, an anti-HDV positive test and developing any liver-related event.We considered AASLD criteria, by adding origin from an endemic region, concomitant HIV and HCV co-infections, elevated ALT values and low or undetected HBV DNA defined as <2000 IU/mL in a separate variable. 9We performed also a sensitivity analysis by including only persons with new HBV diagnoses from the year 1992 (the year when the register started), to adjust for potential survival bias of selecting those with slow disease progression for inclusion in the study.Statistical significance was considered when p-values <.05.All analyses were executed using IBM SPSS Statistics, version 28.0.1.1,and data handling, and figures were done with Microsoft Excel.

| Patient characteristics
An overall of 4095 unique patients with positive HBsAg were identified from 1970 to October 31st, 2022, among which 3703 (90.4%) had been screened for anti-HDV.Among the tested individuals, 310 (8.4%) received a positive anti-HDV result.
(Figure 1) The baseline characteristics of persons with positive HBsAg are shown in Table 1.Age and sex distribution were similar between screened and unscreened individuals, but the latter 392 (9.6%) had been diagnosed with HBV in the earlier time period (the median year of HBV diagnosis was 2004, 50% were diagnosed before 2005 compared to the median year of HDV diagnosis 2013 in those screened, p < .001).Persons of Asian origin constituted a majority of the CHB cohort (1934, 47.2%) followed by patients of African origin (965, 23.6%).Unscreened patients for HDV had more prevalent HIV, more often reported a known route of transmission and had less prevalent criteria for screening (per AASLD).
(All p < .001)Cirrhosis diagnosis was similar between screened and unscreened persons (p = .22),though the APRI score was higher in unscreened persons (p = .004).

| Hepatitis D virus cascade care
Among patients with a positive anti-HDV test, 202 (65.2%) had HDV RNA positivity, 99 (31.9%) had undetectable HDV RNA, and 9 (2.9%) had not been tested for HDV RNA status.In patients with HDV RNA positivity, 55.4% (67/121) had scores of BEA-A, 40.5%  ).In all persons with CHB, the prevalence of persons with positive anti-HDV antibody test was 8.4% (p = .03).Persons with CHD, that is with HDV RNA replication, constituted 5.5% of all tested patients with HBsAg positivity (Figure S1).
The characteristics of patients who were anti-HDV negative or positive are presented in Table 2.Those with a positive anti-HDV test (n = 310, 8.4%) were older at HBV diagnosis, more frequently from Asia, had more prevalent HCV co-infection and had higher serum ALT, AST values and lower platelets count, lower HBV DNA level and higher fibrosis parameters compared to peers who were anti-HDV negative (all p-values ≤ .001).The baseline characteristics of patients with positive HDV RNA replication is shown in Table S1.The baseline characteristics of persons by time to screening (before vs. after 2 years of HBV diagnosis) are shown in Table S2.
Almost two-thirds (n = 2513, 67.9%) received a screening test in a median of 0.72 months (IQR, 0.0-1.9).Persons receiving a screening test within 2 years were older, with more male preponderance, more likely diagnosed after 2005, with higher APRI >1.5, lower serum albumin level and more frequent negative HBeAg.Notably, HIV co-infection was more frequent in persons with late screening.(Table S2).
The proportion of patients with cirrhosis at first presentation is presented in Figure 3, where cirrhosis was consistently more prev-  S3).Of note, 15.6% to 22.0% of patients did not have a recorded possible route of transmission.

| Factors associated with received anti-HDV screening test
The logistic regression analyses are shown in

| DISCUSS ION
[13] A Spanish study described an overall screening frequency of 7.6% in HBsAg-positive individuals, with only 2% screening performed in primary care versus 23% in referral hospitals. 192][13] In a recent Greek study from tertiary liver centres, HDV screening was more frequently performed in small centres, Northern Greece and at more recent patient visits, with overall 53% HDV screening prevalence. 20A prior Greek study reported a decreasing frequency of HDV testing, falling from 57.0% before 2003, to 35.3% thereafter until year 2010. 21w frequency of HDV screening has been also noted in people living with HIV (PLHIV) and HBV, 13,22 where only 58.4% (n = 52/89) underwent at least one anti-HDV test in an Austrian study enrolling 1870 PLHIV. 23Patients with anti-HDV positivity lacked in 60% of cases a known risk factor of transmission in a Spanish study, and 18% did not meet any of the AASLD criteria in a US study. 13,19The  .001* 0.99 (0.98-1.01) .11 Men versus women  In Europe, the prevalence of HDV is currently around 3.0% (2.1-4.2) among CHB carriers. 5Figures of HDV prevalence are swaying in Western and Eastern European hospital-based cohorts from 8.5% to 23%, respectively. 24,25In our study, anti-HDV was prevalent in 8.4% of persons with CHB, and overall, 5.5% had chronic HDV infection agreeing with estimates from similar levels of care from Spain (8%), 19 and Germany (5%-8%). 26and in a Romanian study where 92.8% of the cohort was native women residing in urban regions. 25e difference observed in patients with CHD demographics might reflect regional distinctions of immigration patterns in host countries as well as local cohorts of patients surviving old infections and patients at high risk of blood-borne infections such as PWID.
In our study, the prevalence of HIV and HCV co-infection among persons with anti-HDV positivity was 11% and 2.6%, respectively.In the Swiss HIV cohort, HDV infection was prevalent in 15.2% (95% CI 13.5-17.1) of persons with HBV/HIV co-infection; associated with a higher risk of developing HCC and liver-related mortality. 31Our data suggesting that PLHIV were less likely to undergo an anti-HDV test, might be in line with several reports of suboptimal screening for HDV among PLHIV with HBV co-infection in Europe.A cross-sectional Italian study described that 44/316 (13.9%) were not screened for HDV infection, and among those with positive anti-HDV test (n = 48), 7 (15%) were not tested for HDV RNA. 32Analysis of a nationwide prospective cohort of PLHIV (ICONA cohort), 61% had not been screened for HDV and with decreasing frequency of screening from 1997 to 2015. 33In an Austrian study, 58.4% of PLHIV with HBV co-infection were not screened for HDV. 23Importantly in this study 4.9% of HBV vaccinated PLHIV acquired de-novo HBV infection during a median of 6.5 years follow-up, highlighting the challenges for HBV and HDV screening in the PLHIV population. 23While different liver societies recommend screening persons with HBV/HDV for HIV co-infection, the reciprocal recommendation in HIV societies might not be enough emphasized. 34Changes in screening practices across different disciplines of care have been demonstrated (primary care and gastroenterology care) 19 and possibly might reflect a low awareness of HDV as the least common among chronic hepatides.In our cohort, 95% of patients with anti-HDV positivity met the AASLD criteria, although 43% of them reported a known route of transmission. 9Published data show that the probability of getting a screening test is strongly associated with the existence of a reflex screening policy (automated screening for HDV when HBV is diagnosed), 19 a specialized level of care possibly leading to more awareness, compared to risk-based screening which may be susceptible to recall bias. 13Our data also suggests that the HDV screening rate was A marked improvement in screening frequency reaching ~99.5% of HBsAg-positive samples could be seen when adopting reflex screening. 19,22e increased risk of HCC in CHD, regardless of ongoing HBV DNA suppressive NA therapies, further call for comprehensive anti-HDV screening. 35,36Also, early treatment of CHD before reaching advanced disease stage may lead to better long-term outcomes. 37is also considering the availability of the recent conditionally approved bulevirtide therapy in the European Union and other upcoming agents. 38Multiple studies showed that developing a liver-related complication correlated with the histological stage of liver disease at baseline. 39,40The beneficial effect of maintained virological response was more pronounced in patients with less advanced liver disease in an analysis of 99 patients with CHD receiving IFN therapy. 40Early treatment before cirrhosis stage has also been associated with favourable clinical courses in other previous studies. 39,41 this study, a high rate of anti-HDV testing was reached in the last decade despite a lack of reflex screening.In the Stockholm region, there is unfortunately an economical barrier introducing reflex testing for anti-HDV.This since the primary HBsAg tests are usually performed in primary care or other contexts as, for example screening before surgery or in pregnant women, while the responsibility to test Continuous variables were presented as mean (standard deviation, SD) when normally distributed and median (IQR, interquartile range) when skewed.Student t-test and Mann-Whitney test were used for the comparison of normal and skewed continuous variables, respectively.Categorical variables were presented as frequencies (numbers) and proportions and were compared using the Chi-Square test or Fisher's exact test, whenever appropriate.The date of the first HBsAg-positive test is considered the baseline for this study.The frequency of HDV testing was assessed across all years, before 2000 and per 5 calendar-year increments and in relation to time of anti-HDV screening (categorized as from HBsAg-positive test <6 months, 6-12 months, 12 months −2 years, 2-5 years and >5 years).

(
49/121) patients BEA-B and 4.1% (5/121) BEA-C at baseline.Among 85 (42.1%) patients who were treated with IFN therapy, 68 (80%) had ≥48 weeks of therapy and 9 (10.6%)patients had an MVR at the last visit.Nineteen (9.4%) patients enrolled in clinical trials for investigational HDV agents were censored at the time of trial entry.Hundred-three (50.9%) patients received nucleos(t)ide analogue (NA) therapy against HBV.The prevalence of HDV screening for persons with HBV diagnosis before the year 2000 was 80.9% and for those diagnosed from 2000 to 2005 was 78.6%.From the year 2005, an increase in the prevalence of screened persons with CHB could be noted with 83.4% screened in 2005 to 2010, 94.5% from 2010 to 2015 and 97.5% from 2015 onwards (Figure 2).Persons diagnosed with HBsAg positivity after 2005 were more likely to undergo a screening test <2 years after HBsAg positivity compared to those diagnosed before 2005 (crude OR = 41.8, 95% CI 31.9-54.7)(Result not shown in Table

F I G U R E 1
Cascade of care for patients with HDV infection.HBsAg, hepatitis B surface antigen; HDV, hepatitis Delta virus; IFN, interferon; MVR, maintained virological response defined as negative HDV RNA at 6 months post treatment end and the last follow-up.xaxis represents the cascade of tests/treatment; y-axis represents the number of patients.TA B L E 1 Baseline characteristics of patients diagnosed with positive HBsAg grouped by ever receiving an anti-HDV screening test.
Patients with HDV RNA positivity (n = 202) were significantly younger at HDV screening (mean age = 38.4 vs. 41.9 years, p = .02)compared to those with HDV RNA negativity.The former group had significantly higher serum AST (p = .01)or ALT levels (p = .02),lower albumin levels (p = .02),higher liver stiffness values (p ≤ .001),APRI (p = .003)and FIB-4 scores (p = .04),more frequent cirrhosis at the time of HDV diagnosis (p ≤ .001).The majority of anti-HDV positive individuals had an HDV screening test less than one year from HBV diagnosis regardless of HDV RNA positivity (79.7% in HDV RNA positive vs. 75% in HDV RNA negative or unknown) with significantly shorter time to screening in HDV RNA-positive group (median 0.93 months vs. 1.5 months, p = .02).
Figure S2.Before the year 2000 and from 2000 to 2010, persons with HBV mono-infection tended to be younger at diagnosis (median age = 21.8 before 2000) compared to persons with anti-HDV

F I G U R E 2 2
(A) Prevalence of HDV screening among patients with HBV diagnosis stratified by years of diagnosis.Clustered columns plot presenting the prevalence of ever HDV screening in patients with positive HBsAg by year of diagnosis.A high frequency of screening (>90%) could be seen from year 2010.The linear trend of the those screened in in dashed line.x-axis represents years of screening by subgroups; y-axis represents number of patients; HBV, hepatitis B virus; HDV, hepatitis D virus.(B) Time from HBsAg test to anti-HDV screening subgrouped by year of HBV diagnosis.Stacked bar plot presenting the prevalence (%) of anti-HDV screening by time to test in relation to years of HBV diagnosis.A successive increase in getting a screening test <6 months (dots pattern) could be seen from year 2000-2005 onwards.x-axis shows patients with positive HBsAg who underwent a screening test, subgrouped by time of HBV diagnosis; y-axis represents the prevalence of screening in percentage.with positive HBsAg (n=3703) by time to screening anti-HDV test Baseline characteristics of patients diagnosed with positive HBsAg who underwent at least one screening test for HDV grouped into anti-HDV negative and positive.
decade.The time to anti-HDV screening from HBsAg-positive test did also improve over the three decades.The treatment-and virological response rates on long-term were low, reflecting the poor availability of potent antiviral therapy against HDV.The delayed anti-HDV screening was independently associated with worsened liver-related outcomes, suggesting that timely anti-HDV screening and diagnosis are important.

F I G U R E 3
Temporal changes of cirrhosis prevalence in patients with positive anti-HDV and those with detected HDV RNA at time of HDV screening.Prevalence of cirrhosis at HDV diagnosis was higher in patients with HDV RNA positivity compared to all patients with positive anti-HDV.x-axis shows overall patients with positive anti-HDV and then chronologically by time of anti-HDV test; y-axis represents the prevalence of patients in percentage.
Abbreviations: ALT, alanine aminotransferase; APRI, AST to Platelet Ratio = AST(/ULN)/platelet (10 9 /L) × 100; AST, aspartate aminotransferase; FIB-4, age(yr) × AST(U/L)/(platelets[10 9  /L] × (ALT[U/L]) 1/2 ; numbers are rounded to the 10th decimal; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis Delta virus; HIV, human immunodeficiency virus; IQR, interquartile range; SD, standard deviation.a Eastern Mediterranean, includes countries from Europe, Asian and Africa (not added to the total number per region).bPer American Association for the Study of the Liver eligible criteria for screening including history of blood transfusion or exposure to blood products, family member with HBV infection, possible sexual contact, intravenous drug use.c Available in 154 patients.d All values are within 3 months of HDV diagnosis; * = values within 6-12 months of diagnosis including corresponding values of persons who undergone liver biopsy.
high rate of HDV screening in our study could be attributed to the coordinated standard routine of care for newly diagnosed persons with HBV infection referred to KUH.The first patient visit involves meeting a nurse for information on CHB, identification of possible transmission routes and contact tracing.The nurse staff also manages HBV vaccination for close contacts and blood tests including liver function, serological tests for HAV, HCV, HIV and HDV and virological tests of HBsAg and HBV DNA level.A baseline liver stiffness measurement is then performed.At the next visit to the unit, a physician will assess the laboratory-and liver stiffness results for evaluation of treatment eligibility and management of patients' liver disease.At this visit, a further test of HDV RNA quantification is offered to those with positive anti-HDV tests.A translator is present at the visits if needed.
unchanged (around 97.5% of HBV diagnoses) during the COVID-19 pandemic in the years 2020 and onwards, compared to the period 2015 to 2020.Yet, an overall decrease in the incidence of new HBV diagnoses from 1113 patients in 2015-2020 to 390 patients in 2020 onwards can be attributed to restrictions on travel owing to the pandemic and possibly different immigration policies in Sweden.
for HDV is allocated to the department of Infectious Diseases with different budgets for the tests.A high rate of anti-HDV screening was, however, reached without double-reflex testing, with a robust standard routine of CHB care with testing for HDV infection at a specialized hepatitis centre.Double-reflex testing may though be generally recommended, considering the overall low rate of anti-HDV testing in other settings.The main limitations of our study are the underreporting/missing data on risk factors among patients with HBV at diagnosis and not assessing loss to follow-up in unscreened persons.Also, we could not rule out other confounders or barriers that might affect testing or commitment to care such as concomitant co-morbidities, level of education, language barriers and/or migration status, especially in patients with absent or remote testing.Our strength is that we have included all patients who have attended our unit during the last three decades with low selection bias.We could assess the total cascade of care for HDV-infected patients, with temporal changes during this long period of inclusion and follow-up.In conclusion, we present a high rate of screening for HDV reaching 95%, one in five persons with CHD with advanced fibrosis at HBV diagnosis received a late screening (after more than 2 years), and 8% of persons meeting AASLD screening criteria did not receive an anti-HDV antibody test.PLHIV were less likely to be tested.This might suggest that adopting double-reflex screening of persons with positive HBsAg might capture a population of patients with advanced fibrosis, where early treatment intervention is important to modify the disease course.

proportions per column All HBsAg-positive HDV-tested No HDV-tested p-value
Eastern Mediterranean includes countries from Europe, Asian and Africa (not added to the total number per region).Per American Association for the Study of the Liver eligible criteria for screening including history of blood transfusion or exposure to blood products, family member with HBV infection, possible sexual contact, intravenous drug use.* = values within 6-12 months of diagnosis including corresponding values of persons who undergone liver biopsy.
a b c Available in 154 patients.TA B L E 1 (Continued) developed HCC, 15 underwent liver transplantation, and 3 died of a liver-related cause.Univariable logistic regression analyses in Table 4 showed that in patients with CHD (n = 202), older age at HDV diagnosis, cirrhosis, IFN exposure as well as receiving an HDV screening test more than 5 years of HBV diagnosis were associated with the development of liver-related outcomes.Delayed screening testing pared to those with testing less than 2 years.In multivariable analyses, significant parameters were baseline cirrhosis (aOR = 34.00,95% CI 10.94-105.66),older age (aOR = 1.04, 95% CI 1.00-1.08)and receiving a screening test more than 5 years from HBV diagnosis which was associated with 7.58-times the odds of developing any liver outcome (aOR = 7.58, 95% CI 1.82-31.58).

24 (3.16-26.99)
Tested in 3703 who underwent at least one anti-HDV ab screening test.*Variableswhich were significant in univariable model, were introduced in multivariable model. b 13

Univariable Multivariable Odds ratio, 95% CI p-value Odds ratio, 95% CI p-value
Logistic regression analysis of variables associated with developing any liver-related event defined as HCC, decompensation event, liver transplantation and/or liver-related death (n = 53) in patients with HDV RNA replication (n = 202).In multivariable models, significant adjusted odds ratio are shown in bold.
TA B L E 4Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis D virus; HIV, human immunodeficiency virus; IFN, interferon; OR, odds ratio.*Variables which were significant in univariable model, were introduced in a multivariable model for adjusted odds ratio.