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Summary

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Background

Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans.

Aim

To perform a systematic review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics and response to anti-viral therapy of Asians with CHC.

Methods

Using a PubMed search of ‘hepatitis C’ and ‘Asia,’ 341 original manuscripts published in peer-reviewed journals were identified, and 99 were selected based on their relevance.

Results

Many Asian CHC patients do not have easily identifiable risk factors and may be underdiagnosed. Rates of HCV infection in Asians on community screening in the US are unexpectedly high, and there is a high prevalence of HCV genotype 6 in Southeast Asia and Southern China. HCV-infected Asians tend to present at older age and may have higher risk of HCC; however, they respond better to anti-viral therapy than non-Asians across all HCV genotypes.

Conclusions

Given the high HCV endemicity in Asia, lack of identifiable risk factors and favourable treatment response rates in Asians, we advocate the screening for HCV infection of all Asians who come from areas where HCV prevalence is ≥2%.


Background

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific (62.3 million) and Southeast Asia (32.3 million) regions.[1] This striking number may be an underestimation as 14 countries in these two World Health Organization (WHO) regions, which encompass the Asian continent, have data that are either lacking or unavailable. Chronic hepatitis C (CHC) is a significant risk factor for both the development of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC), solely responsible for an estimated attributable fraction of 14–62% and 18–66% of cases in the aforementioned WHO regions respectively.[2]

With the exception of Japan where the problem is far more recognised, CHC is an understudied and underappreciated health problem in many Asian countries, perhaps overshadowed by the more prevalent chronic hepatitis B. However, with an estimated prevalence of 3.2%, the projected total number of 39.2 million persons chronically infected in China alone outnumbers those in North America, South America and all of Europe combined (22 million).[3, 4]

In the United States, immigrants from the Asian continent are among the fastest growing ethnic groups with 15.6 million people and rising.[5] Here, 1.3% of the general population or 3.2 million people are chronically infected with HCV, and CHC is responsible for 40–60% of chronic liver disease cases and is the 12th leading cause of death.[6-8] Cirrhosis due to CHC is the most common indication for orthotopic liver transplantation (OLT) in the US.[9]

Aim

The purpose of this synopsis was to perform a systematic and comprehensive review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics, current standard of care and response to treatment of Asians with CHC.

Methods

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Using a PubMed search of ‘hepatitis C’ and ‘Asia,’ 341 original manuscripts published in peer-reviewed journals were identified and reviewed, and 99 were selected based on their relevance. The references of pertinent manuscripts were also reviewed and included where appropriate with no limitations on study date.

Results

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Epidemiology

Prevalence. Several observational studies based in Asia reveal an increase in HCV prevalence with age, potentially due to more recent and improved screening of blood products and adoption of safer injection practices.[10-12] Later age of detection has also been associated with poorer treatment adherence, worsened treatment response and increased risk for HCC.[13, 14]

The increasing incidence of HCC in many countries in recent decades is likely attributable to the increase in HCV-related HCC.[10, 15] In Japan, where HCC rates have more than tripled over the last 40 years, HCV is partially or fully implicated in 70% of cases. In Taiwan, where universal hepatitis B virus (HBV) vaccination has caused dramatic decreases in childhood HCC since implementation in 1984, the decrease in adults has not been as stark as anticipated and could be partly due to HCV.[16, 17]

As with HBV, HCV prevalence (Table 1 and Figure 1) and HCV genotype distribution (Table 2) differ among Asian subgroups and countries of origin, and each will be discussed below.[18-21] Favourable HCV genotype predicts for improved anti-viral treatment response and merits a separate discussion later in this synopsis.

Table 1. Prevalence of hepatitis C virus in Asia
CountryAuthorYearPrevalence (%) n Population
East Asia
Mainland ChinaXia[4] 19963.266 975Community
Hong KongLeung[12] 20060.0842 313Blood donors
TaiwanChen[42] 20074.4157 720Community
South Asia
IndiaChowdhury[64] 20030.873579Community
PakistanKhokhar[66] 20045.3147 538Healthy adult volunteers
JapanTanaka[49] 20040.493 485 648Blood donors
KoreaShin[50] 20061.3124 605Meta-analysis
Southeast Asia
CambodiaAkkarathamrongsin[69] 20112.31431Healthy adult volunteers
IndonesiaSulaiman[75] 19952.17572Blood donors
LaosJutavijittum[77] 20071.113 897Blood donors
MyanmarMyo-Khin[79] 20100.9565 240Blood donors
PhilippinesYanase[74] 20070.474 180Blood donors
SingaporeWang[84] 19950.3765 208Blood donors
ThailandSunanchaikarn[85] 20072.25825Healthy adult volunteers
VietnamWHO[97] 2011<6.1NAMeta-analysis
Table 2. Prevalence of hepatitis C virus genotype in Asia
CountryPredominant genotypes (% range)References
East Asia
Mainland China1b (42–68%), 2a (10–15%) [98-103]
Hong Kong1b (61%), 6a (27%) [105]
Taiwan1b (46–77%), 2a/2c (31–65%) [253, 254]
South Asia
India3 (62–80%) [49, 50, 57, 110-121]
Pakistan3 (79%), 1(7%) [119]
Japan1b (<85%) [48, 120-122]
Korea1b (40%), 2a (40%) [123-126]
Southeast Asia
Cambodia6 (56%), 1 (24%), 3 (20%) [69]
Indonesia1 (58–74%), 3 (11–15%), 2 (4–17%) [133-135]
Laos6 (<96%) [127, 128]
Myanmar6 (21–49%), 3 (39–60%), 1 (11–31%) [69, 80, 82]
Philippines1 (73–82%), 2 (9–26%) [73, 137]
Singapore1 (43%), 2 (17%) [83]
Thailand3 (53%), 1(33%), 6 (9–17%) [85-88]
Vietnam1 (47%), 6 (47%) [129, 132]
image

Figure 1. Hepatitis C virus prevalence by country.

Download figure to PowerPoint

United States. Compared to 1.3% among the general US population, results from several studies suggest that Asian-American rates of HCV positivity more closely mirror those of countries of origin rather than the lower rate in the US (3–6%).[22-24]

East Asia. In mainland China and Taiwan, large national seroepidemiological studies reveal an overall anti-HCV prevalence between 3 and 4% and smaller studies describe large variances by geographical region.[4, 12, 25-46] Hong Kong is thought to have a relatively low prevalence of HCV, although current data may not be representative as patients were either volunteer blood donors or healthy volunteers.[12, 25, 47] Japan and Korea's low HCV prevalence has been determined by studying millions of volunteer blood donors and a meta-analysis of four different population-based studies respectively.[48-52]

South Asia. The prevalence of HCV in India has not been studied systematically with few large, population-based studies. Much of the work on HCV prevalence in India has been done among blood donors with most finding rates below 2%.[53-65] In Pakistan, Khoker et al.'s large study of healthy adults revealed a similar HCV prevalence (5%) to those found by two separate meta-analyses of this topic.[66-68]

Southeast Asia. Studies of HCV prevalence in Cambodia are lacking, with only small scale investigations in specialised populations and widely discordant findings.[69-71] Among the most robust estimates of CHC rates in Indonesia, Laos, Myanmar, the Philippines and Singapore were large-scale studies of volunteer blood donors, a group that may not be representative of the general population.[69, 72-84] A large seroepidemiological study of healthy individuals in Thailand and data compiled by the World Health Organization in Vietnam are, respectively, the best available data currently.[85-97]

Geographical distribution of HCV genotypes

East Asia. Given the area's vast territory, regional differences in genotype distribution have been described in several studies.[98-102] Most reveal that 1b is most common in China, Hong Kong and Taiwan with 6a found in various parts of the Pearl River Delta of China and Hong Kong respectively.[98, 103-106]

South Asia. Genotype 3 appears to be the dominant virus in both India and Pakistan.[54, 55, 62, 107-119] Japan and Korea each have a significant proportion of patients with genotype 1b while the latter also has many patients with genotype 2a.[48, 120-126]

Southeast Asia. In Cambodia, Laos, Myanmar and Vietnam, current literature suggests that genotype 6 is the dominant variant, although it should be noted that earlier studies prior to the classification of genotype 6 likely reported these patients as non-1, 2 or 3.[69, 80, 82, 92, 93, 127-132] Despite the discovery of genotype 6 in Indonesia, genotype 1 is the most common viral variant in the region, as it is in the Philippines and Singapore.[73, 83, 133-137] Thailand appears to have significant viral diversity with genotypes 3, 1 and 6 present in the area.[85-88]

Risk factors

Although published data on risk factors for HCV infection are conflicting, several studies have found that many Asian HCV patients have no identifiable risk factor.[129, 138-141] In a 2008 prospective study, Ho et al. found that only 67% of their 125 Asian American patients could recall HCV risk factors (vs. 94% of Caucasians and 86% of Hispanics) and only 20% had more than one (vs. 74% and 66% respectively) (Ho E, Ha N, Ahmed A, et al., Unpublished Data). In Britain, Freshwater et al. found that only 11% of their mixed Asian cohort had an identifiable HCV risk factor compared to 80% of the Caucasians studied.[138] Studies of Asian-American CHC patients reveal that intravenous drug abuse (IVDA) is only a minor contributor to the overall disease burden and approximately half do not have any commonly known risk factor for CHC.[14, 129, 142]

In developing countries, inadequately sterilised medical equipment and cultural practices like acupuncture or cosmetic tattooing could be implicated in the transmission of HCV.[31, 64, 115, 143-148] Liu et al. found that past history of blood transfusion [odds ratio (OR) 4.55], oesophageal balloon examination (OR 3.78) and therapeutic IV injection (OR 5.83) were independently associated with HCV infection in their case–control study of 69 HCV-positive patients enrolled following a seroprevalence study of 8226 mainland Chinese patients.[31] Among 16 250 Indian blood donors, Thakral et al. found that 32% of donors with reactive anti-HCV had minor percutaneous exposures like sharing of shaving kits or visits to a roadside barber, while 26% and 19% had a prior history of surgery or IV injections respectively.[149] Data from a retrospective chart review of CHC patients by Cheng et al. revealed that 51% of their Asian American study population had a history of unsafe therapeutic injections (reusing needles or syringes) while in Asia and 41% had a history of transfusion prior to 1992.[14] Thus, while the majority of Caucasian patients may have been infected as adults as a consequence of IVDA, Asians are often infected earlier via nosocomial or person-to-person contact, creating a longer duration of infection and possibly contributing to the differences seen in clinical presentation.[142]

Diagnosis and Screening

Exposure to HCV – past, current or resolved – is determined by detection of hepatitis C antibody (anti-HCV), most often by positive high-sensitivity enzyme immunoassay (EIA) also known as enzyme-linked immunosorbent assay (ELISA). Subsequent generations of the EIA have improved the sensitivity of the test and shortened the average window period prior to detectable seroconversion, and false negatives with second-generation EIAs or later are rare.[150-152]

For patients at risk for HCV infection but who may not have mounted the necessary HCV antibody response to produce a positive EIA, e.g. immunocompromised patients, HCV RNA viral load testing should be considered.[153-155]

Current Center for Disease Control (CDC) recommendations for HCV screening only include patients with the signs and symptoms of liver disease or those with traditional risk factors: HIV positivity, maternal history of HCV infection, occupational exposure, history of IV drug use, blood transfusions and/or haemodialysis. The CDC recommendations are equivocal for those with HCV-positive spouses or household contacts, recipients of transplanted tissue, intranasal and other non-IV drug users, those with a history of tattoos or body piercings and anyone with a history of multiple sexual partners.

However, a 2012 study established the cost effectiveness of HCV screening among the 1945–1965 birth cohort.[156] Given the inconsistent findings with respect to identifiable risk factors, the higher than expected rates of HCV positivity found on community screening, and the varying prevalence of HCV by region, we advocate for a screening approach based upon country of origin if country prevalence is 2% or greater to include the many Asian patients who present without a readily identifiable exposure and thus might otherwise be missed by current CDC guidelines.

HCV Genotyping. The most reliable method of genotyping is by direct sequencing of the entire viral genome via direct-sequence analysis of the 5′-Untranslated Region (UTR) (TruGene HCV 5′NC; Visible Genetics, Toronto, ON, Canada) or reverse hybridisation line probe assay of both 5′-UTR and core regions (INNO-LiPA HCV II; Innogenetics, Ghent, Belgium).[157] Selection of assay is crucial as genotype 6 shares identical 5′-UTR sequences with genotype 1b, making earlier genotyping methods based solely on 5′-UTR sequences such as INNO-LiPA HCV I unreliable, while those with additional HCV core-sequencing such as the updated INNO-LiPA HCV II genotyping are preferable.[158-160]

Clinical characteristics

Presentation. Asian patients tend to be older, have a lower body mass index (BMI) and consume less alcohol and tobacco at presentation than their non-Asian counterparts, behaviours known to contribute to progression of liver disease.[19, 161-163] Asians often present with later stage disease than non-Asians; and on histological examination, they appear to have more fibrosis, inflammation and steatosis, although when accounting for duration of disease, rate of fibrosis between ethnic groups is similar.[138, 163] Late presentation in Asian patients may be secondary to the lack of awareness of appropriate screening and the low proportion of patients presenting with identifiable risk factors. Several studies suggest that Asian ethnicity may be an independent risk factor in the development of HCC in patients with HCV and cirrhosis.[164-167]

Data from Wong et al. indicated that Asians present with a lower incidence of hepatic decompensation, lower Child-Pugh and Model for End-Stage Liver Disease (MELD) scores, and less advanced stage of HCC. However, this study included patients with chronic HBV, which has a greater tendency than HCV to progress to HCC prior to cirrhosis and its sequelae.[161] A large study of 214 Asian and 428 non-Asian HCV-HCC patients found that Asian patients were 11 years older and were more likely to have compensated disease but HCC staging was similar.[168] With regards to the various genotypes, a study by Nguyen et al. of 308 Asian Americans found that there were no significant differences among patients with genotype 1, 2/3 and 6 with respect to baseline clinical and virological characteristics including baseline median ALT, liver histology, median HCV RNA level or prevalence of cirrhosis and HCC at presentation.[129]

HBV/HCV Dual Infection. Current literature supports a synergistic effect between HBV and HCV dual infection, leading to an increased risk for cirrhosis and HCC.[169-173] The high endemicity of HBV in the Asia-Pacific region and the similar routes of transmission for HBV and HCV make dual infection especially relevant in Asian patients with prevalence estimates ranging between 3 and 20%.[142, 174-179] Patients with HBV/HCV dual infection are known to exhibit viral dominance of one virus over the other.[169, 172, 175, 180-186] A recent matched case–control study found that Asian ethnicity may predict for HBV dominance in HBV/HCV dual-infected patients. In non-Asian patients with HBV/HCV dual infection, HCV is usually the dominant virus.[187]

While there is no currently established standard of care for patients with HBV/HCV dual infection, the treatment guidelines generally recommend that the dominant/more active virus should be treated first in patients with HBV/HCV dual infection. In addition, reactivation of one virus upon successful suppression of the other has been described in several studies and requires monitoring before, during and after treatment.[188-190] Data from treatment trials is limited, and among the current data, including two trials from Taiwan, the effect of dual infection on sustained virologic response (SVR) rate is conflicting with Liu et al. indicating no difference in SVR between HBV/HCV dual-infected patients compared with their HCV-monoinfected control patients, while Cacciola et al. detected a difference between the same corresponding groups although this did not reach statistical significance.[189, 191-193] Hung et al. were able to demonstrate a significant reduction in HCC rates for the dual-infected patients receiving PEG-IFN+RBV in their Taiwanese cohort.[194]

Interleukin-28B. Single nucleotide polymorphisms near the interleukin (IL)-28B gene responsible for encoding IFN-γ, are believed to play a role in the immune response of both spontaneous and with-treatment clearance of HCV.[195-198] These favourable genotypes are more frequently found in whites compared with African Americans and Hispanics and are associated with two to three times increase in SVR with PEG-IFN and ribavirin therapy.[195, 196, 199] Data on the proportion of Asian patients with this favourable genotype is lacking, although several studies from Japan, Korea and Taiwan appear to support the notion of improved odds of SVR by a factor of nearly three with favourable IL-28B in genome-wide association studies.[200-203] In tandem with viral genotype and other host factors, IL-28B status may become an important adjunct for predicting likely treatment response in a given individual.[204, 205]

Response to treatment

The goal of anti-viral therapy is to achieve complete and durable elimination of virus which is predicted by attainment of SVR, i.e. undetectable viral load 24-weeks posttreatment. Achieving SVR has been associated with improvement in all-cause mortality, liver-related death, rate of liver transplantation, HCC and other liver-related complications.[206-211]

One of the most important predictors of treatment response to IFN-based therapy is HCV genotype. Studies using interferon-α (IFN-α)+ribavirin (RBV), consensus IFN+RBV and pegylated interferon (PEG-IFN)+RBV have also suggested much higher SVR rates among Asian patients and greater success among those retreated compared with their non-Asian counterparts.[212-217] Part of the reason for this observation is likely associated with ethnicity-related distribution of IL-28B phenotypes. SVR rates in treatment-naïve genotype 1 white patients can now be expected to be in the 60–70% range.

Genotype 1. Following the introduction of two direct acting anti-viral (DAA) agents, protease inhibitors boceprevir (BOC) and telaprevir (TVR), the American Association for the Study of Liver Diseases (AASLD) updated their treatment guidelines for CHC patients with genotype 1.[218] Optimal therapy now includes the use of either BOC or TVR in combination with PEG-IFN+RBV, recommendations based largely on the strength of large registration trials, SPRINT-2 for BOC and ADVANCE for TVR. Unfortunately, data on Asian patients was extremely limited in both with only 21 Asians among 1097 patients and 20 Asians out of 1088 total respectively.[219, 220]

The literature on the previous standard of care, 48 weeks of PEG-IFN+RBV, appear to favour higher SVR rates for Asian patients compared with their non-Asian counterparts. Most large-scale randomised controlled trials with a predominantly non-Asian patient population place SVR rates for HCV-1 between 42 and 52%.[221-223] Vutien et al. found similar rates of SVR between Asians and non-Asian genotype 1 patients as well as genotype 2/3 when genotype was more reliably ascertained with core-sequencing. The authors propose that some of the differences in treatment success found in other trials may be in part due to the misclassification of Asian patients with easier-to-treat non-HCV-1 as HCV-1 using the less-accurate INNO-LiPA genotyping method, potentially overestimating the true effect size of ethnicity on treatment outcomes.[162]

A similar SVR rate was also reported in Chinese patients; however, SVR from other studies from Japan, Korea and Taiwan have substantially and consistently exceeded these rates with successful SVR between 61 and 79%. These studies include the 201 Japanese patients Kuboki et al. enrolled into their randomised controlled trial (RCT) as well as the 308 Taiwanese patients in Liu's RCT in which each helped confirm the superiority of 48 weeks vs. 24 weeks in Asians[193, 224-228] (Table 3).

Table 3. Pegylated interferon and ribavirin (PEG-IFN+RBV) treatment outcomes for hepatitis C virus genotype 1
CountryAuthorYearTreatmentDuration (weeks) n SVR (%)
  1. SVR, sustained virologic response.

ChinaYu[227]2007PEG-IFN+RBV48 4444
JapanKuboki[224]2007PEG-IFN+RBV48 20161
KoreaLee[225]2008PEG-IFN+RBV48 8670
TaiwanLiu[226]2008PEG-IFN+RBV48 30876
TaiwanLiu[193]2009PEG-IFN+RBV48 11077
TaiwanYu[228]2008PEG-IFN+RBV48 10079

Data for treatment response to new DAAs in Asian patients is currently limited since they are generally underrepresented in pivotal trials conducted in the West.

Genotype 2/3. The 2009 AASLD treatment guidelines for chronic hepatitis C recommend that patients with HCV-2/3 be treated with PEG-IFN+flat dose RBV for 24 weeks.[229] Multiple studies in predominantly non-Asian cohorts have shown that HCV genotype 2/3 has a more favourable rate of SVR, between 76 and 84% with standard treatment when compared with genotype 1.[221-223, 230, 231] Most trials from Asia also found that Asian patients with genotype 2/3 achieve higher SVR rates (74–94%) than those conducted in the Western hemisphere (Table 4).[193, 225, 227]

Table 4. Pegylated interferon and ribavirin (PEG-IFN+RBV) treatment outcomes for genotype 2/3
CountryAuthorYearTreatmentDuration (weeks) n SVR (%)
ChinaYu[227]2007PEG-IFN+RBV246175
KoreaLee[225]2008PEG-IFN+RBV248694
TaiwanLiu[193]2009PEG-IFN+RBV245084

As with HCV genotype 1, data for Asian patients is currently also lacking for DAAs.

Genotype 4. Data in patients with HCV-4 comes mainly from the Middle East. In retrospective studies of treatment-naïve patients, anti-viral therapy for HCV-4 leads to SVR more frequently than HCV-1 but less so than HCV-2/3.[232, 233] Small randomised controlled trials reveal an SVR rate between 43 and 68% (Table 5).[234-236] A 2009 consensus report recommends 48 weeks of PEG-IFN+RBV for both genotypes 1 and 4 with possible early discontinuation for HCV-4 patients achieving RVR.[237]

Table 5. Pegylated interferon and ribavirin (PEG-IFN+RBV) treatment outcomes for hepatitis C virus genotype 4
CountryAuthorYearTreatmentDuration (weeks) n SVR (%)
KuwaitHasan[235]2004PEG-IFN+RBV486668
Saudi ArabiaAlfaleh[234]2004PEG-IFN+RBV482843
Saudi ArabiaShobokshi[236]2003PEG-IFN+RBV486050

Very limited data exists with respect to DAA usage in genotype 4 and none specific to Asians. For currently approved protease inhibitors, TVR was shown to induce rapid viral decline in a small study when used in combination with PEG-IFN+RBV but had only a modest effect when used alone.[238, 239]

Among investigational agents, compound GS-7977 (formerly PSI-7977, currently sofosbuvir), in combination with PEG-IFN+RBV, induced viral suppression in 11 HCV-4 subjects in a preliminary study.[240] Daclatasvir (BMS-790062), an NS5A inhibitor, PEG-IFN ɣ and Debio-025 (a cyclophilin inhibitor) have been shown in very early clinical studies to have efficacy against HCV genotype 4.[241-243]

Genotype 6. Currently, 48 weeks of PEG-IFN+RBV is appropriate therapy for patients with genotype 6 and its variants given the limited and conflicting data available, though 24 weeks of therapy also lead to similar SVR rates (61–70%) and may be appropriate for patients with lower tolerability to therapy. In retrospective studies of patients receiving PEG-IFN+RBV combination therapy, SVR has been estimated to be between 69 and 76%, most often achieved with a treatment duration of 48 weeks.[14, 244-246] A retrospective study analysing SVR according to actual treatment duration rather than intention-to-treat found a significantly higher rate of SVR in a 48-week cohort compared to the 24-week group (75% vs. 39%).[246] Of the two small randomised controlled trials to date, Lam et al. found similar SVR rates between their 24-week and 48-week treatment arms (70% vs. 79%; Table 6).[247] In another randomised controlled trial, Pham et al. found no statistically significant difference between the genotype 6 patients treated with 24 vs. 48 weeks of PEG-IFN+RBV therapy (61% vs. 70%, P = 0.24).[248] Rapid virological response (undetectable HCV PCR at week 4 of therapy, RVR) and early virological response (undetectable HCV PCR at week 12, EVR) did not seem to assist in the selection of candidates who may benefit from longer treatment. Larger studies may be needed to determine the optimal treatment duration for these patients.

Table 6. Pegylated interferon and ribavirin (PEG-IFN+RBV) treatment outcomes for hepatitis C virus genotype 6
CountryAuthorYearTreatmentDuration(weeks) n SVR
USALam[247]2010PEG-IFN+RBV

24

48

27

33

70(%)

79(%)

VietnamPham[248]2012PEG-IFN+RBV

24

48

35

70

60(%)

71(%)

At present, there has been no data on the efficacy of currently FDA-approved DAAs on HCV-6 or its subtypes, but some investigational agents have been shown to induce viral suppression in small numbers of HCV genotype 6 patients.[241-243]

Adverse Events During Treatment. Hu et al. found that psychiatric adverse events were less common (29% vs. 47% vs. 47%) and ribavirin-induced anaemia was more common (37% vs. 26% vs. 20%) in Asians than either white or Hispanic patients, and that there were no significant difference between whites and Asians with respect to required ribavirin or PEG-IFN dose reductions, findings supported by subsequent studies.[26, 162, 215, 244, 249] Several studies suggest that the risk for interferon-induced subclinical and clinically apparent thyroid dysfunction are increased for Asian patients.[250, 251]

Summary

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Nearly 100 million patients with chronic hepatitis C worldwide are of Asian origin. The majority of Asian patients do not have traditional risk factors for chronic hepatitis C and thus the decision for screening is more appropriately based on prevalences of countries of origin rather than the CDC guidelines based on the presence of well-known traditional risk factors. Accurate classification of genotype 6 patients requires direct-sequence analysis or newer line probe assays (INNO-LiPA HCV II).

Underlying prevalence of HCV infection and genotype distribution appear to be heavily dependent on countries of origin, although epidemiological data were sometimes obtained through the surveillance of specialised populations like blood donors or volunteer patients which may limit the overall generalisability of their results. However, these estimates likely underrepresent the true number of affected and represent the best working assumptions for HCV disease burden in those areas, underscoring the need for further study.

Sustained virologic response rates for Asian patients are generally higher than those seen for non-Asians with genotype 1 (61–79%) and possibly also for those with genotype 2/3 (74–94%) when treated with standard recommended duration of PEG-IFN+RBV. For patients with genotype 6 treated with PEG-IFN+RBV, high SVR was observed in patients treated with either 24 weeks (61–70%) and 48 weeks (70–86%).

Additional studies are needed to evaluate the efficacy of new DAAs in Asians, especially those with lesser known genotypes 4 and 6. Improved awareness and screening of chronic hepatitis C are also needed among practitioners caring for Asian patients.

Authorship

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Guarantor of the article: MHN.

Author contributions: LHN: drafting, revising of manuscript. MHN: conception & design, final approval. All authors approved the final version of the manuscript.

Acknowledgement

  1. Top of page
  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References

Declaration of personal interests: Long H. Nguyen: Digestive Disease Research Foundation research fellowship. Mindie H. Nguyen: Research support: Roche Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Novartis Pharmaceuticals; Consulting: Bristol-Myers Squibb, Novartis Pharmaceuticals.

Declaration of funding interests: This project was supported in part by an unrestricted clinical research grant from the Digestive Disease Research Foundation.

References

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  2. Summary
  3. Background
  4. Methods
  5. Results
  6. Summary
  7. Authorship
  8. Acknowledgement
  9. References
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