Impact of Asian Race on Response to Combination Therapy With Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C

Missiha, Sharif B.; Heathcote, Jenny; Arenovich, Tamara; Khan, Kamran Ahmed

doi:10.1111/j.1572-0241.2007.01431.x

Cited by 85 publications

(79 citation statements)

References 35 publications

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“…The obser vation of a favourable response rate among Asians is in accordance with other reports [14][15][16] . Importantly, the effect of ethnicity on SVR rates remained significant after adjusting for other confounders including age, gender, treatment regimen and the extent of hepatic fibrosis.…”

Section: Discussionsupporting

confidence: 81%

“…More recently, comparative studies between Asians and Caucasians have suggested a higher SVR to antiviral therapy among Asians [14][15][16] . In Asians, HCV prevalence rates are approximately 6% [3] .…”

Section: Introductionmentioning

confidence: 99%

“…Often subjects acquire the infection at a younger age and are therefore at increased risk of developing advanced liver disease and hepatocellular carcinoma. Despite this, Asians seem to be under-represented in clinical trials evaluating SVRs, with the largest available study comprising only 52 individuals [16] . In addition, there has been no head-to-head comparative study evaluating responses to antiviral therapy between Asians and Caucasians.…”

Section: Introductionmentioning

confidence: 99%

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Treatment responses in Asians and Caucasians with chronic hepatitis C infection

Yan¹,

Guirgis²,

Dinh³

et al. 2008

WJG

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AIM:To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C (CHC) treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians. METHODS: Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases. Baseline demographic characteristics, biochemical, virological and histological data and details of treatment were collected. Sustained virological responses (SVR) in this cohort were then compared to that in Caucasian subjects, matched by genotype, age, gender and the stage of hepatic fibrosis. RESULTS: A total of 108 Asians with genotype 1 CHC were identified. The end of treatment response (ETR) for the cohort was 79% while the SVR was 67%. Due to the relatively advanced age of the Asian cohort, only sixty-four subjects could be matched with Caucasians. The ETR among matched Asians and Caucasians was 81% and 56% respectively (P = 0.003), while the SVR rates were 73% and 36% (P < 0.001) respectively. This difference remained significant after adjusting for other predictive variables.CONCLUSION: Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treatment responses in Asians and Caucasians with chronic hepatitis C infection

Yan¹,

Guirgis²,

Dinh³

et al. 2008

WJG

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“…Unlike African Americans, Asians with HCV and who were treatment-naïve were more than twice as likely to achieve SVR following pegylated interferon and ribavirin therapy even after adjustment for genotype, body weight, hepatic fibrosis, and adherence. 37 Differences in response to interferon therapy between Hispanics and non-Hispanic whites have not been observed. 29 These dramatic variations in race-specific differences in response to HCV therapy suggest that there is a genetic influence on antiviral response.…”

Section: Racial Disparities In the Treatment Of Liver Diseasementioning

confidence: 99%

Racial disparity in liver disease: Biological, cultural, or socioeconomic factors

Nguyen¹,

Thuluvath²

2008

Hepatology

144

136

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Chronic liver diseases are a major public health issue in the United States, and there are substantial racial disparities in liver cirrhosis-related mortality. Hepatitis C virus (HCV) is the most significant contributing factor in the development of chronic liver disease, complications such as hepatocellular carcinoma, and the need for liver transplantation. In the United States, African Americans have twice the prevalence of HCV seropositivity and develop hepatocellular carcinoma at more than twice the rate as whites. African Americans are, however, less likely to respond to interferon therapy for HCV than are whites and have considerably lower likelihood of receiving liver transplantation, the only definitive therapy for end-stage liver disease. Even among those who undergo transplantation, African Americans have lower 2-year and 5-year graft and patient survival compared to whites. We will review these racial disparities in chronic liver diseases and discuss potential biological, socioeconomic, and cultural contributions. An understanding of their underlying mechanisms is an essential step in implementing measures to mollify racially based inequities in the burden and management of liver disease in an increasingly racially and ethnically diverse population. (HEPATOLOGY 2008;47:1058-1066

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“…Several factors have been linked to the therapeutical response of patients who have CHC, including viral factors (6)(7)(8)(9)(10)(11), host factors (12)(13)(14)(15), metabolic factors (16)(17)(18), histological factors (19), types of regimen (4), and duration of infection (20). Among these factors, viral kinetics following antiviral therapy has become widely accepted in both clinical trials and daily practice (21) and increasingly recognized as the most outweighing predictor of sustained virological response (SVR) to IFN-based therapy (22).…”

mentioning

confidence: 99%

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

Hsu

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN α-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 ± 3.73) (day −1 , mean ± SD) but lower daily viral production rate (P = 10 6 -10 12 ) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients. H epatitis C virus (HCV) infection is the major etiology of chronic liver disease, liver cirrhosis, and hepatocellular carcinoma (1, 2). According to the estimate from the World Health Organization, there are more than 180 million chronic HCV-infected persons worldwide (1-3); hence, effective treatment of chronic hepatitis C (CHC) is important. Nevertheless, the current standard of care for CHC using pegylated (Peg) IFN plus ribavirin is expensive, is effective in only a certain proportion of patients who have CHC, and has many unpleasant adverse effects (4, 5). Therefore, identifying predictive factors of therapeutical response in patients with CHC is important.Several factors have been linked to the therapeutical response of patients who have CHC, including viral factors (6-11), host factors (12-15), metabolic factors (16-18), histological factors (19), types of regimen (4), and duration of infection (20). Among these factors, viral kinetics following antiviral therapy has become widely accepted in both clinical trials and daily practice (21) and increasingly recognized as the most outweighing predictor of sustained virological response (SVR) to IFN-based therapy (22). Using mathematical models of hepatitis C viral kinetics may further clarify the mechanisms of antiviral therapy, the evolution of resistant viral strains, and the length of time necessary to er...

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Impact of Asian Race on Response to Combination Therapy With Peginterferon Alfa-2a and Ribavirin in Chronic Hepatitis C

Abstract: Asians are more likely to achieve an SVR to treatment with peginterferon alfa-2a and ribavirin than whites with chronic hepatitis C, suggesting a genetic influence on the antiviral response.

Cited by 85 publications

References 35 publications

Treatment responses in Asians and Caucasians with chronic hepatitis C infection

Treatment responses in Asians and Caucasians with chronic hepatitis C infection

Racial disparity in liver disease: Biological, cultural, or socioeconomic factors

Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy

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