Early Prediction of Successful Treatment for Chronic Hepatitis C Virus Infection in Taiwan

Study Overview
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Brief Summary
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Hepatitis C virus (HCV) infection is a global health problem, which may lead to chronic hepatitis, cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). Recently, treatment with peginterferon alfa plus ribavirin has become the standard of care for patients with chronic hepatitis C. While genotype 2 patients can have higher sustained virologic response (SVR) rates to 80-90%, genotype 1 patients generally have low SVR rates of only 40-50%. In contrast, genotype 1 Taiwanese patients have superior SVR rates than those in Western countries. Despite the overall improved response to this combination therapy, more than 75% of patients suffer from treatment-related adverse events and the costs remain high, which make individualized therapy of paramount importance to maximize treatment response and minimize adverse events. HCV viral kinetics with interferon-based therapies have been studied recently to evaluate patient responses. Early viral kinetics shown to have favorable SVR rates, which make shorter treatment duration possible. However, different viral kinetics were found through ethnicity. Recently, a pilot study to evaluate the viral kinetics of 6 Taiwanese patients with HCV infection who received peginterferon alfa plus ribavirin therapy has shown superior early viral kinetics to those in Caucasian patients. Based on the favorable SVR rates in treating Taiwanese patients with chronic hepatitis C, the investigators aimed to conduct a large confirmatory study to evaluate the viral kinetics and try to define the optimal treatment for these patients.

Detailed Description
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Hepatitis C virus (HCV) infection is a global health problem, which may lead to chronic hepatitis, cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). [1,2] Recently, treatment with peginterferon alfa plus ribavirin has become the standard of care for patients with chronic hepatitis C. While genotype 2 patients can have higher sustained virologic response (SVR) rates to 80-90%, genotype 1 patients generally have low SVR rates of only 40-50%. [3-5] In contrast, genotype 1 Taiwanese patients have superior SVR rates that those in Western countries. [6,7] Despite the overall improved response to this combination therapy, more than 75% of patients suffer from treatment-related adverse events and the costs remain high, [8,9] which make individualized therapy of paramount importance to maximize treatment response and minimize adverse events. HCV viral kinetics with interferon-based therapies have been studied recently to evaluate patient responses. [10-14] Early viral kinetics shown to have favorable SVR rates, which make shorter treatment duration possible. [15-18] However, different viral kinetics were found through ethnicity. [19-23] Recently, a pilot study to evaluate the viral kinetics of 6 Taiwanese patients with HCV infection who received peginterferon alfa plus ribavirin therapy has shown superior early viral kinetics to those in Caucasian patients. [24] Based on the favorable SVR rates in treating Taiwanese patients with chronic hepatitis C, the investigators aimed to conduct a large confirmatory study to evaluate the viral kinetics and try to define the optimal treatment for these patients.

Official Title
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Early Prediction of Successful Treatment for Chronic Hepatitis C Virus Infection in Taiwan

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Pegylated interferon alfa and ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naïve Over 18 years old Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months Detectable serum quantitative HCV-RNA (Cobas Amplicor HCV Monitor v2.0, Roche Molecular Systems, Pleasanton, CA) with dynamic range 600 < 500,000 IU/ml Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment A liver biopsy consistent with the diagnosis of chronic hepatitis C Exclusion Criteria: Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women) Neutropenia (neutrophil count < 1,500 per cubic milliliter) Thrombocytopenia (platelet < 90,000 per cubic milliliter) Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) Chronic alcohol abuse (daily consumption > 20 gram per day) Decompensated liver disease (Child-Pugh class B or C) Serum creatinine level more than 1.5 times the upper limit of normal Autoimmune liver disease Neoplastic disease An organ transplant Immunosuppressive therapy Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus Evidence of drug abuse Unwilling to have contraception Unwilling to receive serial blood sampling during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Patients with chronic hepatitis C who receive pegylated interferon plus ribavirin for 24 weeks (genotype 1 or 2) and for 48 weeks (genotype 1) | Drug: Pegylated interferon alfa and ribavirin<br>* Pegylated interferon alfa-2a 180 ug/week or pegylated interferon alfa-2b 1.5 ug/kg/week Ribavrin 800-1200 mg/day (genotype 1: < 75 kg 1000 mg/day, >=75 kg 1200 mg/day; genotype 2: 800 mg/day) HCV genotype: baseline (Day 0) HCV RNA (real time PCR test): baseline (Day 0), Day 1 (4,8,12 hours after pegylated interferon + ribavirin), Day 2 (24,36 hours), Day 3(48 hours), Day 4 (72 hours), Day 5 (96 hours), Week 2,4,6,8,12,16,20,24, and 28,32,36,40,44,48,72 (for genotype 1 with 48 weeks of treatment), and 48 (for genotype 1 or 2 with 24 weeks of treatment)<br>* Other names: Peg-Intron plus Rebetol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virologic response (SVR) |  | 1 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic hepatitis C, Pegylated interferon, Ribavirin, Virokinetics