Chronic Hepatitis C
Conditions
Keywords
Chronic hepatitis C, Pegylated interferon, Ribavirin, Virokinetics
Brief summary
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
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.
Interventions
DRUGPegylated interferon alfa and ribavirin
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)
Sponsors
National Science and Technology Council, Taiwan
National Taiwan University Hospital
Study design
Observational model
CASE_ONLY
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sustained virologic response (SVR) | 1~1.5 years |
Countries
Israel, Taiwan
Contacts
Primary ContactJia-Horng Kao, MD, PhD
Backup ContactAvidan Uriel Neumann, PhD
Outcome results
None listed