Chronic hepatitis C and interferon alfa therapy: Predictors of long term response

Objective: To identify independent patient, disease and viral characteristics that predict a sustained biochemical or viral response to interferon alfa therapy in patients with chronic hepatitis C. Design: Comparison of interferon responders and non-responders by univariate and multivariate analysis. Setting: The hepatitis clinic of the Alfred Hospital, Melbourne (a tertiary referral hospital), between July 1989 and June 1994. Subjects: All patients with chronic hepatitis C who were treated with interferon alfa (IFN-alpha; 3 million IU, three times a week or more) for at least 12 weeks. Outcome measures: Patient demographic and epidemiologic characteristics, pretreatment serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels, histological grading of hepatic steatosis, necroinflammatory activity and fibrosis, serum hepatitis C virus (HCV) RNA titres and genotype and post-treatment serum ALT levels and presence of HCV RNA. Results: Of 58 patients, 13 (22%) had a sustained (six months or longer) biochemical response to IFN-alpha therapy, including 12 (21%) with a sustained viral response. Univariate analysis showed that young patients with a normal serum GGT level, grade 0-1 steatosis and fibrosis, low viral titre and infection with genotypes 3a and 2a were more likely to have a sustained response. Infection with genotypes other than 1a and 1b was the only independent variable associated with both a sustained biochemical and viral response. After adjusting for genotype, a hepatic fibrosis grade of 0-1 was also independently associated with viral response. This logistic regression model accurately predicted the virological response in 80% of cases. Conclusion: In Australian patients with chronic hepatitis C, a sustained viral response to IFN-alpha therapy is most likely in those infected with a genotype other than 1a or 1b and with minimal hepatic fibrosis.