In patients with chronic hepatitis C who have persistently normal serum ALT levels and no detectable serum HCV RNA 6 months after interferon-alpha therapy, a long-term sustained biochemical and virologic response is generally seen. This response is associated with an absence of detectable intrahepatic HCV RNA and marked histologic improvement.

The aim of the study was to determine the respective influence of pretreatment serum hepatitis C virus (HCV) RNA levels and HCV genotype on the response to interferon (IFN) alfa in patients with chronic hepatitis C. We retrospectively studied 141 patients with chronic hepatitis C included in two consecutive controlled trials of IFN alfa. A sustained response was observed in 28, a response followed by relapse in 43, and no response in 70 patients.Pretreatment serum HCV RNA quantitation with the branched DNA (bDNA) assay and HCV genotyping with reverse hybridization assay (LiPA) were performed in all patients. Seventy-four percent of the patients had detectable serum HCV RNA (43%, 77% and 84%) in the three groups of patients with sustained response, relapse, and no response, respectively (P = .005). Mean serum HCV RNA level were 1.4 f 6 x lo6, 4.8 f 6 x lo6, and 3.9 f 5 x lo6 genomeslml in patients with sustained response, response and relapse, and no response, respectively (P < .01). Genotype l b was found in 7%, 47%, and 46V0 of the patients in the three response groups, respectively. By univariate analysis, age, source, and duration of HCV infection, serum HCV RNA levels, and HCV genotypes were significantly different in the three response groups. By multivariate analysis, the only independent factors associated with sustained response were low serum HCV RNA levels and HCV genotype other than lb. Pretreatment serum HCV RNA levels and HCV genotype are the main and independent factors associated with sustained response to IFN therapy. (HEPATOLOGY 1995; 22:1050-1056 Abbreviations: HCV, hepatitis C virus; IFN, interferon; bDNA, branched DNA ALT, alanine transaminase. Diseases.Hepatitis C virus (HCV) has been shown to be the major causal agent of chronic non-A, non-B Although interferon (IFN) is currently the only effective antiviral agent for the treatment of chronic hepatitis c, 50% of the patients treated respond and only 20% have a sustained r e~p o n s e .~.~ The factors influencing the response to IFN therapy are unknown. Several pretreatment features have been reported to be useful in identifying patients with a high probability of response to IFN treatment, such as young age, source of infect i~n ,~ absence of cirrhosis, and short duration of the disease.8 The lack of reliability of these patient-related factors from one study to the other suggests that they do not markedly influence the response to IFN treatment and that virus-related factors might be crucial for response to IFN therapy. Indeed, several studies have shown that pretreatment serum HCV RNA levels and HCV genotype influence the response to IFN treatment.9-i5 However, many of these studies only included small numbers of patients and did not use multivariate analysis. Furthermore, the methods used to quantitate serum HCV RNA and to genotype HCV were not always standardized, leading to difficulties in interpreting the different studies. Two new approaches, branched DNA (bDNA) signal amplification, recently developed for serum HCV RNA quantificatio...

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