Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients

The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76±18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were shortterm responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the shortterm responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II±I and 1 gt II±III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genoytpe, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P<0.01 vs. untreated patient). Thirteen of 18 nonresponders who selected genotype II during follow-up developed cirrhosis, compared with none among the four untreated which also selected for genotype II (P<0.01) and with none of the patients maintaining their baseline genotype (P<0.01). In conclusion, patients with single HCV genotype, other than gt II, respond better to IFN, which seems to easily suppress HCV genotypes other than II. Genotype II is scarcely inhibited and becomes predominant during follow-up. In the patients selecting for genotype II, cirrhosis develops more rapidly than in untreated patients, where the selection for genotype II occurs at much slower rate.