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 pol ymerase chain reaction) was evaluated in 60 patients with anti HCV-pos itive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) thera py] during a mean follow-up period of 76+/-18 months. In untreated pat ients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mix ed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological re mission, 6 were shortterm responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and onl y 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 short term responders, 2/6 patients had genotype II and 4 had a mixed infect ion (3 gt II+/-I and 1 gt II+/-III); gt III became prevalent in the la tter in al but one patient. Of the nonresponders 18/24 had more than o ne genotype, 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 select ed for gt II (P<0.01 vs. untreated patient). Thirteen of 18 nonrespond ers who selected genotype II during follow-up developed cirrhosis, com pared with none among the four untreated which also selected for genot ype II (P<0.01) and with none of the patients maintaining their baseli ne genotype (P<0.01). In conclusion, patients with single HCV genotype , other than gt II, respond better to IFN, which seems to easily suppr ess HCV genotypes other than II. Genotype II is scarcely inhibited and becomes predominant during follow-up. In the patients selecting for g enotype II, cirrhosis develops more rapidly than in untreated patients , where the selection for genotype II occurs at much slower rate.