Detection of Hepatitis C Virus by Polymerase Chain Reaction and Response to Interferon–α Therapy: Relationship to Genotypes of Hepatitis C Virus

Abstract

To investigate the relationship between genotypes of hepatitis C virus and response to interferon–α therapy, hepatitis C virus RNA was assayed by polymerase chain reaction with three sets of primers and probes in 70 patients with non–A, non–B chronic hepatitis who received interferon–α. Twenty–four patients sustained long–term remissions (complete responders). Polymerase chain reaction for 5′–terminal noncoding region detected hepatitis C virus RNA in 94.3% (66 of 70) of the patients. Polymerase chain reaction for nonstructural region 3, in which primers and a probe were synthesized to be identical to hepatitis C virus–J, detected hepatitis C virus RNA in 40 patients. Polymerase chain reaction for nonstructural region 5-in which sequences of primers and a probe were derived from hepatitis C virus–K2, a genotype different from hepatitis C virus–J-detected hepatitis C virus RNA in 17 patients. Only one patient was positive on both nonstructural region 3 and nonstructural region 5 polymerase chain reaction. Nucleotide sequence of clones obtained from 5′ terminal noncoding region polymerase chain reaction products of two patients positive on polymerase chain reaction for nonstructural region 3 and negative on polymerase chain reaction for nonstructural region 5 (group 1) corresponded to that of the hepatitis C virus–J group, and those of clones from two patients negative on polymerase chain reaction for nonstructural region 3 and positive on polymerase chain reaction for nonstructural region 5 (group 2) corresponded to that of hepatitis C virus–K2. A clone from a patient negative on polymerase chain reaction for nonstructural region 3 and polymerase chain reaction for nonstructural region 5 (group 3) showed low nucleotide sequence homology with the hepatitis C virus–J and hepatitis C virus–K2 groups. The complete response rates of group 2 (10 of 16 [62.5%]) and group 3 (6 of 10 [60.0%]) were significantly higher than that of group 1 (5 of 39 [12.8%]) (p < 0.01 for both). Logarithms of hepatitis C virus RNA concentrations (copies per milliliter) were significantly higher in group 1 (5.0 ± 1.1) than in group 2 (3.8 ± 1.1) or group 3 (3.2 ± 1.1) (p <0.01 for either). These results indicate that detection of hepatitis C virus RNA by polymerase chain reactions with different sets of primers and probes may be valuable in classifying hepatitis C virus into genotypes, and that amount of hepatitis C virus RNA in sera and response to interferon–α may vary among different genotypes of HCV. (Hepatology 1992;16:293-299.)