Differences in Viral Kinetics Between Genotypes 1 and 2 of Hepatitis C Virus After Single Administration of Standard Interferon-Alpha
Department of Gastroenterology, Ogaki Municipal Hospital, Japan.Journal of Medical Virology (Impact Factor: 2.35). 08/2009; 81(8):1354-62. DOI: 10.1002/jmv.21533
Hepatitis C virus (HCV) kinetics were determined after a single administration of standard interferon (IFN) according to the HCV genotype that affects the response to antiviral therapy with IFN/peginterferon. A total of 208 patients were investigated. All patients received a single administration of 6 megaunits of standard IFN-alpha. HCV RNA concentration was measured before, and at 24, 48, 72, and 120 hr after administration. Changes in HCV RNA concentration were compared between genotypes. The patient group consisted of 132 patients with genotype 1B, 58 with genotype 2A, and 18 with genotype 2B. In the comparison between genotypes 1 and 2, the reduction in HCV RNA concentration after a single IFN administration was less marked in patients with genotype 1B at both 24 and 48 hr after administration (P < 0.0001). In contrast, an increase in HCV RNA concentration during 24-48 or 24-72 hr after a single administration was comparable between genotypes 1 and 2. In the comparison between genotypes 2A and 2B, the reduction in HCV RNA concentration after a single administration was more marked in patients with genotype 2A, despite the similar rate of sustained virologic response to peginterferon and ribavirin combination therapy. The results of the study indicate that the rapid decrease in HCV RNA concentration observed during IFN or peginterferon therapy in patients with genotype 2 appeared to be due to the difference in sensitivity to IFN. Within genotype 2, HCV genotype 2A was more sensitive to IFN than genotype 2B.
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ABSTRACT: It has been reported that genetic polymorphisms near the IL28B gene or amino acid substitutions in hepatitis C virus (HCV) core protein are associated with the clinical outcome of peginterferon (PEG-IFN) and ribavirin combination therapy. The impact of these factors on the pure sensitivity/resistance to interferon was evaluated. Changes in the HCV RNA levels 24, 48, 72, and 120 hr after administering a single dose of standard interferon (IFN) were measured in 156 HCV-infected patients. The changes were compared based on the genetic polymorphisms near the IL28B gene or amino acid substitutions in the HCV core region. Among patients with HCV genotype 1b, there were differences in the reduction and subsequent increase in HCV RNA levels after administering IFN based on rs8099917 genetic polymorphisms. Amino acid substitutions at residue 70 were associated with differences in the changes in HCV RNA levels only in patients with TG/GG genotype. Multivariate analyses showed that genetic polymorphisms near the IL28B gene was the sole independent factor that was associated with the reduction in HCV RNA levels after administering IFN and the final response to the combination therapy. Among patients infected with HCV genotype 2a or 2b, there were no differences in the changes in HCV RNA levels based on the genetic polymorphisms near the IL28B gene. In HCV genotype 1b, genetic variations near the IL28B gene affected the sensitivity/resistance to IFN strongly. Genetic polymorphisms near the IL28B gene did not affect the sensitivity/resistance to IFN in HCV genotype 2.
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ABSTRACT: To evaluate liver histology of chronic hepatitis C patients, who were relapsers or non-responders to previous conventional therapy. The descriptive case series was conducted in the Hepatology section of Medical Unit-III at the Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from January to December 2008. The study had 109 hepatitis C patients who had relapsed or not responded to the conventional interferon and ribavirin for at least 24 weeks. All the patients were subjected to liver biopsy. The inflammatory activity and fibrosis shown by the liver biopsies were assessed according to the Batts-Ludwig classification. SPSS version 15 was used to analyse data. A majority (n = 57; 52.3%) of the 109 patients were female with hepatitis C virus genotype 3. Among these, 100 (91.7%) patients were non-responders and 9 (8.3%) were relapsers. The mean age of the patients was 38.9 +/- 8.8 years. The non-responders had elevated levels of serum aminotransferase. According to Batts-Ludwig classification, Grade 0 inflammation was not present in the non-responders and relapsers; grade 1 in 51 (46.8%); grade 2 in 47 (43.1%); grade 3 in 10 (9.2%); and grade 4 in 1(0.9%). Stage 0 fibrosis was present in 10 (9.2%); stage 1 in 34 (31.2%); stage 2 in 36 (33.0%); stage 3 in 13 (11.9%); and stage 4 in 16 (14.7%). Results suggested that even if it failed to eradicate hepatitis C virus, the conventional interferon and ribavirin therapy was able to halt the progress of necroinflammation and fibrosis.
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