Variability of hepatitis C virus hypervariable region 1 (HVR-1) during the early phase of pegylated interferon and ribavirin therapy

PurposeGenetic variability of hepatitis C virus (HCV) is considered to be an important factor defining viral pathogenesis, persistence and resistance to treatment. The aim of the present study was to characterize HCV genetic heterogeneity within a hypervariable region 1 (HVR-1) before and during the early period of pegylated interferon alfa (PEG-IFN-α) and ribavirin treatment in correlation with treatment outcome.Material and MethodsThe study involved 24 patients treated with PEG-IFN-α and ribavirin whose sera were collected before (baseline) and at 7, 14, 21 28 and 56 day of treatment. HCV HVR-1 region was amplified by nested RT- PCR and subjected to SSCP (single strand conformational polymorphism) analysis. SSCP changes of HCV HVR-1 over time in each patient were compared to treatment outcome results.ResultsIn 2/11 (18%) SVR+ and 8/13 (62%) SVR- treated patients, HVR-1 genetic changes manifested by new SSCP bands (new genetic variants) and were significantly more frequent in nonresponders (P <0.05).ConclusionsOur results indicate that HCV HVR-1 variability during the early phase of PEG-IFN-α and ribavirin therapy may be predictive of treatment outcome.     

Lack of evidence for hepatitis B virus (HBV) infection in fulminant non-A,non-B hepatitis

We studied eight patients who had orthotopic liver transplantation for fulminant hepatic failure in the course of acute non-A, non-B hepatitis. HBV DNA was searched for extensively in the liver tissue by PCR using several sets of primers in conventional and heminested reactions. All patients were negative for HBV DNA in liver tissue by all assays employed; furthermore, they were negative for HEV RNA, HCV RNA, and HBV DNA in serum. Although the causative role of HEV and HCV in fulminant non-A, non-B hepatitis cannot be excluded, our data do not support a causative association between this syndrome and HBV infection.This study was supported by Grant CR20 from the Mayo Clinic and Foundation. D.H.P. is supported by Public Health Service grants AI 32403, AR 41497, and AI 30548 from the National Institutes of Health.     

Liver disease among Polish alcoholics. Contribution of chronic active hepatitis to liver pathology

A group of 70 chronic alcoholics--65 men and 6 women--has been studied. HBsAg was found in 11 (16%), and at least one marker of HBV infection was present in sera from 31 (44%) persons, these results being significantly higher than in a matched control population. The commonest single histological patterns were: steatosis (18 cases), and alcoholic hepatitis (18 cases), followed by normal liver (14 cases) and chronic active hepatitis (12 cases). Cirrhosis was diagnosed in only 4 cases. Five cases of chronic active hepatitis could be attributed to infection with HBV or HDV; in the remaining 7 cases the etiology was unclear. Infection with HBV seems to play an important role as the cause of liver disease among alcoholics in Poland, and chronic active hepatitis of various etiology may be an important form of liver pathology among them.     

Cytomegalovirus infection presenting as hepatitis

Among 530 consecutive patients hospitalized for acute hepatitis in the years 1986-1988 cytomegalovirus infection was diagnosed in 5 (0.9%). All 5 patients had symptomatic hepatitis with jaundice, 3 had pruritus. Hematological changes were relatively mild and liver function tests were not essentially different from those found in patients with hepatitis A, B, or non-A, non-B. All biochemical abnormalities returned to normal within 3-5 weeks.     

Negative-strand hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells from anti-HCV-positive/HIV-infected women

BACKGROUND: Hepatitis C virus (HCV) has been reported to replicate in peripheral blood mononuclear cells (PBMCs), particularly in patients coinfected with HCV and human immunodeficiency virus (HIV). However, there are limited data regarding the prevalence of and the factors associated with extrahepatic replication. METHODS: The presence of negative-strand HCV RNA in PBMCs was evaluated by a strand-specific assay for 144 anti-HCV-positive/HIV-infected women enrolled in the Women's Interagency HIV Study. One to 5 PBMC samples obtained from each woman were tested. Multivariate analyses were used to assess for associations with the clinical and demographic characteristics of the women. RESULTS: Negative-strand HCV RNA was detected in 78 (25%) of 315 specimens, and, for 61 women (42%), > or = 1 specimen was found to have positive results. The presence of negative-strand HCV RNA in PBMCs was significantly positively associated with an HCV RNA plasma level of > or = 6.75 log copies/mL (P=.04) and consumption of > or = 7 alcoholic drinks per week (P=.02). It was also negatively associated with injection drug use occurring in the past 6 months (P=.03). A negative association with a CD4+ CD38+ DR+ cell percentage of > 10% and a positive association with acquired immunodeficiency syndrome were borderline significant (P=.05). CONCLUSIONS: HCV replication in PBMCs is common among HIV-coinfected women and appears to be a dynamic process related to lifestyle, virologic, and immunologic factors.     

Analysis of hepatitis C virus quasispecies transmission and evolution in patients infected through blood transfusion

BACKGROUND & AIMS: Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection. METHODS: We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2-3 weeks for 6 months, at 10 months, and at 11-16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5' untranslated region (5'UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA). RESULTS: Seven patients cleared infection within 7-24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8-22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5'UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether. CONCLUSIONS: Changes in E2/HVR1 quasispecies 8-22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host.