Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis

Abstract

Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBcAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C100-3 and C33c) and structural regions (C22) of HCV. Among the 129 patients, 61 (47%) had antibody to C100-3, 76 (59%) had antibody to C33c and 74 (57%) had antibody to C22. Seventy-nine (61%) were reactive with at least one and 76 (59%) were reactive with at least two HCV peptides (this is the criterion used for hepatitis C virus antibody reactivity). A proportion of patients with chronic hepatitis and cirrhosis (55 of 91; 60%) similar to that of patients without cirrhosis (21 of 38; 55%) had hepatitis C virus antibody. No significant clinical, serum biochemical or histological differences were noted between the group of patients with hepatitis C virus antibody and those without this antibody reactivity. Thus more than half the patients with cryptogenic chronic liver disease had hepatitis C virus antibody, suggesting that chronic HCV infection plays a major role in the origin of cryptogenic chronic hepatitis and cirrhosis.

Hepatitis C Virus (HCV) NS5A Binds RNA-dependent RNA Polymerase (RdRP) NS5B and Modulates RNA-dependent RNA Polymerase Activity

“…Approximately 0.2 g of FLAG-NS5A wild type and mutants were mixed with 1 g of GST-NS5Bt and pulled down with GST resin after preblocking by 1% bovine serum albumin. After washing with PBST, each bound protein was fractionated by SDS-10% PAGE and subjected to Western blot analysis with anti-FLAG monoclonal antibody (C, lanes [2][3][4][5]. 0.2 g of FLAG-NS5A wild type was mixed with 1 g of GST after preblocking and then pulled down, fractionated, and detected as GST-NS5Bt (C, lane 1).…”

“…The virus has the ability to establish persistent infections in the great majority of infected persons, many of whom develop evidence of chronic inflammatory liver disease (3). These chronically infected persons are at risk for cirrhosis and development of hepatocellular carcinoma (4,5). The virus is a positive-stranded RNA virus of genomic size of ϳ9.5 kilobases that is classified within the genus Hepacivirus of the family Flaviviridae.…”

Epidemiological, clinical and biological characteristics of acute non-A, non-B hepatitis with and without hepatitis C virus infection

“…The introduction of second generation assays, adding another nonstructural protein, c33c, and a Structural one, c22-3, has increased the detectable prevalence of anti-HCV in both parenteral and sporadic acute and chronic non-A, non-B hepatitis [6]. However, there is still a proportion of patients in whom, in spite of the improvement of the sensitivity of the assays, anti-HCV is not detected [7,8]. In some of these patients, showing anti-HCV nega 2 tivity by both first and second generation tests, HCV-RNA has been detected after amplification with the polymerase chain reaction (PCR) [9,10].…”

Nonstructural 5A gene variability of hepatitis C virus (HCV) during a 10-year follow up

“…2,3 Chronic HCV infection may eventually lead to cirrhosis and hepatocellular carcinoma.As occurs with other RNA viruses, rapid replication and absence of RNA polymerase proofreading result in the accumulation of mutations at a rate of 0.4 ϫ 10 Ϫ3 to 1.2 ϫ 10 Ϫ3 base substitutions per site per year. 4-6 Consequently, many distinct but highly related variants coexist in the blood and liver of an individual, which indicates that HCV exists as quasispecies.…”