Christopher Tibbs

Ribavirin therapy for hepatitis C infection following liver transplantation

Abstract  Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40 % by this time. Ribavirin‐induced haemolysis was clinically

Recurrence of hepatitis C following orthotopic liver transplantation: a polymerase chain reaction and histological study

Hepatitis C virus was sought by nested polymerase chain reaction in the preoperative biopsy or the explanted liver of 100 consecutive adult patients undergoing orthotopic liver transplantation. In those found to be positive preoperatively, polymerase chain reaction was performed on subsequent biopsies. Of the 12 patients in whom HCV-RNA was identified in the liver by polymerase chain reaction preoperatively, viral recurrence was documented in ten of the 11 with posttransplant liver tissues available for study. In the one exception, hepatitis C virus was undetectable in the liver graft despite repeated co-amplification of albumin mRNA as an internal control, which may indicate viral clearance. In eight of the ten positive cases, HCV-RNA was also detectable in serum postoperatively, while HCV-RNA was undetectable in serum in both the cases in whom HCV-RNA was undetectable in tissue and in the patient who declined post-transplant biopsy. Two of the 12 patients infected with hepatitis C virus preoperatively have died during the follow-up period from causes unrelated to hepatitis C virus infection. While biochemical liver function in seven of those remaining has been excellent, histological evidence of at least mild chronic active hepatitis has been present in all ten cases for whom long-term biopsies are available. Three cases have progressed to severe, symptomatic chronic active hepatitis within 2 years of transplantation. Recurrent hepatitis C is associated with progressive liver disease and appreciable morbidity in a significant proportion of patients.

Usefulness and limitation of phylogenetic analysis for hepatitis C virus core region: application to isolates from Egyptian and Yemeni patients

SummaryWe report here the nucleotide sequences of the core region of HCV isolates from Egyptian and Yemeni patients and the method for classifying these HCV isolates by phylogenetic analysis. Sequence comparison suggested that the genotypes of these isolates were the same. Preliminary phylogenetic analysis of the HCV core region indicated that the genotypes of both isolates were 1c. However, an additional phylogenetic tree of the HCV core region constructed using a greater number of HCV isolates than that used in the preliminary analysis and on the basis of alignment of nucleotide sequences in an appropriate length indicated that the genotypes of these isolates were 4 and not 1c. For a more detailed analysis, the nucleotide sequences of the HCV E1 region as well as the core region for the same Yemeni patient were determined. A phylogenetic tree of the E1 region confirmed that the genotype of the HCV isolate from the Yemeni patient was 4. These data indicate that even when classifying HCV isolates using phylogenetic analysis, the misclassification would occur if care is not taken regarding the number and sequence lengths of the isolates included in the analysis.

Cellular and humoral immune reactions against autoantigens and hepatitis C viral antigens in chronic hepatitis C

BACKGROUND/AIMS Previous reports have suggested that the hepatitis C virus (HCV) may induce autoimmune hepatitis. The aim of this study was to examine this hypothesis by investigating humoral and cellular immune responses to HCV-related antigens and various autoantigens in patients with chronic HCV infections. METHODS Lymphoproliferative responses in vitro and/or circulating antibodies to an HCV core peptide, the putative autoantigen GOR, the liver-specific hepatic asialoglycoprotein receptor (ASGP-R), and other autoantigens were investigated in 27 adults with chronic hepatitis C. RESULTS Five patients with HCV (18.5%) showed cellular immune responses to ASGP-R and two others had antibodies to ASGP-R, whereas 6 of 14 patients (42.8%) showed cellular responses to GOR and 7 of 14 patients (50%) showed responses to HCV core. Other autoantibodies were detected in three patients (11%). Nine patients with autoimmune hepatitis studied concurrently for comparison showed cellular and/or humoral responses to ASGP-R but not to GOR. Only 2 of 11 patients with other chronic liver disorders showed immune responses to any antigen tested. CONCLUSIONS Specific immunocompetence against HCV-related antigens can often be shown in patients with chronic hepatitis C but is infrequently accompanied by autoreactions against liver-specific or nonspecific antigens. A reported association between T-cell responses to HCV core and lack of liver damage could not be confirmed.

Absence of hepatitis C virus in British patients with type 1 autoimmune chronic active hepatitis — a polymerase chain reaction and serological study

Despite several studies from continental Europe reporting a high prevalence of antibodies to the hepatitis C virus (HCV), there has been little evidence of such infection in patients from the United Kingdom. The use of the polymerase chain reaction combined with two separate second generation anti-HCV assays is reported here in 58 UK patients with well-documented autoimmune chronic active hepatitis. All patients were in corticosteroid induced remission. All sera were collected prospectively for the specific purpose of this study. HCV-RNA was not detected by use of the polymerase chain reaction in any of the patients and antibodies to HCV were only detected in one patient. No evidence was found for the involvement of the hepatitis C virus in UK patients with classical, corticosteroid sensitive autoimmune chronic active hepatitis.

Hepatitis C and haemophilia: a report of a meeting held at The Royal Free Hospital, London, 12 December 1994

A recent meeting at the Royal Free Hospital in London was an opportunity for haematologists, virologists, histopathologists and hepatologists to meet and discuss what is and what is not known about the outlook and management of clotting factor concentrate recipients who have contracted hepatitis C infection. Dr Ludlam (Edinburgh), the chairman of the first session, listed the various factors which may influence the eventual outcome of the estimated 3000 haemophiliacs in the UK who are infected with HCV; these patients have mainly been infected early in life, many (before heat treatment of clotting factors in 1986) had multiple exposures to several different strains of HCV which may have led to a change in the predominant infecting genotype, and many are also infected with other viruses, particularly HIV. In addition, the irnmunomodulatory effect of clotting factors is difficult to assess, invasive investigation (liver biopsy) is often not performed, and the effect of interferon treatment in this subgroup has not been fully investigated. H e emphasized the use in those with end-stage liver disease of liver transplantation, with the prospect not only of cure of their liver disease but also cure of haemophilia as has been reported from King’s College Hospital. Professor Zuckerman (Royal Free) stated that not only HCV but also HBV and HAV were more prevalent in haemophiliacs. He then presented disturbing data from Japan that up to 15% of those presenting with chronic HCV hepatitis may develop hepatocellular carcinoma in a 10-year period [l] .

GB virus C/hepatitis G virus infection in patients with chronic hepatitis C virus infection

Abstract GB virus C/hepatitis G virus (GBV-C/HGV) infection was examined in 96 chronic hepatitis C virus (HCV) patients from 23 different countries. GBV-C/HGV RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) with primers derived from the 5′-untranslated region of GBV-C/HGV. All amplicons were sequenced and analyzed by molecular evolutionary methods. Although GBV-C/HGV RNA was detected in 18 of 96 patients (18.8%), we did not find any correlation between specific HCV genotypes and the positivity for GBV-C/HGV. GBV-C/HGV RNA was found predominantly among intravenous drug users (IVDUs) in European patients. The phylogenetic tree showed that the isolates could be grouped into three clusters. These data indicated that GBV-C/HGV is (i) already present in HCV patients of various countries, (ii) frequent among European IVDUs, (iii) a heterogeneous virus, and (iv) clustered into three different phylogenetic groups.

Hepatitis B and C in Patients with Hepatocellular Carcinoma in Brazil

The relative roles of hepatitis B (HBV) and hepatitis C (HCV) virus infections in primary liver cancer in Brazil have been established. In the present study, the prevalence of HBV and HCV infections was determined in 32 Brazilian patients with hepatocellular carcinoma (HCC), of whom 30 had elevated serum alpha-fetoprotein levels (median 285ng/ml, range 10–1380), but only 14 (44%) were found to have cirrhosis on liver biopsy. Fifteen (47%) had a history of excessive alcohol consumption (>80g/day). All patients were screened for serological markers of HBV (HBsAg, anti-HBe, anti-HBc, and anti-HBs) and of HCV (anti-HCV). Additionally, HBV-DNA was determined by a radiological molecular hybridization assay, and HCV-RNA was measured by nested polymerase chain reaction (PCR). Eight (25%) patients were found to be HBsAg- and anti-HBe- positive, five of whom were seropositive for HBV-DNA. Thirteen (41%) patients were found to have anti-HBs and/or anti-HBc. Anti-HCV was found in 8 (25%), of whom four were HCV-RNA-positive, and one had HBV coinfection (HBsAg- positive). Cirrhotic patients were significantly (P < 0.05) older (mean age 59 years, range 41–77 years) than noncirrhotic patients (mean age 43 years, range 22–68 years), but there was no significant difference between these two groups with respect to overall prevalence of HBV and HCV markers. Nine (28%) of the 32 patients had no markers of HBV or HCV infection and no history of heavy alcohol intake. These findings suggest that, in a significant proportion (56%) of Brazilian patients, HCC develops in noncirrhotic livers and in 50% of these is not related to either HCV or HBV infection or alcohol intake.