G. M. Dusheiko

HCV RNA levels and HIV infection: evidence for a viral interaction in haemophilic patients

Summary. In order to investigate a possible interaction between HIV and HCV infections, we compared HCV RNA levels in 29 matched pairs of haemophilic patients seropositive for HCV and serodiscordant for HIV. Levels were assayed using the new Chiron Quantiplex bDNA assay and were found to be significantly higher in HIV seropositive patients. There was no association between HCV RNA and age, duration of HCV infection, concentrate usage, markers of HIV progression, or use of zidovudine. Our study supports the hypothesis that HIV infection facilitates HCV replication and leads to more severe liver damage.

A rational approach to the management of hepatitis C infection

Key messages Summary points The natural course of chronic hepatitis C is not fully defined A range of disease exists—from mild asymptomatic infection with few consequences to serious disease with dire sequelae Pretreatment assessments of viral load and genotype or serotype may help in predicting response It is difficult to indicate the prognosis for younger patients with mild disease; they may need to be considered for treatment, so that the opportunity to avoid later disease is not forfeited It is not yet clear whether patients who are more responsive to interferon have a better prognosis

Review article: 2014 UK consensus guidelines – hepatitis C management and direct‐acting anti‐viral therapy

Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting.

Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles.

CYTOTOXIC T LYMPHOCYTE RESPONSES AND CTL EPITOPE ESCAPE MUTATION IN HBSAG, ANTI-HBE POSITIVE INDIVIDUALS

BACKGROUND/AIMS Clearance of hepatitis B virus (HBV) is characterised by a strong cytotoxic T cell response. Persistence of HBV in chronic hepatitis B carriers may be related to failure of this response. The aim of this study was to determine whether HLA class I restricted cytotoxic T lymphocyte (CTL) responses persist in anti-hepatitis B e (HBe) positive / HBV DNA negative individuals, and to correlate the presence of viral CTL epitope mutation with clinical outcome. METHODS An HLA/HBV dual transfectant model was used to demonstrate these CTL responses in individuals chronically infected with HBV. Subsequently, a known hepatitis B core (HBc) CTL epitope was sequenced in a family of five chronically infected individuals all sharing a HLA allele (HLA-A68.1). RESULTS Low level HLA class I restricted cytotoxic T cell responses were detected in the peripheral blood of five of eight anti-HBe positive individuals. In the family of HLA-A68.1 positive chronically infected individuals, mutation of the HLA-A68.1 restricted hepatitis B core antigen (HBcAg) CTL epitope STLPETTVVRR was found in all four anti-HBe positive individuals but not in the sole hepatitis B e antigen (HBeAg) positive patient. CONCLUSION These data are consistent with a continued immune selection pressure on HBV in anti-HBe positive chronically infected individuals with low replicating HBV infection and suggest that mutation of a CTL epitope may be a consequence of the immune response, as opposed to the cause of viral persistence.

Influence of HIV-1 infection on GBV-C infection in multiply infected haemophilic patients

Two hundred thirteen haemophilic patients were studied for the presence of GBV‐C RNA and anti‐E2 antibodies soon after their first treatment with unsterilised factor concentrates and in their most recent sample. An assessment was made to determine whether coinfection with HIV had any effect on the progression of GBV‐C infection. All of the patients were infected with HCV and 81 patients (37%) were also infected with HIV. GBV‐C RNA was detected using the Abbott LCx™ assay and by RT‐PCR. Anti‐E2 antibodies were detected using the μPLATE Anti‐HGenv assay and by Abbott Laboratories. The HIV‐negative patients were more likely than the HIV‐positive patients to lose GBV‐C RNA between the two time points. A proportion of the patients lost their anti‐E2 antibodies over the time period, however, the majority of these were HIV‐positive. This study shows that infection with HIV does affect the progression of GBV‐C infection, however, this effect is little understood as yet. J. Med. Virol. 56:316–320, 1998.

A clinical evaluation of a new method for HBV DNA quantitation in patients with chronic hepatitis B

Selection of HBsAg‐positive patients for antiviral therapy requires an estimation of disease activity and viral replication. Serum transaminases and histological analysis are commonly used to assess disease activity, and viral replication is assessed by serological testing of HBeAg and serum hepatitis B virus (HBV) DNA. Dot blot hybridisation may be insufficiently sensitive to corroborate low‐grade replication in patients with active hepatitis, and polymerase chain reaction (PCR) may be testing too sensitive for this role. Theoretically an assay of intermediate sensitivity is therefore required. Our aim was to evaluate whether the branched chain DNA (bDNA) assay would fulfil this function. Seventy‐one HBsAg‐positive patients were tested for HBV DNA by the bDNA assay; 64 were also tested by dot blot hybridisation and, when appropriate, also by PCR. Thirty‐seven (52%) patients were positive for HBV DNA by the bDNA assay. HBV DNA was detected in the majority (21/28; 75%) of HBeAg‐positive patients but also in 14 of 36 (39%) anti‐HBe‐positive patients. HBV DNA was detected by the bDNA assay in 20 of 48 (42%) patients negative for HBV DNA by dot blot hybridisation assay. All patients positive for HBV DNA by dot blot hybridisation were also positive by the bDNA assay. Sixteen of twenty‐five (64%) patients negative for HBV DNA by the bDNA assay were positive for HBV DNA by PCR. The bDNA assay is a sensitive and reliable method for the detection of HBV DNA. As nucleoside analogue therapy becomes more widely available, the assay should provide a useful tool for the selection for and monitoring of patients on antiviral therapy.

Rolling review–the pathogenesis, diagnosis and management of viral hepatitis

Five major hepatotrophic viruses have been identified. The pathogenesis, diagnosis and treatment of chronic viral hepatitis continues to be intensely researched. Experimental evidence suggests that HLA restricted virus‐specific T cells play a role in hepatocellular injury in type A hepatitis. The absence of chronic infection indicates the effectiveness of the host immune response to hepatitis A virus (HAV). It is postulated that HAV may rarely trigger an autoimmune chronic hepatitis. Active prophylaxis of hepatitis A is possible.

Review article: the management of hepatitis A, B, D and non-A non-B

This paper reviews the modern management of viral hepatitis: hepatitis A, hepatitis B, hepatitis D and non‐A non‐B hepatitis. It describes the treatment of uncomplicated acute viral hepatitis, complicated acute viral hepatitis, and chronic viral hepatitis. The roles for corticosteroids, synthetic nucleotides, and interferons are reviewed. Finally, passive and active immunization against viral hepatitis are discussed.