8 research outputs found
Clinical relevance of total HCV Core antigen testing for hepatitis C monitoring and for predicting patients` response to therapy
Pretreatment predictive factors for hepatitis C therapy outcome: relevance of anti-E1E2 antibodies compared to IP-10 and IL28B genotypes.
Animal models for the study of HBV infection and the evaluation of new anti-HBV strategies
International audienc
PreS1 antigen/antibody patterns following interferon therapy in acute and chronic hepatitis B
The relation between preS1 antigen/antibody system and different phases of hepatitis B virus infection were studied in 425 serum samples from 50 hepatitis B patients before, during and after antiviral therapy using interferon alone or in combination with corticosteroid withdrawal. A typical profile of self-limited acute hepatitis B was characterized by hepatitis B virus-DNA clearance using polymerase chain reaction and preS antigens using monoclonal radioimmunoassays and by antibody responses to the middle and the large HBs proteins (gp33/gp36 and p39/gp42) using immunoblotting quantitative analysis. After interferon therapy in patients with protracted hepatitis B, complete eradication of the virus was observed in 70% of patients, and antibody response directed to middle HBs and large HBs proteins could be induced. Conversely, this antibody response was never detected in follow-up studies of chronic active hepatitis B patients who responded well to antiviral therapy and lost HBs, preS2 and preS1 antigens. Most interesting, in 50% of patients with HBeAg-positive chronic active hepatitis B who received combination therapy and in 67% of patients with anti-HBe-positive chronic active hepatitis B given interferon alone, the elevated serum preS1Ag/HBsAg ratio persisted after treatment was discontinued and even increased until the end of the follow-up when hepatitis B virus DNA was undetectable in serum by the conventional hybridization technique. This rebound of preS1 antigen expression following antiviral therapy in patients with chronic active hepatitis B may indicate virus persistence, suggesting the possibility of relapse through wild-type hepatitis B virus or the emergence of hepatitis B virus mutants
The predictive value of core antigen testing for the management of hepatitis C patients receiving pegylated interferon/ribavirin treatment
Inhibition of Hepatitis B Virus Replication by the Interferon-Inducible MxA Protein
Human MxA is an alpha/beta interferon-inducible intracytoplasmic protein that mediates antiviral activity against several RNA viruses. We had previously shown that overexpression of the hepatitis B virus (HBV) capsid led to selective downregulation of MxA gene expression, suggesting a mechanism by which the virus escapes from the host defense system (O. Rosmorduc, H. Sirma, P. Soussan, E. Gordien, P. Lebon, M. Horisberger, C. Brechot and D. Kremsdorf, J. Gen. Virol. 80:1253–1262, 1999). In the present study, we investigated the antiviral activity of MxA protein against HBV. MxA-expressing HuH7 clones were established and transiently transfected with HBV, and viral replication was then studied. Viral protein secretion was profoundly reduced in MxA-expressing clones by 80% for HBV surface antigen (HBsAg) and 70% for HBV e antigen (HBeAg). The levels of intracytoplasmic HBsAg and HBeAg were reduced by about 80 and 50% in the two MxA-positive clones tested. A nearly complete disappearance of HBV DNA replicative intermediates was observed in MxA-expressing clones. Although the expression of total viral RNAs was not modified, two- to fourfold reductions in HBV cytoplasmic RNAs were found in MxA-expressing clones. This suggests the inhibition of HBV replication at a posttranscriptional level. Indeed, using the well-characterized posttranscriptional regulation element (PRE) reporter system, we were able to demonstrate a marked reduction (three- to eightfold) in the nucleocytoplasmic export of unspliced RNA in MxA-expressing clones. In addition, MxA protein did not interact with HBV nucleocapsid or interfere with HBV nucleocapsid formation. Our results show an antiviral effect of MxA protein on a DNA virus for the first time. MxA protein acts, at least in part, by inhibiting the nucleocytoplasmic export of viral mRNA via the PRE sequence
Infection with hepatitis B and C viruses and risk of lymphoid malignancies in theEuropean Prospective Investigation into Cancer and Nutrition (EPIC).
Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC).
BACKGROUND: Case-control studies suggested a moderate, but consistent, association of hepatitis C virus (HCV) infection with lymphoid tissue malignancies, especially non-Hodgkin lymphoma (NHL). More limited data suggested that hepatitis B virus (HBV) infection might also be associated with NHL. However, prospective studies on the topic are few. METHODS: A nested case-control study was conducted in eight countries participating in the EPIC prospective study. Seven hundred thirty-nine incident cases of NHL, 238 multiple myeloma (MM), and 46 Hodgkin lymphoma (HL) were matched with 2,028 controls. Seropositivity to anti-HCV, anti-HBc, and HBsAg was evaluated and conditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for NHL, MM, or HL, and their combination. RESULTS: Anti-HCV seropositivity among controls in different countries ranged from 0% to 5.3%; HBsAg from 0% to 2.7%; and anti-HBc from 1.9% to 45.9%. Similar nonsignificant associations were found with seropositivity to HBsAg for NHL (OR = 1.78; 95% CI: 0.78-4.04), MM (OR = 4.00; 95% CI: 1.00-16.0), and HL (OR = 2.00; 95% CI: 0.13-32.0). The association between HBsAg and the combination of NHL, MM, and HL (OR = 2.21; 95% CI: 1.12-4.33) was similar for cancer diagnosed less than 3 and 3 or more years after blood collection. No significant association was found between anti-HCV and NHL, MM, or HL risk, but the corresponding CIs were very broad. CONCLUSIONS: Chronic HBV infection may increase the risk of lymphoid malignancies among healthy European volunteers. IMPACT: Treatment directed at control of HBV infection should be evaluated in HBsAg-seropositive patients with lymphoid tissue malignancies