Evidence of a significant role for Fas-mediated apoptosis in HCV clearance during pegylated interferon plus ribavirin combination therapy.

BACKGROUND: The role of apoptosis in treatment-induced HCV clearance is controversial. We sought to assess the kinetics of serum apoptosis-related cytokines during pegylated interferon-α2a or -α2b plus weight-based ribavirin therapy for genotype 1 chronic HCV infection. METHODS: Serum levels of soluble Fas (sFas), soluble Fas ligand (sFasL) and soluble tumour necrosis factor receptor I (sTNF-RI) were measured at baseline, week 12 and 24 weeks after the end of therapy. RESULTS: Sustained virological response (SVR) was achieved in 46% of the 164 included patients, 29% had a non-response (NR) and 25% had relapse (RR). NR patients presented with higher levels of sFasL at baseline and lower levels of sTNF-RI at week 12 as compared to RR and SVR patients. Lower concentrations of sFas were observed in SVR patients 24 weeks after treatment as compared to RR and NR patients. An increase in sFas at week 12 followed by a significant drop 24 weeks after therapy was observed among SVR patients. An increase in sFasL during and after treatment was observed in RR and SVR patients. NR patients exhibited an earlier drop in sTNF-RI levels as compared to RR and SVR patients. CONCLUSIONS: Virological response during HCV therapy was associated with an increase of sFas and sFasL, and maintenance of increased concentrations of sTNF-RI.

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C.

BACKGROUND: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV-DNA detection. AIMS: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. METHODS: This cross-sectional study included hepatitis B surface antigen- and human immunodeficiency virus-negative subjects with positive HCV-RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV-DNA using a commercial assay. The METAVIR system was used for histological analysis. RESULTS: One-hundred and eleven patients were evaluated. Thirty-one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti-HBc). HBV-DNA was not detected in any sample. Anti-HBc-positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti-HBc-positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti-HBc-negative subjects who acquired HCV before the age of 30 and in 57% of those anti-HBc-positive patients who were infected by HCV after 30 years of age (P<0.001). CONCLUSION: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.

Anti-HCV reactive blood donors: clinical and epidemiological factors associated with false-reactive results.

BACKGROUND: In certain clinical settings, false-reactive anti-hepatitis C virus (HCV) results are rare because the majority of persons being tested have evidence of liver disease and the specificity of the screening assays is high. However, among healthy populations, such as blood donors, mainly in regions with a low prevalence of HCV infection, this situation does occur. In this study, we sought to assess clinical, epidemiological, and laboratory characteristics of blood donors with false-reactive anti-HCV screening tests. METHODS: This retrospective cross-sectional study included 537 anti-HCV reactive blood donors referred to a tertiary care centre for liver diseases. RESULTS: The mean age was 36.5+/-11.2 years and 71.8% were men. Blood donors of older age (P=0.010), history of alcohol abuse (P=0.039), past transfusion (P<0.001), intravenous drug use (P<0.001), and with antibody against core antigen of hepatitis B virus reactivity (P=0.003) were less likely to have a false-reactive anti-HCV result. By multivariate analysis, only the absence of parenteral risk factors (prior transfusion and intravenous drug use) was independently associated with false-reactive anti-HCV tests. CONCLUSION: Blood donors with reactive anti-HCV screening tests with no risk factors for parenterally acquired HCV infection are more likely to present with false-reactive results.

Optimized cutoffs improve performance of the aspartate aminotransferase to platelet ratio index for predicting significant liver fibrosis in human immunodeficiency virus/hepatitis C virus co-infection.

AIM: To assess the diagnostic value of modified cutoffs for aspartate aminotransferase to platelet ratio index (APRI) to predict significant liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients. PATIENTS AND METHODS: This retrospective cross-sectional study included consecutive patients with HIV/HCV co-infection who underwent percutaneous liver biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4 METAVIR) was evaluated by estimating the positive and negative predictive values (PPV and NPV respectively) and by measuring the area under the receiver operating characteristics curve (AUROC). RESULTS: One hundred and eleven patients were included (73% men, mean age 40.2+/-7.8 years). Significant fibrosis was observed in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was 0.774+/-0.045. An APRI > or = 1.8 showed a PPV of 75% for the presence of significant fibrosis, and an index < 0.6 excluded significant fibrosis with an NPV of 87%. If biopsy indication was based only on APRI and restricted to scores in the intermediate range (> or = 0.6 and < 1.8), 46% of liver biopsies could have been avoided as compared with 40% using the classical cutoffs. CONCLUSION: APRI with adjusted cutoffs can predict significant liver fibrosis in patients with HIV/HCV co-infection and might obviate the need to perform a biopsy in a considerable percentage of those subjects.

Simple blood tests as noninvasive markers of liver fibrosis in hemodialysis patients with chronic hepatitis C virus infection.

UNLABELLED: HCV infection is common among patients with end-stage renal disease (ESRD) on hemodialysis, and it has been considered an independent risk factor for mortality in this setting. Although liver biopsy in ESRD patients with HCV infection is useful before kidney transplantation, it carries a high risk of complications. We sought to assess the diagnostic value of noninvasive markers to stage liver fibrosis in 203 ESRD HCV-infected patients. Univariate and multivariate analysis were used to identify variables associated with significant fibrosis (METAVIR F2, F3, or F4 stages). Significant liver fibrosis was observed in 48 patients (24%). Logistic regression analysis identified AST and platelet count as independent predictors of significant fibrosis (P < 0.001 and P = 0.001, respectively). The area under the receiver operating characteristic curve of the AST to platelet ratio index (APRI) for predicting significant fibrosis was 0.801. An APRI < 0.40 accurately identified patients with fibrosis stage 0 or 1 in 93% of the cases (NPV = 93%), and all misclassified subjects were F2. A cutoff > or = 0.95 to confirm significant fibrosis had a PPV of 66%. If biopsy indication was restricted to APRI scores in the intermediate range (> or = 0.40 and < 0.95), 52% of liver biopsies could have been correctly avoided. CONCLUSION: Stage of liver fibrosis can be reliably predicted in ESRD HCV-infected subjects by simple and widely available blood tests such as AST levels and platelet count. These tests might obviate the requirement for a liver biopsy in a significant proportion of those patients.