ursodoxicoltaurine and Hepatitis-C--Chronic

The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.. To assess the beneficial and harmful effects of bile acids for viral hepatitis.. Searches were performed of the trial registers of The Cochrane Hepato-Biliary Group (September 2002), The Cochrane Library (Issue 2, 2002), MEDLINE (September 2002), EMBASE (September 2002), and The Chinese Biomedical Database (April 2001).. Randomised clinical trials comparing any dose or duration of bile acids versus placebo or no intervention for viral hepatitis were included, irrespective of language, publication status, or blinding.. Two reviewers extracted the data independently. The methodological quality of the trials was evaluated with respect to generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The outcomes were presented as relative risks (RR) or weighted mean differences (WMD) with 95% confidence intervals (CI).. We identified 27 randomised trials of bile acids for hepatitis B or C; none were of high methodological quality. In one trial, ursodeoxycholic acid (UDCA) versus placebo for acute hepatitis B significantly reduced the risk of hepatitis B surface antigen positivity at the end of treatment and serum HBV DNA level at the end of follow-up. In another trial, UDCA versus no intervention for chronic hepatitis B significantly reduced the risk of having abnormal serum transaminase activities at the end of treatment. Twenty-five trials compared bile acids (21 trials UDCA; four trials tauro-UDCA) versus placebo or no intervention with or without co-interventions for chronic hepatitis C. Bile acids did not significantly reduce the risk of having detectable serum HCV RNA (RR 0.99, 95% CI 0.91 to 1.07), cirrhosis, or portal and periportal inflammation score at the end of treatment. Bile acids significantly decreased the risk of having abnormal serum alanine aminotransferase activity at the end of treatment (RR 0.82, 95% CI 0.76 to 0.90) and follow-up (RR 0.91, 95% CI 0.85 to 0.98). Bile acids significantly increased the Knodell score (WMD 0.20, 95% CI 0.08 to 0.31) at the end of treatment. No severe adverse events were reported. We did not identify trials including patients with hepatitis A, acute C, D, or E.. Bile acids lead to a significant improvement in serum transaminase activities in hepatitis B and C. There is insufficient evidence either to support or to refute effects on viral markers, mortality, incidence of cirrhosis, or liver histology. Trials with high methodological quality are required.

Topics: Antiviral Agents; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis, Viral, Human; Humans; Randomized Controlled Trials as Topic; Taurochenodeoxycholic Acid; Ursodeoxycholic Acid

Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/β-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/β-catenin signaling is needed.. Cell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection.. Both chronic HCV infection and replicon-induced Wnt/β-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3β-mediated Wnt/β-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3β-mediated Wnt/β-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection.. Targeting ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/β-catenin signaling by DAA treatment. Video Abstract.

Topics: Antiviral Agents; beta Catenin; Carcinoma, Hepatocellular; Cells, Cultured; Endoplasmic Reticulum Stress; Glycogen Synthase Kinase 3 beta; Hepacivirus; Hepatitis C, Chronic; Humans; Liver Neoplasms; Protein Kinase Inhibitors