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Background & Aims: There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported., Methods: HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined by undetectable HCV-RNA 12weeks after treatment cessation. Exact logistic regression analysis was used to identify factors associated with SVR12., Results: A total of 323 patients (74% men) with a median age of 53years were included, 99% of whom were on combination antiretroviral therapy (cART). HIV RNA load was <50 copies/ml in 88% of patients; median CD4 cell count was 540/mm 3 ; 60% of patients were cirrhotic; 68% had previously received unsuccessful anti-HCV treatment. cART was protease inhibitor (PI)-based in 23%, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 15%, and integrase inhibitor (II)-based in 38%, while 24% of patients received other regimens. The SVR12 rate was 93.5% overall (95% confidence interval [CI]: 90.2-95.9), 93.3% (88.8-96.4) in patients with cirrhosis and 93.8% (88.1-97.3) in patients without cirrhosis. The SVR12 rates were 93.1% (84.5-97.7), 91.8% (80.4-97.7) and 95.8% (90.5-98.6) respectively, in patients receiving PI-based, NNRTI-based and II-based cART. In adjusted analysis, SVR12 was not associated with HIV RNA load, the cART regimen, cirrhosis, prior anti-HCV treatment, the duration of anti-HCV therapy, or ribavirin use. The most common adverse effects were fatigue and digestive disorders., Conclusions: New all-oral DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients., Lay Summary: We evaluated efficacy and safety of all-oral DAA regimens in a large French nationwide observational cohort study of HIV/HCV co-infected patients. Sustained virological response 12weeks after treatment cessation was 93.5% overall. The all-oral DAA regimens were well-tolerated and most common adverse effects were fatigue and digestive disorders., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Immunity and genetic factors govern the recovery from acute hepatitis C virus (HCV) infection. No predictive factors have been yet identified in patients coinfected with the human immunodeficiency virus (HIV). We investigated whether early T cell responses to HCV producing transforming-growth-factor beta (TGF-β) predict the outcome of acute HCV coinfection, independently of the IL-28B gene polymorphism., Methods: Intracellular cytokine staining assays against HCV-core, E1, NS2, and NS4 overlapping peptides were used for the analysis of peripheral HCV-specific TGF-β-producing T cells. Patients were genotyped for IL-28B polymorphisms. Healthy donors' samples were tested as controls. Twenty-four acute hepatitis C-HIV+ patients were followed-up for 15 months defining two groups: (A) Recovered (n=16, 5 spontaneous recoveries, 11 sustained virologic response after treatment), (B) Chronic HCV (n=8, 4 spontaneous chronic course, 4 therapeutic failures)., Results: During the acute pretreatment phase, core/NS2-specific TGF-β-producing CD4+ and/or CD8+ T cells were detected in 8/24 (33%) patients. Lack of anti-HCV TGF-β+ cells was characteristic of healthy donors and Group A, except for 2 cases, with frequencies significantly lower than in Group B (p=0.04 and 0.01), and was associated with recovery in 14/16 cases. Presence of anti-HCV TGF-β+ cells was associated with persistent viremia in 6/8 cases (p=0.005). This profile remained stable over time. Such TGF-β production was independent of the rs129679860 SNP (p=1.0) which was not associated with recovery (p=1.0)., Conclusions: During acute hepatitis C, pre-therapeutic HCV-specific TGF-β-producing T cells are a new marker independent of the IL-28B gene polymorphism, predicting the lack of spontaneous or therapeutic HCV clearance., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and, by measuring organ damage and tumor stage, can influence treatment. Moreover, elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma. We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment Randomized Protocol (SHARP) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, and bilirubin; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment., Methods: Patients (n=602) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase (not significantly elevated, mildly elevated, or moderately elevated), alpha-fetoprotein (normal or elevated), and bilirubin (normal or elevated). Bilirubin was measured at baseline and on day 1 of each cycle., Results: Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin had shorter overall survival (OS) than those with normal baseline concentrations, irrespective of treatment group. No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin. Median changes from baseline in bilirubin concentration at the last cycle of treatment were +0.17 and +0.19 mg/dl in the sorafenib and placebo groups, respectively., Conclusions: These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma, irrespective of baseline alanine aminotransferase/aspartate aminotransferase, alpha-fetoprotein, or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Hepatitis C virus (HCV) coinfection is one of the leading causes of mortality in human immunodeficiency virus-infected patients. The current standard of care leads to cure only in a part of these patients. The course of the disease is determined by the rapidity of liver fibrosis progression (LFP). The influence of interferon on LFP in coinfected patients has yet not been evaluated by comparative liver biopsies., Methods: We extracted data of patients who had serial liver biopsies from a hospital database. Histopathological findings were compared to factors possibly linked to fibrosis progression. Furthermore, we studied the impact of response to interferon treatment on fibrosis progression., Results: Hundred and twenty-six patients were included, 68 had received anti-HCV treatment, and 58 had not. The median time between the first and the last biopsy was 4 years. Worsened fibrosis was observed in 35 of 58 (60%) untreated patients, and 22 of 50 (44%) patients in the nonresponder/relapser group, and in 5 out of 18 (28%) in the SVR group. Liver fibrosis evolution was significantly better in patients achieving a SVR than in untreated and NR/R patients (p<0.02, odds-ratio [95% CI] for improvement vs. stability vs. worsening=3.16 [1.24-8.07]). This result persisted after adjustment for known predictors of liver fibrosis progression, HBsAg, CD4, and alcohol consumption: adjusted odds ratio=2.89 [1.09-7.68], p=0.03., Conclusions: HCV treatment can stop fibrosis progression and induce its regression. Nonresponders to treatment may even have a fast fibrosis progression. It remains to be clarified if the same factors that induce nonresponse to treatment may also induce faster fibrosis progression., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background/aims: To use bile acids as shuttles for directing cytostatic drugs toward liver tumors, the ability of the tumor to take up these compounds must be maintained. Thus, we investigated whether glycocholate (GC) derivatives such as the fluorescent FITC-GC and the cytostatic Bamet-R2 are taken up by neoplastic tissue at different stages of chemically-induced rat liver carcinogenesis., Methods: Placental glutathione-S-transferase (GST-P) was immunohistochemically detected. Uptake studies were carried out on pure GST-P-positive cell cultures, obtained by treatment with ethacrinic acid. FITC-GC, Bamet-R2 or cisplatin was administered (i.v.) to anaesthetized rats. Platinum in culture cells, liver and kidney was measured by flameless atomic absorption., Results: Co-localization after FITC-GC i.v. administration revealed that only 15% (20 weeks) and 30% (32 weeks) of GST-P-positive tissue was not able to take up FITC-GC. GC uptake was lower in GST-P-positive cells than in normal hepatocytes. Bamet-R2, uptake was lower than that for GC, but similar in both cell types. The amount of Bamet-R2 or cisplatin retained by GST-P-positive tissue after in vivo administration was progressively increased during carcinogenesis. Moreover, this amount was higher for Bamet-R2 than for cisplatin. By contrast, in the kidney, it was higher for cisplatin than for Bamet-R2., Conclusion: These results indicate that at the different stages of rat hepatocarcinogenesis most GST-P-positive tissue is able to take up bile acid derivatives, such as Bamet-R2.

Background/aim: Dextran-70 is frequently used as a plasma expander in patients with cirrhosis treated with large-volume paracentesis to prevent post-paracentesis hypovolemia, which is thought to develop after 24 h following the procedure. However, there are no studies on Dextran-70 pharmacokinetics in cirrhosis., Methods: Nine patients with alcoholic cirrhosis and tense ascites treated with a 5-1 paracentesis were given 500 ml of Dextran-70. Blood samples to measure the plasma concentration of dextran were obtained 15 and 30 min, 1, 2, 3, 6, 12 and 24 h and 2 and 6 days after the end of the infusion. Nine healthy volunteers were studied in identical fashion after infusion of 100 ml of Dextran-70. The plasma concentration of dextran was determined by the anthrone method. A bicompartmental model was used to analyze the pharmacokinetic parameters., Results: There were no significant differences between patients with cirrhosis and controls in the volume of distribution (7.7 +/- 0.6 vs. 7.3 +/- 1.21), half-life of the first and second component of plasma disappearance (2.96 +/- 0.69 and 80.3 5.9 h in patients with cirrhosis vs 2.82 +/- 0.69 and 67.1 +/- 10.7 h in controls)., Conclusions: The pharmacokinetics of Dextran-70 in patients with cirrhosis and ascites after large-volume paracentesis is similar to that in controls. This may explain why Dextran-70 is less effective than albumin in preventing paracentesis-induced hypovolemia, which starts after most Dextran fraction has disappeared from plasma.