Journal of hepatology
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Journal of hepatology · Oct 2015
Randomized Controlled Trial Multicenter StudySafety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study.
Tigatuzumab is a humanized monoclonal antibody that acts as a death receptor-5 agonist and exerts tumour necrosis factor-related apoptosis-inducing ligand-like activity. In this phase II study, safety and tolerability of the combination of tigatuzumab and sorafenib was evaluated in patients with advanced hepatocellular carcinoma. ⋯ Tigatuzumab combined with sorafenib vs. sorafenib alone in adults with advanced hepatocellular carcinoma did not meet its primary efficacy end point, although tigatuzumab plus sorafenib is well tolerated in hepatocellular carcinoma.
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Journal of hepatology · Oct 2015
Randomized Controlled Trial Multicenter StudyPharmacokinetics and safety of co-administered paritaprevir plus ritonavir, ombitasvir, and dasabuvir in hepatic impairment.
Paritaprevir, ombitasvir, and dasabuvir are direct-acting antivirals for treatment of chronic hepatitis C virus (HCV) infection. The aim of this study was to characterize the effects of mild, moderate, and severe hepatic impairment on the pharmacokinetics of these drugs. ⋯ The changes observed in paritaprevir, ritonavir, ombitasvir, and dasabuvir exposures in subjects with mild or moderate hepatic impairment do not necessitate dose adjustment. Subjects with severe hepatic impairment had substantially higher paritaprevir and dasabuvir exposures.
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Journal of hepatology · Sep 2015
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis.
Insulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH. ⋯ Liraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.
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Journal of hepatology · Sep 2015
Randomized Controlled Trial Multicenter StudySofosbuvir plus ribavirin for treating Egyptian patients with hepatitis C genotype 4.
Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection in the world, and more than 90% of patients are infected with genotype 4 virus. We evaluated the efficacy and safety of the HCV polymerase inhibitor sofosbuvir in combination with ribavirin in HCV genotype 4 patients in Egypt. ⋯ Sofosbuvir plus ribavirin for 12 or 24 weeks is effective in treating both treatment-naïve and treatment-experienced Egyptian patients with genotype 4 HCV.
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Journal of hepatology · Sep 2015
Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis.
Liver injury is a common complication of heat stroke (HS), and often constitutes a direct cause for patient death. The cellular and molecular mechanism underlying HS-induced liver injury remains unclear. Recent evidence indicates that inflammasome plays an important role in mediating sterile inflammation triggered by tissue damage. Using a rat HS model, we identified a novel mechanism by which inflammasome-dependent interleukin-1β (IL-1β) activation and hepatocyte pyroptosis mediate HS-induced liver injury. ⋯ These findings demonstrate an important role of HMGB1 in mediating inflammasome activation in the development of liver injury following HS, and suggest that targeting inflammasome may represent a novel therapeutic strategy to limit cell death and prevent liver failure after HS.