Journal of hepatology
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Journal of hepatology · Jul 2013
Randomized Controlled Trial Clinical TrialThe Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. ⋯ Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.
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Journal of hepatology · Jul 2013
Multicenter StudyA phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1.
ABT-450 (combined with low-dose ritonavir, ABT-450/r) is a potent HCV NS3 protease inhibitor, and ABT-072 is a non-nucleoside NS5B polymerase inhibitor. The goal of this study was to evaluate the safety, tolerability, and efficacy of the peginterferon-free combination of ABT-450/r and ABT-072 with ribavirin in treatment-naïve patients with IL28B CC genotype, infected with HCV genotype 1. ⋯ A 12-week regimen of ABT-450/r and ABT-072 with ribavirin was well tolerated with 9/11 patients achieving sustained virologic response through 36 weeks of post-treatment observation. These findings suggest that peginterferon-free regimens may have the potential to cure a high proportion of HCV genotype 1-infected patients.
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Journal of hepatology · Jul 2013
Lessons from look-back in acute liver failure? A single centre experience of 3300 patients.
Acute liver failure (ALF) is a rapidly progressive critical illness with high mortality. Complex intensive care unit (ICU) protocols and emergency liver transplantation (ELT) are now often available, but rarity and severity of illness have limited its study and evidence-base for care. We reviewed patients treated over a 35-year period at a specialist high-volume ICU, quantifying changes in disease aetiology, severity and evolution of ICU support and ELT use and outcome. ⋯ The nature and outcome of ALF have transformed over 35 years, with major improvements in survival and a fall in prevalence of cerebral oedema and ICH, likely consequent upon earlier illness recognition, improved ICU care, and use of ELT.
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Journal of hepatology · Jul 2013
Endoplasmic reticulum stress induces fibrogenic activity in hepatic stellate cells through autophagy.
Metabolic stress during liver injury enhances autophagy and provokes stellate cell activation, with secretion of scar matrix. Conditions that augment protein synthesis increase demands on the endoplasmic reticulum (ER) folding capacity and trigger the unfolded protein response (UPR) to cope with resulting ER stress. Generation of reactive oxygen species (ROS) is a common feature of hepatic fibrogenesis, and crosstalk between oxidant stress and ER stress has been proposed. The aim of our study was to determine the impact of oxidant and ER stress on stellate cell activation. ⋯ These data implicate mechanisms underlying protein folding quality control in regulating the fibrogenic response in hepatic stellate cells.
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Journal of hepatology · Jul 2013
Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis.
Sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) axis is involved in multiple biological processes, including liver fibrosis. Angiogenesis is an important pathophysiological process closely associated with liver fibrosis; however, the functional role of SphK/S1P/S1PR in this process remains incompletely defined. ⋯ SphK1/S1P/S1PR1/3 axis plays a crucial role in the angiogenic process required for fibrosis development, which may represent an effective therapeutic strategy for liver fibrosis.