Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD.

Blocking integrin αβ-mediated CD4 T cell recruitment to the intestine and liver protects mice from western diet-induced non-alcoholic steatohepatitis.

Background & Aims: The heterodimeric integrin receptor αβ regulates CD4 T cell recruitment to inflamed tissues, but its role in the pathogenesis of non-alcoholic steatohepatitis (NASH) is unknown. Herein, we examined the role of αβ-mediated recruitment of CD4 T cells to the intestine and liver in NASH.

Methods: Male littermate F11r (control) and junctional adhesion molecule A knockout F11r mice were fed a normal diet or a western diet (WD) for 8 weeks.

Western diet-induced increase in colonic bile acids compromises epithelial barrier in nonalcoholic steatohepatitis.

There is compelling evidence implicating intestinal permeability in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain poorly understood. Here we examined the role of bile acids (BA) in western diet (WD)-induced loss of colonic epithelial barrier (CEB) function in mice with a genetic impairment in intestinal epithelial barrier function, junctional adhesion molecule A knockout mice, F11r . WD-fed knockout mice developed severe NASH, which was associated with increased BA concentration in the cecum and loss of CEB function.