It is a commentary intended to outline and try to clarify some of the issues that have led to confusion in the field regarding acute-on-chronic liver failure.

We summarize evidence indicating that oxidative stress is more than an unbalance between oxidants (ROS) and antioxidants, and that a subtle balance among antioxidants, particularly in mitochondria, is required to prevent the generation of undesirable oxidants and ROS.

This brief report details the experience of a post-liver transplant patient with recurrent hepatitis C genotype 3 infection. The patient was successfully treated with sofosbuvir, velpatasvir, and voxilaprevir without drug-drug interactions involving tacrolimus. This treatment combination can be considered for treatment of recurrent hepatitis C infection after transplantation.

Triple DAA-based therapy, targeting three steps in the HCV replication cycle have a profound effect in restoration of the T-cell impairments and perturbations such as reducing immune activation, exhaustion and restoring immune function in HIV/HCV co-infected patients.

Studies in the past two decades demonstrated that genetics and insulin resistance are two major drivers of nonalcoholic fatty liver diseases (NAFLD). This study tested the feasibility of using a novel measurement of insulin resistance and a genetic score to predict NAFLD disease severity. This pathogenesis-based strategy has many advantages over the conventional liver-centric approach for risk stratification in the management of NAFLD.

Plasminogen activator inhibitor-1 (PAI-1) is a pro-fibrotic protein that is increasingly implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). We determined the effect of genetic deletion and pharmacologic inhibition of PAI-1 on the development of NASH-related fibrosis in mice. We find that PAI-1 regulates hepatic lipid accumulation but does not promote the inflammatory or fibrotic responses that characterize NASH progression.

Perinatal exposure to high fat, fructose, and cholesterol (FFC) in mice primes the fetal liver to fibrosing NASH, likely secondary to nutritional reprograming of the liver methylome. This association is further confirmed, upon re-exposure to the FFC diet in adulthood, where mice develop an accentuated, rapidly progressive NASH phenotype.

ER-stress induction strongly reduces NTCP protein expression, plasma membrane abundance and NTCP-mediated bile acid uptake. This is not controlled via a single UPR-pathway but mainly depends on the interaction of NTCP with calnexin, an ER chaperone. In mice, expression of both Ntcp and calnexin is reduced by thapsigargin or cholestasis-induced ER-stress. Calnexin downregulation in vitro recapitulates the effect of ER-stress on NTCP. In concluion, ER stress-induced downregulation of calnexin provides an additional mechanism to dampen NTCP-mediated bile acid uptake and protect hepatocytes against bile acid overload during cholestasis.

A combination of FXR disruption in liver and intestine results in elevated taurocholic acid TCA) and Myc induction, resulting in age-dependent hepatocarcinogenesis in farnesoid X receptor deficient mice. This study reveals relatively a low incidence of hepatic tumors by FXR deficiency in either hepatocytes or enterocytes alone, likely due to the lack of increased TCA. These findings provide novel insights into the tight association between disruption of BA metabolism, FXR signaling, Myc overexpression, and hepatic tumorigenesis.

Increased intestinal permeability is key in the translocation of small bacterial antigens, which are associated with poor disease outcomes in cirrhosis.

Treg cells help maintain an improved gut barrier integrity, restrict an exacerbated pro-inflammatory Th commitment and preserve the most representative anti-inflammatory SCFAs in experimental cirrhosis.

Promoting Treg cells differentiation might prevent bacterial antigen translocation derived complications in advanced cirrhosis.