BackgroundAugmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway.MethodsThe level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively.ResultsDuring the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls.ConclusionWe demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury.

Background:The prognosis of primary bile cholangitis (PBC) is linked to gut microbiota dysbiosis. This study investigated the association between the gut microbiome and elevated total bilirubin (TB) level in PBC patients treated with ursodeoxycholic acid (UCDA). Methods: A total of 47 PBC patients with 12 months of UCDA treatment were enrolled. Patients were divided into the TB (+) (TB>1× upper limit of the normal range [ULN]; n = 20) and TB(−) (TB≤1× ULN; n = 27) groups. Stool and serum specimens were collected, and microbiota composition and functional characteristics in the 2 groups were evaluated by 16S RNA gene sequencing and bioinformatic analysis.Results: Bacterial diversity was lower in the TB(+) group than in the TB(−) group, although there was no significant difference in bacterial community profile. The phylum Saccharibacteria showed differential abundance in the 2 groups. Meanwhile, the TB(−) group had lower abundance of the Gemmiger, Blautia, Anaerostipes and Coprococcus genera than the TB(+) group, whereas Holdemania was absent. The abundance of Gemmiger formicillis and Coprococcus eutactus was positively correlated with that of Faecalibacterium prausnitzii, while Blautia, Anaerostipes and Coprococcus were negatively correlated with total bile acid level. Conclusion:TB level in PBC patients treated for 12 months with UCDA is associated with a distinct gut microbiome profile.

Background The prevalence of primary biliary cholangitis (PBC), which is an autoimmune liver disease, has increased over time. PBC often leads to severe consequences, such as liver failure and death. Stratification tools using biochemical liver tests are needed to assess and predict the progression of this disease at the time of PBC diagnosis. Methods We searched PubMed, Cochrane Library, Web of Science, and Embase for studies focused on the relationship between positive rates of Gp210 antibodies and poor prognosis of PBC. The primary end point was the number of PBC patients with poor outcome in the Gp210 antibody (+) and Gp210 antibody (−) groups. The secondary end point was the basic serum level of alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), and IgM in the two groups. The age and number of female patients were also measured. Results A total of 5 studies, comprising 737 patients, were included in this analysis. A positive rate of Gp210 antibodies was positively correlated with poor outcomes and with many types of progression in PBC, especially liver failure. Mortality was also higher in the Gp210 antibody (+) group. Furthermore, the serum levels of ALP and IgM were associated with the positive rate of Gp210 antibodies, while the serum levels of ALT and TBIL were not. The age and number of female patients were also not associated with the positive rate of Gp210 antibodies. Conclusion PBC-specific Gp120 antibodies are optimal predictors of PBC prognosis at the time of diagnosis. Some other liver function indicators, such as ALP and IgM, can be used as predictors to complement Gp210 antibodies to establish a stratification tool to predict the prognosis of PBC at the time of diagnosis.