Optimized Treatment Of HBeAg Negative Chronic Hepatitis B And Necroptosis In Liver Failure

FIRST PART Aims: Explore the optimal treatment of chronic hepatitis B for functional cure.Methods: A retrospective study enrolled 101 patients entecavir treated with HBV DNA undetectable,and according to the antiviral strategy,the patients were divided to 3 groups,entecavir sequential pegylated interferon group,entecavir combined with pegylated interferon group and entecavir monotherapy group.HBsAg clearance and decline after 48 weeks of treatment of three groups was anglyzed,and factors affecting the decline of HBsAg were explored and then screen the dominant pop?lation.Results: HBsAg clearance was higher in the pegylated interferon add-on or switch-to group than that in entecavir monotherapy group,and HBsAg clearance was higher in patients with HBsAg less than 1000 IU/ml at baseline and HBsAg reduction was over than 0.2 logIU/ml at 24 weeks of treatment(22%).Conclusions: Entecavir add-on or switch-to pegylated interferon can improve HBsAg clearance in patients with HBeAg negative chronic hepatitis B.High HBsAg clearance was achieved in the patients with HBsAg titers at baseline <1000 IU/ml and HBsAg reduction > 0.2 log IU/ml.SECOND PARTAims: Explore the regulation of necroptosis in liver failure.Methods: A cell model of necroptosis and a mouse model of acute liver failure were established to target the intervention of MLKL expression to explore the role of programmed necrosis in liver failure.Results: The liver injury of MLKL overexpression group was worse than that of the control group.The MDA of MLKL overexpressing mice was significantly higher than that of the control group.The cell survival of the MLKL overexpression group was lower than that of the MLKL low expression group when AML12 cell line teated with TSZ which induced necroptosis.Conclusions: Necroptosis plays an important role in liver failure and may be achieved by affecting the oxidative stress and mitochondrial damage in hepatocytes.