BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in regulating cytokine-induced inflammatory responses. This study aimed to investigate the role of HNF4α in the development of fulminant hepatic failure (FHF) induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). METHODS: The FHF model was induced by simultaneous intraperitoneal injection of LPS/D-GalN in mice. Three days prior to LPS/D-GalN administration, HNF4α short-hairpin interfering RNA expression plasmid or physiological saline was injected via the tail vein with a hydrodynamics-based procedure. The degree of hepatic damage and cumulative survival rate were subsequently assessed. RESULTS: The expression of HNF4α was increased in the early stage after LPS/D-GalN administration. Inhibiting the expression of HNF4α reduced serum levels of alanine aminotransferase and aspartate aminotransferase, alleviated histological injury, and improved the survival of mice with FHF. In addition, both serum and hepatic tumor necrosis factor alpha expression were suppressed when HNF4α expression was inhibited in mice with FHF. CONCLUSION: Inhibiting HNF4α expression protects mice from FHF induced by LPS/D-GalN, but the exact mechanism behind this needs further investigation.
En-Qiang Chen, Dao-Yin Gong, Xiao-Hua Leng, Lang Bai, Cong Liu, Li-Chun Wang , Hong Tang Center for Infectious Diseases, West China Hospital and State Key Laboratory of Biotherapy ,Department of Forensic Pathology, College of Basic Medicine and Forensic Medicine , Sichuan University, Chengdu 610041, China
With the improved efficacy and accessibility of antiviral agents as well as the concerns about disease progression,there is a hot discussion on whether HBeAg-negative chronic hepatitis B(CHB)patients with normal alanine aminotransferase(ALT)and positive HBV DNA should be treated.According to the international guidelines on the stages of the natural history of HBV infection,HBeAgnegative CHB patients with normal ALT and positive HBV DNA can be divided into two groups:one is the well-known“inactive carrier phase”,which is defined as serum HBV DNA<2000 IU/ml and no significant liver inflammation;and the other is the“indeterminate phase”,which is defined as serum HBV DNA≥2000 IU/mL regardless of the pathological changes in liver tissue,or HBV DNA<2000 IU/mL but accompanied by significant pathological changes in the liver.In this minireview,we will expound the disease characteristics,disease progression,and clinical management status of these two groups.Based on the analysis,we propose that HBeAg-negative patients with normal ALT but detectable serum HBV DNA should be treated,regardless of their age,family history of hepatocellular carcinoma(HCC)or the severity of liver necroinflammation.Expanding the indications of antiviral therapy will help improve the survival and quality of life of patients by preventing disease progression,and consequently reduce the risk of HCC development.
