Establishment of a new acute-on-chronic liver failure model

To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48 h. Other animals were killed at 0, 4, 8 and 12 h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48 h was 80%. ALT and AST levels increased markedly at 4 h, but decreased significantly at 8 and 12 h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12 h. Clotting times, TNF-α and IL-6 levels increased significantly, except for 12 h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochrome c expression peaked at 8 h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.     

The Use of Electronic Medical Records-Based Big-Data Informatics to Describe ALT Elevations Higher than 1000 IU/L in Patients with or without Hepatitis B Virus Infection

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.     

乙肝相关慢加急性肝衰竭患者Th17细胞水平及其临床意义

目的探讨乙肝相关慢加急性肝衰竭(HBV-ACLF)外周血Th17细胞的表达及其与临床转归的关系。方法采用流式细胞术分析外周血中Th17细胞比例,flowcytomix技术检测血清中IL-17的水平,荧光PCR检测HBV-DNA载量,ELISA检测HBeAg的状态,分析Th17细胞及IL-17的表达与HBV病毒及预后的关系。结果与健康对照组及慢乙肝组相比,HBV-ACLF患者Th17细胞及IL-17水平明显升高(P<0.01),且Th17细胞与IL-17水平成正相关;进一步分析发现不同病毒复制水平及HBeAg状态的HBV-ACLF患者Th17细胞及IL-17的差异无统计学意义;与预后好转患者相比,预后不佳HBV-ACLF患者Th17细胞及IL-17水平明显增高(P<0.05),且IL-17的水平与终末期肝病评分成正相关。结论 Th17细胞可能参与了HBV-ACLF的发病机制,且IL-17的表达越高可能提示患者的预后不佳。     

乙肝相关慢加急性肝衰竭患者Th17细胞水平及其临床意义

目的探讨乙肝相关慢加急性肝衰竭（HBV-ACLF）外周血Th17细胞的表达及其与临床转归的关系。方法采用流式细胞术分析外周血中Th17细胞比例,flowcytomix技术检测血清中IL-17的水平,荧光PCR检测HBV-DNA载量,ELISA检测HBeAg的状态,分析Th17细胞及IL-17的表达与HBV病毒及预后的关系。结果与健康对照组及慢乙肝组相比,HBV-ACLF患者Th17细胞及IL-17水平明显升高（P〈0.01）,且Th17细胞与IL-17水平成正相关;进一步分析发现不同病毒复制水平及HBeAg状态的HBV-ACLF患者Th17细胞及IL-17的差异无统计学意义;与预后好转患者相比,预后不佳HBV-ACLF患者Th17细胞及IL-17水平明显增高（P〈0.05）,且IL-17的水平与终末期肝病评分成正相关。结论 Th17细胞可能参与了HBV-ACLF的发病机制,且IL-17的表达越高可能提示患者的预后不佳。