Short-term mortality of acute-on-chronic liver failure in patients with chronic hepatitis B following lamivudine versus entecavir antiviral treatment / 中国感染与化疗杂志

Objective To compare the short-term mortality of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B following lamivudine versus entecavir antiviral treatment. Methods All chronic hepatitis B patients associated with ACLF were included in this analysis if they were treated with lamivudine or entecavirat the Department of Infectious Diseases, Huashan Hospital, Fudan University, from August 2010 to August 2016. Results A total of 56 patients were included (36 in lamivudine group and 20 in entecavir group). The 7-day, 14-day and 28-day survival rate was 94％, 72％ and 64％ in lamivudine group, and 70％, 65％ and 65％ in entecavir group. Lamivudine group showed significantly lower 7-day mortality than entecavir group, but no significant difference in 14-day and 28-day mortality. Subgroup analysis did not show significant difference in 28-day mortality between the two groups either in model for end-stage liver disease (MELD)≤30 patients or in ACLF grade 0-1 patients. Lamivudine treatment was associated with significantly lower 7-day mortality than entecavir in cirrhosis patients, but no significant difference in 14-day and 28-day mortality. Conclusions Lamivudine treatment is associated with significantly higher 7-day survival rate than entecavir. However, the short-term (within 28 days) mortality of acute on chronic liver failure in chronic hepatitis B patients is similar between lamivudine and entecavir treatment. Lamivudine is also appropriate for the patients with cirrhosis or waiting for liver transplantation.

The effect of antiviral therapy on the clinical outcomes of chronic hepatitis B / 中华实验和临床病毒学杂志

Chronic hepatitis B (CHB) is a chronic inflammation of liver which infected with the hepatitis B virus (HBV). The chronic inflammation of liver will lead to cirrhosis, complications of liver decompensation from cirrhosis, hepatocellular carcinoma (HCC) and even death.There are two kinds of drugs are available for the treatment: interferon(IFN)which including IFN-αand pegylated IFN, and nucleoside analog(NAs) which including lamivudine, adefovir dipivoxil, entecavir, telbivudine and Tenofovir disoproxil fumarate.We will describe the mechanisms of the CHB, INF and NAs to state the effect on the clinical outcome(cirrhosis, complications from cirrhosis, hepatocellular carcinoma and death) of the therapy of antiviral therapies.

Treatment of HBV recurrence after liver transplantation for HBV related liver diseases / 中华器官移植杂志

Objective To analyze the HBV recurrence and summarize the experiences in treatment of HBV recurrence after liver transplantation for HBV related liver diseases.Method A total of 650 patients subject to liver transplantation for HBV related liver diseases from September 2002 to February 2007 were included,and the clinical data were retrospectively analyzed.Result Twenty-five (3.85％) of 650 patients experienced HBV recurrence.All liver functions recovered to normal after nucleoside or nucleotide analogs treatment.Two cases lost to follow-up,2 cases were died of tumor recurrence,and 1 case died of tumor recurrence after re-transplantation.Eleven cases were positive for serum HBsAg,and HBV DNA was converted to undetectable levels in 10 cases.One case developed to decompensated liver cirrhosis,and HBsAg was negative after re-transplantation.In 7 cases,after nucleos(t)ide analogs treatment,HBsAg titer was decreased gradually to a lower level,and continuous intravenous drip of large doses of HBIG for 3 to 5 days achieved anti-HBs seroconversion.Conclusion Nucleos(t) ide analogs can effectively suppress viral replication of HBV recurrence after liver transplantation.When the HBsAg titer is decreased to a lower level,large doses of HBIG can achieve anti-HBs seroconversion.

Short-term exposure to stavudine results in neuron apoptosis, neurite shrink and down-regulated expression of thymidine kinase 2 / 中华传染病杂志

Objective To investigate the central neurotoxicity induced by nucleoside analog reverse transcriptase inhibitors (NRTIs)-stavudine (D4T).Methods Mouse primary cortical neurons were cultured and treated with different concentrations of stavudine.Neuron apoptosis was analyzed by calcein/acetomethoxy/propidium iodide (AM/PI) staining. Morphological change of neuron was confirmed by immunofluorescence.Mitochondrial DNA copies which were usually evaluated through Cycloxygenase 2 (COX-2) and thymidine kinase2 (TK2) mRNA were determined by real-time quantitative polymerase chain reaction.Chi-square test,student t test and Wilcoxon nonparameter test were used to analyze the data.Results Neuronal apoptosis observed in 50 μmol/L D4T treatment group was more significant than that in 0μmol/L D4T treatment group and 25 μmol/L D4T treatment group (51.3％±12.4％ vs 24.9％±8.2％ and 26.5％±10.6％,respectively; x2 =7.25 and 6.93,respectively; both P＜0.01).The average neurite numbers of each neuron were 11.2±3.6 in 0μmol/L D4T treatment group,8.6±2.8 in 25 μmol/L D4T treatment group and 4.3±2.4 in 50 μmol/L D4T treatment group.The difference was statistically significant between 25 μmol/L D4T treatment group and 0 μmol/L D4T treatment group (t=4.06,P＜0.01) and between 50 μmol/L D4T treatment group and 25 μmol/L D4T treatment group (t =4.35,P＜ 0.01). Furthermore,the average lengths of neuritis were (319.9±100.2) μm in 0 μmol/L D4T treatment group,(298.3±83.9) μm in 25 μmol/L D4T treatment group and (258.4±82.2) μm in 50 μmol/L D4T treatment group.The difference was statistically significant between 25 μmol/L D4T treatment group and 0 μmol/L D4T treatment group (t=4.58,P＜0.01) and between 50 μmol/L D4T treatment group and 25 μmol/L D4T treatment group (t=4.65,P＜0.01).TK2 mRNA expression dramatically decreased along with the increasing D4T concentration.The fold changes were 0.34 in 25 μmol/L D4T treatment group and 0.08 in 50 μmol/L D4T treatment group. The difference was statistically significant between 25 μmol/L D4T treatment group and 0μmol/L D4T treatment group (Z=- 3.28,P＜0.01) and between 50 μmol/L D4T treatment group and 25 μmol/L D4T treatment group (Z=-4.25,P＜0.01).Compared with 0μmol/L D4T treatment group,the relative fold changes of COX-2 copies were 1.01 in 25 μmol/L D4T treatment group and 1.12 in 50 μmol/L D4T treatment group.The differences were not significant among the three groups (Z=0.98 and 1.24,respectively; both P＞0.05).Conclsion It suggests that short-term exposure to D4T may result in neuron apoptosis,neurite shrink and down-regulated expression of TK2,but the level of mitochondrial DNA copies keeps stable.