Objective: To observe the efficacy and safety of de novo combination of Lamivudine(LAM) and Adefovir Dipivoxil (ADV) therapy counter to Entecavir (ETV) monotherapy in patients with chronic hepatitis B (CHB)- related compensated liver cirrhosis. Methods: Patients with chronic hepatitis B-related compensated cirrhosis who were initially treated with LAM and ADV for more than 1 year were randomly assigned to two groups, one half replaced with ETV monotherapy, and the other half continued LAM and ADV co-therapy. Liver biochemistry, renal biochemistry, estimated glomerular filtration rate, alpha-fetoprotein, HBV serology markers and serum HBV DNA were measured every 3 months. Urine β2-microglobulin was measured every 6 months And retinol binding protein, followed up for 3 years. The mean values of the two groups were compared with t-test, and the rate of comparison was analyzed by x2 test. Results: A total of 580 cases were collected, 290 cases were replaced with ETV monotherapy, the other 290 patients continued to LAM and ADV combination therapy. In the ETV group, the rates of HBV DNA negative conversion at 1 year, 2 years and 3 years were 77.6%, 84.5% and 94.5% respectively, while the HBV DNA negative conversion rates at 1, 2 and 3 years in the LAM and ADV combination groups were 69.3%, 73.4% and 80.3% respectively. Among them, the negative rates of HBV DNA in the second year and the third year were P < 0.05, the difference was statistically significant. The 3-year cumulative gene-resistant rate in the ETV group was 1.4%, while the combined treatment was as high as 8.6%, and the difference was statistically significant in the two groups. The estimated value of serum creatinine and glomerular filtration rate in ETV group was followed by 3 years, and the baseline level was maintained, in the same group, the serum creatinine was higher than baseline, and the estimated value of glomerular filtration rate decreased. The results showed that there were 6.2%, 12.1%, 22.1% and 0, 0.3%, 1%, respectively, in 1, 2 and 3 years for the group of consecutive treatment and the replacement of ETV Group. The estimated glomerular filtration rate decreased by more than 30% compared with the baseline. The difference was statistically significant; the proportion of serum creatinine in the 1 year, 2 years and 3 years of the combined treatment group was 1.7%, 4.5% and 6.6%, compared with the baseline rise of > 50 μmol/l, and the ETV group was replaced in the 1 year, The values of 2 and 3 years were 0,0,0.7%, of which the 2nd and 3rd years were statistically significant; the proportion of microalbuminuria and retinol-binding protein in patients with combined treatment group was also significantly higher than that of Β2-m ETV Group. Conclusion The initial combination of LAM and ADV therapy is inferior in terms of ETV monotherapy. Single therapy with ETV increase the rate of viral response, reduce the incidence of drug resistance, and also reduce the incidence of renal impairment in patients with chronic hepatitis B -related compensated liver cirrhosis.

To assess the protective effects of luteolin(LT)on liver fibrosis in rats with autoimmune hepatitis(AIH)and to explore the underlying mechanisms,total of 62 rats were recruited and randomly divided into normal control group(CT),AIH model group(AIH),LT low-dose group(LT L),LT medium-dose group(LT M),LT high-dose group(LT H)and prednisolone group(PSL),with 10 rats in each group.The rat in CT group were injected with an equivalent volume of physiological saline via the tail vein,when the rat in the other groups were received tail vein injection of concanavalin A(Con A)dissolved in physiological saline to induce the AIH model.Then,the rat in LT L,M,and H groups were administered intraperitoneal injections of LT dissolved in physiological saline(at doses of 5,25,and 50 mg/kg,respectively),and the rat in the PSL group received intraperitoneal injections of PSL dissolved in physiological saline(at a dose of 10.0 mg/kg),while the rat in the CT and AIH groups received equivalent volumes of physiological saline intraperitoneally.All treatments were administered twice daily for 7 consecutive days.The day after the last treatment,liver function indices,peripheral blood lymphocyte subsets,and hepatic hydroxyproline content were measured.Furthermore,Masson staining was used to assess the liver fibrosis was assessed using,and Western blot analysis was performed to detect the expression levels of activated nuclear factor κB(NF-κB),phosphorylated NF-κB(p-NF-κB),inhibitor of nuclear factor κBα(IκBα),and phosphorylated IκBα(p-IκBα)proteins in liver tissue.Compared to the CT group,the AIH group exhibited significantly higher serum levels of alanine aminotransferase(ALT),total bilirubin(TBIL),CD4+T lymphocyte ratio,CD4+/CD8+ratio,and hepatic hydroxyproline content(P<0.05),while albumin(ALB)levels and the CD8+T lymphocyte ratio were significantly lower(P<0.05).LT in all doses could reverse these changes mentioned above in AIH rats in a dose-dependent manner(P<0.05),and no significant differences were observed between the LT H group and the PSL group in these parameters(P>0.05).Masson staining results revealed that liver fibrosis in the LT groups was less severe than that in the AIH group,with a clear dose-dependent effect.The PSL group exhibited similar antifibrotic effects to the LT H group.Furthermore,the AIH group showed significantly higher levels of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios in liver tissue,as compared to the CT group(P<0.05),while LT could suppress the increase of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios(P<0.05)in a dose-dependent manner(P<0.05),and no significant differences in these ratios were observed between the LT H group and the PSL group(P>0.05).Taken together,Luteolin can improve liver function and immune function,and alleviate liver fibrosis by inhibiting the NF-κB pathway in AIH rats.