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.

Objective:To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection.Methods:Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results:A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group ( P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [ OR, 2.667 ( CI: 1.389-5.122); P=0.003], increased CK [ OR, 2.544 ( CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] ( CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [ OR, 0.424 ( CI: 0.254-0.709); P=0.001]. Conclusion:Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.