Retrospective comparison of the safety and effectiveness of tenofovir disoproxil, tenofovir alafenamide fumarate and entecavir patients diagnosed with chronic hepatitis B.

Objective: Chronic hepatitis B virus (HBV) infection continues to be a global public health problem and is a leading cause of cirrhosis, hepatocellular carcinoma, and end-stage liver failure. Current guidelines recommend tenofovir disoproxil fumarate (TDF), entecavir (ETV), and tenofovir alafenamide (TAF) as primary treatments for chronic HBV. Our study aimed to compare the efficacy and safety of these treatment regimens in real life. Materials and Methods: This retrospective cohort study included a total of 225 patients over the age of 18 who received TDF, ETV or TAF for at least 6 months for chronic HBV treatment at the Gastroenterology Clinic of Karadeniz Technical University Faculty of Medicine between January 2013 and August 2023. The treatment groups were compared in terms of efficacy and safety. Treatment efficacy was assessed by virological response, serological response and biochemical response, while changes in renal functions, lipid panel and calcium and phosphorus levels were evaluated for safety. Results: A total of 225 patients were included in the study, 143 (63.6%) male, 82 (36.4%) female, and the mean age was 48.8 (19-91). 112 (49.8%) of the patients were in the TDF group, 76 (33.8%) in the ETV group, and 37 (16.4%) in the TAF group. The follow-up period was significantly shorter in the TAF group than in the other groups (mean 25.87±15.44 months in the TAF group, mean 48.17±36.77 months in the TDF group, and mean 42.93±31.84 months in the ETV and TDF groups). All patients in the ETV and TDF groups were naive to antiviral treatment, while only 8 (22%) of the patients in the TAF group were naive to treatment. A similar significant decrease in HBV DNA was observed in all treatment groups. HBsAg seroconversion was detected in 3 patients in both the TDF group (2.7%) and the ETV group (3.9%), while it was not detected in the TAF group. In all treatment groups, ALT levels were statistically significantly lower after treatment compared to pre-treatment and no statistically significant difference was found between the groups in terms of ALT normalization (p=0.522). While a statistically significant decrease in GFR levels was observed in the ETV and TDF groups after treatment (p<0.001), there was also a decrease in GFR in the TAF group, but this decrease was not statistically significant (p>0.05). In the ETV and TDF groups, creatinine values after treatment were statistically significantly higher than before treatment (p<0.05), but no statistically significant difference was found between the creatinine values of the patients in the TAF group before and after treatment (p=0.338). Total cholesterol, LDL and triglyceride levels were statistically significantly lower in the TDF group and total cholesterol and LDL levels in the ETV group compared to before treatment. HDL and triglyceride levels were significantly higher in the TAF group. Conclusion: In conclusion, we found that TDF, ETV and TAF treatments were similarly effective in terms of virological, serological and biochemical response in the treatment of chronic HBV. Renal functions were less affected in the TAF group than in the TDF and ETV groups, while renal function deterioration was similar in the TDF and ETV groups. While phosphorus levels decreased after treatment in the TDF group, phosphorus levels were similar before and after treatment in the TDF and ETV groups. Calcium levels were similar before and after treatment in all treatment groups. While lipid profiles generally increased in the TAF group, lipid profiles decreased in the TDF and ETV groups. Larger prospective studies are needed to evaluate the safety of these treatment groups in particular. Keywords: Chronic HBV, Entecavir, Tenofovir Disoproxil Fumarate, Tenofovir Alafenamide