Comparison of efficacy and safety of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate treatment in patients with high viral load of hepatitis B virus.

Nucleos(t)ide analogues (NAs) have demonstrated potent efficacy in suppressing viral replication in chronic hepatitis B (CHB). This 48-week study compared the efficacy and safety of NA treatment for CHB patients with high viral load (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] > 7 log10 IU/mL). This retrospective study included 180 nucleos(t)ide-naïve CHB patients with high viral load undergoing NA monotherapy, which were stratified into 3 groups: entecavir (ETV, n = 82), tenofovir disoproxil fumarate (TDF, n = 58), and tenofovir alafenamide fumarate (TAF, n = 40). The primary endpoint was the proportion of patients achieving HBV DNA < 20 IU/mL, with safety assessed by lipid profiles and renal function. The study subjects' mean baseline HBV DNA levels were 7.68, 7.73, and 7.75 log10 IU/mL in ETV, TDF, and TAF groups, respectively. At week 48, TDF had a higher viral suppression (HBV DNA < 20 IU/mL) rate (67.74%) than TAF (37.50%) cohort (P = .004) and ETV (54.88%) was comparable to both (P > .05). Hepatitis B e antigen loss and seroconversion were comparable across all groups, with no hepatitis B surface antigen loss observed. Similar proportions of patients with high alanine aminotransferase levels at baseline achieved normalization by week 48 in all regimens. Low-density lipoprotein, total cholesterol, and triglyceride elevations were comparable across all groups. High-density lipoprotein reductions were 15.63%, 35.71%, and 17.86% in ETV, TDF, and TAF, respectively (P = .043), with TDF reducing high-density lipoprotein and total cholesterol more than ETV (P = .014 and P < .001). No significant differences were found in serum creatinine elevation or estimated glomerular filtration rates reduction among the groups. TDF was preferentially recommended for high viral load CHB patients, as its superior antiviral efficacy and comparable safety profile.