Tenofovir Alafenamide Fumarate Reduces Virological Replication in HBeAg ‐Negative Patients With Normal Alanine Aminotransferase: A 48‐Week Randomised Controlled Trial

ABSTRACT The optimal strategy for chronic hepatitis B virus (HBV) infected patients with negative hepatitis B e‐antigen (HBeAg) and normal alanine aminotransferase (ALT) remains uncertain. This study aimed to evaluate the safety and efficacy of tenofovir alafenamide fumarate (TAF) treatment in this patient population. This prospective, open‐label, randomised controlled trial enrolled HBeAg‐negative patients with normal ALT and randomised them 1:1 to either the treatment group (TAF) or the control group (no treatment). The primary endpoint was the reduction in hepatitis B surface antigen (HBsAg) levels from baseline to week 48. A total of 62 patients were enrolled and followed up by 48 weeks ( n = 31 per group). No serious adverse events were reported. At week 48, there was no significant difference in the change in HBsAg between the treatment and control groups [0.01 (−0.06, 0.05) vs. −0.05 (−0.12, 0.06) log 10 IU/mL, p = 0.354]. However, HBV DNA levels were significantly lower in the treatment group (0 vs. 2.86 log 10 IU/mL, p < 0.001). All patients achieved HBV DNA below 20 IU/mL after treatment. Additionally, chitinase‐3‐like protein 1 level was lower in the treatment group (23.8 vs. 44.8 ng/mL, p = 0.019). TAF was well‐tolerated in HBeAg‐negative patients with normal ALT and low‐level HBV DNA viremia. Treatment for 48 weeks led to a high rate of HBV DNA suppression and may potentially delay liver fibrosis progression. Accordingly, early antiviral treatment may benefit this patient population. Trial Registration: Clinical trial number: NCT 04231565