Potential benefits of early antiviral treatment with tenofovir alafenamide (TAF) in chronic hepatitis B patients with moderate to high viremia
Lim YS et al, Lancet Gastroenterol Hepatol. 2025;10(4):295-305
The ATTENTION trial investigates early treatment with TAF in chronic hepatitis B patients with moderate to high viraemia without severe liver disease to prevent liver-related endpoints. Participants were randomized to receive either TAF or a placebo. Interim results after a median follow-up of 17.7 months indicate that early TAF treatment reduces risks of severe hepatic complications. While this study is ongoing, the results may support early treatment initiation for hepatitis B patients.
Background: Current guidelines for chronic hepatitis B recommend antiviral therapy for individuals with non-cirrhotic chronic hepatitis B only if they have significant liver fibrosis or elevated alanine aminotransferase (ALT) concentrations. The authors aimed to assess the efficacy of early antiviral treatment in preventing serious liver-related adverse events in individuals with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated ALT concentrations. Methods: ATTENTION is an ongoing randomised controlled trial being conducted at 22 centres in South Korea and Taiwan. Adults aged 40–80 years with non-cirrhotic chronic hepatitis B and serum hepatitis B virus (HBV) DNA concentrations between 4 log10 IU/ml and 8 log10 IU/ml, and ALT concentrations lower than 70 U/l for males and 50 U/l for females were recruited and randomly assigned (1:1) to receive either oral tenofovir alafenamide (25 mg daily) or no antiviral treatment (observation). The primary endpoint was a composite of hepatocellular carcinoma, hepatic decompensation (e.g., development of portal hypertensive complications including ascites, gastro-oesophageal varices, or Child-Pugh score of ≥ 7), liver transplantation, or death from any cause, analysed in the intention-to-treat population. The safety population comprised all randomly assigned participants who received at least 1 dose of the study treatment. This interim analysis was prespecified at 4 years after enrolment of the first participant. Findings: Between February 8, 2019 and October 17, 2023 (the cutoff date for the first interim analysis), 798 individuals were screened and 734 were randomly assigned (369 to tenofovir alafenamide and 365 to observation). At a median follow-up of 17.7 months (interquartile range [IQR], 8.3–24.4), the primary endpoint occurred in 11 participants: 2 in the tenofovir alafenamide group (both hepatocellular carcinoma) and 9 in the observation group (7 hepatocellular carcinoma, 1 hepatic decompensation, and 1 death), corresponding to an incidence rate of 0.33 per 100 person-years in the tenofovir alafenamide group and 1.57 per 100 person-years in the observation group (hazard ratio = 0.21 [97.5% confidence interval: 0.04–1.20]; p = 0.027). The difference between the 2 groups did not surpass the prespecified boundaries required to stop the trial early. Serious adverse events, excluding primary endpoints, were reported in 23 (6%) participants in the tenofovir alafenamide group and 24 (7%) in the observation group.
Interpretation: The results of this interim analysis suggest that early treatment with tenofovir alafenamide reduces the risk of liver-related serious adverse events compared with observation in adults with non-cirrhotic chronic hepatitis B and moderate or high viraemia but normal or mildly elevated alanine aminotransferase (ALT) concentrations. Although these findings await confirmation in planned future analyses, they suggest that existing guidelines could be expanded to allow early antiviral therapy in patients with a moderate or high hepatitis B virus viral load, irrespective of ALT concentrations.