Multinational randomized trial to investigate the efficacy of tenofovir alafenamide in reducing adverse clinical events in chronic hepatitis B patients who are beyond treatment indications by current guidelines (ATTENTION trial): first interim analysis

초록

Background and aims: There is lack of robust evidence regarding the efficacy of early antiviral therapy in reducing adverse clinical events among non-cirrhotic chronic hepatitis B (CHB) patients with significant viremia but without notable alanine aminotransferase (ALT) level elevation. Method: The ATTENTION trial, an ongoing randomized, open-label, multicenter, phase 4 study (NCT03753074), is actively enrolling 780 participants across 22 sites in Korea and Taiwan. Key inclusion criteria are: age between 40 and 80 years, serum HBV DNA levels between 4–8 log10 IU/ml, serum ALT levels <70 U/L for males and <50 U/L for females, and absence of cirrhosis. Participants are randomly assigned at a 1:1 ratio to receive either 25 mg/day of tenofovir alafenamide (TAF) or no antiviral treatment (observation). The primary end point was a composite of hepatocellular carcinoma (HCC), death, liver transplantation, or hepatic decompensation, with the first interim analysis planned at year 4. Results: From 2019 to 2023, 734 patients were randomized to either TAF group (n = 369) or observation group (n = 365). As of October 2023, the median follow-up duration was 1.5 years. Participants in the first interim analysis set had an average age of 53.4 years, with 46.5% male, and 82.7% HBeAg-negative. The median ALT level was 31 U/L. No significant differences were observed in baseline characteristics between the two groups. A total of 11 primary clinical events occurred: 2 in the TAF group (both HCC) and 9 in the observation group (7 HCC, 1 death, 1 hepatic decompensation), corresponding to incidence rates of 0.33 and 1.57 per 100 person-years, respectively. The hazard ratio for TAF was 0.21 (99.997% CI: 0.01–5.45). The logrank test yielded Z = 2.22 (p = 0.027), which did not exceed the predefined upper stopping boundary (Z = 4.17; p = 0.00003) in this first interim analysis. Conclusion: Preliminary findings from the ATTENTION trial suggest that early initiation of TAF treatment may significantly reduce the risk of liver-related adverse clinical events in non-cirrhotic CHB patients with significant viremia, but without elevated ALT levels. These results highlight the potential benefit of proactive antiviral therapy in these patients.