Tenofovir alafenamide (Vemlidy) reduced the risk of serious liver-related events in adults with chronic hepatitis B virus (HBV) and moderate or high viraemia compared to a group not taking the antiviral, according to a study published in The Lancet Gastroenterology and Hepatology. 1
“At a median follow-up of 17.7 months (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% CI 0·04–1·20]; p=0·027),” the investigators wrote.1
They noted there was not enough of a difference between the 2 cohorts to stop the trial early according to their prespecified boundaries. Excluding the primary endpoints, there were serious adverse events in 23 (6%) participants in the antiviral cohort and 24 (7%) in the observation cohort.1
According to Gilead, the antiviral’s manufacturer, tenofovir alafenamide is a targeted prodrug of tenofovir that was FDA approved in 2016 as a once-daily treatment for adults with chronic HBV infection with compensated liver disease.2
In 2022, the FDA approved tenofovir alafenamide for the treatment of chronic HBV infection in pediatric patients 12 years of age and older with compensated liver disease. And last year, the antiviral was expanded further to include patients as young as 6.2
Tenofovir alafenamide is recommended as a preferred or first-line treatment for adults with chronic HBV with compensated liver disease by the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines.2
What You Need to Know
The study found that tenofovir alafenamide significantly lowered the incidence of serious liver-related events, including hepatocellular carcinoma and hepatic decompensation, in adults with chronic HBV and moderate or high viraemia compared to an untreated observational group (0.33 vs. 1.57 events per 100 person-years; HR 0.21, p=0.027).
Despite not meeting the threshold to halt the trial early, the findings suggest that antiviral therapy could be beneficial for patients with a moderate or high HBV viral load, regardless of ALT levels, potentially influencing future HBV treatment guidelines.
Tenofovir alafenamide is already a first-line treatment for adults with compensated liver disease per AASLD and EASL guidelines. Its FDA approval has expanded over the years, now including pediatric patients as young as six years old.
Study Parameters and Other Takeaways
The study was conducted within the ATTENTION trial, which is an ongoing randomized controlled trial being conducted in South Korea and Taiwan across 22 medical centers. In terms of trial participants, investigators recruited adult patients between the ages of 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. Participants were randomly assigned, 1 to 1 to receive either oral tenofovir alafenamide, at 25 mg daily, or in a second cohort, which consisted of no antiviral treatment, and were just observed.1
The study’s primary endpoint was a composite of hepatocellular carcinoma, hepatic decompensation, which could include the development of portal hypertensive complications including ascites, gastro-oesophageal varices, or Child-Pugh score of ≥7), liver transplantation, or death from any cause. 1
In terms of another important takeaway from the study, the investigators say the findings could have future ramifications in treatment management.
“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 HBV viral load, irrespective of ALT concentrations,” the investigators wrote.1
References
1.Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomized controlled trial. The Lancet Gastroenterology and Hepatology.
2. FDA Expands Indication for Gilead's Vemlidy (Tenofovir Alafenamide) to Treat Chronic HBV Infection in Pediatric Patients as Young as Six. Gilead press release. March 28, 2024. Accessed February 6, 2025.
https://www.gilead.com/news/news-details/2024/fda-expands-indication-for-gileads-vemlidy-tenofovir-alafenamide-to-treat-chronic-hbv-infection-in-pediatric-patients-as-young-as-six#
