Letter: Tenofovir Alafenamide—The “Star of Potential” for Long-Term Chronic Hepatitis B Treatment. A Deep-Dive Analysis of Phase 3 Clinical Trials

I read with great interest the article titled “Eight - Year Efficacy and Safety of Tenofovir Alafenamide for Chronic Hepatitis B Virus Infection: Final Results of Two Randomized Phase 3 Clinical Trials [1].” This study provides valuable insights into the long—term management of chronic hepatitis B (CHB) using tenofovir alafenamide (TAF), which is a significant advancement in the field of hepatology.

The findings of this study are indeed remarkable. The sustained virological suppression rate over 8 years highlights the potent antiviral efficacy of TAF. Given the chronic nature of hepatitis B infection, long-term viral control is crucial for preventing disease progression to cirrhosis and hepatocellular carcinoma. Although the overall rate of hepatitis B surface antigen (HBsAg) loss is relatively low, it is still noteworthy. HBsAg loss is considered a functional cure for CHB, and any increase in this outcome represents an important step forward in managing this challenging disease.

Moreover, the safety profile of TAF is commendable. Compared with tenofovir disoproxil fumarate (TDF), TAF has a lower incidence of renal and bone adverse events, which is a major advantage. These side effects have long been a concern in long-term nucleos (t) ide analog therapy, and the improved safety of TAF offers a more favourable risk–benefit ratio for patients who require lifelong treatment. This is especially true for elderly patients or those with comorbidities that may exacerbate renal or bone issues.

However, I would like to raise some points that merit further discussion. First, although the study demonstrates impressive long-term outcomes, the long-term impact on liver histology and clinical endpoints (such as cirrhosis reversal or hepatocellular carcinoma incidence) would provide a more comprehensive understanding of the benefits of TAF. Longitudinal liver biopsies or non-invasive liver fibrosis markers could offer valuable reference for histological changes associated with long-term TAF treatment [2].

Second, the study population is relatively homogeneous in terms of baseline characteristics. Future research should strive to include more diverse cohorts, including patients with different racial backgrounds, stages of liver disease, and co-infections. This will help to better understand the efficacy and safety of TAF in real-world settings and its applicability in different patient subgroups [3].

Lastly, especially in resource–limited settings, the cost–effectiveness of TAF deserves further investigation. Although its superior safety profile may make it valuable for certain populations, the economic burden of long–term treatment needs to be considered. Cost–effectiveness analyses compared with other available treatment options can guide clinical decision–making and health policy [4].

In summary, the eight-year results of the Phase 3 clinical trials of TAF for CHB are very encouraging. They highlight the potential of TAF as a cornerstone for long-term CHB management. However, further research is needed to fully elucidate its long-term clinical impact, applicability in diverse patient populations, and cost-effectiveness. I look forward to seeing more research based on these promising results and contributing to the improvement of outcomes for patients with chronic hepatitis B.

Thank you for your consideration.

Yours sincerely

YaoYao Dai: writing – original draft, conceptualization. JunFeng Zhu: supervision.

The authors declare no conflicts of interest.

This article is linked to Buti et al. papers. To view these articles, visit https://doi.org/10.1111/apt.18278 and https://doi.org/10.1111/apt.70358.