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First-line antiviral for chronic hepatitis B: Tenofovir alafenamide vs. entecavir

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Created On: 18/03/2026

Chronic hepatitis B (CHB) poses a substantial global health burden requiring effective long-term antiviral therapy.

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Key take away

Tenofovir alafenamide shows slightly higher virologic and complete response rates than entecavir in chronic hepatitis B, while biochemical response rates remain similar.

Background

Chronic hepatitis B (CHB) poses a substantial global health burden requiring effective long-term antiviral therapy. Current treatment guidelines recommend tenofovir alafenamide (TAF) and entecavir (ETV) as first-line agents. However, real-world evidence directly comparing the long-term effectiveness of these two antivirals is still limited. This study compared the virologic response, biochemical response, and complete response in treatment-naïve CHB patients receiving TAF or ETV.

Method

This retrospective study included treatment-naïve CHB patients who initiated TAF or ETV therapy across 22 international centers. Baseline differences between treatment groups were balanced using inverse probability of treatment weighting (IPTW). Clinical outcomes were evaluated via Fine–Gray competing-risk regression analysis in the weighted cohort.

Result

A total of 1,605 patients were analyzed, including 784 receiving TAF and 821 receiving ETV, with notable baseline differences. Most participants (96.8%) were from Asia. After IPTW adjustment, the weighted cohort included 1,660 patients (822 TAF and 838 ETV) with comparable baseline characteristics. Both antiviral therapies illustrated high long-term effectiveness for alleviating hepatitis B virus (HBV) infection. TAF showed slightly higher virologic and complete response rates, while biochemical response rates were similar between groups (Table 1).

Subgroup findings

Among patients with high HBV DNA levels, complete response rates were 96.9% with TAF vs 87.9% with ETV.
In patients with alanine aminotransferase (ALT) ≥2× the upper limit of normal, complete response rates were 97.3% vs. 90.6%.
No prominent differences were observed in those with lower baseline HBV DNA or ALT levels.

Conclusion

Both TAF and ETV provided excellent long-term viral suppression in CHB treatment. Although TAF achieved slightly higher virologic and complete response rates, the overall difference between therapies was modest (generally less than 5% overall, and 7–9% in high-risk subgroups). Therefore, treatment decisions between TAF and ETV should consider patient preference, drug cost, safety profile, and comorbid conditions.

Source:

The American Journal of Gastroenterology

Link:

https://pubmed.ncbi.nlm.nih.gov/41384853/

Article:

Long-Term Effectiveness of Tenofovir Alafenamide Versus Entecavir in Treatment-Naive Chronic Hepatitis B: A Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus