Risk of hepatocellular carcinoma after curative treatment when switching from tenofovir disoproxil fumarate or entecavir to tenofovir alafenamide: A real‐world multicenter cohort study

Abstract Aim Antiviral treatment reduces the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, there is a lack of high‐quality evidence regarding the preventive effects of tenofovir alafenamide (TAF) on HCC. We evaluated the impact of TAF use after curative treatment on HCC recurrence. Methods Patients who underwent surgery or radiofrequency ablation as a curative treatment for HCC were selected. Those patients who continued antiviral treatment with nucleos(t)ide analogs (NAs; entecavir [ETV] or tenofovir disoproxil fumarate [TDF]) or switched to TAF were included. The primary outcome was HCC recurrence, and the time‐varying effect of NA use on HCC recurrence was analyzed using various statistical methods. Results Among 2794 consecutive patients with chronic hepatitis B who received curative treatment for HCC, 199 subsequently switched from ETV or TDF to TAF. After a median of 3.0 years, 1303 patients (46.6%) experienced HCC recurrence. After propensity score matching (ratio 1:10), switching to TAF was not associated with an increased HCC recurrence (HR 1.00, 95% CI 0.68–1.47; p = 1.00) by time‐varying Cox analysis. Switching to TAF was not associated with HCC recurrence in subgroups of NA (HR 1.06, 95% CI 0.67–1.67; p = 0.81 for TDF, and HR 1.09, 95% CI 0.51–2.33; p = 0.82 for ETV). Kaplan–Meier analysis showed comparable HCC recurrence‐free survival between patients who switched to TAF and those who continued with their NA ( p = 0.08). Time‐varying Cox analyses in various subgroups confirmed the primary findings. Conclusions TAF is as effective as TDF and ETV in preventing HCC recurrence after curative treatment.