Background: Everolimus is approved for treating breast, renal, and pancreatic neuroendocrine cancers but carries the risk of hepatitis B virus (HBV) reactivation (HBVr) and hepatitis. However, data on HBVr in everolimus-treated patients are limited. This study evaluates the risk of hepatitis and HBVr in cancer patients with current or past HBV infection. Methods: This retrospective study analyzed patients prescribed everolimus between 1 January 2011 and 31 May 2022, using a private healthcare system database in Taiwan. Patients with HBsAg positivity or HBsAg negativity and anti-HBs or anti-HBc results were included. The cumulative incidence function and risk of hepatitis from a competing risk model, which estimates Fine-Gray subdistribution hazard (SDH), were analyzed across different HBV serological subgroups. The risk of hepatitis B reactivation was also calculated. Results: Of 377 patients, 45% (36/80) of HBsAg-positive and 0.67% (2/297) of HBsAg-negative patients received nucleos(t)ide analogues (NUCs) prophylaxis. Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients. Baseline HBsAg positivity and exemestane use increased hepatitis risk. HBVr occurred in 11.36% (5/44) of HBsAg-positive patients without NUCs and 5.56% (2/36) with prophylaxis. Two HBsAg-negative, anti-HBc-positive patients developed severe HBVr-related hepatitis. Conclusion: Hepatitis occurred in 28.75% of HBsAg-positive and 17.85% of HBsAg-negative patients on everolimus. HBVr was common in HBsAg-positive patients but rare in HBsAg-negative individuals. HBV screening and liver function monitoring are critical for patients with past or current HBV infection receiving everolimus, especially in endemic areas.
