Both CHB and MASLD can lead to hepatic inflammation and liver fibrosis, increasing the risk of adverse liver outcomes [3]. However, CHB patients with concurrent steatosis tend to have lower HBV activity, including lower proportions of hepatitis B e antigen (HBeAg) positivity, lower serum HBV DNA levels, as well as higher rates of hepatitis B surface antigen (HBsAg) seroclearance, and are more likely to achieve functional cure [4,5]. Studies on animals and cells show that hepatic steatosis can decrease HBV activity and induce lower levels of HBsAg, HBeAg, and HBV DNA [6]. The molecular mechanism might be explained as liver fat activating innate immunity, disrupting the liver’s metabolic environment, and increasing liver cell apoptosis, reducing HBV survival [7].

In the phase 3, randomized, controlled trial of resmetirom in MASH with liver fibrosis, both the resmetirom treatment groups significantly improved hepatic steatosis and inflammation [8]. It is unclear if resmetirom can be used to treat MASH patients with concurrent CHB. We recommend the answer is YES, because both CHB and MASLD can increase the risk of adverse liver outcomes. However, close monitoring of HBV activity is necessary as resmetirom could potentially alleviate steatosis and increase HBV activity. Further research is needed to determine if more aggressive antiviral therapy (e.g., entecavir combined with tenofovir, nucleotide analogues combined with interferon, etc.) is necessary when using resmetirom to treat MASH patients with concurrent CHB. The field remains blank, and more clinical data are needed to reveal the answers and guide drug treatment choices in this large population.