Chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease: Metabolic risk factors are key drivers of hepatocellular carcinoma

Abstract

Objective: Chronic hepatitis B (CHB) and metabolic dysfunction-associated steatotic liver disease (MASLD) are the leading causes of hepatocellular carcinoma (HCC). This study aimed to explore the impact of baseline MASLD on the risk of HCC development in patients with CHB receiving antiviral treatment. Methods: We consecutively recruited 535 patients with CHB who initiated antiviral treatment between January 2007 and January 2023. The exclusion criteria included coexisting HDV, HCV, or HIV infection; other chronic liver diseases; extrahepatic malignancies; prior HCC; and HCC development within one year. A baseline liver biopsy was performed in 467 patients (87 %). MASLD was defined as hepatic steatosis diagnosed histologically or by imaging, combined with one cardiometabolic risk factor. The cumulative incidence of HCC and its associated factors was analyzed in patients with CHB, with and without MASLD. Results: In total, 535 treatment-naïve patients with CHB were included, with a median follow-up of 6.05 years. MASLD was not associated with an increased incidence of HCC in patients with CHB (HR: 1.17; 95 % CI: 0.77–1.79; p = 0.466). The cumulative incidence of HCC increased with the number of fulfilled cardiometabolic criteria (0–2 criteria vs. ≥ 3 criteria) (HR: 3.93; 95 % CI: 1.89–8.19; p < 0.001). Age (HR: 1.03, 95 % CI 1.01–1.06, p = 0.010), male sex (HR: 3.17; 95 % CI 1.34–7.53, p = 0.009), diabetes (HR: 2.81; 95 % CI 1.54–5.12, p < 0.001), and cirrhosis (HR:3.03; 95 % CI 1.57–5.5.86, p < 0.001) were independently associated with HCC development. Conclusions: It was not MASLD, but rather the presence of multiple cardiometabolic risk factors in patients with CHB that was associated with the risk of HCC in those receiving antiviral treatment. Furthermore, older age, male sex, diabetes, and cirrhosis aggravated the risk of HCC in patients with CHB.