Metabolic dysfunction-associated fatty liver disease increases risk of adverse outcomes in patients with chronic hepatitis B

Background & Aims: A recent consensus document has defined metabolic dysfunction-associated fatty liver disease (MAFLD) as hepatic steatosis together with overweight, diabetes, and/or a combination of other metabolic risk factors. The clinical relevance of this novel diagnosis is unknown among patients with chronic hepatitis B (CHB). We studied the association between MAFLD (with or without steatohepatitis) and adverse clinical outcomes in patients with CHB. Methods: We performed a retrospective long-term follow-up cohort study at 2 tertiary hospitals in patients with CHB who underwent liver biopsy. Biopsies were reassessed for steatosis, degree of fibrosis, and presence of steatohepatitis. Associations with event-free hepatocellular carcinoma (HCC)-free and transplant-free survival were explored. Results: In our cohort, 1076 patients were included, median follow-up was 9.8 years (25th–75th percentile: 6.6−14.0), and 107 events occurred in 78 patients, comprising death (n = 43), HCC (n = 36), liver decompensation (n = 21), and/or liver transplantation (n = 7). MAFLD was present in 296 (27.5%) patients and was associated with reduced event-free (adjusted hazard ratio [aHR] 2.00, 95% CI 1.26–3.19), HCC-free (aHR 1.93, 95% CI 1.17–3.21), and transplant-free survival (aHR 1.80, 95% CI 0.98–3.29) in multivariable analysis. Among patients with MAFLD, the presence of steatohepatitis (p = 0.95, log-rank test) was not associated with adverse outcomes. Conclusions: The presence of MAFLD in patients with CHB was associated with an increased risk for liver-related clinical events and death. Among patients with MAFLD, steatohepatitis did not increase the risk of adverse outcomes. Our findings highlight the importance of metabolic dysfunction in patients with CHB. Lay summary: Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been defined as fatty liver disease with signs of metabolic dysfunction. Among patients with chronic hepatitis B, MAFLD was associated with liver-related events and death. Metabolic health assessment should be encouraged among patients with chronic hepatitis B, especially in those with fatty liver disease.