Effect of metabolic dysfunction-associated fatty liver disease on liver cancer risk in a population with chronic hepatitis B virus infection: A nationwide study

Background: The association between metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatocellular carcinoma (HCC) lacks clinical validation in at-risk populations. We assessed this relationship among chronic hepatitis B (CHB) patients. Methods: Data was collected from the National Health Insurance System database in South Korea. Chronic hepatitis B patients aged over 40 years receiving health examinations between 2011 and 2012 were recruited. The primary outcome was HCC. Metabolic dysfunction-associated fatty liver disease was defined as hepatic steatosis in combination with at least one of the following: (i) overweight, (ii) diabetes, or (iii) lean/normal weight with two or more metabolic components. Multivariable Cox regression analysis was used to estimate adjusted hazard ratios (aHRs). Results: Of 197 346 participants, 66 149 had MAFLD; 19 149, 44 475, and 2525 fulfilled diabetes (regardless of overweight), overweight alone, and lean/normal weight with two or more metabolic components, respectively. During follow-up (median 7 years), 13 771 developed HCC. Metabolic dysfunction-associated fatty liver disease was independently associated with increased risk of HCC, with aHR of 1.36 (p < 0.001). Propensity score matching confirmed the same phenomena, with aHR of 1.37 (p < 0.001). Furthermore, when stratified by liver cirrhosis and/or antiviral therapy, independent significances of MAFLD for HCC risk were maintained (all p < 0.001). Compared with the persistent non-MAFLD subgroup during the entire follow-up, diagnosis of MAFLD from at least one health examination significantly increased HCC risk with aHRs of 1.41, 1.37, and 1.14 among subgroups with persistent MAFLD, MAFLD to non-MAFLD, and non-MAFLD to MAFLD, respectively (all p < 0.05). Conclusions: Metabolic dysfunction-associated fatty liver disease consistently increases HCC risk among CHB patients. Further studies are needed to develop an effective preventive strategy through control of metabolic health.