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

Abstract 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.