Association of metabolic traits with occurrence of nonalcoholic fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis of longitudinal cohort studies

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the leading etiologies of hepatocellular carcinoma (HCC), but risk factors for NAFLD-related HCC occurrence have not been defined. NAFLD is often complicated by metabolic abnormalities, and there is a bidirectional association of metabolic abnormalities with NAFLD progression. This study aimed to systematically evaluate the relationship between metabolic traits and HCC occurrence in patients with NAFLD. METHOD: This study reviewed eight eligible studies that included 297,956 participants, to determine the relationship between metabolic traits and the occurrence of HCC in patients with NAFLD. RESULTS: Presence of diabetes mellitus (DM) was associated with increased risk of HCC (HR: 2.65, 95%CI: 2.02 ~ 3.49, P(heterogeneity) = 0.589, I(2) = 0.0%). Stratified analysis revealed that this risk was higher in NAFLD patients with advanced fibrosis/cirrhosis (HR: 4.55, 95%CI: 2.34 ~ 8.87, P(heterogeneity) = 0.870, I(2) = 0.0%). Nonetheless even in patients without cirrhosis, DM remained a high risk factor for HCC incidence (HR: 1.80, 95%CI: 1.05 ~ 3.06, P(heterogeneity) = 0.291, I(2) = 10.4%). Overweight/obesity had a slight correlation with increased risk of HCC occurrence in NAFLD patients (HR: 1.31, 95%CI: 1.00 ~ 1.71, P(heterogeneity) = 0.888, I(2) = 0.0%), while presence of hypertension and dyslipidemia had no correlation. CONCLUSION: DM and overweight/obesity are high risk factors for NAFLD-related HCC. In particular, DM increases 4-fold the risk of HCC incidence in NAFLD patients with advanced fibrosis/cirrhosis. There is a need to strengthen surveillance for HCC in NAFLD patients with DM, especially in those with advanced fibrosis/cirrhosis.