Risk factors of hepatocellular carcinoma associated with nonalcoholic fatty liver disease: Systematic review and meta-analysis

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is currently an important chronic liver disease threatening human life and health. OBJECTIVE: To investigate the risk factors of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) by systematic review. METHODS: We conducted a systematic review and meta-analysis. A systematic search of Chinese and English databases (PubMed, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang database, and VIP database) was performed until June 30, 2023. Studies were included to investigate the risk factors for HCC in patients with NAFLD. Quality evaluation was performed using the Newcastle-Ottawa Literature Quality Evaluation Scale, and then hazard ratios (HRs) for different influencing factors were combined. RESULTS: We reviewed the results of 12 high-quality cohort studies involving 738,934 patients with NAFLD and 1,480 developed HCC. A meta-analysis based on a random-effects model showed that advanced age (HR = 1.81, 95% CI: 1.51–2.17), male gender (HR = 2.51, 95% CI: 1.67–3.78), hypertension (HR = 1.87, 95% CI: 1.05–3.33), and diabetes (HR = 2.27, 95% CI: 1.63–3.16) were risk factors for HCC in NAFLD, and the differences were statistically significant. However, there was no statistically significant effect of current smoking (HR = 1.45, 95% CI: 0.72–2.92) and dyslipidemia (HR = 1.03, 95% CI: 0.72–1.47) on HCC incidence in this study. CONCLUSION: Age, sex, hypertension and diabetes are risk factors for HCC in NAFLD patients. Diabetic NAFLD patients have a 2.27-fold increased risk of HCC, and health education and intervention for elderly, male, NAFLD patients with diabetes and hypertension need to be strengthened to promote a reduction in the risk of HCC.