Incidence of Hepatocellular Carcinoma in Patients with Non-alcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression.

Abstract Background & Aims Nonalcoholic fatty liver disease (NAFLD) may be a risk factor for hepatocellular carcinoma (HCC), but the extent of this association still needs to be addressed. Pooled-incidence rates of HCC across the disease spectrum of NAFLD have never been estimated by meta-analysis. Methods In this systematic review, we searched Web of Science, Embase, Pubmed, and the Cochrane library from January 1st, 1950 through July 30th, 2020. We included studies reporting on HCC incidence in patients with NAFLD. The main outcomes were pooled HCC incidences in patients with NAFLD at distinct severity stages. Summary estimates were calculated with random-effects models. Sensitivity analyses and meta-regression analyses were carried out to address heterogeneity. Results We included 18 studies involving 470,404 patients. In patients with NAFLD at a stage earlier than liver cirrhosis, the incidence rate of HCC was 0.03 per 100 person-years (95% confidence interval [CI] 0.01–0.07, I2 = 98%). In patients with liver cirrhosis, the incidence rate was 3.78 per 100 person-years (95% CI 2.47–5.78, I2 = 93%). Patients with liver cirrhosis undergoing regular screening for HCC had an incidence rate of 4.62 per 100 person-years (95% CI 2.77–7.72, I2 = 77%). Conclusion Patients with NAFLD-related liver cirrhosis have a risk of developing HCC similar to that reported for patients with cirrhosis from other aetiologies. Evidence documenting the risk in patients with nonalcoholic steatohepatitis or simple steatosis is limited, but the incidence of HCC in these populations may lie below thresholds used to recommend a screening. Well-designed prospective studies in these subpopulations are needed. Protocol registration number The protocol for this systematic review is registered in the Prospero database (registration number CRD42018092861).