Risk factors of hepatocellular carcinoma in non-alcoholic fatty liver disease: a systematic review and meta-analysis

This study aimed to systematically review and quantitatively synthesize the existing evidence to better identify the high-risk population of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease (NAFLD).

We searched databases including MEDLINE, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov up to February 2023. The meta-analysis was performed using RevMan5.3 software, and we calculated the estimated combined effect using inverse variance weighting of OR. I2 statistics were used to quantify the inter-study heterogeneity. Funnel plots and Egger test were used to assess publication bias, and sensitivity analysis was carried out through the transformation effect model or the removal of literature one by one.

Finally, 29 articles were included in the study, which involved a total of 726,656 patients with NAFLD. A total of 15 major risk factors were evaluated. Statistically significant risk factors were: advanced liver fibrosis (OR=6.40), diabetes (OR=2.38), obesity (OR=1.46), hypertension (OR=1.75), older age (OR=3.57), male (OR=2.45), alcohol intake (OR=2.98), smoking (OR=1.44), PNPLA3 genotype variation (OR=1.76), elevated liver enzymes (OR=2.92), low platelet counts (OR=4.61), and low albumin levels (OR=2.11).

Our results showed that advanced liver fibrosis, diabetes, obesity, hypertension, older age, male, alcohol intake, smoking, PNPLA3 genotype variation, elevated liver enzymes, low platelet counts, and low albumin levels were all significant risk factors for HCC in NAFLD. However, dyslipidemia was not found to be a risk factor. Further exploration is needed to confirm whether Hispanic ethnicity and high ferritin levels are also risk factors.