An umbrella review of the association between dietary factors and hepatocellular carcinoma risk

Abstract

Background: Several meta-analyses have summarized the associations between dietary factors and the risk of hepatocellular carcinoma (HCC). However, no research has comprehensively assessed the certainty of this evidence. Methods: PubMed, Embase, and the Cochrane Library were searched from inception to August 2024. The credibility of the evidence was assessed using the pre-specified evidence classification criteria, graded as convincing (“class I”), highly suggestive (“class II”), suggestive (“class III”), weak (“class IV”), or no evidence (“class V”). To evaluate the quality of evidence, the GRADE framework was applied, categorized as “high”, “moderate”, “low”, or “very low” quality. This study was registered at PROSPERO (CRD42023417373). Results: In total, 22 meta-analyses describing 33 non-dose–response and 10 dose–response associations were included. In the non-dose–response associations, convincing evidence (class I) supported an inverse association between coffee intake [risk ratio (RR) 0.50, 95% confidence interval 0.42 to 0.59, GRADE = very low] and risk for HCC. Suggestive evidence (class III) supported the effect of fish (RR 0.81, 0.73 to 0.90; very low), fiber (RR 0.71, 0.61 to 0.84; low), and the Mediterranean diet (RR 0.67, 0.56 to 0.80; very low) in lowering the risk for HCC. Weak evidence (class IV) suggested the protective effects of ginseng, selenium, cruciferous vegetables, whole grains, and vegetables, against HCC, and the negative effect of saturated fat in increasing the risk for HCC. In the dose–response association, convincing evidence (class I) supported that an additional two cups of coffee per day (RR 0.71, 0.60 to 0.77; moderate) lowered HCC risk, and suggestive evidence (class III) indicated that an increase of 10 g day⁻¹ in fiber intake (RR 0.83, 0.76 to 0.91; moderate) lowered HCC risk. Weak evidence (class IV) suggests positive associations between HCC risk and a 1% daily increase in energy from saturated fat and a 100 mg day⁻¹ increase in cholesterol. Conclusions: Dietary factors, especially coffee, fish, fiber, and the Mediterranean diet, are associated with HCC risk. These findings provide a theoretical basis for developing and evaluating dietary interventions to reduce HCC risk.