Association of nonselective β blockers with the development of hepatocellular carcinoma in liver cirrhosis: a meta-analysis

Nonselective β blockers (NSBBs) may be involved in reducing gut-derived inflammation and intrahepatic inflammation to prevent hepatocellular carcinoma (HCC). This study aimed to systematically investigate their association. PubMed, EMBASE, and Cochrane Library databases were searched to identify all relevant studies evaluating the association of NSBBs with HCC in liver cirrhosis patients. Sensitivity analyses were performed to explore potential sources of heterogeneity. Risk ratios (RRs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the study design, regions, type of NSBBs, and indications of NSBBs. Twenty-four studies were finally included. Overall meta-analyses demonstrated that NSBBs were associated with a significantly reduced risk of HCC development in liver cirrhosis patients (RR=0.86; P=0.048). Sensitivity analysis did not find the source of heterogeneity. Subgroup analyses based on adjusted cohort studies with propensity-score matching (RR=0.85; P=0.01) and multivariable regression model (HR=0.66; P<0.00001), studies performed in America (RR=0.83; P=0.007) and Europe (RR=0.72; P=0.05), studies included patients receiving carvedilol (RR=0.72; P<0.00001), nadolol (RR=0.86; P<0.0001), and propranolol with dosage > 40 mg (RR=0.28; P<0.00001) or follow-up duration < 20 months (RR=0.38; P=0.04) demonstrated that NSBBs significantly decrease the risk of developing HCC in liver cirrhosis patients. However, studies included patients receiving primary or secondary prophylaxis of variceal bleeding did not reveal the protective effect of NSBBs on HCC. NSBBs may play a role in preventing the occurrence of HCC in liver cirrhosis patients. Future research should focus on risk stratification and monitoring protocols to advance personalized prevention.