Association Between Nonselective Beta-Blocker Use and Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Without Cirrhosis and Decompensation

Abstract

Background: Nonselective beta-blockers (NSBBs) can reduce the incidence or mortality of certain types of cancers, and NSBBs exert a protective effect on hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the potential preventive effect of NSBBs has not yet been investigated in patients with chronic hepatitis B (CHB) who have a high HCC risk regardless of the presence of underlying cirrhosis.Aim: This study evaluated the association between NSBB use and HCC incidence in patients with CHB without cirrhosis and decompensation.Methods: From the 2000 Longitudinal Generation Tracking Database, we enrolled patients who were newly diagnosed as having CHB from January 2001 to December 2011 and then followed them up for at least 5 years. To estimate the causal effect of NSBBs on the time-to-event outcomes of HCC, a marginal Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: After adjustment, no significant benefit of HCC risk reduction was observed between the NSBB users and nonusers (adjusted HR, 0.82; 95% CI, 0.52–1.31). The cumulative defined daily dose (cDDD) analysis revealed no significant dose correlation among the three groups [adjusted HR (95% CI): 1.08, (0.56–2.05), 0.54 (0.17–1.77), and 0.76 (0.40–1.42) in the <90 cDDD, 90 to <180 cDDD, and ≥180 cDDD groups, respectively]. Duration-dependent associations were not observed. Multivariable stratified analysis results demonstrated that HCC risk markedly decreased in the patients aged >55 years (adjusted HR, 0.49; 95% CI, 0.25–0.96; p = 0.04).Conclusion: NSBB did not significantly prevent HCC in the patients with CHB infection without cirrhosis and decompensation. This study provided one of valuable results that it is not clinically required to use NSBBs as recommended chemoprevention for HCC in high-risk patients who have CHB.

Long-Term Prognosis and Related Factors in Patients with Cirrhosis Treated with Balloon-Occluded Retrograde Transvenous Obliteration

“…Most cases were treated with CCBs or ARBs, and beta-blockers were used in few cases. The recent studies proved that beta-blockers not only prevented the variceal bleeding but also improved the prognosis of patients with cirrhosis [21][22][23], but in Japan, the administration of beta-blockers tends to be avoided due to concerns about symptoms caused by their hypotensive effects, and this was demonstrated in this study. Based on the result of animal models that showed the anti-fibrotic effects of ACEI and ARB, the impact of these agents on the liver-related events in non-alcoholic fatty liver disease was evaluated.…”

Anticancer effect of propranolol on diethylnitrosamine‐induced hepatocellular carcinoma rat model

“…It has been shown that non-selective β-blockers demonstrated lower frequency or mortality of the solid tumors, including the upper gastrointestinal cancers in clinical and human research studies. 63 Propranolol, a nonselective β-blocker, exhibits a potential in reducing oxidative stress and pro-tumorigenic inflammatory response. It also inhibits tumorigenesis through a variety of molecular and cellular mechanisms that are dependent on concentration and time.…”

“…Therefore, more effective strategies are demanded. It has been shown that non‐selective β‐blockers demonstrated lower frequency or mortality of the solid tumors, including the upper gastrointestinal cancers in clinical and human research studies 63 . Propranolol, a non‐selective β‐blocker, exhibits a potential in reducing oxidative stress and pro‐tumorigenic inflammatory response.…”

Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

“…In animal experiments it inhibited nuclear translocation of ERK despite its effect on ERK phosphorylation ( 68 ). The effect of NSBB on HCC development is under debate ( 69 , 70 ). Here, it would be interesting to have more specific data for carvedilol.…”