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. 2019 May 24;14(5):e0216828.
doi: 10.1371/journal.pone.0216828. eCollection 2019.

The effect of propranolol on the prognosis of hepatocellular carcinoma: A nationwide population-based study

Ping-Ying Chang  1 , Chi-Hsiang Chung  2   3 , Wei-Chou Chang  4 , Chun-Shu Lin  5 , Hsuan-Hwai Lin  6 , Ming-Shen Dai  1 , Ching-Liang Ho  1 , Wu-Chien Chien  2   3
Affiliations

The effect of propranolol on the prognosis of hepatocellular carcinoma: A nationwide population-based study

Ping-Ying Chang et al. PLoS One. .

Abstract

Background: Beta-blockers can reduce recurrence, metastasis, and mortality in various cancers. In this study, we investigated the effect of propranolol, a non-selective beta-blocker on overall survival (OS) in unresectable/metastatic hepatocellular carcinoma (HCC) and on recurrence-free survival (RFS) in resectable, curable HCC.

Methods: Data were retrieved from the Taiwan National Health Insurance Research Database between January 2000 and December 2013. Propranolol users (for >1 year) and non-propranolol users were matched using a 1:2 propensity score in both cohorts.

Results: The unresectable/metastatic HCC cohort comprised 1,560 propranolol users and 3,120 non-propranolol users (control group). On multivariate Cox regression analysis of HCC mortality, propranolol significantly reduced the mortality risk by 22% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.72-0.84, P <0.001). On stratified Cox regression analysis, propranolol also reduced the mortality risk in HCC patients with hepatitis B (HR = 0.92, 95% CI 0.85-0.99, P = 0.045), hepatitis C (HR = 0.85, 95% CI = 0.78-0.92, P = 0.001), liver cirrhosis (HR = 0.78, 95% CI = 0.72-0.85, P <0.001), and diabetes mellitus (HR = 0.87, 95% CI = 0.81-0.94, P = 0.008). The resectable, curable HCC cohort comprised 289 propranolol users and 578 non-propranolol users (control group), but there was no significant difference in RFS (P = 0.762) between propranolol and non-propranolol users.

Conclusion: This study revealed that propranolol could improve OS in unresectable/metastatic HCC.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart for matching patients with unresectable/metastatic HCC according to propranolol exposure.
LHID, Longitudinal Health Insurance Database; HCC, hepatocellular carcinoma; RFA, radiofrequency ablation. Operations include lobectomy, segmentectomy, hepatectomy, and liver transplantation.
Fig 2
Fig 2. Kaplan-Meier plot for the probability of overall survival in patients with unresectable/metastatic hepatocellular carcinoma according to propranolol exposure.
Fig 3
Fig 3. Flowchart for matching patients with resectable, curable HCC according to propranolol exposure.
LHID, Longitudinal Health Insurance Database; HCC, hepatocellular carcinoma; TACE, transarterial chemoembolization; RFA, radiofrequency ablation; CT, chemotherapy; RT, radiotherapy.
Fig 4
Fig 4. Kaplan-Meier plot for the probability of recurrence of resectable, curable hepatocellular carcinoma according to propranolol exposure.
See this image and copyright information in PMC

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