Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis
Portal vein thrombosis (PVT), which is associated with reduced portal vein velocity, is considered to be an indicator for worse outcomes in liver cirrhosis. Nonselective beta-blockers (NSBBs), which are widely used for primary and secondary prophylaxis of esophageal variceal bleeding in liver cirrhosis, can significantly decrease the portal vein velocity. We proposed a hypothesis that the use of NSBBs might facilitate the development of PVT in cirrhotic patients. The PubMed, EMBASE, and Cochrane Library databases were searched. Major meeting abstracts and randomized-controlled trials regarding the use of NSBBs in liver cirrhosis were also hand-searched. The number of patients who developed PVT in groups treated with or without NSBBs was pooled. Odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Subgroup meta-analyses were performed according to the type of studies, region, and study quality. Meta-regression and sensitivity analyses were performed to explore the source of heterogeneity. Nine of the 6416 retrieved papers were finally included. Overall, meta-analysis demonstrated that NSBBs were significantly associated with the development of PVT (OR 4.62, 95% CI 2.50–8.53; p < 0.00001). The heterogeneity was statistically significant (I2 = 80%; p < 0.00001). Subgroup meta-analyses still demonstrated a significantly positive association of NSBBs with the development of PVT in cohort studies (RR 2.57, 95% CI 1.46–4.51; p = 0.001) and case–control studies (OR 8.17, 95% CI 2.46–27.06; p = 0.0006). Sensitivity analyses based on subgroups find the source of heterogeneity. Based on the systematic review and meta-analysis, we found that the use of NSBBs increased a 4.62-fold risk of PVT in cirrhotic patients.
KeywordsNonselective beta-blockers Portal vein thrombosis Liver cirrhosis Portal hypertension Propranolol
Portal vein thrombosis
American Association for the Study of Liver Diseases
European Association for the Study of the Liver
Esophageal variceal ligation
Digestive Disease Week
Model for end-stage liver disease
Magnetic resonance imaging
The authors express their gratitude to Prof. Dominique Valla (Clichy, France) for his constructive comments for the improvement of the manuscript.
XX: performed the literature search and selection, data extraction, quality assessment, and drafted manuscript. XG, VDS, and GS-J: gave critical comments and revised the manuscript. HG: improved language, gave critical comments, and revised the manuscript. ZB and QZ: reviewed the literature and performed the quality assessment and statistical analysis. XQ: conceived the work, reviewed the literature, gave critical comments, and revised the manuscript.
Compliance with ethical standards
Conflict of interest
Xiangbo Xu, Xiaozhong Guo, Valerio De Stefano, Gilberto Silva-Junior, Hemant Goyal, Zhaohui Bai, Qingchun Zhao and Xingshun Qi declare that they have no conflict of interest.
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