Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis

  • Xiangbo Xu
  • Xiaozhong Guo
  • Valerio De Stefano
  • Gilberto Silva-Junior
  • Hemant Goyal
  • Zhaohui Bai
  • Qingchun Zhao
  • Xingshun QiEmail author
Original Article


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.


Nonselective beta-blockers Portal vein thrombosis Liver cirrhosis Portal hypertension Propranolol 



Nonselective beta-blockers


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


Randomized-controlled trial


Newcastle–Ottawa Scale


Odds ratio


Risk ratio


Mean difference


Confidence interval




Model for end-stage liver disease


Alanine aminotransferase


Aspartate aminotransaminase


Computed tomography


Magnetic resonance imaging



The authors express their gratitude to Prof. Dominique Valla (Clichy, France) for his constructive comments for the improvement of the manuscript.

Author contributions

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.

Supplementary material

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Supplementary fig. 1. Meta-analysis regarding the association of portal vein velocity with risk of portal vein thrombosis. (JPG 1259 kb)
12072_2019_9951_MOESM2_ESM.jpg (1.4 mb)
Supplementary fig. 2. Meta-analysis regarding the association of platelet count with risk of portal vein thrombosis. (JPG 1429 kb)
12072_2019_9951_MOESM3_ESM.docx (49 kb)
Supplementary table 1 (DOCX 48 kb)
12072_2019_9951_MOESM4_ESM.docx (17 kb)
Supplementary table 2 (DOCX 17 kb)
12072_2019_9951_MOESM5_ESM.docx (17 kb)
Supplementary table 3 (DOCX 16 kb)


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Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  1. 1.Liver Cirrhosis Study Group, Department of GastroenterologyGeneral Hospital of Northern Theater Command (Formerly Called General Hospital of Shenyang Military Area)ShenyangChina
  2. 2.Postgraduate CollegeShenyang Pharmaceutical UniversityShenyangChina
  3. 3.Fondazione Policlinico A. Gemelli IRCCS, Istituto Di EmatologiaUniversità CattolicaRomeItaly
  4. 4.Department of General Medicine and HepatologyQuinta D’Or HospitalRio de JaneiroBrazil
  5. 5.Department of Internal Medicine, School of MedicineMercer UniversityMaconUSA

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