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

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Abstract

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.

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Abbreviations

NSBBs:

Nonselective beta-blockers

PVT:

Portal vein thrombosis

AASLD:

American Association for the Study of Liver Diseases

EASL:

European Association for the Study of the Liver

EVL:

Esophageal variceal ligation

DDW:

Digestive Disease Week

RCT:

Randomized-controlled trial

NOS:

Newcastle–Ottawa Scale

OR:

Odds ratio

RR:

Risk ratio

MD:

Mean difference

CI:

Confidence interval

CP:

Child–Pugh

MELD:

Model for end-stage liver disease

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransaminase

CT:

Computed tomography

MRI:

Magnetic resonance imaging

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Acknowledgements

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

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Author notes

  1. Xiangbo Xu, Xiaozhong Guo, Valerio De Stefano, and Gilberto Silva-Junior have equally contributed to the work.

Authors and Affiliations

  1. Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly Called General Hospital of Shenyang Military Area), No. 83 Wenhua Road, Shenyang, 110840, Liaoning, China

    Xiangbo Xu, Xiaozhong Guo, Zhaohui Bai & Xingshun Qi

  2. Postgraduate College, Shenyang Pharmaceutical University, Shenyang, China

    Xiangbo Xu, Zhaohui Bai & Qingchun Zhao

  3. Fondazione Policlinico A. Gemelli IRCCS, Istituto Di Ematologia, Università Cattolica, Rome, Italy

    Valerio De Stefano

  4. Department of General Medicine and Hepatology, Quinta D’Or Hospital, Rio de Janeiro, Brazil

    Gilberto Silva-Junior

  5. Department of Internal Medicine, School of Medicine, Mercer University, Macon, GA, USA

    Hemant Goyal

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  1. Xiangbo Xu
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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.

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Correspondence to Xingshun Qi.

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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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12072_2019_9951_MOESM1_ESM.jpg

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

Supplementary fig. 2. Meta-analysis regarding the association of platelet count with risk of portal vein thrombosis. (JPG 1429 kb)

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Supplementary table 2 (DOCX 17 kb)

Supplementary table 3 (DOCX 16 kb)

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Xu, X., Guo, X., De Stefano, V. et al. Nonselective beta-blockers and development of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis. Hepatol Int 13, 468–481 (2019). https://doi.org/10.1007/s12072-019-09951-6

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