Abstract
Purpose
To date, the optimal treatment for portal vein thrombosis (PVT) in cirrhotic patients has not been established in guidelines or consensus. We conducted a systematic review and meta-analysis to evaluate the effect of anticoagulation therapy in patients with cirrhosis and PVT.
Methods
PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched (until 31st October 2020) for studies evaluating the effect of anticoagulation therapy on treating PVT in patients with cirrhosis. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using the Mantel–Haenszel method.
Results
A total of 13 studies were included in the analysis, comprising 6005 patients. Of these, three were prospective cohort studies, nine were retrospective cohort studies and one was case–control study. Compared to no treatment, anticoagulation therapy was associated with higher rates of PVT recanalization (OR 4.29; 95% CI 3.01–6.13). Anticoagulation therapy demonstrated a significant 74% reduction in PVT extension compared to no treatment (OR 0.26; 95% CI 0.14–0.49). Anticoagulation therapy was associated with a nonsignificantly lower risk of death (OR 0.53; 95% CI 0.20–1.40). However, anticoagulation therapy was associated with slightly higher risk of bleeding compared to no treatment (OR 1.16; 95% CI 1.02–1.32).
Conclusions
In cirrhotic patients with PVT, anticoagulation therapy helps increase rate of PVT recanalization and improve survival, but may also carry higher risks of bleeding compared to no treatment. Our findings support the use of anticoagulation in cirrhotic patients with PVT.
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Availability of data and material
All data generated or analyzed during this study are included in the manuscript and the Appendix.
Code availability
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References
Rodriguez-Castro KI, Porte RJ, Nadal E, Germani G, Burra P, Senzolo M. Management of nonneoplastic portal vein thrombosis in the setting of liver transplantation: a systematic review. Transplantation 2012;94(11):1145–1153.
Qi X, Guo X, Yoshida EM, Mendez-Sanchez N, De Stefano V, Tacke F, et al. Transient portal vein thrombosis in liver cirrhosis. BMC Med 2018;16(1):83.
Maruyama H, Okugawa H, Takahashi M, Yokosuka O. De novo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am J Gastroenterol 2013;108(4):568–574.
Francoz C, Belghiti J, Vilgrain V, Sommacale D, Paradis V, Condat B, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005;54(5):691–697.
John BV, Konjeti R, Aggarwal A, Lopez R, Atreja A, Miller C, et al. Impact of untreated portal vein thrombosis on pre and post liver transplant outcomes in cirrhosis. Ann Hepatol 2013;12(6):952–958.
Intagliata NM, Caldwell SH, Tripodi A. Diagnosis, development, and treatment of portal vein thrombosis in patients with and without cirrhosis. Gastroenterology 2019;156(6):1582–1599.
Simonetto DA, Singal AK, Garcia-Tsao G, Caldwell SH, Ahn J, Kamath PS. ACG clinical guideline: disorders of the hepatic and mesenteric circulation. Am J Gastroenterol 2020;115(1):18–40.
Loffredo L, Pastori D, Farcomeni A, Violi F. Effects of anticoagulants in patients with cirrhosis and portal vein thrombosis: a systematic review and meta-analysis. Gastroenterology 2017;153(2):480–487.
Noronha Ferreira C, Reis D, Cortez-Pinto H, Tato Marinho R, Goncalves A, Palma S, et al. Anticoagulation in cirrhosis and portal vein thrombosis is safe and improves prognosis in advanced cirrhosis. Dig Dis Sci 2019;64(9):2671–2683.
Scheiner B, Stammet PR, Pokorny S, Bucsics T, Schwabl P, Brichta A, et al. Anticoagulation in non-malignant portal vein thrombosis is safe and improves hepatic function. Wien Klin Wochenschr 2018;130(13–14):446–455.
Pettinari I, Vukotic R, Stefanescu H, Pecorelli A, Morelli M, Grigoras C, et al. Clinical impact and safety of anticoagulants for portal vein thrombosis in cirrhosis. Am J Gastroenterol 2019;114(2):258–266.
Acuna-Villaorduna A, Tran V, Gonzalez-Lugo JD, Azimi-Nekoo E, Billett HH. Natural history and clinical outcomes in patients with portal vein thrombosis by etiology: a retrospective cohort study. Thromb Res 2019;174:137–140.
Alaber OA, Chandar AK, Dahash BA, Mistry SN, Cohen SM, Chak A, et al. Anticoagulation increases bleeding rates in portal vein thrombosis: a national database study. Blood 2019;134(1):5860.
Liberati AAD, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700.
Qi X, De Stefano V, Li H, Dai J, Guo X, Fan D. Anticoagulation for the treatment of portal vein thrombosis in liver cirrhosis: a systematic review and meta-analysis of observational studies. Eur J Intern Med 2015;26(1):23–29.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21(11):1539–1558.
Senzolo M, Sartori TM, Rossetto V, Burra P, Cillo U, Boccagni P, et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int 2012;32(6):919–927.
Ai MH, Dong WG, Tan XP, Xu L, Xu C, Zhang Q, et al. Efficacy and safety study of direct-acting oral anticoagulants for the treatment of chronic portal vein thrombosis in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2020;32(10):1395–1400.
Cai M, Zhu K, Huang W, Meng X, He K, Zhou B, et al. Portal vein thrombosis after partial splenic embolization in liver cirrhosis: efficacy of anticoagulation and long-term follow-up. J Vasc Interv Radiol 2013;24(12):1808–1816.
Chung JW, Kim GH, Lee JH, Ok KS, Jang ES, Jeong SH, et al. Safety, efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: a propensity score matching analysis. Clin Mol Hepatol 2014;20(4):384–391.
Chen H, Liu L, Qi X, He C, Wu F, Fan D, et al. Efficacy and safety of anticoagulation in more advanced portal vein thrombosis in patients with liver cirrhosis. Eur J Gastroenterol Hepatol 2016;28(1):82–89.
Garcovich M, Zocco MA, Ainora ME, Annicchiarico BE, Ponziani FR, Cesario V, et al. Clinical outcome of portal vein thrombosis (pvt) in cirrhotic patients: observe or treat? Hepatology 2011;54:1261–1262.
Risso A, Stradella D, Martini S, Rizzetto M, Salizzoni M. Liver transplantation in cirrhotic patients with portal vein thrombosis: a single centre experience. Digest Liver Dis 2014;46:e40.
Wang Z, Jiang MS, Zhang HL, Weng NN, Luo XF, Li X, et al. Is post-TIPS anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology 2016;279(3):943–951.
Abdel RA, El-Serougy LG, Saleh GA, Abd ER, Shabana W. Interobserver agreement of magnetic resonance imaging of liver imaging reporting and data system version 2018. J Comput Assist Tomogr 2020;44(1):118–123.
Abdel RA, El-Serougy LG, Saleh GA, Shabana W, Abd ER. Liver imaging reporting and data system version 2018: what radiologists need to know. J Comput Assist Tomogr 2020;44(2):168–177.
Razek AA, Massoud SM, Azziz MR, El-Bendary MM, Zalata K, Motawea EM. Prediction of esophageal varices in cirrhotic patients with apparent diffusion coefficient of the spleen. Abdom Imaging 2015;40(6):1465–1469.
Villa E, Camma C, Marietta M, Luongo M, Critelli R, Colopi S, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012;143(5):1253–1260.
La Mura V, Braham S, Tosetti G, Branchi F, Bitto N, Moia M, et al. Harmful and beneficial effects of anticoagulants in patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2018;16(7):1146–1152.
Intagliata NM, Saad WE, Caldwell SH. Effects of restoring portal flow with anticoagulation and partial splenorenal shunt embolization. Hepatology 2015;61(3):1088–1090.
Nery F, Chevret S, Condat B, de Raucourt E, Boudaoud L, Rautou PE, et al. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: results of a longitudinal study. Hepatology 2015;61(2):660–667.
Amitrano L, Guardascione MA, Menchise A, Martino R, Scaglione M, Giovine S, et al. Safety and efficacy of anticoagulation therapy with low molecular weight heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol 2010;44(6):448–451.
Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP. Oral anticoagulation in patients with liver disease. J Am Coll Cardiol 2018;71(19):2162–2175.
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Contributions
YJL and RSZ designed research of this study. SJD, HHQ and MA performed the data extraction and performed the analyses. SJD and YL drafted the paper. YJL, RSZ PM and YTZ critically revised the paper for important intellectual content. All authors designed the study and reviewed the manuscript.
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Appendices
Appendix 1
Search strategy for this study
Pubmed
#1 Anticoagulants[Mesh].
#2 Anticoagulation Agents[Title/Abstract] OR Agents, Anticoagulation[Title/Abstract] OR Anticoagulant Agents[Title/Abstract] OR Agents, Anticoagulant[Title/Abstract] OR Anticoagulant Drugs[Title/Abstract] OR Drugs, Anticoagulant[Title/Abstract] OR Anticoagulant[Title/Abstract].
#3 Liver Cirrhosis[Mesh].
#4 Hepatic Cirrhosis[Title/Abstract] OR Cirrhosis, Hepatic[Title/Abstract] OR Cirrhosis, Liver[Title/Abstract] OR Fibrosis, Liver[Title/Abstract] OR Liver Fibrosis[Title/Abstract].
#5 Portal Vein[Mesh].
#6 Portal Veins[Title/Abstract] OR Vein, Portal[Title/Abstract] OR Veins, Portal[Title/Abstract].
#7 Thrombosis[Mesh].
#8 Thromboses[Title/Abstract] OR Thrombus[Title/Abstract] OR Blood Clot[Title/Abstract] OR Blood Clots[Title/Abstract] OR Clot, Blood[Title/Abstract] OR Clots, Blood[Title/Abstract].
#9 (#1 OR #2) AND (#3 OR #4) AND (#5 OR #6) AND (#7 OR #8)
EMBASE
#1 'anticoagulation'/exp OR 'anticoagulation agents':ab,ti OR 'agents, anticoagulation':ab,ti OR 'anticoagulant agents':ab,ti OR 'agents, anticoagulant':ab,ti OR 'anticoagulant drugs':ab,ti OR 'drugs, anticoagulant':ab,ti OR 'anticoagulant':ab,ti OR 'anticoagulants':ab,ti.
#2 'liver cirrhosis'/exp OR 'hepatic cirrhosis':ab,ti OR 'cirrhosis, hepatic':ab,ti OR 'cirrhosis, liver':ab,ti OR 'fibrosis, liver':ab,ti OR 'liver fibrosis':ab,ti.
#3 'hepatic portal vein'/exp OR 'portal veins':ab,ti OR 'vein, portal':ab,ti OR 'veins, portal':ab,ti.
#4 'thrombosis'/exp OR 'thromboses':ab,ti OR 'thrombus':ab,ti OR 'blood clot':ab,ti OR 'blood clots':ab,ti OR 'clot, blood':ab,ti OR 'clots, blood':ab,ti.
#5 #1 AND #2 AND #3 AND #4
Cochrane:
#1 MeSH descriptor: [Anticoagulants] explode all trees.
#2 ('anticoagulation agents' OR 'agents, anticoagulation' OR 'anticoagulant agents' OR 'agents, anticoagulant' OR 'anticoagulant drugs' OR 'drugs, anticoagulant' OR 'anticoagulant' OR 'anticoagulants'):ti, ab, kw.
#3 MeSH descriptor: [Liver Cirrhosis] explode all trees.
#4 ('hepatic cirrhosis' OR 'cirrhosis, hepatic' OR 'cirrhosis, liver' OR 'fibrosis, liver' OR 'liver fibrosis'):ti, ab, kw.
#5 MeSH descriptor: [Portal Vein] explode all trees.
#6 ('portal veins' OR 'vein, portal' OR 'veins, portal'):ti, ab, kw.
#7 MeSH descriptor: [Thrombosis] explode all trees.
#8 ('thromboses' OR 'thrombus' OR 'blood clot' OR 'blood clots' OR 'clot, blood' OR 'clots, blood'):ti, ab, kw.
#9 (#1 OR #2) AND (#3 OR #4) AND (#5 OR #6) AND (#7 OR #8)
Appendix 2
Funnel plot for PVT recanalization
Funnel plot for PVT unchanged
Funnel plot for PVT extension
Funnel plot for Death
Funnel plot for Bleeding
Funnel plot for Variceal bleeding
Funnel plot for Complete PVT recanalization
Funnel plot for each outcome.
Appendix 3
PRISMA 2009 Checklist
Section/topic | # | Checklist item | Reported on page # |
|---|---|---|---|
Title | |||
Title | 1 | Identify the report as a systematic review, meta-analysis, or both | 1 |
Abstract | |||
Structured summary | 2 | Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number | 2 |
Introduction | |||
Rationale | 3 | Describe the rationale for the review in the context of what is already known | 3 |
Objectives | 4 | Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS) | 3 |
Methods | |||
Protocol and registration | 5 | Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number | None |
Eligibility criteria | 6 | Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale | 4 |
Information sources | 7 | Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched | 3, 4 |
Search | 8 | Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated | 4, Appendix |
Study selection | 9 | State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis) | 4 |
Data collection process | 10 | Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators | 4 |
Data items | 11 | List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made | 4 |
Risk of bias in individual studies | 12 | Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis | 4,5 |
Summary measures | 13 | State the principal summary measures (e.g., risk ratio, difference in means) | 4,5 |
Synthesis of results | 14 | Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis | 4,5 |
Risk of bias across studies | 15 | Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies) | 4,5 |
Additional analyses | 16 | Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified | 4,5 |
Results | |||
Study selection | 17 | Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram | 5 |
Study characteristics | 18 | For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations | 5 |
Risk of bias within studies | 19 | Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12) | 5, 6 |
Results of individual studies | 20 | For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot | 5, 6 |
Synthesis of results | 21 | Present results of each meta-analysis done, including confidence intervals and measures of consistency | 5, 6 |
Risk of bias across studies | 22 | Present results of any assessment of risk of bias across studies (see Item 15) | 6 |
Additional analysis | 23 | Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item 16]) | 5, 6 |
Discussion | |||
Summary of evidence | 24 | Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers) | 6, 7, 8, 9 |
Limitations | 25 | Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias) | 9 |
Conclusions | 26 | Provide a general interpretation of the results in the context of other evidence, and implications for future research | 9 |
Funding | |||
Funding | 27 | Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review | 1 |
From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7): e1000097
For more information, visit: www.prisma-statement.org.
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Dong, S., Qi, H., Li, Y. et al. A systematic review and meta-analysis of anticoagulation therapy for portal vein thrombosis in patients with cirrhosis: to treat or not to treat?. Hepatol Int 15, 1356–1375 (2021). https://doi.org/10.1007/s12072-021-10233-3
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DOI: https://doi.org/10.1007/s12072-021-10233-3