Risk factors for PVT / Results of univariate analysis / Multivariate analysis performed? / Results of multivariate analysis / Interpretation of results / Sources of evidence
Type of analysis / Study design / Patients (n) / Relevant papers
Characteristics of portal flow
Decreased portal flow velocity (cut-off: 15cm/s) / P<0.001 / Yes / OR=44.9 (95% CI 5.3–382.7, P<0.001) / Significant in both univariate and multivariate analyses / Chi-square test, logistic regression analysis / Prospective cohort study / 73 / Zocco et al. (2009)S1
Lower mean portal vein flow velocity / P<0.001 / Yes / OR=4.5 (95% CI 3.7–8.2, P<0.001) / Significant in both univariate and multivariate analyses / Chi-square test, logistic regression analysis / Retrospective study / 56 / Pellicelli et al. (2011)S2
Portal trunk vessel diameter / NS / Uncertain / N/A / NS in univariate analysis / Student’s ttest / Retrospective study / 150 / Maruyama et al. (2013)S3
Portal trunk flow velocity / NS / Uncertain / N/A / NS in univariate analysis
Lower portal trunk flow volume / P=0.016 / Uncertain / N/A / Significant in univariate analysis
Characteristics of largest collateral vessel
Larger vessel diameter / HR=1.422 (95% CI 1.210–1.732, P=0.0103) / Yes / N/A / Significant in univariate, but not in multivariate analysis / Cox regression analysis / Retrospective study / 150 / Maruyama et al. (2013)S3
Higher flow velocity (cut-off: 10.2cm/s) / HR=2.876 (95% CI 2.691–3.170, P<0.0001) / Yes / N/A / Significant in univariate, but not in multivariate analysis
Higher flow volume (cut-off: 398ml/min) / HR=3.894 (95% CI 3.189–4.798, P<0.0001) / Yes / HR=3.992 (95% CI 3.697–4.415, P<0.0001) / Significant in both univariate and multivariate analyses
Characteristics of coagulation abnormalities
Factor V Leiden mutation / P=0.78 / No / N/A / NS in univariate analysis / Chi-square test / Retrospective study / 63 / Amitrano et al. (2000)S4
P<0.05 / No / N/A / Significant in univariate analysis / Chi-square test / Retrospective study / 64 / Erkan et al. (2005)S5
NS / No / N/A / NS in univariate analysis / Chi-square test / Retrospective study / 219 / Mangia et al. (2005)S6
OR=1.52 (95% CI 0.64–3.60, NS) / No / N/A / NS / Meta-analysis / Meta-analysis / 5 studies / Dentali et al. (2008)S7
Prothrombin G20210A mutation / P=0.002 / No / N/A / Significant in univariate analysis / Chi-square test / Retrospective study / 63 / Amitrano et al. (2000)S4
P<0.01 / No / N/A / Significant in univariate analysis / Chi-square test / Retrospective study / 64 / Erkan et al. (2005)S5
NS / No / N/A / NS in univariate analysis / Chi-square test / Retrospective study / 219 / Mangia et al. (2005)S6
OR=3.68 (95% CI 1.58–8.57) / No / N/A / Significant in univariate analysis / Meta-analysis / Meta-analysis / 3 studies / Dentali et al. (2008)S7
MTHFR C667T mutation / P<0.001 / No / N/A / Significant in univariate analysis / Chi-square test / Retrospective study / 63 / Amitrano et al. (2000)S4
NS / No / N/A / NS / Chi-square test / Retrospective study / 64 / Erkan et al. (2005)S5
NS (homozygous) / No / N/A / NS in univariate analysis / Chi-square test / Retrospective study / 219 / Mangia et al. (2005)S6
P=0.037 (homozygous) / No / N/A / Significant / Chi-square test / Retrospective study / 76 / Gabr et al. (2010)S8
P<0.001 (homozygous) / Yes / OR=4.1 (95% CI 3.2–7.3, P<0.001) / Significant in both univariate and multivariate analyses / Chi-square test, logistic regression analysis / Retrospective study / 56 / Pellicelli et al. (2011)S2
Positive anticardiolipin antibodies / P=0.015 / No / N/A / Significant in univariate analysis / Chi-square test / Retrospective study / 73 / Violi et al. (1994)S9
Positive lupus anticoagulant / P=0.0008 / No / N/A / Significant in univariate analysis
Hypofibrinolysis / TAFI: P=0.001; activated TAFI: P=0.037; PAI1: P=0.004 / No / N/A / Significant in univariate analysis / Nonparametric Mann-Whitney U test / Retrospective study / 66 / Rossetto et al. (2013)S10
PAI1: P=0.947; tPA: P=0.205 / No / N/A / NS in univariate analysis / Mann-Whitney Utest & student’s ttest / Retrospective study / 116 / Zhang et al. (2010)S11
Increased levels of Ddimer / P<0.001 / Yes / OR=15.57 (95% CI 4.09–59.14, P<0.01) / Significant in univariate and multivariate analysis / Mann-Whitney Utest & student’s ttest / Retrospective study / 116 / Zhang et al. (2010)S11
P<0.01 / No / N/A / Significant in univariate analysis / Mann-Whitney Utest / Retrospective study / 188 / Zhang et al. (2013)S12
Decreased levels of AT, PC and PS / NS / No / N/A / NS in univariate analysis / Student’s t-test / Retrospective study / 63 / Amitrano et al. (2000)S4
NS / No / N/A / NS in univariate analysis / Student’s t-test / Retrospective study / 64 / Erkan et al. (2005)S5
NS / No / N/A / NS in univariate analysis / Student’s t-test / Retrospective study / 76 / Gabr et al. (2010)S8
AT: P=0.119; PS: P=0.028; PC: P=0.007 / Yes / PS: NS; Increased PC: OR=0.48 (95% CI 0.24–0.95, P=0.036) / PC and PS were significant in univariate analysis, but only PC was significant in multivariate analysis / Student’s ttest & logistic regression analysis / Retrospective study / 116 / Zhang et al. (2010)S11
AT: P=0.24; PS: P=0.006; PC: P=0.16 / No / N/A / Only PS was significant in univariate analysis / Meta-analysis / Meta-analysis / 9 studies / Qi et al. (2013)S13
AT: P=0.53; PS: P=0.125; PC: P=0.058 / No / N/A / NS in univariate analysis / Student’s t-test / Retrospective study / 60 / Chen et al. (2013)S14
Abbreviations: AT, antithrombin; HR, hazard ratio; N/A, not available; NS, not significant; OR, odds ratio; PC, protein C; PS, protein S; PVT, portal vein thrombosis; PAI1, plasminogen activator inhibitor; TAFI, thrombin activatable fibrinolysis inhibitor; tPA, tissue-type plasminogen activator.
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S2. Pellicelli, A.M. etal. Clinical and genetic factors associated to development of portal vein thrombosis in cirrhotic patients without hepatocellular carcinoma. J. Hepatol. 54, S77 (2011).
S3. Maruyama, H., Okugawa, H., Takahashi, M. & Yokosuka, O. Denovo portal vein thrombosis in virus-related cirrhosis: predictive factors and long-term outcomes. Am. J. Gastroenterol. 108, 568–574 (2013).
S4. Amitrano, L. etal. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 31, 345–348 (2000).
S5. Erkan, O. etal. Thrombophilic gene mutations in cirrhotic patients with portal vein thrombosis. Eur. J. Gastroenterol. Hepatol. 17, 339–343 (2005).
S6. Mangia, A. etal. Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and acquired factors. Eur. J. Gastroenterol. Hepatol. 17, 745–751 (2005).
S7. Dentali, F., Galli, M., Gianni, M. & Ageno, W. Inherited thrombophilic abnormalities and risk of portal vein thrombosis. A meta-analysis. Thromb. Haemost 99, 675–682 (2008).
S8. Gabr, M.A., Bessa, S.S. & El-Zamarani, E.A. Portal vein thrombosis in Egyptian patients with liver cirrhosis: Role of methylenetetrahydrofolate reductase C677T gene mutation. Hepatol. Res. 40, 486–493 (2010).
S9. Violi, F. etal. Relation between lupus anticoagulant and splanchnic venous thrombosis in cirrhosis of the liver. BMJ 309, 239–240 (1994).
S10. Rossetto, V. etal. Does decreased fibrinolysis have a role to play in the development of non-neoplastic portal vein thrombosis in patients with hepatic cirrhosis? Intern. Emerg. Med. http://dx.doi.org/10.1007/s11739-013-0929-7
S11. Zhang, D., Hao, J. & Yang, N. Protein C and Ddimer are related to portal vein thrombosis in patients with liver cirrhosis. J. Gastroenterol. Hepatol 25, 116–121 (2010).
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S13. Qi, X., Chen, H. & Han, G. Effect of antithrombin, protein C and protein S on portal vein thrombosis in liver cirrhosis: a meta-analysis. Am. J. Med. Sci 346, 38–44 (2013).
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Supplementary table 2 | Effect of portal vein thrombosis on the prognosis of cirrhotic patients with bleedingEffect of PVT on prognosis / Results of univariate analysis / Multivariate analysis performed? / Results of multivariate analysis / Interpretation of results / Sources of evidence
Type of analysis / Study design / Target population / Patients (n) / Relevant papers
5-day failure (failure to control bleeding, rebleeding, or death within 5days of admission)
Increased 5day failure / P<0.05 / Yes / OR=3.19 (95% CI 1.53–6.67, P=0.002)* OR=3.06 (95% CI 1.396.68, P=0.005)# / Significant in both univariate and multivariate analyses / Logistic regression analysis / Multi-center, prospective cohort study / LC with hematemesis and/or melena / 291* 207# / D’Amico et al. (2003)S15
P=0.047 / Yes / OR=2.942 (95% CI 0.884–9.790, P=0.079) / Significant in univariate, but not in multivariate analysis / Logistic regression analysis / Prospective study / LC with EVB / 185 / Amitrano et al. (2012)S16
Bleeding
Increased 2week rebleeding / OR=7.54 (95% CI 3.25–17.50, P<0.01) / No / N/A / Significant in univariate analysis / Logistic regression analysis / Retrospective study / LC with acute EVB / 342 / Xu et al. (2011)S17
Increased 6week rebleeding / HR=2.62 (95% CI 1.18–5.79, P=0.018) / Yes / HR= 2.734 (95% CI 1.228–6.088, P=0.014) / Significant in both univariate and multivariate analyses / Cox regression analysis / Cohort study / LC with active EVB / 101 / Chen et al. (2012)S18
P=0.141 / No / N/A / NS in univariate analysis / Fisher’s exact test / Retrospective study / LC with EVB / 97 / Lee et al. (2009)S19
Increased 1year rebleeding / P=0.543 / No / N/A / NS in univariate analysis / Chi-square test / Prospective study / LC with recent EVB / 383 / Amitrano et al. (2012)S20
Increased rebleeding during final follow-up / P=0.382 / No / N/A / NS in univariate analysis / Chi-square test / Prospective study / LC with recent EVB / 83 / Amitrano et al. (2012)S20
HR=3.344 (95% CI 1.613–6.897, P=0.001) / Yes / HR=4.049 (95% CI 1.908–8.621, P<0.001) / Significant in both univariate and multivariate analyses / Cox regression analysis / Randomized controlled trial / LC with acute GVB / 95 / Hung et al. (2012)S21
NS / Yes / OR=0.17 (95% CI 0.02–1.69, NS) / NS in both univariate and multivariate analyses / Logistic regression analysis / Retrospective study / LC with acute GVB / 83 / Wu et al. (2002)S22
Mortality
Increased 6week mortality / HR=3.19 (95% CI 1.59–6.41, P=0.001) / Yes / N/A / Significant in univariate, but not in multivariate analysis / Cox regression analysis / Cohort study / LC with active EVB / 101 / Chen et al. (2012)S18
P=0.102 / No / N/A / NS in univariate analysis / Univariate (Cox regression analysis) / Retrospective study / LC with EVB / 97 / Lee et al. (2010)S23
P=0.01 / No (PVT was not included in multivariate analysis) / N/A / Significant in univariate analysis / Logistic regression analysis / Prospectively built cohort / LC with acute EVB / 164 / Augustin et al. (2009)S24
Increased mortality during 1year follow-up / P=0.382 / No / N/A / NS in univariate analysis / Chi-square test / Prospective study / LC with recent EVB / 383 / Amitrano et al. (2012)S20
Increased mortality during final follow-up / P=0.040 / No / N/A / Significant in univariate analysis / Chi-square test / Prospective study / LC with recent EVB / 383 / Amitrano et al. (2012)S20
HR=6.024 (95% CI: 2.770–13.158, P<0.001) / Yes / HR=3.390 (95% CI 1.499–7.692, P=0.003) / Significant in both univariate and multivariate analyses / Cox regression analysis / Randomized controlled trial / LC with acute GVB / 95 / Hung et al. (2012)S21
HR=12.6 (95% CI 5.93–26.72, P<0.01) / Yes / HR=6.99 (95% CI 2.42–20.16, P<0.01) / Significant in both univariate and multivariate analyses / Cox regression analysis / Retrospective study / LC with acute GVB / 83 / Wu et al. (2002)S22
Notes: * data in patients independent of source of bleeding; # data in patients with bleeding from varices.
Abbreviations: EVB, esophageal variceal bleeding; GV, gastric variceal bleeding; HR, hazard ratio; LC, liver cirrhosis; N/A, not available; NS, not significant; OR, odds ratio; PVT, portal vein thrombosis.
S15. D’Amico, G. & De Franchis, R. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology 38, 599–612 (2003).
S16. Amitrano, L. etal. The effectiveness of current acute variceal bleed treatments in unselected cirrhotic patients: refining short-term prognosis and risk factors. Am. J. Gastroenterol 107, 1872–1878 (2012).
S17. Xu, L., Ji, F., Xu, Q.W. & Zhang, M.Q. Risk factors for predicting early variceal rebleeding after endoscopic variceal ligation. World J. Gastroenterol. 17, 3347–3352 (2011).
S18. Chen, P.H. etal. Delayed endoscopy increases re-bleeding and mortality in patients with hematemesis and active esophageal variceal bleeding: a cohort study. J. Hepatol. 57, 1207–1213 (2012).
S19. Lee, S.W., Lee, T.Y. & Chang, C.S. Independent factors associated with recurrent bleeding in cirrhotic patients with esophageal variceal hemorrhage. Dig. Dis. Sci. 54, 1128–1134 (2009).
S20. Amitrano, L. etal. Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis. Eur. J. Gastroenterol. Hepatol. 24, 1381–1385 (2012).