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ORIGINAL ARTICLE
Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang 110840, China
Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xian 710032, China
c
Library of Fourth Military Medical University, Xian 710032, China
d
Department of Digestive Diseases, Sanmenxia Central Hospital, Henan University of Science and
Technology, Xiaoshan Road, Sanmenxia 472000, China
e
Department of Gastroenterology, Songgang Peoples Hospital, Shenzhen 518105, China
f
Department of Digestive Diseases, Shaanxi Provincial Peoples Hospital, Xian 710068, China
b
Summary
Aims: A systematic review of the literature was conducted to explore the association of portal
vein thrombosis (PVT) with the risk of bleeding in liver cirrhosis.
Methods: PubMed, EMBASE, and Cochrane library databases were searched for all relevant
papers, which compared the prevalence of bleeding at baseline and/or incidence of bleeding
during follow-up between cirrhotic patients with and without PVT.
Results: Eighteen papers were eligible for this systematic review. The heterogeneity among
studies was marked with regards to the treatment modalities, sources of bleeding, lengths
of follow-up, and ways of data expression. But most of their ndings were homozygous and
suggested that the cirrhotic patients with PVT were more likely to have previous histories of
bleeding at their admission and to develop de novo bleeding and/or rebleeding during the
short- and long-term follow-up. The association of PVT with the risk of bleeding might be
weakened in the multivariate analyses. Additionally, as for the cirrhotic patients with gastric
variceal bleeding treated with medical/endoscopic therapy, the association of PVT with the
risk of rebleeding remained controversial in 2 studies; as for the cirrhotic patients undergoing
transjugular intrahepatic portosystemic shunts for the management of variceal bleeding, a
pre-existing PVT was not associated with the risk of rebleeding.
Corresponding authors. Department of Gastroenterology, General Hospital of Shenyang Military Area, No. 83 Wenhua Road, Shenyang
110840 China. Tel.: +86 24 288 976 03; fax: +86 24 288 511 13.
E-mail addresses: xingshunqi@126.com (X. Qi), guo xiao zhong@126.com (X. Guo).
http://dx.doi.org/10.1016/j.clinre.2015.02.012
2210-7401/ 2015 Published by Elsevier Masson SAS.
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
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CLINRE-736; No. of Pages 9
ARTICLE IN PRESS
X. Qi et al.
Conclusions: Based on a systematic review of the literature, there was a positive association
between the presence of PVT and risk of bleeding in liver cirrhosis in most of clinical conditions.
However, whether PVT aggravated the development of bleeding during follow-up needed to be
further explored.
2015 Published by Elsevier Masson SAS.
Introduction
Gastroesophageal varices can be found in approximately
50% of cirrhotic patients at the time of diagnosis [1,2].
The development of varices is primarily attributed to an
increased portal pressure caused by brosis and regenerative nodules (as the hepatic venous pressure gradient is
more than 10 mmHg, varcies will develop [3]). Once the
varices are ruptured, the mortality is up to 1520% within
6 weeks and as high as 40% within 1 year [4,5]. The most
common predictors for the rst occurrence or recurrence
of variceal bleeding include the diameter of varices, red
signs on endoscopy, and Child-Pugh score [6]. Recently, the
researchers also have cast more attention to the effect of
portal vein thrombosis (PVT) on the development of variceal
bleeding in liver cirrhosis [7,8], because it can further elevate the resistance to portal inow. The important topic may
inuence the risk stratication of variceal bleeding, thereby
improving the algorithm for the management of variceal
bleeding in liver cirrhosis. Herein, we systematically review
the relevant literature to clarify the association between
PVT and risk of bleeding in liver cirrhosis.
Methods
Search strategy and study selection
As previously described, we retrieved all papers regarding
PVT via the PubMed, EMBASE, and Cochrane library
databases [9,10]. After this systematic search, more
recently published publications were also hand-searched.
Among the clinical studies with more than 10 patients, we
further identied the studies that evaluated the association
between PVT and risk of bleeding in liver cirrhosis. Exclusion
criteria were as follows:
only malignancy was enrolled;
PVT developed after surgery, therapeutic endoscopy, or
interventional treatments;
PVT developed in non-cirrhotic patients;
the control group (i.e., patients without PVT) was missing;
the association between PVT and risk of bleeding was not
evaluated.
Data extraction
We extracted the following characteristics of the included
studies: rst author, publication year, study design, enrolment period, target population, treatment modalities, total
Grade of evidence
The evidence was classied into high- and low-grade. The
evidence was of high-grade, if any one of the 2 following
points was met:
a multivariate analysis was performed to explore the statistically signicant difference;
if only a univariate analysis was performed, the baseline Child-Pugh class or MELD score should be matched
between patients with and without PVT.
Otherwise, the evidence was of low-grade.
Results
Characteristics of studies
Initially, 10,936 papers regarding PVT were identied.
Among them, 14 papers were eligible for this systematic
review [1124] (Fig. 1). Another 4 eligible papers, which
were published after the systematic search, were also identied by hand searching [2528]. Thus, 18 studies were
nally included. The characteristics of included studies were
summarized in Table 1. According to the regions, 5 studies
were performed in China Taiwan, 5 studies in Italy, 3 studies in USA, 2 studies in France, 1 study in Canada, 1 study in
Switzerland, and 1 study in France and Belgium. According to
the enrolment periods, 3 studies were launched before 1990,
5 studies between 1990 and 2000, and 10 studies after 2000.
According to the publication forms, 2 studies were published
in abstracts, and 16 studies in full-texts. Hepatocellular carcinoma was excluded in 7 studies, but not in 9 studies. The
information regarding the exclusion of hepatocellular carcinoma was not reported in 2 other studies. The prevalence
of PVT in liver cirrhosis was 725%.
Multivariate analyses were performed in 8 studies
[11,13,14,17,18,23,24,28], and only univariate analyses
were performed in 10 others. Of these studies without multivariate analyses, 5 had similar proportions of
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
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CLINRE-736; No. of Pages 9
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Figure 1
Prior bleeding
Three studies showed that the cirrhotic patients with PVT
had a higher proportion of history of variceal bleeding than
those without PVT [15,16,22]. First, Schmassmann et al.
enrolled 60 cirrhotic patients with and without previous
hemorrhage [22]. In the hemorrhage group, 10 of 30 patients
had PVT; by contrast, in the non-hemorrhage group, only
3 of 30 patients had PVT. Second, Francoz et al. enrolled
251 cirrhotic patients listed for the rst liver transplantation [16]. Of the patients with splanchnic vein thrombosis,
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
+Model
ARTICLE IN PRESS
X. Qi et al.
Table 1
First author
(year)
Country
Design
Period
Target population
Amitrano
et al., 2012
[11]
Amitrano
et al., 2012
[25]
Attili et al.,
2012 [12]
Italy
Prospective
cohort study
(full-text)
Cohort study
(full-text)
January 2010
July 2011
185
32 (17%)
387
67 (17.3%)
February 2000
July 2005
129
25 (19%)
Chen et al.,
2012 [13]
Taiwan
25 (25%)
Italy
291a
37 (13%)a
DellEra et al.,
2014 [27]
Italy
Retrospective
study (full-text)
February 1995
February 2009
214
44 (11%)
Doumit et al.,
2009 [15]
Canada
NA
(abstract)
2002
398
44 (11%)
Francoz et al.,
2005 [16]
Hung et al.,
2012 [17]
France
NA
(full-text)
RCT
(full-text)
Jan 1996
December 2001
April 2007
March 2011
251
38 (15%)
95
13 (14%)
John, et al.
2013 [26]
USA
Prospective
cohort study
(full-text)
Retrospective
study
(full-text)
Satellite study of
a multicenter
RCT (full-text)
July 2004
June 2009
101
DAmico et al.,
2003 [14]
Prospective
longitudinal
study
(abstract)
Retrospective
study
(full-text)
Multicenter,
prospective,
cohort study
(full-text)
Italy
Italy
Taiwan
France,
Belgium
January 2001
December 2010
July 2005
December 2009
October
1997January
1998a
Decemeber 2005
February 2008
June 2000
March 2006
LC without HCC
Total number
of patients
290
No. PVT
(%)
70b (24%)
97
19 (20%)
1243
118c (9%)
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
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(Continued)
First author
(year)
Country
Design
Period
Target population
Total number
of patients
No. PVT
(%)
Orloff et al.,
1997 [19]
USA
Prospective
cohort study
(full-text)
19581991
1300
85 (7%)
Retrospective
study
(full-text)
19902004
273
27 (10%)
Sarfeh, 1979
[21]
USA
Retrospective
study
(full-text)
19721978
86
18 (21%)
Schmassmann
et al., 1993
[12]
Wu et al., 2002
[23]
Switzerland
NA
(full-text)
January 1989
Decemeber 1990
60
13 (22%)
Taiwan
Retrospective
study
(full-text)
November 1992
October 1998
83
15 (18%)
Yang et al.,
2007 [24]
Taiwan
NA
(full-text)
May 2002
October 2004
96
9 (9%)
EVB: esophageal variceal bleeding; EVL: endoscopic variceal ligation; GVB: gastric variceal bleeding; HCC: hepatocellular carcinoma;
LC: liver cirrhosis; LT: liver transplantation; NA: not available; PVT: portal vein thrombosis; RCT: randomized controlled trial; TIPS:
transjugular intrahepatic portosystemic shunt.
a The data in the training set.
b Forty-seven patients were diagnosed with PVT at baseline, and 23 patients developed PVT during follow-up.
c One hundred and eighteen patients developed PVT during follow-up.
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
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ARTICLE IN PRESS
X. Qi et al.
Table 2
Outcomes observed
CI: condence interval; HR: hazard ratio; OR: odds ratio; LC: liver cirrhosis; LT: liver transplantation; NA: not available; PVT: portal
vein thrombosis.
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
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CLINRE-736; No. of Pages 9
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Discussion
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
+Model
CLINRE-736; No. of Pages 9
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X. Qi et al.
we just described the relevant outcomes from every individual study. Another limitation was that most of included
studies (9/14) did not exclude the patients with hepatocellular carcinoma. Thus, we could not identify whether the
nature of PVT should be attributed to malignancy or not. If
PVT originated from the tumor invasion, the patients would
be considered to have advanced HCC (BCLCC stage) with a
very short survival time [41], which might preclude from the
development of bleeding. Finally, the degree of PVT was not
reported in any included studies. Therefore, we could not
clarify the risk of bleeding in the subgroups with complete
versus partial PVT [42,43].
In conclusions, based on the present systematic review of
the literature, the presence of PVT should be positively associated with the risk of portal hypertension-related bleeding
in liver cirrhosis. However, this issue regarding whether or
not PVT aggravated the development of bleeding during
follow-up needed to be further explored by well-designed
observational studies. If the answer was Yes, an early
diagnosis and treatment of PVT would be further encouraged
to minimize the risk of bleeding. Otherwise, a wait-and-see
strategy would be considered.
Author contributions
Xingshun Qi conceived and drafted the manuscript. Xingshun Qi, Chunping Su, Weirong Ren, Man Yang, Jia Jia, Junna
Dai, and Wenda Xu performed the literature search and
selection, and data extraction; Xiaozhong Guo gave critical comments and revised the manuscript. All authors have
made an intellectual contribution to the manuscript and
approved the submission.
Disclosure of interest
The authors declare that they have no conicts of interest
concerning this article.
References
[1] Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and
management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46:92238.
[2] Garcia-Tsao G, Bosch J. Management of varices and variceal
hemorrhage in cirrhosis. N Engl J Med 2010;362:82332.
[3] Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to
prevent gastroesophageal varices in patients with cirrhosis. N
Engl J Med 2005;353:225461.
[4] de Franchis R. Revising consensus in portal hypertension:
report of the Baveno V consensus workshop on methodology
of diagnosis and therapy in portal hypertension. J Hepatol
2010;53:7628.
[5] DAmico G, Pagliaro L, Bosch J. The treatment of portal hypertension: a meta-analytic review. Hepatology 1995;22:33254.
[6] Prediction of the rst variceal hemorrhage in patients with
cirrhosis of the liver and esophageal varices. A prospective
multicenter study. N Engl J Med 1988;319:9839.
[7] Qi X, Bai M, Yang Z, et al. Occlusive portal vein thrombosis
as a new marker of decompensated cirrhosis. Med Hypotheses
2011;76:5226.
[8] Garcia-Pagan JC, Valla DC. Portal vein thrombosis: a predictable milestone in cirrhosis? J Hepatol 2009;51:6324.
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012
+Model
CLINRE-736; No. of Pages 9
ARTICLE IN PRESS
9
[27] DellEra A, Iannuzzi F, Fabris FM, et al. Impact of portal vein
thrombosis on the efcacy of endoscopic variceal band ligation.
Dig Liver Dis 2014;46:1526.
[28] Nery F, Chevret S, Condat B, et al. Causes and consequences of
portal vein thrombosis in 1243 patients with cirrhosis: results
of a longitudinal study. Hepatology 2015;61:6607.
[29] Huang YH, Yeh HZ, Chen GH, et al. Endoscopic treatment
of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl) injection: long-term efcacy and safety. Gastrointest
Endosc 2000;52:1607.
[30] Seewald S, Ang TL, Imazu H, et al. A standardized injection technique and regimen ensures success and safety of
N-butyl-2-cyanoacrylate injection for the treatment of gastric fundal varices (with videos). Gastrointest Endosc 2008;68:
44754.
[31] Qi X, Han G, Yin Z, et al. Transjugular intrahepatic portosystemic shunt for portal cavernoma with symptomatic
portal hypertension in non-cirrhotic patients. Dig Dis Sci
2012;57:107282.
[32] Han G, Qi X, He C, et al. Transjugular intrahepatic portosystemic shunt for portal vein thrombosis with symptomatic
portal hypertension in liver cirrhosis. J Hepatol 2011;54:
7888.
[33] Senzolo MT, Rossetto MSV, et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt
for the management of portal vein thrombosis in cirrhosis. Liver
Int 2012;32:91927.
[34] Delgado MG, Seijo S, Yepes I, et al. Efcacy and safety
of anticoagulation on patients with cirrhosis and portal vein thrombosis. Clin Gastroenterol Hepatol 2012;10:
77683.
[35] Amitrano L, Guardascione MA, Menchise A, et al. Safety and
efcacy of anticoagulation therapy with low molecular weight
heparin for portal vein thrombosis in patients with liver cirrhosis. J Clin Gastroenterol 2010;44:44851.
[36] 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;26:1545.
[37] 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;108:56874.
[38] Luca A, Caruso S, Milazzo M, et al. Natural course of extrahepatic non-malignant partial portal vein thrombosis in patients
with cirrhosis. Radiology 2012;265:12432.
[39] Qi X, Yang Z, Fan D. Spontaneous resolution of portal vein
thrombosis in cirrhosis: where do we stand, and where will
we go? Saudi J Gastroenterol 2014;20:2656.
[40] Qi X, Han G, Fan D. Management of portal vein thrombosis in
liver cirrhosis. Nat Rev Gastroenterol Hepatol 2014;11:43546.
[41] EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 2012;56:90843.
[42] Qi X, Han G, Fan D. Degree of portal vein thrombosis might
be associated with recanalization during anticoagulation. Clin
Gastroenterol Hepatol 2012;10:820.
[43] Qi X, Han G, Wang J, Wu K, Fan D. Degree of portal vein thrombosis. Hepatology 2010;51:108990.
Please cite this article in press as: Qi X, et al. Association between portal vein thrombosis and risk of
bleeding in liver cirrhosis: A systematic review of the literature. Clin Res Hepatol Gastroenterol (2015),
http://dx.doi.org/10.1016/j.clinre.2015.02.012