10 1016@j Rlfa 2014 12 002

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CLINRE-736; No. of Pages 9
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Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxxxxx
Available online at
ScienceDirect
www.sciencedirect.com
ORIGINAL ARTICLE
Association between portal vein thrombosis

and risk of bleeding in liver cirrhosis:
A systematic review of the literature
Xingshun Qi a,b,, Chunping Su c, Weirong Ren b,d, Man Yang b,e,
Jia Jia b,f, Junna Dai a, Wenda Xu a, Xiaozhong Guo a,
a
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),
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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
number of observed patients, and number of patients with

PVT. Additionally, we collected the data regarding the proportion of bleeding in cirrhotic patients with and without
PVT. If the original data were not reported, we collected
the odds or hazard ratios to express the difference in the
proportion of bleeding between the two groups. Data were
not synthesized, because they were expressed in different
ways.
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
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PVT and bleeding in liver cirrhosis
Figure 1
Flowchart of study selection.
Child-Pugh classes between patients with and without PVT

[12,15,20,25,27], 1 had similar MELD scores between the
two groups [26], 3 had signicantly different proportions of
Child-Pugh classes between the two groups [16,19,21], and
1 did not clearly report any relevant information [22]. Thus,
14 studies were considered to have relatively high-grade
evidence.
The results regarding the association between PVT and
the risk of bleeding were shown in Table 2.
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,
47% (18/38) had a previous history of variceal bleeding; by

comparison, 23% (48/213) of the patients without splanchnic
vein thrombosis had a previous history of variceal bleeding.
Third, Doumit et al. also reported that signicantly more cirrhotic patients with PVT had a history of variceal bleeding at
admission (the detailed data were missing in the abstract)
[15].
By contrast, one study by Amitrano et al., in which 387
patients presenting with esophageal variceal bleeding within
recent 4 weeks were included, reported a similar proportion
of previous bleeding between patients with and without PVT
(10/67, 14.9% versus 60/316, 19.0%; P = 0.435) [25]. But the
source of previous bleeding was not shown.
All bleeding (de novo or rebleeding) during the

total follow-up
Two studies reported a higher rate of bleeding in cirrhotic
patients with PVT than in those without PVT. John et al.
prospectively collected 290 cirrhotic patients evaluated for
liver transplantation [26]. Among them, 47 patients were
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Table 1
Characteristics of included studies.
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
LC with acute EVB treated

with somatostatin,
antibiotics, EVL
LC with hematemesis
and/or melena
(treatments include
vasoactive drugs,
endoscopic therapy,
combination of
endoscopic and
vasoactive therapy,
balloon tamponade alone,
or none)
LC treated with EVL in the
primary and secondary
prophylaxis of variceal
bleeding (advanced HCC
was excluded)
LC who underwent portal
vein doppler US and who
had no pre-existing HCC,
TIPS or surgical shunt
in-situ, or prior LT
LC listed for a rst LT with
or without hemorrhage
LC with acute GVB after
primary hemostasis using
gastric variceal
obturation therapy
(randomized to repeated
gastric variceal
obturation alone or in
combination with
non-selective -blockers)
LC evaluated for LT (HCC
was excluded, follow-up
> 6 months)
LC after the cessation of
acute EVB
101
DAmico et al.,
2003 [14]
Prospective
longitudinal
study
(abstract)
Retrospective
study
(full-text)
Multicenter,
prospective,
cohort study
(full-text)
LC with acute EVB

vasoactive therapy,
antibiotics, and EVL
LC and recent EVB
treated by band ligation
(HCC was excluded)
LC without HCC
Italy
Italy
Taiwan
Lee et al., 2009 Taiwan

[18]
Nery, et al.
2015 [28]
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%)
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Table 1
(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%)
Perarnau et al., France

2010 [20]
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
LC with acutely bleeding

esophagogastric varices
or a previous episode of
bleeding esophagogastric
varices treated with
emergency or elective
portacaval shunt
LC undergoing TIPS for
emergency bleeding
hemostasis or rebleeding
prevention
Biopsy-proved LC treated
with portal
decompression surgery
for active or previous
variceal hemorrhage
Biopsy-proved LC with or
without hemorrhage
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
LC with acute GVB

treated with endoscopic
N-butyl-2-cyanoacrylate
injection
LC with esophageal
varices treated with
elective or emergent EVL
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.
diagnosed with PVT at baseline, and another 23 patients

developed PVT during the follow-up period. The incidence
of upper gastrointestinal bleeding was 21.3% (10/47) in
patients with PVT at baseline, 17.4% (4/23) in those who
developed PVT, and 11.4% (25/220) in those without PVT.
A trend toward a higher incidence of bleeding in patients
with PVT was observed (14/70 versus 25/220, P = 0.065).
DellEra et al. performed a retrospective analysis to explore
the impact of PVT on the efcacy of endosopic variceal
band ligation in 214 cirrhotic patients (22 with PVT and 192
without PVT) [27]. The rate of bleeding was higher in PVT
patients than in non-PVT patients (2/22, 9.1% versus 15/192,
7.8%), but no signicant difference was achieved. Notably,
one bleeding episode in non-PVT patients was attributed to
endoscopic treatment-related ulcer.
In addition, a multicenter prospective study by Nevy
et al. compared the risk of decompensation between
patients who developed PVT during follow-up and those
who did not [28]. Variceal bleeding was one of 4 features
for decompensation. In the univariate analysis, the risk of
decompensation was signicantly associated with the development of PVT. However, the signicance disappeared in the
multivariate analysis.
De novo bleeding during the total follow-up

Two follow-up studies reported a higher incidence of de novo
bleeding in cirrhotic patients with PVT than in those without PVT [12,15]. Notably, the detailed treatment modalities
were not reported. First, in a 5-year follow-up study of 398
cirrhotic patients, the incidence of de novo variceal bleeding was 39% and 20% in PVT (n = 44) and no PVT (n = 354)
groups, respectively [15]. Second, Attili et al. also reported
a signicantly higher cumulative incidence of gastrointestinal bleeding in cirrhotic patients who developed PVT during
the follow-up than in those who did not (P < 0.00001, by
log-rank test) [12].
De novo bleeding within 14 days after endoscopic

therapy
One study by Yang et al. analyzed the risk factors associated
with early bleeding in cirrhotic patients undergoing elective
or emergent endoscopic variceal band ligation [24]. Early
bleeding was dened as the bleeding episode or rebleeding within 14 days after endoscopic therapy. The proportion
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Table 2
Results of included studies.
First author (year)
Outcomes observed
Comparative data (statistical signicance)
Amitrano et al., 2012

[11] AJG
Proportion of PVT in patients with and

without 5-day failure after acute variceal
bleeding
Rebleeding at the 1-year follow-up in
patients with and without PVT
Rebleeding at the nal follow-up in patients
with and without PVT
Gastrointestinal bleeding from any sources
in patients with and without PVT
PVT for predicting the 6-week rebleeding
8/31 versus 24/154 (P = 0.047)
Amitrano et al., 2012

[11] EJGH
Attili et al., 2012 [12]

Chen et al., 2012 [13]
DAmico et al., 2003 [14]
PVT for predicting the 5-day failure after

acute upper digestive bleeding
DellEra et al., 2014 [27]
Bleeding from esophageal varices in

Percentage of variceal bleeding during
follow-up in patients with and without PVT
History of variceal bleed at baseline in
History of variceal bleed in patients with
and without PVT
PVT for predicting the gastric variceal
rebleeding
Doumit et al., 2009 [15]

Francoz et al., 2005 [16]
Hung et al., 2012 [17]
John et al., 2013 [26]

Lee et al., 2009 [18]
Nery et al., 2014 [28]
Orloff et al., 1997 [19]

Perarnau et al., 2010
[20]
Sarfeh, 1979 [21]
Schmassmann et al.,
1993 [12]
Wu et al., 2002 [22]
Yang et al., 2007 [23]
Upper gastrointestinal bleeding in patients

with and without PVT
Percentage of PVT in patients with and
without rebleeding
PVT for predicting the decompensation
(including variceal bleeding)
Percentage of variceal rebleeding in

Percentage of rebleeding in patients with
and without rebleeding
Proportion of rebleeding in PVT and
non-PVT groups
Proportion of PVT in hemorrhage and
non-hemorrhage groups
PVT for predicting the gastric variceal
rebleeding
Proportion of PVT in bleeding and

non-bleeding groups
8/67 versus 30/316 (P = 0.543)

14/67 versus 52/316 (P = 0.382)
No detailed data were reported. (P < 0.00001
by log-rank test)
Univariate: HR = 2.62, 95% CI: 1.185.79
(P = 0.018)
Multivariate: HR = 2.734, 95% CI: 1.2286.088
(P = 0.014)
For any sources of bleeding: multivariate:
OR = 3.19, 95% CI: 1.536.67 (P = 0.002)
For variceal bleeding: multivariate: OR = 3.06,
95% CI: 1.396.68 (P = 0.005)
2/22 versus 15/192 (P = 0.761)
39% versus 20% (P < 0.05)
Data were not reported (P = 0.05)
18/38 versus 48/165 (P = 0.001)
Univariate: HR = 3.344, 95% CI: 1.6136.897
(P = 0.001)
Multivariate: HR = 4.049, 95% CI: 1.9088.621
(P < 0.001)
14/70 versus 25/220 (P = 0.065)
5/14 versus 14/83 (P = 0.141)
For partial PVT: univariate: HR = 1.77, 95% CI:
1.072.92 (P = 0.027)
For partial PVT: multivariate: HR = 1.60, 95%
CI: 0.693.74 (P = 0.28)
For partial or complete PVT: univariate:
HR = 1.61, 95% CI: 0.982.62 (P = 0.058)
For partial or complete PVT: multivariate:
HR = 1.37, 95% CI: 0.623.03 (P = 0.44)
5% versus 1% (emergency) or 0.3% (elective)
2/29 versus 18/402 (not signicant)
8/18 versus 4/68 (P < 0.01)
Univariate: OR = 0.96, 95% CI: 0.248.89 (not
signicant)
Multivariate: OR = 0.17, 95% CI: 0.021.69 (not
signicant)
CI: condence interval; HR: hazard ratio; OR: odds ratio; LC: liver cirrhosis; LT: liver transplantation; NA: not available; PVT: portal
vein thrombosis.
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of PVT was higher in bleeding group than in non-bleeding
group (4/19, 21% versus 5/77, 7%), but the difference was
not statistically signicant.
Five-day failure after medical/endoscopic therapy

Two prospective cohort studies demonstrated a higher rate
of 5-day failure in cirrhotic patients with PVT than in those
without PVT [11,14]. Five-day failure was dened as the failure to control bleeding, rebleeding, or death within 5 days.
First, DAmico et al. evaluated the short-term outcomes and
prognostic indicators of cirrhotic patients with upper digestive bleeding [14]. In the training cohort, 37 of 251 cirrhotic
patients had PVT. In the multivariate logistic regression
analysis, the presence of PVT was the independent predictor for 5-day failure (for any sources of bleeding: odds
ratio = 3.19, 95% condence interval: 1.536.67, P = 0.002;
for variceal bleeding: odds ratio = 3.06, 95% condence
interval: 1.396.68, P = 0.005). Second, Amitrano et al.
collected the data from 185 cirrhotic patients with acute
variceal bleeding [11]. In the univariate analysis, PVT was
more prevalent in patients with 5-day failure than in
those without (26%, 8/31 versus 16%, 24/154, P = 0.047).
But only a trend was showed without any statistical
signicance in a multivariate logistic regression analysis
(odds ratio = 2.942, 95% condence interval: 0.8849.790,
P = 0.079).
Six-week rebleeding after medical/endoscopic

therapy
Two retrospective studies found a higher rate of 6-week
rebleeding in cirrhotic patients with PVT than in those without PVT [13,18]. First, Chen et al. enrolled 101 cirrhotic
patients with endoscopy-proven active esophageal variceal
bleeding who underwent esophageal variceal ligation [13].
Among them, 25 patients were diagnosed with PVT. Univariate Cox regression analysis demonstrated a signicant
relationship between PVT and 6-week rebleeding (hazard
ratio = 2.62, 95% condence interval: 1.185.79, P = 0.018).
The statistical signicance was conrmed by a multivariate analysis (hazard ratio = 2.734, 95% condence interval:
1.2286.088, P = 0.014). Lee et al. also showed a higher proportion of PVT in patients who developed variceal rebleeding
within 6 weeks after the cessation of initial esophageal
variceal bleeding than in those who did not (5/14, 36% versus 14/83, 17%) [18]. But the difference between the two
groups was not statistically signicant.
Gastric variceal rebleeding after

medical/endoscopic therapy during the total
follow-up
In 2 studies, the ndings regarding the association between
gastric variceal rebleeding and PVT in liver cirrhosis were
opposite [17,23]. First, Wu et al. retrospectively analyzed
the risk factors of gastric variceal rebleeding in 83 patients
undergoing endoscopic N-butyl-2-cyanoacrylate injection
[23]. Fifteen of them had PVT. The odds ratios for PVT were
0.96 (95% condence interval: 0.248.89) and 0.17 (95%
condence interval: 0.021.69) in univariate and multivariate logistic regression analyses, respectively. This suggested
a similar incidence of gastric variceal rebleeding between
cirrhotic patients with and without PVT. Second, a randomized controlled trial by Hung et al. evaluated the predictors
for rebleeding in 95 cirrhotic patients with acute gastric
variceal bleeding after gastric variceal obturation in combination with and without non-selective beta-blockers [17].
Cox regression analysis identied the presence of main portal vein thrombosis as a major predictor for rebleeding
(univariate analysis: hazard ratio = 3.344, 95% condence
interval: 1.6136.897, P = 0.001; multivariate analysis: hazard ratio = 4.049, 95% condence interval: 1.9088.621,
P = 0.001).
Rebleeding after shunt surgery during the total

follow-up
Two studies demonstrated a higher rate of rebleeding after
shunt surgery in cirrhotic patients with PVT than in those
without [19,21]. First, in an early report, Sarfeh observed
the probability of rebleeding in cirrhotic patients who had
undergone portal decompression surgery for variceal hemorrhage [21]. Seven of 68 patients with the patent portal
veins rebled from varices, whereas 9 of 18 patients with
the thrombosed portal veins rebled (P < 0.01). Second, in a
prospective cohort study, Orloff et al. enrolled 1300 cirrhotic
patients who underwent emergency (n = 400) and elective
(n = 900) portacaval shunt surgery [19]. The incidence of
variceal rebleeding was 5% in 85 patients with PVT, 1% in
335 patients without PVT undergoing emergency surgery,
and 0.3% in 880 patients without PVT undergoing elective
surgery.
Rebleeding after transjugular intrahepatic

portosystemic shunt during the total follow-up
In a retrospective study by Perarnau et al., the incidence
of rebleeding after transjugular intrahepatic portosystemic
shunt was similar between cirrhotic patients with and without PVT (8% versus 7%) [20].
Rebleeding after medical/endoscopic therapy

during the total follow-up
Discussion
One study by Amitrano et al. showed a higher incidence of

rebleeding from varices in patients with PVT than in those
without PVT at the 1-year follow-up (8/67, 11.9% versus
30/316, 9.5%; P = 0.543) and at the nal follow-up (14/67,
20.9% versus 52/316, 16.5%; P = 0.382) [25].
This is the rst systematic review of the literature to explore

whether or not the presence of PVT can increase the risk of
bleeding in liver cirrhosis. In this study, the relevant papers
were identied from an extensive search strategy. Additionally, the reliability of their ndings was assessed according
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X. Qi et al.
to the pre-specied criteria. A majority of studies reported

relatively high-grade evidence.
Several positive correlations were summarized as follows:
at admission, a higher proportion of cirrhotic patients
with PVT had experienced bleeding;
regardless of treatment modalities, previous histories of
bleeding, or sources of bleeding, PVT increased the risk
of de novo bleeding;
as for the cirrhotic patients with acute variceal bleeding
treated with medical/endoscopic therapy, PVT increased
the risk of 5-day failure and 6-week rebleeding;
as for the cirrhotic patients undergoing surgical shunts for
the management of variceal bleeding, a pre-existing PVT
increased the risk of rebleeding.
Unexpectedly, as for the cirrhotic patients with gastric
variceal bleeding treated with medical/endoscopic therapy,
whether or not PVT would increase the risk of rebleeding
remained controversial in 2 studies. This might be explained
by the fact that gastric variceal bleeding was more likely to
develop at a relatively low portal pressure than esophageal
variceal bleeding [29,30]. In addition, as for the cirrhotic
patients undergoing transjugular intrahepatic portosystemic
shunts for the management of variceal bleeding, a preexisting PVT was not associated with the risk of rebleeding.
However, it should be noticeable that a transjugular intrahepatic portosystemic shunt becomes technically complex
in the setting of complete PVT and even impossible when an
occluded portal vein progresses into brotic cord [31,32].
Generally, these ndings suggested that PVT should increase
the risk of bleeding in liver cirrhosis in nearly all clinical
conditions but after transjugular intrahepatic portosystemic
shunt.
Given the detrimental effect of PVT on the risk of bleeding, the necessity of recanalizing the thrombosed portal
vein in a timely fashion might be considered. Several case
series have recently showed a relatively high rate of portal vein recanalization after anticoagulation in cirrhotic
patients with PVT with or without gastroesophageal varices
[16,3335]. And few serious drug-related adverse events
were reported [36]. On the other hand, the researchers have
suggested the possibility of spontaneous portal vein recanalization in cirrhotic patients with partial PVT [26,37,38].
However, the probability of disease progression appeared
to be higher in the absence of anticoagulation therapy
[36]. More importantly, once PVT worsened, the prognosis of liver cirrhosis would be further deteriorated [38].
Unfortunately, no predictors for the thrombus extension in
untreated patients are well established [39]. Thus, anticoagulation should be recommended to cirrhotic patients with
PVT, if its contraindications are excluded [40].
A major limitation of this study was that the treatment
modalities (medical/endoscopic therapy, shunt surgery, or
transjugular intrahepatic portosystemic shunt), sources of
bleeding (esophageal varices, gastric varices, or unknown),
lengths of observation (short-term or total follow-up), and
ways of data expression (number of events, hazard ratio,
or odd ratios) were very heterogeneous among studies.
Because only a few studies were eligible for every outcome, the meta-analyses might be inappropriate. Instead,
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.
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CLINRE-736; No. of Pages 9

Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxxxxx

Association between portal vein thrombosis

number of observed patients, and number of patients with

PVT and bleeding in liver cirrhosis

Flowchart of study selection.

Child-Pugh classes between patients with and without PVT

47% (18/38) had a previous history of variceal bleeding; by

All bleeding (de novo or rebleeding) during the

CLINRE-736; No. of Pages 9

Characteristics of included studies.

LC with acute EVB treated

LC with acute EVB

Lee et al., 2009 Taiwan

CLINRE-736; No. of Pages 9

PVT and bleeding in liver cirrhosis

Perarnau et al., France

LC with acutely bleeding

LC with acute GVB

diagnosed with PVT at baseline, and another 23 patients

De novo bleeding during the total follow-up

De novo bleeding within 14 days after endoscopic

CLINRE-736; No. of Pages 9

Results of included studies.

First author (year)

Comparative data (statistical signicance)

Amitrano et al., 2012

Proportion of PVT in patients with and

8/31 versus 24/154 (P = 0.047)

Amitrano et al., 2012

Attili et al., 2012 [12]

DAmico et al., 2003 [14]

PVT for predicting the 5-day failure after

DellEra et al., 2014 [27]

Bleeding from esophageal varices in

Doumit et al., 2009 [15]

Hung et al., 2012 [17]

John et al., 2013 [26]

Orloff et al., 1997 [19]

Yang et al., 2007 [23]

Upper gastrointestinal bleeding in patients

Percentage of variceal rebleeding in

Proportion of PVT in bleeding and

8/67 versus 30/316 (P = 0.543)

PVT and bleeding in liver cirrhosis

Five-day failure after medical/endoscopic therapy

Six-week rebleeding after medical/endoscopic

Gastric variceal rebleeding after

Rebleeding after shunt surgery during the total

Rebleeding after transjugular intrahepatic

Rebleeding after medical/endoscopic therapy

One study by Amitrano et al. showed a higher incidence of

This is the rst systematic review of the literature to explore

to the pre-specied criteria. A majority of studies reported

PVT and bleeding in liver cirrhosis

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