Gastroenterology

Gastroenterology

Volume 143, Issue 5, November 2012, Pages 1253-1260.e4
Gastroenterology

Original Research
Clinical—Liver
Enoxaparin Prevents Portal Vein Thrombosis and Liver Decompensation in Patients With Advanced Cirrhosis

https://doi.org/10.1053/j.gastro.2012.07.018Get rights and content

Background & Aims

We performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis.

Methods

In a nonblinded, single-center study, 70 outpatients with cirrhosis (Child–Pugh classes B7–C10) with demonstrated patent portal veins and without hepatocellular carcinoma were assigned randomly to groups that were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks; n = 34) or no treatment (controls, n = 36). Ultrasonography (every 3 months) and computed tomography (every 6 months) were performed to check the portal vein axis. The primary outcome was prevention of PVT. Radiologists and hepatologists that assessed outcomes were blinded to group assignments. Analysis was by intention to treat.

Results

At 48 weeks, none of the patients in the enoxaparin group had developed PVT, compared with 6 of 36 (16.6%) controls (P = .025). At 96 weeks, no patient developed PVT in the enoxaparin group, compared with 10 of 36 (27.7%) controls (P = .001). At the end of the follow-up period, 8.8% of patients in the enoxaparin group and 27.7% of controls developed PVT (P = .048). The actuarial probability of PVT was lower in the enoxaparin group (P = .006). Liver decompensation was less frequent among patients given enoxaparin (11.7%) than controls (59.4%) (P < .0001); overall values were 38.2% vs 83.0%, respectively (P < .0001). The actuarial probability of liver decompensation was lower in the enoxaparin group (P < .0001). Eight patients in the enoxaparin group and 13 controls died. The actuarial probability of survival was higher in the enoxaparin group (P = .020). No relevant side effects or hemorrhagic events were reported.

Conclusions

In a small randomized controlled trial, a 12-month course of enoxaparin was safe and effective in preventing PVT in patients with cirrhosis and a Child–Pugh score of 7–10. Enoxaparin appeared to delay the occurrence of hepatic decompensation and to improve survival. www.isrctn.>org: ISRCTN32383354; www.clinicaltrialsregister.eu: EudraCT2007-007890-22.

Section snippets

Study Design and Participants

Between April 2008 and November 2010, all consecutive patients seen at a tertiary referral liver unit (Azienda Ospedaliero-Universitaria, Modena) and satisfying predefined inclusion criteria were recruited. Eligible patients were 18 years and older and had cirrhosis of any etiology, a Child–Pugh score between B7 and C10, absence of ascites, spontaneous bacterial peritonitis (SBP), portal hypertensive bleeding or portosystemic encephalopathy for at least 3 months before enrollment, and no

Results

Supplementary Figure 1 shows the trial profile. A total of 396 patients with cirrhosis were screened for study eligibility: 326 patients were excluded (Supplementary Figure 1), and 70 patients were assigned randomly to the enoxaparin (n = 34) or control group (n = 36). All patients but 1 (withdrawn for thrombocytopenia) completed the treatment. The trial was completed as planned in November 2011. There were no missing values for the primary outcome. There were no significant differences in

Discussion

The results of this RCT in a cohort of patients with advanced cirrhosis showed that anticoagulant treatment with enoxaparin is safe and effective, significantly reducing risk of PVT development and liver decompensation, markedly improving liver function and Child–Pugh score, and increasing overall survival. Our findings are consistent with data showing that successful PVT recanalization is accompanied by improvement of the Child–Pugh score.23

It is plausible that PVT prevention has a protective

Acknowledgments

E.V., M.L., R.C., B.L., V.B., R.V., A.K., M.D.B., E.T., and A.F. on behalf of the Research Network “Women_in_Hepatology.”

The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and statistical analysis.

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    This article has an accompanying continuing medical education activity on page e17. Learning Objective: Upon completion of this exam, successful learners will be able to correctly identify patients with cirrhosis who should be considered for prophylactic anticoagulation, to formulate a correct surveillance protocol, to select the appropriate treatment schedule, and to prevent PVT.

    Conflicts of interest The authors disclose no conflicts.

    Funding This study was independently designed and was not supported by any pharmaceutical company. The National Health System provided enoxaparin. This study adheres to the standards of accountability, access to data, and control of publications of the International Committee of Medical Journal Editors.33 The study protocol was approved by the Ethics Committee of Azienda Ospedaliero-Universitaria, Modena (ISRCTN32383354, EudraCT 2007-007890-22).

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