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Portal vein thrombosis (PVT) can be seen in patients with cirrhosis in association with hepatocellular carcinoma or following splenectomy for the treatment of hypersplenism. PVT can also occur spontaneously in patients with cirrhosis; it is this group that is the subject of this discussion.
Incidence, Etiology, and Clinical Consequences
PVT may be complete, partial, or associated with cavernous transformation of the portal vein (Fig. 1). The thrombi can be in any part of the portal venous system but are seen most commonly in the main portal vein or its intrahepatic branches. The prevalence of PVT varies widely in patients with cirrhosis, ranging from 5% to 26% in different series of patients who were either evaluated for or underwent liver transplantation. Most of these patients had partial PVT, and many were diagnosed at the time of surgery.1 In a series of 701 hospitalized patients with cirrhosis undergoing Doppler ultrasound, 11.2% were found to have PVT. In 43% of those with PVT, there were no symptoms, whereas 39% had portal hypertensive bleeding and 18% had abdominal pain, usually associated with intestinal ischemia.2 There were no clear clinical differences between those patients with cirrhosis who did and those who did not have PVT. In one prospective trial of patients with Child class B/C cirrhosis, 6 of 36 patients (16.6%) developed PVT during a 48‐week period of observation,3 suggesting many patients with advanced cirrhosis are at significant risk for developing this complication. PVT may progress or resolve spontaneously. In one series of 42 patients, partial PVT progressed in 48%, improved in 45%, and remained the same in 7%.4
Figure 1.
(A) Complete PVT. (B) Partial PVT. (C) Cavernous transformation of the portal vein. Note the bridging collaterals as indicated by arrows in C. Images are courtesy of Dr. Bobby Kalb.
The pathogenesis of PVT in cirrhosis is not clear. Factors thought to play a role include reduced flow in the portal vein as a consequence of increased resistance in the liver, inherited defects in coagulation (such as factor V Leiden or prothrombin mutations), and an imbalance between pro‐ and anticoagulant factors that develop in the patient with cirrhosis due to impaired hepatic function.1, 2
Individuals with PVT and abdominal pain frequently have mesenteric ischemia. The impact of PVT of insidious onset on disease progression and complications of cirrhosis is unclear. Patients with PVT tend to have smaller livers and more severe portal hypertension than those without PVT, but it is unclear whether this difference is a consequence of the PVT. Perhaps the most compelling argument for the negative impact of PVT on disease progression is the recent controlled trial in which 70 outpatients with Child class B/C cirrhosis and no PVT were randomized to enoxaparin (4000 IU/day subcutaneously) or no treatment for 48 weeks. During active treatment, none of the patients receiving enoxaparin developed PVT compared with 17% of controls. In the treated group, the probability of decompensation was significantly reduced, and survival was improved.3 The most common cause of decompensation was the development of ascites, which was significantly less in treated patients. Seventy percent of those who developed PVT in the control group developed ascites. The incidence of encephalopathy, sepsis, or variceal bleeding did not differ between the two groups. Which factor accounted for the beneficial effects of enoxaparin is unclear. The use of the drug clearly decreased the incidence of PVT, but its use was also associated with significantly fewer bacterial infections. The data suggest that PVT and perhaps microvascular thrombosis play a role in disease progression in patients with cirrhosis and that their prothrombotic state may require some type of treatment. Further studies are required before one can generally recommend anticoagulants in patients with cirrhosis as a preventative therapy. Limited data suggest the presence of asymptomatic PVT in patients with cirrhosis does not affect overall survival, although in some patients it may add to the technical difficulty of liver transplantation.5,6
Treatment of PVT
This discussion focuses on the treatment of PVT as a single problem (Table 1). The issues associated with performing transjugular portosystemic shunt (TIPS) for variceal bleeding in the presence of PVT or PVT thrombosis found during liver transplantation is not discussed in any detail. Patients with cavernous transformation of the portal vein are not candidates for treatment. Patients with small thrombi in the intrahepatic branches of the portal vein probably do not require treatment, though the data on this group of patients are limited. Lastly, it is unclear whether resolving the PVT has any impact on patient outcome, as there are no controlled trials comparing anticoagulation with no treatment. Thus, the only two issues tested are improvement in the PVT and risk of bleeding.
Table 1.
Treatment of PVT
| Efficacy | Safety | Effect Complications: Portal Hypertension | |
|---|---|---|---|
| Prevention of PVT | |||
| Anticoagulation | ++++ | +++ | +++ |
| Treatment of PVT | |||
| Anticoagulation | ++++ | +++ | ? |
| TIPS | +++ | ++ | ++++ |
Plus symbols represent a range from no effect (+) to better (++++).
Anticoagulation
There has been only one controlled trial on the prevention of PVT using anticoagulation.3 The use of warfarin or low molecular weight heparin to treat patients with PVT has been reported in several series. These series are prospective or retrospective case reports, not randomized controlled trials. In some reports, a group of patients with untreated cirrhosis were used as a control population. With treatment, recanalization occurred in 33% to 45% of cases and partial recanalization in 15% to 35%.7 When anticoagulation was discontinued, PVT recurred in 39% of patients.8 Long‐term anticoagulation is therefore required in these patients. In patients with untreated PVT, there was progression in 71%.9 Clinical benefit was not shown in any of the reports due to a lack of a suitable control population. Five to 10 percent of patients had an episode of bleeding ascribable to the anticoagulation.
TIPS
The alternative to anticoagulation is the creation of a TIPS. TIPSs have been used in patients who have failed anticoagulation or who have a complication such as variceal bleeding or refractory ascites in the presence of PVT. TIPS can be created in most of these patients even if they have a portal cavernoma.9,10 It is important to note that the indication for TIPS was not the PVT but a complication of portal hypertension. Patients with partial PVT found preceding liver transplantation have received TIPSs. The TIPS was effective in maintaining patency of the portal vein, but there was no clear benefit compared with patients whose PVT was not treated.11
Conclusions
PVT is a common finding in patients with cirrhosis, especially those with advanced liver disease. The impact of asymptomatic PVT on patient outcomes is unclear. Patients with mesenteric thrombosis appear to be at increased risk of intestinal ischemia, and complete thrombosis of the superior mesenteric and portal vein adds to the difficulty of liver transplantation. PVT can be treated with anticoagulants safely, and many patients will have complete or partial recanalization of their portal vein. The benefit to the patients of anticoagulation is unclear. Because recurrence of PVT is likely following discontinuation of anticoagulants, patients awaiting liver transplantation who have a finite period of treatment appear to be the best candidates. Use of TIPSs in patients with PVT is only indicated for management of complications of portal hypertension and not for the thrombosis per se. The results on preventing de novo PVT with anticoagulation are exciting, but we need to understand further how preventing thrombosis improves liver function and clinical outcomes.
Abbreviations
- PVT
portal vein thrombosis
- TIPS
transjugular portosystemic shunt.
Potential conflict of interest: Nothing to report.
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