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PVT in cirrhosis, not always an innocent bystanderMarco Senzolo

Portal vein thrombosis occurs frequently in patients with cirrhosis, but it is unclear whether it is a cause or consequence of decompensation in cirrhosis. The heterogeneity of data on the influence of portal vein thrombosis on the natural history of cirrhosis has been added to in a new study.Senzolo, M. Nat. Rev. Gastroenterol. Hepatol. advance online publication 16 December 2014; doi:10.1038/nrgastro.2014.218

In an article published in Hepatology, Nery et al.1 have investigated the natural course of portal vein thrombosis (PVT) in patients with liver cirrhosis. The authors performed a satellite study of a multicentre randomized controlled trial comparing 3 month versus 6 month intervals between ultrasonography for the screening of hepatocellular carcin­oma. Liver function was very stable in all patients with normal prothrombin time and plasmatic albumin concentration. Amongst the 1,243 patients screened during the fo llow­up the incidence of PVT was 9.23%, and 73% of these patients had partial PVT; occurrence of PVT did not correlate with severity of liver disease or decompensation but only with more severe portal hyperten­sion, which was defined by the presence of large oesophageal varices. During the 80 months of follow­up, 70% of patients had spontaneous complete recanalization of the portal vein, with 19% of this group having recurrence of PVT. In addition, the presence of PVT did not correlate with an increased risk of liver decompensation e pisodes or mortality.

The influence of PVT on the natural history of cirrhosis is still a matter of debate and conflicting results are present in the lit­erature, owing to different study populations and the lack of large dedicated prospective studies taking into account both the severity

of liver disease and the characteristics of thrombosis. Most reports have found a cor­relation between the prevalence of PVT and severity of liver disease; however, Nery et al.1 only found a correlation between the inci­dence of PVT and severity of oesophageal varices. Moreover, the rate of spontane­ous repermeation of the portal vein in this cohort was exceptionally high (70%) com­pared to only 1 in 42 patients in a prospective study assessed by serial CT scan2 and even compared to the number of patients who obtained complete thrombus disappearance (40–75%) after anticoagulation treatment in our own published cohort.3 The high rate of spontaneous repermeation could have seriously jeopardized the analysis of the effect of PVT on liver disease progression, decompensation and survival. In addition, the authors did not analyse the subgroup of patients with complete PVT separately.

Until now, few published papers have described the outcomes for patients with PVT who are not treated and all describe heterogeneous populations in terms of liver disease severity, incidence of progres­sion or stabilization of the thrombus and occurrence of liver decompensation epi­sodes and deaths (Supplementary Table 1). Luca et al.2 showed increased mortality in patients who had stable or progressed thrombus (39.1%) versus those who improved (15.8%); in a single centre study describing 70 patients untreated for PVT, a statistically significant increase in decom­pensation episodes (P = 0.05) was found in patients with PVT than the non­PVT control group.4 Moreover, another small study evaluating patients with untreated

PVT have a clear correlation between progressed or stable PVT and occurrence of decompensation episodes and deaths.5 These findings might represent differences in populations, because patients in these two latter cohorts4,5 were diagnosed as having PVT when decompensated, sympto­matic for abdominal pain or during admis­sion for acute variceal bleeding; therefore, these patients might have a more long­lasting thrombus or a thrombus that had already progressed.

Clinically, the appearance of an incom­plete PVT in very stable patients with cirrhosis but without severe portal hyperten­sion might not substantially affect survival and progression of liver disease, similar to those with PVT but without underlying liver disease. On the contrary, in a multicentre prospective cohort study on the risk factors for failure and mortality in 465 patients with cirrhosis and variceal bleeding, multivariate analysis showed that PVT was indepen­dently associated with 5 days failure (defined as uncontrolled bleeding, rebleeding or death) (OR 3.18; P = 0.002).6 A similar pro­spective study on 185 patients with cirrhosis who bled from varices con­firmed this data.7 During the natural history of a patient with cirrho­sis and PVT, about 40–70% of thrombo­ses will progress to complete occlusion of the portal vein3 or extension into other splanchnic

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‘‘Most reports have found a correlation between the prevalence of PVT and severity of liver diseasee...’’

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vessels; if the underlying severity of liver disease progresses simultaneously, the patient will become a candidate for liver transplantation. In this clinical scenario, PVT acquires a different role in the natural history of the patient’s condition. In a sys­tematic review on the effect on outcomes of PVT in candidates for liver transplantation, it has been shown that PVT is significantly correlated with increased mortality after liver transplantation (18.8% PVT versus 15.4% non­PVT; with a HR of 1.39; 95% CI 1.18–1.64; P = 0.01).7 Interestingly, most of the detrimental effect on survival was owing to complete PVT, which was exacerbated if the thrombus extended into the superior mesen­teric vein or if non­anatomical reconstruc­tion of portal vein anastomosis was needed during transplantion.8 Moreover, whilst waiting for liver transplantation, patients with cirrhosis might develop hepato cellular carcinoma and the presence of an occluded portal vein hampers the performance of transarterial c hemoembolization to treat a multifocal tumour.

The hepatological community might think—based on the work by Nery and c olleagues1—that partial PVT has to be left untreated and that treatment should be

considered only if PVT progresses. This approach would need frequent screening and anticoagulation could have a different efficacy on an older thrombus. A prospec­tive study has shown that anticoagulation is more efficient when given within 6 months from estimated diagnosis of PVT and that treatment­based recanalization rarely occurs in patients with a thrombus >12 months old.3 A dedicated randomized control trial on anticoagulation versus no treatment in patients with partial PVT followed by even­tual treatment if thrombosis progresses should be performed to answer these ques­tions and avoid potentially unnecessary anti­coagulation. However, evidence exists that anticoagulation might be beneficial per se in preventing decompensation episodes and reducing mortality in patients with Child­Pugh B disease.9

Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Via Giustiniani 2, 35128 Padua, Italy. marcosenzolo@hotmail.com

Competing interestsThe author declares no competing interests.

1. Nery, F. et al. Causes and consequences of portal vein thrombosis in 1243 patients with cirrhosis: results of a longitudinal study. Hepatology http://dx.doi.org/10.1002/hep.27546.

2. Luca, A. et al. Natural course of extrahepatic nonmalignant partial portal vein thrombosis in patients with cirrhosis. Radiology 265, 124–132 (2012).

3. Senzolo, M. et al. Prospective evaluation of anticoagulation and transjugular intrahepatic portosystemic shunt for the management of portal vein thrombosis in cirrhosis. Liver Int. 32, 919–927 (2012).

4. John, B. V. et al. Impact of untreated portal vein thrombosis on pre and post liver transplant outcomes in cirrhosis. Ann. Hepatol. 12, 952–958 (2013).

5. Girleanu, I. et al. Natural course of nonmalignant partial portal vein thrombosis in cirrhotic patients. Saudi J. Gastroenterol. 20, 288–292 (2014).

6. D’Amico, G. et al. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology 38, 599–612 (2003).

7. Amitrano, L. et al. Splanchnic vein thrombosis and variceal rebleeding in patients with cirrhosis. Eur. J. Gastroenterol. Hepatol. 24, 1381–1385 (2012).

8. Rodríguez-Castro, K. I. et al. Management of nonneoplastic portal vein thrombosis in the setting of liver transplantation: a systematic review. Transplantation 94, 1145–1153 (2012).

9. Villa, E. et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 143, 1253–1260 (2012).

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