Portal vein thrombosis in patients with cirrhosis

Gastroenterology Report, 5(2), 2017, 148–156 doi: 10.1093/gastro/gox014 Review REVIEW Portal vein thrombosis in patients with cirrhosis Leona von Köckritz1,†, Andrea De Gottardi1,2,†, Jonel Trebicka3,4,5,*,†, Michael Praktiknjo3,† 1 Hepatology, Clinic of Visceral Surgery and Medicine, Inselspital, Bern, Switzerland, 2Department of Clinical Research, University of Bern, Bern, Switzerland, 3Department of Internal Medicine I, University of Bonn, Bonn, Germany, 4Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark and 5European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain *Corresponding author. Laboratory for Liver Fibrosis and Portal Hypertension, Department of Internal Medicine I, University Clinic Bonn, Sigmund-FreudStr. 25, 53127 Bonn, Germany. Email: † All authors contributed equally to this review. Abstract Portal vein thrombosis (PVT) is frequent in patients with liver cirrhosis and possible severe complications such as mesenteric ischemia are rare, but can be life-threatening. However, different aspects of clinical relevance, diagnosis and management of PVT are still areas of uncertainty and investigation in international guidelines. In this article, we elaborate on PVT classification, geographical differences in clinical presentation and standards of diagnosis, and briefly on the current pathophysiological understanding and risk factors. This review considers and highlights the pitfalls of the various treatment approaches and prophylactic treatments. Finally, we review the controversial issue of clinical impact of PVT on prognosis, especially considering liver transplantation and future perspectives. Key words: portal vein thrombosis; liver cirrhosis; thrombophilia tests; low-molecular-weight heparin; transjugular intrahepatic portosystemic shunt; liver transplantation Introduction Portal vein thrombosis (PVT) in the general population is a rare event, but it occurs relatively frequently in patients with liver cirrhosis and its prevalence increases with the severity of the disease. PVT can develop in the intra- or extrahepatic segments of the portal vein and extend to the superior mesenteric vein and/or the splenic vein. Moreover, PVT can progress from a partial obstruction due to the presence of a thrombus in the lumen of the vein to a complete blockade of portal venous blood flow. In cirrhotic patients, the prevalence of PVT ranges between 0.6% and 26% [1]. However, prevalence can vary depending on age, underlying hepatic disease, velocity of portal venous blood flow and the pro- versus anticoagulant status of the patient. In patients with cirrhosis of Child-Pugh A and B, incidence of newly diagnosed PVT after 1 and 5 years has been reported to be 4.6% and 10.7%, respectively [2]. The relative risk of developing PVT in the presence of cirrhosis is increased more than seven-fold above the risk observed in the general population, which is estimated to be < 1.0% [3]. While patients with compensated cirrhosis are rarely affected, PVT is frequently detected in advanced stages, increasing up to 25% in liver-transplantation candidates and Submitted: 17 March 2017; Accepted: 17 March 2017 C The Author(s) 2017. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University. V This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact . 148 Portal vein thrombosis in patients with cirrhosis 35% in cirrhotic patients with hepatocellular carcinoma (HCC) [4]. However, in large studies including patients evaluated for liver transplantation, 6.3% were diagnosed with PVT, in particular when cirrhosis was related to nonalcoholic steatohepatitis [5]. Moreover, in patients with advanced cirrhosis and those undergoing liver transplantation, a prevalence of between 5% and 16% has been reported [6]. The signs and symptoms of PVT are very heterogeneous and range from incidental diagnosis during diagnostic procedures for unrelated reasons to severe complications due to intestinal infarction or to the development of portal hypertension, such as variceal bleeding that can occur from esophageal and/or gastric fundic varices when splenic vein thrombosis is present. Therefore, prognosis and treatment of PVT depend on the localization, the degree of extension and the rapidity of development, as well as risk factors for thrombosis and the stage of chronic advanced liver disease. The causal relationships and the clinical presentation are often complex. As PVT may cause short-term as well as longterm complications, correct management by adopting adequate diagnostic and therapeutic measures is paramount. In this review article, we discuss the classification, the symptoms and signs, and the pathogenesis of PVT in cirrhosis, its clinical relevance, diagnostic procedures and the main lines of management. Definitions and classification PVT refers to partial or complete occlusion by a blood clotting of the portal vein trunk that can also include its right and left intrahepatic branches. Extension to either superior mesenteric or splenic veins or secondary intrahepatic portal branches is possible. However, the definitions show geographic differences. In European guidelines, recent PVT has been defined as a recent formation of a thrombus within the portal vein and/or right or left branches [7]. In the absence of recanalization, the portal venous lumen is obliterated, while porto-portal collaterals develop, resulting in the cavernomatous transformation of the portal vein, which might represent chronic PVT. The American Association for the Study of Liver Diseases (AASLD), however, defines acute PVT as the sudden formation of a thrombus within the portal vein lumen, and chronic PVT when the obstructed portion is replaced by a network of hepato-petal collaterals bypassing the thrombosed portion of the portal vein [8]. Although these definitions are easily interpreted and practiceoriented, they are based purely on anatomic findings and are limited by the fact that they only consider occlusion as defining criteria, omitting any clinically significant consequences. In patients with liver cirrhosis, PVT may be more accurately defined as a clinical syndrome that presents either as an incidental finding on abdominal imaging (performed for reasons unrelated to PVT) or with highly variable signs and symptoms resulting from portal vein obstruction and/or portal hypertension [9]. PVT in patients with cirrhosis has been shown to have little influence on the course of liver disease, except for patients with PVT at liver transplantation in whom 90-day mortality and graft failure have been reported to be higher than in those without PVT [10,11]. Mo (...truncated)