G. Tosetti

Cirrhosis and portal hypertension: The importance of risk stratification, the role of hepatic venous pressure gradient measurement

Portal hypertension is the main prognostic factor in cirrhosis. The recent emergence of potent antiviral drugs and new algorithm of treatment for the management of complications due to portal hypertension have sensibly changed our perception of cirrhosis that can be now considered as a multistage liver disease whose mortality risk can be reduced by a tailored approach for any stage of risk. Experts recommend to move toward a pathophysiological classification of cirrhosis that considers both structural and functional changes. The hepatic venous pressure gradient HVPG, is the reference gold standard to estimate the severity of portal hypertension in cirrhosis. It correlates with both structural and functional changes that occur in cirrhosis and carries valuable prognostic information to stratify the mortality risk. This article provides a general overview of the pathophysiology and natural course of cirrhosis and portal hypertension. We propose a simplified classification of cirrhosis based on low, intermediate and high mortality stage. The prognostic information provided by HVPG is presented according to each stage. A comparison with prognostic models based on clinical and endoscopic variables is discussed in order to evidence the additional contribute given by HVPG on top of other clinical and instrumental variables widely used in clinical practice.

Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis

Portal vein thrombosis (PVT) is frequently observed in cirrhosis and may be a clinically important complication. In vitro assays for endogenous thrombin potential (ETP) demonstrated that in cirrhosis plasma has intrinsic resistance to the anticoagulant action of thrombomodulin (TM‐R). This study retrospectively explores the association of TM‐R with de novo PVT and its clinical impact on cirrhosis.

Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis (PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs (low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs (DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time.

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis

The effect of direct‐acting‐antivirals (DAA) on coagulation of hepatitis‐C‐virus (HCV)‐related cirrhosis is unknown.

Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis

Background & Aims: Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis. Methods: We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non‐neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension‐related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls. Results: The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper‐gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper‐gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension–related event‐free and transplantation‐free survival times. Conclusions: In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension–related, event‐free, and transplantation‐free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.

Splanchnic vein thrombosis in myeloproliferative neoplasms: facing the opposite risks of thrombosis recurrence and bleeding

The article “ Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients ”, recently published in the Blood Cancer Journal (1), retrospectively addresses the issue of thrombotic recurrence in patients with Philadelphia-negative myeloproliferative neoplasms (MPN), after a first episode of splanchnic vein thrombosis (SVT).