Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

Current concepts in the management of non-cirrhotic non-malignant portal vein thrombosis

Non-cirrhotic non-malignant portal vein thrombosis(NCPVT)is an uncommon condition characterised by thrombosis of the portal vein,with or without extension into other mesenteric veins,in the absence of cirrhosis or intra-abdominal malignancy.Complications can include intestinal infarction,variceal bleeding and portal biliopathy.In this article,we address current concepts in the management of NCPVT including identification of risk factors,classification and treatment,and review the latest evidence on medical and interventional management options.

Simultaneous portal vein thrombosis and splenic vein thrombosis in a COVID-19 patient:A case report and review of literature

BACKGROUND It is well-described that the coronavirus disease 2019(COVID-19)infection is associated with an increased risk of thrombotic complications.While there have been many cases of pulmonary emboli and deep vein thrombosis in these patients,reports of COVID-19 associated portal vein thrombosis(PVT)have been uncommon.We present a unique case of concomitant PVT and splenic artery thrombosis in a COVID-19 patient.CASE SUMMARY A 77-year-old-male with no history of liver disease presented with three days of left-sided abdominal pain.One week earlier,the patient was diagnosed with mildly symptomatic COVID-19 and was treated with nirmatrelvir/ritonavir.Physical exam revealed mild right and left lower quadrant tenderness,but was otherwise unremarkable.Significant laboratory findings included white blood cell count 12.5 K/μL,total bilirubin 1.6 mg/dL,aminoaspartate transferase 40 U/L,and alanine aminotransferase 61 U/L.Computed tomography of the abdomen and pelvis revealed acute PVT with thrombus extending from the distal portion of the main portal vein into the right and left branches.Also noted was a thrombus within the distal portion of the splenic artery with resulting splenic infarct.Hypercoagulable workup including prothrombin gene analysis,factor V Leiden,cardiolipin antibody,and JAK2 mutation were all negative.Anticoagulation with enoxaparin was initiated,and the patient’s pain improved.He was discharged on apixaban.CONCLUSION It is quite uncommon for PVT to present simultaneously with an arterial thrombotic occlusion,as in the case of our patient.Unusual thrombotic manifestations are classically linked to hypercoagulable states including malignancy and hereditary and autoimmune disorders.Viral infections such as Epstein-Barr virus,cytomegalovirus,viral hepatitis,and COVID-19 have all been found to increase the risk of splanchnic venous occlusions,including PVT.In our patient,prompt abdominal imaging led to early detection of thrombus,early treatment,and an excellent outcome.This case is unique in that it is the second known case within the literature of simultaneous PVT and splenic artery thrombosis in a COVID-19 patient.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibration curves and DCA revealed its good clinical performance.Finally,the optimal cutoff value for the total nomogram score was 0.513.The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706,respectively.CONCLUSION A nomogram for predicting PVT occurrence was successfully developed and validated,and a network calculator was constructed.This can enable clinicians to rapidly and easily identify high PVT risk groups.

Predictors of portal vein thrombosis after splenectomy in patients with cirrhosis

BACKGROUND Portal vein thrombosis(PVT)is a commonthsn complication after splenectomy in patients with cirrhosis.However,the predictors of postoperative PVT are not known.AIM To investigate the predictors of PVT after splenectomy in patient with cirrhosis.METHODS A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December 2018.The incidence of PVT at 1 months,3 months,and 12 months after splenectomy in patients with cirrhosis was observed.The hematological indicators,biochemical and coagulation parameters,and imaging features were recorded at baseline and at each observation point.The univariable,multivariable,receiver operating characteristic curve and timedependent curve analyses were performed.RESULTS The cumulative incidence of PVT was 40.0%,46.6%,and 48.9%at 1 months,3 months,and 12 months after splenectomy.Multivariable analysis showed that portal vein diameter(PVD)≥14.5 mm and monthsdel end-stage liver disease(MELD)score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy(P<0.05).Time-dependent curve showed that the cumulative incidence of PVT was significantly different between patients with MELD score≤10 and>10(P<0.05).In addition,the cumulative incidence of PVT in the PVD≥14.5 mm group was significantly higher than that in the PVD<14.5 mm group(P<0.05).CONCLUSION Wider PVD and MELD score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy in patient with cirrhosis.

Portal Venous Thrombosis and Splenic Hemangioma, Secondary to Acute Pancreatitis: Case Report

We present an unusual case of portal vein thrombosis with a splanchnic hemangioma secondary to acute biliary pancreatitis. We report a 45-year-old patient, who has systemic arterial hypertension in treatment, was admitted for abdominal pain in the epigastrium, with irradiation to the right hypochondrium, accompanied by nausea and vomiting of 10 occasions of bile content, physical examination with pain in the right hypochondrium, Murphy positive. We have laboratory studies with a lipase of 788, so a diagnosis of pancreatitis is made with an etiology to be determined. The laboratories suggestive of acute biliary pancreatitis (lipase 788.71);an imaging study was subsequently performed (ultrasonography) with the result of stone in the common bile duct. A laparoscopy was performed with relative improvement, so he was discharged and returned 20 days after surgery due to abdominal pain of the same intensity in the left hypochondrium. Ending his hospitalization with a splenectomy for splenic hemangioma with portal vein thrombosis.

Portal vein arterialization in 25 liver transplant recipients:A Latin American single-center experience

BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.

Wandering spleen torsion with portal vein thrombosis:A case report

BACKGROUND Wandering spleen is rare clinically.It is characterized by displacement of the spleen in the abdominal and pelvic cavities and can have congenital or acquired causes.Wandering spleen involves serious complications,such as spleen torsion.The clinical symptoms range from asymptomatic abdominal mass to acute abdominal pain.Surgery is required after diagnosis.Cases of wandering spleen torsion with portal vein thrombosis(PVT)are rare.There is no report on how to eliminate PVT in such cases.CASE SUMMARY Ultrasound and computed tomography revealed a diagnosis of wandering spleen torsion with PVT in a 31-year-old woman with a history of childbirth 16 mo previously who received emergency treatment for upper abdominal pain.She recovered well after splenectomy and portal vein thrombectomy combined with continuous anticoagulation,and the PVT disappeared.CONCLUSION Rare and nonspecific conditions,such as wandering splenic torsion with PVT,must be diagnosed and treated early.Patients with complete splenic infarction require splenectomy.Anticoagulation therapy and individualized management for PVT is feasible.

Application of transmesenteric vein extrahepatic portosystemic shunt in treatment of symptomatic portal hypertension with cavernous transformation of portal vein

Purpose:To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt(TmEPS)for the treatment of cavernous transformation of the portal vein(CTPV).Materials and methods:The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020and January 2022 at Henan Provincial People’s Hospital were retrospectively collected.The superior mesenteric vein(SMV)trunk was patent or partially occluded in these patients.An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy.The technical success,efficacy,and complication rates were evaluated,and the preand postoperative SMV pressures were compared.Patients’clinical outcomes and shunt patency were assessed.Results:TmEPS was successfully performed in 20 patients.The initial puncture success rate of the balloon-assisted puncture technique is 95%.The mean SMV pressure decreased from 29.1±2.9 mmHg to 15.6±3.3 mmHg(p<0.001).All symptoms of portal hypertension resolved.No fatal procedural complications occurred.During the follow-up period,hepatic encephalopathy occurred in two patients.The remaining patients remained asymptomatic.All shunts were patent.Conclusions:TmEPS is a feasible,safe,and effective treatment option for patients with CTPV.

Portal vein thrombosis:Insight into physiopathology,diagnosis,and treatment

Portal vein thrombosis (PVT) is a relatively common complication in patients with liver cirrhosis, but might also occur in absence of an overt liver disease. Several causes, either local or systemic, might play an important role in PVT pathogenesis. Frequently, more than one risk factor could be identified; however, occasionally no single factor is discernable. Clinical examination, laboratory investigations, and imaging are helpful to provide a quick diagnosis, as prompt treatment might greatly affect a patient's outcome. In this review, we analyze the physiopathological mechanisms of PVT development, together with the hemodynamic and functional alterations related to this condition. Moreover, we describe the principal factors most frequently involved in PVT development and the recent knowledge concerning diagnostic and therapeutic procedures. Finally, we analyze the implications of PVT in the setting of liver transplantation and its possible influence on patients' future prognoses.

Portal vein thrombosis in cirrhosis: Controversies and latest developments

Portal vein thrombosis(PVT) is encountered in livercirrhosis, particularly in advanced disease. It has been a feared complication of cirrhosis, attributed to significant worsening of liver disease, poorer clinical outcomes and potential inoperability at liver transplantation; also catastrophic events such as acute intestinal ischaemia. Optimal management of PVT has not yet been addressed in any consensus publication.We review current literature on PVT in cirrhosis; its prevalence, pathophysiology, diagnosis, impact on the natural history of cirrhosis and liver transplantation,and management. Studies were identified by a search strategy using MEDLINE and Google Scholar. The incidence of PVT increases with increasing severity of liver disease: less than 1% in well-compensated cirrhosis, 7.4%-16% in advanced cirrhosis. Prevalence in patients undergoing liver transplantation is 5%-16%.PVT frequently regresses instead of uniform thrombus progression. PVT is not associated with increased risk of mortality. Optimal management has not been addressed in any consensus publication. We propose areas for future research to address unresolved clinical questions.

Portal vein thrombosis in liver cirrhosis

Portal vein thrombosis(PVT) is considered to be a frequent complication of liver cirrhosis. However, unlike PVT in patients without cirrhosis, very few data are available on the natural history and management of PVT in cirrhosis, despite its association with potentially life-threatening conditions, such as gastroesophageal bleeding and acute intestinal ischemia. Moreover, no consensus regarding PVT in cirrhosis exists. Suggested causes of PVT in cirrhosis include reduced portal blood flow velocity, multiple congenital or acquired thrombophilic factors, inherited or acquired conditions, and derangement of liver architecture. However, the understanding of PVT in cirrhosis is incomplete. In addition, information on the management of PVT in cirrhosis is inadequate. The aims of this review are to:(1) assemble data on the physiopathological mechanism, clinical findings, diagnosis and management of PVT in cirrhosis;(2) describe the principal factors most frequently involved in PVT development; and(3) summarize the recent knowledge concerning diagnostic and therapeutic procedures.

Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

Although the current standard treatment for hepatocellular carcinoma(HCC) with portal vein tumor thrombosis(PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy(RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.

Portal vein thrombosis in cirrhosis: Why a well-known complication is still matter of debate

Portal vein thrombosis(PVT)represents a well-known complication during the natural course of liver cirrhosis(LC),ranging from asymptomatic cases to lifethreating conditions related to portal hypertension and hepatic decompensation.Portal flow stasis,complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development.However,PVT occurrence remains unpredictable and many issues regarding its natural history,prognostic significance and treatment are still elusive.In particular although spontaneous resolution or disease stability occur in most cases of PVT,factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet.Moreover,PVT impact on LC outcome is still debated,as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression.Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases,even if the safer therapeutic option and the optimal therapy duration are still unknown.Nevertheless,their impact on mortality rates should be addressed more extensively.In this review we present the most debated questions regarding PVT,whose answers should come from prospective cohort studies and large sample-size randomized trials.

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

Risk factors and clinical characteristics of portal vein thrombosis after splenectomy in patients with liver cirrhosis

BACKGROUND:Portal vein thrombosis(PVT) is a potential lethal complication and may have negative influence on the prognosis after splenectomy in patients with liver cirrhosis.Prevention and timely detection of PVT are quite significant.There is a lack of knowledge about the clinical features and risk factors of PVT.Our study aimed to investigate the risk factors and clinical characteristics of PVT in order to figure out the high-risk individuals.METHODS:We collected the clinical data of 472 consecutive patients with non-neoplastic liver cirrhosis who had undergone splenectomy from January 2008 to December 2010 in our institution.Clinical and surgical characteristics of patients who developed PVT postoperatively and those who did not develop PVT were compared.Univariate and multivariate analyses of risk factors of PVT were performed.The mortality and rebleeding rate of the patients were also evaluated.RESULTS:Of the 472 patients,52 were excluded from the study.PVT developed in 71(71/420,16.9%) patients.Multivariate analysis revealed that wider preoperative portal vein diameter,postoperative thrombocytosis,prolonged prothrombin time and periesophagogastric devascularization were significantly correlated with PVT development [odds ratio(OR):5.701,2.807,1.850 and 2.090,respectively].The incidence of PVT in patients who took antiplatelet drugs was not lower than that in those who did not.Follow-up showed that patients in the PVT group had a tendency towards reduced overall survival but it was not statistically significant.Gastrointestinal bleeding occurred more often in the PVT group than that in the non-PVT group(P=0.044).CONCLUSIONS:Wider preoperative portal vein diameter,postoperative thrombocytosis,prolonged prothrombin time and periesophagogastric devascularization are independent risk factors of PVT.PVT is related with higher risk of postoperative gastrointestinal hemorrhage but has no significant impact on the overall survival.

Clinical outcomes of transcatheter selective superior mesenteric artery urokinase infusion therapy vs transjugular intrahepatic portosystemic shunt in patients with cirrhosis and acute portal vein thrombosis

AIM To compare the outcomes of transcatheter superior mesenteric artery(SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt(TIPS) for acute portal vein thrombosis(PVT) in cirrhosis.METHODS From January 2013 to December 2014, patients with liver cirrhosis and acute symptomatic PVT who met the inclusion criteria were randomly assigned to either an SMA group or a TIPS group. The two groups accepted transcatheter selective SMA urokinase infusion therapyand TIPS, respectively. The total follow-up time was24 mo. The primary outcome measure was the change in portal vein patency status which was evaluated by angio-computed tomography or Doppler ultrasound.Secondary outcomes were rebleeding and hepatic encephalopathy.RESULTS A total of 40 patients were enrolled, with 20 assigned to the SMA group and 20 to the TIPS group. The symptoms of all patients in the two groups improved within 48 h. PVT was improved in 17(85%) patients in the SMA group and 14(70%) patients in the TIPS group. The main portal vein(MPV) thrombosis was significantly reduced in both groups(P < 0.001), and there was no significant difference between them(P= 0.304). In the SMA group, superior mesenteric vein(SMV) thrombosis and splenic vein(SV) thrombosis were significantly reduced(P = 0.048 and P = 0.02),which did not occur in the TIPS group. At 6-, 12-,and 24-mo follow-up, in the SMA group and the TIPS group, the cumulative rates free of the first episode of rebleeding were 80%, 65%, and 45% vs 90%, 80%,and 60%, respectively(P = 0.320); the cumulative rates free of the first episode of hepatic encephalopathy were 85%, 80%, and 65% vs 50%, 40%, and 35%,respectively(P = 0.022).CONCLUSION Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.

Management of hepatocellular carcinoma with portal vein thrombosis

Management of hepatocellular carcinoma(HCC) with portal vein thrombosis(PVT) is complex andrequires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival.

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.