Development of a Model to Predict Portal Vein Thrombosis in Liver Transplant Candidates: The Portal Vein Thrombosis Risk Index.
ABSTRACT: Portal vein thrombosis (PVT) is associated with inferior pretransplantation and posttransplantation outcomes. We aimed to create a predictive model to risk stratify transplant candidates for PVT. Data on adult transplants in the United States during the Model for End-Stage Liver Disease (MELD) era through September 2016 were reviewed. We constructed and validated a scoring system composed of routine, readily available clinical information to predict the development of incident PVT at 12 months from transplantation listing. A total of 66,568 liver transplant candidates were dichotomized into 2 groups to construct (n = 34,751) and validate (n = 31,817) a scoring system. In general, the derivation and validation cohorts were clinically similar. Although nonalcoholic steatohepatitis was a significant predictor of incident PVT (hazard ratio, 1.29; 95% confidence interval, 1.08-1.54; P < 0.001), age, MELD score, and moderate-to-severe ascites were also associated with increased risk. African American race was associated with decreased risk. A scoring system (PVT risk index [RI]) of these 5 variables had an area under the curve of 0.71 and 0.70 in both derivation and validation cohorts, respectively. By applying the low cutoff score of 2.6, incident PVT could be accurately excluded (negative predictive value 94%). Using the high cutoff score of 4.6 (positive predictive value 85%), PVT could be diagnosed with high accuracy. The PVT-RI predicts which candidates awaiting lifesaving liver transplantation will and will not develop future PVT. Although this scoring system will require prospective validation, it provides a powerful new tool for the clinician when risk stratifying cirrhosis patients prior to liver transplantation for future PVT development.
Project description:Portal vein thrombosis is an important cause of portal hypertension. PVT occurs in association with cirrhosis or as a result of malignant invasion by hepatocellular carcinoma or even in the absence of associated liver disease. With the current research into its genesis, majority now have an underlying prothrombotic state detectable. Endothelial activation and stagnant portal blood flow also contribute to formation of the thrombus. Acute non-cirrhotic PVT, chronic PVT (EHPVO), and portal vein thrombosis in cirrhosis are the three main variants of portal vein thrombosis with varying etiological factors and variability in presentation and management. Procoagulant state should be actively investigated. Anticoagulation is the mainstay of therapy for acute non-cirrhotic PVT, with supporting evidence for its use in cirrhotic population as well. Chronic PVT (EHPVO) on the other hand requires the management of portal hypertension as such and with role for anticoagulation in the setting of underlying prothrombotic state, however data is awaited in those with no underlying prothrombotic states. TIPS and liver transplant may be feasible even in the setting of PVT however proper selection of candidates and type of surgery is warranted. Thrombolysis and thrombectomy have some role. TARE is a new modality for management of HCC with portal vein invasion.
Project description:Portal vein thrombosis (PVT) is encountered in liver cirrhosis, 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.
Project description:BACKGROUND AND AIMS:Non-O blood type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non-O-BT is a risk factor for PVT and (II) whether non-O-BT impacts VWF/factor VIII in patients with ACLD. METHODS:Retrospective analysis comprising two cohorts: (I) "US" including all adult liver transplantations in the US in the MELD era and (II) "Vienna" comprising patients with a hepatic venous pressure gradient (HVPG) ?6 mmHg. RESULTS:(I) The "US cohort" included 84 947 patients (non-O: 55.43%). The prevalence of PVT at the time of listing (4.37% vs 4.56%; P = .1762) and at liver transplantation (9.56% vs 9.33%; P = .2546) was similar in patients with O- and non-O-BT. (II) 411 patients were included in the "Vienna cohort" (non-O: 64%). Mean HVPG was 18(9) mmHg and 90% had an HVPG ?10 mmHg. Patients with non-O-BT had slightly increased VWF levels (318(164)% vs 309(176)%; P = .048; increase of 23.8%-23.9% in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non-O-BT explained only 1% of the variation in VWF and had no effect on FVIII. CONCLUSIONS:Although non-O-BT impacts VWF in patients with early stage ACLD, its contribution to VWF variation is considerably smaller than in the general population. Moreover, non-O-BT had no impact on FVIII. These findings may explain the absence of an association between non-O-BT and PVT in patients with advanced cirrhosis.
Project description:Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.
Project description:BACKGROUND: Portal vein thrombosis (PVT) is a well recognized complication of patients with end-stage cirrhosis and its incidence ranges from 2 to 26%. The aim of this study was to analyze the results and long-term follow-up of a consecutive series of liver transplants performed in patients with PVT and compare them with patients transplanted without PVT. PATIENTS AND METHODS: Between July 1995 and June 2006, 26 liver transplants were performed in patients with PVT (8.7%). Risk factors and variables associated with the transplant and the post-transplant period were analyzed. A comparative analysis with 273 patients transplanted without PVT was performed. RESULTS: The patients comprised 53.8% males, average age 40, 7 years. PVT was detected during surgery in 65%. Indications for transplantation were: post-necrotic cirrhosis 73%, cholestatic liver diseases 23%, and congenital liver fibrosis 4%. Child-Pugh C: 61.5%. Techniques were trombectomy in 21 patients with PVT grades I, II, IV, and extra-anatomical mesenteric graft in 5 with grade III. Morbidity was 57.7%, recurrence of PVT was 7.7%, and in-hospital mortality was 26.9%. Greater operative time, transfusion requirements, and re-operations were found in PVT patients. One-year survival was 59.6%: 75.2% for grade 1 and 44.8% for grades 2, 3, and 4. DISCUSSION: The study demonstrated a PVT prevalence of 8.7%, a higher incidence of partial thrombosis (grade 1), and successful management of PVT grade 4 with thrombectomy. Liver transplant in PVT patients was associated with an increased operative time, transfusion requirements, re-interventions, and lower survival rate according to PVT extension.
Project description:This retrospective study investigated factors influencing the portal vein thrombosis (PVT) volume and recurrence in 52 cirrhosis patients with PVT from November 2008 to September 2018. All patients were treated with danaparoid sodium with or without additional antithrombin III. Blood platelet counts significantly correlated with the PVT volume (r2 = 0.17; P < 0.01). Computed tomography confirmed recurrence as PVT aggravation was reported in 43 patients, with ?50% PVT volume reduction following anticoagulation therapy. In 43 patients, recurrence significantly correlated with the pretreatment PVT volume (P = 0.019). Factors influencing recurrence included a Child-Pugh score >8 (P = 0.049) and fibrosis index ?7.0 based on four factors (FIB-4) (P = 0.048). Moreover, the relationship between recurrence and correlating factors showed that 15 patients who received warfarin experienced recurrence more often when Child-Pugh scores were >8 (P = 0.023), regardless of maintenance treatment. For patients who did not receive warfarin, a PVT volume ?3.0 mL significantly influenced recurrence (P = 0.039). Therefore, the platelet count influences the PVT volume. The pretreatment PVT volume correlated with recurrence after anticoagulation therapy. According to the Kaplan-Meier curve, risk factors for PVT recurrence after anticoagulation therapy included Child-Pugh scores >8 and FIB-4 ?7.0. Therefore, the FIB-4 is a unique factor that shows trends opposing other liver function markers.
Project description:The clinical management of portal vein thrombosis (PVT) remains ambiguous due to its heterogeneous presentations and its associations with liver disease, malignancy, and hypercoagulable states. The natural history and clinical outcome of PVT are highly variable, dependent upon size, extent and degree of the thrombotic occlusion, as well as the physiological impact of patient comorbidities. While existing clinical guidelines consistently recommend low molecular weight heparin or vitamin K antagonist anticoagulation in cirrhotic patients with symptomatic acute PVT, management of asymptomatic and chronic PVT may need to be determined on a case-by-case basis, factoring in the state of underlying liver disease. In general, patients with PVT and underlying malignancy should be anticoagulated to alleviate symptoms and prevent recurrences that could disrupt the cancer management. However, existing clinical data does not support routine anticoagulation of cirrhotic patients with asymptomatic PVT in the absence of underlying cancer. While low molecular weight heparin and vitamin K antagonist remain the most commonly used agents in PVT, an emerging body of clinical evidence now suggests that direct-acting oral anticoagulants may be used safely and effectively in PVT. As such, direct-acting oral anticoagulants may offer a more convenient anticoagulation alternative for PVT management in future practice.
Project description:We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD40L (Spearman's rank correlation coefficient [rs ], -0.33; P < 0.001), sNox2-dp (rs , -0.57; P < 0.0001), and urinary excretion of isoprostanes (rs, -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2?-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation.
Project description:Introduction ?Timely diagnosis and treatment of portal vein thrombosis (PVT) is crucial to prevent morbidity and mortality. However, current imaging tests cannot always accurately differentiate acute from chronic (nonocclusive) PVT. Magnetic resonance noncontrast thrombus imaging (MR-NCTI) has been shown to accurately differentiate acute from chronic venous thrombosis at other locations and may also be of value in the diagnostic management of PVT. This study describes the first phase of the Rhea study (NTR 7061). Our aim was to select and optimize MR-NCTI sequences that would be accurate for differentiation of acute from chronic PVT. Study Design ?The literature was searched for different MRI sequences for portal vein and acute thrombosis imaging. The most promising sequences were tested in a healthy volunteer followed by one patient with acute PVT and two patients with chronic PVT, all diagnosed on (repetitive) contrast-enhanced computed tomography (CT) venography to optimize the MR-NCTI sequences. All images were evaluated by an expert panel. Results ?Several MR-NCTI sequences were identified and tested. Differentiation of acute from chronic PVT was achieved with 3D T1 TFE (three-dimensional T1 turbo field echo) and 3D T1 Dixon FFE (three-dimensional T1 fast field echo) sequences with best image quality. The expert panel was able to confirm the diagnosis of acute PVT on the combined two MR-NCTI sequences and to exclude acute PVT in the two patients with chronic PVT. Conclusion ?Using 3D T1 TFE and 3D T1 Dixon FFE sequences, we were able to distinguish acute from chronic PVT. This clinical relevant finding will be elucidated in clinical studies to establish their test performance.
Project description:Yttrium-90 ((90)Y) radioembolization is a microembolic procedure. Hence, it is commonly used in hepatocellular carcinoma (HCC) patients with portal venous thrombosis (PVT). We analyzed liver function, imaging findings, and treatment options (local/systemic) at disease progression following (90)Y treatment in HCC patients with PVT.We treated 291 HCC patients with (90)Y radioembolization. From this cohort, we included patients with liver-only disease, PVT and Child-Pugh (CP) score ? 7; this identified 63 patients with HCC and PVT (CP-A:35, CP-B7:27). Liver function, CP status, and imaging findings at progression were determined in order to assess potential candidacy for systemic treatment/clinical trials. Survival, time-to-progression (TTP), and time-to-hepatic decompensation analyses were performed using Kaplan-Meier methodology.Of 35 CP-A and 28 CP-B7 patients, 29 and 15 progressed, respectively. Median survival and TTP were 13.8 and 5.6 months in CP-A and 6.5 and 4.9 months in CP-B7 patients, respectively. Of the 29 CP-A patients who progressed, 45% maintained their CP status at progression (55% decompensated to CP-B). Of the 15 CP-B7 patients who progressed, 20% improved to CP-A, 20% maintained their CP score and 60% decompensated.Knowledge of liver function and CP score of HCC with PVT progressing after (90)Y is critically relevant information, as these patients may be considered for systemic therapy/clinical trials. If a strict CP-A status is mandated, our study demonstrated that 64% of cases exhibited inadequate liver function and were ineligible for systemic therapy/clinical trials. An adjuvant approach using local therapy and systemic agents prior to progression should be investigated.