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A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.

Introduction Benefit and risk of anticoagulation in cirrhotic patients with portal vein thrombosis (PVT) remain controversial, especially in those with asymptomatic PVT and in non-liver transplant candidates. Furthermore, the predictors of portal vein recanalization and bleeding events after anticoagulation are critical for making clinical decisions, but still unclear. We conducted a meta-analysis to investigate the outcomes of anticoagulation for PVT in liver cirrhosis and explore the predictors of portal vein recanalization and bleeding events after anticoagulation. Methods All studies regarding anticoagulation for PVT in liver cirrhosis were searched via PubMed, EMBASE, and Cochrane Library databases. Thrombotic outcomes, bleeding events, and survival were compared between anticoagulation and non-anticoagulation groups. Predictors of portal vein recanalization and bleeding events were pooled. Risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results Thirty-three studies including 1696 cirrhotic patients with PVT were included. Anticoagulation significantly increased portal vein recanalization (RR = 2.61; 95% CI 1.99–3.43; P

Significant morbidity and mortality have been associated with liver complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Causes and consequences of these hepato-biliary complications are various and might be life-threatening. A high misdiagnosis rate has been reported because of a weak correlation between clinical, laboratory and imaging data. Liver elastography, a liver stiffness measure, is able to assess liver fibrosis and portal hypertension in most liver diseases, but data after allo-HSCT are scarce. Our aim was to determine the interest of sequential liver stiffness measurements for the diagnosis of early hepatic complications after allo-HSCT. Over a 2-year time period, 161 consecutive adult patients were included and 146 were analyzed. Ultrasonography and elastography measurements were performed before transplantation, at day+7 and day+14 by three different experienced radiologists unaware of the patients’ clinical status. Eightyone (55%) patients had liver involvements within the first 100 days after allo-HSCT. Baseline elastography was not predictive for the occurrence of overall liver abnormalities. A significant increase in two-dimensional real-time shearwave elastography (2D-SWE) was found in patients with sinusoidal obstruction syndrome (SOS). Fifteen patients (10%) fulfilled European Society for Blood and Marrow Transplantation (EBMT) score criteria and twelve (8%) reached Baltimore criteria for SOS diagnosis, but only six (4%) had a confirmed SOS. 2D-SWE at day+14 allowed early detection of SOS (AUROC=0.84, P=0.004) and improved sensibility (75%), specificity (99%) and positive predictive value (60%) over the Seattle, Baltimore or EBMT scores. A 2D-SWE measurement above 8.1 kPa at day+14 after allo-HSCT seems a promising, non-invasive, and reproducible tool for early and accurate diagnosis of SOS.

Porto-sinusoidal vascular disorder (PSVD) is a rare and commonly overlooked cause of portal hypertension. The interest of CT analysis, including quantification of liver surface nodularity (LSN) for PSVD diagnosis has not been established. This study aimed at assessing the performance of LSN and CT features for a PSVD diagnosis in patients with signs of portal hypertension.This retrospective case-control study included a learning cohort consisting of 50 patients with histologically proven PSVD, according to VALDIG criteria, and 100 control patients with histologically proven cirrhosis, matched on ascites. All patients and controls had at least one sign of portal hypertension and CT available within 1 year of liver biopsy. Principal component analysis of CT features separated patients with PSVD from patients with cirrhosis. Patients with PSVD had lower median LSN than those with cirrhosis (2.4 vs. 3.1, p 0.001). Multivariate analysis identified LSN 2.5 and normal-sized or enlarged segment IV as independently associated with PSVD. Combination of these two features had a specificity of 90% for PSVD and a diagnostic accuracy of 84%. Even better results were obtained in an independent multicenter validation cohort including 53 patients with PSVD and 106 control patients with cirrhosis (specificity 94%, diagnostic accuracy 87%).This study that included a total of 103 patients with PSVD and 206 patients with cirrhosis demonstrates that LSN 2.5 combined with normal-sized or enlarged segment IV strongly suggests PSVD in patients with signs of portal hypertension.

Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.

International audience; Vascular disorders of the liver are rare diseases, some of which are diagnosed mainly with non-invasive tests and others by liver biopsy. Non-invasive methods can be used to diagnose and monitor these diseases. However, their evaluation needs to be performed by expert centers. Liver biopsy is needed each time there is an unexplained abnormality.

To compare the magnetic resonance imaging (MRI) features of benign liver lesions developed on Budd-Chiari syndrome (BCS) with those on Fontan-associated liver disease (FALD) and to describe their long-term progression.Patients with BCS or FALD who underwent MRI between 2010 and 2020 were retrospectively included. MRI features of nodules (≥ 5 mm) at baseline and at final follow-up were reviewed. The final diagnosis of benign lesion was based on a combination of clinical and biological data and findings at follow-up MRI examination.Two-hundred and thirty benign liver lesions in 39 patients with BCS (10 men, 29 women; mean age, 36 ± 11 [SD] years; age range: 15-66 years) and 84 benign lesions in 14 patients with FALD (2 men, 12 women; mean age, 31 ± 10 [SD] years; age range: 20-48 years) were evaluated. On baseline MRI, BCS nodules were more frequently hyperintense on T1-weighted (183/230, 80%) and hypointense on T2-weighted (142/230; 62%) images, while FALD nodules were usually isointense on both T1- (70/84; 83%) and T2-weighted (64/84; 76%) images (all P0.01). Most lesions showed arterial phase hyperenhancement (222/230 [97%] vs. 80/84 [95%] in BCS and FALD, respectively; P = 0.28) but wash-out was more common in BCS (64/230 [28%] vs. 9/84 [11%]; P0.01). At follow-up, changes were more frequent in BCS nodules with more frequent disappearance (P0.01), changes in size, signal intensity on T2-weighted, portal, and delayed phase, and in the depiction of washout and capsule (all P ≤ 0.03).MRI features of benign lesions are different at diagnosis and during the course of the disease between BCS and FALD. Changes in size and MRI features are more frequent in benign lesions developed in BCS.

Background & Aims: Vascular liver diseases (VLDs) are represented mainly by portosinusoidal vascular disease (PSVD), noncirrhotic splanchnic vein thrombosis (SVT), and Budd Chiari syndrome (BCS). It is unknown whether patients with VLDs constitute a high-risk population for complications and greater coronavirus disease 2019 (COVID-19)-related mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to assess the prevalence and severity of SARS-CoV-2 infection among patients with VLDs, as well as to assess its impact on hepatic decompensation and survival. Methods: This is an observational international study analyzing the prevalence and severity of SARS-CoV-2 infection in VLDs between March 2020 and March 2021, compared with the general population (GP). Patients from Spain (5 centers; n = 493) and France (1 center; n = 475) were included. Results: Nine hundred sixty-eight patients were included: 274 with PSVD, 539 with SVT, and 155 with BCS. Among them, 138 (14%) were infected with SARS-CoV-2: 53 with PSVD, 77 with SVT, and 8 with BCS. The prevalence of SARS-CoV-2 infection in patients with PSVD (19%) and SVT (14%) was significantly higher than in the GP (6.5%; P < .05), whereas it was very similar in patients with BCS (5%). In terms of infection severity, patients with VLDs also presented a higher need of hospital admission (14% vs 7.3%; P < .01), intensive care unit admission (2% vs 0.7%; P < .01), and mortality (4% vs 1.5%; P < .05) than the GP. Previous history of ascites (50% vs 8%; P < .05) and post-COVID-19 hepatic decompensation (50% vs 4%; P < .05) were associated with COVID-19 mortality. Conclusions: Patients with PSVD and SVT could be at higher risk of infection by SARS-CoV-2 and at higher risk of severe COVID-19 disease. © 2021 AGA Institute

Liver blood test anomalies are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their cause often remains difficult to identify. Our objective was to evaluate the safety and utility of liver biopsies in patients who underwent allo-HSCT. In a retrospective single-center cohort study, we reviewed all cases of patients who underwent liver biopsy between June 2005 and July 2017. During this period, 54 biopsies were performed in 45 patients, in which 38 patients underwent allo-HSCT for malignant and 7 for nonmalignant hematological disorders. Median time between allo-HSCT and liver biopsy was 213 days. Seven biopsies were percutaneous, and 47 were transjugular. No adverse event related to the biopsy procedure occurred; 94.5% biopsies (51 of 54) led to a histological diagnosis. Cholestatic graft-versus-host disease was histologically demonstrated in 16 biopsies (30%); hepatitis-like graft-versus-host disease in 9 biopsies (17%); nonalcoholic steatohepatitis in 6 biopsies (9%); regenerative nodular hyperplasia in 4 biopsies (5%); and drug-induced liver injury, sinusoidal obstruction syndrome, and viral hepatitis each in 3 biopsies (5%). Association between clinical, laboratory, imaging and pathological features was poor. Only 34% of physicians' prebiopsy hypotheses were confirmed by pathological findings. Patient management was influenced by liver biopsy results in 65% of cases, allowing us to identify a new diagnosis (n = 13), rule out a differential diagnosis (n = 14), or confirm the main hypothesis (n = 6). In conclusion, liver biopsy is a safe and useful technique to investigate liver blood test anomalies following allo-HSCT.

International audience; BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study’s conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.

Background Vascular liver disease (VLD) are rare liver diseases, which affect women at reproductive ages. Main complications are bleeding (portal hypertension, thrombopenia or anticoagulation related) and thromboembolism. Failure of liver function can occur. Thus endocrine abnormalities management and contraception are challenging. Purpose to evaluate the impact on the menstrual cycles and related endocrine abnormalities in women with VLD and respective roles of liver function and portal hypertension. Study design This was a single-center observational cohort study. Forty-seven premenopausal women with vascular liver disease were included for endocrine and gynecological assessments. Endocrine evaluation was performed at inclusion. Tolerance of contraception was followed up and assessed at 3 and 12 months. Participants, Setting, Methods Forty-seven women (aged 16–50) followed in a Reference Center for Liver Vascular Disease between February 2009 and November 2016 were included and addressed for gynecological and endocrinological management. Twenty-five women had extrahepatic portal vein obstruction, 17 had Budd Chiari Syndrome and five had a porto-sinusoidal vascular disease. We explored gonadotropin at baseline and after GnRH, testosterone, sex hormone binding globulin (SHBG), androstenedione, GH axis and glucose metabolism. All women underwent pelvic ultrasonography. Results Vascular liver disease was associated with abnormal menstrual cycles in 53% of the women and clinical and/or biological hyperandrogenism and/or a polycystic ovary morphology was identified in 38%. Portal hypertension was correlated to higher testosterone levels (P = 0.04), whereas higher elevated levels SHBG in 28%, correlated with liver failure (P = 0.01). Sixteen had glucose intolerance profile or diabetes. IGF-1 levels were highly correlated with hepatic failure. Abnormal uterine bleeding occurred in 21% of women, 87% of which were due to gynecological pathologies revealed by anticoagulant treatment. Progestin contraception was well tolerated and helped to control bleeding. Conclusion and implications endocrine abnormalities, prior described in association with cirrhosis, are also identified in patients with vascular liver disease, and require specific management. Glucose intolerance profile is frequent, further studies are needed to assess significant consequences on cardio-vascular system.

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6–7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10–62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94–29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Myeloproliferative neoplasms (MPNs) are the most frequent underlying causes of splanchnic vein thromboses (SVTs). MPN patients with SVTs (MPN-SVT) often have a unique presentation including younger age, female predominance, and low Janus kinase 2 (JAK2) mutation allele burden. This study aimed at identifying risk factors for adverse hematologic outcomes in MPN-SVT patients. We performed a retrospective study of a fully characterized cohort of MPN-SVT patients. The primary outcome was the incidence of evolution to myelofibrosis, acute leukemia, or death. Eighty patients were included in the testing cohort. Median follow-up was 11 years. Most of the patients were women with a mean age of 42 years and a diagnosis of polycythemia vera. The primary outcome was met in 13% of the patients and was associated with a JAK2V617F allele burden ≥50% (odds ratio [OR], 14.7) and presence of additional mutations in genes affecting chromatin/spliceosome (OR, 9). We identified high-risk patients (29% of the cohort) as those harboring at least 1 molecular risk factor: JAK2-mutant allele burden ≥50%, presence of chromatin/spliceosome/TP53 mutation. High-risk patients had worse event-free survival (81% vs 100%; P = .001) and overall survival at 10 years (89% vs 100%; P = .01) than low-risk patients. These results were confirmed in an independent validation cohort of 30 MPN-SVT patients. In conclusion, molecular profiling identified MPN-SVT patients with dismal outcome. In this high-risk population, a disease-modifying therapy should be taken into consideration to minimize the probability of transformation.

Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease, is characterized by concentric and non-thrombotic obstruction of the sinusoid and central vein lumen with no identified primitive or thrombotic hepatic vein lesions. The initial lesion is a result of endothelial denudation, corresponding to the migration of damaged sinusoidal cells to the central veins of the hepatic lobules, leading to sinusoidal and veno-occlusive congestive obstruction. SOS may be associated with other lesions such as centrilobular perisinusoidal fibrosis, peliosis, or nodular regenerative hyperplasia. The first cases of SOS were documented in 1920 in South Africa, after ingestion of food sources contaminated by pyrrolizidine alkaloids. SOS is a well-known complication of hematopoietic stem cell transplantation (HSCT). Numerous toxins and drugs have been associated with SOS, mainly chemotherapies and immunosuppressive therapies, as well as total body or liver irradiation and ABO mismatch platelet transfusion. The pathogenesis of this entity remains unknown.

Chronic non cirrhotic extrahepatic portal vein obstruction (EHPVO) refers to the cavernomatous transformation of the portal vein (the so-called "portal cavernoma") which occurs following acute thrombosis of the portal vein in the absence of recanalization. In adults, EHPVO mainly occurs following thrombosis, while in children it may be related to congenital malformations and/or neonatal umbilical venous catheterization. However, 50% of the cases of EHPVO remain idiopathic [1]. Risk factors and associated diseases should be investigated (chapter 1). Indeed, the presence of a thrombophilic alteration, in particular myeloproliferative neoplasm impacts prognosis and determine a causal treatment.

Background and objectives Noncirrhotic nontumoral extrahepatic portal vein obstruction (EHPVO) is the second leading cause of portal hypertension (PHT) and is mainly related to prothrombotic disorders. Patients with EHPVO often require prolonged oral anticoagulation therapy (OAT) together with variceal band ligation (VBL) to prevent thrombosis recurrence and PHT-related bleeding, respectively. The benefit-risk balance of VBL in this context remains unknown. We aimed to assess upper gastrointestinal bleeding (UGB) risk and variceal eradication efficacy in EHPVO patients undergoing a VBL program without stopping OAT. Patients and methods All patients with EHPVO treated (group A) or not (group B) with OAT and undergoing the VBL program were included between 2001 and 2010 in two tertiary French liver centers. We compared the incidence, source, and severity of UGB and variceal eradication efficacy. All EHPVO patients were then matched 1 : 1 with compensated cirrhotic patients with PHT not receiving OAT (group C) to compare UGB incidence and VBL efficacy. Results Forty-three EHPVO patients (30 with and 13 without OAT) and 43 cirrhotic patients were included for a total of 471 VBL sessions. The incidence of UGB was similar between group A (nine episodes/121 sessions) and group B (6/130), and tended to be higher in EHPVO patients (group A and B) than in cirrhotic patients (2/220). There was no difference between groups when considering bleeding source or severity and variceal eradication efficacy (84%). Conclusion VBL can be performed safely and efficiently without stopping anticoagulation therapy in EHPVO patients.

Background & Aims The Baveno VI consensus meeting concluded that an early transjugular intra-hepatic porto-systemic shunt (TIPS) must be considered in high-risk patients with cirrhosis, presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. The aim of this study was to determine (i) the proportion of patients eligible for early-TIPS among patients with cirrhosis and VB, (ii) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (iii) the outcomes of patients who experienced early-TIPS placement. Methods A large, national, prospective, multicentre audit of academic and non-academic centres, in which all French centres recruiting patients with gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and portal hypertension-related bleeding were included. Results A total of 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex 77%; age 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic 67%, viral 15%, other 18%); source of bleeding (oesophageal varices 80%, gastric varices 11%, other 9%); active bleeding at endoscopy 34%; Child A 21%, B 44%, C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7 ± 0.07% vs. 58.9 ± 0.03%, p = 0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. Conclusion In this real-life study, one-third of the patients with cirrhosis, admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival. Lay summary Bleeding from oesophageal or gastric varices is a severe complication of cirrhosis, related to an increased pressure in the portal vein perfusing the liver. Some patients are described as “severe”, either because their liver disease is already severe, or because the bleeding is very important. Those patients could benefit from a prothesis, placed inside the liver by an interventional radiologist, aiming to decrease the pressure in the portal vein, just after the control of bleeding by medications and endoscopic treatment. New studies are warranted to demonstrate a real beneficial effect of this therapeutic attitude, which is not adopted in real-life practice, as shown by this national French audit of practice.

Background and Aims Myeloproliferative neoplasms (MPN) are the leading cause of splanchnic vein thrombosis (SVT). Janus kinase 2 gene ( JAK2 ) V617F mutations are found in 80 to 90% of patients with SVT and MPN. Mutations of the calreticulin ( CALR ) gene have also been reported. However, as their prevalence ranges from 0 to 2%, the utility of routine testing is questionable. This study aimed to identify a group of patients with SVT at high risk of harboring CALR mutations and thus requiring this genetic testing. Methods CALR , JAK2 V617F and thrombopoietin receptor gene ( MPL ) mutations were analysed in a test cohort that included 312 patients with SVT. Criteria to identify patients at high risk of CALR mutations in this test cohort was used and evaluated in a validation cohort that included 209 patients with SVT. Results In the test cohort, 59 patients had JAK2 V617F , five had CALR and none had MPL mutations. Patients with CALR mutations had higher spleen height and platelet count than patients without these mutations. All patients with CALR mutations had a spleen height ⩾16cm and platelet count >200×10 9 /L. These criteria had a positive predictive value of 56% (5/9) and a negative predictive value of 100% (0/233) for the identification of CALR mutations. In the validation cohort, these criteria had a positive predictive value of 33% (2/6) and a negative predictive value of 99% (1/96). Conclusion CALR mutations should be tested in patients with SVT, a spleen height ⩾16cm, platelet count >200×10 9 /L, and no JAK2 V617F . This strategy avoids 96% of unnecessary CALR mutations testing. Lay summary: Mutations of the CALR gene are detected in 0 to 2% of patients with SVT, thus the utility of systematic CALR mutation testing to diagnose MPN is questionable. This study demonstrates that CALR mutations testing can be restricted to patients with SVT, a spleen height ⩾16cm, a platelet count >200×10 9 /L, and no JAK2 V617F . This strategy avoids 96% of unnecessary CALR mutations testing.

Purpose To evaluate the long-term safety, technical success, and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in a series of patients with Budd-Chiari syndrome (BCS), and to determine the predictors of shunt dysfunction. Materials and Methods From 2004 to 2013, all patients with primary BCS referred for TIPS placement were included in the study. The primary and secondary technical success rates and the number and types of early (ie, before day 7) complications were noted. Factors associated with dysfunction were analyzed with uni- and multivariate analyses. Survival was analyzed with Kaplan-Meier curves. Results Fifty-four patients (34 women [63%]; mean age, 36 years ± 12 [standard deviation]) were included. Twenty-eight patients (52%) had myeloproliferative neoplasms. The mean Model for End-Stage Liver Disease score was 14.5 ± 4. The most frequent indication for TIPS was refractory ascites (50 of 54; 93%). Primary and secondary technical success rates were 93% and 98%, respectively. Early complications occurred in 17 patients (32%). After a mean follow-up of 56 months ± 41 (interquartile range, 22-92), 22 patients (42%) experienced at least one episode of TIPS dysfunction (median delay between administration of TIPS and first episode of dysfunction, 10.8 months). Cumulative 1-, 2-, 3-, 5-, and 10-year primary patency rates were 64%, 59%, 54%, 45%, and 45%, respectively. Dysfunction was associated with a myeloproliferative neoplasm (hazard ratio, 8.18; 95% confidence interval: 1.45, 46.18; P = .017), more than two initial stents (hazard ratio, 3.90; 95% confidence interval:1.16, 13.10; P = .027), and the occurrence of early complications (hazard ratio, 11.34; 95% confidence interval: 1.82, 70.69; P = .009). The 10-year survival rate was 76%. Conclusion TIPS placement in patients with chronic primary BCS was associated with a nonnegligible rate of early complications and required endovascular revision or revisions in 42% of patients. Nevertheless, secondary patency was close to 100%, and long-term survival was good. © RSNA, 2016 Online supplemental material is available for this article.

Management of Budd–Chiari syndrome (BCS) is complex, mostly due to the variability of clinical presentation, cumulating bleeding, and thrombotic risk; symptoms vary from asymptomatic to severe portal hypertension and liver failure, in the context of concurring multifactorial prothombotic diseases. These modifications result in precarious hemostatic equilibrium with an increased risk of bleeding and thrombosis in a situation where a multidisciplinary approach combining medical and interventional therapy is considered. For more than 15 years, a stepwise treatment strategy according to response to previous therapy (from less to more invasiveness) has been proposed and is largely used worldwide. The first step consists of pharmacological management with anticoagulation therapy, specific therapy of underlying thrombotic disease, and medical or endoscopic management of liver-related complications. Recanalization of accessible stenosis is systematically considered and performed with angioplasty or stenting when it is feasible. In patients who do not respond to this first step therapy, transjugular intrahepatic portosystemic shunt is proposed, and as a fourth step, orthotopic liver transplantation. This chapter reviews the current rationale, indications, and modalities of anticoagulation therapy in BCS patients considering the balance of efficacy and safety, in this unstable situation of high bleeding vs high recurrent thrombosis risk.

It remains unclear whether the classic imaging criteria for the non-invasive diagnosis of hepatocellular carcinoma (HCC) can be applied to chronic vascular liver diseases, such as Budd-Chiari syndrome (BCS). Herein, we aimed to evaluate the diagnostic value of washout for the discrimination between benign and malignant lesions in patients with BCS.This retrospective study included all patients admitted to our institution with a diagnosis of BCS and focal lesions on MRI from 2000 to 2016. MRI images were reviewed by 2 radiologists blinded to the nature of the lesions. Patient and lesion characteristics were recorded, with a focus on washout on portal venous and/or delayed phases. Lesions were compared using Chi-square, Fisher's, Student's t or Mann-Whitney U tests.A total of 49 patients (mean age 35 ± 12 years; 34 women [69%] and 15 men [31%]) with 241 benign lesions and 12 HCC lesions were analyzed. Patients with HCC were significantly older (mean age 44 ± 16 vs. 33 ± 9 years, p = 0.005), with higher alpha-fetoprotein (AFP) levels (median 16 vs. 3 ng/ml, p = 0.007). Washout was depicted in 9/12 (75%) HCC, and 69/241 (29%) benign lesions (p0.001). A total of 52/143 (36%) lesions ≥1 cm with arterial hyperenhancement showed washout (9 HCC and 43 benign lesions). In this subgroup, the specificity of washout for the diagnosis of HCC was 67%. Adding T1-w hypointensity raised the specificity to 100%. A serum AFP15 ng/ml was associated with 95% specificity.Washout was observed in close to one-third of benign lesions, leading to an unacceptably low specificity for the diagnosis of HCC. The non-invasive diagnostic criteria proposed for cirrhotic patients cannot be extrapolated to patients with BCS.Washout on MRI is depicted in a significant proportion of benign nodules in patients with Budd-Chiari syndrome (BCS), limiting its value for the differentiation between benign and malignant lesions. Criteria proposed for the non-invasive diagnosis of hepatocellular carcinoma in patients with cirrhosis cannot be extrapolated to patients with BCS. Additional imaging findings and patient characteristics, including alpha-fetoprotein serum level, can help determine the probability of a nodule being HCC in patients with BCS.