Jildou Hoekstra

Good long-term outcome of Budd-Chiari syndrome with a step-wise management

Budd‐Chiari syndrome (BCS) is a rare, life‐threatening disease caused by obstruction of hepatic venous outflow. The aim of the study was to assess long‐term outcome and identify prognostic factors in BCS patients managed by a step‐wise approach using anticoagulation, angioplasty/thrombolysis, transjugular intrahepatic portosystemic shunting (TIPS), and orthotopic liver transplantation (OLT). We reviewed long‐term data on 157 patients previously included by the European Network for Vascular Disorders of the Liver, a multicenter prospective study of newly diagnosed BCS patients in nine European countries. Patients were followed for a median of 50 months (range, 0.1‐74.0). During the study, 88 patients (56%) received at least one invasive intervention (22 patients angioplasty/thrombolysis, 62 TIPS, and 20 OLT) and 36 (22.9%) died. Most interventions and/or deaths occurred in the first 2 years after diagnosis. The Rotterdam score was excellent in predicting intervention‐free survival, and no other variable could significantly improve its prognostic ability. Moreover, BCS‐TIPS prognostic index (PI) score (based on international normalized ratio, bilirubin, and age) was strongly associated with survival and had a discriminative capacity, which was superior to the Rotterdam score. Conclusions: The current study confirms, in a large cohort of patients with BCS recruited over a short period, that a step‐wise treatment approach provides good long‐term survival. In addition, the study validates the Rotterdam score for predicting intervention‐free survival and the BCS‐TIPS PI score for predicting survival. (HEPATOLOGY 2013;)

Paroxysmal nocturnal hemoglobinuria in Budd-Chiari Syndrome: Findings from a cohort study

BACKGROUND/AIMS A well recognized cause of Budd-Chiari syndrome (BCS) is paroxysmal nocturnal hemoglobinuria (PNH). PNH is an acquired disorder of hematopoietic stem cells, characterized by intravascular hemolysis and venous thrombosis. Testing for this hematological disorder should be considered in all BCS patients. METHODS Using data from the EN-Vie study, a multi-center study of 163 patients with BCS, we investigated the relationship between BCS and PNH in 15 patients with combined disease and compared the results to 62 BCS patients in whom PNH was excluded. RESULTS Median follow-up for the study group (n=77) was 20 months (range 0-44 months). BCS patients with PNH presented with a significantly higher percentage of additional splanchnic vein thrombosis (SVT) as compared to BCS patients without PNH (47% vs. 10%, p=0.002). During follow-up, type and frequency of interventions for BCS was similar between both groups. Six patients with BCS and PNH were successfully treated with a transjugular intrahepatic portosystemic shunt (TIPS). Of 15 patients with PNH, six underwent allogenic stem cell transplantation after diagnosis of BCS. PNH was successfully cured in five cases. There was no significant difference in survival between BCS patients with and without PNH. CONCLUSIONS This study shows that despite a higher frequency of additional SVT, short-term prognosis of BCS patients with PNH does not differ from BCS patients without PNH. Treatment with TIPS can be safely performed in patients with PNH. Stem cell transplantation appears to be a feasible treatment option for PNH in BCS patients.

Anticoagulant therapy in patients with non-cirrhotic portal vein thrombosis: Effect on new thrombotic events and gastrointestinal bleeding

It remains unclear when anticoagulant therapy should be given in patients with non‐cirrhotic portal vein thrombosis (PVT). The aim of this study was to assess the effect of anticoagulation on recurrent thrombotic events and gastrointestinal bleeding in non‐cirrhotic PVT patients.

Impaired fibrinolysis as a risk factor for Budd-Chiari syndrome

In Budd-Chiari syndrome (BCS), thrombosis develops in the hepatic veins or inferior vena cava. To study the relationship between hypofibrinolysis and BCS, we measured plasma levels of fibrinolysis proteins in 101 BCS patients and 101 healthy controls and performed a plasma-based clot lysis assay. In BCS patients, plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than in controls (median, 6.3 vs 1.4 IU/mL, P < .001). Thrombin-activatable fibrinolysis inhibitor and plasmin inhibitor levels were lower than in controls (13.8 vs 16.9 microg/mL and 0.91 vs 1.02 U/L, both P < .001). Median plasma clot lysis time (CLT) was 73.9 minutes in cases and 73.0 minutes in controls (P = .329). A subgroup of cases displayed clearly elevated CLTs. A CLT above the 90th or 95th percentile of controls was associated with an increased risk of BCS, with odds ratios of 2.4 (95% confidence interval, 1.1-5.5) and 3.4 (95% confidence interval, 1.2-9.7), respectively. In controls, only PAI-1 activity was significantly associated with CLT. Analysis of single nucleotide polymorphisms of fibrinolysis proteins revealed no significant differences between cases and controls. This case-control study provides the first evidence that an impaired fibrinolytic potential, at least partially caused by elevated PAI-1 levels, is related to the presence of BCS.

Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms

Summary.  Background: Myeloproliferative neoplasms (MPNs) are frequently identified as an underlying cause in patients with non‐cirrhotic portal vein thrombosis (PVT). The aim of this study was to describe the long‐term outcome of patients with PVT and MPN. Methods: A cohort study was performed including all adult patients referred to our hospital between 1980 and 2008 with non‐cirrhotic, non‐malignant PVT and confirmed MPN. Results: A total of 44 patients (70% female) were included, with a median age at PVT‐diagnosis of 48 years (range 18–79). In 31 patients (70%) PVT was the first manifestation of an MPN. Additional risk factors for thrombosis were present in 20 patients (45%). Median follow‐up was 5.8 years (range 0.4–21). Twenty‐three patients (52%) were treated with oral anticoagulants after diagnosis of PVT, of whom 15 (34%) received long‐term therapy. During follow‐up, 17 patients (39%) experienced at least one episode of gastrointestinal bleeding. Additional thrombotic events occurred in 12 patients (27%). Twelve patients (27%) had progression of the underlying MPN. Seventeen patients (39%) died at a median age of 64 years (range 30–88). Death was directly related to end‐stage MPN in eight patients (47%) and to a new thrombotic event in three patients (18%). No patients died from gastrointestinal bleeding. Conclusions: PVT is often the presenting symptom of an underlying MPN, highlighting the need for thorough screening for this disease. Recurrent thrombosis is a common and severe complication in patients with PVT and MPN. Mortality is primarily related to the underlying MPN and not to complications of portal hypertension.

Pregnancy in women with portal vein thrombosis: Results of a multicentric European study on maternal and fetal management and outcome

BACKGROUND & AIMS Women of childbearing age account for approximately 25% of patients with non-cirrhotic portal vein thrombosis (PVT). We aimed at assessing maternal and fetal outcome in pregnant women with known PVT. METHODS We performed a retrospective analysis of the files of women with chronic PVT in three European referral centers between 1986 and 2010. RESULTS Forty-five pregnancies, 28 (62%) treated with low molecular weight heparin, occurred in 24 women. Nine (20%) were lost before gestation week 20. Preterm birth occurred in 38% of deliveries: there were 3 births at week 24-25, 7 at week 32-36, and 26 after week 37. A term birth with a healthy infant occurred in 58% of pregnancies. Cesarean section was used in 53% of deliveries. Two women developed HELLP syndrome. A favorable outcome happened in 64% of pregnancies. Pregnancies with an unfavorable outcome were associated with a higher platelet count at diagnosis. Bleeding from esophageal varices occurred in 3 patients during pregnancy, all without adequate primary prophylaxis. Genital or parietal bleeding occurred postpartum in 4 patients, only one being on anticoagulation therapy. Thrombotic events occurred in 2 patients, none related to lower limbs or mesenteric veins. There were no maternal deaths. CONCLUSIONS In pregnant PVT patients treated with anticoagulation on an individual basis, the rate of miscarriage and preterm birth appears to be increased. However, fetal and maternal outcomes are favorable for most pregnancies reaching gestation week 20. High platelet counts appear to increase the risk for unfavorable outcome. Pregnancy should not be contraindicated in stable PVT patients.

Proteomic analysis reveals that apolipoprotein A1 levels are decreased in patients with Budd-Chiari syndrome.

BACKGROUND & AIMS Budd-Chiari syndrome (BCS) is a rare vascular liver disorder caused by thrombosis of the hepatic veins. In some patients, no known thrombophilic factor can be identified. This study aimed to identify novel factors that might play a role in thrombosis in BCS-patients by using a proteomic approach. METHODS The abundance of plasma clot-bound proteins was compared between nine BCS-patients and nine controls by using two-dimensional difference gel electrophoresis. The protein with the most significant decrease in patients was identified by mass spectrometry. Plasma levels of this protein were measured and the results were validated in a large cohort of BCS-patients. RESULTS A total of 26 protein spots significantly differed (p<0.001). The spot that decreased with the highest statistical significance in patients was identified by mass spectrometry as apolipoprotein A1 (apo A1). The mean level of apo A1 in the plasma of these BCS-patients (0.74 g/L) was also significantly lower than in controls (1.45 g/L, p=0.002). This finding was validated in a large cohort of 101 BCS-patients and 101 controls (0.97 g/L vs. 1.32 g/L, p<0.0001). There was no major correlation between plasma levels of apo A1 and various liver function tests. CONCLUSIONS BCS-patients show decreased clot-bound protein abundance and plasma levels of apo A1. Decreased levels of apo A1 may play a role in the etiology of thrombosis in BCS-patients and possibly in other patients with venous thrombosis.

GI ischemia in patients with portal vein thrombosis: A prospective cohort study

BACKGROUND AND AIMS GI ischemia is a concerning adverse event of portal vein thrombosis (PVT). Minimally invasive techniques, such as visible light spectroscopy (VLS), have greatly improved the ability to diagnose GI ischemia. The aim of this study was to assess the clinical presentation and characteristics of GI ischemia in patients with PVT. METHODS Patients with noncirrhotic, nonmalignant PVT were included in this prospective cohort study. Clinical symptoms of GI ischemia were assessed by a structured questionnaire, VLS, and radiologic evaluation of the mesenteric vasculature. VLS measurements were compared with those in patients with cirrhosis and with a reference population. RESULTS We included 15 patients with chronic PVT and 1 patient with acute PVT (median age 46.1 years [interquartile range [IQR], 30.9-53.7]; 44% male). Decreased mucosal oxygenation in at least 1 location of the GI tract was found in 12 patients (75%). Compared with the reference population (median 60.0 [IQR, 56.2-61.7]), VLS measurements were mostly decreased in the descending duodenum in patients with PVT (median 55.5 [IQR, 52.3-58.8]; P = .02) and patients with cirrhosis (median 52.0 [IQR, 46.5-54.0], P = .003). Symptoms typical for GI ischemia, such as postprandial pain and exercise-induced pain, were reported in 10 patients (63%) with PVT. In patients with extension of thrombosis into the superior mesenteric vein and splenic vein and/or presence of hypercoagulability, decreased VLS measurements were observed compared with historical control subjects. CONCLUSIONS In patients with chronic PVT, GI ischemia is frequent. VLS enables objective and quantitative determination of GI mucosal ischemia. Onset of abdominal symptoms such as postprandial pain should prompt the physician to re-evaluate extent, cause, and treatment of PVT.

P633 Decision-making, counselling and course of pregnancy in female inflammatory bowel disease patients

Background: An epidemiological association implicating diet in Inflammatory Bowel Disease (IBD) risk or protection is widely accepted. Despite unprecedented advances in aetio-pathogenesis, nutritional research has been limited by heterogeneity of study design, variability of diet, and difficulty in obtaining accurate longitudinal dietary data. Patients with IBD often make links to diet in clinical consultations, but there is a dearth of literature exploring dietary perceptions and practices in an IBD population [1]. The aim of the study was to evaluate dietary beliefs and behaviours in patients with IBD. Methods: We developed a 25-item questionnaire assessing demographics, dietary beliefs and habits, impact on social life and patients’ use of resources for dietary advice. The questionnaire was prospectively administered to consecutive IBD patients attending our IBD clinics from September to November 2013. Results: A total of 187 patients participated in the study. The average age was 48 years; 55% were female and 85% Caucasian. The median disease duration was 6 years. Thirty-nine percent had Crohn’s Disease and 52% had Ulcerative Colitis. Of the respondents, 49% felt that diet could be the initiating factor in IBD and 58% felt it could trigger a flare. Fifty-nine percent reported a modification in their diet and 38% reported taking dietary supplements. Worsening of symptoms with certain food and drinks was reported by 62%, the commonest being spicy food (46%), fatty food (33%) and alcohol (22%). A minority (17%) reported improvement in symptoms with certain foods and 66% deprived themselves of certain foods to prevent relapse with 24% refusing to dine outside of home for fear of causing relapse. Seventy-four percent of respondents believed that IBD affects appetite. On a visual analogue scale of 1 10, mean scores for appetite in disease remission and during disease relapse were 8 (SD 2.0) and 4 (SD 2.9) respectively (p = 0.001). Nearly half of respondents (47%) had never received any formal dietary advice, and most (67%) requested further dietary advice from dieticians (43%), nurses (34%) and patient information leaflets (28%). Conclusions: Patients express a belief that diet affects IBD symptoms and disease activity, with a high level of consistency around key perceived triggers. Whether all the symptoms reported are due to active inflammation cannot be ascertained, but the potential exists for dietary components triggering active disease and perpetuating gut injury, impacting on quality of life and health care costs. This should serve as an impetus for further patient centered research.