Clinical and Radiologic Characteristics of Intra-Abdominal Fistulizing Crohn's Disease.

BACKGROUND: Few studies describe the radiological and laboratory characteristics of patients with Crohn's disease (CD) with intra-abdominal fistulae. OBJECTIVES: We aimed to describe a cohort of CD patients with intra-abdominal fistulae and determine characteristics associated with complex fistulae. METHODS: Data were gathered from medical records and imaging studies of patients. Evaluation included type of fistula, number of fistulae, and radiological characteristics. RESULTS: A total of 205 fistulae in 132 patients were identified with an average patient age of 31 (±12) years. The average time from CD diagnosis to fistula development was 7 years. The most common type of fistula was entero-enteric (53%). Patients with an extra-intestinal fistula presented with an average of 1.96 fistulae, compared with an average of 1.28 fistulae for those with a fistula limited to the bowel (p =0.01). Except for the number of fistula no other significant differences were observed in radiological characteristics of patients who were diagnosed with a fistula at time of CD diagnosis compared to those diagnosed with a fistula later. CONCLUSIONS: The most common CD-associated intra-abdominal fistulae are entero-enteric and entero-colonic fistulae. An extra-intestinal fistula and diagnosis of a fistula subsequent to diagnosis of CD were associated with an increased number of fistulae per patient.

The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: We investigated the effects of the fatty acid-bile acid conjugate 3ß-arachidyl-amido, 7α-12α-dihydroxy, 5ß-cholan-24-oic acid (Aramchol; Trima Israel Pharmaceutical Products Ltd, Maabarot, Israel) in a phase 2 trial of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We performed a randomized, double-blind, placebo-controlled trial of 60 patients with biopsy-confirmed NAFLD (6 with nonalcoholic steatohepatitis) at 10 centers in Israel. Patients were given Aramchol (100 or 300 mg) or placebo once daily for 3 months (n = 20/group). The main end point was the difference between groups in the change in liver fat content according to magnetic resonance spectroscopy. The secondary end points focused on the differences between groups in alterations of liver enzyme levels, levels of adiponectin, homeostasis model assessment scores, and endothelial function. RESULTS: No serious or drug-related adverse events were observed in the 58 patients who completed the study. Over 3 months, liver fat content decreased by 12.57% ± 22.14% in patients given 300 mg/day Aramchol, but increased by 6.39% ± 36.27% in the placebo group (P = .02 for the difference between groups, adjusted for age, sex, and body mass index). Liver fat content decreased in the 100-mg Aramchol group, by 2.89% ± 28.22%, but this change was nonsignificant (P = .35), indicating a dose-response relationship (P for trend = .01). Groups given Aramchol had nonsignificant improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin, but homeostasis model assessment scores did not change. The appropriateness of a single daily dose was confirmed by pharmacokinetic analysis. CONCLUSIONS: Three months' administration of the fatty acid-bile acid conjugate Aramchol is safe, tolerable, and significantly reduces liver fat content in patients with NAFLD. The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements, indicating that Aramchol might be used for the treatment of fatty liver disease. ClinicalTrials.gov number: NCT01094158.

Non-high-density lipoprotein cholesterol independently predicts new onset of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular disease (CVD) risk. Non-high-density lipoprotein cholesterol (non-HDL-C), i.e. total cholesterol minus HDL, is a well-established risk factor for CVD; however, its association with NAFLD development has not been established. Our aim was to test whether non-HDL-C is an independent predictor of new onset of NAFLD. METHODS: A prospective cohort study of 213 subjects from the general population, without liver disease, was studied. Evaluation of medical history, dietary and physical activity habits, fasting blood tests and ultrasonographic evidence of NAFLD was performed at baseline and after a 7-year follow-up by identical protocols. RESULTS: From 147 patients that did not have NAFLD at baseline, 28 (19%) developed NAFLD at the 7-year follow-up. The baseline levels of non-HDL-C were higher among subjects who developed NAFLD (179.5 ± 37.1 vs. 157.3 ± 35.1 mg/dl, P = 0.003). Non-HDL-C independently predicted new onset of NAFLD adjusting for age, gender, BMI or waist circumference, lifestyle and serum insulin (OR = 1.02 for every mg/dl increment, 1.01-1.04 95% CI, P = 0.008). Non-HDL-C was a stronger predictor for NAFLD than total cholesterol, low-density lipoprotein cholesterol, triglycerides and HDL. No patients with non-HDL-C < 130 mg/dl developed NAFLD, whereas 20.8% of those with values between 130 to 160 and 24.6% of those with values >160 mg/dl developed NAFLD (P for trend = 0.015). CONCLUSIONS: Non-HDL-C is an independent predictor for NAFLD and a stronger predictor than other lipoproteins. This association may stem from the combined hepato-toxic effect of non-HDL-C and may explain the association between NAFLD and CVD.

Non-alcoholic fatty liver disease independently predicts prediabetes during a 7-year prospective follow-up.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is suspected to confer an increased risk for developing type 2 diabetes (DM). However, only a few prospective studies evaluated NAFLD as a predictor for DM, most did not adjust for the full range of potential cofounders and none used an objectively quantified degree of steatosis. Our aim was to evaluate the independent role of NAFLD in predicting the development of pre-DM in a 7-year prospective follow-up of healthy volunteers. METHODS: A prospective cohort of a subsample of the Israeli National Health Survey evaluated at baseline and after 7 years by identical protocols. Metabolic parameters and ultrasonographic evidence of NAFLD were evaluated in 213 subjects, without known liver disease or history of alcohol abuse. Exclusion criteria were pre-DM at the baseline survey. Steatosis was quantified by ultrasound with the hepato-renal ultrasound index (HRI). RESULTS: The study included 141 volunteers (mean age 48.78 ± 9.68, 24.82% with NAFLD) without pre-DM/DM at baseline. Both NAFLD on regular US (OR=2.93, 1.02-8.41 95%CI) and HRI (OR=7.87, 1.83-33.82) were independent predictors for the development of pre-DM, adjusting for age, gender, BMI, family history of DM, baseline insulin, adiponectin and glucose. Further adjustment for physical activity and dietary intake did not weaken the association. Furthermore, NAFLD was a stronger predictor for pre-DM than the metabolic syndrome. Subjects with both NAFLD and glucose ≥89 had 93.3% incidence rate of pre-DM. CONCLUSION: Non-alcoholic fatty liver disease is a strong and independent risk factor for pre-DM in the general adult population; thus, NAFLD patients should be classified as a population at risk.

Dipeptidyl peptidase 4-deficient rats have improved bile secretory function in high fat diet-induced steatosis.

BACKGROUND/AIMS: Rodent obesity models have been shown to display impaired bile secretory functions. We have shown that glucagon-like peptide 1 (GLP-1) attenuates hepatic lipogenesis, and in the present study we investigated whether GLP-1 also improves high fat diet-associated cholestatic injury. METHODS: Wild type (WT) and dipeptidyl peptidase 4-deficient rats (DPP4-) with chronic elevated serum levels of active GLP-1 were fed regular chow and a Western diet for 2 months. Primary hepatocytes were used to assess GLP-1 effects on mRNA expression and transcription of genes encoding bile acid synthesis enzymes and transporters. RESULTS: DPP4- exhibited attenuated liver injury as expressed by lower serum AST and ALT after 2 months of a Western diet. In addition, DPP4- had better insulin sensitivity, lower serum triglycerides, cholesterol and bile acids. Hepatic expression of cyp7A1, the rate limiting enzyme in conversion of cholesterol into bile acids, was strongly attenuated in DPP4- fed with a Western diet. Moreover, hepatic expression of bile transporter, ABCB11, was increased, facilitating a higher rate of bile secretion. Mechanistically, we showed that GLP-1 directly reduced basal and LXR-induced cyp7A1 mRNA expression and suppressed cyp7A1 transcription in transient transfection assays in primary hepatocytes. However, GLP-1 and its analog exendin 4 also induced mRNA expression of bile acid transporter ABCC3 in primary rat hepatocyte cultures. CONCLUSIONS: Our data suggest that GLP-1 analogs may serve as a novel therapeutic drug to alleviate obesity-induced liver injury by reducing bile acid synthesis and improving liver bile secretory function.

Predictors for incidence and remission of NAFLD in the general population during a seven-year prospective follow-up.

BACKGROUND & AIMS: Data on the incidence and remission rates of non-alcoholic fatty liver disease (NAFLD) as well as predictive factors are scant. This study aims at evaluating NAFLD's epidemiology in prospective follow-up of individuals sampled from the general population. METHODS: Evaluation of metabolic parameters and ultrasonographic evidence of NAFLD was performed in 213 subjects, with no known liver disease or history of alcohol abuse. The evaluation was performed at baseline and after a 7-year period by identical protocols. RESULTS: Of the 147 patients who did not have NAFLD at baseline, 28 (19%) were found to have NAFLD at a 7-year follow-up. Baseline BMI, HOMA score, blood cholesterol, triglycerides, leptin levels, and weight gain (5.8±6.1 vs. 1.4±5.5kg, p<0.001) were significantly higher and adiponectin was lower among those who developed NAFLD at 7-year follow-up, compared with those who remained NAFLD-free. However, only weight gain and baseline HOMA were independent predictors for the development of NAFLD. Of the 66 patients who were found to have NAFLD at baseline, as many as 24 patients (36.4%) had no evidence of NAFLD at 7years. Weight loss of 2.7±5.0kg was significantly associated with NAFLD remission. Moreover, there was a 75% remission rate among NAFLD patients who lost 5% or more from their baseline weight. CONCLUSIONS: Among the general population, weight gain, and baseline insulin resistance are predictors for NAFLD incidence. One third of NAFLD patients may have remission of disease within a 7-year follow-up, mostly depending on modest weight reduction.

[Israeli guidelines for the treatment of chronic hepatitis C infection--2012 Israeli Association for the Study of the Liver].

The current standard of care for the treatment of hepatitis C virus (HCV) is a combination of pegylated interferon alpha (PeglFN] -2a/2b and ribavirin for 24-48 weeks, according to the viral genotype. This treatment is associated with significant side effects and achieves sustained virologic response (SVR) in only 40%-50% of genotype 1 HCV-infected patients. The recent development of direct-acting antiviral agents (DAAs] targeting critical steps of the virus life-cycle led to a major breakthrough in the management of HCV infection. The DAAs include protease inhibitors and polymerase inhibitors. The recently approved protease inhibitors boceprevir and telaprevir, when given with PeglFN and ribavirin in HCV genotype 1 patients, result in a much higher SVR rate [70%] among treatment-naïve and treatment-experienced patients, compared with Peg-IFN and ribavirin. In specific groups of patients this enables a shorter duration of treatment. The DAA-containing regimens are approved for HCV genotype 1 infection in HCV treatment-naïve and HCV treatment-experienced including cirrhotic patients. The Israeli Ministry of Health has recently approved the use of boceprevir (Victretis) and telaprevir (Incivo) in combination with PeglFN and ribavirin for the current standard of care treatment of HCV genotype 1 patients. The consensus opinion of a panel of national HCV-experts appointed by the Israeli Association for the Study of the Liver is presented in this report. These Israeli consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection.

Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase.

BACKGROUND & AIMS: Glucagon-like peptide-1 (GLP-1), a gut-derived peptide degraded by dipeptidyl peptidase-4 (DPP4), stimulates insulin secretion in response to nutrients, yet its direct effect on the liver is controversial. We investigated the effects of GLP-1 on hepatic fat and glucose metabolism and elucidated its mechanism of action. METHODS: Hepatic fat metabolism, including lipogenic enzymes and signal transduction regulators, was assessed in livers of DPP4-deficient rats (DPP4-) with chronically elevated GLP-1 and in GLP-1-treated primary hepatocytes. The effect of chronic elevated GLP-1 on insulin sensitivity was measured using the hyperinsulinemic-euglycemic clamp. RESULTS: Normal and high fat diet fed DPP4-rats displayed reduced hepatic triglycerides, accompanied by down-regulation of lipogenesis enzymes and parallel up-regulation of carnitine palmitoyltransferase-1, a key enzyme in fatty acid ß-oxidation. In vitro studies demonstrated that these effects were directly induced by GLP-1. Mechanistically, GLP-1 increased cAMP in hepatocytes, resulting in the phosphorylation of cAMP-activated protein kinase (AMPK), a suppressor of lipogenesis. Indeed, hepatocytes expressing a dominant negative Ad-DN-AMPK displayed attenuated GLP-1 effects on AMPK phosphorylation and its downstream lipogenic targets. Importantly, normoglycemic DPP4-rats did not display improved hepatic insulin sensitivity in vivo, suggesting a direct effect of GLP-1 on fat metabolism. Finally, DPP4-rats expressed lower levels of hepatic proinflammatory and profibrotic cytokines in response to nutrient stimuli. CONCLUSIONS: GLP-1 suppresses hepatic lipogenesis via activation of the AMPK pathway. GLP-1 inhibitory effects on hepatic fat accumulation and nutrient-induced hepatic proinflammatory response suggest GLP-1 analogs as novel therapies for non-alcoholic fatty liver diseases.

Thyroid hormones induce activation of rat hepatic stellate cells through increased expression of p75 neurotrophin receptor and direct activation of Rho.

We have previously shown that hyperthyroidism is detrimental for liver fibrosis and in this study we have investigated the mechanisms regulating triiodothyronine (T3) and L-thyroxine (T4) activation of hepatic stellate cells (HSC). Expression of alpha-smooth muscle actin (alphaSMA) and p75 neurotrophin receptor (p75NTR) was determined by western blot analyses and transient transfection of the promoters. Rho activation was assayed using a pull-down assay and by ELISA. Expression of thyroid hormone receptor alpha1 decreases, whereas T4 receptor integrin alphaVbeta3 increases, with transdifferentiation of HSC to myofibroblasts. T3 and T4 enhance HSC activation, without affecting proliferation or phosphorylation of mitogen-activated protein kinase, signal transducer and activator of transcription 3 or Akt. Addition of 10(-7) M T3 or T4 to thyroid hormone-depleted serum induces a twofold increase in activation marker alphaSMA, as well as upregulation of p75NTR protein levels. Both hormones enhance transcription of alphaSMA and p75NTR. We report a novel signaling pathway for thyroid hormones, activation of Rho. T4 induces activation of Rho acting through alphavbeta3 integrin, and the activation is abolished by the T4 antagonist, tetraiodothyroacetic acid, by peptide RGD and by a function-blocking antibody to integrin beta3. T3 and T4 increase phosphorylation of non-muscle myosin light chain II, a downstream signal to Rho/Rho-kinase activation. T3 also induces expression of tumor necrosis factor-alpha. In vivo, administration of T3 or T4 together with thioacetamide (TAA) enhances fibrosis after 3 weeks, compared with the TAA-treated group, accompanied by increased alphaSMA in T3- and T4-treated groups, and of p75NTR in T4-treated rats. Thyroid hormones enhance activation of HSC through increased p75NTR and alphaSMA expression and activation of Rho, therefore accelerating development of liver fibrosis.

Transjugular intrahepatic portosystemic shunt: current indications, patient selection and results.

BACKGROUND: Inserting a transjugular intrahepatic portosystemic shunt by means of interventional radiology has become the procedure of choice for decompression of portal hypertension. The indications and criteria for patient selection have been expanded and refined accordingly. OBJECTIVES: To review our experience with TIPS and analyze the results with emphasis on patient selection and indication (conventional vs. atypical). METHODS: In this retrospective analysis in a single center all cases were managed by a multidisciplinary team (comprising liver surgery and transplantation, hepatology, imaging, interventional radiology and intensive care). RESULTS: Between August 2003 and December 2009, 34 patients (mean age 51, range 27-76 years) were treated with TIPS. The cause of portal hypertension was cirrhosis (23 cases), hypercoagulability complicated by Budd-Chiari syndrome (n=6), and acute portal vein thrombosis (n=5). Clinical indications for TIPS included treatment or secondary prevention of variceal bleeding (10 cases), refractory ascites (n=18), mesenteric ischemia due to acute portal vein thrombosis (n=5), and acute liver failure (n=1). TIPS was urgent in 18 cases (53%) and elective in 16. Three deaths occurred following urgent TIPS. The overall related complication rate was 32%: trasient encephalopathy (6 cases), ischemic hepatitis (n=2), acute renal failure (n=2) and bleeding (n=1). Long-term results of TIPS were defined as good in 25 cases (73%), fair in 4 (12%) and failure in 5 (15%). In three of five patients with mesenteric ischemia following acute portal vein thrombosis, surgery was obviated. Revision of TIPS due to stenosis or thrombosis was needed in 7 cases (20%). CONCLUSIONS: TIPS is safe and effective. While its benefit for patients with portal hypertension is clear, the role of TIPS in treatment of portal-mesenteric venous thrombosis needs further evaluation. Patient selection, establishing the indication and performing TIPS should be done by a multidisciplinary dedicated team.

Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study.

UNLABELLED: Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross-sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty-nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P

Syndecan 1 (CD138) serum levels: a novel biomarker in predicting liver fibrosis stage in patients with hepatitis C.

BACKGROUND AND AIMS: Syndecan 1 (CD 138) is a cell surface proteoglycan shed by cells in several pathological conditions, including wound healing. The aim of this study was to test whether CD138 could serve as a non-invasive marker for detection of liver fibrosis and thereby reduce the need for liver biopsy. PATIENTS AND METHODS: An estimation set of 134 patients and a validation set of 67 patients with chronic hepatitis C were studied. There were 80 normal healthy volunteers. Patients were staged according to liver biopsies (Metavir fibrosis staging, stage F0, n=35; F1, n=40; F2, n=37, F3, n=39; F4, n=51). Serum CD138 levels were retrospectively measured by enzyme-linked immunoabsorbent assay the same day of the liver biopsy. The primary endpoints were the diagnostic values of CD138 for F2-F4, F3-F4 and F4. RESULTS: Respective areas under receiver operating characteristic curve of CD138 for F2-F4, F3-F4 and F4 diagnosis were 0.82, 0.76 and 0.81. CD138 had a positive predictive value of 82% for F2-F4 diagnosis and a high negative predictive value (86%) and specificity (84%) for exclusion of F4. CONCLUSION: CD138 is a new simple non-invasive marker for predicting liver fibrosis in patients with chronic hepatitis C. The relevance of this marker in combination with other fibrosis markers should be explored.

Diagnostic value of a computerized hepatorenal index for sonographic quantification of liver steatosis.

OBJECTIVE: Quantification of liver steatosis is clinically relevant in various liver diseases but cannot be done by conventional sonography, which only provides a qualitative assessment with significant observer variability. The aim of this study was to assess sonography as an objective tool for the quantification of liver steatosis. MATERIALS AND METHODS: Files of 111 patients with chronic liver disease who were referred for sonographically guided liver biopsy were collected. A hepatorenal sonographic index was calculated on the basis of the ratio between the echogenicity of the liver and that of the right kidney cortex using histogram echo intensity. Liver steatosis was graded by histology. RESULTS: A significant correlation was found between histologic steatosis and the hepatorenal sonographic index (r = 0.82, p < 0.001). The validity of the hepatorenal sonographic index for the diagnosis of fatty liver was compared with liver biopsies with a steatosis level > 5%. The area under the receiver operating characteristic curve was 99.2% (95% CI, 98-100%). The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis > 5% was 1.49, with sensitivity of 100% and specificity of 91%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis >/= 25% was 1.86, with sensitivity of 90% and specificity of 90%. The optimal hepatorenal sonographic index cutoff point for the prediction of steatosis >/= 60% was 2.23, with sensitivity of 90% and specificity of 93%. CONCLUSION: The hepatorenal sonographic index is a sensitive noninvasive method for steatosis quantification. It can diagnose small amounts of liver fat that would be missed by conventional sonography. It is reproducible and operator independent and can serve as an efficient tool to follow patients with steatosis and evaluate the efficacy of new treatment techniques.

Pulmonary manifestations of liver diseases.

Respiratory problems are common in patients with chronic liver diseases. The most common causes are disorders that are not related to liver diseases such as asthma and COPD. In addition certain liver diseases that are associated with specific pulmonary abnormalities, and conditions associated with end stage liver disease like tense ascites and intercostal muscular wasting are considered. Finally two unique disorders characterizing by vascular abnormalities independent of cardiorespiratory disorder-the hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are observed. These disorders have different pathogenesis, different clinical pictures, treatment and prognosis. This article reviews the epidemiology, pathophysiology, clinical features, evaluation and current therapy of these two disorders.

Non invasive assessment of liver fibrosis.

Liver fibrosis is the final common pathway of most chronic liver diseases of various etiologies.The development of fibrosis determines the management policy as well as the prognosis. In recent years it became clear that the fibrotic process is reversible. Therefore early detection of liver fibrosis is critical. At present, liver biopsy is considered the gold standard for the detection of fibrosis. Nevertheless liver biopsy is an invasive procedure limiting both its acceptance by patients, and their compliance for repeated procedures. More over it is a questionable gold standard due to significant sample error and intra and inter observer variability. These limitations have led to the development of noninvasive techniques for assessing the presence and the degree of liver fibrosis, such as biomarkers and transient elastography. The accuracy of these methods as compared to liver biopsy, as well as their use and limitations are reviewed in the article.

Multi-disciplinary patient-centered model for the expedited provision of costly therapies in community settings: the case of new medication for hepatitis C.

BACKGROUND: In January 2015, the first interferon-free direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection was approved for inclusion in Israel's national basket of health services. During 2015, HCV genotype 1 patients with advanced liver fibrosis (stage F3-F4) were eligible for treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir (OMB/PTV/r + DSV) provided through the four national health plans. As all health plans committed to identifying eligible patients nationwide, risk-sharing agreements created an additional incentive to develop an innovative model for rapid treatment delivery. AIM: This article aims to describe the development and implementation of a multi-disciplinary patient-centered model for the expedited provision of costly therapies in a community setting, based on experience delivering new HCV therapy in 2015. METHODS: We present the case of the Central District in Maccabi Healthcare Services (MHS), one of five districts in a 2-million-member healthcare provider. We describe the dimensions of the model and its implementation, including the composition and responsibilities of the multi-disciplinary team, screening for patient eligibility, provision of care, and barriers and facilitators identified at each stage. RESULTS: The experience of the MHS Central District indicates that good communication between all stakeholders was the key driver of successful implementation of the model. Overall, monthly treatment uptake increased following the intervention and by the end of 2015 a total of 99 patients were treated with OMB/PTV/r + DSV in this district. Early data indicate high effectiveness in this population and evaluation in ongoing. CONCLUSIONS: This multi-disciplinary patient-centered model enabled rapid integration of screening and disease staging to identify and treat eligible HCV patients in the MHS central district. The model forms the basis of the 2017 project to deliver DAAs according to broader health basket criteria and may be adapted for the provision of other innovative health technologies in different healthcare settings.

Budd-Chiari syndrome and acute portal vein thrombosis: management by a transjugular intrahepatic portosystemic shunt (TIPS) and portal vein interventions via a TIPS.

Acute portal vein thrombosis (PVT) is a devastating complication of Budd-Chiari syndrome (BCS). Conservative approach, anticoagulation, systemic or transarterial thrombolysis, and urgent liver transplantation were applied in this scenario but with poor results. We present and discuss an approach to treat BCS complicated by acute PVT. Two young female patients presented with acute liver failure, rapidly progressive tense ascites, renal- and respiratory failure. The diagnosis of chronic BCS complicated by acute PVT was confirmed with ultrasound Doppler. Initial treatment was supportive. Right portal vein localization was by transarterial portogram or by computed tomography-guided microcoil placement. Transjugular intrahepatic portosystemic shunt (TIPS) was performed and included Wallstents and a Jograft in one case and Viatorr stentgraft that was extended later with a Hemobahn stentgraft in another. Mechanical clot removal from the portal system was performed in the primary procedure and in a revision procedure in the following few days. Stents were placed precisely with no extension into the inferior vena cava or deeply into the main portal vein. Patients were fully anticoagulated and patency was assessed by ultrasound Doppler. The procedures were performed on days 5 and 10 following admission. In both cases, successful thrombectomies were revised and maintained. Partial occlusion of the TIPS and reaccumulation of ascites were reversed with repeated procedure. Both patients were discharged without ascites and normal liver function. In conclusion, urgent TIPS and portal vein thrombectomy via TIPS are emerging therapeutic options that offer a safe and effective treatment to patients with BCS complicated by acute portal vein thrombosis.

Is the model of end-stage liver disease (MELD) valid in Israel? A critical analysis of liver transplant waiting list mortality.

BACKGROUND: The model for end-stage liver disease is the best available predictor of waiting list mortality among liver transplant candidates. OBJECTIVES: To validate the applicability of MELD in Israel. METHODS: All candidates awaiting liver transplantation in our institution were followed prospectively since 2002. We measured the concordance (c-statistic) equivalent to the area under the receiver operating characteristic curve in order to assess the predictive power of MELD. Other independent mortality risk factors were identified by a separate multivariate analysis. Mortality rates within different MELD and Child-Pugh-Turcotte scores were compared to the original (United States) MELD data. RESULTS: Of 86 patients listed for transplantation, 40 were transplanted (36 in Israel and 4 abroad). Of the other 46 patients, 24 are alive and still listed, and 22 died (25%, approximately 7%/year). The area under the ROC curve for MELD score was 0.79 (0.83 USA) compared to a CPT score of 0.71 (0.76 USA). High MELD scores, occurrence of spontaneous bacterial peritonitis, and diagnosis of hepatocellular carcinoma were independent risk factors of mortality. Death rates per mid-MELD score (20-29) were significantly higher than the USA results. CONCLUSIONS: MELD is valid in Israel and superior to CPT in predicting waiting list mortality. Although longer waiting time due to organ scarcity is a key factor, death rates in the mid-range (10-29) MELD groups indicate further audit of the care of patients with end-stage liver disease.

Factors associated with surgery in patients with intra-abdominal fistulizing Crohn's disease.

AIM: To characterize radiological and clinical factors associated with subsequent surgical intervention in Crohn's disease (CD) patients with intra-abdominal fistulae. METHODS: From a cohort of 1244 CD patients seen over an eight year period (2006 to 2014), 126 patients were identified as having intra-abdominal fistulae, and included in the study. Baseline patient information was collected from the medical records. Imaging studies were assessed for: anatomic type and number of fistulae; diameter of the inflammatory conglomerate; length of diseased bowel; presence of a stricture with pre-stenotic dilatation; presence of an abscess; lymphadenopathy; and the degree of bowel enhancement. Multivariate analysis for the prediction of abdominal surgery was calculated via Generalized Linear Models. RESULTS: In total, there were 193 fistulae in 132 patients, the majority (52%) being entero-enteric. Fifty-nine (47%) patients underwent surgery within one year of the imaging study, of which 36 (29%) underwent surgery within one month. Radiologic features that were associated with subsequent surgery included: multiple fistulae (P = 0.009), presence of stricture (P = 0.02), and an entero-vesical fistula (P = 0.01). Evidence of an abscess, lymphadenopathy, or intense bowel enhancement as well as C-reactive protein levels was not associated with an increased rate of surgery. Patients who were treated after the imaging study with combination immunomodulatory and anti-TNF therapy had significantly lower rates of surgery (P = 0.01). In the multivariate analysis, presence of a stricture [RR 4.5 (1.23-16.3), P = 0.02] was the only factor that increased surgery rate. CONCLUSION: A bowel stricture is the only factor predicting an increased rate of surgery. Radiological parameters may guide in selecting treatment options in patients with fistulizing CD.