Bleeding risk of variceal band ligation in extrahepatic portal vein obstruction is not increased by oral anticoagulation.

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.

First description of ABCB4 gene deletions in familial low phospholipid-associated cholelithiasis and oral contraceptives-induced cholestasis.

The wide clinical spectrum of the ABCB4 gene (ATP-binding cassette subfamily B member 4) deficiency syndromes in humans includes low phospholipid-associated cholelithiasis (LPAC), intrahepatic cholestasis of pregnancy (ICP), oral contraceptives-induced cholestasis (CIC), and progressive familial intrahepatic cholestasis type 3 (PFIC3). No ABCB4 mutations are found in a significant proportion of patients with these syndromes. In the present study, 102 unrelated adult patients with LPAC (43 patients) or CIC/ICP (59 patients) were screened for ABCB4 mutations using DNA sequencing. Heterozygous ABCB4 point or short insertion/deletion mutations were found in 37% (16/43) of the LPAC patients and in 27% (16/59) of the ICP/CIC patients. High-resolution gene dosage methodologies were used in the 70 negative patients. Here, we describe for the first time ABCB4 partial or complete heterozygous deletions in 7% (3/43) of the LPAC patients, and in 2% (1/59) of the ICP/CIC patients. Our observations urge to systematically test patients with LPAC, ICP/CIC, and also children with PFIC3 for the presence of ABCB4 deletions using molecular tools allowing detection of gross rearrangements. In clinical practice, a comprehensive ABCB4 alteration-screening algorithm will permit the use of ABCB4 genotyping to confirm the diagnosis of LPAC or ICP/CIC, and allow familial testing. An early diagnosis of these biliary diseases may be beneficial because of the preventive effect of ursodeoxycholic acid on biliary complications. Further comparative studies of patients with well-characterized genotypes (including deletions) and phenotypes will help determine whether ABCB4 mutation types influence clinical outcomes.

Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study.

UNLABELLED: Current recommendations for early anticoagulation in acute portal vein thrombosis unrelated to cirrhosis or malignancy are based on limited evidence. The aim of this study was to prospectively assess the risk factors, outcome, and prognosis in patients managed according to these recommendations. We enrolled 102 patients with acute thrombosis of the portal vein, or its left or right branch. Laboratory investigations for prothrombotic factors were centralized. Thrombus extension and recanalization were assessed by expert radiologists. A local risk factor was identified in 21% of patients, and one or several general prothrombotic conditions in 52%. Anticoagulation was given to 95 patients. After a median of 234 days, the portal vein and its left or right branch were patent in 39% of anticoagulated patients (versus 13% initially), the splenic vein in 80% (versus 57% initially), and the superior mesenteric vein in 73% (versus 42% initially). Failure to recanalize the portal vein was independently related to the presence of ascites (hazard ratio 3.8, 95% confidence interval 1.3-11.1) and an occluded splenic vein (hazard ratio 3.5, 95% confidence interval 1.4-8.9). Gastrointestinal bleeding and intestinal infarction occurred in nine and two patients, respectively. Two patients died from causes unrelated to thrombosis or anticoagulation therapy. CONCLUSION: Recanalization occurs in one-third of patients receiving early anticoagulation for acute portal vein thrombosis, whereas thrombus extension, intestinal infarction, severe bleeding, and death are rare. Alternative therapy should be considered when ascites and splenic vein obstruction are present.

Does regular blood transfusion prevent progression of cerebrovascular lesions in children with sickle cell disease?

A retrospective study was conducted to assess changes in cerebrovascular lesions, as assessed by magnetic resonance (MR) imaging and angiography in 18 children with sickle cell disease (SCD) receiving optimised chronic transfusions for primary stroke prevention (abnormal transcranial Doppler flow, nine patients, median follow-up 14.3 months (range, 7.9-48.9)) or secondary stroke prevention (nine patients, median follow-up 59.6 months (range, 11.0-127.9)). An experienced neuroradiologist blinded to patient data reviewed the 41 MR scans (median/patient, three (2-4)). Standard scores were used to evaluate parenchymal and vascular abnormalities at baseline and last follow-up. Within-patient score changes evaluated using Wilcoxon's paired rank test indicated lesion progression in the secondary-prevention group (p = 0.027). Optimised transfusion therapy does not prevent progression of cerebral vasculopathy in SCD children with a history of stroke.

Long-term portosystemic shunt patency as a determinant of outcome in Budd-Chiari syndrome.

BACKGROUND/AIMS: Portosystemic shunting, whether surgical or transjugular intrahepatic, has been a cornerstone of therapy for Budd-Chiari syndrome. However, the long-term impact of shunt dysfunction remains unknown. We have assessed this long-term impact in patients with surgical shunting. METHODS: Thirty-nine consecutive patients operated on between 1978 and 2000 were analyzed using time-dependent multivariate Cox model. RESULTS: Median follow-up was 110 months. Prosthetic shunts and high preshunt portal venous pressure were predictors of subsequent shunt dysfunction. Among 19 patients with persistently patent shunt, as compared to 20 patients with shunt dysfunction, 1 versus 18 developed refractory ascites; 1 versus 7 had variceal bleeding; 7 versus 2 had encephalopathy; 3 versus 11 (55%) died or underwent liver transplantation; and 0 versus 10 died from end-stage liver disease. Shunt dysfunction was associated with a shorter survival (p=0.001). Out of 20 patients with shunt dysfunction, seven had successful revision of the shunt. None of these seven patients had refractory ascites after revision or died from end-stage liver disease. CONCLUSIONS: In patients with Budd-Chiari syndrome treated with portosystemic shunting, shunt dysfunction has a major impact on morbidity and mortality.

Aiming at minimal invasiveness as a therapeutic strategy for Budd-Chiari syndrome.

The 1-year spontaneous mortality rate in patients with Budd-Chiari syndrome (BCS) approaches 70%. No prospective assessment of indications and impact on survival of current therapeutic procedures has been performed. We evaluated a therapeutic strategy uniformly applied during the last 8 years in a single referral center. Fifty-one consecutive patients first received anticoagulation and were treated for associated diseases. Symptomatic patients were considered for hepatic vein recanalization; then for transjugular intrahepatic portosystemic shunt (TIPS), and finally for liver transplantation. The absence of a complete response led to the next procedure. Assessment was according to the strategy, whether procedures were technically applicable and successful. At entry, median (range) Child-Pugh score and Clichy prognostic index were 8 (5-12), and 5.4 (3.1-7.7), respectively. A complete response was achieved on medical therapy alone in 9 patients; after recanalization in 6, TIPS in 20, liver transplantation in 9, and retransplantation in 1. Of the 41 patients considered for recanalization, the procedure was not feasible in 27 and technically unsuccessful in 3. Of the 34 patients considered for TIPS, the procedure was considered not feasible in 9 and technically unsuccessful in 4. At 1 year of follow-up, a complete response to TIPS was achieved in 84%. One- and 5-year survival from starting anticoagulation were 96% (95% CI, 90-100) and 89% (95% CI, 79-100), respectively. In conclusion, excellent survival can be achieved in BCS patients when therapeutic procedures are introduced by order of increasing invasiveness, based on the response to previous therapy rather than on the severity of the patient's condition.

A simple biological score for predicting low risk of short-term relapse in Crohn's disease.

BACKGROUND: In Crohn's disease, studies have evaluated the ability of biological markers to predict relapse in the next 12 to 18 months, without differentiating early from late relapses. The aim of this study was to look for biological markers of short-term relapse. MATERIALS AND METHODS: In a previous therapeutic trial, patients with a medically induced clinical remission had biological markers evaluated and updated every 6 weeks. A Cox model with time-dependent covariates was used for analysis. RESULTS: Among the 71 patients, 38 had a relapse. Multivariate analysis selected 2 markers predictive of relapse: C-reactive protein >20 mg/L and erythrocyte sedimentation rate >15 mm. A binary biological predictive score was derived: "negative" when both were lower than their limits, "positive" when otherwise. The relative risk of short-term relapse for patients with a positive score compared to those with a negative score was 8.0 (95% confidence interval 2.8-22.9). Sensitivity of the score was 89% and specificity was 43%. Assuming a 10% relapse rate every 6 weeks, negative and positive predictive values were 97% and 15%, respectively. CONCLUSIONS: This simple biological score can predict short-term maintenance of remission in Crohn's disease and may help physicians in the follow-up of patients in clinical remission.

Percutaneous radiofrequency ablation for hepatocellular carcinoma before liver transplantation: a prospective study with histopathologic comparison.

OBJECTIVE: The aims of this study were to determine the feasibility and efficacy of percutaneous radiofrequency ablation in patients with hepatocellular carcinoma waiting for liver transplantation and to compare the radiologic and pathologic findings. SUBJECTS AND METHODS: Twenty-six patients with 35 hepatocellular carcinomas were addressed for transplantation. Complications of the procedures were recorded. Primary and secondary technique effectiveness and causes of exclusion from the waiting list were assessed. After transplantation, tumor recurrence was evaluated for at least 1 year in all patients. Radiologic-pathologic comparison of the explant was performed. RESULTS: Percutaneous radiofrequency ablation was performed in 21 (81%) patients for 28 tumors. Both minor and major complications occurred in three patients (10% each per session). The rates of primary technique effectiveness, secondary technique effectiveness for percutaneous radiofrequency ablation alone (seven tumors), and combined percutaneous radiofrequency ablation and transcatheter arterial chemoembolization (three tumors) were 56%, 76%, and 86%, respectively. After a mean follow-up of 11.9 months, 16 patients (76%) received transplants, whereas five patients were excluded from the waiting list because of distant tumor progression (n =3, 14%) or other causes (n = 2, 10%). After transplantation, tumor recurred in one (6%) of 16 patients. Histopathologic examinations were performed for 13 (81%) of 16 patients and showed complete necrosis and satellite nodules in, respectively, 12 (75%) and seven (44%) of 16 tumors. CONCLUSION: Percutaneous radiofrequency ablation can be performed on hepatocellular carcinoma patients waiting for transplantation, allows most patients to undergo transplantation, and does not impair posttransplantation outcomes. The procedure produces complete necrosis of the treated tumor in most cases but is associated with a high rate of satellite nodules.

Acute pulmonary embolism: a rare complication of a large non-parasitic hepatic cyst.

A 56-year-old patient with a non-parasitic hepatic cyst developed acute dyspnoea. Pulmonary embolism was diagnosed. Bleeding into the hepatic cyst, leading to its enlargement and compression of the inferior vena cava, was the only likely cause of the pulmonary embolism. This complication of a non-parasitic liver cyst has not been reported previously. The patient was treated with heparin. Surgical evacuation of the cyst using the 'fenestration' technique was also performed. There was no recurrent pulmonary embolism or hepatic cyst during a 1-year follow-up period.

Underestimation of the influence of satellite nodules as a risk factor for post-transplantation recurrence in patients with small hepatocellular carcinoma.

Liver transplantation offers good results in patients with small hepatocellular carcinoma. However, 3 to 15% of patients still have recurrence, suggesting that factors other than the size and number of nodules are implicated. The aim of our study was to identify predictive factors of recurrence in patients with small hepatocellular carcinoma. Seventy consecutive patients fulfilling Milano criteria and who were transplanted for hepatocellular carcinoma were studied. Forty-six patients had pretransplantation adjuvant local therapy. The size and number of tumors, the clinical and biological characteristics of the patients were recorded before liver transplantation, and histological analysis was performed on the explanted liver. Overall survival rates at 1 and 3 years were 81% and 66%, respectively. Recurrence-free survival rates at 1 and 3 years were 80% and 65%, respectively. Seven patients had tumor recurrence with 1- and 3-year recurrence rates of 5% and 10%, respectively. Satellite nodules on the explanted liver were the only statistically significant predictor of recurrence (P=.0003). None of the patients who did not have satellite nodules had recurrence. There was a significant correlation between satellite nodules and microvascular invasion. Patients with pretransplantation adjuvant therapy had significantly more tumor necrosis, but did not have less satellite nodules. In conclusion, microscopic satellite nodules are a significant predictive factor of tumor recurrence in patients transplanted for small hepatocellular carcinoma.

Coagulation disorders in patients with cirrhosis and severe sepsis.

BACKGROUND: In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation. AIMS: To compare 23 patients with severe sepsis to 13 infected patients without severe sepsis and 18 patients without infection. METHODS: Zymogen forms of clotting factors involved in the extrinsic pathway (i.e., factors VII + X, V, prothrombin), and the presence of soluble fibrin were assessed. RESULTS: Zymogen forms of clotting factors were significantly lower, while Child-Pugh score and the proportion of patients with soluble fibrin were higher in the severe-sepsis group than in the other groups. Decreased zymogen levels were independently correlated with an elevated Child-Pugh score and the presence of severe sepsis. In the severe-sepsis group, after adjustment for the severity of cirrhosis, decreased zymogen levels were associated with significant increases in the relative risk ratios of in-hospital death. CONCLUSIONS: Cirrhotic patients with severe sepsis have decreased blood levels of zymogen forms of factors VII+X, V, and prothrombin, which may be due not only to the severity of cirrhosis but also, at least in part, to the consumption of these zymogens by the extrinsic coagulation pathway.