Effects of Long-term Norfloxacin Therapy in Patients With Advanced Cirrhosis.

BACKGROUND & AIMS: There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis. METHODS: We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up. RESULTS: The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations <15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. CONCLUSIONS: In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.

Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis.

BACKGROUND & AIMS: More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC. METHODS: Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS). RESULTS: From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients' inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5-95.4), 80.3% (95% CI 76.9-83.9), and 3.2% (95% CI 1.6-4.8) respectively. CONCLUSION: This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%. LAY SUMMARY: Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening.

Covered vs. uncovered stents for transjugular intrahepatic portosystemic shunt: a randomized controlled trial.

BACKGROUND & AIMS: The first studies comparing covered stents (CS) and bare stents (BS) to achieve Transjugular Intrahepatic Portosystemic Shunt (TIPS) were in favor of CS, but only one randomized study has been performed. Our aim was to compare the primary patency of TIPS performed with CS and BS. METHODS: The study was planned as a multicenter, pragmatic (with centers different in size and experience), randomized, single-blinded (with blinding of patients only), parallel group trial. The primary endpoint was TIPS dysfunction defined as either a portocaval gradient ⩾12mmHg, or a stent lumen stenosis ⩾50%. A transjugular angiography with portosystemic pressure gradient measurement was scheduled every 6months after TIPS insertion. RESULTS: 137 patients were randomized: 66 to receive CS, and 71 BS. Patients who were found to have a hepato-cellular carcinoma, or whose procedure was cancelled were excluded, giving a sample of 129 patients (62 vs. 67). Median follow-up for CS and BS were 23.6 and 21.8months, respectively. Compared to BS, the risk of TIPS dysfunction with CS was 0.60 95% CI [0.38-0.96], (p=0.032). The 2-year rate of shunt dysfunction was 44.0% for CS vs. 63.6% for BS. Early post TIPS complications (22.4% vs. 34.9%), risk of hepatic encephalopathy (0.89 [0.53-1.49]) and 2-year survival (70% vs. 67.5%) did not differ in the two groups. The 2-year cost/patient was 20k€ [15.9-27.5] for CS vs. 23.4k€ [18-37] for BS (p=0.52). CONCLUSIONS: CS provided a significant 39% reduction in dysfunction compared to BS. We did not observe any significant difference with regard to hepatic encephalopathy or death.

Pentoxifylline does not decrease short-term mortality but does reduce complications in patients with advanced cirrhosis.

BACKGROUND & AIMS: Pentoxifylline, an inhibitor of tumor necrosis factor-alpha, is given to patients with liver diseases, but its effects in patients with advanced cirrhosis are unknown. We performed a randomized, placebo-controlled, double-blind trial of its effects in patients with cirrhosis. METHODS: A total of 335 patients with cirrhosis (Child-Pugh class C) were assigned to groups given either pentoxifylline (400 mg, orally, 3 times daily; n = 164) or placebo (n = 171) for 6 months. The primary end point was mortality at 2 months. Secondary end points were mortality at 6 months and development of liver-related complications. RESULTS: By 2 months, 28 patients in the pentoxifylline group (16.5%) and 31 in the placebo group (18.2%) had died (P = .84). At 6 months, 50 patients in the pentoxifylline group (30.0%) and 54 in the placebo group (31.5%) had died (P = .75). The proportions of patients without complications (eg, bacterial infection, renal insufficiency, hepatic encephalopathy, or gastrointestinal hemorrhage) were higher in the pentoxifylline group than in the placebo group at 2 months (78.6% vs 63.4%; P = .006) and 6 months (66.8% vs 49.7%; P = .002). The probability of survival without complications was higher in the pentoxifylline group than in the placebo group at 2 and 6 months (P = .04). In multivariate analysis, the factors associated with death were age, the Model for End-Stage Liver Disease score, and presence of early-stage carcinoma. Treatment with pentoxifylline was the only factor associated with liver-related complications. CONCLUSIONS: Although pentoxifylline does not decrease short-term mortality in patients with advanced cirrhosis, it does reduce the risk of complications.

Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis.

BACKGROUND AND AIMS: There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis. METHODS: PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS). RESULTS: 160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib. CONCLUSION: In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib. CLINICAL TRIAL REGISTRATION: The study was referenced in clinicaltrials.gov (NCT01357486).

Large-scale screening of lipase acid deficiency in at risk population.

BACKGROUND: Lysosomal acid lipase deficiency (LALD, OMIM#278000) is a rare lysosomal disorder with an autosomal recessive inheritance. The main clinical manifestations are related to a progressive accumulation of cholesteryl esters, triglycerides or both within the lysosome in different organs such as the liver, spleen, and cardiovascular system. A wide range of clinical severity is associated with LALD including a severe very rare antenatal/neonatal/infantile phenotype named Wolman disease and a late-onset form named cholesteryl ester storage disease (CESD). METHODS: This study aimed to investigate a cohort of at-risk patients (4174) presenting with clinical or biological signs consistent with LALD using the assessment of LAL activity on dried blood spots. RESULTS: LAL activity was lower than 0.05 nmol/punch/L (cut-off: 0.12) in 19 patients including 13 CESD and 6 Wolman. Molecular study has been conducted in 17 patients and succeeded in identifying 34 mutated alleles. Fourteen unique variants have been characterized, 7 of which are novel. CONCLUSION: This study allowed to identify a series of patients and expanded the molecular spectrum knowledge of LALD. Besides, a new screening criteria grid based on the clinical/biological data from our study and the literature has been proposed in order to enhance the diagnosis rate in at risk populations.

Immediate listing for liver transplantation versus standard care for Child-Pugh stage B alcoholic cirrhosis: a randomized trial.

BACKGROUND: Liver transplantation improves survival of patients with end-stage (Child-Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain. OBJECTIVE: To compare the outcomes of patients with Child-Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease. DESIGN: Randomized, controlled trial. SETTING: 13 liver transplantation programs in France. PATIENTS: 120 patients with Child-Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation. INTERVENTIONS: Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients). MEASUREMENTS: Overall and cancer-free survival over 5 years. RESULTS: Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [CI, 2.395 to 24.154]), recovery from Child-Pugh stage C (hazard ratio, 7.633 [CI, 2.392 to 24.390]), and baseline Child-Pugh score less than 8 (hazard ratio, 2.664 [CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care. LIMITATION: Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings. CONCLUSION: Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child-Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer. FUNDING: The French National Program for Clinical Research.

Ten-year experience of transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is considered to be well suited for the treatment of noncirrhotic portal hypertension (NCPHT) because of a usually severe portal hypertension (PHT) and a mild liver failure, but very less data are available. PATIENTS AND METHODS: Records of patients referred for TIPS between 2004 and 2015 for NCPHT were reviewed. No patient should have clinical or biological or histological features of cirrhosis. RESULTS: Twenty-five patients with a wide variety of histological lesions (sinusoidal dilatations, granulomatosis, regenerative nodular hyperplasia, obliterative portal venopathy, or subnormal liver) and a wide variety of associated diseases (thrombophilia, sarcoidosis, common variable immunodeficiency, scleroderma, Castleman's disease, early primitive biliary cirrhosis, congenital liver fibrosis, chemotherapy, purinethol intake, and congenital varices) were included. Two complications occurred during the procedure: one periprosthetic hematoma and the other misposition of a covered stent. During the first month, two other patients had an early thrombosis, another had induced encephalopathy, and one died of early rebleeding. Two of these complications occurred in patients with cavernoma. With a mean follow-up of 39 months, 10 patients experienced at least one episode of spontaneous encephalopathy, with three of these patients requiring a stent reduction. Five patients had a recurrence of their initial symptoms, and one had an asymptomatic hemodynamic dysfunction. CONCLUSION: TIPS is effective in NCPHT but can be technically difficult, especially in the case of cavernoma. Good liver function does not prevent the occurrence of long-term encephalopathy.

Recipient Selection for Optimal Utilization of Discarded Grafts in Liver Transplantation.

BACKGROUND: In France, liver grafts that have been refused by at least 5 teams are considered for rescue allocation (RA), with the choice of the recipient being at the team's discretion. Although this system permits the use of otherwise discarded grafts in a context of organ shortage, outcomes and potential benefits need to be assessed. METHODS: Between 2011 and 2015, outcomes of RA grafts (n = 33) were compared with SA grafts (n = 321) at a single French center. RESULTS: Liver grafts in the RA group were older (63 ± 17 years vs 54 ± 18 years, P = 0.007) and had a higher DRI (1.86 ± 0.45 vs 1.61 ± 0.47, P = 0.010). Recipients in this group had a lower Model for End-Stage Liver Disease score (14 ± 5 vs 22 ± 10, P < 0.001) and had mostly hepatocellular carcinoma (67.0% vs 40.4%, P = 0.010). The balance of risk score was significantly lower in the RA group (5.5 ± 2.9 vs 9.2 ± 5.5, P < 0.001). There were higher rates of early and delayed hepatic artery thrombosis (15.2% vs 3.1%, P = 0.001) and retransplantation (18.2% vs 4.7%, P = 0.002) in the RA group. Patient survival was not different between groups, but graft survival was impaired (95% vs 82% at 1 year and 94% vs 74% at 3 years, P = 0.001). CONCLUSION: Our results show that discarded liver grafts can be used provided that there is a strict recipient selection process, although hepatic artery thrombosis and retransplantation are more frequent. This strategy enables utilization of otherwise discarded grafts in the context of organ shortage.

Does Portopulmonary Hypertension Impede Liver Transplantation in Cirrhotic Patients? A French Multicentric Retrospective Study.

BACKGROUND: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension associated with portal hypertension. Its presence is a major stake for cirrhotic patients requiring liver transplantation (LT), with increased postoperative mortality and unpredictable evolution after transplantation. The aim was to study outcomes after liver transplantation in patients with portopulmonary hypertension and to identify factors associated with normalization of pulmonary hypertension. METHODS: Patients with portopulmonary hypertension who underwent LT between 2008 and 2016 in 8 French centers were retrospectively included. Pulmonary artery pressure was established by right heart catheterization before and after LT. Primary endpoint was the normalization of pulmonary artery pressure after LT. RESULTS: Twenty-three patients who received liver transplant between 2008 and 2016 were included. Two (8.7%) patients died in the immediate posttransplant period from right heart failure. With appropriate vasoactive medical treatment and LT, pulmonary arterial pressure was normalized in 14 patients (60.8%), demonstrating recovery from portopulmonary hypertension. In univariate analysis, the use of vasoactive combination therapy was the only prognostic factor for pulmonary arterial hypertension normalization after LT. CONCLUSIONS: Treatment of portopulmonary hypertension with a combination of vasoactive drugs allows LT with acceptable postoperative cardiovascular-related mortality and normalization of pulmonary hypertension in the majority of the patients.

The epidemiology of Budd-Chiari syndrome in France.

INTRODUCTION: Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France. METHODS: Two approaches were used: (1) A nationwide survey in specialized liver units for French adults. (2) A query of the French database of discharge diagnoses screening to identify incident cases in adults. BCS associated with cancer, alcoholic/viral cirrhosis, or occurring after liver transplantation were classified as secondary. RESULTS: Approach (1) 178 primary BCS were identified (prevalence 4.04 per million inhabitants (pmi)), of which 30 were incident (incidence 0.68 pmi). Mean age was 40 ±â€¯14 yrs. Risk factors included myeloproliferative neoplasms (MPN) (48%), oral contraceptives (35%) and factor V Leiden (16%). None were identified in 21% of patients, ≥2 risk factors in 25%. BMI was higher in the group without any risk factor (25.7 kg/m2 vs 23.7 kg/m2, p < 0.001). Approach (2) 110 incident primary BCS were admitted to French hospitals (incidence 2.17 pmi). MPN was less common (30%) and inflammatory local factors predominated (39%). CONCLUSION: The entity of primary BCS as recorded in French liver units is 3 times less common than the entity recorded as nonmalignant hepatic vein obstruction in the hospital discharge database. The former entity is mostly related to MPN whereas the latter with abdominal inflammatory diseases.

Evaluation of Doppler-ultrasonography in the diagnosis of transjugular intrahepatic portosystemic shunt dysfunction: A prospective study.

AIM: To prospectively evaluate the performance of Doppler-ultrasonography (US) for the detection of transjugular intrahepatic portosystemic shunt (TIPS) dysfunction within a multicenter cohort of cirrhotic patients. METHODS: This study was conducted in 10 french teaching hospitals. After TIPS insertion, angiography and liver Doppler-US were carried out every six months to detect dysfunction (defined by a portosystemic gradient ≥ 12 mmHg and/or a stent stenosis ≥ 50%). The association between ultrasonographic signs and dysfunction was studied by logistic random-effects models, and the diagnostic performance of each Doppler criterion was estimated by the bootstrap method. This study was approved by the ethics committee of Tours. RESULTS: Two hundred and eighteen pairs of examinations performed on 87 cirrhotic patients were analyzed. Variables significantly associated with dysfunction were: The speed of flow in the portal vein (P = 0.008), the reversal of flow in the right (P = 0.038) and left (P = 0.049) portal branch, the loss of modulation of portal flow by the right atrium (P = 0.0005), ascites (P = 0.001) and the overall impression of the operator (P = 0.0001). The diagnostic performances of these variables were low; sensitivity was < 58% and negative predictive value was < 73%. Therefore, dysfunction cannot be ruled out from Doppler-US. CONCLUSION: The performance of Doppler-US for the detection of TIPS dysfunction is poor compared to angiography. New tools are needed to improve diagnosis of TIPS dysfunction.

Transjugular intrahepatic portosystemic shunt for the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal hepatic fibrosis.

Non-cirrhotic perisinusoidal hepatic fibrosis is a process of imprecise pathogenesis involving collagenization of the space of Disse. Exposure to chemicals, auto-immunity, thrombophilia and/or infections are suspected primary agents. Here, we present the case of a patient who developed severe portal hypertension with histological features suggesting a non-cirrhotic perisinusoidal hepatic fibrosis. A 52-year-old man was hospitalized for oesophageal variceal haemorrhage. Liver cirrhosis or portal vein thrombosis were absent as attested by laboratory tests, duplex sonography, computed tomography scan and histological examination of a liver biopsy specimen. Presinusoidal portal hypertension was suggested by a normal wedge-free hepatic vein gradient. Only electron microscopy examination of a liver biopsy specimen could disclose perisinusoidal fibrosis. This was most probably secondary to a combined chemotherapy received 4 years earlier for non-Hodgkin large-cell lymphoma. As variceal ligation failed to control oesophageal varices while liver function tests were normal, a transjugular intrahepatic portosystemic shunt (TIPS) was performed. This dramatically improved the signs of portal hypertension. This case illustrates the use of TIPS in the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal fibrosis.

Transjugular preoperative portal embolization (TJPE) a pilot study.

BACKGROUND/AIMS: Because of our previous experience with transjugular intrahepatic portosystemic shunt, we decided to apply the transjugular approach to preoperative portal embolization. The aim of this pilot study was to determine the feasibility and the potential advantages and disadvantages of this new method. METHODOLOGY: Under ultrasound guidance the right or left portal branch was punctured from the right, median or left hepatic vein. Then, a catheter was placed near the portal bifurcation and used to perform right portal branch embolization with a mixture of Histoacryl and Lipiodol. Pre- and post-transjugular preoperative portal embolization duplex ultrasound and CT scan were performed to assess portal flow and liver tissue growth. Hospital stay, pain and hepatic enzymes were monitored. RESULTS: Fifteen patients underwent a transjugular preoperative portal embolization without any serious complication. Mean of hospital stay was 3.3 +/- 0.6 days. (2-5 days). Portal embolization was successful in all cases; left portal branch velocity increased from 11.8 +/- 7.5 cm/s before, to 16.5 +/- 3.5 cm/s on day one, and 14.8 +/- 3.3 cm/s on day 28 after transjugular preoperative portal embolization; volume of non-embolized segments increased by 10% within the 4 weeks after transjugular preoperative portal embolization. Right hepatectomy was possible in 12 patients CONCLUSIONS: This method is safe, painless, and can be proposed in cases of impossibility to perform the standard percutaneous transhepatic portal embolization (tumor interposition, impaired hemostasis).

Predictive factors of alcohol relapse after orthotopic liver transplantation for alcoholic liver disease.

OBJECTIVES: The objective of this prospective study was to determine whether sociological and/or alcohol-related behavioral factors could be predictive of relapse after orthotopic liver transplantation for alcoholic liver disease. METHODS: Fifty-five liver-transplanted patients out of a series of 120 alcoholic cirrhotic patients were enrolled in a randomized prospective study. This study was initially designed to compare the 2 year survival in intent-to-transplant patients versus in-intent-to-use conventional treatment patients. For all patients, an identical questionnaire was completed at inclusion, and every 3 months for 5 years to collect data on alcohol-related behavior factors. RESULTS: Fifty-one patients fulfilled the criteria for the study. The mean follow-up was 35.7 months (range: 1-86). Rate of alcohol relapse was 11% at one year and 30% at 2 years. Alcohol intake above 140 g a week was declared by 11% and 22% of patients at one and 2 years, respectively. The only variable leading to a significantly lower rate of relapse was abstinence for 6 months or more before liver transplantation (23% vs 79%, P=0.0003). This variable was also significant for patients whose alcohol intake was greater than 140 g per week (P=0.003) (adjusted relative risk=5.5; 95%CI=1.3-24.5; P=0.02). Multivariate analysis (Cox model) showed that abstinence for 6 months or more before liver transplantation was the unique predictive variable. CONCLUSION: In this prospective study of 51 patients transplanted for alcoholic liver disease, abstinence before liver transplantation was the only predictive factor of alcohol relapse after liver transplantation.

Pregnancies after transjugular intrahepatic portosystemic shunt for noncirrhotic portal hypertension.

With the growing role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension complications, a number of women of childbearing age are now being treated with TIPS. However, if pregnancy is unusual in patients with cirrhosis, it can occur in the case of noncirrhotic portal hypertension. To our knowledge, there are no data on pregnancy safety after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies. She presented with HIV-associated obliterative portopathy with recurrent variceal bleeding treated by TIPS. Pregnancies occurred later and progressed normally without maternal or fetal morbidity. There was no effect on TIPS patency, but only a moderate increase in the flow velocity in the portal vein, the stent, and the hepatic artery. Thus, TIPS does not seem to impair progression of pregnancy.

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

BACKGROUND AND AIMS: Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. METHODS: We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. RESULTS: Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. CONCLUSION: Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances.

Feasibility and long-term evolution of TIPS in cirrhotic patients with portal thrombosis.

AIM: Many researchers consider portal thrombosis (PT) as a contraindication to transjugular intrahepatic portosystemic shunt (TIPS). The aim of this retrospective study was to compare the feasibility and long-term prognosis of TIPS in cirrhotic patients, with and without, complete PT. PATIENTS AND METHODS: Four hundred and thirty-six consecutive cirrhotic patients with portal hypertension were referred for TIPS, between 1990 and 2004. These patients were divided into two groups according to their portal patency. PT+: 34 patients with complete PT with cavernoma (19) or without (15) cavernoma versus PT-: 402 patients with normal portal patency (308) and partial PT (94). Epidemiological data were compared using the chi and Student's t-tests, and comparative evolution was made from actuarial data using the log-rank test. RESULTS: PT+ patients were more frequently women with viral hepatitis, and TIPS was performed more often for bleeding indications. The TIPS success rate was significantly lower in the PT+ group (79%) than in the PT- group (99.5%) (P<10). Presence of a cavernoma decreased the success rate to 63%. TIPS was always feasible in cases of recent PT and portal cavernoma with an accessible intrahepatic patent portal branch. Early and late outcome and complications were not significantly different between the two groups. CONCLUSION: Complete PT does not modify TIPS' long-term outcome. Rather than a contraindication, PT should be considered as an indication for TIPS in cirrhotic patients with accessible intrahepatic portal vein. Further randomized studies should be planned in cirrhotic patients with recent PT to better qualify TIPS and anticoagulation indications, respectively.