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.

Severe liver failure rather than cirrhosis is associated with mortality in patients with infectious endocarditis: a retrospective case-control study.

BACKGROUND: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC. PATIENTS AND METHODS: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013. RESULTS: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P<0.001), but not for Child-Pugh A (33.3%) or B patients (25.0%). A Child-Pugh score of above C10 was the best predictor of in-hospital mortality. In LC, Child-Pugh score (odds ratio=1.5; 95% confidence interval: 1.2-2.0; P=0.002) and history of decompensation (odds ratio=3.1; 95% confidence interval: 1.1-9.0; P=0.003) were independent predictive factors for in-hospital mortality. CONCLUSION: Severe liver failure but not cirrhosis is the strongest predictive factor of mortality related to IE in LC. Use of aminosides and rifamycin should be reassessed in LC, and cardiac surgery should be considered for selected patients.

Cardiovascular events in chronic hepatitis C: prognostic value of liver stiffness evolution.

BACKGROUND AND AIMS: Chronic hepatitis C is also a metabolic disease that may increase cardiovascular events. FibroScan is a diagnostic tool for fibrosis and a prognostic tool for cirrhosis complications and mortality. The aim of our study was to investigate the prognostic value of liver stiffness evolution and initial stiffness in cardiovascular events occurring in patients with chronic hepatitis C. PATIENTS AND METHODS: Between 2006 and 2013, chronic hepatitis C patients followed in a reference center with two valid liver stiffness measurements by FibroScan were included. Cardiovascular events occurring after the initial FibroScan were collected retrospectively. 'Rapid stiffness progression' was defined as an evolution of at least 0.3 kPa/year and 'high initial stiffness' as at least 7 kPa. RESULTS: Among 561 patients with chronic hepatitis C, 135 were included, mean follow-up 5.2 years, 56% men, mean age 55.3 years, infected with genotype 1 (71%). Among these, 27 were overweight, 12 had type 2 diabetes, 41 had steatosis, and 89 had been treated. During follow-up, seven patients had a cardiovascular event (four myocardial infarctions, three strokes). Among the 35 patients with rapid stiffness progression, 6% had a cardiovascular event compared with 5% of 100 patients with slow progression (P=1.0). Among the 57 patients with high initial stiffness, 11% had a cardiovascular event compared with 1% of the 78 patients with low initial stiffness (P=0.04). CONCLUSION: In chronic hepatitis C, initial stiffness of at least 7 kPa was associated with cardiovascular events. Rapid progression of liver stiffness does not seem to be associated with these events.

High plasma levels of the pro-inflammatory cytokine IL-22 and the anti-inflammatory cytokines IL-10 and IL-1ra in acute pancreatitis.

BACKGROUND/OBJECTIVES: Pancreatic acinar cells are major targets of IL-22. Our aim is to study early plasma levels of IL-22, of pro- and anti-inflammatory cytokines in acute pancreatitis, and their association with severity or necrosis infection. METHODS: Consecutive patients admitted to the Department of Hepato-Gastroenterology at Poitiers University of Medicine Hospital (France) with a diagnosis of AP were prospectively enrolled. Plasma concentrations of IL-22, IL-6, IL-8, IL-1 α, IL-1ß, TNF- α, IFN-γ, IL-17A, IL-10, IL-1ra and IL-4 were assessed by multiple immunoassay at the admission time. A thoracoabdominal contrast-enhanced CT scan was performed at day 2. RESULTS: Sixty-two patients were included; 13 patients (21%) had a severe acute pancreatitis, 5 patients (8%) developed necrosis infection and 29 patients (47%) had pleural effusion. Plasma levels of IL-22 were high in AP (135 ± 31 vs 4.2 ± 1.8 pg/ml for controls, p < 0.05), but did not correlate with the severity of the disease, whereas IL-6, IL-10 and IL-1ra where enhanced in patients with severe acute pancreatitis and with pleural effusion. Patients who further developed necrosis infection had higher levels of IL-1ra at admission (p = 0.0004). CONCLUSION: In acute pancreatitis, high plasma levels of IL-22 are observed, regardless the severity of the disease. In contrast, severe forms were associated with increased levels of IL-6, IL-10 and IL-1ra. The beneficial or deleterious role of IL-22 in AP remains to be further studied.

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.

Atherosclerosis risk in HIV-infected patients: the influence of hepatitis C virus co-infection.

BACKGROUND: The influence of hepatitis C virus (HCV) infection on atherosclerosis risk in HIV-infected patients has not been adequately evaluated in real-life situations. OBJECTIVES AND METHODS: We compared indexes of early atherosclerosis evaluated by echo-Doppler ultrasound (presence of plaque in carotid or femoral arteries) in 18 HCV-HIV co-infected patients versus 22 HIV mono-infected patients. RESULTS: Prevalence of subclinical carotid plaque was significantly higher in HCV-HIV co-infected patients (p=0.04), despite of the fact LDL-cholesterol and blood pressure (BP) were lower in the co-infected patients (p=0.003). HCV chronic infection (OR=10; IC: 1.5-72; p=0.02) was an independent risk factor. CONCLUSION: This cross sectional study suggests that HCV infection might be an independent cardiovascular risk factor in HCV-HIV co-infected patients. HCV infection might be considered as not only a liver infection but also as a metabolic disease in HIV patients, justifying regular cardiovascular surveillance.

Serum bilirubin and platelet count: a simple predictive model for survival in patients with refractory ascites treated by TIPS.

BACKGROUND & AIMS: Refractory ascites in patients with cirrhosis is associated with poor survival. TIPS is more effective than paracentesis for the prevention of recurrence of ascites but increases the risk of encephalopathy while survival remains unchanged. A more accurate selection of the patients might improve these results. The aim of the present study was to identify parameters of prognostic value for survival in patients with refractory ascites treated with TIPS. METHODS: One hundred and five consecutive French patients with cirrhosis and refractory ascites treated with TIPS were used to assess parameters associated with 1-year survival. The model was then tested in two different cohorts: a local and prospective one including 40 patients from Toulouse, France, and an external one including 48 patients from Barcelona, Spain. RESULTS: The actuarial rate of survival in the first 105 patients was 60% at 1 year. Using multivariate analysis, only lower bilirubin levels and higher platelet counts were independently associated with survival. The actuarial 1-year survival rate in patients with both a platelet count above 75×10(9)/L and a bilirubin level lower than 50 µmol/L [3mg/dl] was 73.1% as compared to 31.2%, in patients with a platelet count below 75×10(9)/L or a bilirubin level higher than 50 µmol/L. These results were confirmed in the two different validation cohorts. CONCLUSIONS: The combination of a bilirubin level below 50 µmol/L and a platelet count above 75×10(9)/L is predictive of survival in patients with refractory ascites treated with TIPS. This simple score could be used at bedside to help choose the best therapeutic options.

Short-term and long-term vital outcomes of cirrhotic patients admitted to an intensive care unit.

OBJECTIVE: To evaluate short-term and long-term vital outcomes of cirrhotic patients admitted to a general ICU, to evaluate the prognostic value of severity scores and to identify risk factors associated with death. METHODS: Observational retrospective single-center epidemiological study. All cirrhotic patients admitted to the ICU were eligible for the study. Clinical data, general ICU severity scores, and liver-specific severity scores were recorded. The mortality rate was analyzed during the stay in ICU, at day 28 and month 6 after admission. Risk factors for death were identified by univariate and multivariate analyses. RESULTS: During the study period, 86 cirrhotic patients were admitted to the ICU. The in-ICU, day-28 and month-6 mortality rates were 37, 48, and 60%, respectively. In the multivariate analysis, mechanical ventilation, the prothrombin time, and the plasma albumin level on admission were associated with the in-ICU mortality, whereas only the plasma albumin level was associated with the 6-month mortality [odds ratio 0.80; 95% confidence interval (0.70-0.92)]. The Sequential Organ Failure Assessment score was more predictive than liver-specific scores for mortality in the ICU, but not at day 28 or month 6. CONCLUSION: ICU admission should not be ruled out for patients with complicated cirrhosis. Although common in cirrhotic patients, low plasma albumin level was the only factor independently associated with short-term and long-term mortalities.

Prognostic indices for Budd-Chiari syndrome: valid for clinical studies but insufficient for individual management.

OBJECTIVES: Several prognostic indices (PIs) have been proposed for Budd-Chiari syndrome (BCS). However, patient characteristics, causal factors, and treatment outcomes have changed since these indices have been elaborated. Validation in a recent patient population and comparison of predictive accuracy between these PIs are needed. METHODS: A database of 96 BCS patients diagnosed between 1995 and 2005 was analyzed. Cox survival models were fitted with time to liver transplantation or death, and time to invasive therapy or death, as end points. The prognostic values of known indices (Child-Pugh score, model for end-stage liver disease (MELD), Clichy, Rotterdam BCS index, New Clichy, and BCS-TIPS (transjugular intrahepatic portosystemic shunt)) at diagnosis were assessed in Cox models using the chi-square test, the Kent and O'Quigley measure of dependence, and unrestricted bootstrapping analysis. Areas under receiver operating characteristic curves (AUROCs) were built for both end points and compared. RESULTS: All prognostic indices, except BCS-TIPS, were significant predictors of transplant-free and invasive therapy-free survival. However, only 31 and 37% of the variance in transplant-free and invasive therapy-free survival, respectively, were explained by the best performing indices. For transplant-free survival, AUROCs were < 0.70. For invasive therapy-free survival, AUROCs were < 0.80. For both end points, BCS-TIPS PI AUROCs were significantly lower than others. CONCLUSIONS: Most PIs are valid for transplant-free survival and invasive therapy-free survival in a population of current BCS patients, and thus can be used for stratification in clinical studies. However, predictive accuracy is insufficient to be used for individual patients.

Gender differences in vascular reactivity of aortas from rats with and without portal hypertension.

BACKGROUND: Inflammatory responses related to portal hypertension may be different in male and female rats. Most experimental studies of portal hypertension have involved male animals, and little information is available on gender differences in this setting. The aim of the present study was to compare aortic reactivity in female and male rats with and without portal hypertension. METHODS: Contraction response curves to phenylephrine were studied with aortic rings, with and without endothelium. For relaxation studies, rings were precontracted with phenylephrine 10(-7) mol/L and then exposed to acetylcholine 10(-4) mol/L. Portal hypertension was provoked by calibrated portal stenosis performed 2 weeks before experiments. RESULTS: In non-hypertensive conditions, the contractile response to increasing phenylephrine concentrations was significantly stronger in rings from male than female rats, both with and without endothelium. In male rats with portal hypertension, the phenylephrine concentration-response curves were lowered and shifted to the right in aortic rings both with and without endothelium. In female rats, portal hypertension did not induce significant changes in the phenylephrine concentration-response curves. In female rats, portal hypertension induced a marked increase in relaxation (157 +/- 123% vs 81 +/- 64% in controls); the increase was also stronger than that in male rats with portal hypertension (95 +/- 6%; P < 0.01). CONCLUSION: Clear gender differences were observed in vasoconstrictor responsiveness of aortic rings from rats with and without portal hypertension. Contrary that in male rats, portal hypertension did not induce vascular hyporesponsiveness in female rats. Further investigations are required to explain these differences.