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Patients with acute-on-chronic liver failure (ACLF) have a devastating prognosis and therapeutic options are limited. Granulocyte-colony stimulating factor (G-CSF) mobilizes immune and stem cells and possess immune-modulatory and proregenerative capacities. In this review, we aim to define the current evidence for the treatment with G-CSF in end-stage liver disease. Several smaller clinical trials in patients with different severity grades of end-stage liver disease have shown that G-CSF improves survival and reduces the rate of complications. Adequately powered multicenter European trials could not confirm these beneficial effects. In mouse models of ACLF, G-CSF increased the toll-like receptor (TLR)-mediated inflammatory response which led to an increase in mortality. Adding a TLR4 signaling inhibitor allowed G-CSF to unfold its proregenerative properties in these ACLF models. These data suggest that G-CSF requires a noninflammatory environment to exert its protective properties.

First reported in 1976, hepatic angiomyolipoma (HAML) is a rare mesenchymal liver tumor occurring mostly in middle-aged women. Diagnosis of the liver mass is often incidental on abdominal imaging due to the frequent absence of specific symptoms. Nearly 10% of HAMLs are associated with tuberous sclerosis complex. HAML contains variable proportions of blood vessels, smooth muscle cells and adipose tissue, which renders radiological diagnosis hazardous. Cells express positivity for HMB-45 and actin, thus these tumors are integrated into the group of perivascular epithelioid cell tumors. Typically, a HAML appears on magnetic resonance imaging (or computed tomography scan) as a hypervascular solid tumor with fatty areas and with washout, and can easily be misdiagnosed as other liver tumors, particularly hepatocellular carcinoma. The therapeutic strategy is not clearly defined, but surgical resection is indicated for symptomatic patients, for tumors showing an aggressive pattern (i.e., changes in size on imaging or high proliferation activity and atypical epithelioid pattern on liver biopsy), for large (> 5 cm) biopsy-proven HAML, and if doubts remain on imaging or histology. Conservative management may be justified in other conditions, since most cases follow a benign clinical course. In summary, the correct diagnosis of HAML is challenging on imaging and relies mainly on pathological findings.

The management of inflammatory rheumatic diseases has substantially changed in recent years, as has the profile of patients. The advent of biotherapies has been a revolution in rheumatology and the impact of co-morbidities in the management of these patients is now becoming increasingly important. Metabolic syndrome (MetS) is one of the most frequent comorbidities, and hepatic complications of MetS are not uncommon. MetS is responsible for Non-alcoholic fatty liver disease (NAFLD), characterized by excessive hepatic fat accumulation. In extreme cases, progression to cirrhosis is possible. NAFLD ranks among the top three indications for liver transplantation. We review available data on the safety, especially the risk of infections, of TNF inhibitors (TNFi) in case of NAFLD and in case of liver cirrhosis, in patients with rheumatic disease. In cases of NAFLD without severe fibrosis, available data are reassuring and tend to show a beneficial effect of TNFi on hepatic tissue. In case of cirrhosis, data are conflicting. Further large, well-designed studies are needed to explore this specific issue.

International audience; 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.

BACKGROUND: In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. AIM: To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. METHODS: Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. RESULTS: Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7 months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases

Purpose To describe the computed tomography (CT) and magnetic resonance imaging (MRI) features of severe acute alcoholic hepatitis (SAAH) and estimate the capabilities of CT and MRI in differentiating SAAH from alcoholic cirrhosis and non-alcoholic steato-hepatitis (NASH) cirrhosis. Materials and methods Fifty patients with pathologically proven SAAH (SAAH group) who underwent CT or MRI examinations up to 30 days before or 15 days after liver biopsy between January 2008 and June 2018 were retrospectively included. There were 31 men and 29 women with a mean age of 52 ± 9 (SD) years (range: 33–67 years). Imaging features of the SAAH group were compared to those obtained in two control groups including 62 patients with alcoholic cirrhosis without acute alcoholic hepatitis (control group 1) and 19 patients with NASH cirrhosis (control group 2) by two independent radiologists blinded to the final diagnosis. Univariate analyses were performed to compare imaging characteristics between the three groups, followed by diagnostic performance analysis for the diagnosis of SAAH of the main CT features. Results Heterogeneous steatosis was significantly more frequent in SAAH group than in the control groups (41/50; 82% vs. 7/62; 10% and 1/19; 5% in control groups 1 and 2, respectively for reader 1 and 34/50; 68% vs. 8/62; 13% and 1/19; 5% in control groups 1 and 2, respectively for reader 2; both P = 0.01). Transient perfusion disorders were more frequent in SAAH group than in the control groups (35/50; 70% vs. 12/62; 21% and 5/19; 26% in control groups 1 and 2, respectively for reader 1 and 39/50; 78% vs. 14/62; 23% and 13/19; 6% in control groups 1 and 2, respectively for reader 2; both P = 0.01). The combination of these two findings yielded 100% specificity (45/45; 95% CI: 92–100) for readers 1 and 2 for the diagnosis of SAAH vs. alcoholic cirrhosis and NASH cirrhosis. Conclusion The imaging features of SAAH are specific and mainly associate transient heterogeneous steatosis and liver perfusion disorders. CT/MRI may be useful to differentiate SAAH from alcoholic cirrhosis and NASH cirrhosis.

The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.

Summary Background and aims The reported hepatotoxicity of methotrexate underlines the need for a repeated non-invasive and reliable evaluation of liver fibrosis. We estimated, using a non-invasive strategy, the prevalence of significant liver fibrosis in patients treated by methotrexate and the predictors of significant fibrosis (fibrosis ≥ F2). Methods Fibrosis was prospectively evaluated using 9 non-invasive tests in consecutive patients with psoriasis, rheumatoid arthritis, or Crohn's disease. Significant fibrosis was assessed without liver biopsy by defining a “specific method” (result given by the majority of the tests) and a “sensitive method” (at least one test indicating a stage ≥ F2). Results One hundred and thirty-one patients (66 Psoriasis, 40 rheumatoid arthritis, and 25 Crohn's disease) were enrolled, including 83 receiving methotrexate. Seven tests were performed on average per patient, with a complete concordance in 75% of cases. Fibroscan® was interpretable in only 61% of patients. The best performances (AUROC > 0.9) for predicting significant fibrosis were obtained by tests dedicated to steatohepatitis (FibroMeter NAFLD, NFS and FPI). The prevalence of fibrosis ≥ F2 according to the “specific” or the “sensitive” assessment of fibrosis was 10% and 28%, respectively. Methotrexate exposure did not influence the fibrosis stage. Factors independently associated with significant fibrosis according our “sensitive method” were age, male gender, and metabolic syndrome. Conclusion We provided a non-invasive approach for identifying liver fibrosis ≥ F2 by using 8 biochemical tests and Fibroscan®. In this population, the risk of significant fibrosis was related to age, male gender, and presence of metabolic syndrome, but was not influenced by methotrexate.

IF 4.5; International audience; Background & AimsThe quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3‐hydroxymyristate (3‐HM), a lipid component of LPS, and to evaluate correlations between 3‐HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage.MethodsPlasma from 90 noninfected cirrhotic patients (30 Child‐Pugh [CP]‐A, 30 CP‐B, 30 CP‐C) was prospectively collected. The concentration of 3‐HM was determined by high‐performance liquid chromatography coupled with mass spectrometry.Results3‐HM levels were higher in CP‐C patients (CP‐A/CP‐B/CP‐C: 68/70/103 ng/mL, P = 0.005). Patients with severe acute alcoholic hepatitis (n = 16; 113 vs 74 ng/mL, P = 0.012), diabetic patients (n = 22; 99 vs 70 ng/mL, P = 0.028) and those not receiving beta blockers (n = 44; 98 vs 72 ng/mL, P = 0.034) had higher levels of 3‐HM. We observed a trend towards higher baseline levels of 3‐HM in patients with hepatic encephalopathy (n = 7; 144 vs 76 ng/mL, P = 0.45) or SIRS (n = 10; 106 vs 75 ng/mL, P = 0.114). In multivariate analysis, high levels of 3‐HM were associated with CP (OR = 4.39; 95%CI = 1.79‐10.76) or MELD (OR = 8.24; 95%CI = 3.19‐21.32) scores. Patients dying from liver insufficiency (n = 6) during a 12‐month follow‐up had higher baseline levels of 3‐HM (106 vs 75 ng/mL, P = 0.089).ConclusionsIn noninfected cirrhotic patients, 3‐HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3‐HM appears reliable to detect transient endotoxaemia and promising to manage the follow‐up of cirrhotic patients.

Introduction Microvesicles (MVs) with procoagulant properties may favor liver parenchymal extinction, then cirrhosis-related complications and mortality. In a longitudinal cohort of cirrhotic patients, we measured plasma levels of platelet-derived MVs (PMVs), endothelial-derived MVs, and red blood cell-derived MVs, expressing phosphatidylserine (annexin V-positive [AV+]) or not, and evaluated their impact on Model for End-Stage Liver Disease (MELD) score and transplant-free survival. Methods MVs were quantified using flow cytometry in plasma from 90 noninfected cirrhotic patients and 10 healthy volunteers matched for age and sex. Impact of plasma microvesicle levels on 6-month transplant-free survival was assessed using log-rank tests and logistic regression. Results Microvesicle levels, mostly platelet-derived, were 2.5-fold higher in healthy volunteers compared with cirrhotic patients. Circulating small AV+ PMV levels were lower in cirrhotic patients (P = 0.014) and inversely correlated with MELD scores (R = -0.28; P = 0.0065). During 1-year follow-up, 8 patients died and 7 underwent liver transplantation. In the remaining patients, circulating microvesicle levels did not change significantly. Six-month transplant-free survival was lower in patients with low baseline small AV+ PMV levels (72.6% vs 96.2%; P = 0.0007). In multivariate analyses adjusted for age, ascites, esophageal varices, encephalopathy, clinical decompensation, total platelet counts, MELD score, and/or Child-Pugh C stage, patients with lower small AV+ PMV levels had a significant 5- to 8-fold higher risk of 6-month death or liver transplant. Other PMV levels did not impact on survival. Discussion Decreased circulating small AV+ PMV levels are associated with significantly lower transplant-free survival in cirrhotic patients independently of MELD score and platelet counts.

Biliary complications represent a turning point in the course of Alveolar Echinococcosis (AE). We conducted a European survey to collect data on the current usage and results of perendoscopic interventions (PEIs) for their treatment.Patient's characteristics and follow-up until January 31st, 2015 were recorded using an online questionnaire.From 18 centers 129 PEIs were analyzed in 38 patients; 139 plastic stents were inserted during 85 PEIs; median time between stent placements was significantly longer when 3 stents or more were placed. Initial symptoms disappeared in 95% and long-term bile duct patency was obtained in 73% of cases. Cholangitis was a more frequent complication of the PEIs (10%) than in other indications; intensive lavage of the bile ducts may prevent this complication.European centers use perendoscopic biliary drainage as an efficient and safe alternative to surgery to treat AE biliary complications. Insertion of multiple plastic stents delays stent occlusion and leads to effective and prolonged bile duct patency.

Background/aims The variations in C-reactive protein (CRP) levels have been reported to have prognostic significance in decompensated cirrhotic patients. We aimed to provide an external validation of a prognostic model combining model for end-stage liver disease (MELD) and 'sustained high CRP levels' as main variables and to optimize the model to the context of liver transplantation by focusing on 3-month mortality with no consideration of severe chronic extrahepatic diseases. Patients and methods Data from cirrhotic patients enrolled in the CANONIC study were collected. Multivariate analyses used the competing risk model. The prognostic performance [area under receiver operating characteristic curve (AUROC)] of the model incorporating CRP variations within 15 days was compared with that of the MELD score alone. Results 583 decompensated cirrhotic patients with Child-Pugh more than B7 and serial CRP measures available were included. Of these, 111 patients had baseline CRP at least 29 mg/l and 60 still had CRP at least 29 mg/l at day 15 +/- 6 (group A). Multivariate analysis (competing risk) identified three predictors of 3-month mortality: high MELD score [hazard ratio (HR) = 1.14; 95% confidence intervals (CI): 1.11-1.17, P

International audience; 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

Background & aims Copeptin is a stable cleavage product of the arginine vasopressin (AVP) precursor and is equimolarly secreted with AVP. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. We aimed to investigate the association between severity of cirrhosis and copeptin concentrations and to confirm whether copeptin is of prognostic significance in cirrhosis. Methods One hundred and eighty-four cirrhotic patients hospitalized in two tertiary referral centres were studied. Serum copeptin was measured in samples obtained at hospital admission. Differences in serum copeptin between Child-Pugh classes were evaluated using the Kruskal-Wallis test. Cox proportional hazard regression and Kaplan-Meier analyses were performed to evaluate associations of copeptin and other possible prognostic factors with 6- and 12-month mortality. Results Median serum copeptin (interquartile range) increased significantly through Child-Pugh classes A [5.4 (3.1-10.7) pmol/L], B [9.6 (6.0-17.3) pmol/L] and C [13.8 (5.8-34.1) pmol/L, P 12.3 pmol/L displayed significantly higher mortality rates at 6 and 12 months as compared to those with serum copeptin ≤12.3 pmol/L (Log-rank test: P 12.3 pmol/L was significantly associated with mortality, particularly at 6 months, independently of age, clinical parameters and Model for End stage Liver Disease (MELD), MELD-sodium and Child-Pugh score. Conclusions Serum copeptin concentration increases significantly along with the severity of cirrhosis as defined by the Child-Pugh classification. A high serum copeptin concentration predicts survival, particularly at 6 months, independently of liver-specific scoring systems in a heterogeneous population of hospitalized cirrhotic patients.

Introduction The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists. Methods All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations. Results Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax. Conclusions In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

Hormonal factors, like oral contraceptives, create a predisposition to hepatocellular adenoma. We present the case of a young woman with an inflammatory hepatocellular adenoma occurring in the context of a polycystic ovary syndrome. In view of this possible relationship, it would be recommended to follow up patients with hyperandrogenism with repeated liver tests and ultrasonographics. Furthermore, this observation illustrated some difficulties to differentiate remodelled inflammatory hepatocellular adenoma and focal nodular hyperplasia and underlined the interest of immunohistochemical markers for the right diagnosis.

Copeptin, secreted stoichiometrically with vasopressin, demonstrated its prognostic role in various diseases other than cirrhosis.We investigated the association between severity of cirrhosis and plasma concentrations of copeptin, and the prognostic value of copeptin in 95 non-septic cirrhotic patients (34 Child-Pugh A, 29 CP-B, 32 CP-C), 30 septic patients with a Child-Pugh8 ('group D'), and 16 healthy volunteers. Patients were followed for at least 12 months to assess the composite endpoint death/liver transplantation.Median copeptin concentrations (interquartile range) increased through healthy volunteers group [5.95 (3.76-9.43) pmol/L] and 'group D' patients [18.81 (8.96-36.66) pmol/L; P0.001)]. During a median follow-up of 11.0 ± 6.1 months, 28 non-transplanted patients died and eight were transplanted. In receiver operated characteristic curves analysis, the area under the curve values were as follows: Child-Pugh score 0.80 (95% CI: 0.71-0.86), model of end-stage liver disease (MELD) score 0.80 (0.70-0.86), C-reactive protein (CRP) 0.71 (0.60-0.80) and copeptin 0.70 (0.57-0.79). By stratifying the values of these variables into tertiles, the risk of death/liver transplantation for patients belonging to the highest tertile of copeptin (13 pmol/L) was high (Log-rank test: P = 0.0002) and 2.3-fold higher than for patients with lower concentrations after adjusting for MELD score (21) and CRP (24 mg/L) in a Cox model. Other potential predictors (age, total cholesterol, natraemia and serum free cortisol) did not reach a significant level.In cirrhotic patients, copeptin concentrations increased along with the severity of liver disease. In our cohort, the 1-year mortality or liver transplantation was predicted by high MELD score and high concentrations of CRP and copeptin.

Summary Background Guidelines recommend antibiotic prophylaxis (AP) in well-selected groups of cirrhotic patients, but the impact of these recommendations has not been assessed in France. Aim To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP). Methods Practitioners (n = 1,159) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire. Results Three hundred and eighty-nine (33.6%; GH 35% and UH 30.4%) practitioners responded. AP was prescribed by 97.7%, 72.3% and 94.8% of practitioners, without significant differences between UH and GH, respectively, for gastrointestinal bleeding (quinolones 48.2%, third-generation cephalosporins 27.7% and amoxicillin-clavulanic acid 22.2%), primary (quinolones 97.2%) and secondary prophylaxis of SBP (quinolones 99%). For gastrointestinal bleeding, ofloxacin (47.6%) and norfloxacin (37.4%) were the main quinolones prescribed, and ceftriaxone (77%) was the main third-generation cephalosporin prescribed. The principal reasons for prescribing AP were a decrease in bacterial infection (88.9% for gastrointestinal bleeding, 91.3% for primary and 94.3% for secondary prophylaxis of SBP), a recommendation by a consensus conference (83%, 38% and 74.4% respectively) and an improvement in survival (72.8%, 41.3% and 57.7% respectively). Only 31.7% of practitioners (39.6% for UH vs. 28.6% for GH; P = 0.038) believed that AP may reduce the risk of bleeding recurrence. Reported side effects (28%) of AP mainly concerned the risk of quinolone resistance (62% of cases). Conclusion Antibiotic prophylaxis is well-recognized by French practitioners, but its routine use depends on the expertise of practitioners. Quinolones remain the main antibiotic class prescribed irrespective of the type of prophylaxis.

Hydrothorax liver is defined by the presence of pleural effusion greater than 500mL secondary to portal hypertension in cirrhotic patients. Poor tolerance of hepatic hydrothorax makes the therapeutic management of these fragile patients and is associated with iatrogenic complications. The mechanism of hydrothorax formation cirrhosis is due to a unidirectional transfer of the abdominal ascites through the diaphragmatic gaps (that were identified macroscopically and microscopically) in the pleural cavity. The treatment of hepatic hydrothorax is determined by the possibility or not of liver transplantation. In some patients, anastomosis portocaval transjugular (TIPS) may however be sufficient.

International audience; BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices.METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire.RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: β-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; PCONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies.

International audience; OBJECTIVES: We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm(3). Ascites not related to portal hypertension were excluded. RESULTS: Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P

This population-based study aimed to assess thedeterminants of the outcome of chronic hepatitis C withanalysis of the impact of antiviral therapy with or withoutsustained virological response (SVR) on cirrhosis decom-pensation, hepatocellular carcinoma, liver-related and non-liver-related mortality. A total of 1159 HCV-positive patientsnewly detected between 1994 and 2001 were included. Foreach outcome, the prognostic effect of patients baselinecharacteristics was estimated by time-dependent Cox modelsusing age as the time-scale and adjusting for treatmentreceived during follow-up. The impact of antiviral therapywas assessed by using a propensity score in a sampleincluding 184 patients treated in the first 24 months fol-lowing diagnosis who were matched to 184 untreatedpatients. At the end of a 59-month median follow-up, 100cases of compensated disease, 58 liver cancer and 163deaths (55 liver related) were recorded. The 5-year rates ofdecompensated cirrhosis, hepatocellular carcinoma, liver-related and non-liver-related death were 4.4%, 2.7%, 5.0%and 8.9%, respectively. Multivariate analyses identified twovariables with pejorative influence: alcohol consumption(RR = 4.29 for CD; RR = 5.76 for HCC; RR = 6.69 for liver-related death; P < 0.0001); HCV diagnosis unrelated tosystematic screening (RR = 2.25 for CD; RR = 3.05 forHCC; RR = 4.31 for liver-related death, P < 0.03). In thematched subset, no significant benefit of antiviral therapywas observed. Nevertheless, among the 144 patients whoachieved SVR, no death was observed. This population-basedstudy showed substantial rates of decompensated cirrhosis,hepatocellular carcinoma and non-liver-related mortality.Alcohol consumption and absence of systematic screeningwere significant determinants of poor outcome, whereastreatment did not have significant influence.Keywords: antiviral therapy, hepatitis C, liver-related mor-tality, non-liver-related mortality, outcome, population-based cohort study, survival bias.

International audience; BACKGROUND/AIMS: In severe alcoholic hepatitis (AH), 40% of patients will obtain no benefit from corticosteroids. Improvement in management of non-responders is warranted and only pentoxifylline can be considered an alternative. A two-step strategy was evaluated consisting of early withdrawal of corticosteroids and a switch to pentoxifylline for 28 additional days in non-responders identified using early change in bilirubin level. METHODS: One hundred and twenty-one patients with AH were treated prospectively with corticosteroids, and the two-step strategy was proposed to 29 non-responders treated according to a two-step strategy who were compared to 58 matched non-responders treated with corticosteroids only. RESULTS: Clinical and biological features of the two groups were similar. There was no survival improvement at 2 months in patients treated with the two-step strategy compared to controls: 35.5+/-6.3% vs 31+/-8.6%. After 21 days, biological evolution was similar for prothrombin time (-0.25s vs +0.2s), bilirubin (0.8 mg/dl vs 2.03 mg/dl) and creatinine (+0.16 mg/dl vs -0.7 mg/dl). In multivariate analysis, only age, evolution of bilirubin during the first week, creatinine and DF were associated with 2-month survival. CONCLUSIONS: Non-responders to corticosteroids do not obtain any benefit from an early switch to pentoxifylline. Thus, the issue of management of non-responders remains unresolved.

Introduction Acute E hepatitis becomes more frequent in immunocompromised patients. No guidelines are available to date for the management of this infection and of the immunosuppressive treatment. Methods We report a case of acute E hepatitis treated with ribavirine in a patient known for rheumatoid arthritis and treated with rituximab. Case A 51-year-old woman known for rheumatoid arthritis and treated with rituximab was hospitalized for a jaundice secondary to an acute E hepatitis. She was treated with ribavirin 800 mg twice a day during 2 months with a good efficacy and tolerance. Finally, 3 months after the acute E hepatitis, she benefited from 2 new 1000 mg rituximab infusions because of the rheumatoid arthritis activity. The treatment was well tolerated without acute hepatitis. The follow-up of the HVE infection was realized with HVE PCR in the blood and 8 months after the last infusions, there were no chronic courses or acute hepatitis recurrence. Conclusion This case highlights the safety and the efficacy of the reintroduction of rituximab after 2 months of treatment with ribavirin and a negative PCR.

Adrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol.Because 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis.43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured.T0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p0.001). In acute hepatitis (n=74), patients with "low" corticosteroid-binding globulin (28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2-157] vs. 56.6 [43.6-81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p0.001) or healthy controls (p0.001).In severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.

International audience; BACKGROUND & AIMS: Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial.METHODS: A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate.RESULTS: Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (pCONCLUSIONS: In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.

No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune).To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included.213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p0.0001), sex (p0.0008) and alanine transaminase (p0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase).When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.

OBJECTIVE Spontaneous bacterial peritonitis (SBP) is one of the potentially life-threatening complications in ascitic cirrhotic patients with a mortality rate ranging between 30 and 50%. The improved survival might be explained by a more rapid diagnosis and treatment. The aim of our study was to assess the utility of two reagent strips, the Multistix test and the Combur(2) test LN, for the rapid diagnosis of SBP. METHODS Thirty-one unselected consecutive cirrhotic patients with ascites were included and a total of 100 paracenteses were performed. All ascitic fluid was analysed with the two reagent strips, leucocyte and polymorphonuclear (PMN) leucocyte cell count and blood-bottle culture if the strips were positive. The strips were considered positive if the colour turned to purple: i.e. grade 3 or 4 for the Multistix test and 2 or 3 for the Combur(2) test LN on a colorimetric scale. RESULTS We diagnosed nine infections of which four were SBP defined by PMN > or = 250 cells/mm(3) and a positive culture in ascitic fluid and five were culture negative neutrocytic ascites (PMN > or = 250 cells/mm(3) and a negative culture). The results of the two strips were concordant and were negative in only one SBP. The sensitivity, specificity, positive and negative predictive values of these two strips were 89%, 100%, 100% and 99%, respectively. CONCLUSIONS These reagent strips are very sensitive and specific for the diagnosis of SBP, allowing immediate commencement of empirical antibiotic therapy. These strips should be used for the diagnosis of SBP, especially on an emergency basis.

The outcome of chronic hepatitis B and the efficacy of interferon alfa (IFN-alpha) remain controversial in human immunodeficiency virus (HIV)-positive patients. We analyzed the influence of HIV coinfection on the response to IFN-alpha therapy, long-term virologic status, progression to cirrhosis, and mortality.This was a retrospective follow-up cohort study of 141 consecutive hepatitis B e antigen-positive patients (69 HIV positive) followed up for 45 months.The short-term response to IFN-alpha therapy was not significantly different in HIV-positive and HIV-negative patients (28% vs. 51%; P = 0.06) but was poorer in cases of low CD4 cell count (P = 0.038). The hepatitis B virus (HBV) reactivation rate was higher in HIV-positive patients (P = 0.033) and was associated with low CD4 cell count. The risk of cirrhosis was higher in HIV-positive patients with a CD4 cell count200/mm(3) (relative risk [RR], 4.57; P = 0.007), in IFN-alpha-untreated patients (RR, 2.63; P = 0.041), in patients older than 33 years (RR, 4.59; P = 0.008), and in cases of high necroinflammatory score at baseline (RR, 1.27; P = 0.010). Cirrhosis-related death was more frequent in HIV-positive patients with low CD4 cell count at baseline (P = 0.041), in alcohol consumers (P = 0.001), in IFN-alpha-untreated patients (P = 0.052), and in patients with high histology activity index at baseline (P = 0.005).HIV coinfection was associated with poorer response to IFN-alpha therapy, more frequent HBV reactivations, and increased incidence of cirrhosis and cirrhosis-related death in cases of low CD4 count. IFN-alpha therapy decreased the incidence of HBV cirrhosis regardless of HIV status or serologic response.

Objective Although discrepancies between histological and virological responses to anti-hepatitis C virus (HCV) therapy are well-established in HIV-negative patients, the liver histological outcome has never been assessed in HIV–HCV co-infected patients receiving anti-HCV therapy. We compared histological responses to interferon (IFN) α therapy between HIV-positive and HIV-negative injecting drug users (IDU) and determined factors associated with histological response. Design Retrospective cohort study. Setting Hepatology unit of a tertiary referral hospital. Patients/interventions Seventy-nine HCV-infected IDU (32 HIV-positive) receiving a 6-month course of IFN-α2b therapy, 3 × 106 U three times a week. Primary outcome measure Histological response, defined by a ≥ 2 point decrease in total Knodell score measured on paired liver biopsies over a 2-year follow-up period. Results The sustained response rate to IFN therapy was lower in HIV-positive patients than in HIV-negative patients (6.2% versus 29.8%;P = 0.012). Conversely, the rates of histological response (40.6% versus 36.2%) were not different between HIV-positive and HIV-negative patients. Independent factors associated with histological response were first total Knodell score (P = 0.0007) and sustained response to IFN therapy (odds ratio, 12.34;P = 0.005). Histological response was observed in 25% of IFN non-responders whatever their HIV status. In HIV-positive patients, the CD4 cell count did not influence the histological response. Conclusions in HIV–HCV co-infected patients treated with IFN, liver histological improvement is frequently observed, similarly to that observed in HIV-negative patients. Such beneficial effect of interferon therapy supports early treatment of chronic hepatitis C in HIV-infected patients.

Identifying cirrhosis with a poor short-term prognosis remains crucial for improving the allocation of liver grafts. The purpose of this study was to assess the prognostic value of a model combining the variation of C-reactive protein (CRP) levels within 15 days, the Model for End-Stage Liver Disease (MELD) score, and the presence of comorbidities in patients with decompensated cirrhosis with a Child-Pugh score > B7 and to test the relevance of this model in patients with compensated cirrhosis. We collected data for cirrhotic patients without hepatocellular carcinoma, extrahepatic malignancy, human immunodeficiency virus infection, organ transplantation, seen between January 2010 and December 2011. Multivariate analyses of predictors of 3-month mortality used Cox models adjusted with the age-adjusted Charlson comorbidity index. The prognostic performance [area under receiver operating characteristic curves (AUROCs)] of the 3-variable model was compared to that of the MELD score. The 241 patients who met the inclusion criteria included 109 patients with a Child-Pugh score > B7 who were hospitalized for decompensation. In these patients with severe cases, the 3-month mortality was independently predicted by the MELD score [hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.05-1.14; P 32 mg/L at the baseline and on day 15 (HR, 2.21; 95% CI, 1.03-4.76; P = 0.042). This model was better than MELD alone (AUROC, 0.789 versus 0.734; P = 0.043). In the whole population with cirrhosis, the 3-month mortality was also predicted by high MELD scores (HR, 1.11; 95% CI, 1.07-1.16; P 10 mg/L at the baseline and on day 15 (HR, 2.89; 95% CI, 1.29-6.48; P

Summary Background and objective Advances in the management of variceal bleeding (VB) have been highlighted recently. We aimed at assessing whether changing the management of VB has improved the outcome (mortality and rebleeding rates). Methods The files of two cohorts ( n = 57, 2000–2001 and n = 64, 2008–2009) of patients referred to our university center were reviewed after a cross-searching using two coding systems. Data were recorded during the six months after VB. Results As compared to 2000–2001, more use of general anesthesia (25.4% vs. 11.1%; P = 0.049), band ligations (96.1% vs. 71.4%; P = 0.001), octreotide (95.3% vs. 80.7%; P = 0.012) and antibiotic prophylaxis (93.8% vs. 82.5%; P = 0.09) were performed in 2008–2009, whereas the number of red-cell units transfused during the hospital stay (4.3 ± 3.2 vs. 7.1 ± 5.7; P = 0.005) decreased. Surprisingly, more than 60% of patients reached the emergency department from home without medical assistance in both periods. In 2008–2009, patients had more comorbidities and no patients underwent early-TIPS but the 6-week mortality rate (24.6% vs.10.9%; P = 0.048) was lower. The 6-week mortality was associated with high MELD score (HR = 1.13; 95%CI: 1.08–1.18) and hypovolemic shock (HR = 5.36; 95%CI: 1.96–14.67) at admission. In multivariate analysis adjusted on MELD and comorbidities, the 2008–2009 period (HR: 0.42; 95%CI: 0.20–0.87; P = 0.02) was associated with a lower 6-month mortality rate. Conclusions Although cirrhotic patients with VB had more comorbidities in 2008–2009 and received no early-TIPS, their prognosis has improved during this last decade concomitantly to a more intensive care and a lower transfusion strategy.

To determine adverse events of ribavirin in the treatment of chronic hepatitis C, 41 patients (18 with cirrhosis), treated with ribavirin at an initial dose of 600-1200mg day(-1), were analysed retrospectively (six patients were treated twice because adverse effects during the first treatment necessitated cessation of ribavirin). Indications for ribavirin included a contraindication (n = 15) an intolerance (n = 11) or a non-response (n = 15) to interferon (IFN). Ribavirin was combined with IFN 3 million units (MU) three times weekly for 15 patients and with azathioprine for six patients (five of whom were transplant patients). No cirrhotics and only one patient treated with ribavirin + IFN received azathioprine. The mean duration of treatment was 5 months (range 1-18 months). Sixteen of 47 treatments (34%) with ribavirin were stopped: four because of vomiting (8.5%), two for psychiatric disorder, one for dry cough, one for an unrelated cause, and eight (at 1-2 months) because of a fall in the level of haemoglobin (Hb) of 4.6 g dl(-1) (range 2.7-5.9 g dl[-1]); however, according to the rules of international protocol, we would have expected only four treatments (two in patients receiving azathioprine) with Hb < 8.5 g dl(-1) to be stopped. The decrease in Hb level occurred more slowly in patients treated with IFN plus ribavirin than in patients treated with ribavirin alone and was of lower clinical significance in patients with cirrhosis than in patients without cirrhosis. After exclusion of patients receiving azathioprine, there was no significant difference in the fall of Hb level between cirrhotic and non-cirrhotic patients and between patients treated with IFN plus ribavirin and patients treated with ribavirin alone. Interestingly, the platelet count of patients treated with IFN plus ribavirin fell less than in patients treated with IFN alone. The most important and expected adverse event associated with ribavirin was haemolysis. Anaemia < 8.5 g dl(-1), requiring cessation of ribavirin therapy, was present in 9% of patients and was worsened by azathioprine. Abdominal discomfort and dry cough were other, potentially important, clinical adverse events found in our study.

The aims of this study were to evaluate the benefits of higher doses or of longer duration in comparison with a standard interferon regimen (3 MU three times per week for 6 months) in chronic hepatitis C, and to assess the efficacy of interferon in acute hepatitis C. Meta-analysis made use of the Peto et al. and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses. In chronic hepatitis, a total of 17 trials versus controls and of 16 trials comparing different interferon regimens were included. Standard regimen, 3 MU three times per week for 6 months, was associated with an increase of the complete alanine transaminase (ALT) response rate and sustained (ALT) response rate by 45% (95% confidence interval: 35% to 55%; P < .001) and 21% (13% to 28%; P < .001), respectively, with the natural course being less than 2% of spontaneous responses. There was a significant dose effect (6 vs. 3 MU three times per week) upon the sustained response rate at 12 months, with a mean 17% increase (7% to 28%; P < .001), but not at 6 months. There was a significant duration effect (12 vs. 6 months) upon the sustained response rate both at the dose of 3 MU with a mean of 16% (9% to 23%; P < .001), and at the dose of 6 MU three times per week with a mean of 20% (7% to 33%; P = .003). In acute hepatitis C, 3 months of interferon treatment showed significant efficacy versus controls (4 trials), upon the complete ALT response (69% vs. 29%; P < .001), the sustained response rate during the 12 months following treatment (53% vs. 32%; P = .02), and hepatitis C virus (HCV)-RNA clearance (41% vs. 4%; P < .001). The best efficacy/risk ratio was in favor of 3 MU three times per week for at least 12 months in patients with chronic hepatitis C who had never been treated with interferon. Patients with acute hepatitis should be treated with at least 3 MU three times per week for 3 months.

We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC.Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality.Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC138 nmol/L) and 49.4% (change in STC250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin.One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.

A b s t r ac t Background Mortality among patients with severe acute alcoholic hepatitis is high, even among those treated with glucocorticoids. We investigated whether combination therapy with glucocorticoids plus N-acetylcysteine would improve survival. Methods We randomly assigned 174 patients to receive prednisolone plus N-acetylcysteine (85 patients) or only prednisolone (89 patients). All patients received 4 weeks of pred nisolone. The prednisolone– N-acetylcysteine group received intravenous N-acetylcys teine on day 1 (at a dose of 150, 50, and 100 mg per kilogram of body weight in 250, 500, and 1000 ml of 5% glucose solution over a period of 30 minutes, 4 hours, and 16 hours, respectively) and on days 2 through 5 (100 mg per kilogram per day in 1000 ml of 5% glucose solution). The prednisolone-only group received an infusion in 1000 ml of 5% glucose solution per day on days 1 through 5. The primary outcome was 6-month survival. Secondary outcomes included survival at 1 and 3 months, hepatitis complications, adverse events related to N-acetylcysteine use, and changes in bilirubin levels on days 7 and 14. Results Mortality was not significantly lower in the prednisolone– N-acetylcysteine group than in the prednisolone-only group at 6 months (27% vs. 38%, P = 0.07). Mortality was significantly lower at 1 month (8% vs. 24%, P = 0.006) but not at 3 months (22% vs. 34%, P = 0.06). Death due to the hepatorenal syndrome was less frequent in the prednisolone– N-acetylcysteine group than in the prednisolone-only group at 6 months (9% vs. 22%, P = 0.02). In a multivariate analysis, factors associated with 6-month survival were a younger age (P

We aimed at improving prediction of short-term mortality in cirrhotic inpatients by evaluating C-reactive protein (CRP) as a surrogate marker of systemic inflammatory response syndrome (SIRS).One-hundred and forty-eight consecutive cirrhotic patients with Child-Pugh score ≥ B8 and without hepatocellular carcinoma were prospectively included and followed for 182 days. The primary end point was 6-month survival.Main baseline characteristics were as follows: alcoholic liver disease in 88.5%; bacterial infection in 37%; hepatorenal syndrome in 7% of cases. CRP range was 1-240 mg/L (median 26 mg/L); 42 patients (28.4%) had SIRS as defined by ACCP/SCCM-criteria. CRP levels were higher in patients with SIRS (50 vs. 21 mg/L; p0.0001), infection (46 vs. 27 mg/L; p0.0001), and alcoholic hepatitis (44 vs. 32 mg/L, p=0.049). Forty-two patients died within the first 6 months of follow-up. Short-term mortality was associated with extrahepatic co-morbidities (p=0.002), high MELD score (p0.001; AUROC=0.67), renal failure (p=0.008), elevated blood lactates (p0.001), and high baseline CRP levels (p=0.003; AUROC=0.63; best cut-off value at 29 mg/L). Among patients with baseline CRP ≥ 29 mg/L, 32 still had CRP ≥ 29 mg/L at day 15 (group A). Group A was associated with 6-month mortality in the overall population (p0.001) and also through sensitivity analyses restricted to patients without infection or alcoholic hepatitis. Multivariate analysis (Cox) adjusted for age identified three predictors of mortality: high MELD score (HR=1.08; 95% CI: 1.03-1.12; p0.001), extrahepatic co-morbidities (HR=2.51; 95% CI: 1.31-4.84; p=0.006), and CRP level (group A) (HR=2.73; 95% CI: 1.41-5.26; p=0.003). The performance of the three variables taken together for predicting death was 0.80 (AUROC).In Child-Pugh score ≥ B8 cirrhotic patients, persistent CRP levels ≥ 29 mg/L predicted short-term mortality independently of age, MELD, and co-morbidities, and better than infection or clinically-assessed SIRS.

Because over 90% of serum cortisol is bound to albumin and corticosteroid-binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum-free and salivary cortisol concentrations.We assessed basal (T₀) and post-synacthen (T₆₀) serum total cortisol, serum-free and salivary cortisol in 125 consecutive cirrhotics (95 non-septic and 30 septic patients with a Child8).Serum total cortisol levels significantly decreased from the Child A-C non-septic group, as did albumin and CBG levels, with a non-significant rise in serum-free cortisol concentrations. Non-septic patients with low albumin (≤25 g/L) or CBG levels (≤35 mg/L) had lower T₀ serum total cortisol levels than patients with near-normal albumin (303.4 vs. 382.6 nmol/L; P=0.0035) or with normal CBG levels (289.9 vs. 441.4 nmol/L; P0.0001), respectively, despite similar serum-free cortisol or salivary cortisol concentrations. Subnormal T₆₀ serum total cortisol concentrations (510.4 nmol/L) were measured in 7.2% of all patients (Child C: 14.5% vs. Child A and B: 0%; P=0.0013) but no patients exhibited symptoms suggesting adrenal insufficiency. Patients with or without subnormal T₆₀ total cortisol had similar T₀ salivary cortisol and serum-free cortisol concentrations. A trend was observed towards high serum-free cortisol concentrations and mortality in multivariate analysis.Serum total cortisol levels overestimated the prevalence of adrenal dysfunction in cirrhotics with end-stage liver disease. Since serum-free cortisol cannot be measured routinely, salivary cortisol testing could represent a useful approach but needs to be standardized.

International audience; The present study aimed to identify a sub-group of inoperable alveolar echinococcosis (AE) patients undergoing long-term treatment with benzimidazole (BZM) who presented with an evolution suggestive of a parasitocidal effect. An evolution compatible with parasite death was observed in five patients.

International audience; BACKGROUND & AIMS: Complications and technical problems of paracentesis in cirrhotic patients are infrequent. However, the severity and the incidence of these events and their risk factors have not been assessed prospectively. METHODS: Cirrhotic patients (n = 171) undergoing paracentesis were included. Of the 515 paracenteses, 8.8% were diagnostic, and 91.2% were therapeutic. Technical features, demographic data, and adverse events during a period of 72 hours after the procedure were examined. RESULTS: Major complications occurred in 1.6% of procedures and included 5 bleedings and 3 infections, resulting in death in 2 cases. Major complications were associated with therapeutic but not diagnostic procedures and tended to be more prevalent in patients with low platelet count (