Prediction of esophagogastroduodenoscopy therapeutic usefulness for in-ICU suspected upper gastrointestinal bleeding: the SUGIBI score study.

BACKGROUND: Suspected upper gastrointestinal bleeding (SUGIB) is a common issue during ICU stay. In the absence of specific guidelines on the indication and timing of esophagogastroduodenoscopy (EGD), there is substantial variability in EGD indication depending on accessibility and clinical presentation. This study aimed to investigate factors associated with the need for per-EGD hemostatic therapy and to create a score predicting therapeutic benefit of emergency bedside EGD in ICU patients with SUGIB. METHODS: We conducted a retrospective study in our ICU to identify factors associated with the need for hemostatic procedure during EGD performed for SUGIB. From this observational cohort, we derived a score predicting the need for hemostasis during EGD, the SUGIBI score. This score was subsequently validated in a retrospective multicenter cohort. RESULTS: Two hundred fifty-five patients not primarily admitted for GI bleeding who underwent a bedside EGD for SUGIB during their ICU stay were analyzed. The preeminent EGD indication were anemia (79%), melena (19%), shock (14%), and hematemesis (13%). EGD was normal in 24.7% of cases, while primary lesions reported were ulcers (23.1%), esophagitis (18.8%), and gastritis (12.5%). Only 12.9% of patients underwent hemostatic endotherapy during EGD. A SUGIBI score < 4 had a negative predictive value of 95% (91-99) for hemostatic endotherapy [AUC of 0.81; 0.75-0.91 (p < 0.0001)]. The SUGIBI score for predicting the need for an EGD-guided hemostatic procedure was next validated in a multicenter cohort with an AUC of 0.75 (0.66-0.85) (p < 0.0001), a score < 4 having a negative predictive value of 95% (92-97). CONCLUSIONS: Our study shows that the therapeutic usefulness of bedside emergency EGD for SUGIB in critically ill patients is limited to a minority of patients. The SUGIBI score should help clinicians stratify the probability of a therapeutic EGD.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results: Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT02281929.

Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort.

BACKGROUND & AIMS: The harmful impact of heavy alcohol consumption and recurrence in patients with alcohol-related cirrhosis is long-established, although this is based on old studies. However, the drivers of long-term outcome still need to be clearly investigated. METHOD: All patients with biopsy-proven compensated alcohol-related cirrhosis included in the CIRRAL cohort (22 centers) were prospectively studied. Prognostic variables of survival and liver event-free survival were assessed using multivariable Cox models with stepwise selection. The prognostic impact of alcohol recurrence during follow-up (computed in glass-years in the same way as pack-years for tobacco) was assessed using a time-dependent covariable. RESULTS: From 2010 to 2016, 650 patients were included. The median age at baseline was 58.4 years, 67.4% were men and the median BMI was 27.8 kg/m2, 63.8% had a history of liver decompensation, and 70.2% had discontinued alcohol. At 5 years, recurrence occurred in 30.9% of abstinent patients and this risk was higher in patients with a history of drug abuse and in those with shorter alcohol discontinuation times. Median survival was 97 months. Age, alcohol consumption at baseline, platelet count and Child-Pugh score >5 were associated with overall and liver event-free survival on multivariate analysis. Alcohol consumption of more than 25 glass-years during follow-up was independently associated with lower survival and with a trend toward lower liver event-free survival, with the risk increasing from 1 glass-year, though not significantly. Simon & Makuch plots confirm the benefit of no alcohol consumption (<1 glass/week) on both outcomes and the dose-dependent impact of alcohol over time. CONCLUSION: This prospective study in patients with compensated alcohol-related cirrhosis identifies factors predictive of alcohol recurrence during follow-up and shows that moderate alcohol consumption during follow-up negatively impacts outcomes. Patients with alcohol-related cirrhosis should be advised to completely stop drinking alcohol. REGISTRATION: CIRRAL (NCT01213927) cohort was registered at ClinicalTrials.gov and the full protocol is available at the following link: https://clinicaltrials.gov/ct2/show/NCT01213927. IMPACT AND IMPLICATIONS: In patients with alcohol-related cirrhosis, data are lacking about the impact of the amount of alcohol consumed on both survival and liver-related events. The present study based on the CIRRAL cohort demonstrates that alcohol recurrence occurs in more than 30% of patients with compensated cirrhosis and that even a moderate recurrence strongly influences outcomes. Patients with compensated alcohol-related cirrhosis should be advised to completely discontinue alcohol consumption, even in small amounts, as the present study shows that no alcohol consumption can be regarded as safe when cirrhosis has developed.

Evaluation by a Machine Learning System of Two Preparations for Small Bowel Capsule Endoscopy: The BUBS (Burst Unpleasant Bubbles with Simethicone) Study.

Background: Bubbles often mask the mucosa during capsule endoscopy (CE). Clinical scores assessing the cleanliness and the amount of bubbles in the small bowel (SB) are poorly reproducible unlike machine learning (ML) solutions. We aimed to measure the amount of bubbles with ML algorithms in SB CE recordings, and compare two polyethylene glycol (PEG)-based preparations, with and without simethicone, in patients with obscure gastro-intestinal bleeding (OGIB). Patients & Methods: All consecutive outpatients with OGIB from a tertiary care center received a PEG-based preparation, without or with simethicone, in two different periods. The primary outcome was a difference in the proportions (%) of frames with abundant bubbles (>10%) along the full-length video sequences between the two periods. SB CE recordings were analyzed by a validated computed algorithm based on a grey-level of co-occurrence matrix (GLCM), to assess the abundance of bubbles in each frame. Results: In total, 105 third generation SB CE recordings were analyzed (48 without simethicone and 57 with simethicone-added preparations). A significant association was shown between the use of a simethicone-added preparation and a lower abundance of bubbles along the SB (p = 0.04). A significantly lower proportion of "abundant in bubbles" frames was observed in the fourth quartile (30.5% vs. 20.6%, p = 0.02). There was no significant impact of the use of simethicone in terms of diagnostic yield, SB transit time and completion rate. Conclusion: An accurate and reproducible computed algorithm demonstrated significant decrease in the abundance of bubbles along SB CE recordings, with a marked effect in the last quartile, in patients for whom simethicone had been added in PEG-based preparations, compared to those without simethicone.

Multidisciplinary support for ethics deliberations during the first COVID wave.

BACKGROUND: The first COVID-19 wave started in February 2020 in France. The influx of patients requiring emergency care and high-level technicity led healthcare professionals to fear saturation of available care. In that context, the multidisciplinary Ethics-Support Cell (EST) was created to help medical teams consider the decisions that could potentially be sources of ethical dilemmas. OBJECTIVES: The primary objective was to prospectively collect information on requests for EST assistance from 23 March to 9 May 2020. The secondary aim was to describe the Cell's functions during that period. RESEARCH DESIGN: This observational, real-time study of requests for Cell consultations concerned ethical dilemmas arising during a public health crisis. The EST created a grid to collect relevant information (clinical, patient's/designated representative's preferences and ethical principles strained by the situation), thereby assuring that each EST asked the same questions, in the same order. PARTICIPANTS AND RESEARCH CONTEXT: Only our university hospital's clinicians could request EST intervention. ETHICAL CONSIDERATIONS: The hospital Research Ethics Committee approved this study (no. CER-2020-107). The patient, his/her family, or designated representative was informed of this ethics consultation and most met with EST members, which enabled them to express their preferences and/or opposition. FINDINGS/RESULTS: 33 requests (patients' mean age: 80.8 years; 29 had COVID-19: 24 with dyspnea, 30 with comorbidities). 17 Emergency Department solicitations concerned ICU admission, without reference to resource constraints; others addressed therapeutic proportionality dilemmas. DISCUSSION: Intervention-request motives concerned limited resources and treatment intensity. Management revolved around three axes: the treatment option most appropriate for the patient, the feasibility of implementation, and dignified care for the patient. CONCLUSIONS: COVID-19 crisis forced hospitals to envisage prioritization of ICU access. Established decision-making criteria and protocols do not enable healthcare professionals to escape ethical dilemmas. That acknowledgement highlights ethical risks, enhances the added-value of nursing and encourages all players to be vigilant to pursue collective deliberations to achieve clear and transparent decisions.

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.

BACKGROUND: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. METHODS: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. FINDINGS: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). INTERPRETATION: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. FUNDING: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

ABO blood group does not influence Child-Pugh A cirrhosis outcome: An observational study from CIRRAL and ANRS CO12 CIRVIR cohorts.

BACKGROUND AND AIMS: Non-O blood group promotes deep vein thrombosis and liver fibrosis in both general population and hepatitis C. We aimed to evaluate the influence of Non-O group on the outcome of Child-Pugh A cirrhotic patients. METHODS: We used two prospective cohorts of Child-Pugh A cirrhosis due to either alcohol or viral hepatitis. Primary end point was the cumulated incidence of 'Decompensation' at 3 years, defined as the occurrence of ascites , hydrothorax, encephalopathy, gastrointestinal bleeding related to portal hypertension, or bilirubin >45 µmol/L. Secondary end points were the cumulated incidences of (1) 'Disease Progression' including a « decompensation¼ or « the occurrence of one or more parameters ¼ among: prothrombin time (PT) <45%, albumin <28 g/L, Child-Pugh worsening (B or C vs A or B, C vs B), hepatorenal syndrome, and hepato-pulmonary syndrome, (2) other events such as non-malignant portal vein thrombosis (nmPVT), and (3) overall survival. RESULTS: Patients (n = 1789; 59.9% Non-O group; 40.1% group O) were followed during a median of 65.4 months. At 3 years cumulated incidence of Decompensation was 8.3% in Non-O group and 7.2% in group O (P = .27). Cumulated incidence of Disease Progression was 20.7% in Non-O group and 18.9% in group O (P = .26). Cumulated incidence of nmPVT was 2.7% in Non-O group and 2.8% in group O (P = .05). At 3 years overall survival was 92.4% in Non-O group and 93.4% in group O (P = 1). CONCLUSION: Non-O group does not influence disease outcome in Child-Pugh A cirrhotic patients. Clinicals trial number NCT03342170.

The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.

BACKGROUND: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. OBJECTIVE: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. DESIGN: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196). PARTICIPANTS: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. INTERVENTION: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. MEASUREMENTS: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. RESULTS: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. LIMITATIONS: The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. CONCLUSION: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. PRIMARY FUNDING SOURCE: French Public Health Ministry.

Experience with the use of a hemostatic powder in 152 patients undergoing urgent endoscopy for gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: In the recent years, topical hemostatic powders have been used for the management of upper gastrointestinal bleeding. The aim of this study was to report on the use of an hemostatic powder (Hemospray®), outside regular hours, by on-call endoscopists during urgent endoscopic procedures. MATERIAL AND METHODS: In this retrospective multicenter cohort study, consecutive patients having undergone an urgent endoscopy with the use of Hemospray® from November 2015 to December 2018 in the Paris and suburbs area were included. We collected clinical, biological and endoscopic variables. The outcomes such as the recurrence, repeat endoscopy and hemostatic treatment need, complications and survival were also collected. RESULTS: A total of 152 patients (mean 65 years old, 70.4% male) were included. Amongst the 31 endoscopists, 11 were "more experienced", and performed 48% of the endoscopies. The most common causes of bleeding were peptic ulcer (47.7%), malignancy (22.2%) and esophagitis (12.4%). Most bleedings originated from the upper GI tract (95.0%). Hemospray® was used as a salvage therapy in 60.8% of cases. Other hemostatic techniques were used in 52.9% of cases. Immediate bleeding cessation was noted in 79.0% of cases, recurrence in 39.9% of cases, and 26.4% of patients benefited from a repeat endoscopic hemostasis. 34 (23.0%) patients required a non-endoscopic treatment. At day 30, the survival rate was 71.6%. One complication was reported (perforation). CONCLUSIONS: Hemostatic powder application by on-call endoscopists outside regular hours is technically feasible, but comes with a high risk of rebleeding in severely ill patients.

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.

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.

Recalibrated MELD and hepatic encephalopathy are prognostic factors in cirrhotic patients with acute variceal bleeding.

BACKGROUND & AIMS: Early TIPS placement must be considered in patients with Child-Pugh B and active bleeding at endoscopy or in patients with Child-Pugh C 10-13 and variceal bleeding. However, active bleeding at endoscopy is a subjective criterion. Moreover, a previous study has shown that a MELD-based score accurately predicted 6-week mortality and helped to stratify patients. Using a prospective series of patients included in a multicentre study before the era of early TIPS, we aimed (i) to identify factors associated with 6-week mortality, focusing on the prognostic value of active bleeding; and (ii) to assess whether a recalibrated MELD-based score accurately predicted 6-week mortality. METHODS: Ancillary study of the prospective multicentre Baveno IV study, including patients with acute variceal bleeding. RESULTS: Two hundred and nineteen patients were analysed (Child-Pugh A/B/C = 18/45/37%). The overall actuarial likelihood of survival on day 42 was 84%. The variability for the diagnosis of active bleeding at endoscopy was high (range, 41.4% to 84.6% among the centres). Active bleeding at endoscopy was not associated with 6-week mortality in the entire population or in Child-Pugh B patients. In a multivariate analysis, independent factors associated with mortality were liver function, infection, HE and HCC. The recalibrated MELD-based score was accurate in predicting 6-week mortality (AUROC = 0.787). The recalibrated MELD-based score demonstrated better performance compared to the MELD score. CONCLUSION: The recalibrated MELD-based score accurately predicted mortality in our prospective cohort. Active bleeding at endoscopy had no prognostic value in cirrhotic patients presenting with acute variceal bleeding. Standardizing active bleeding assessment at endoscopy is warranted.

Cirrhotic patients with portal hypertension-related bleeding and an indication for early-TIPS: a large multicentre audit with real-life results.

BACKGROUND: The Baveno VI consensus meeting concluded that an early TIPS must be considered in high-risk cirrhotic patients presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. AIMS: To determine (1) the proportion of patients eligible for early-TIPS among cirrhotic patients with VB, (2) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (3) the outcomes of patients who experienced early-TIPS placement in a large, national, prospective, multicentre audit including academic and non-academic centres. MATERIALS AND METHODS: All French centres recruiting gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and PHT-related bleeding were included. RESULTS: 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex, 77%; age, 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic,viral/other, 67%/15%/18%); source of bleeding (EV/GV/other, 80/11/9%); active bleeding at endoscopy 34%; Child A 21%/B 44%/C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7±0.07% vs 58.9±0.03%, p=0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. CONCLUSION: In this real-life study, one-third of the cirrhotic patients admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival.

Albumin Use in Patients With Cirrhosis in France: Results of the "ALBU-LIVE" Survey: A Case for Better EASL Guidelines Diffusion and/or Revision.

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.

Transjugular Intrahepatic Portosystemic Shunts With Covered Stents Increase Transplant-Free Survival of Patients With Cirrhosis and Recurrent Ascites.

BACKGROUND & AIMS: There is controversy over the ability of transjugular intrahepatic portosystemic shunts (TIPS) to increase survival times of patients with cirrhosis and refractory ascites. The high rate of shunt dysfunction with the use of uncovered stents counteracts the benefits of TIPS. We performed a randomized controlled trial to determine the effects of TIPS with stents covered with polytetrafluoroethylene in these patients. METHODS: We performed a prospective study of 62 patients with cirrhosis and at least 2 large-volume paracenteses within a period of at least 3 weeks; the study was performed at 4 tertiary care centers in France from August 2005 through December 2012. Patients were randomly assigned to groups that received covered TIPS (n = 29) or large-volume paracenteses and albumin as necessary (LVP+A, n = 33). All patients maintained a low-salt diet and were examined at 1 month after the procedure then every 3 months until 1 year. At each visit, liver disease-related complications, treatment modifications, and clinical and biochemical variables needed to calculate Child-Pugh and Model for End-Stage Liver Disease scores were recorded. Doppler ultrasonography was performed at the start of the study and then at 6 and 12 months after the procedure. The primary study end point was survival without a liver transplant for 1 year after the procedure. RESULTS: A higher proportion of patients in the TIPS group (93%) met the primary end point than in the LVP+A group (52%) (P = .003). The total number of paracenteses was 32 in the TIPS group vs 320 in the LVP+A group. Higher proportions of patients in the LVP+A group had portal hypertension-related bleeding (18% vs 0%; P = .01) or hernia-related complications (18% vs 0%; P = .01) than in the TIPS group. Patients in LVP+A group had twice as many days of hospitalization (35 days) as the TIPS group (17 days) (P = .04). The 1-year probability of remaining free of encephalopathy was 65% for each group. CONCLUSIONS: In a randomized trial, we found covered stents for TIPS to increase the proportion of patients with cirrhosis and recurrent ascites who survive transplantation-free for 1 year, compared with patients given repeated LVP+A. These findings support TIPS as the first-line intervention in such patients. ClinicalTrials.gov ID: NCT00222014.

The Periscreen Strip Is Highly Efficient for the Exclusion of Spontaneous Bacterial Peritonitis in Cirrhotic Outpatients.

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/mm3. 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<0.001) and 7.2% in patients with symptoms suggestive of SBP (3% in outpatients vs. 11.3% in inpatients; P<0.001). The κ value for inter-reader agreement was 0.81 (95% confidence interval: 0.77-0.84) when using the "trace" threshold. Considering discordant results (n=131) as positive to interpret the diagnostic performance of the strip at the "trace" threshold, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.7, 57.1, 12.0, and 99.1%, respectively. At this "trace" threshold, sensitivity and NPV were both 100% in outpatients, and 89.5 and 97.9% in inpatients, respectively. At the "small" threshold, sensitivity, specificity, PPV and NPV were 81.0, 85.9, 25.9 and 98.7%, respectively. CONCLUSIONS: The Periscreen strip is a rapid and highly efficient tool for excluding SBP in the outpatient setting.

Role of the transjugular intrahepatic portosystemic shunt in the management of severe complications of portal hypertension in idiopathic noncirrhotic portal hypertension.

UNLABELLED: Idiopathic noncirrhotic portal hypertension is a heterogeneous group of diseases characterized by portal hypertension in the absence of cirrhosis. The efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in this population are unknown. The charts of patients with idiopathic noncirrhotic portal hypertension undergoing TIPS in seven centers between 2000 and 2014 were retrospectively reviewed. Forty-one patients were included. Indications for TIPS were recurrent variceal bleeding (n = 25) and refractory ascites (n = 16). Patients were categorized according to the presence (n = 27) or absence (n = 14) of significant extrahepatic comorbidities. Associated conditions were hematologic, prothrombotic, neoplastic, immune, and exposure to toxins. During follow-up (mean 27 ± 29 months), variceal rebleeding occurred in 7/25 (28%), including three with early thrombosis of the stent. Post-TIPS overt hepatic encephalopathy was present in 14 patients (34%). Eleven patients died, five due the liver disease or complications of the procedure and six because of the associated comorbidities. The procedure was complicated by hemoperitoneum in four patients (10%), which was fatal in one case. Serum creatinine (P = 0.005), ascites as indication for TIPS (P = 0.04), and the presence of significant comorbidities (P = 0.01) at the time of the procedure were associated with death. Mortality was higher in patients with significant comorbidities and creatinine ≥100 µmol/L (P < 0.001). CONCLUSION: In patients with idiopathic noncirrhotic portal hypertension who have normal kidney function or do not have severe extrahepatic conditions, TIPS is an excellent option to treat severe complications of portal hypertension. (Hepatology 2016;64:224-231).

A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases.

OBJECTIVE: No efficient medical treatment is available for severe acute hepatitis (SAH) except N-acetylcysteine for acetaminophen-induced acute liver failure. The human C-type lectin Reg3α, referred to as ALF-5755, improved survival in an animal model of acute liver failure and was well tolerated in a phase 1 trial in humans. We performed a phase 2a trial of ALF5755 in non-acetaminophen induced SAH. DESIGN: double-blind, randomized, placebo-controlled study. The primary end-point was the improvement in the coagulation protein synthesis assessed by the change of Prothrombin (PR) during the 72 hours following treatment initiation calculated as PRH0 minus PRH72 divided by 72 (PR slope H0H72). Intention to treat (ITT) and per-protocol (PP) analysis of the entire group and the Hepatitis B virus (HBV)/AIH (auto-immune hepatitis) sub-group were done separately. RESULTS: 57 patients were included. Twenty-eight received ALF-5755, 29 the placebo. Etiologies were: Hepatitis A (n = 10), HBV (n = 13), AIH (n = 9), drug-induced (n = 8), other (n = 17). On the whole group, nor the PR slope H0H72 (0.18±0.31 vs 0.25±0.32), nor the transplant-free survival rate at day 21 (75 vs 86%) differed between groups. Conversely, in the HBV-AIH subgroup, in which ALF was more severe, PR slope H0-H72 was higher in the ALF-5755 arm, the difference being significant in PP analysis (0.048±0.066 vs -0.040±0.099, p = 0.04); the median length of hospitalization was lower in the ALF-5755 group (8 vs 14 days, p = 0.02). CONCLUSION: ALF-5755 was not efficient in a ITT analysis performed on the whole sample; however it led to a significant, although moderate, clinical benefit in a PP analysis of the sub-group of patients with HBV or AIH related SAH. As HBV is the major cause of SAH in Asia and Africa and AIH a growing cause, this study emphasizes the need to pursuit the evaluation of this novel medical treatment of SAH. TRIAL REGISTRATION: ClinicalTrials.gov NCT01318525.

Management of gastric varices: a French national survey.

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: ß-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%; P<0.001) and TIPS (78.5 vs. 3.5%; P<0.001). Early TIPS was proposed by 53.6% (72.1 vs. 39.2%; P<0.001). Glue obliteration was performed under general anesthesia (86.1%) using Glubran (43.1%) or Histoacryl (52.9%), and lipiodol (78.8%) with varying degrees of dilution (1 : 10 to 3 : 4). The injected volume per varix varied widely (1-20 ml). Glue obliteration, band ligation, or both were used by, respectively, 64.2, 18.2, and 17.5% of practitioners. Almost all hepatogastroenterologists (98%) performed secondary prophylaxis: ß-blockers 74.7% (75.0 vs. 74.4%, university vs. general hospitals; P=0.93), glue obliteration 66.0% (76.9 vs. 57.6%; P=0.013), and TIPS 30.0% (39.1 vs. 23.3%; P=0.037). CONCLUSION: 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.