Alcohol-related cognitive impairments in patients with and without cirrhosis.

AIMS: up to 80% of patients with alcohol use disorder display cognitive impairments. Some studies have suggested that alcohol-related cognitive impairments could be worsened by hepatic damage. The primary objective of this study was to compare mean scores on the Brief Evaluation of Alcohol-Related Neurocognitive Impairments measure between alcohol use disorder patients with (CIR+) or without cirrhosis (CIR-). METHODS: we conducted a prospective case-control study in a hepatology department of a university hospital. All patients were assessed using the Evaluation of Alcohol-Related Neuropsychological Impairments test. RESULTS: a total of 82 patients (50 CIR+, 32 CIR-) were included in this study. CIR- patients were significantly younger than CIR+ patients (respectively, 45.5 ± 6.8 vs 60.1 ± 9.0; P < .0001). After adjusting for age and educational level, the mean Evaluation of Alcohol-Related Neuropsychological Impairments total scores in the CIR+ group were significantly lower than in the group of CIR- patients (14.1 ± 0.7 vs 7.8 ± 0.4, respectively, P < .0001). The mean subscores on delayed verbal memory, alphabetical ordination, alternating verbal fluency, visuospatial abilities, and ataxia subtests were also significantly lower in the CIR+ than in the CIR- group (respectively, 1.9 ± 0.2 vs 2.8 ± 0.2; 1.8 ± 0.2 vs 2.7 ± 0.2; 2.2 ± 0.2 vs 3.6 ± 0.2; 0.7 ± 0.2 vs 1.6 ± 0.2; 0.7 ± 0.2 vs 3.1 ± 0.2; P < .0001 for all comparisons). CONCLUSIONS: in the present study, alcohol use disorder patients with cirrhosis presented more severe cognitive impairments than those without cirrhosis. Longitudinal studies are needed to investigate how cirrhosis can influence cognitive impairments.

Liver disease in germline mutations of telomere-related genes: Prevalence, clinical, radiological, pathological features, outcome, and risk factors.

BACKGROUND AND AIM: Germline mutations of telomere-related genes (TRG) induce multiorgan dysfunction, and liver-specific manifestations have not been clearly outlined. We aimed to describe TRG mutations-associated liver diseases. APPROACH AND RESULTS: Retrospective multicenter analysis of liver disease (transaminases > 30 IU/L and/or abnormal liver imaging) in patients with TRG mutations. Main measurements were characteristics, outcomes, and risk factors of liver disease in a TRG mutations cohort. The prevalence of liver disease was compared to a community-based control group (n = 1190) stratified for age and matched 1:3 for known risk factors of liver disease. Among 132 patients with TRG mutations, 95 (72%) had liver disease, with associated lung, blood, skin, rheumatological, and ophthalmological TRG diseases in 82%, 77%, 55%, 39%, and 30% of cases, respectively. Liver biopsy was performed in 52/95 patients, identifying porto-sinusoidal vascular disease in 48% and advanced fibrosis/cirrhosis in 15%. After a follow-up of 21 months (12-54), ascites, hepato-pulmonary syndrome, variceal bleeding, and HCC occurred in 14%, 13%, 13%, and 2% of cases, respectively. Five-year liver transplantation-free survival was 69%. A FIB-4 score ≥ 3·25 and ≥1 risk factor for cirrhosis were associated with poor liver transplantation-free survival. Liver disease was more frequent in patients with TRG mutations than in the paired control group [80/396, (20%)], OR 12.9 (CI 95%: 7.8-21.3, p < 0.001). CONCLUSIONS: TRG mutations significantly increase the risk of developing liver disease. Although symptoms may be mild, they may be associated with severe disease. Porto-sinusoidal vascular disease and cirrhosis were the most frequent lesions, suggesting that the mechanism of action is multifactorial.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Unresectable hepatocellular carcinoma at dawn of immunotherapy era: real-world data from the French prospective CHIEF cohort.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma epidemiological data are limited in France. The Epidemio Liver Immunotherapy Tecentriq outcome research (ELITor) retrospective study, based on real-world data from the Carcinome HépatocellulaIrE en France (CHIEF) French cohort of hepatocellular carcinoma patients, aimed to get insight into the treatment patterns, the sociodemographic, clinical, biological, and etiological characteristics, and the quality of life of patients with unresectable hepatocellular carcinoma. METHODS AND RESULTS: Between 1 September 2019 and 4 December 2020, 367 patients from the CHIEF cohort received at least one locoregional (52.8%) chemoembolization or radioembolization or systemic treatment (88.3%) and were selected for ELITor. Most patients had a Barcelona Clinic Liver Cancer (BCLC) C (93.2%) hepatocellular carcinoma stage and were affected by cirrhosis (67.7%). Alcohol was confirmed as the main etiology both as a single etiology (29.1%) and in association with other risk factors (26.9%), mainly metabolic disorders (16.2%).Tyrosine-kinase inhibitors, mainly sorafenib, were the most administered systemic treatments in first line. Patients who received at least one combination of atezolizumab and bevacizumab during the study period ( N  = 53) had a better performance status and less portal hypertension frequency than the overall population and more hepatitis B virus infection and fewer metabolic disorders as single etiology. Overall, the global health score before treatment (62.3 ±â€…21.9) was in line with that of reference cancer patients and worsened in 51.9% of the cases after first-line palliative-intent treatment. CONCLUSION: This study provided real-life data on advanced hepatocellular carcinoma characteristics and treatment patterns and described the first patients to receive the atezolizumab-bevacizumab combination before it became the new standard of care for advanced hepatocellular carcinoma.

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.

Positive margins and plexitis increase the risk of recurrence after ileocecal resection: A systematic review and meta-analysis.

INTRODUCTION: There is debate over the impact of residual microscopic disease after ileocecal resection in Crohn's disease (CD) to predict recurrence. We conducted a meta-analysis to evaluate the impact of positive histological margins and plexitis after ileocecal resection on the risk of postoperative recurrence. METHODS: Using a systematic search, we identified. 30 studies evaluating the impact of inflammatory margins on CD recurrence. The primary outcome was the postoperative clinical recurrence and secondary outcomes were surgical, and endoscopic recurrence. We performed random-effects meta-analysis and estimated odds ratio (OR) and 95% CIs. RESULTS: Thirty studies were analyzed, seven focused on myenteric plexitis, six on submucosal plexitis and twenty-three on positive margins. Inflammatory margins were associated with a higher rate of clinical and surgical recurrences: respectively 14 studies - OR 2.38; 95% CI, 1.54 - 3.68- I2 = 68.2%, Q test-p = 0.0003 and 8 studies - OR, 1.52; 95% CI, 1.07-2.16 - I2 =0%; Q test-p = 0.43. The presence of myenteric plexitis was associated with a higher rate of clinical recurrence (4 studies- OR, 1.60; 95%CI, 1.12-2.29; I2= 0%, Q-test-p = 0.61), and of endoscopic recurrence (4 studies - OR, 4.25; 95%CI; 2.06-8.76; I2= 0%, Q test-p = 0.97). Submucosal plexitis was not associated with an increased risk of endoscopic recurrence (4 studies - OR, 0.94; 95%CI; 0.58-1.52; I2= 0%, Q test-p = 0.79). CONCLUSION: Inflammatory margins and/or plexitis were associated with postoperative recurrence after ileocecal resection for CD. These elements should be taken into account in future algorithm for prevention of postoperative recurrence.

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.

Neo-Adjuvant Use of Sorafenib for Hepatocellular Carcinoma Awaiting Liver Transplantation.

Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study. A clinical and biological evaluation was performed every month. Radiological tumor response evaluation was realized every 3 months on the waiting list and every 6 months after LT. Among 327 patients listed for HCC, 62 (19%) were treated with Sorafenib. Sorafenib was initiated for HCC progression after loco-regional therapy (LRT) in 50% of cases and for impossibility of LRT in 50% of cases. The mean duration of treatment was 6 months. Thirty six patients (58%) dropped-out for tumor progression and 26 (42%) patients were transplanted. The 5-year overall and recurrent-free survival after LT was 77% and 48% respectively. Patients treated for impossibility of LRT had acceptable 5-year intention-to-treat overall and post-LT survivals. Conversely, patients treated for HCC progression presented high dropout rate and low intention-to-treat survival. Our results suggest that it is very questionable in terms of utility that patients treated for HCC progression should even be kept listed once the tumor progression has been observed.

Endoscopic treatment of large gastric leaks after gastrectomy using the combination of double pigtail drains crossing a covered stent.

BACKGROUND: Endoscopy is the gold standard for the treatment of postoperative gastric leaks (GL). Large fistulas are associated with high rate of treatment failure. The objective of this study was to assess the clinical efficacy of a combining technique using a covered stent (CS) crossing through pigtails (PDs) for large postsurgical GL leaks. METHODS: All consecutive patients with large (> 10 mm) postsurgical GL treated endoscopically with a combination of a CS and PDs were included in a single-center retrospective study. The primary endpoint was the rate of GL closure. RESULTS: A total of 29 patients were included. Twenty-five patients underwent sleeve gastrectomy. The fistula (median diameter 15 mm) was diagnosed 6 days (IQR 4-9) after surgery. Technical success was observed in all procedures. After a median follow-up of 10.7 months (IQR 3.8-20.7), GL closure was observed in 82.7% with a median time of 63 days (IQR 40-90). Surgical management was finally necessary in four patients after a median of 186 days (IQR 122-250). No complications related to combined endoscopic treatment were observed especially stent migration during the follow-up. CONCLUSION: An endoscopic strategy combining CS crossing through PDs appears to be effective, safe and well tolerated for the treatment of large GL.

Alfapump® implantable device in management of refractory ascites: An update.

Refractory ascites (RA) is a frequent and life-threatening complication of cirrhosis. In selected patients with RA, transjugular intrahepatic portosystemic shunt (TIPS) placement and liver transplantation (LT) are currently considered the best therapeutic alternatives to repeated large volume paracentesis. In patients with a contraindication to TIPS or LT, the alfapump® system (Sequana Medical, Ghent, Belgium) has been developed to reduce the need for iterative paracentesis, and consequently to improve the quality of life and nutritional status. We report here recent data on technical progress made since the first implantation, the efficacy and tolerance of the device, the position of the pump in the therapeutic arsenal for refractory ascites, and the grey areas that remain to be clarified regarding the optimal selection of patients who are potential candidates for this treatment.

Mechanisms of chronic alcohol exposure-induced aggressiveness in cellular model of HCC and recovery after alcohol withdrawal.

Alcohol-related liver disease is the most prevalent chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. However, the knowledge on mechanisms by which alcohol consumption leads to cancer progression and its aggressiveness is limited. Better understanding of the clinical features and the mechanisms of alcohol-induced HCC are of critical importance for prevention and the development of novel treatments. Early stage Huh-7 and advanced SNU449 liver cancer cell lines were subjected to chronic alcohol exposure (CAE), at different doses for 6 months followed by 1-month alcohol withdrawal period. ADH activity and ALDH expression were much lower in SNU449 compared with Huh-7 cells and at the 270 mM dose, CAE decreased cell viability by about 50% and 80%, respectively, in Huh-7 and SNU449 cells but induced mortality only in Huh-7 cells. Thus, Huh-7 may be more vulnerable to ethanol toxicity because of the higher levels of acetaldehyde. CAE induced a dose-dependent increase in cell migration and invasion and also in the expression of cancer stem cells markers (CD133, CD44, CD90). CAE in Huh-7 cells selectively activated ERK1/2 and inhibited GSK3ß signaling pathways. Most of the changes induced by CAE were reversed after alcohol withdrawal. Interestingly, we confirmed the increase in CD133 mRNA levels in the tumoral tissue of patients with ethanol-related HCC compared to other HCC etiologies. Our results may explain the benefits observed in epidemiological studies showing a significant increase of overall survival in abstinent compared with non-abstinent patients.

Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines.

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe how patients with ARLD should be managed nowadays and discuss the main unsettled issues in the field.

Complete endoscopic healing is associated with lower disability than partial endoscopic healing in Crohn's disease: A prospective multicenter study.

INTRODUCTION: Crohn's disease (CD) has a significant impact on health status and quality of life, affecting physical and emotional well-being and impairing social and functional abilities. In the era of the treat-to-target concept, endoscopic healing has emerged as the goal to achieve to prevent intestinal damage and disability. It is not clear what level of endoscopic healing is associated with lower disability. We therefore aimed to compare disability associated with complete endoscopic healing to disability with partial endoscopic healing in patients with CD. METHODS: We conducted a multicenter prospective study, between September 2019 and November 2020, in one university hospital, one general hospital, and one private practice center. Consecutive patients with CD in clinical remission were included, having either complete endoscopic healing (CDEIS = 0) or partial endoscopic healing (CDEIS >0 and <4). The 10-item IBD-Disk self-assessment questionnaire was used to assess disability. Moderate to severe disability was defined as an overall IBD-Disk score ≥40. RESULTS: A total of 82 patients were included. Forty-four (53%) were women, the median age and disease duration were respectively 35.3 years (interquartile range [IQR], 28.6-45.2) and 8.0 years (IQR, 3.0-17.0). The median overall IBD-Disk score was 26.5 (IQR, 9 -45.0), and 30 (36.6%) patients had moderate to severe disability. Complete endoscopic healing was observed in 48 patients (57.3%). The median IBD-Disk score was respectively 24 (IQR, 9.0-40.5) and 34 (IQR, 9.5-51.5) for patients with complete and partial endoscopic healing (p = 0.068). Respectively, 13/48 (27%) and 17/34 (50%) of patients with complete and partial endoscopic healing had moderate to severe disability (p = 0.039). In multivariate analysis, partial endoscopic healing (OR=5.82, 95% CI [1.65, 24.69], p = 0.0009), female gender (OR=4.0, 95%CI [1.13, 16.58], p = 0.04), and smoking (OR=8.33, 95% CI [1.96, 50.0] p = 0.006) were significantly associated with moderate to severe disability. Among the IBD-Disk sub scores, the defecation score (median, IQR) (0.0 [0.0-3.0] vs 4.0 [0.0-7.5], p = 0.028) and energy score (4.0 [0.0-6.0] vs 6.0 [2.5-8.0], p = 0.023) were significantly lower with complete endoscopic healing. CONCLUSIONS: One-third of patient with endoscopic healing reported moderate to severe disability. Complete endoscopic healing (CDEIS = 0) was associated with lower disability than partial endoscopic healing (CDEIS >0 and <4). Deeper endoscopic healing may be needed to reduce the risk of disability in CD.

Rescuing SLAMF3 Expression Restores Sorafenib Response in Hepatocellular Carcinoma Cells through the Induction of Mesenchymal-to-Epithelial Transition.

BACKGROUND: Acquired resistance to sorafenib in hepatocellular carcinoma (HCC) patients results in poor prognosis. Epithelial-to-mesenchymal transition (EMT) is the major mechanism implicated in the resistance to sorafenib. We have reported the tumor suppressor role of SLAMF3 (signaling lymphocytic activation molecules family 3) in HCC progression and highlighted its implication in controlling the MRP-1 transporter activity. These data suggest the implication of SLAMF3 in sorafenib resistance mechanisms. METHODS: We evaluated the resistance to sorafenib in Huh-7 cells treated with progressive doses (Res cells). We investigated the link between acquired resistance to sorafenib and SLAMF3 expression by flow cytometry and Western blot methods. Furthermore, we analyzed the EMT and the stem cell potential of cells resistant to sorafenib. RESULTS: Sorafenib resistance was confirmed in Res cells by analyzing the cell viability in the presence of sorafenib. The mesenchymal transition, in Res cells, was confirmed by high migratory index and the expression of EMT antigens. Interestingly, we found that loss of SLAMF3 expression corresponded to sorafenib-resistant phenotypes. The overexpression of SLAMF3 reversed EMT, decreased metastatic potential and inhibited mTOR/ERK1/2 in Res cells. CONCLUSIONS: We propose that rescuing SLAMF3 expression in resistant cells could represent a potential therapeutic strategy to enhance sorafenib efficacy in HCC patients.

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.

Non-invasive diagnosis and follow-up of autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a liver disease characterised by necrotico-inflammatory lesions of hepatocytes, the presence of specific autoantibodies and response to corticosteroid treatment. AIH must be considered in any patient with acute or chronic liver disease. As there is no pathognomonic sign of AIH, the diagnosis is based on a combination of clinical, biological, immunological and histological findings, after excluding other causes of liver disease. The clinical and biological presentation of AIH is variable and AIH can be associated with an autoimmune biliary disease, primary biliary cholangitis or primary sclerosing cholangitis in an overlap syndrome. For these reasons, diagnosis of AIH can be challenging. Even if liver histology remains essential in the diagnosis of AIH, non-invasive tests can be used at different steps of the management of AIH: diagnosis of AIH, notably diagnosis of an overlap syndrome, assessment of severity of AIH, searching for extra-hepatic disease frequently associated to AIH, evaluation of response to therapy, decision of treatment withdrawal. This review aims to provide practical guidelines for the use of non-invasive tests for the diagnosis and the follow-up of AIH.

Non-invasive diagnosis and follow-up of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a rare and chronic cholestatic liver disease of unknown cause commonly associated with inflammatory bowel disease (IBD) and characterized by progressive obliterative fibro-inflammation of the biliary tree. Although the natural course is highly variable, PSC is often progressive, leading to biliary cirrhosis and its complications. In addition, PSC is a condition harbouring broad neoplastic potential with increased susceptibility for the development of both biliary and colon cancer. As in other chronic liver diseases, non-invasive methods play a major role in the diagnosis and monitoring of PSC. MR cholangiography is the key exam for the diagnosis and has replaced diagnostic endoscopic retrograde cholangiopancreatography (ERCP). A strict and standardised protocol for carrying out MR cholangiography is recommended. Liver stiffness measured by FibroScan® correlates with the degree of liver fibrosis, has a prognostic value and should be repeated during follow-up. Invasive methods still play an important role, especially ERCP which is indicated for therapeutic purposes or for endo-biliary sample collection in suspected cholangiocarcinoma (following discussion in a multidisciplinary team meeting) and total colonoscopy which is recommended at the initial diagnosis of any PSC and annually in patients with IBD.

Endoscopic Treatment of Enterocutaneous Fistulas in Crohn's Disease.

BACKGROUND: Management of enterocutaneous fistulas in Crohn's disease is challenging. Most patients still need intestinal resection in the biologic era. OBJECTIVE: The aim of this study was to evaluate the efficacy of endoscopic treatment for enterocutaneous fistulas. DESIGN: This is a retrospective study of medical records. SETTINGS: This study was conducted in a single institution. PATIENTS: All consecutive patients with Crohn's disease with an enterocutaneous fistula who underwent endoscopic fistula closure with the use of an over-the-scope clip or a hemostatic clip were included. MAIN OUTCOME MEASURES: The main outcome measured was the clinical success 3 months after the procedure, which was defined as the complete closure of all fistulas at physical examination and complete cessation of the drainage from the external opening, without surgery. RESULTS: Eight patients (men, 25%; median age 45 years [interquartile range, 33-51]) were followed. Fistulas were localized at the ileocolonic or colocolonic anastomosis in 7 patients and at the stomach in 1 patient. Seven patients were treated with an over-the-scope clip, and one was treated with a hemostatic clip. Technical success was achieved in all cases. Clinical success at 3 months was achieved in 75% of cases (6/8 patients). After a median 16-month (interquartile range, 13-23) follow-up, 3 of 8 (37.5%) patients had enterocutaneous fistula closure and 2 of 8 (25%) needed intestinal resection. No complications were observed. LIMITATIONS: The retrospective nature, the small sample size of the study, and the heterogeneity of the population limit the interpretation of the results. CONCLUSIONS: Endoscopic treatment of enterocutaneous fistulas is feasible with a short-term effectiveness. Additional studies are needed to confirm these results. See Video Abstract at http://links.lww.com/DCR/B614. TRATAMIENTO ENDOSCPICO DE FSTULAS ENTEROCUTNEAS EN ENFERMEDAD DE CROHN: ANTECEDENTES:Es desafiante el manejo de las fístulas enterocutáneas en enfermedad de Crohn. En la era biológica, la mayoría de los pacientes todavía requieren de resección intestinal.OBJETIVO:Evaluar la eficacia por tratamiento endoscópico de fístulas enterocutáneas.ENTORNO CLINICO:Estudio retrospectivo de registros médicos.AJUSTE:Realizado en una sola institución.PACIENTES:Se incluyeron todos los pacientes consecutivos con fístula enterocutánea en enfermedad de Crohn, sometidos a cierre endoscópico de la fístula con clip sobre el endoscopio o clip hemostático.PRINCIPALES MEDIDAS DE VALORACION:El éxito clínico a los 3 meses después del procedimiento. Definido al examen físico, como el cierre completo de todas las fístulas y cese completo del drenaje por la abertura externa, sin cirugía.RESULTADOS:Se estudiaron a ocho pacientes (hombres, 25%, mediana de edad de 45 años (rango intercuartílico, 33-51)). En 7 pacientes, las fístulas se localizaron en la anastomosis ileocolónica o colocolónica y un paciente, en el estómago. Siete pacientes fueron tratados con clip sobre el endoscopio y uno con clip hemostático. Se logró éxito técnico en todos los casos. Se logró éxito clínico a los 3 meses en 75% de los casos (6/8 pacientes). Después de una mediana de 16 meses (rango intercuartílico, 13-23), de seguimiento 3/8 (37,5%) pacientes presentaron cierre de fístulas enterocutáneas y 2/8 (25%) requirieron resección intestinal. No se observaron complicaciones.LIMITACIONES:Estudio retrospectivo, pequeño tamaño de la muestra y heterogeneidad de la población, limitaron la interpretación de los resultados.CONCLUSIONES:Es posible el tratamiento endoscópico de fístulas enterocutáneas con efectividad a corto plazo. Se requieren nuevos estudios para confirmar estos resultados. Consulte Video Resumen en http://links.lww.com/DCR/B614. (Traducción-Dr. Fidel Ruiz Healy).