Alcoholic Liver Disease

Alcohol-induced liver injury is made up of fatty liver, fibrosis and alcoholic hepatitis (AH), elementary lesions that may occur separately, simultaneously or sequentially in a same patient. Among these histological features, alcoholic hepatitis, a necro-inflammatory process is associated with the fastest fibrosis progression leading to cirrhosis in 40% of cases and a pivotal lesion driving increased risk of liver decompensation. The non-invasive methods for the diagnosis of fibrosis open new perspectives for a better understanding of the natural history of disease-progression from early injury to the cirrhotic stage, for the identification of subgroup patients at risk of developing cirrhosis at medium term and for proposing a strategy of screening of patients with extensive cirrhosis at risk of liver-threatening events. There is an urgent need to perform studies in asymptomatic heavy drinkers in order to identify cut-offs associated with significant risk of development of cirrhosis at medium term. Such objectives require large-scale screening of heavy drinkers. Each of non-invasive methods have been tested to predict with of extensive fibrosis with a high predictive performance as shown below. A screening policy cannot be accepted without answering the following questions: a) are the requirements of public health screening fulfilled? b) Is the group of patients undergoing screening defined? c) is there a reliable method for of testing? Indeed, the detection of a disease is subject to certain public health requirements and may be proposed to health authorities only if it modifies the management of subjects screened. In the specific case of mass screening of liver fibrosis in heavy drinkers, only the detection of extensive fibrosis could fulfill this criterion because of the potential survival benefit resulting from the screening of hepatocellular carcinoma (HCC) in patients with extensive fibrosis. Indeed, recent studies have found that the probability of receiving curative treatment of HCC was significantly higher in patients who received a six-month surveillance ultrasound. Therefore, the detection of extensive fibrosis seems reasonable in the light of these studies when considering that the yearly risk of development of HCC in the subgroup of heavy drinkers with extensive fibrosis is approximately 3%. Taking into account the above scientific arguments, the most recent EASL clinical practical guidelines on ALD recommend longitudinal studies using non-invasive tools to evaluate screening of extensive fibrosis and disease progression in heavy drinkers.

Alcoholic hepatitis carries a risk of high mortality at short term, especially in its severe form. Its diagnosis is confirmed by liver biopsy. The prevalence of alcoholic hepatitis, severe or not severe, is poorly known and prospective data are needed. The present observational study aims to define the prevalence of alcoholic hepatitis among patients admitted for jaundice and determine their outcome according to the severity. Survival and markers of liver dysfunction will be assessed. A biobank including genetic samples will be created to identify the disease profile in terms of inflammation and regeneration. The performance of non-invasive criteria for diagnosis will also be studied.

Alcoholic hepatitis (AH) is a serious complication of alcoholic liver disease (ALD). The histological presentation of AH is characterized by neutrophilic lobular inflammation, macrovesicular steatosis, hepatocyte ballooning and necrosis and the presence of Mallory bodies. In cases of severe HA, defined by a modified Maddrey score of 32 or above, mortality at 1 month is estimated at between 10 and 50%. The only treatment to reduce early mortality is corticosteroid therapy. However, only 60% of patients respond to corticosteroids, and no benefit has been demonstrated on late mortality. Identifying new therapeutic targets is therefore a major challenge in this disease. Numerous pre-clinical studies and human data suggest the involvement of the intestinal microbiota in the pathogenesis of AH. Translocation of viable bacteria and microbial products from the digestive tract to the liver contributes to local and systemic inflammation, hepatocyte death and fibrogenesis. However, the intrahepatic microbial environment has never been characterized in HA. The study hypothesis is that the intrahepatic microbiota is modulated by bacterial translocation and is associated with clinical outcomes. The aim of this study is to determine the composition of the intrahepatic (obtained from transjugular liver biopsy), blood and fecal microbiota in patients with suspected severe AH from a monocentric prospective cohort in the Hepatology Department at Croix-Rousse Hospital (Lyon). Fifty consecutive patients with clinical suspicion of AH and indication for transjugular liver biopsy will be included. About thirty-five patients are expected in the confirmed AH group, and 15 in the group "alcoholic liver disease with no AH", based on data from the literature. The composition of the various microbiota will be determined by sequencing the 16S rRNA gene, and the results will be correlated with clinical data (corticosteroid sensitivity, overall survival, transplant-free survival, MELD score in particular) and histological data. This exploratory study will enable to analyze the intra-hepatic microbiota, and to study its link with intra-hepatic inflammation and the clinical course of patients with AH. The data generated by HepMAH will thus help identify potential new therapeutic targets linked to the gut microbiota, and provide a scientific basis for the development of therapeutic interventions targeting the microbiota in HA.

This is an observational study that will explore the hypothesis that by combining data from patients with liver disease with novel blood biomarkers, single nucleotide polymorphism (SNP) analysis and faecal microbiome analysis. The Investigators will improve diagnosis of liver fibrosis compared to the current available diagnostic tools.

In this study we plan to demonstrate that ethanol induces skeletal muscle autophagy to degrade MAA adducts.

Patients with COVID-19 and comorbidities including alcohol associated liver disease (ALD) are at risk for severe illness and abrupt or sudden clinical deterioration with ventilatory failure. â-hydroxy â-methyl butyrate (HMB), a non-nitrogenous leucine metabolite with anabolic properties, increases muscle mass and contractile function and enhances immune function. We aim to study the natural course of COVID-19 in patients with ALD and test whether HMB can affect ventilatory deterioration and improve short and long-term morbidity, mortality, and recovery from critical illness in symptomatic COVID-19 patients with ALD.

The investigators conduct a randomized, double-blind, placebo-controlled study to investigate the effects of Fermented Protaetia brevitarsis seulensis powder on Alcohol-induced Liver Disease in adults for 8 weeks.

Excessive alcohol consumption is a major public health problem, particularly in France. It is the leading cause of cirrhosis and hepatocellular carcinoma. Among subjects with heavy alcohol consumption, the majority of patients develop fatty liver overload (steatosis), but only 10 to 35% develop acute alcoholic hepatitis (AAH) and 8 to 20% progress to cirrhosis. Steatosis is the earliest lesion, rapidly reversible after abstinence from alcohol. On the other hand, the occurrence of AAH leads to a strong progression of fibrosis. The investigators have shown on serial liver biopsies that a subgroup of heavy drinkers develop episodes of AAH and progress to cirrhosis. Therefore, factors other than the amount of alcohol consumed alone influence the development and progression of alcoholic liver disease (ALD). Among these factors, it is now accepted that the gut microbiome plays an important role in the pathogenesis of ALD. Increased intestinal permeability and activation of the innate immune system by lipolysaccharide (LPS) of digestive origin is a key factor in the initiation of AAH. The alteration of the intestinal barrier induced by alcohol abuse seems to involve dysbiosis. Furthermore, the investigatorshave shown that the sensitivity of the liver to alcohol toxicity is transmissible from humans to mice via the gut microbiome. Despite these advances, the causal relationship between mycobiome disruption and ALD in humans requires confirmation in prospective studies. The intestinal microbiome represents all the microorganisms found in the digestive tract: bacteria (bacterial microbiome), viruses (virome), fungi (mycobiome). Recent data point to the role of disturbances of the mycobiome and the virome in human pathology. The intestinal virome consists of two major types of viruses: eukaryotic RNA and DNA viruses that infect host cells and prokaryotic or bacteriophage viruses that infect the bacterial microbiome. Recent evidence suggests that the virome participates in immune system homeostasis. Infection of axenic mice with murine norovirus restores the functionality of intestinal lymphocytes. However, the involvement of the intestinal virome in ALD has never been studied. Cessation of alcohol consumption has a beneficial effect in all stages of ALD . It reduces the risk of complications of cirrhosis and, for early stages of liver damage, prevents progression to advanced stages (severe AAH and cirrhosis). Unfortunately, most patients with alcohol addiction do not achieve long-term abstinence or significant reduction in their consumption despite psychological and medical support. Depression and anxiety are also associated with gut dysbiosis in humans. The causal role, at least partial, of this dysbiosis in addictive phenomena, whether alcohol or other addictions such as cocaine, has been shown. Thus, the modification of MI influences the addictive behavior of cocaine-dependent mice (. All these data show the major role of the microbiota-central nervous system (CNS) axis in mental disorders such as alcohol addiction and its consequences (craving, depression, anxiety). This interaction is mediated by several mechanisms such as the production of active metabolites by the intestinal microbiome and the translocation of bacteria or bacterial derivatives. Primary Objective: To characterize temporal changes in the gut microbiome (bacterial, viral, and fungal) within sequential specimens (stool, saliva, serum) prior to the occurrence of acute alcoholic hepatitis episodes Secondary Objectives: * Demonstrate that specific fecal, serum, or saliva microbiome profiles (bacterial, viral, and fungal) can predict the progression of alcoholic liver disease to severe alcoholic hepatitis, fibrosis, and cirrhosis. * Characterize changes in the composition of the gut microbiome (bacterial, viral and fungal) associated with the progression of alcoholic liver disease to severe alcoholic hepatitis and cirrhosis. * Characterize the changes in the microbiome during alcohol withdrawal. * Identify microbiome profiles associated with alcohol dependence and anxiety-depressive events related to alcohol addiction. * To identify bacterial species with a protective effect in alcoholic liver disease. * To identify beneficial bacterial species against alcohol dependence. * To study the microbiome-host interaction in alcoholic liver disease and alcohol addiction. * To identify microbiome profiles with prognostic value in severe alcoholic hepatitis and alcoholic cirrhosis. Number of centers: 7 Number of subjects expected 1000 Population concerned: The study will include a population of patients with excessive alcohol consumption seen in consultation or hospitalized for alcohol addiction problems and/or exploration of alcohol-related liver damage Inclusion period: January 2020 - January 2030 Patient observation period: 5 to 20 years Study duration: 30 years

The goal of this clinical trial is to evaluate the efficacy of screening for liver disease with liver stiffness measurement on abstinence or light consumption after 6 months in individuals who are receiving treatment for alcohol use disorder and without a history of liver disease. The investigators will conduct a randomized controlled trial with concealed allocation comparing A) an invitation to a liver stiffness measurement, blood sampling and leaflet on alcohol-related disease (intervention) with B) an invitation to blood sampling (control). The primary outcome is 'abstinence or light consumption' (≤ 10 units/week) throughout the last months, and assessed 6 months after randomization.

This prospective, analytic observational study will investigate alcohol recidivism in patients with alcoholic liver disease. All adult subjects presenting with alcoholic liver disease are considered for inclusion. Subjects able to give consent are included.

Alcoholic liver disease represents the major health issues and it ranges from simple steatosis to cirrhosis. There is a paucity of data to support the allopathic intervention among these group of patients. Livitol-17 consist of the 3 whole herbs and extract which has antioxidant, hepatoprotective as well as reno-protective properties. The aim of this trial is to study the efficacy of herbal supplement to improve the liver function of alcoholic liver disease subject.