intra-hepatic microbiota in alcoholic hepatitis

Conditions: Cirrhosis; Alcoholic Liver Disease; Alcoholic Hepatitis

Summary: 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.


Eligibility criteria:
inclusion criteria: * patients suffering from alcoholic liver disease and clinical suspicion of alcoholic hepatitis (subacute jaundice, heavy alcohol consumption active or weaned for ≤ 3 months, modified maddrey score ≥32) and indication for diagnostic transjugular liver biopsy; * non-objection obtained from the patient or trusted person in case of impaired judgment or consciousness before performing liver biopsy; * aged ≥ 18 years at the time of study entry; exclusion criteria: * patients who have been treated with antibiotics or probiotics within the last 15 days prior to liver biopsy, with the exception of antibiotics used for prophylaxis of ascites infection or hepatic encephalopathy * contraindication to transjugular liver biopsy (hepatocellular carcinoma on predicted puncture site) * pregnant, parturient or breast-feeding women * persons deprived of their liberty by judicial or administrative decision * adults under legal protection (guardianship, curators)

Keywords: alcoholic hepatis bacterial translocation microbiota 16s rrna intra-hepatic microbiota cirrhosis alcoholic liver disease