French National MICMAF Cohort

Conditions studied

Alcoholic Liver Disease

About this study

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…

Interventions

• Genetic: Sequential sampling (stool, saliva, serum) . — Sequential sampling (stool, saliva, serum) prior to the occurrence of AAH episodes in heavy drinking patients to identify protective or deleterious profiles.

Primary outcomes

• Temporal changes in the gut microbiome (every 6 months until 240 months)

Eligibility information

Study locations

• Cosmin Voican, Clamart, Île-de-France Region 92140 France