View clinical trials related to Alcoholic Liver Disease.
Filter by: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.
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.
The fecal mycobiome, which refers to the community of fungi that resides in the human gut, is an important component of the gut microbiome. Research has shown that changes in the gut microbiome, including alterations in the fecal mycobiome, may play a role in the development and progression of alcoholic liver disease (ALD).One study published in the journal Gut Microbes found that individuals with ALD had a different gut microbiome composition compared to healthy individuals, including alterations in the levels of certain fungal species. Specifically, the study found that there was an increase in the abundance of the fungal genus Saccharomyces in individuals with ALD. This is significant because Saccharomyces is known to produce ethanol, which can contribute to liver damage in individuals with ALD.Another study published in the journal PLOS One found that there were differences in the levels of fungal metabolites in the fecal samples of individuals with ALD compared to healthy individuals. Specifically, the study found that there were higher levels of certain fungal metabolites, including acetaldehyde and ethanol, in the fecal samples of individuals with ALD.These findings suggest that the fecal mycobiome may play an important role in the development and progression of ALD. Maintaining a healthy gut microbiome through a balanced diet and other lifestyle factors may be an important strategy for preventing and managing ALD, and further research into the role of the fecal mycobiome in this condition is warranted.
This research programme seeks to combine the resources of NHS primary care, with the leading spectroscopic work in low-magnetic fields of the Wilson Group (Nottingham Trent University) to demonstrate the potential for benchtop Nuclear Magnetic Resonance (NMR) spectroscopy in human clinical pathology. This is an instrument assessment study for point of care viability which will also result in enhanced patient care (pending their consent) in blood screenings and metabolic health data.
The goal of this study is to investigate the role of gut leakiness in alcoholic liver disease. Gut leakiness may be the missing susceptibility factor that explains why some alcoholics develop liver disease and others don't. For this study, subjects 480 (240 male, 240 female, ages 18-80) will be recruited. Alcoholic subjects will be recruited from outpatient & inpatient alcohol detoxification units from Rush, Loyola & two halfway houses (one for women, one for men); patients with liver disease from GI/Hepatology Services at Rush, Hines VA Hosp & Loyola University; and controls from hospital staffs. All subjects will fill out a detailed questionnaire, be interviewed by the study coordinator & undergo an exam by the PI to ensure that all inclusion criteria are satisfied. All subjects will have a urine collection for tests of intestinal permeability (urinary sugars). Gut leakiness will be determined by the amount of sugars in the urine.
Background: Significant sex differences exist in regard to alcohol use disorder (AUD) and alcoholic liver disease (ALD). To date, no studies have examined the brain-gut-microbiome (BGM) axis (which is the relationship between the gut, brain, and the bacteria within the gut) and sex-differences in AUD and ALD. Aims: 1) Demonstrate baseline sex differences in the microbiome and metatranscriptome of AUD and ALD and correlate those differences to severity, 2) determine if these baseline sex differences predicts abstinence or ALD related outcomes, and 3) show how altering the microbiome can decrease the severity of AUD and ALD in a sexdependent manner. Hypothesis: Our project is aimed to explore the hypothesis that sex-related differences of the BGM axis in AUD and ALD explains the variation in patient severity and outcome by sex, and that alterations of the BGM axis can decrease the severity of AUD and ALD in a sex-dependent manner. Methods: A pilot randomized placebo (VSL#3 vs placebo) control trial will be performed in patients with AUD and ALD for 6 months. Questionnaire data, clinical labs, serum, and feces for shotgun metagenomics will be collected at baseline, 3-months, and 6-months. Anticipated Results: Patients with severe AUD/ALD will have more microbes and microbial genes associated with inflammation. These differences will predict outcomes at 6-months and that changes of this baseline microbiome with VSL#3 will lead to more positive outcomes than placebo, with men having greater benefit from VSL#3 than women. Implications and Future Studies: The discovery of the mechanisms underlying sex-related differences in AUD/ALD is needed for the development of personalized recommendations for prevention and treatment in men and women
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.
A Phase I clinical trial to determine the safety and tolerability of an anti-IL23 antibody for the treatment of patients with alcoholic liver disease
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.