Invasive Fungal Infections in Severe Alcohol-associated Hepatitis

NCT04103840 | Unknown DMC

• 1 other identifier: IEC-08/2019-1270
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet little is known about the role of intestinal fungi, or mycobiota in liver disease. Although the intestinal microbiome contains bacteria, fungi, and viruses, research in the field of liver disease has almost exclusively focused on the interaction between the host and gut bacteria. The fungal microbiota is an integral part of the gastrointestinal micro-ecosystem with up to 106 microorganisms per gram of faeces. Numerous interactions between fungi and bacteria and the complex immune response to gastrointestinal commensal or pathogenic fungi have been demonstrated in prior studies. Alcohol-dependent patients display a reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients also demonstrate systemic exposure and immune response to mycobiota. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease especially alcoholic hepatitis. In this study, we will attempt to find out the natural fungal mycobiome in Severe alcoholic hepatitis when compared with apparently healthy asymptomatic controls from their family. This will allow us to therapeutically modify the unbalanced gut microbiota and improve patient outcomes. Secondly, it will provide further insight as to why alcohol-associated hepatitis patients are particularly susceptible to fungal infections. In the age of frequent antibacterial drug therapy, the role of commensal and pathogenic fungi in the human gut has gained paramount importance.

Conditions

Severe Alcoholic Hepatitis; Chronic Liver Disease and Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Survival

  Patients who survive till Day 28 and Day 90

  at Day 28 and Day 90

Secondary Outcomes (3)

• Non-elective hospital admissions

  90 Days

• Clinical and biochemical parameters will be compared at 0 and 90 days

  90 days

• Clinical events like decompensation in the form of new onset ascites, variceal bleed, renal dysfunction, hepatic encephalopathy, infections

  90 days

Study Arms (2)

Severe alcohol- associated hepatitis

Severe alcohol associated hepatitis as defined by probable/ conformed National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria

Other: Testing stool mycobiota

Control

Apparently healthy Family controls

Other: Testing stool mycobiota

Interventions

Testing stool mycobiota OTHER

Both cohorts of SAH and their family controls will be tested for fecal mycobiota

Control; Severe alcohol- associated hepatitis

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Alcohol-associated hepatitis (AH) is defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria as biopsy proven or clinically diagnosed AH in patients with heavy alcohol use and typical liver tests without confounding factors

You may qualify if:

• Severe Alcoholic Hepatitis
• Aged between 18 Years to 70 Years
• Either gender
• Study will also include age matched healthy controls from the patient's family

You may not qualify if:

• Inability to obtain informed consent from patient or relatives.
• Severe cardiopulmonary disease
• Pregnancy
• HIV infection
• Recent abdominal surgery (with in last 6 months)
• Patient on immunosuppressive drugs
• Malignancies including Hepatocellular carcinoma
• Gastrointestinal (GI bleed) in the last 4 weeks
• Oral antibiotics or antifungals taken in last 2 weeks.

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Postgraduate Institute of Medical Education and Research

Chandigarh, Choose Any State/Province, 160012, India

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Fecal mycobiota

MeSH Terms

Conditions

Hepatitis, Alcoholic; Fibrosis

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Radha Dhiman, MD DM

  Post Graduate Institute of Medical Education and Research, Chandigarh

  STUDY CHAIR

Central Study Contacts

Madhumita Premkumar, DM

CONTACT

01722756344; drmadhumitap@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Hepatology

Study Record Dates

• First Submitted: September 1, 2019
• First Posted: September 26, 2019
• Study Start: August 27, 2019
• Primary Completion: October 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 1, 2020

Record last verified: 2020-03

Locations

IN (1)