Invasive Fungal Infections in Severe Alcohol-associated Hepatitis

Chronic Liver Disease and Cirrhosis Clinical Trial

Official title:

Assessment of Invasive Fungal Infections as a Result of Fungal Dysbiosis in Patients With Severe Alcohol-associated Hepatitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04103840
• Other study ID #: IEC-08/2019-1270
• Status: Recruiting
• Start date: August 27, 2019
• Est. completion date: December 1, 2022

Study information

• Verified date: March 2020
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Madhumita Premkumar, DM
• Phone: 01722756344
• Email: drmadhumitap[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The patients of severe alcohol-associated hepatitis admitted under Department of Hepatology, in Liver intensive Care Unit (LICU) Male or Female medical wards or coming to follow up in Liver clinic of Postgraduate Institute of Medical Education and Research, Chandigarh, India from will be screened for enrolment after ethical approval from the institute ethics committee. Both previously compensated and decompensated patients will be enrolled in this prospective observational pilot study. All patients will be followed up at 30 and 90 days from inclusion into the study.

Estimation of sample size Sample size will be estimated based on previous studies. This is a pilot prospective observational study. Based on currently available data from our centre on acute-on chronic liver failure, 22.5% of cirrhotics have suspected IFI, and up to 25% of SAH have suspicion for IFI, it is estimated that a total sample size of 60 patients would be required, with an effect size of 0.5, alpha 0.05, and power 0.85. Therefore, 80 patients will be required to enroll to account for 15% attrition. Hence, we propose to enroll 80 consecutive patients with SAH with 80 matched controls from their family starting from 15th August 2019.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 1, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

1. Inability to obtain informed consent from patient or relatives.

2. Severe cardiopulmonary disease

3. Pregnancy

4. HIV infection

5. Recent abdominal surgery (with in last 6 months)

6. Patient on immunosuppressive drugs

7. Malignancies including Hepatocellular carcinoma

8. Gastrointestinal (GI bleed) in the last 4 weeks

9. Oral antibiotics or antifungals taken in last 2 weeks.

Related Conditions & MeSH terms

• Chronic Liver Disease and Cirrhosis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic
• Invasive Fungal Infections
• Liver Diseases
• Mycoses
• Severe Alcoholic Hepatitis

Intervention

Other:
• Testing stool mycobiota
Both cohorts of SAH and their family controls will be tested for fecal mycobiota

Locations

Country	Name	City	State
India	Postgraduate Institute of Medical Education and Research	Chandigarh	Choose Any State/Province

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	Patients who survive till Day 28 and Day 90	at Day 28 and Day 90
Secondary	Non-elective hospital admissions	Number of hospital admissions will be documented	90 Days
Secondary	Clinical and biochemical parameters will be compared at 0 and 90 days	Change in biochemical parameters including liver function tests, renal function tests, ammonia etc.	90 days
Secondary	Clinical events like decompensation in the form of new onset ascites, variceal bleed, renal dysfunction, hepatic encephalopathy, infections	Number of decompensation events [ascites, variceal bleed, renal dysfunction, hepatic encephalopathy, infections]	90 days