Invasive Fungal Infections in Severe Alcohol-associated Hepatitis

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

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.

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.

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.