Fecal Microbiota Therapy in Steroid Ineligible Alcoholic Hepatitis

AIM- To assess survival benefit at 3 month, in patients of severe alcoholic hepatitis who are steroid ineligible.

Methodology:

Study population: Fecal microbiota therapy in steroid ineligible Alcoholic hepatitis: Randomized controlled trial.

Study design:

A prospective, randomized controlled trial. The study will be conducted on the consecutive patients presenting with severe Alcoholic hepatitis to the wards of Department of Hepatology, ILBS, New Delhi from feb 2022 to February 2023 who meet the inclusion criteria.

Study period: 2 years from the date of ethics approval

Techinue for FMT Healthy donor will be screen as per ILBS FMT proforma- donor should be from family and emotionly attached.

Stool collection

1. Donors will be supplied clean, sealable containers for collection and transport of stool. Containers will be labeled with the name, UHID and date/time of stool collection.
2. Collected stool will be immediately transferred to the laboratory facility for processing and used within 6 hours collection
3. Stool sample from Healthy donor will be processed
4. Patient preparation
5. Patient was kept NPO for 4 hours prior to stool instillation
6. Iv antibiotics were continued as per treating doctor in the event of sepsis
7. The patient was allowed to consume the prescribed diet 2 hours after the procedure instillation
8. Methods of FMT infusion.
9. Seven doses (30gm one dose) of FMT will be given via jejunal port of NJ/NG tube

Sample size with justification:

Assuming that the survival in FMT group is 87.5% and 33% in SMT Group with alpha 5 %, power 95% we need to enroll 52 in FMT group and 26 in SMT Group so that the FMT versus SMT ration is 2. Further assuming 5% defaulter rate /drop out rate we decided to enroll 56 and 28 on FMT and SMT arm.We will enroll 84 patients, block size of 6

Intervention:

1. Patients will be randomized into two Arms A \& B.
2. Arm A will receive fecal microbioata therapy for 7 Days, Seven doses (30gm stool prepared in 100 ml Ns everyday as described ) of FMT will be given via jejunal port of NJ/NG tube.
3. Arm B will receive standard medical therapy.
4. Patient preparation in Arm A
5. Patient was kept NPO for 4 hours prior to stool instillation
6. Iv antibiotics were continued as per treating doctor in the event of sepsis
7. The patient will be allowed to consume the prescribed diet 2 hours after the procedure.
8. Both groups received Antibiotics, multivitamins, albumin infusions, nutrition will be used as per clinical discretion in both groups.

Data to be collected:

1. Baseline - CBC, LFT, RFT, Serum albumin, total protein, Chest X Ray, Serum electrolytes, PT, INR baseline and then for first 7 days then at 28 days ,90 and 180 days then whenever needed
2. PCT and CRP baseline and whenever needed
3. Amylase, lipase baseline if needed
4. HIV,IgM,HAV Ab,IgM HEV, HBsAg, HB core Ab (total),AntiHCV- baseline
5. Blood cultures x2- baseline and whenever needed
6. Urine culture \& urinalysis-Baseline and whenever needed
7. Ascites for albumin, total protein, TLC cell count and differential, SAAG, G/S, C/s (if present)
8. TNF alpha, TGF B, IL 1, IL 6, IL22 baseline then at 28 days,90 and 180 days.
9. Stool studies (if diarrhea): C. difficile, culture,
10. stool Microbioata analysis baseline and whenever needed
11. Glucose H2 Breath test if needed
12. UGI endoscopy with (D2 biopsy/Aspirate whenever feasible), and NJ placement done at baeline for FMT insertion.
13. Complete abdominal ultrasound or cross-sectional radiology
14. Liver Biopsy (If Feasible)

Statistical Analysis:

Data will be reported as mean + SD. Categorical variables will be compared using the chi-square test or Fisher exact test. Normal continuous variables will be compared using the Student's t test Non normal continuous variables will be compared using the Mann Whitney rank-sum test (unpaired data) or the Wilcoxon test (paired data). The actuarial probability of survival will be calculated by the Kaplan-Meier method and compared using the log-rank test. A Cox regression analysis will be performed to identify independent prognostic factors for survival.Univariate and multivariate analysis will be used whenever applicable.

Adverse effects:

Side effects related to FMT will be noted. Abdominal Pain, Bloating, loss of appetite Gas/Flatulence, Constipation, Diarrhea , Nausea ,Vomiting Fever

Stopping rule of study:

1. New onset infection (sepsis)
2. Patient refusal After starting Therapy
3. Liver transplantation

Expected outcome of the project-Modulation of gut microbiota and correction of dysbiosis in severe Alcoholic hepatitis through healthy donor Fecal Implantation therapy improves gut dysbiosis and provide survival benefit at 3 months