Abstract
Background
Severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure (ACLF) carries a high short-term mortality. Alteration of gut microbiota is a crucial component implicated in its pathogenesis, whose modulation has been suggested as a potential therapeutic tool. We evaluated the safety of fecal microbiota transplantation (FMT) and its efficacy in improving short-term survival and clinical severity scores in patients with SAH–ACLF.
Methods
Thirty-three patients [13 in the FMT arm; 20 in the standard of care arm (SOC)] with SAH–ACLF were included in this open-label study. A single FMT session was administered as a freshly prepared stool suspension from pre-identified healthy family member stool donors through a nasojejunal tube. Patients were followed up on days 7, 28, and 90.
Results
Survival at 28 and 90 days was significantly better in the FMT arm (100% versus 60%, p = 0.01; 53.84% versus 25%, p = 0.02). Hepatic encephalopathy resolved in 100% versus 57.14% (FMT versus SOC, p = 0.11) patients, while ascites resolved in 100% versus 40% survivors (p = 0.04). Major adverse event rates, including spontaneous bacterial peritonitis and gastrointestinal bleeding, were similar in both groups (p = 0.77; p = 0.70). Median IL1beta decreased by 21.39% (IQR − 73.67 to 7.63) in the FMT group, whereas it increased in the SOC by 27.44% (IQR − 0.88 to 128.11) (p = 0.01). Percentage changes in bilirubin and ALT between baseline and day 7 emerged as predictors of 90-day mortality.
Conclusion
FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH–ACLF.
Clinical trial number
NCT03827772 available from http://clinicaltrials.gov/ct2/show/NCT03827772
CTRI Reference number: CTRI/2019/02/017538 dated 7 February 2019.
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Data and code availability
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Abbreviations
- ACLF:
-
Acute on chronic liver failure
- APASL:
-
Asian Pacific Association for the study of the liver
- ALT:
-
Alanine aminotransferase
- Anti-HBc:
-
Antibodies to hepatitis B core antigen
- AST:
-
Aspartate aminotransferase
- CANONIC:
-
Chronic Liver Failure (CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis
- CDI:
-
Clostridium difficile Infection
- CDR:
-
Cirrhosis dysbiosis ratio
- CLIF-C:
-
ACLF Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure Score
- CLIF-C:
-
OF Chronic Liver Failure Consortium-Organ Failure score
- CLIF-SOFA:
-
Chronic Liver Failure-Sequential Organ Failure Assessment score
- CTP:
-
Child–Turcotte–Pugh score
- FMT:
-
Fecal microbiota transplantation
- GM:
-
Gut microbiota
- HAV:
-
Hepatitis A virus
- HBsAg:
-
Surface antigen for hepatitis B
- HCV:
-
Hepatitis C virus
- HE:
-
Hepatic encephalopathy
- HIV:
-
Human immunodeficiency virus
- IL:
-
Interleukin
- INR:
-
International normalized ratio
- LFT:
-
Liver function tests
- mDF:
-
Maddrey’s discriminant function
- MELD:
-
Score model for end-stage liver disease
- MELD-Na+ :
-
Score model for end-stage liver disease sodium score
- PAMPs:
-
Pathogen-associated molecular patterns
- PGIMER:
-
Postgraduate Institute of Medical Education and Research
- PRR:
-
Pattern recognition receptor
- SAH:
-
Severe alcoholic hepatitis
- SOC:
-
Standard of care
- VDRL:
-
Venereal Disease Research Laboratory test
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AS and AR: data compilation and manuscript writing; RKD: concept, manuscript writing, and editing; MPK: manuscript editing and revision; NV: statistical analysis; AD: manuscript editing and revision; SG: data compilation; MC: data extraction; ST: manuscript revision.
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Anima Sharma, Akash Roy, Madhumita Premkumar, Nipun Verma, Ajay Duseja, Sunil Taneja, Sandeep Grover, Madhu Chopra and Radha K. Dhiman declare that they have no conflict of interest.
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Sharma, A., Roy, A., Premkumar, M. et al. Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial. Hepatol Int 16, 433–446 (2022). https://doi.org/10.1007/s12072-022-10312-z
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DOI: https://doi.org/10.1007/s12072-022-10312-z