The Liver-Related Digestive Diseases Group of the Chinese Society of Hepatology, Chinese Medical Association, has developed an expert consensus on Fecal Microbiota Transplantation (FMT) for chronic liver diseases. This consensus aims to standardize and guide clinicians in the application of FMT, recognizing the crucial role of gut microbiota in liver function and host health.
Background
The gut-liver axis is a significant area of research. Chronic liver diseases, including chronic viral hepatitis, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), autoimmune liver disease (AILD), liver cirrhosis (LC), hepatic encephalopathy (HE), and liver cancer, are associated with gut microbiota dysbiosis. FMT is considered a promising therapy to restore microbiota balance, improve liver function, reduce inflammation, and enhance patient quality of life. This consensus addresses the previously undefined indications, contraindications, and standardized protocols for FMT in these conditions.
Methodology
The consensus was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system, classifying evidence quality as high (A), moderate (B), or low/very low (C), and recommendation strength as strong (1) or weak (2). The Delphi method and nominal group technique were used to finalize recommendations.
Key Recommendations
Indications
FMT is applicable for various etiologies of chronic liver diseases (excluding drug-induced liver injury), including:
- Chronic hepatitis B (CHB)
- Alcoholic liver disease (ALD)
- Metabolic dysfunction-associated steatotic liver disease (MASLD)
- Autoimmune liver disease (AILD)
- Liver cirrhosis (LC)
- Hepatic encephalopathy (HE)
- Liver cancer (to enhance sensitivity to antitumor therapy)
Evidence suggests FMT can correct microbiota imbalance and modulate intestinal immune and metabolic pathways, thereby alleviating hepatic inflammation and fibrosis.
Contraindications
Conditions requiring careful risk-benefit assessment or precluding FMT use include:
- Unstable vital signs
- Severe intestinal barrier impairment
- Severe immunosuppression
- Pregnancy
Efficacy and Safety
FMT, when used alongside standard treatments, has demonstrated safety and efficacy for patients with CHB, alcoholic hepatitis (AH), MASLD, primary sclerosing cholangitis (PSC), LC, and HE. It may also enhance tumor sensitivity to anticancer therapy in hepatocellular carcinoma (HCC). Mild, self-limiting gastrointestinal symptoms are the most common adverse reactions. Rigorous donor screening is crucial for safety.
Donor Selection and Management
- Donor Selection: Standard non-related donors are prioritized. Mandatory comprehensive screening includes health history, psychological evaluation, and extensive laboratory tests (blood and stool) to exclude pathogens, multidrug-resistant organisms, and other risks.
- Donor Management: Donors require ongoing management for stability and sustainability, involving regular health re-evaluations and retention of stool samples. Dietary advice includes emphasizing plant-based, high-fiber foods and avoiding high-fat, high-protein, irritant, or hard-to-digest foods.
Transplantation Route
FMT can be delivered via upper GI (oral capsules), mid-GI (gastroscopy, nasoduodenal/nasojejunal tube), or lower GI (colonoscopy, enema) routes. A multidisciplinary team should determine the optimal route based on patient tolerance and disease specifics, with essential informed consent.
Pre-transplant Preparation
Antibiotic use should generally be avoided before FMT to prevent negative impacts on engraftment success and microbiota diversity. Bowel preparation is recommended for lower GI routes.
Dose, Frequency, and Form
Higher doses and more frequent administrations are typically associated with better efficacy in restoring microbiota balance and reducing recurrence. Fresh fecal samples are reported to yield better outcomes than frozen ones. Regimens should be tailored to individual patient responses.
Follow-up Principles
- Short-term: Within 24 hours to monitor tolerance.
- Long-term: Evaluating symptoms and relevant tests at 4 weeks.
- Follow-up duration should be at least 8 weeks.
- If the initial response is inadequate, a donor change or repeat FMT may be considered.
Adverse Reactions and Management
Most adverse reactions are mild, self-limiting gastrointestinal symptoms. Risks can be mitigated by strict donor screening and thorough patient assessment. Patient education on potential reactions and management is important.
Precautions for Special Populations
- Children and Pregnant Women: FMT in these populations requires extreme caution and careful evaluation. There are currently no reports on FMT in children with chronic liver disease, and it is not recommended for pregnant women.
- Multidisciplinary assessment, physician-patient trust, and transparent informed consent are paramount.
Conclusion
This expert consensus provides a structured framework for the standardized application of FMT in chronic liver diseases, based on current evidence and clinical experience. It emphasizes the therapeutic potential of FMT across various liver conditions, while highlighting the critical need for rigorous donor screening, patient selection, and procedural safety. The consensus aims to guide clinicians in optimizing FMT use and calls for further high-quality research, particularly concerning long-term efficacy and application in special populations.