Expert guidance on fecal microbiota transplantation in liver disease

The gut microbiota plays a crucial role in maintaining host health and liver function. Fecal microbiota transplantation (FMT), an emerging therapeutic modality, has demonstrated promising potential in the treatment of chronic liver diseases. To assist clinicians in rapidly mastering and standardizing the clinical application of FMT for chronic liver disease, the Liver-Related Digestive Diseases Group of the Chinese Society of Hepatology, Chinese Medical Association, has developed this expert consensus. The consensus comprehensively addresses key aspects of FMT application, including indications, contraindications, efficacy, safety, donor selection and management, transplantation routes, precautions, and the prevention and management of adverse reactions for chronic liver conditions such as chronic hepatitis, cirrhosis, and liver cancer, thereby providing reference and guidance for clinical practice.

Introduction

The gut-liver axis has become a central focus in life sciences research in recent years. Chronic liver diseases encompass a wide spectrum of pathological conditions, 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. A substantial body of evidence supports the presence of gut microbiota dysbiosis in these diseases. Restoring the balance of the gut microbiota, for instance through FMT, holds promise for improving liver function, alleviating inflammatory responses, and enhancing patients' quality of life. However, the indications, contraindications, and standardized protocols for FMT in chronic liver disease remain incompletely defined. This consensus aims to provide systematic guidance for clinicians in this field.

Quality of evidence and strength of recommendations

This consensus was developed following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The quality of evidence was categorized as high (A), moderate (B), or low/very low (C). The strength of each recommendation was classified as strong (1) or weak (2). The Delphi method and nominal group technique were employed to formulate the final recommendations.

Key clinical issues and recommendations

1. Indications for FMT in chronic liver disease: FMT is applicable to chronic liver diseases of various etiologies (excluding drug-induced liver injury), including chronic hepatitis B (CHB), ALD, MASLD, AILD, LC, HE, and liver cancer (to enhance sensitivity to antitumor therapy). Evidence suggests FMT can correct microbiota imbalance, modulate intestinal immune and metabolic pathways, thereby alleviating hepatic inflammation and fibrosis. 

2. Contraindications and contraindicated populations: Contraindications include unstable vital signs, severe intestinal barrier impairment, severe immunosuppression, and pregnancy. These conditions necessitate careful risk-benefit assessment or preclude FMT use. 

3. Efficacy and safety: In addition to standard treatment for the underlying disease, FMT is safe and effective for patients with CHB, alcoholic hepatitis (AH), MASLD, primary sclerosing cholangitis (PSC), LC, and HE. It may also be beneficial in enhancing tumor sensitivity to anticancer therapy in hepatocellular carcinoma (HCC). The most common adverse reactions are mild, self-limiting gastrointestinal symptoms. Strict donor screening is paramount for safety. 

4. Donor selection: Standard non-related donors should be prioritized. Mandatory comprehensive screening must include health history, psychological evaluation, and extensive laboratory tests (blood and stool) to rule out pathogens, multidrug-resistant organisms, and other risks. 

5. Donor management: Donors require appropriate management to ensure donation stability and sustainability, including regular health re-evaluations and retention of stool samples for analysis. Dietary advice is recommended, emphasizing plant-based, high-fiber foods while avoiding high-fat, high-protein, irritant, or hard-to-digest foods. 

6. Transplantation route selection: FMT can be delivered via upper GI (oral capsules), mid-GI (gastroscopy, nasoduodenal/nasojejunal tube), or lower GI (colonoscopy, enema) routes. The optimal route should be determined through comprehensive evaluation by a multidisciplinary team, considering patient tolerance and disease specifics. Patient informed consent is essential. 

7. Pre-transplant preparation: Antibiotic use should be avoided whenever possible before FMT, as it may negatively impact overall engraftment success and microbiota diversity restoration. Bowel preparation is recommended for lower GI routes to facilitate mucosal contact and engraftment. 

8. Transplantation dose, frequency, and form: Higher doses and more frequent administrations are generally associated with better efficacy in restoring microbiota balance and reducing recurrence. Fresh fecal samples yield better outcomes than frozen ones. The regimen should be flexibly adjusted based on individual patient response. 

9. Follow-up principles: A combination of short-term (within 24 hours to monitor tolerance) and long-term follow-up (evaluating symptoms and relevant tests at 4 weeks) should be adopted to assess efficacy comprehensively. Follow-up should last at least 8 weeks. Donor change or repeat FMT may be considered if initial response is inadequate. 

10. Adverse reactions and management: The most common adverse reactions are mild, self-limiting gastrointestinal symptoms. Strict donor screening and thorough patient assessment can mitigate risks. Patient education on potential reactions and management strategies is crucial for compliance. 

11. Precautions for special populations (children, pregnant women): FMT application in children and pregnant women with chronic liver disease requires extreme caution and careful evaluation. There are no reports yet on FMT in children with chronic liver disease. FMT is not recommended for pregnant women. Multidisciplinary assessment, physician-patient trust, and transparent informed consent are paramount. 

Conclusion

This expert consensus, based on current evidence and clinical experience, provides a structured framework for the standardized application of FMT in managing chronic liver diseases. It highlights the therapeutic potential of FMT across a spectrum of liver conditions while emphasizing the critical importance of rigorous donor screening, patient selection, and procedural safety. The recommendations aim to guide clinicians in optimizing FMT use to improve patient outcomes, while calling for further high-quality research to strengthen the evidence base, particularly regarding long-term efficacy and application in special populations.