A total of 100 individuals with recurrent HE will be recruited from 31 hospitals throughout China: (1) Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, (2) Huzhou Central Hospital, (3) Hainan General Hospital Branch—Ding’an Hospital, (4) Shandong Public Health Clinical Center, (5) Department of Hepatology, Qilu Hospital of Shandong University, (6) Zhengzhou Third People’s Hospital, (7) Shulan (Quzhou) Hospital, (8) Taizhou Hospital of Zhejiang, (9) Zhejiang Provincal People’s Hospital, (10) the First Affiliated Hospital of Henan University of CM, (11) Ningbo No. 2 Hospital, (12) Luoyang Central Hospital, (13) Ningbo Zhenhai District People’s Hospital, (14) Hangzhou Xixi Hospital Affiliated to Zhejiang University School of Medicine, (15) the Second Affiliated Hospital of Zhejiang Chinese Medical University, (16) Shanghai Public Health Clinical Center, (17) the First Affiliated Hospital of Soochow University, (18) Zouping People’s Hospital, (19) ALMETTE Hospital & the First Hospital of Kunming, (20) Zoucheng People’s Hospital, (21) Shenzhen Bao’an District Songgang People’s Hospital, (22) Baoan Central Hospital of Shenzhen, (23) the People’s Hospital of Jiulongpo District, Chongqing, China, (24) Lishui People’s Hospital, (25) People’s Hospital of Xinjiang Uygur Autonomous Region, (26) Department of Infectious Disease and Hepatic Disease, First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China, (27) Department Of Infectious Diseases, Huashan Hospital, Fudan University, (28) the First Affiliated Hospital of Xi’an Jiaotong University, (29) Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, (30) Affiliated Hospital of Shaoxing University, and (31) Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.

Eligible patients for this study must meet the following criteria: (1) age between 18 and 75 years at the time of enrollment; (2) have HE in remission upon enrollment; (3) have experienced at least two episodes of significant HE (West Haven grade 2 or higher) associated with liver cirrhosis within the past 6 months; episodes of HE caused by blood transfusions (at least 2 units), sedative drug use, renal failure requiring dialysis, or central nervous system injury do not count towards this criterion; (4) have a Model for End-Stage Liver Disease (MELD) score of 25 or below; (5) be medically suitable for FMT delivery via the nasal jejunal tube; and (6) provide signed informed consent from the participant (or their legal guardian).

The exclusion criteria are outlined as follows: (1) patients anticipated to undergo liver transplantation within 1 month; (2) patients who have had known causes of HE, including gastrointestinal bleeding and portosystemic shunt or transjugular intrahepatic portosystemic shunt placement within three months; (3) patients with chronic kidney disease (creatinine level > 2.0 mg/dl), respiratory failure, anemia (Hb < 8 g/dl), and electrolyte disorders (serum sodium < 125 µmol/L; serum calcium > 10 mg/dl [2.5 µmol/L]; or serum potassium of < 2.5 mmol/l); (4) patients who are not active drinkers, defined as consuming alcohol in excess of 140 g/week for women and 210 g/week for men; (5) use of drugs that can affect the Psychometric Hepatic Encephalopathy Score (PHES) within the last 4 weeks, such as antidepressants and sedative-hypnotics; (6) patients who are allergic to antibiotics prior to FMT treatment; (7) patients with existing infection before FMT (pathogens acquired through sterile sites); (8) patients diagnosed with chronic gastrointestinal disease, including inflammatory bowel disease (such as ulcerative colitis, Crohn’s disease, or microscopic colitis) as well as those with irritable bowel syndrome; (9) patients who have neurological disorders, including stroke, epilepsy, dementia, and Parkinson’s disease; (10) patients with uncontrolled malignant liver tumor or malignant tumors of other organs; (11) women who are pregnant or breastfeeding (confirmed through a urinary pregnancy test); (12) patients who refuse to sign the informed consent form; (13) patients who are unwilling or unable to undergo the nasal jejunal tube procedure; (14) patients have other conditions that do not meet the inclusion criteria in the trial.

Prior to screening, potentially eligible patients will undergo a thorough explanation of the trial’s purpose, procedure, potential risks, and benefits. This ensures that they have a comprehensive understanding of the trial before proceeding. Eligible patients who wish to participate will be required to sign two informed consents forms, one to be retained by the researcher and the other by the patient themselves.

The consent form approved by the patients includes their consent to utilize the data in subsequent, pertinent research studies. Furthermore, participants will be requested to authorize the research team to share pertinent data with individuals affiliated with the universities involved in the research or with regulatory bodies, whenever necessary.