Etiology and Prognostic Factors in Patients With Acute Liver Failure

A Bidirectional Cohort Study on the Etiology and Prognostic Factors of Acute Liver Failure and Development of a Dynamic Prediction Model

Acute liver failure (ALF) is a rare but life-threatening condition with high mortality. Despite advances in supportive care and liver transplantation, prognosis varies significantly across etiologies, particularly in patients with indeterminate causes.

This study aims to investigate the dynamic changes of clinical and biochemical indicators, identify potential etiologies-especially in indeterminate ALF-and evaluate prognostic risk factors. A dynamic prediction model will be developed to optimize clinical decision-making, including liver transplantation timing.

Both retrospective and prospective cohorts will be included. Multi-omics analyses (including transcriptomics, proteomics, metabolomics, and metagenomic sequencing) will be performed on liver tissue and biological samples to explore disease mechanisms and etiology.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Liver Failure

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Wan-Ting Zhang, MD; Phone Number: +86 13699189579; Email: 13699189579@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients diagnosed with acute liver failure who are treated at Beijing Friendship Hospital, Capital Medical University. Both adult and pediatric patients meeting established diagnostic criteria for acute liver failure will be included.

The study includes two cohorts: a retrospective cohort of patients treated between November 2016 and February 2026, and a prospective cohort of newly diagnosed patients enrolled from March 2026 onward.

Patients will be followed longitudinally to evaluate clinical outcomes, including survival, liver transplantation, and transplant-free survival.

Description

Inclusion Criteria:

• Patients meeting diagnostic criteria for acute liver failure:

Adults: Acute onset without pre-existing liver disease, development of hepatic encephalopathy ≥ grade II within 4 weeks Pediatrics: Acute onset (<26 weeks), no chronic liver disease, coagulopathy not corrected by vitamin K: INR ≥1.5 with encephalopathy OR; INR >2 regardless of encephalopathy

• Patients (or guardians) who provide informed consent

Exclusion Criteria:

• Presence of end-stage extrahepatic disease without effective treatment
• Pregnant or breastfeeding women
• Inability or unwillingness to provide informed consent or comply with study procedures

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Death
Liver transplantation
Spontaneous survival

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Up to 3 years after enrollment (every 3 months during the first year, then annually until year 3)
Transplant-Free Survival	Up to 3 years after enrollment (every 3 months during the first year, then annually until year 3)
Liver Transplantation Rate	Up to 3 years after enrollment (every 3 months during the first year, then annually until year 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Etiologic features identified by multi-omics analysis	Etiologic features in participants with acute liver failure will be assessed through multi-omics analyses of biospecimens, including liver tissue obtained from resected diseased liver during surgery (approximately 3 cm³) or from one ultrasound-guided liver biopsy core (approximately 2 cm in length), together with blood, urine, and stool samples. Multi-omics testing includes transcriptomic sequencing, proteomic analysis, metabolomic analysis, and metagenomic sequencing.	From enrollment to completion of biospecimen collection and etiologic multi-omics assessment, up to 7 days
Short-Term Mortality		90 days after enrollment
Development of Prognostic Prediction Model	A prognostic model will be developed using clinical variables, laboratory parameters, and dynamic changes over time. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis will be used to evaluate model performance, including discrimination and calibration.	Up to 3 years after enrollment
Change in alanine aminotransferase (ALT) over time	Serial serum ALT measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in aspartate aminotransferase (AST) over time	Serial serum AST measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in total bilirubin over time	Serial total bilirubin measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in international normalized ratio (INR) over time	Serial INR measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in prothrombin time (PT) over time	Serial PT measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in serum creatinine over time	Serial serum creatinine measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in C-reactive protein (CRP) over time	Serial serum C-reactive protein measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in direct bilirubin over time	Serial direct bilirubin measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in prothrombin activity (PTA) over time	Serial prothrombin activity (PTA) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in blood ammonia over time	Serial blood ammonia measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in blood phosphorus over time	Serial blood phosphorus measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in white blood cell count (WBC) over time	Serial white blood cell count (WBC) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in red blood cell count (RBC) over time	Serial red blood cell count (RBC) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in hemoglobin (HGB) over time	Serial hemoglobin (HGB) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in platelet count (PLT) over time	Serial platelet count (PLT) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in D-dimer over time	Serial D-dimer measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in serum albumin over time	Serial serum albumin measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in arterial lactate over time	Serial arterial lactate measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in blood glucose over time	Serial blood glucose measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in arterial pH over time	Serial arterial pH measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in CD4+ T-cell count over time	Serial CD4+ T-cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in CD8+ T-cell count over time	Serial CD8+ T-cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in CD19+ B-cell count over time	Serial CD19+ B-cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in CD56+ natural killer cell count over time	Serial CD56+ natural killer cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in CD4+/CD8+ ratio over time	Serial CD4+/CD8+ ratio measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in immunoglobulin M (IgM) over time	Serial serum immunoglobulin M (IgM) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in immunoglobulin G (IgG) over time	Serial serum immunoglobulin G (IgG) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in immunoglobulin A (IgA) over time	Serial serum immunoglobulin A (IgA) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in complement C3 over time	Serial serum complement C3 measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days
Change in complement C4 over time	Serial serum complement C4 measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization.	Every 48 hours from admission to discharge, assessed up to 30 days

Collaborators and Investigators

• Sponsor: Li-Ying Sun

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2026
• Primary Completion (Estimated): December 31, 2036
• Study Completion (Estimated): December 31, 2037

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute
• Other Study ID Numbers: BFHHZS20260102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No