Acute Liver Failure
Conditions
Brief summary
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.
Interventions
None listed
Sponsors
Li-Ying Sun
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Etiologic features identified by multi-omics analysis | From enrollment to completion of biospecimen collection and etiologic multi-omics assessment, up to 7 days | 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. |
| Short-Term Mortality | 90 days after enrollment | — |
| Development of Prognostic Prediction Model | Up to 3 years after enrollment | 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. |
| Change in alanine aminotransferase (ALT) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum ALT measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in aspartate aminotransferase (AST) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum AST measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in total bilirubin over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial total bilirubin measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in international normalized ratio (INR) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial INR measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in prothrombin time (PT) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial PT measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in serum creatinine over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum creatinine measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in C-reactive protein (CRP) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum C-reactive protein measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in direct bilirubin over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial direct bilirubin measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in prothrombin activity (PTA) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial prothrombin activity (PTA) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in blood ammonia over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial blood ammonia measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in blood phosphorus over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial blood phosphorus measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in white blood cell count (WBC) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial white blood cell count (WBC) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in red blood cell count (RBC) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial red blood cell count (RBC) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in hemoglobin (HGB) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial hemoglobin (HGB) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in platelet count (PLT) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial platelet count (PLT) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in D-dimer over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial D-dimer measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in serum albumin over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum albumin measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in arterial lactate over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial arterial lactate measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in blood glucose over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial blood glucose measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in arterial pH over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial arterial pH measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in CD4+ T-cell count over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial CD4+ T-cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in CD8+ T-cell count over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial CD8+ T-cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in CD19+ B-cell count over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial CD19+ B-cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in CD56+ natural killer cell count over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial CD56+ natural killer cell count measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in CD4+/CD8+ ratio over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial CD4+/CD8+ ratio measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in immunoglobulin M (IgM) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum immunoglobulin M (IgM) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in immunoglobulin G (IgG) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum immunoglobulin G (IgG) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in immunoglobulin A (IgA) over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum immunoglobulin A (IgA) measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in complement C3 over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum complement C3 measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
| Change in complement C4 over time | Every 48 hours from admission to discharge, assessed up to 30 days | Serial serum complement C4 measurements will be obtained every 48 hours from admission until discharge to assess dynamic changes during hospitalization. |
Contacts
CONTACTWan-Ting Zhang, MD
Outcome results
None listed