A Prognostic Model for Drug-induced Liver Injury in China

Study Overview
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Brief Summary
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A prospective, multi-center, non-interventional cohort study is going to conduct to explore the clinical characteristics, culprit drug(s) or herb(s), outcomes and risk factors of Drug-induced liver injury (DILI) in China and screen novel serum markers. A prognostic model incorporating with the novel serum marker(s) for DILI would be established and validated to imporve the prognosis of patients in China .

Detailed Description
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Research Objectives: To establish a standardized multi-center, prospective DILI cohort nationwide and obtain long-term prognostic data. To establish and verify prognostic model(s) of DILI in China. To explore novel serum biomarkers for the prognosis of DILI.

Official Title
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A Prognostic Model for Drug-induced Liver Injury in China : A Multi-center, Prospective Cohort Study

Conditions
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Drug-induced Liver Injury

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: RUCAM ≥6 and met one of the following biochemical conditions: (1) ALT≥5 ULN, (2) or ALP ≥2 ULN, (3) or ALT≥3 ULN and TBil≥2 ULN. RUCAM between 3-5, five experienced hepatologists in leading site evaluate and vote the diagnosis of DILI, the case would be enrolled if only ≥4 out of 5 hepatologists agree with the diagnosis. Onset to enrollment ≤3 months. Exclusion Criteria: Hepatotropic viral infection: hepatitis A, B, C, D and E. Non-hepatotropic viral infection: cytomegalovirus (CMV) and Epstein-Barr virus (EBV), etc. Hypoxic ischemic hepatitis and congestive liver disease. Alcohol consumption: male >40g/d, female >20g/d, and ≥5 years. Biliary obstruction, primary biliary cholangitis; primary sclerosing cholangitis. Autoimmune hepatitis: International Autoimmune Hepatitis Group (IAHG) simplified score ≥6 or complicated score ≥10, or differentiation from autoimmune hepatitis is impossible during enrollment. Parasitic infection. Sepsis. Previous liver transplantation or bone marrow transplantation. Pregnancy or lactation. Genetic and metabolic liver diseases.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Modeling group<br>The data of modeling group is used to construct a predictive model of DILI endpoint events. | |
| Validation group<br>Validation group is used to validate the predictive model externally. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death/liver transplantation | DILI has a primary, contributory role for the death (liver-related mortality) or no role for the death (all-cause mortality) . DILI is the primary indication for liver transplantation. | 1 year | 
| acute liver failure | Acute liver failure is defined as elevated bilirubin and prolonged international normalized ratio (INR) ≥1.5 accompanied by mental disturbance within 26 weeks after DILI onset without underlying chronic liver diseases. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chronic DILI | Chronicity is defined as the presence of any one of the following: (i) persistently elevated liver biochemistry indexes; (ii) radiological or histological evidence of persistent liver injury at one year after DILI onset. | 2 years | 
| recovery | Recovery status is defined as clinical and biochemical resolution within 1 year after DILI onset, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤40 U/L, alkaline phosphatase (ALP) ≤150 U/L, and total bilirubin (TB) ≤1.5 upper limits of normal (ULN) (25.65 μmol/L). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prognostic model(s), biomarker(s), endpoint event(s)