A Prognostic Model for Drug-induced Liver Injury in China (DILI-PM)

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

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 .

Study Overview

• Status: Recruiting
• Conditions: Drug-induced Liver Injury

Detailed Description

Research Objectives:

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

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Yan Wang; Phone Number: 18810530724; Email: wangyanpku@163.com
• Study Contact Backup: Name: Zikun Ma; Phone Number: 18311270304; Email: maazikun0114@163.com

Study Locations

• China
  • Beijing, China, 100050
    • Recruiting
    • Beijing Friendship Hospital, Capital Medical University
    • Contact: Zikun Ma; Email: mazikun0114@163.com
    • Principal Investigator: Xinyan Zhao
  • Beijing, China, 100191
    • Active, not recruiting
    • Peking University Third Hospital
  • Beijing, China, 100069
    • Recruiting
    • Beijing You 'an Hospital, Capital Medical University
    • Contact: Yu Chen
    • Principal Investigator: Liwei Liu
    • Sub-Investigator: Lixia Qiu
  • Beijing, China, 100102
    • Active, not recruiting
    • Beijing Ditan Hospital
  • Dalian, China, 116023
    • Recruiting
    • The Second Affiliated Hospital of Dalian Medical University
    • Contact: Fangcheng Zhao
    • Principal Investigator: Rongkuan Li
  • Guangxi, China, 535009
    • Active, not recruiting
    • Qinzhou First People's Hospital
  • Hebei, China, 050011
    • Active, not recruiting
    • Hebei CNPC Central Hospital
  • Jiaozuo, China, 454002
    • Recruiting
    • Jiaozuo People's Hospital
    • Sub-Investigator: Hui Wang
    • Contact: Huahua Wang
    • Principal Investigator: Jikang Yang
  • Lanzhou, China, 730046
    • Recruiting
    • The Second Hospital of Lanzhou University
    • Contact: Liang Wang
  • Qingdao, China, 266003
    • Recruiting
    • The Affiliated Hospital of Qingdao University
    • Contact: Qiuju Tian
  • Qinghai, China, 810007
    • Recruiting
    • Qinghai People's Hospital
    • Contact: Juan Li
    • Principal Investigator: Pingying Li
  • Yuncheng, China, 044099
    • Recruiting
    • Yuncheng Central Hospital
    • Contact: Liuyi Chang
    • Principal Investigator: Liuyi Chang
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100166
      • Recruiting
      • Beijing 302 Hospital
      • Contact: Zhengsheng Zou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult with drug-induced liver injury

Description

Inclusion Criteria:

1. 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.
2. 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.
3. Onset to enrollment ≤3 months.

Exclusion Criteria:

1. Hepatotropic viral infection: hepatitis A, B, C, D and E.
2. Non-hepatotropic viral infection: cytomegalovirus (CMV) and Epstein-Barr virus (EBV), etc.
3. Hypoxic ischemic hepatitis and congestive liver disease.
4. Alcohol consumption: male >40g/d, female >20g/d, and ≥5 years.
5. Biliary obstruction, primary biliary cholangitis; primary sclerosing cholangitis.
6. Autoimmune hepatitis: International Autoimmune Hepatitis Group (IAHG) simplified score ≥6 or complicated score ≥10, or differentiation from autoimmune hepatitis is impossible during enrollment.
7. Parasitic infection.
8. Sepsis.
9. Previous liver transplantation or bone marrow transplantation.
10. Pregnancy or lactation.
11. Genetic and metabolic liver diseases.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Modeling group; The data of modeling group is used to construct a predictive model of DILI endpoint events.
Validation group; Validation group is used to validate the predictive model externally.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Zhengsheng Zou, Beijing 302 Hospital; Study Chair: Xinyan Zhao, Beijing Friendship Hospital; Principal Investigator: Yu Chen, Beijing You 'an Hospital, Capital Medical University; Principal Investigator: Juan Li, Qinghai People's Hospital; Principal Investigator: Pingying Li, Qinghai People's Hospital; Principal Investigator: Xiaoju Liu, Qinzhou First People's Hospital; Principal Investigator: Juan Luo, Hebei CNPC Central Hospital; Principal Investigator: Doudou Hu, Qingdao Municipal Hospital; Principal Investigator: Qiuju Tian, The Affiliated Hospital of Qingdao University; Principal Investigator: Rongkuan Li, The Second Affiliated Hospital of Dalian Medical University; Principal Investigator: Huahua Wang, Jiaozuo People's Hospital; Principal Investigator: Hui Wang, Jiaozuo People's Hospital; Principal Investigator: Jikang Yang, Jiaozuo People's Hospital; Principal Investigator: Lu Li, Peking University Third Hospital; Principal Investigator: Liuyi Chang, Yuncheng Central Hospital; Principal Investigator: Lu Zhang, Beijing Ditan Hospital; Principal Investigator: Yuanjiao Gao, Beijing Ditan Hospital; Principal Investigator: Liang Wang, Lanzhou University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 24, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: biomarker(s); prognostic model(s); endpoint event(s)
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Poisoning; Chemical and Drug Induced Liver Injury
• Other Study ID Numbers: 2021-P2-290-01

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