Clinicopathological Features and Genetic Susceptibility Screening of Recurrent Drug-induced Liver Injury (RDILI-GS)

The goal of this observational study is to screening for clinical, pathological and HLA features in patients with recurrent drug-induced liver injury. The main question it aims to answer is: Which patients with drug-induced liver injury need to be more cautious when re-dosing?

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Drug-induced Liver Injury

Detailed Description

Research Objectives:

1. To summarise the clinicopathological characteristics of patients with recurrent drug-induced liver injury (DILI) in the Liver Disease Centre of Beijing Friendship Hospital in the past 10 years.
2. Compare the differences in clinicopathological characteristics between patients with only one episode of different drug use and those with recurrent DILI, and predict the risk/protective factors in patients with recurrent DILI.
3. Explore the susceptibility genes in patients with recurrent DILI.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, China

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult with recurrent drug-induced liver injury

Description

Inclusion Criteria:

• Inclusion criteria for recurrent drug induced liver injury:

  1. Liver enzymes returns to normal or has a tendency to remission after the first drug liver injury;
  2. Signs and symptoms of liver injury after the patient takes the different drugs for liver injury again, and the liver enzymes returns to normal through follow-up.

Inclusion criteria for drug induced liver injury:

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?

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 accompaniedby mental disturbance within 26 weeks after DILI onset without underlying chronic liver diseases.	1 year
Recovery	Recovery status is defined as clinical and biochemical resolution within 1 year after DILI onset, with alanineaminotransferase (ALT) or aspartate aminotransferase (AST) ≤40 U/L, alkaline phosphatase (ALP) ≤150 U/L, and totalbilirubin (TB) ≤1.5 upper limits of normal (ULN) (25.65 μmol/L).	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

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Study Chair: Xinyan Zhao, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 7, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: HLA; Drug-induced Liver Injury; Genetic Susceptibility; Endpoint Event(s)
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Pathologic Processes; Disease Attributes; Liver Diseases; Drug-Related Side Effects and Adverse Reactions; Poisoning; Wounds and Injuries; Recurrence; Disease Susceptibility; Genetic Predisposition to Disease; Chemical and Drug Induced Liver Injury
• Other Study ID Numbers: 2024-P2-238

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
• product manufactured in and exported from the U.S.: No