Clinicopathological Features and Genetic Susceptibility Screening of Recurrent Drug-induced Liver Injury

Active, not recruiting

• Conditions: Recurrent Drug-induced Liver Injury

• Registration Number: NCT06547229
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

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?

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 Timeline

• Study Start: 2024-07-15
• Status Verified: 2024-08
• Study First Submitted: 2024-08-07
• Study First Submitted QC: 2024-08-07
• Study First Posted: 2024-08-09
• Last Update Submitted: 2024-08-09
• Last Update Posted: 2024-08-12
• Primary Completion: 2026-09
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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.

  2. 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.

  3. Autoimmune hepatitis: International Autoimmune Hepatitis Group (IAHG)simplified score ≥6 or complicated score ≥10, or differentiation from autoimmune hepatitis is impossible during enrollment.

  4. Parasitic infection. 8. Sepsis. 9. Previous liver transplantation or bone marrow transplantation. 10. Pregnancy or lactation. 11. Genetic and metabolic liver diseases.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Death/Liver transplantation	1 year	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.
Recovery	1 year	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).
Acute Liver Failure	1 year	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.

Secondary Outcome Measures

Name	Time	Method
chronic DILI	2 years	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.

Trial Locations

Locations (1)

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; 🇨🇳 Beijing, Beijing, China