Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia

Efficacy and Safety of Glucocorticoids for Acute Drug Induced Liver Injury With Hyperbilirubinemia: A Multicenter Randomized Controlled Trial

Drug-induced liver injury (DILI) can lead to potentially fatal complications, such as acute liver failure and even death. In clinical practice, glucocorticoids have been considered in some cases of DILI, especially patients with hyperbilirubinemia. However, the available evidence remains controversial and its quality is also very limited. Herein, a multicenter randomized controlled trial (RCT) has been designed to explore the efficacy and safety of glucocorticoids in patients with acute DILI and hyperbilirubinemia.

Study Overview

• Status: Recruiting
• Conditions: Drug Induced Liver Injury
• Intervention / Treatment: Drug: Methylprednisolone; Drug: Magnesium isoglycyrrhizinate; Drug: Glutathione; Drug: Silymarin; Drug: Polyene Phosphatidylcholine; Drug: Ursodeoxycholic acid capsules; Drug: Ademetionine 1,4-Butanedisulfonate; Procedure: Plaslna exchange; Procedure: Liver transplantation

Detailed Description

Overall, 232 patients with acute DILI with hyperbilirubinemia will be enrolled. They will be randomly assigned at a ratio of 1:1 to the conventional treatment alone or combined with glucocorticoids groups. The primary endpoint is the improvement of DILI after treatment on second week. Secondary endpoints include the improvement of DILI on fourth week, rates of progressive liver injury, liver failure, liver transplantation, survival, and adverse events. Exploratory endpoints will assess the beneficial population and changes of inflammatory factors following glucocorticoid treatment.

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xingshun Qi; Phone Number: 18909881019; Email: xingshunqi@126.com
• Study Contact Backup: Name: Qianqian Li; Phone Number: 13940307473; Email: 1208594776@qq.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110840
      • Recruiting
      • Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area)
      • Contact: Xingshun Qi; Phone Number: 18909881019; Email: xingshunqi@126.com
      • Contact: Qianqian Li; Phone Number: 13940307473; Email: 1208594776@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• A definite diagnosis of acute DILI;
• 5×ULN ≤ TBIL level at baseline ≤ 20×ULN;
• Age 18-80 years old;
• Sign the informed consent form.

Exclusion Criteria:

• Other causes of liver injury, including viral hepatitis, cytomegalovirus infection, Epstein-Barr virus infection, Herpes virus infection, autoimmune liver disease, alcoholic liver disease, hypoxic/ischemic liver disease, Budd-Chiari syndrome, biliary tract disease, Wilson's disease, hemochromatosis, and α1-antitrypsin deficiency;
• Immune checkpoint inhibitors or gynura segetum induced DILI;
• Absolute contraindications to glucocorticoids, such as systemic mold infections or allergies;
• A history of glucocorticoid therapy within 3 months before enrollment;
• A history of diseases requiring glucocorticoid maintenance therapy, such as rheumatoid arthritis, systemic lupus erythematosus, systemic dermatomyositis, etc;
• A history of liver transplantation;
• Received artificial liver therapy before enrollment;
• Malignant tumor of the liver, bile duct, pancreas or liver metastasis
• Acute liver failure;
• Renal dysfunction, creatinine Cr≥133μmol/L;
• Neutrophil count <1,000,000,000/L;
• Active tuberculosis;
• Severe cardiopulmonary diseases;
• Recent surgery or trauma;
• Mental illness;
• Pregnancy or lactation;
• Participated in other clinical studies within 3 months before enrollment;
• Other conditions judged by the clinician to be inappropriate for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glucocorticoids group; Glucocorticoids step-down therapy combined with conventional treatment.	Drug: Methylprednisolone; Initially, an intravenous dose of 1 mg/kg/day of methylprednisolone will be administered for one week, with the possibility of extending treatment to two weeks if necessary. Following this, participants will receive oral methylprednisolone tablets, starting at a dose of 40 mg/day. The oral dosage will be gradually tapered based on the participants' condition over a period of 1 to 3 months.; Other Names: Medrol; Drug: Magnesium isoglycyrrhizinate; It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 0.15g to 0.2g; Drug: Glutathione; It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 1.2g to 1.8g; Drug: Silymarin; It is suitable for patients with hepatocellular or mixed DILI. The dosage is 140 mg, taken 2 to 3 times per day.; Other Names: Legalon; Drug: Polyene Phosphatidylcholine; It is suitable for patients with hepatocellular or mixed DILI. The dosage is 228mg-456mg, taken 3 times per day.; Other Names: Essentiale; Drug: Ursodeoxycholic acid capsules; It is suitable for patients with cholestatic or mixed DILI. A daily dose of 10mg-15mg/kg/day.; Other Names: Ursofalk; Drug: Ademetionine 1,4-Butanedisulfonate; It is suitable for patients with cholestatic or mixed DILI. A daily dose of 0.5g to 1g.; Other Names: Transmeti; Procedure: Plaslna exchange; It is suitable for patients whose condition continues to worsen or even develop to liver failure.; Other Names: Artificial liver support; Procedure: Liver transplantation; It is suitable for patients whose condition continues to worsen or even develop to liver failure.
Active Comparator: Conventional treatment; Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI.	Drug: Magnesium isoglycyrrhizinate; It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 0.15g to 0.2g; Drug: Glutathione; It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 1.2g to 1.8g; Drug: Silymarin; It is suitable for patients with hepatocellular or mixed DILI. The dosage is 140 mg, taken 2 to 3 times per day.; Other Names: Legalon; Drug: Polyene Phosphatidylcholine; It is suitable for patients with hepatocellular or mixed DILI. The dosage is 228mg-456mg, taken 3 times per day.; Other Names: Essentiale; Drug: Ursodeoxycholic acid capsules; It is suitable for patients with cholestatic or mixed DILI. A daily dose of 10mg-15mg/kg/day.; Other Names: Ursofalk; Drug: Ademetionine 1,4-Butanedisulfonate; It is suitable for patients with cholestatic or mixed DILI. A daily dose of 0.5g to 1g.; Other Names: Transmeti; Procedure: Plaslna exchange; It is suitable for patients whose condition continues to worsen or even develop to liver failure.; Other Names: Artificial liver support; Procedure: Liver transplantation; It is suitable for patients whose condition continues to worsen or even develop to liver failure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of DILI on the second week	TBIL level decreases by 50% as compared to the baseline level.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	All participants will be followed by telephone to record survival status, including the major cause and date of death.	3 months
Improvement of DILI on the fourth week	TBIL level decreases by 50% as compared to the baseline level.	4 weeks
Progressive liver injury on the second week	TBIL level increases as compared to the baseline level.	2 weeks
Progressive liver injury on the fourth week	TBIL level increases as compared to the baseline level.	4 weeks
Improvement of liver enzymes on the second week	Proportion of 50% reduction from baseline in ALT, AST, ALP, and GGT levels.	2 weeks
Improvement of liver enzymes on the fourth week	Proportion of 50% reduction from baseline in ALT, AST, ALP, and GGT levels.	4 weeks
Liver failure	Participants develop overt hepatic encephalopathy with an INR of ≥1.5.	3 months
Liver transplantation	Participants undergo liver transplantation due to liver failure.	3 months
Adverse events	Adverse events related to glucocorticoids mainly include infection, water-sodium retention, Cushing syndrome, poor glycemic, gastrointestinal ulcer, thromboembolic disease, neuropsychiatric symptoms, osteoporosis, increased intraocular pressure, and withdrawal syndrome. They will be closely recorded during the period of glucocorticoids treatment.	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population who will be more suitable for glucocorticoids treatment	Characteristics of patients with DILI in whom glucocorticoids treatment is more beneficial.	3 months
Changes of inflammatory factors	Changes of IL-6 and TNF-α levels.	4 weeks

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region
• Investigators: Principal Investigator: Qing Ye, Tianjin Third Central Hospital; Principal Investigator: Xingshun Qi, Department of Gastroenterology, General Hospital of Northern Theater Command; Principal Investigator: Weifen Xie, Shanghai changzheng hospital, Naval Medical University; Principal Investigator: Xin Zeng, Shanghai East Hospital,Tongji University School of Medicine; Principal Investigator: Lu Zhou, General Hospital, Tianjin Medical University; Principal Investigator: Fengmei Wang, Tianjin First Central Hospital; Principal Investigator: Yanjing Gao, Qilu Hospital of Shandong University

Publications and helpful links

General Publications

• Hou FQ, Zeng Z, Wang GQ. Hospital admissions for drug-induced liver injury: clinical features, therapy, and outcomes. Cell Biochem Biophys. 2012 Nov;64(2):77-83. doi: 10.1007/s12013-012-9373-y.
• Hu PF, Wang PQ, Chen H, Hu XF, Xie QP, Shi J, Lin L, Xie WF. Beneficial effect of corticosteroids for patients with severe drug-induced liver injury. J Dig Dis. 2016 Sep;17(9):618-627. doi: 10.1111/1751-2980.12383.
• Chai L, Wang R, Teschke R, Jin S, Deng J, Qi X. Successful corticosteroid therapy for severe liver injury secondary to herbal traditional Chinese medicine, Mega Defends X, assessed for causality by the updated RUCAM: A case report. Medicine (Baltimore). 2024 Aug 23;103(34):e39439. doi: 10.1097/MD.0000000000039439.
• Mao Y, Ma S, Liu C, Liu X, Su M, Li D, Li Y, Chen G, Chen J, Chen J, Zhao J, Guo X, Tang J, Zhuge Y, Xie Q, Xie W, Lai R, Cai D, Cai Q, Zhi Y, Li X; Technology Committee on DILI Prevention, Management, Chinese Medical Biotechnology Association; Study Group on Drug-Induced Liver Disease, Chinese Society of Hepatology, Chinese Medical Association. Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update. Hepatol Int. 2024 Apr;18(2):384-419. doi: 10.1007/s12072-023-10633-7. Epub 2024 Feb 24.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: clinical trial; liver failure; Hyperbilirubinemia; glucocorticoids; Drug induced liver injury
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Poisoning; Hepatic Insufficiency; Pathological Conditions, Signs and Symptoms; Liver Failure; Chemical and Drug Induced Liver Injury; Hyperbilirubinemia; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Pyrans; Surgical Procedures, Operative; Polycyclic Compounds; Transplantation; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Digestive System Surgical Procedures; Pregnadienetriols; Cell- and Tissue-Based Therapy; Biological Therapy; Benzopyrans; Flavonoids; Chromones; Prednisolone; Tissue Transplantation; Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Cholanes; Flavonolignans; Organ Transplantation; Methylprednisolone; Ursodeoxycholic Acid; Silymarin; Liver Transplantation; Glutathione; 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate; polyene phosphatidylcholine; essential 303 forte
• Other Study ID Numbers: XHNKKY-ASDILI-RCT

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