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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucocorticoids group | Experimental | Glucocorticoids step-down therapy combined with conventional treatment. |
|
| Conventional treatment | Active Comparator | Only conventional treatment according to the Chinese practice guidelines regarding the management of DILI. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylprednisolone | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Improvement of DILI on the second week | TBIL level decreases by 50% as compared to the baseline level. | 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xingshun Qi | Contact | 18909881019 | xingshunqi@126.com | |
| Qianqian Li | Contact | 13940307473 | 1208594776@qq.com |
| Name | Affiliation | Role |
|---|---|---|
| Xingshun Qi | Department of Gastroenterology, General Hospital of Northern Theater Command | Principal Investigator |
| Weifen Xie | Shanghai changzheng hospital, Naval Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area) | Recruiting | Shenyang | Liaoning | 110840 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22806342 | Result | 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. | |
| 27426618 | Result | 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. |
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|
|
| Magnesium isoglycyrrhizinate | Drug | It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 0.15g to 0.2g |
|
| Glutathione | Drug | It is suitable for patients with hepatocellular or mixed DILI. A daily dose of 1.2g to 1.8g |
|
| Silymarin | Drug | It is suitable for patients with hepatocellular or mixed DILI. The dosage is 140 mg, taken 2 to 3 times per day. |
|
|
| Polyene Phosphatidylcholine | Drug | It is suitable for patients with hepatocellular or mixed DILI. The dosage is 228mg-456mg, taken 3 times per day. |
|
|
| Ursodeoxycholic acid capsules | Drug | It is suitable for patients with cholestatic or mixed DILI. A daily dose of 10mg-15mg/kg/day. |
|
|
| Ademetionine 1,4-Butanedisulfonate | Drug | It is suitable for patients with cholestatic or mixed DILI. A daily dose of 0.5g to 1g. |
|
|
| Plaslna exchange | Procedure | It is suitable for patients whose condition continues to worsen or even develop to liver failure. |
|
|
| Liver transplantation | Procedure | It is suitable for patients whose condition continues to worsen or even develop to liver failure. |
|
| 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 |
| Survival | All participants will be followed by telephone to record survival status, including the major cause and date of death. | 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 |
Changes of IL-6 and TNF-α levels.
| 4 weeks |
| Xin Zeng | Shanghai East Hospital of Tongji University | Principal Investigator |
| Lu Zhou | General Hospital, Tianjin Medical University | Principal Investigator |
| Fengmei Wang | Tianjin First Central Hospital | Principal Investigator |
| Qing Ye | Tianjin Third Central Hospital | Principal Investigator |
| Yanjing Gao | Qilu Hospital of Shandong University | Principal Investigator |
|
| 39183394 | Result | 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. |
| 38402364 | Result | 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. |
| 42080196 | Derived | Li Q, Lin Y, Zeng X, Zhou L, Wang F, Ye Q, Gao Y, Guo L, Zhu J, Li J, Li Y, Shao L, Hu Y, Xiao J, Jia A, Wang D, Chang L, Wang J, Zhang J, Wang R, Gao F, Wu Q, Hu P, Zhu C, Cai L, Ran Y, Li Y, Zhang J, Ran Y, Wang C, Wang N, Zhang J, Zhang X, Li J, Sun J, Chu Y, Ma Y, Wang T, Zheng Z, Shen Y, Qi X, Xie W. Efficacy and safety of glucocorticoids for acute drug-induced liver injury with hyperbilirubinemia: protocol of a multicenter randomized controlled trial. Ther Adv Gastroenterol. 2026 Apr 26;19:17562848261440777. doi: 10.1177/17562848261440777. eCollection 2026. |
| ID | Term |
|---|---|
| D056486 | Chemical and Drug Induced Liver Injury |
| D017093 | Liver Failure |
| D006932 | Hyperbilirubinemia |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011041 | Poisoning |
| D048550 | Hepatic Insufficiency |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008775 | Methylprednisolone |
| C521270 | 18alpha,20beta-hydroxy-11-oxo-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranurosyl-alpha-D-glucopyranosiduronate magnesium tetrahydrate |
| D005978 | Glutathione |
| D012838 | Silymarin |
| C029449 | polyene phosphatidylcholine |
| C011246 | essential 303 forte |
| D014580 | Ursodeoxycholic Acid |
| D016031 | Liver Transplantation |
| ID | Term |
|---|---|
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D044947 | Flavonolignans |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003840 | Deoxycholic Acid |
| D002793 | Cholic Acids |
| D001647 | Bile Acids and Salts |
| D002757 | Cholanes |
| D016378 | Tissue Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D013505 | Digestive System Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D016377 | Organ Transplantation |
| D014180 | Transplantation |
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