Steroids in Fulminant Hepatitis A in the Pediatric Age Group

Safety and Efficacy of Steroids in the Management of Fulminant Hepatic Failure Due to Hepatitis A Virus in the Pediatric Age Group

Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. For that, it is suggested that corticosteroids modulate the activity of the disease by suppressing the immune system.

Study Overview

• Status: Completed
• Conditions: Fulminant Hepatic Failure
• Intervention / Treatment: Drug: prednisolone; Drug: methylprednisolone

Detailed Description

Fulminant hepatic failure (FHF) in children is a potentially devastating disease. The mortality rate may reach 80-90% in the absence of liver transplantation. FHF is the clinical manifestation of liver cell death of a critical degree with insufficient hepatocellular regeneration and characterized by coagulopathy with or without hepatic encephalopathy.

Liver injury is considered to be mainly immune mediated with augmentation of cytolytic pathways of infected hepatocytes. For that, it was suggested that corticosteroids modulate the activity of the disease by suppressing the immune system.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Menoufia, Egypt, 32511
    • National Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 14 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The patient is diagnosed to have FHF, if he fulfilled all the following criteria:

1. Evidence of liver dysfunction within 8 weeks of onset of symptoms (neonates may have only deranged liver functions without overt symptoms).
2. Uncorrectable coagulopathy (6-8 hours after administration of one dose of parenteral vitamin K) with International Normalized Ratio (INR) >1.5 in patients with hepatic encephalopathy, or INR> 2.0 in patients without encephalopathy.
3. No evidence of chronic liver disease.

Exclusion Criteria:

1. Presence of absolute contra-indications to steroid therapy (as presence of an active gastrointestinal bleeding, renal failure, acute pancreatitis, active tuberculosis, uncontrolled diabetes and psychosis).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: prednisolone; This group includes patients with FHF without encephalopathy	Drug: prednisolone; Oral administration of 1 mg/Kg/day; Other Names: Hostacortin-H
Active Comparator: methylprednisolone; This group includes patients with FHF with encephalopathy	Drug: methylprednisolone; Intravenous injection of 0.8 mg/kg/day; Other Names: Solumedrol
No Intervention: Non-intervention; FHF patients without any of the proposed intervention as controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effect 1 Number of patients with anaphylaxis	Number of patients with anaphylaxis	2 months
Side effect 2 Number of patients with angioedema	Number of patients with angioedema	2 months
Side effect 3 Number of patients with cardiac arrest	Number of patients with cardiac arrest	2 months
Side effect 4 Number of patients with arrhythmias	Number of patients with arrhythmias	2 months
Side effect 5 Number of patients with circulatory collapse	Number of patients with circulatory collapse	2 months
Side effect 6 Number of patients with congestive heart failure	Number of patients with congestive heart failure	2 months
Side effect 7 Number of patients with pulmonary edema	Number of patients with pulmonary edema	2 months
Side effect 8 Number of patients with pancreatitis	Number of patients with pancreatitis	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy 1 Number of survivors	number of living patients	2 months
Efficacy 2 Number of deaths	number of died patients	2 months
Efficacy 3 serum prothrombin time	serum prothrombin time	72 hour
Efficacy 3 grade of encephalopathy	grade of encephalopathy	72 hour
Efficacy 4 duration of encephalopathy	duration of encephalopathy	2 months

Collaborators and Investigators

• Sponsor: National Liver Institute, Egypt
• Collaborators: Quesna Central Hospital, Ministry Of Health, Egypt
• Investigators: Principal Investigator: Hanaa El-Araby, M.D., Pediatric Hepatology Department, National Liver Institute, Egypt; Study Director: Mostafa M Sira, M.D., Pediatric Hepatology Department, National Liver Institute, Egypt; Study Chair: Haydi M Zakaria, M.Sc., Quesna Central Hospital, Ministry Of Health, Egypt; Study Chair: Tahany A Salem, M.Sc., Pediatric Hepatology Department, National Liver Institute, Egypt

Publications and helpful links

General Publications

• Cochran JB, Losek JD. Acute liver failure in children. Pediatr Emerg Care. 2007 Feb;23(2):129-35. doi: 10.1097/PEC.0b013e3180308f4b.
• Bernal W, Auzinger G, Dhawan A, Wendon J. Acute liver failure. Lancet. 2010 Jul 17;376(9736):190-201. doi: 10.1016/S0140-6736(10)60274-7.
• Fujiwara K, Kojima H, Yasui S, Okitsu K, Yonemitsu Y, Omata M, Yokosuka O. Hepatitis A viral load in relation to severity of the infection. J Med Virol. 2011 Feb;83(2):201-7. doi: 10.1002/jmv.21958.
• Fujiwara K, Yasui S, Yonemitsu Y, Fukai K, Arai M, Imazeki F, Suzuki A, Suzuki H, Sadahiro T, Oda S, Yokosuka O. Efficacy of combination therapy of antiviral and immunosuppressive drugs for the treatment of severe acute exacerbation of chronic hepatitis B. J Gastroenterol. 2008;43(9):711-9. doi: 10.1007/s00535-008-2222-5. Epub 2008 Sep 20.
• Lahuna O, Rastegar M, Maiter D, Thissen JP, Lemaigre FP, Rousseau GG. Involvement of STAT5 (signal transducer and activator of transcription 5) and HNF-4 (hepatocyte nuclear factor 4) in the transcriptional control of the hnf6 gene by growth hormone. Mol Endocrinol. 2000 Feb;14(2):285-94. doi: 10.1210/mend.14.2.0423.
• Seshadri R, Feldman BM, Ilowite N, Cawkwell G, Pachman LM. The role of aggressive corticosteroid therapy in patients with juvenile dermatomyositis: a propensity score analysis. Arthritis Rheum. 2008 Jul 15;59(7):989-95. doi: 10.1002/art.23829.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: February 14, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): March 3, 2015

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: December 14, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Liver Failure; Hepatic Insufficiency; Hepatitis A; Liver Failure, Acute; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: NLI-FHF-S-PED