Fulminant hepatic failure of autoimmune aetiology in children.

Abstract

OBJECTIVE:

Autoimmune hepatitis (AIH) is considered an underdiagnosed cause of fulminant hepatic failure (FHF). Autoimmune FHF (AI-FHF) is believed to lead invariably to liver transplantation (LTX) or death. We aimed to describe the autoimmune features of children diagnosed as having AI-FHF and indeterminate FHF (ID-FHF), and describe the outcome of patients with AI-FHF treated with immunosuppressive drugs.

METHODS:

In this case-control study, the files of patients with AI-FHF and ID-FHF were reviewed and compared. AIH was diagnosed based on positive autoantibodies, raised immunoglobulin G, and histology when available. FHF was defined by raised transaminases, international normalised ratio ≥ 2.0, presence of encephalopathy, and no previously recognised liver disease.

RESULTS:

A total of 46 children with FHF were managed in the last 15 years: 10/46 (22%) had AI-FHF, 20/46 (43%) ID-FHF, and 16 had other diagnosis. The mean follow-up time was 4.6 years. AI-FHF and ID-FHF differed for the presence of autoantibodies (10/10, 6/10 liver/kidney microsome [LKM]-type, vs 3/20, none LKM, P < 0.0001), immunoglobulin G level (1845 vs 880 mg/dL, P < 0.001), median age at diagnosis (6.4 vs 1.8 years, P = 0.017), and alanine aminotransferase level (1020 vs 2386 IU/L, P = 0.029). Liver histology did not allow to differentiate the 2 conditions. Among the patients with AI-FHF, 4/9 who received steroids recovered; 5/9 required LTX and 1 died awaiting treatment.

CONCLUSIONS:

AIH is a much more common cause of FHF than previously suggested, and a complete autoantibody testing including LKM-type is essential in this setting. Autoantibodies are uncommon in ID-FHF, and histology cannot distinguish it from AI-FHF. A cautious steroid trial may avoid LTX in some of the patients with AI-FHF.

• Authors: A Di Giorgio, M Bravi, E Bonanomi, G Alessio, A Sonzogni, Y Zen, M Colledan, L D'Antiga
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 60 Issue 2 Pg. 159-64 (Feb 2015) ISSN: 1536-4801 [Electronic] United States
• PMID: 25304891 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antibodies, Antinuclear
• Autoantibodies
• Immunoglobulin G
• Immunosuppressive Agents
• anti-liver kidney microsome antibody
• Cyclosporine
• Alanine Transaminase
• Azathioprine
• Methylprednisolone

Topics

• Adolescent
• Age Factors
• Alanine Transaminase (blood)
• Antibodies, Antinuclear (blood)
• Autoantibodies (blood)
• Azathioprine (therapeutic use)
• Case-Control Studies
• Child
• Child, Preschool
• Cyclosporine (therapeutic use)
• Follow-Up Studies
• Hepatitis, Autoimmune (complications)
• Humans
• Immunoglobulin G (blood)
• Immunosuppressive Agents (therapeutic use)
• Infant
• Liver Failure, Acute (etiology, pathology, therapy)
• Liver Transplantation
• Methylprednisolone (therapeutic use)
• Retrospective Studies
• Survival Rate