Liver disease in children with primary immunodeficiencies

doi:10.1016/j.jpeds.2004.05.037

The Journal of Pediatrics

Volume 145, Issue 3, September 2004, Pages 333-339

https://doi.org/10.1016/j.jpeds.2004.05.037 Get rights and content

Abstract

Objective

To investigate clinical features and to establish optimal management in children with primary immunodeficiency (PID) and liver disease.

Study design

A retrospective analysis of medical records of 147 children with PID who presented with abnormal liver tests to a tertiary center.

Results

Clinical evidence of liver disease was documented in 35 (23.8%) patients. Of these, 22 (63%) had hepatomegaly and 14 (40%) had splenomegaly. Sclerosing cholangitis (SC) was diagnosed in 21 children (60%), based on radiological and histological criteria; 4 patients with SC on cholangiography had no biliary changes in the liver biopsy. Ultrasonography demonstrated a dilated biliary system in 14 (67%) children with SC. Of 27 children investigated for Cryptosporidium parvum (CSP), 12 (44%) were positive, including 9 of 12 with SC. Overall, 7 (20%) patients died, including 3 boys with disseminated recurrent CSP infection after successful liver transplantion (LT). Temporary deterioration of liver injury was observed in 2 CSP-positive boys with CD40 ligand deficiency (CD40LD) who were undergoing nonmyeloablative hematopoietic stem cell transplantation (HSCT). Successive liver and HSCT was curative in 1 patient with CD40LD and end-stage liver disease.

Conclusion

SC is the most common hepatic complication of PID. Mild liver involvement could be arrested by early nonmyeloablative HSCT, whereas advanced disease may warrant combined liver and HSCT.

Section snippets

Patients and methods

The Pediatric Liver Service at King's College Hospital and the Department of Immunology at Great Ormond Street Hospital, London, are the two largest tertiary centers in the United Kingdom for management of liver disease and PIDs, respectively. The registry of all 147 patients with PID who were referred to the Immunology Service at Great Ormond Street Hospital between 1989 and 2002 was analyzed, and 35 patients with abnormal liver tests were selected. Hepatologic assessment included clinical

Results

The 35 children (27 boys, 23.8%) with PIDs and liver involvement presented to the Pediatric Liver Service at a median age of 9.2 years (range, 0.8-17.9). The most frequent diagnoses were combined immune deficiency (CID) of undefined molecular type in 14 patients, hyper-IgM syndrome in 8 patients (7 with mutation-proven CD40LD), and common variable immunodeficiency in 5 patients (Table).

Five children (4 boys, median age at referral 14.7 years; range, 0.8-16.7) were referred because of acute

Discussion

This retrospective series represents a single center's experience regarding hepatic involvement in PIDs. Following a relatively aggressive diagnostic approach, we have demonstrated that a significant proportion of children with a variety of PID disorders have clinical, biochemical, histologic, and radiologic evidence of liver disease.

A high incidence of liver involvement, ranging from mild biochemical abnormalities to severe SC, hepatitis, cirrhosis, and end-stage liver disease, has been

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^☆: Some data from this manuscript were presented in abstract form at 50th Annual AASLD Meeting, Dallas, Texas, USA, 1999 and 36^th EASL Annual Meeting, Prague, Czech Republic, 2001.

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Original ArticlesLiver disease in children with primary immunodeficiencies☆

Abstract

Objective

Study design

Results

Conclusion

Section snippets

Patients and methods

Results

Discussion

J Pediatr

Pediatr Clin North Am

Lancet

Lancet

J Pediatr

Blood

J Hepatol

Gastroenterology

Gastroenterology

Hepatology

Gastroenterology

Blood

Transplant Proc

Primary sclerosing cholangitis associated with immunodeficiency

Am J Dis Child

Sclerosing cholangitis associated with chronic cryptosporidiosis in a child with a congenital immunodeficiency disorder

Am J Gastroenterol

Chronic unexplained liver disease in children with primary immunodeficiency syndromes

J Clin Gastroenterol

Cholangiopathy and tumours of the pancreas, liver and biliary tree in boys with X-linked immunodeficiency with hyper-IgM syndrome

J Immunol

Original Articles
Liver disease in children with primary immunodeficiencies☆