Clinico-laboratory study on children with auto-immune hepatitis in Upper Egypt

doi:10.1016/j.ajg.2011.11.003

Arab Journal of Gastroenterology

Volume 12, Issue 4, December 2011, Pages 178-183

https://doi.org/10.1016/j.ajg.2011.11.003 Get rights and content

Abstract

Background and study aims

Auto-immune hepatitis (AIH) in children is a rare chronic progressive liver disorder. It is characterised serologically by high aminotransferase levels, elevated immunoglobulin G (IgG) and the presence of autoantibodies. AIH is divided into two types according to the autoantibody profile. This study aims to assess frequency, clinical manifestations, biochemical features and outcome of AIH in children attending Assuit University Hospitals in Upper Egypt with acute icteric hepatitis and seronegative viral markers (anti-hepatitis A virus (HAV) IgM, HbsAg, anti-hepatitis C virus (anti-HCV) Ab).

Patients and methods

The study includes 34 children with AIH, diagnosed on the basis of the International Scoring Criteria of Auto-immune Hepatitis, recruited from Assuit University Hospitals, during the period from January 2005 to December 2009. All patients received prednisolone 2 mg kg^–1 day^–1. Follow-up was done for 1 year.

Results

Among 34 children diagnosed as AIH, 24 were females (70.5%) and 10 were males (29.5%). Jaundice represented the most consistent finding in all patients. According to the autoantibody profile, 25 children were classified as type 1 and nine children were classified as type 2. Corticosteroid therapy was started. Complete remission was observed in 67.6% of patients and partial remission in 17.6%. There was no significant statistical difference in clinical and biochemical features of AIH in patients regarding the response to treatment. Mild side effects of steroid therapy were encountered in 48.2% of patients. After complete withdrawal of corticosteroids, six patients (20.7%) developed relapse.

Conclusion

AIH type 1 was the main form of AIH in children referred to Assiut University Hospitals. Girls were more affected than boys. AIH type 1 exhibited a more active, ongoing immunologic process. Steroid alone can be used successfully in most cases. Children with AIH type 2 had a higher frequency of relapse after corticosteroid withdrawal. Further studies on a larger number of cases and long-term follow-up are recommended.

Introduction

Auto-immune hepatitis (AIH) is a chronic disorder of the immune system targeting the liver, characterised by loss of immunological tolerance against the hepatocytes and including chronic inflammatory destruction of the liver parenchyma, cirrhosis and, eventually, liver failure [1], [2]. It has been described since the early 1950s, but its aetiology remains unknown [3] and is characterised serologically by high aminotransferase levels, elevated immunoglobulin G (IgG) and the presence of autoantibodies [4]. AIH is divided into two types according to the autoantibody profile: patients with type 1 are positive for antinuclear antibody (ANA) and/or anti-smooth muscle antibody (ASM), and patients with type 2 are positive for anti-liver–kidney–microsomal antibody type-1 (anti-LKM-1) [4], [5]. In keeping with other auto-immune disorders, AIH predominantly affects female patients at any age; the disease has been diagnosed as early as the age of 6 months, and its onset may range from asymptomatic to hyperacute with liver failure [5], [6]. Without treatment, AIH may develop into liver cirrhosis with potentially fatal outcomes. Early diagnosis and prompt intervention are thus important to save lives [7]. There is an increase in the yearly prevalence of AIH in childhood. The mode of presentation in childhood is variable, and the disease should be suspected and excluded in all children presenting with symptoms and signs of prolonged or severe liver disease [8].

This study aims to assess frequency, clinical manifestations, biochemical features and outcome of AIH in children attending Assuit University Hospitals in Upper Egypt with acute icteric hepatitis and seronegative viral markers (anti-hepatitis A virus (HAV) IgM, HbsAg, anti-hepatitis C virus antibody (anti-HCV Ab)).

Section snippets

Patients and methods

During the period from January 2005 to December 2009, 75 children with acute icteric hepatitis and seronegative viral markers (anti-HAV IgM, hepatitis B surface antigen, anti-HCV antibodies) were referred to the gastroenterology and hepatology unit of the Pediatric Department and the Department of Tropical Medicine of Assuit University Hospitals (a tertiary care referral hospital in Upper Egypt) for further diagnosis. AIH could be diagnosed in 34 children (45.3%). They were 24 females and 10

Statistical methods

Analysis was carried using Statistical Package for Social Sciences (SPSS) (version 16). The numerical data were represented as mean ± SD. For comparison of the two groups, Student’s t-test was used. Qualitative variables were compared using Fisher’s exact test. For all tests, the difference was considered significant if the probability (P) was <0.05.

Results

Out of 75 children with acute icteric hepatitis and seronegative viral marking (anti-HAV IgM, HbsAg and anti-HCV Ab), AIH could be diagnosed in 34 (45.3%).

Among 34 children diagnosed as AIH, 24 were females (70.5%) with a mean age of 8.7 ± 3.4 years and 10 were males (29.5%) with a mean age of 9.5 ± 2.8 years at time of presentation.

None of the patients included in this study had a previous history of blood transfusion, surgery or drug intake, and their first-degree relatives did not have history of

Discussion

In our study AIH could be detected in 34 out of 75 children (45.3%), based on the International Scoring Criteria of Autoi-mmune Hepatitis [9]. This strongly suggests that AIH should be included in the differential diagnosis of children with unexplained hepatitis-like manifestations. The designation of probable AIH by the international scoring systems is based on differences in clinical manifestations and does not reflect differences in the validity of the diagnosis or its treatment response;

Conflicts of interest

The authors declared that there was no conflict of interest.

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Autoimmune Hepatitis (AIH) is a chronic inflammatory disease of the liver of unknown aetiology characterized by polyclonal hypergammaglobulinemia and circulating autoantibodies. Objective of the study is to find out the prevalence of autoimmune hepatitis and its causative autoantibody (Anti-nuclear, anti-smooth muscle, anti-liver kidney microsomes-1) following comprehensive diagnostic criteria given by International Autoimmune Hepatitis Group.
250 patients with raised aminotransferase but, negative for the commonest three clinical conditions viz, viral hepatitis, drug induced liver injury and alcohol induced liver injury were suspected to be a case of autoimmune hepatitis. Recent IAIHG criteria was followed in making diagnosis of autoimmune hepatitis. We did the investigation for viral hepatitis (acute/chronic), drug induced liver injury and alcohol induced liver injury and then measured serum IgG. Indirect Immunofluorescence (IIF) was done for Anti-nuclear antibody and was also done for anti-smooth muscle antibody and anti-liver kidney microsomes-1 antibody simultaneously.
As per IAIHG criteria, out of 250 patients, Ig “G” was elevated in 88 patients with significant titres for Anti-nuclear antibody (50 patients), anti-smooth muscle antibody (65 patients), anti-liver kidney microsomes-1 antibody (7 patients) and Anti-mitochondrial antibody (18 patients) were found. As per International Autoimmune Hepatitis Group Comprehensive scoring system, probable diagnosis was made in 83 patients (33.2%) and 12 were confirmed for autoimmune hepatitis (4.8%).
Female preponderance was observed and type 1 Autoimmune Hepatitis was most common whereas type 2 Autoimmune Hepatitis was found in few cases. Most patients had anti-smooth muscle antibody and anti-nuclear antibody positivity indicating the type, but no significant difference was seen in clinical symptoms or biochemical parameters between the different types. 162 patients couldn't be evaluated for autoimmune hepatitis because of serum IgG cut-off criteria >1500 mg/l.
Paediatric autoimmune liver diseases: A descriptive study of patients from Saudi Arabia
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This is again in line with the present data, where there were no cases of fulminant hepatic failure. Liver cirrhosis is found at the time of diagnosis of AIH in 25–60% of cases [16,18]. The present data showed a similar rate of cirrhosis, at 32%.
Autoimmune liver diseases (ALDs) are a clinico-pathologic spectrum of disorders that share some similarities. They are formally classified as autoimmune hepatitis (AIH), isolated autoimmune sclerosing cholangitis (ASC), and the overlap syndrome of these. We describe the clinical, biochemical, and outcomes data of a cohort of autoimmune ALDs patients in a tertiary care centre.
This is a cross-sectional study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Data were collected in 2007–2018. All cases were 18 years old or younger at the time of diagnosis. The data collection comprised clinical, laboratory, imaging, treatment, and longitudinal follow-up data.
Twenty-five patients were identified; 14 (56%) were females. Twenty-one patients (84%) had AIH-1,1 patient (4%) had AIH-2, and 3 patients (12%) had autoimmune sclerosing cholangitis (ASC). An insidious course was found in 21 (84%) cases. Acute hepatitis and fulminant hepatic failure was found to be very rare. Eight cases (32%) had cirrhosis at diagnosis. A total of 20 cases (80%) had complete remission following therapy. The median follow-up period was 45 months. There was no mortality, and only one patient was referred for transplant. Thus, the transplant-free survival was 96%.
Our study showed predominance of AIH-1 over AIH-2. Response to treatment in our cohort was found to be similar to the results found in some other key studies. Prognosis and transplant-free survival is better than many published paediatric studies.
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Immunosuppressive therapy is the cornerstone of treatment for AIH (Fig. 3). In juvenile AIH, remission is defined as complete clinical recovery with transaminase levels within the normal range and is achieved in 60%–90% of patients [2,9,64–66]. More recently, three more criteria have been added to the definition of remission: normalization of IgG levels, negative or very low-titer autoantibodies (ANA and SMA negative or ≤1:20; anti-LKM1 and anti-LC-1 ≤1:10 or negative), and histological resolution of inflammation [67].
Autoimmune hepatitis (AIH) is a rare, chronic disease that affects both adults and children, including infants. The disease is probably triggered by environmental factors in genetically predisposed individuals. The clinical presentation ranges from asymptomatic patients or patients with non-specific symptoms, such as fatigue, to fulminant liver failure, many children presenting with symptoms indistinguishable from those of acute hepatitis. Raised transaminase and immunoglobulin G (IgG) levels, in association with circulating autoantibodies, guide towards the diagnosis. The histological hallmark is interface hepatitis, which however is non-specific and may be absent. There are no bile duct changes on cholangiography. Presence of anti-nuclear antibody (ANA) and/or anti-smooth muscle antibody (SMA) is characteristic for type 1 AIH, whereas presence of anti-liver kidney microsomal type 1 (LKM1) antibody and/or anti-liver cytosol type 1 (LC1) antibody defines type 2 AIH. The latter accounts for about one third of the juvenile AIH cases, presents more acutely than type 1 AIH and is very rare in adults. Immunosuppressive therapy, based on steroids and azathioprine, is required, and in the vast majority of patients leads to clinical and biochemical remission, defined as absence of symptoms, normal transaminase and IgG levels, and negative or low-titer autoantibodies. In patients intolerant or non-responder to standard therapy, a number of second line drugs have been employed with variable results. For the rare cases who progress to end-stage liver disease, liver transplantation is life-saving, but recurrence of the disease is possible. A better understanding of the underlying pathogenic mechanisms will help to develop new, more effective and less toxic therapies, and to tailor treatment regimens to the individual patient.
Retrospective, single-center analysis of autoimmune hepatitis in Jordanian children: clinical features, treatments, and outcomes
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KASL clinical practice guidelines for management of autoimmune hepatitis 2022
2023, Clinical and Molecular Hepatology
Seronegative autoimmune hepatitis in children: A real diagnostic challenge
2022, Wiener Klinische Wochenschrift

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Original ArticleClinico-laboratory study on children with auto-immune hepatitis in Upper Egypt

Abstract

Background and study aims

Patients and methods

Results

Conclusion

Introduction

Section snippets

Patients and methods

Statistical methods

Results

Discussion

Conflicts of interest

J Hepatol

J Hepatol

Gastroenterology

J Autoimmun

J Hepatol

Am J Gastroenterol

Clin Liver Dis

Autoimmune hepatitis

N Engl J Med

Autoimmune hepatitis, from mechanisms to therapy

Hepatology

Aetiopathogenesis of autoimmune hepatitis

World J Gastroenterol

Autoimmune hepatitis: a childhood disease

Curr Pediatr Rev

Guidelines for therapy of autoimmune liver disease

Semin Liver Dis

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World J Gastroenterol

Original Article
Clinico-laboratory study on children with auto-immune hepatitis in Upper Egypt