Background. Autoimmune hepatitis (AIH) is increasingly seen in children worldwide and it is more severe in children compared to adults. This study highlights the biochemical and clinical aspect, treatment given and outcome of the disease including pediatric liver transplantation. Study. Retrospective review (2012-2022) was done in Shifa International Hospital, Islamabad. Patients under 18 years diagnosed with AIH were included. Data related to age, gender, clinical features, laboratory investigations including liver function test, liver biopsy findings and imaging modalities were included. Results. Fifteen patients were included 7 (47%) were males and 8 (53%) females. AIH type 1 was the most common type seen in 7 (46%), AIH type 2 in 5 (33%) and seronegative in 3 (20%). Jaundice was the most common symptom. Liver biopsy showed findings characteristic of AIH. Liver transplant performed in 3 patients. Conclusion. The study highlights the varied clinical presentation of AIH in Pakistani children.

Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.

Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children, although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis. Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated. The absence of autoantibody positivity, hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease. In general, seronegative autoimmune hepatitis often presents with acute hepatitis, and its treatment and prognosis similar to seropositive autoimmune hepatitis. The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood, and those of which current knowledge is vague.

The aim of this study is to study the association of human leukocyte antigen (HLA) DRB1 alleles with treatment response in Indian children with autoimmune liver disease (AILD).

HLA DRB1 alleles of 71 Indian children with pediatric AILD (pAILD) were analyzed along with 25 genetically confirmed patients with Wilson disease as controls. After 1 year of therapy, all those who failed to normalize aspartate & alanine transferase (AST/ ALT) (below 1.5 times of upper limit of normal) and/or failed to normalize IgG levels, or who had >2 relapses (AST/ALT levels >1.5 times of upper limit of normal) while on treatment, were labeled as difficult to treat (DTT).

HLA DRB1∗3 was found to be significantly associated with AIH type 1 (46.2% vs. 4% in controls; P corrected = 0.011). Majority of the patients [55 (77.5%)] had chronic liver disease at presentation, with 42 (59.2%) having portal hypertension and 17 (23.9%) having ascites. Out of the 71 with pAILD, 19 (26.8%) were DTT. HLA DRB1∗14 was found to be independently associated with DTT cases (36.8% vs. 9.6%, OR 5.87, 95% CI 1.07-32.09, P = 0.041). Other factors independently associated with DTT were presence of autoimmune sclerosing cholangitis (OR 8.57, P = 0.008) and high-risk varices (OR 7.55, P = 0.016), improving the correctness of classification of the model from 73.2% to 84.5%.

HLA DRB1∗14 is independently associated with treatment response in pAILD and HLA DRB1∗3 is associated with AIH type 1. HLA DRB1 alleles may thus provide supportive information for diagnosis and prognosis of AILD.

Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, characterized by hypergammaglobulinemia, the presence of specific autoantibodies, and typical abnormalities in liver histology. Prompt diagnosis and initiation of immunosuppressive treatment are necessary for both chronic and acute onset AIH to prevent progression to end-stage liver disease or fatal liver failure. However, the diagnosis of AIH is challenging mainly because of its heterogeneous clinical, serological and pathological features. Although portal lymphoplasmacytosis and interface hepatitis are the most typical histological features of AIH, many other histological features can be observed in AIH, including emperipolesis, hepatocyte rosettes, and Kupffer cell hyaline globules. Recent studies have questioned emperipolesis and hepatocyte rosette formation as typical features of AIH, and atypical clinical and histological presentations have also been recognized. This led an international working group to propose the modified AIH diagnostic criteria. However, it is well recognized that there are no pathognomonic characteristics that can be used to diagnose AIH and careful clinicopathological correlation is required to arrive at the correct diagnosis. The aim of this review is to summarize the histological features of AIH, its varied histopathologic spectrum, recent updates and major differential diagnoses in routine clinical practice.

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren's syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.