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Hepatology and Transplantation

Cite as: Archiv EuroMedica. 2026. 16; 4. DOI 10.35630/2026/16/Iss.4.06

Received 18 June 2026;
Accepted 23 July 2026;
Published 2 August 2026

AUTOIMMUNE HEPATITIS IN CHILDREN AND ADOLESCENTS: DIFFERENCES IN CLINICAL PRESENTATION, DIAGNOSIS AND MANAGEMENT

Katarzyna Łysynkiewicz1 email orcid id logo, Zuzanna Wątek1 orcid id logo,
Patrycja Krawczyk2 orcid id logo, Izabela Grzyb3 orcid id logo,
Jan Szewczyk3 orcid id logo, Alicja Smolińska3 orcid id logo,
Maria Bołoz1 orcid id logo, Sylwia Haba4 orcid id logo,
Ewa Dapkiewicz5 orcid id logo, Dawid Gąsowski6 orcid id logo

1 Jędrzej Śniadecki Regional Hospital, Białystok, Poland
2 The Primary Regional Hospital in Kielce, Poland
3 Polish Red Cross Maritime Hospital, Gdynia, Poland
4 University Clinical Hospital of Białystok, Poland
5 Independent Public Health Care Facilities of the Ministry of Interior and Administration in Białystok, Poland
6 Independent Public Health Care Facility in Łapy, Poland

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  kstepaniuk12@gmail.com

ABSTRACT

Background

Autoimmune hepatitis is a chronic immune-mediated inflammatory liver disease with a heterogeneous spectrum, ranging from asymptomatic liver enzyme elevation to acute liver failure, cirrhosis, and liver transplantation. Juvenile autoimmune hepatitis is clinically important because it may present acutely and with advanced liver injury.

Aims

This narrative review summarizes current evidence on autoimmune hepatitis in children and adolescents, focusing on presentation, diagnosis, treatment, long-term care, and differences from adult management.

Methods

PubMed/MEDLINE and Google Scholar were searched for English-language publications from January 1997 to June 17, 2026. Forty-five publications were included in the narrative synthesis.

Results

Type 2 autoimmune hepatitis accounts for approximately one third of pediatric cases, and up to 80% of type 2 cases are diagnosed before age 18. Approximately 25-34% of pediatric patients may be asymptomatic, whereas 25-40% present acutely. Diagnosis requires biochemical, serological, histological, and differential assessment. Pediatric autoantibody thresholds may be lower than adult thresholds, including ANA/SMA ≥1:20 and anti-LKM1 ≥1:10. First-line therapy is corticosteroids with azathioprine; one pediatric study reported biochemical remission after a mean of 36 days. In 10–20% of cases, intolerance or inadequate response requires mycophenolate mofetil, tacrolimus, or cyclosporine.

Conclusions

Early recognition, individualized immunosuppression, and long-term follow-up are essential to achieve remission, prevent relapse, and reduce progression to end-stage liver disease.

Keywords: autoimmune hepatitis; juvenile autoimmune hepatitis; pediatric hepatology; immunosuppressive therapy; azathioprine; corticosteroids; autoantibodies; liver biopsy; chronic liver disease; liver transplantation.

INTRODUCTION

Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease of unknown etiology. If left untreated or diagnosed at a late stage, the condition may lead to serious complications [1,2]. The clinical presentation of autoimmune hepatitis varies widely, ranging from asymptomatic forms to acute hepatitis progressing to cirrhosis and even acute liver failure requiring liver transplantation [3]. Features suggestive of AIH include elevated serum immunoglobulin G (IgG) levels, characteristic histological findings of liver inflammation with periportal necrosis, and the presence of specific autoantibodies [1].

A distinct form of AIH is juvenile autoimmune hepatitis (JAIH), a severe autoimmune liver disease that may progress to cirrhosis and liver failure if it is not diagnosed and treated early [4]. Type 1 AIH is typically associated with antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA), whereas type 2 AIH is characterized by anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) antibodies. However, the absence of these antibodies does not exclude the diagnosis or indicate that treatment is unnecessary. Such cases are classified as seronegative AIH [5]. Therefore, diagnosis requires a comprehensive and multidisciplinary approach. Due to advanced disease progression, some pediatric patients may require liver transplantation during adolescence or early adulthood. Early diagnosis and timely initiation of immunosuppressive therapy are essential to prevent disease progression and achieve sustained remission [4,6].

AIMS

This review aims to present current knowledge on autoimmune hepatitis in children and adolescents and to compare key pediatric management considerations with therapeutic approaches used in adults. Particular attention is given to diagnostic uncertainty, the role of liver biopsy, first-line and second-line immunosuppression, long-term monitoring, adherence during adolescence, and transition from pediatric to adult care.

MATERIALS AND METHODS

This study was designed as a narrative review of the literature concerning autoimmune hepatitis in children and adolescents. Its purpose was to integrate and critically discuss current evidence on clinical presentation, diagnostic evaluation, treatment strategies, long-term follow-up, adherence during adolescence, and transition from pediatric to adult hepatology care. The literature search was carried out using PubMed/MEDLINE and Google Scholar and included publications from January 1997 to June 17, 2026. Search strings were selected to cover the disease entity, pediatric population, diagnostic procedures, and immunosuppressive therapies.

The PubMed/MEDLINE search included the following terms: "autoimmune hepatitis", "juvenile autoimmune hepatitis", "children", "adolescents", "pediatric", "paediatric", "diagnosis", "treatment", "azathioprine", "corticosteroids", "prednisone", "prednisolone", "mycophenolate mofetil", "tacrolimus", "cyclosporine", "autoantibodies", "liver biopsy", and "autoimmune sclerosing cholangitis". A simplified search strategy based on the same main terms was applied in Google Scholar.

Publications were considered eligible if they were written in English, available as full texts, and clinically relevant to autoimmune hepatitis or autoimmune sclerosing cholangitis in pediatric patients. Eligible sources included original clinical and observational studies, cohort studies, systematic reviews, meta-analyses, clinical guidelines, consensus statements, and high-quality narrative reviews. Studies were included when they addressed diagnosis, treatment, prognosis, long-term monitoring, adherence, transition of care, or pediatric-specific aspects of disease management.

Publications were excluded if they were duplicates, written in languages other than English, available only as conference abstracts, unrelated to autoimmune liver disease, based solely on animal or laboratory research, or focused exclusively on adults without relevance to pediatric practice. Articles with insufficient clinical information or unclear methodological value were also excluded.

The final narrative synthesis included 45 publications. The selection of literature was guided by clinical relevance and contribution to a balanced analysis of juvenile autoimmune hepatitis. Priority was given to pediatric guidelines, consensus documents, systematic reviews, large observational studies, and original studies reporting clinically useful data. Adult studies were used only when they helped interpret pediatric practice or when evidence in children was limited. The included literature was reviewed narratively and analysed qualitatively, with attention to areas of agreement, differences between pediatric and adult management, limitations of available evidence, and implications for clinical care.

RESULTS

The review identified clinically relevant findings in four main areas: clinical presentation, diagnostic assessment, treatment, and long-term follow-up. The main quantitative and comparative findings are presented below and summarized in the accompanying tables.

Epidemiology and pathogenesis

AIH is a chronic autoimmune disease that occurs in all age groups. It affects both adults and children, including the infant population. AIH is classified into two main serological types, with type 1 predominating overall and type 2 being more strongly associated with childhood and adolescence. In children and adolescents, type 2 disease represents around one third of cases, usually manifests with a more acute onset compared to type 1, and is uncommon in adulthood [7,8,9].

AIH is a disease that particularly affects the pediatric population. Approximately 40% of type 1 AIH cases and up to 80% of type 2 cases are diagnosed before the age of 18 years [10]. Juvenile autoimmune hepatitis may occur in children of all ethnic backgrounds worldwide [11,12]. The peak age at diagnosis is approximately 10 to 11 years in type 1 AIH and six to seven years in type 2 AIH. Similar to many autoimmune diseases, AIH demonstrates a marked female predominance. Females are affected more frequently than males, with female-to-male ratios of approximately 3:1 in type 1 AIH and 9:1 in type 2 AIH [4].

The exact pathogenesis of AIH remains incompletely understood and is likely multifactorial. The disease is believed to develop as a result of environmental triggers acting in genetically predisposed individuals, with susceptibility influenced by factors such as sex, age, and genetic background. AIH does not follow a Mendelian pattern of inheritance; therefore, no single genetic locus has been identified as responsible for the disease. The strongest genetic associations have been observed within the human leukocyte antigen (HLA) region on chromosome 6, particularly with HLA-DR3 and HLA-DR4 alleles in European and North American populations [13]. Different susceptibility alleles have also been identified among various ethnic groups, suggesting population-related genetic variability. In addition to HLA-related genes, polymorphisms affecting immune regulation, including CTLA-4, FAS, vitamin D receptor, and TNF-alpha genes, may contribute to disease susceptibility and severity [10].

The environmental trigger responsible for disease initiation remains unclear. Viral infections, medications, and chemical agents are regarded as potential triggers that may disrupt immune tolerance and promote autoimmune-mediated liver injury. Several mechanisms have been proposed, including activation of autoreactive T cells, molecular mimicry, exposure of previously hidden antigens, and changes in gene expression [10].

Clinical presentation

The clinical presentation of JAIH is highly heterogeneous, ranging from asymptomatic elevation of liver enzymes to acute liver failure requiring urgent liver transplantation. Common symptoms include fatigue, abdominal pain, nausea, anorexia, and jaundice, while hepatomegaly and splenomegaly may be present at diagnosis. In some cases, the disease presents with an acute hepatitis-like onset, whereas in others symptoms develop insidiously over a prolonged period. An acute presentation may represent either a true sudden-onset disease or an acute exacerbation of previously unrecognized chronic liver disease. Cirrhosis may already be present at diagnosis in a considerable proportion of pediatric patients [11,12,14]. Compared with type 1 AIH, type 2 disease typically occurs in younger children and is more often associated with an acute clinical presentation [4].

A proportion of patients, approximately 25-34%, may remain asymptomatic, with the disease being detected incidentally due to elevated serum transaminases. Despite the absence of clinical symptoms, histological changes may be similar to those observed in symptomatic patients. In symptomatic patients, fatigue is the most common complaint, often accompanied by jaundice and other non-specific symptoms such as malaise or arthralgia. In a subset of cases, JAIH may present with an acute onset, accounting for approximately 25-40% of patients [11,12]. JAIH may also be associated with other autoimmune conditions, such as celiac disease, systemic lupus erythematosus, or autoimmune polyendocrinopathy syndromes, reflecting its potential occurrence within broader immune dysregulation [3,4].

Compared with adult patients, juvenile autoimmune hepatitis more often presents with an acute hepatitis-like onset and a more severe clinical course. Children are more likely to be diagnosed during symptomatic phases, including acute liver failure or advanced liver disease, whereas adults more frequently present with a chronic, indolent course or incidental elevation of liver enzymes. In addition, type 2 AIH is predominantly a pediatric disease. This broad clinical spectrum contributes to diagnostic delays and highlights the importance of early recognition and a high index of clinical suspicion in pediatric patients [4,7].

The key clinical differences between juvenile and adult autoimmune hepatitis are summarized in Table 1.

Table 1. Key clinical differences between juvenile and adult autoimmune hepatitis.

Aspect Juvenile autoimmune hepatitis Adult autoimmune hepatitis Supporting references
Typical presentation More often acute or severe; advanced liver disease may be present at diagnosis More often chronic, indolent, or incidentally detected [4,7]
Serological type Type 2 AIH is relatively more common in childhood and adolescence Type 2 AIH is uncommon in adults [7]
Autoantibody titers ANA/SMA ≥1:20 and anti-LKM1 ≥1:10 may be clinically meaningful Adult cut-offs are generally higher [15,16]
Differential diagnosis Autoimmune sclerosing cholangitis is a key pediatric differential diagnosis Overlap syndromes are more often discussed in adult practice [15,17,18]
Monitoring domains Growth, puberty, bone health, steroid toxicity, and adherence Biochemical remission, fibrosis, comorbidities, and drug toxicity [4,15,16,18,19]
Transition of care Adolescence and early adulthood are high-risk periods for non-adherence and loss to follow-up Transition is not usually a central management issue [18,20]

Diagnostic approach

The diagnosis of autoimmune hepatitis in children and adolescents is based on the clinical picture, biochemical, serological, and histopathological tests, as well as the exclusion of other causes of liver injury that may mimic AIH clinically, biochemically, serologically, or histologically. Important alternative diagnoses include viral hepatitis types A, B, C, and E, Epstein-Barr virus infection, Wilson disease, alpha-1 antitrypsin deficiency, metabolic dysfunction-associated steatotic liver disease, and drug-induced liver injury [15,17].

Due to the absence of pathognomonic features for this disease entity, the International Autoimmune Hepatitis Group (IAIHG) developed diagnostic scoring systems in which points are assigned depending on the presence or absence of specific diagnostic features [21,22]. In children, IAIHG scoring systems are auxiliary and should not replace comprehensive clinical assessment, as they were developed mainly on the basis of data from adult populations, and pediatric modifications may improve diagnostic performance in children [16,17,23]. Recent diagnostic reviews similarly emphasize that autoimmune hepatitis should be diagnosed through an integrated clinical, biochemical, serological, and histological assessment rather than by any single test result [24].

Biochemical assessment

In the diagnosis of AIH, the assessment of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity is important. Their elevation reflects an inflammatory-necrotic process in the liver parenchyma; however, it is not specific for AIH and may also occur in viral, metabolic, toxic, or drug-induced liver injury [16]. In addition to aminotransferases, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) activity, as well as total and direct bilirubin levels, should be assessed. These parameters are helpful in evaluating the presence of cholestasis and are important in the differential diagnosis with autoimmune sclerosing cholangitis in children. Elevated values may suggest ASC and indicate the need to extend the diagnostic work-up by performing magnetic resonance cholangiopancreatography (MRCP) [15,17].

Differential diagnosis with ASC is particularly important in the pediatric population [25,26,27], as autoimmune sclerosing cholangitis may initially resemble type 1 AIH in terms of biochemical, serological, and histopathological findings. In adults, classic overlap syndromes are more often discussed, whereas in children ASC represents one of the key differential diagnoses [15,18,25,26,27]. In assessing disease severity, it is important to measure albumin concentration, prothrombin time, and international normalized ratio (INR), which reflect the synthetic function of the liver. Decreased albumin concentration or prolonged prothrombin time may indicate advanced liver damage or an acute severe form of the disease [4,16]. In acute AIH in children, higher levels of aminotransferases, bilirubin, and INR, as well as lower albumin concentration, have been described compared with a more chronic presentation [4].

One of the key biochemical tests in the diagnosis of AIH is the measurement of IgG concentration. Elevated IgG levels are characteristic of AIH and have been included in diagnostic criteria developed by the IAIHG [16]. At disease onset, especially in acute AIH, IgG levels may be normal; therefore, a normal concentration does not exclude the diagnosis [4]. In addition to its diagnostic value, IgG is also used to monitor treatment response, as a normal concentration together with normalization of aminotransferase activity indicates disease remission [15,28].

Autoantibodies

The diagnosis of seropositive AIH in children and adolescents is based, among other factors, on the detection of circulating autoantibodies. Their presence, however, is not entirely specific, as autoantibodies may also occur in other liver diseases, such as primary sclerosing cholangitis or ASC, viral hepatitis, drug-induced liver injury, as well as in systemic autoimmune diseases [29,30]. Nevertheless, a positive serological result, interpreted together with the clinical picture, aminotransferase activity, IgG concentration, and liver biopsy findings, significantly supports the diagnosis of AIH and allows classification of the disease into type 1 and type 2 [15,29].

In type 1 AIH, ANA and SMA are most commonly detected. ANA are markers of low specificity, as they may also occur in PSC/ASC, viral hepatitis, non-alcoholic and alcoholic liver disease, drug-induced liver injury, and autoimmune diseases such as systemic lupus erythematosus, Sjogren syndrome, or systemic sclerosis. SMA are also not entirely specific and may appear, among others, in autoimmune sclerosing cholangitis, rheumatic diseases, and infectious diseases [29,30]. In the pediatric population, lower autoantibody titers than in adults are considered clinically significant; according to ESPGHAN recommendations, ANA or SMA titers of ≥1:20 may already be considered positive [15].

Markers of type 2 AIH include anti-LKM1 and anti-LC1 antibodies. Anti-LKM1 antibodies are directed against the CYP2D6 enzyme and, apart from AIH, may also occur in hepatitis C virus infection and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome [29]. Anti-LC1 antibodies may occur alone or together with anti-LKM1, and their target antigen is formiminotransferase cyclodeaminase, an enzyme involved in folate metabolism. In children, low titers of anti-LKM1 antibodies, usually from ≥1:10, may already be clinically significant, while the presence of anti-LC1 antibodies also strongly supports the diagnosis of type 2 AIH [4,15].

Additional autoantibodies may support the diagnosis of AIH. Anti-soluble liver antigen antibodies are highly specific for AIH and occur mainly in type 1 AIH, including overlap syndromes [29,31,32]. In turn, perinuclear antineutrophil cytoplasmic antibodies may occur in type 1 AIH, PSC, and inflammatory bowel diseases. However, serological test results should always be interpreted in the context of the entire clinical picture, as the presence of autoantibodies alone is not sufficient to diagnose AIH [15,30]. In the serological diagnosis of AIH in children, it is particularly important to avoid directly applying adult cut-off values. In pediatric patients, lower autoantibody titers may be clinically significant; therefore, applying adult thresholds may lead to false-negative results and delayed diagnosis [15,17].

Liver biopsy

In histopathological examination, AIH typically presents with interface hepatitis. It is characterized by a lymphoplasmacytic inflammatory infiltrate in the portal tracts, which crosses the limiting plate and involves the adjacent liver parenchyma [4,16]. Biopsy may also show hepatocyte rosettes, emperipolesis, the presence of lymphocytes and plasma cells within the cytoplasm of hepatocytes, piecemeal or bridging necrosis, lobular hepatitis, and varying degrees of fibrosis. These features are typical of AIH and support the diagnosis; however, they are not pathognomonic or entirely specific, and therefore should be interpreted together with the clinical, biochemical, and serological picture [4].

Recent studies indicate that PAS-positive hyaline deposits in Kupffer cells, corresponding to Russell bodies, may be specific for AIH and may constitute an additional helpful diagnostic feature [33]. Apoptotic lymphocytes in portal areas may also be diagnostically useful and have been described as a potential marker supporting the diagnosis of AIH [4].

Treatment

Clinical management requires individualized assessment of disease severity, treatment tolerance, comorbidities, and the likelihood of adherence, particularly in adolescents and in patients who require prolonged immunosuppression [34]. The principal goals of therapy are to induce biochemical remission, prevent progression of fibrosis, avoid liver failure, minimize treatment-related toxicity, and maintain long-term follow-up through adolescence and transition to adult care.

First-line therapy

Treatment of AIH in children is based on immunosuppressive drugs [15,17]. First-line treatment includes glucocorticoids, particularly prednisone or prednisolone [15]. Their use leads to a reduction in inflammatory activity and improvement of biochemical parameters; however, adverse effects such as Cushing syndrome, hypertension, weight gain, and growth impairment limit prolonged exposure [15,19]. Azathioprine is used as a glucocorticoid-sparing agent and allows gradual reduction of the steroid dose while maintaining disease control [15,16]. Due to the potential hepatotoxicity of azathioprine, it should be used cautiously in children with severe jaundice or cirrhosis [15]. Before starting azathioprine therapy, thiopurine methyltransferase activity testing is recommended in all patients, and regular monitoring of blood count, aminotransferase activity, bilirubin, cholestasis parameters, and IgG concentration is necessary during treatment [16].

Clinical and observational data support the efficacy of prednisone combined with azathioprine. In a Polish retrospective study by Pniewska et al., children treated with prednisone and azathioprine achieved biochemical remission after an average of 36 days of therapy, although steroid-related adverse effects occurred in most patients [35]. Unlike in adults, therapeutic decisions in children must take into account not only control of inflammatory activity but also the impact of chronic immunosuppression on growth and sexual maturation. Therefore, early reduction of exposure to glucocorticoids while maintaining effective disease control is particularly important in the pediatric population [4,19].

Monitoring, maintenance, and withdrawal

Remission is primarily assessed by resolution of symptoms and normalization of aminotransferase activity and IgG concentration. Autoantibody titers may decrease during treatment but should be interpreted cautiously. Histological remission is defined by the resolution of inflammatory activity on liver biopsy [15,28]. Frequent laboratory monitoring is recommended in the first weeks of treatment, as steroid doses require gradual modification depending on response and tolerance. ESPGHAN indicates that during the first six to eight weeks, liver tests should be monitored even weekly in order to adjust doses appropriately and limit adverse effects of glucocorticoids [15].

After remission is achieved, treatment enters the maintenance phase, which consists of using glucocorticoids at the lowest possible doses and, in some patients, azathioprine monotherapy or an attempt to withdraw immunosuppression [15,16]. In children with AIH, maintenance therapy is usually long-term. ESPGHAN recommends continuing immunosuppression for at least two to three years before considering withdrawal [15]. Monitoring of treatment in children is broader than in adults because, in addition to liver parameters, it should include assessment of growth, body weight, maturation, bone mineral density, and adverse effects of steroid therapy. This is particularly important in patients requiring long-term maintenance treatment [17,19].

Treatment withdrawal may be considered only after at least two to three years of therapy in patients whose aminotransferase activity, IgG concentration, and negative or low autoantibody titers have remained normal for at least one year [15,16]. Follow-up liver biopsy may be considered before treatment withdrawal, particularly when there is concern about persistent histological activity despite biochemical remission [15]. This stage of treatment consists of gradual dose reduction to zero, most commonly of prednisone or prednisolone, followed by azathioprine [15]. An important difference in the adolescent population is the risk of non-adherence to therapeutic recommendations, which may lead to exacerbations and disease relapses. In this age group, treatment should therefore include not only drug selection but also patient education, assessment of adherence, and preparation for transition from pediatric to adult care [4,28,36].

Second-line therapy

In 10-20% of cases, first-line treatment is ineffective or poorly tolerated, requiring the use of other drugs such as mycophenolate mofetil, tacrolimus, and cyclosporine [37]. In the study by Aw et al., which included children with autoimmune liver disease resistant to standard treatment or intolerant of previous therapy, 18 children responded to mycophenolate mofetil, and normalization of AST activity was observed in 14 patients [38]. The study by Efe et al. also demonstrated the efficacy of both mycophenolate mofetil and tacrolimus in children with AIH requiring second-line therapy. In patients non-responsive to standard treatment, tacrolimus was associated with a higher response rate than mycophenolate, although this difference did not reach statistical significance [39].

The randomized study by Cuarterolo et al. compared prednisone with azathioprine versus cyclosporine as initial treatment and showed similar efficacy of both strategies, although remission was achieved more rapidly in the prednisone-azathioprine group [40]. Mycophenolate mofetil and tacrolimus, used in children with AIH as second-line drugs, differ in their adverse effect profiles. In the systematic review by Zizzo et al., adverse effects were reported in 48% of patients treated with mycophenolate and in 54% of patients receiving tacrolimus [37].

Mycophenolate more commonly causes gastrointestinal and hematological symptoms, such as diarrhea, nausea, abdominal pain, leukopenia, anemia, and increased susceptibility to infections [37,38]. An important limitation of its use is teratogenicity, particularly in girls of reproductive age [37]. Tacrolimus is mainly associated with the risk of nephrotoxicity, neurotoxicity, and metabolic disturbances. Typical adverse effects include increased creatinine concentration, hypertension, hyperkalemia, hyperglycemia, tremor, and headache [37,39]. For this reason, it requires monitoring of drug blood levels, kidney function, blood pressure, electrolytes, and glycemia [39]. In the systematic review by Zizzo et al., cyclosporine was characterized by the highest response rate after six months of treatment, but also by the highest frequency of adverse effects among the analyzed second-line drugs [37]. The most important adverse effects of cyclosporine include nephrotoxicity, hypertension, tremor, gingival hyperplasia, and hypertrichosis [37,41].

Budesonide has been evaluated in selected non-cirrhotic patients, particularly adults, but its role in routine first-line pediatric treatment remains limited. Current guidance places greater emphasis on conventional corticosteroids and azathioprine, especially when the disease is severe or cirrhosis cannot be excluded [18].

The roles, limitations, and adverse-effect profiles of selected immunosuppressive therapies used in pediatric autoimmune hepatitis are summarized in Table 2.

Table 2. Practical considerations for selected immunosuppressive therapies in pediatric autoimmune hepatitis.

Therapy Role in pediatric AIH Reported limitations or adverse effects
Prednisone or prednisolone First-line induction therapy [15] Cushingoid features, hypertension, weight gain, growth impairment, bone and metabolic complications [15,19]
Azathioprine Steroid-sparing maintenance therapy [15,16] Potential hepatotoxicity and myelotoxicity; TPMT activity affects toxicity risk [16]
Mycophenolate mofetil Second-line option in intolerance or inadequate response [37,38] Gastrointestinal and hematological toxicity; teratogenicity in females of reproductive age [37,38]
Tacrolimus Second-line option, particularly in refractory disease [37,39] Nephrotoxicity, neurotoxicity, hypertension, electrolyte disturbances, hyperglycemia, tremor, and headache [37,39]
Cyclosporine Alternative second-line or selected induction strategy [37,40,41] Nephrotoxicity, hypertension, tremor, gingival hyperplasia, and hypertrichosis [37,41]

Pediatric-specific considerations and evidence gaps

Several aspects of pediatric autoimmune hepatitis remain challenging because much of the evidence base is derived from retrospective cohorts, expert consensus, or adult studies. This is particularly relevant for second-line therapy, where mycophenolate mofetil, tacrolimus, and cyclosporine are commonly discussed but comparative pediatric data remain limited [37,39]. Therapeutic decisions should therefore balance expected efficacy against toxicity, feasibility of monitoring, reproductive counseling in adolescent girls, and the likelihood of adherence.

Children and adolescents also differ from adults in clinically important ways. Pediatric patients more often present with acute or severe disease, may have lower diagnostic autoantibody titers, require evaluation for autoimmune sclerosing cholangitis, and need long-term monitoring of growth, puberty, bone health, and steroid-related complications [4,15,17,28]. These differences support early referral to pediatric hepatology and structured transition planning before transfer to adult care [36].

Prognosis and long-term care

Available long-term data suggest that type 1 and type 2 JAIH may have comparable long-term outcomes [28]. After achieving remission, the main goal of treatment is to maintain it while using the lowest possible dose of immunosuppressive drugs. This strategy helps prevent JAIH relapses while minimizing the risk of medication-related adverse effects. Immunosuppressive therapy is associated with numerous side effects. Therefore, dose reduction after achieving remission is crucial for long-term management [42].

Current recommendations suggest continuing immunosuppressive treatment for at least two to three years, with withdrawal considered only in patients with persistent and complete biochemical remission. Such an approach allows for better disease control and lowers the risk of relapse [15,16]. Juvenile autoimmune hepatitis is associated with a risk of portal hypertension, cirrhosis, and liver transplantation [43,44]. In some patients, especially with type 1 AIH, features of autoimmune sclerosing cholangitis or PSC-like biliary involvement may become apparent during follow-up [25-28].

Relapse remains a major challenge in JAIH, particularly due to poor treatment adherence during adolescence. Studies indicate that adolescence and early adulthood represent a risk zone characterized by worse clinical outcomes and a higher risk of complications when medical care is not continuous and well organized [18,20,36]. Sustained remission rates after treatment withdrawal vary widely, ranging from 3% to 87% [45]. It is essential that the transition from pediatric to adult healthcare services is conducted in a structured and well-coordinated manner. Both premature and delayed transfer may increase the risk of patients being lost to follow-up, resulting in poorer treatment adherence, reduced disease control, and a higher likelihood of adverse clinical outcomes [4,28].

From a clinical perspective, long-term care should not be limited to biochemical monitoring. Durable remission requires education, shared decision-making with patients and caregivers, active assessment of adherence, prevention and management of treatment adverse effects, and clear transition pathways. These elements are particularly important during adolescence, when lapses in medication adherence and follow-up may translate into relapse, progressive fibrosis, and avoidable complications [36,43,44].

DISCUSSION

The findings of this review indicate that juvenile autoimmune hepatitis differs from adult autoimmune hepatitis in clinically important ways. The high proportion of pediatric diagnoses, particularly in type 2 disease, and the younger peak age at onset show that childhood autoimmune hepatitis is not simply an early presentation of the adult disease. The female predominance, especially the approximately 9:1 ratio in type 2 disease, also reflects a distinct pediatric phenotype.

The clinical significance of these differences is substantial. Since 25–34% of children may be asymptomatic and 25–40% may present acutely, clinicians must consider autoimmune hepatitis both in children with incidental aminotransferase elevation and in those with acute hepatitis-like illness. The possibility of cirrhosis or advanced liver injury at diagnosis further supports rapid diagnostic evaluation.

Diagnostic interpretation requires particular caution in children. Lower autoantibody titers, such as ANA/SMA ≥1:20 and anti-LKM1 ≥1:10, may be meaningful in pediatric patients. Applying adult cut-offs may therefore lead to false-negative interpretation and delayed diagnosis. In addition, autoimmune sclerosing cholangitis is more relevant in pediatric practice than in many adult diagnostic algorithms, which means that cholestatic parameters and biliary imaging may be necessary in selected cases.

Treatment also has pediatric-specific implications. Although corticosteroids and azathioprine remain effective first-line therapy, children require additional monitoring for growth impairment, pubertal development, bone health, weight gain, hypertension, and other steroid-related adverse effects. The need for second-line treatment in 10–20% of cases highlights the importance of individualized therapy, especially because comparative pediatric data for mycophenolate mofetil, tacrolimus, and cyclosporine remain limited.

Long-term follow-up is particularly important because remission after treatment withdrawal is highly variable, ranging from 3% to 87%. This wide range reflects heterogeneity in patient selection, treatment duration, remission definitions, and follow-up strategies. Adolescence is a critical period because non-adherence and loss to follow-up may increase the risk of relapse and progression. Therefore, transition to adult care should be planned as a clinical process, not only as an administrative transfer.

Limitations

This article is a narrative review and has several methodological limitations. Although the literature search was structured, it was not conducted as a systematic review. No registered review protocol, PRISMA-based selection process, meta-analysis, or formal risk-of-bias assessment was performed.

The available evidence is heterogeneous. Included studies differ in diagnostic criteria, patient age, disease subtype, treatment protocols, definitions of remission and relapse, and length of follow-up. Many pediatric data are derived from retrospective cohorts, small observational studies, expert consensus, or extrapolation from adult literature. Therefore, the findings should be interpreted as a qualitative synthesis of current evidence rather than as precise quantitative estimates of treatment efficacy, relapse risk, or long-term prognosis.

CONCLUSIONS

Autoimmune hepatitis in children and adolescents is a chronic and potentially progressive liver disease that requires early recognition, careful diagnostic confirmation, and timely immunosuppressive treatment. The diagnosis should be based on an integrated interpretation of clinical presentation, aminotransferase activity, immunoglobulin G concentration, autoantibody profile, liver histology, and exclusion of alternative causes of liver injury. Pediatric patients require special attention because they may present acutely, may have clinically meaningful autoantibody titers below adult thresholds, and may have autoimmune sclerosing cholangitis or advanced liver disease at diagnosis.

Most children respond to corticosteroids and azathioprine, but long-term management must balance disease control against treatment toxicity, growth and pubertal development, adherence, and quality of life. Second-line therapies are important for refractory or intolerant cases, yet the pediatric evidence base remains limited and individualized decision-making is essential. Sustained remission, relapse prevention, and safe transition to adult care should be considered core outcomes of management, not secondary administrative steps.

DISCLOSURE

Author Contributions

All authors contributed substantially to the conception and design of the study, literature analysis and interpretation, drafting and critical revision of the manuscript, and approved the final version for publication.

Conceptualization and methodology: Katarzyna Łysynkiewicz, Jan Szewczyk, Zuzanna Wątek, Patrycja Krawczyk, Maria Bołoz, Sylwia Haba.

Literature review and data extraction: Katarzyna Łysynkiewicz, Zuzanna Wątek, Patrycja Krawczyk, Sylwia Haba, Izabela Grzyb.

Writing, original draft preparation: Jan Szewczyk, Zuzanna Wątek, Alicja Smolińska, Patrycja Krawczyk, Ewa Dapkiewicz, Dawid Gąsowski, Maria Bołoz.

Writing, review and editing: Katarzyna Łysynkiewicz, Izabela Grzyb, Jan Szewczyk, Zuzanna Wątek, Sylwia Haba, Dawid Gąsowski.

Supervision: Katarzyna Łysynkiewicz.

Funding

The article did not receive any funding.

Conflict of Interest

The authors declare no conflicts of interest.

Use of Artificial Intelligence

The authors would like to acknowledge the use of artificial intelligence tools for language editing and improvement of grammatical accuracy. All content was critically reviewed and supervised by the author to ensure scientific accuracy and logical consistency.

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