Autoimmune Hepatitis In Children Research Articles

Leptin gene Polymorphism and Leptin protein levels in Pediatric Autoimmune Hepatitis

ABSTRACT Background Leptin plays a role in regulating energy balance, immunity, and inflammation. Studies suggest higher leptin levels might be associated with various autoimmune diseases. Most of them were in adult. To our knowledge, our study is one of the few that describe serum leptin level and leptin gene polymorphism in children with autoimmune hepatitis (AIH). Objective Our study aims to explore the association between serum leptin level and genetic variations in leptin gene with the likelihood of AIH in children. Patients and methods Thirty-one children with AIH and 29 healthy children serving as a control group were included. Serum leptin levels were measured by ELISA assays. Leptin rs2167270 genotyping was done using the real time-PCR. The relationship of serum leptin level and leptin gene polymorphism with patients’ data was studied. Patients follow up to assess treatment response. Results Children with AIH had significantly higher levels of leptin compared to healthy controls. GG genotype was significantly more prevalent in the AIH group compared to controls. Conclusion High serum leptin levels and leptin gene polymorphism may play a role in AIH development. It is worthy to recognize if leptin can serve as diagnostic and/or therapeutic target in AIH in children.

Primary Sclerosing Cholangitis in Very Early Age: Two Case Reports

Primary Sclerosing Cholangitis (PSC) is a rare, chronic, progressive cholestatic liver disease which affects intrahepatic and extrahepatic bile ducts. That eventually progresses to end stage liver disease that requires liver transplantation. It mostly occurs in adolescent males and boys. Pediatric disease appears milder in contrast to adult-onset PSC. The diagnosis is made by Magnatic Resonance Cholangiopancreatography (MRCP). Though there is no practical guideline available in pediatric patients for treating PSC UDCA is prescribed chronically in over 80% of patients. There is close association of PSC with inflammatory bowel disease and autoimmune hepatitis in children. So the treatment is complex in case of children. We reported here two cases of PSC, because of rarity of this disease in such a young age.
 BANGLADESH J CHILD HEALTH 2022; VOL 46 (1) : 30-34

Chronic non-bacterial osteomyelitis with autoimmune hepatitis: a case report and literature review

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.

Seronegative autoimmune hepatitis in childhood.

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.

Different presentation of autoimmune hepatitis in children: Case series.

Autoimmune hepatitis (AIH) is a disorder causing chronic hepatic inflammation. Its clinical presentation is highly variable from the affected child might have only biochemical evidence of liver dysfunction or present in hepatic failure. It is important to distinguish AIH from other forms of chronic hepatitis because a high percentage of cases respond to immunosuppressive therapy. In this article, we describe the clinical presentation, biochemical and histological findings, treatment, and clinical outcome of the four children with AIH in a tertiary care center in Mumbai. Most patients with AIH have high levels of immunoglobulin. All four cases showed high serum Ig G levels and responded to oral prednisolone only. AIH should be excluded for all patients with symptoms or signs of prolonged, relapsing, or severe liver disease so that treatment can be promptly initiated and morbidity can be reduced.

Hepatitis-associated Aplastic Anemia.

Hepatitis-associated aplastic anemia (HAAA) accounts for 4% of autoimmune hepatitis in children. An episode of seronegative autoimmune hepatitis is followed a few days or months later by aplastic anemia or full aplasia. This autoimmune disease could be due to a regulation defect in the immune response to a viral trigger, in a genetically predisposed individual. Other causes of hepatitis or aplastic anemia have to be ruled out. Steroids and azathioprine usually control the liver damage but do not prevent the development of aplastic anemia. Aplastic anemia is treated with either hematopoietic stem cell transplantation in patients with a sibling donor or anti-thymocyte globulins and cyclosporine. We propose guidelines to explore and treat this rare disease. We emphasize on the necessary close collaboration between hepatologists and hematologists.

КЛИНИЧЕСКИЕ И ГЕМОСТАЗИОЛОГИЧЕСКИЕ ОСОБЕННОСТИ ЦИРРОЗА ПЕЧЕНИ АУТОИММУННОЙ ЭТИОЛОГИИ У ДЕТЕЙ

Objective of the study: to determine clinical, hemostasiological features and evaluate the relationship of autoantibodies with hemostasiological disorders in children with liver cirrhosis (LC) class A according to Child–Pugh score in the outcome of autoimmune hepatitis (AIH). Materials and methods of research: a single-center, retrospective, controlled, non-randomized study. From 2017 to 2021, 31 children aged 13 (10; 15.5) years old [15 girls (48%) and 16 boys (52%)] with LC class A according to Child–Pugh classification in the outcome of AIH and 15 children aged 13 (10; 15.5) years [8 girls (53%) and 7 boys (47%)], belonging to health groups I–II. All participants were examined according to the medical standard for specialized medical care for children with LC in accordance with the «Autoimmune hepatitis in children” of the Federal clinical guidelines (Moscow, 2016) and the medical standard for specialized medical care for children with AIH. The parameters of the hemostatic system were determined on the ACL-TOP 500 hemocoagulation analyzer (Instrumentation Laboratory Company, USA) using standard kits: activated partial thromboplastin time (aPTT), Prothrombin time (PT) calculated as % of prothrombin activity according to Quick, thrombin time, fibrinogen content, activity of antithrombin III (ATIII), protein C, plasminogen, alpha2-antiplasmin (α2-AP). To determine the factor XII-dependent fibrinolysis activity (XIIa-DF) and the content of Soluble fibrin monomer complexes (SFMCs), reagent kits from the Tekhnologiya-Standard company (Russia) were used. The platelet count was determined using a Cell-Dyn 610 hematology analyzer (Abbott Diagnostics, USA). The study of platelet aggregation activity was carried out on a platelet aggregation analyzer using adenosine diphosphate (ADP) at a concentration of 1.25 mg/ml and collagen at a concentration of 2.0 microns/ml as an aggregation inducer. Measurement of plasma endothelin-1 was carried out by using Endothelin 1-21 ELISA Assay kit. Homocysteine concentration and VWF activity were determined on an ACL-TOP 500 hemocoagulation analyzer (Instrumentation Laboratory Company, USA) using standard kits. Results: the clinical picture was characterized by asthenoneurotic (100%), abdominal pain (45%), hemorrhagic [ecchymosis (55%), epistaxis (30%), bleeding gums (16%)] syndromes, hepatomegaly (90%), splenomegaly ( 65%). Hemostasiological disorders were characterized by a decrease in the content of platelets (p=0.001), an increase in the degree (ADP inducer, p=0.001; collagen inducer, p=0.023) and speed (ADP inducer, p=0.003; collagen inducer, p=0.032) of their aggregation, inhibition coagulation (p=0.001) and anticoagulant (p=0.002) components of hemostasis in comparison with a group of healthy children. Positive autoantibodies were diagnosed in 97% of patients, in 49% of cases, which is typical for Type 2 AIH. Indicators of vascular-platelet hemostasis can be used to assess autoimmune activity in children with Child–Pugh class A cirrhosis: VWF activity 200.0% is associated with an increase in antinuclear antibodies (ANA) in the blood (sensitivity – 83%, specificity – 69% ). Conclusion: indicators of vascular-platelet hemostasis can be used to assess autoimmune activity in children with class A cirrhosis according to Child–Pugh in the outcome of AIH.

Treatment and outcomes of autoimmune hepatitis in children

Introduction. Autoimmune hepatitis (AIH) is one of the auto­im­mune liver disorders recognized in children, along with autoimmune sclerosing cholangitis (ASC) and de novo AIH after liver transplant. This study aimed to as­sess the treatment in children with AIH, and to identify cor­re­la­tions with disease outcomes. Materials and method. In this retrospective study, we included 30 hospitalized chil­­dren with AIH, followed-up in our clinic over six years. All patients met the International Autoimmune Hepatitis Group’s simplified diagnostic criteria (IAIHG criteria). Results. Pediatric patients with AIH were aged between 4 months old and 17 years and 8 months old, with a mean age of 6.5 years old. There were 19 girls and 11 boys. Most pa­tients had an acute onset of the disease. Three patients de­ve­loped acute liver failure. All patients had elevated tran­sa­mi­na­ses and 16 patients had cholestasis. Most pa­tients had increased IgG levels. There were 20 children with type I AIH with SMA and ANA, and 10 children with type II AIH with anti-LKM-1 and anti-LC-1. All patients re­ceived prednisone from the diagnosis. Fifteen patients re­quired the addition of azathioprine. Full clinical recovery with a normal level of transaminases was achieved in 18 pa­tients. Complete remission was achieved in 10 patients. Most children had a favorable outcome, with only five pa­tients presenting cirrhosis. Two children died due to com­pli­ca­tions of autoimmune cirrhosis. Conclusions. The out­come of chil­dren with AIH treated with immediate im­mu­no­sup­pres­sive therapy is favorable, with good long-term survival rates and with a positive effect on the quality of life.

Overlap-синдром болезни Вильсона — Коновалова и аутоиммунного гепатита: клинический случай

В статье приведены данные литературных источников и собственное наблюдение клинического случая сосуществования болезни Вильсона — Коновалова и аутоиммунного гепатита у подростка. Рассмотрены вопросы диагностики аутоиммунного гепатита и болезни Вильсона — Коновалова у детей в соответствии с рекомендациями Европейского общества детских гастроэнтерологов, гепатологов и нутрициологов. Акцентировано внимание на трудностях интерпретации клинических данных и оценки результатов лабораторно-инструментального обследования данной группы пациентов. Представлен алгоритм диагностики болезни Вильсона — Коновалова и аутоиммунного гепатита у детей.

Evaluation of Validity and Efficiency of Diagnostic Criteria in Autoimmune Hepatitis in Children.

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease with various clinical symptoms, but treatment and prevention of hepatic failure and cirrhosis is possible with early diagnosis. However, no specific test has been approved for the diagnosis of AIH. In 2008, the International Autoimmune Hepatitis Group (IAIHG) developed a simplified diagnostic scoring system that has been widely used in practice. Nevertheless, it cannot distinguish AIH from Primary Sclerosing Cholangitis (PSC) and consensus is lacking with respect to its validity, sensitivity, and applicability for children patients. The newer 2018 version also requires validation. The present study intends to evaluate the validity and efficiency of the IAIHG simplified scoring system and new scoring system in children with AIH. The present study is a non-interventional case-control study covering 152 patients with hepatic diseases (83 patients with AIH and 69 patients with Wilson disease (WD)). Titers of autoantibodies, IgG levels, hepatic histology, and absence of viral hepatitis were scored and calculated according to IAIHG diagnostic criteria. Statistics software package (SPSS) and draft receiver operating characteristic (ROC) curves was used to analyze data and determine value of diagnostic criteria. In our study, both scoring systems' accuracy was good in AIH diagnosis, although new score displays higher sensitivity and specificity, suggestive of greater accuracy and predictive strength. Our study is the first validation study of the new scoring system in diagnosing AIH, and further studies require verifying this scoring system.

Seronegative autoimmune hepatitis in children: a single-center experience

Seronegative autoimmune hepatitis (AIH) is a diagnostic challenge with unclear prognosis. This study describes the features and outcomes of seronegative AIH in children. Patients under 18 years of age, who had been diagnosed with AIH between April 2014 and April 2020, were retrospectively evaluated. Seronegative AIH was identified by the absence of the three conventional non-organ-specific autoantibodies (anti-nuclear antibody [ANA], anti-smooth muscle antibody [ASMA], and anti-liver kidney microsomal [anti-LKM] type 1 antibody), alongside the characteristic AIH liver histopathology and a positive response to immunosuppressive therapy in the absence of other liver diseases. The study included 54 patients with AIH. 15 (27.77%) were seronegative at the time of diagnosis. 13 of the 15 seronegative patients presented with acute hepatitis or acute liver failure (ALF). Mean follow-up duration was 27.48 months in seronegative patients. Two seronegative patients had lymphocytopenia on admission, and, although the liver disease improved after corticosteroid treatment, they developed aplastic anemia (AA). Other seronegative patients responded well to immunosuppressive therapy. Patients with seronegative AIH present frequently with acute hepatitis or ALF. AIH diagnosis can be confirmed by observing the effects of corticosteroid therapy in seronegative patients with characteristic AIH liver histopathological features. However, the presence of lymphocytopenia in seronegative patients is a sign of bone marrow failure.

Incidence of de novo autoimmune hepatitis in children and adolescents with increased autoantibodies after liver transplantation: a meta-analysis.

The objective of this meta-analysis was to assess the incidence of de novo autoimmune hepatitis (AIH) in children and adolescents with increased autoantibodies after liver transplantation. We systematically retrieved studies from PubMed, Embase, Central, CNKI, VIP and Wanfang published before February 1, 2020. All analyses were conducted using R-4.0.1 statistical package (Meta). Seven studies with high quality were pooled in our final analysis (N=251 participants). The incidence of de novo AIH was 9% [95% confidence interval (CI) 1-23%, I2 =86%]. Subgroup analysis suggested that publications not using the International Autoimmune Hepatitis Group (IAIHG) criteria have marginally significantly higher incidence of de novo AIH than those using IAIHG criteria (P for interaction=0.08). The incidence of chronic rejection was 8% (95% CI 2-17%, I2 =72%). Meta-regression indicated significant correlation (P=0.04; estimate: 1.51) between the incidence of de novo AIH and the rate of increase of antibodies to liver/kidney microsome (anti-LKM). It is still challenging to distinguish de novo AIH and chronic rejection in children and adolescents with increased autoantibodies after liver transplantation. The diagnostic criteria for de novo AIH in children and adolescents and the role of anti-LKM in the development of de novo AIH deserve future investigation.

An updated advance of autoimmune hepatitis in children

Autoimmune liver disease is not common in children. In addition to autoimmune hepatitis, it also includes autoimmune sclerosing cholangitis, Giant cell hepatitis with autoimmune hemolytic anemia, and de novo autoimmune hepatitis after liver transplantation as well as two acquired autoimmune liver diseases: neonatal lupus and Gestational alloimmune liver disease (alternate name neonatal hemochromatosis). The age-specific systemic developmental characteristics and immune system association determine the type of autoimmune liver disease in children, and its clinical manifestations and prognostic transition may vary from adults. Here, we discuss the rising clinical incidence of autoimmune hepatitis in children.

Autoimmiune Hepatitis in Children: Two Case Report

Autoimmune hepatitis (AIH) is the disease of immune mediated inflammation of liver. Presentation of AIH in children is variable, ranging from acute hepatitis to cirrhosis of liver and also as only asymptomatic raised ALT. AIH can present at any age and female are more affected. Here we are presenting two cases. Case 1 presented with jaundice and H/O epistaxis, having cutaneous echymosis, hepato-splenomegaly and ascites. Case 2 was a diagnosed case of Systemic Lupus Erythematosus (SLE) presented with only persistent raised of serum ALT. Both were diagnosed as autoimmune hepatitis on the basis of positive auto antibodies, histopathology of liver tissues and exclusion of all other causes of acute and chronic hepatitis.
 Bangladesh Med J. 2020 Jan; 49 (1): 45-50

Characteristics of clinical and anamnestic data and of condition of primary hemostasis in chronic diseases of liver in children

Aim. To perform a comparative analysis of clinical and anamnestic data and of the condition of primary hemostasis in chronic liver diseases in children and to identify additional informative diagnostic criteria that reflect severity of the course of autoimmune hepatitis (AIH) and chronic viral hepatitis C (CVHC) in children.
 Materials and Methods. 91 Patients from 3 to 7 years old were examined, of them: 60 children with AIH and 31 children with CVHC. The control group included 15 children of I and II health groups. In all the patients the clinic-anamnestic data and the condition of the primary hemostasis were evaluated. Concentrations of endothelin-1 and homocysteine, activity of Willebrand factor, amount of platelets and their aggregation activity were determined.
 Results. AIH is characterized by a more aggressive course as compared to CVHC manifested by clinical signs of a severe liver damage, significant biochemical changes and a high rate of fibrosis within the first two years. In all the children there were found disorders in the primary hemostasis interrelated with the main clinical and laboratory syndromes reflecting the severity of the liver damage. AIH is characterized by a higher concentration of homocysteine (р=0.007) and of the activity of Willebrand factor (р=0.037) in comparison with CVHC.
 Conclusions. Signs of a severe liver damage are not characteristic of children with CVHC in the first 10 years of the disease, however, disorders of the primary hemostasis are present characterized by hyperaggregation of platelets and by endothelial dysfunction. AIH in children is characterized by aggressive course and more pronounced deviations of the primary hemostasis in comparison with CVHC. In AIH and CVHC, the pathology of the primary hemostasis is closely related to some clinical-laboratory symptoms that reflect severity of the disease.

Efficiency of azathioprine monotherapy for maintenance treatment of autoimmune hepatitis in children.

Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with low dose prednisolone and azathioprine (AZA). The aim of this study is to evaluate the efficiency of AZA monotherapy for maintenance treatment of children with AIH. This study was a retrospective analysis of the 55 children with AIH. Patients were divided into two groups: combination therapy (CT) and AZA group based on maintenance therapy. Results of these two different maintenance treatments were compared in children with AIH. The mean age of the children was 10.67 ± 4.30 years (61.8% females) with a mean follow-up period of 46.8 ± 33.6 months. For maintenance treatment, 39 (70.9%) patients received AZA and 16 (29.1%) patients received CT. Relapse was observed in nine (19.6%) cases in the follow-up period; two were in the CT group (2/16; 12.5%) and seven (7/39; 17.9%) were in the AZA group (P = 0.620). In AZA group, the duration of remission was 22.2 ± 6.1 months and that was longer than CT group (P = 0.025). Our study suggests that AZA monotherapy is an effective and safe therapy for maintaining remission in children with AIH. AZA monotherapy may be used for maintenance treatment of children with AIH, except in cases of overlap syndrome and also to avoid side effects of long-term used steroids and to improve treatment compliance in proper cases.

Features of the course of autoimmune hepatitis in children as a variant of autoimmune polyglandular syndrome

Features of the course of autoimmune hepatitis in children as a variant of autoimmune polyglandular syndrome

Diagnostic value of soluble programmed cell death protein-1 in type-1 autoimmune hepatitis in Egyptian children

Programmed cell death protein-1 (PDCD1) is considered a key factor in immune regulation and is expressed mainly on activated T cells. The current study aimed to assess the clinical value of soluble PDCD1/PD1 as a marker for diagnosing type-1 autoimmune hepatitis in children. Sixty children with chronic hepatitis as patients' groups further divided into autoimmune hepatitis group and other chronic liver disease group and 20 healthy children as a control group were enrolled in this study. All children have been studied for clinical profile, biochemical, histological features and serum level of soluble programmed cell death protein-1 by ELISA. There was a significant increase regarding soluble PDCD1/PD1 in the autoimmune hepatitis group than the chronic liver disease group, with the lowest level in the control group. Soluble PDCD1/PD1 level increased with higher fibrosis stage and higher Child Pugh score, also higher in relapsed patients than patients with complete remission in AIH groups. There was a positive correlation between soluble PDCD1/PD1 and PT, IgG, fibrosis stage, HAI, ALT, AST, simplified and revised score system, PELD and MELD among the AIH group. The best cutoff value of PDCD1/PD1 in the prediction of autoimmune hepatitis was 1.73 ng/ml with AUC:0.895 that has a sensitivity of 80%, specificity of 78%. sPDCD1/PD1 level represents a possible promising biomarker of AIH patients who will represent an incomplete response for regular treatment. This finding can be considered as the first step to prove the pivotal role of soluble PDCD1/PD1 in the diagnosis of AIH.

Acute onset of autoimmune hepatitis in children and adolescents

BackgroundAutoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF). MethodsForty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). ResultsAcute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. ConclusionRapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.

A review of the utility of tacrolimus in the management of adults with autoimmune hepatitis

Background: There is paucity of data on alternative drug therapies for patients with autoimmune hepatitis (AIH). Tacrolimus (TAC) is a promising salvage agent. We present a review of TAC therapy in AIH patients.Methods: A search for studies with keywords ‘autoimmune hepatitis’ and ‘tacrolimus’ was performed. Reviews, studies of AIH post-transplant and AIH in children were excluded. Diagnosis of AIH was based on criteria established by the International Autoimmune Hepatitis Group. Complete biochemical response was defined as normalisation of aspartate aminotransferase (AST <45) and alanine aminotransferase (ALT <50). No biochemical response was defined as failure to return to normalisation at the end of follow-up. Demographic information and details of pre- and post-treatment liver biopsy were collected.Results: Seven articles achieved the inclusion criteria and reported data for a total of 162 adult patients. The majority of studies reported average ages approximately 35 years old. Treatment duration ranged from 1 to 136 months. Indications for therapy were mostly AIH refractory to steroid treatment or inability to tolerate standard steroid treatment. Eighty-three patients (51.2%) were reported to have pre-therapy liver biopsy. Of 49 patients for whom stage was reported, 6 patients were stage 1, 16 were stage 2, 14 were stage 3 and 13 were stage 4. Of 40 patients for whom grade was reported, 1 patient was grade 0, 3 were grade 1, 9 were grade 2, 14 were grade 3 and 13 were grade 4. Dosing regimens were between 1 and 8 mg/day. Target trough TAC serum concentrations ranged from 0.5 to 10.7 ng/mL TAC was discontinued in 28 (17.3%) patients for various reasons. Renal function remained stable in most patients. One hundred and twenty-one patients (74.7%) demonstrated complete biochemical response to treatment. Post-therapy liver biopsy was obtained for 30 (18.5%) patients, and 25 (15.4%) of these patients were noted to have histological remission according to the grade of inflammation or stage of fibrosis.Conclusion: TAC is relatively effective in the treatment of AIH refractory to traditional therapy. It appears that liver function can be enhanced at a minimal cost to renal function.Key PointsThere is a cohort of patients with autoimmune hepatitis (AIH) who do not respond to standard therapy.Alternative treatment options for these patients have been explored, but outcomes have not been comprehensively examined.We report the use and efficacy of tacrolimus (TAC) in patients with AIH.We found that TAC can be safely and effectively used in patients with AIH with minimal side effects.TAC can be a potential treatment option for patients with AIH refractory to standard therapy.