Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology which may affect any patient irrespective of age, sex, and ethnicity. At baseline, the clinical spectrum of the disease varies largely from asymptomatic cases to acute liver failure with massive hepatocyte necrosis. The aim of these EASL guidelines is to provide updated guidance on the diagnosis and management of AIH both in adults and children. Updated guidance on the management of patients with variants and specific forms of AIH is also provided, as is detailed guidance on the management of AIH-associated cirrhosis, including surveillance for portal hypertension and hepatocellular carcinoma, as well as liver transplantation in decompensated cirrhosis.

Autoimmune hepatitis (AIH) is a rare immune-mediated chronic liver disease that is diagnosed based on a combination of biochemical, immunologic, and histologic features and the exclusion of other causes of liver disease. According to the new consensus criteria of the International Autoimmune Hepatitis Pathology Group (IAIHPG), the likely histologic features include a chronic hepatitis pattern of injury with a lymphoplasmacytic portal infiltrate, interface activity, and portal-based fibrosis. More than mild lobular hepatitis with any of the above features can also be diagnosed as likely AIH in the absence of features of another liver disease. Centrilobular injury with prominent hepatocellular necrosis and mononuclear inflammation may represent an acute-onset disease and indicate possible AIH in the absence of concurrent liver disease. Kupffer cell hyaline bodies and portal lymphocyte apoptosis are significantly associated with AIH, whereas emperipolesis and hepatocellular rosette formation are nonspecific features indicative of disease severity. Liver histology is an integral part of the clinical diagnostic scoring system and is required to confirm or support AIH diagnosis. Substitution of the histologic component of the simplified AIH scoring system with the consensus IAIHPG criteria has been proposed to optimize clinical diagnosis. This review explores the significant role of histopathology in AIH by analyzing its main features and current histologic diagnostic criteria, different AIH presentations, differential diagnosis, assessment of concurrent liver disease, and identification of AIH variants with primary cholangiopathy.

The three major autoimmune liver diseases are autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC).These conditions are assumed to result from a breakdown in immunological tolerance, which leads to an inflammatory process that causes liver damage.The self-attack is started by T-helper cell-mediated identification of liver autoantigens and B-cell production of autoantibodies,and it is maintained by a reduction in the number and activity of regulatory T-cells.Infections and environmental factors have been explored as triggering factors for these conditions, in addition to a genetic predisposition.Allelic mutations in the HLA locus have been linked to vulnerability, as have relationships with single nucleotide polymorphisms in non-HLA genes.Despite the advances in the management of these diseases, there is no curative treatment for these disorders, and a significant number of patients eventually progress to an end-stage liver disease requiring liver transplantation.In this line, tailored immune-therapeutics have emerged as possible treatments to control the disease.In addition, early diagnosis and treatment are pivotal for reducing the long-lasting effects of these conditions and their burden on quality of life.Herein we present a review of the etiology, clinical presentation, diagnosis, and challenges on ALDs and the feasible solutions for these complex diseases.

Autoimmune hepatitis (AIH) is a relatively infrequent and complex liver disease characterized by acute or chronic inflammation, interface hepatitis in histology examination, elevation of immunoglobulin G (IgG), production of autoantibodies, and is often responsive to immunosuppression. The incidence of AIH has been increasing worldwide, affecting people of all ages and sexes. AIH represents a diagnostic challenge because of its heterogeneous presentation and the lack of pathognomonic findings. Even when treated, AIH can remain a progressive disease. In this review, we present recent data on the natural history of AIH and the developing evidence on the management of patients with AIH.

This review outlines the clinical presentation, risk factors linked to poorer clinical outcomes, the diagnostic algorithm, and the current management strategies for individuals living with AIH.

AIH remains a clinical challenge, and new tools for better diagnosis and stratification of risk are needed. In addition, better treatments are needed as a complete response is achieved in less than 60% of cases, and intolerance to first-line treatment is frequent. The use of biological treatment in AIH seems to improve the response rate and minimize the risk of side effects of current medication in this increasingly prevalent disease.

Background/Objectives: This article presents the case of a 31-year-old primigravida who experienced acute liver failure in the 23rd week of pregnancy, along with a review of the literature on this rare condition during pregnancy. The purpose of this publication is to highlight the diagnostic and therapeutic challenges associated with acute liver failure in pregnant women. Methods: The patient presented with jaundice, pruritus, and dark-colored urine. Laboratory tests revealed a significant increase in aminotransferase, bilirubin, and bile acid levels, suggesting liver problems; however, due to the patient's rapidly deteriorating condition and test results, autoimmune hepatitis was considered. Viral infections and other causes of liver damage were excluded. No clear diagnosis was established. The patient was administered ursodeoxycholic acid and due to her worsening condition, a cesarean section was performed at 23 weeks of gestation. After delivery, the patient's condition improved, although she did experience cardiac arrest during hospitalization. The patient was discharged with a diagnosis of acute liver failure in the course of an overlap syndrome of autoimmune hepatitis and primary cholangitis or intrahepatic cholestasis of pregnancy. No abnormalities were noted during a follow-up visit 6 weeks after delivery. Despite a detailed case analysis, a final diagnosis was not established, which complicates planning for future pregnancies. Discussion: Several liver conditions can occur during pregnancy, including intrahepatic cholestasis of pregnancy, primary biliary cholangitis, and autoimmune hepatitis. Diagnosing these conditions can be challenging due to overlapping symptoms and metabolic and immunological adaptations during pregnancy that can affect the course of liver diseases. Rapid intervention is crucial to protect the health of both the mother and the fetus. Conclusions: In summary, this article aims to increase awareness of the complexities surrounding acute liver failure during pregnancy, highlighting the diagnostic challenges and importance of prompt medical intervention for the well-being of both the mother and the child. This paper aims to provide a comprehensive overview of the complexities surrounding acute liver failure during pregnancy, aiming to improve the understanding, diagnosis, and management of this condition.

Autoimmune hepatitis (AIH) is a rare chronic liver disease with an increasing incidence in many countries. Chronic autoimmune responses against the liver can cause hepatic and extrahepatic symptoms, decreased quality of life and reduced liver transplant-free survival if inadequately treated. Although standard treatment with corticosteroids and thiopurines improves the life expectancy of patients with AIH, remission rates and tolerability are generally overestimated and the development of alternative first-line and salvage therapies has been disappointingly slow compared to in rheumatological diseases or inflammatory bowel disease. Other gaps include the lack of disease-specific diagnostic markers for AIH. Similarly, the new entity of drug-induced autoimmune-like hepatitis underscores the need to re-evaluate previous diagnostic criteria. The International AIH Group (IAIHG) has initiated a series of research workshops over the last decade to promote the identification of research gaps and subsequently improve the pace of scientific progress by stimulating collaboration between expert centres. This review reports on the results of the 5th Research Workshop, held in Hannover, Germany in June 2024, and summarises the progress made since the 4th Workshop in 2022. Patient representatives from the European Reference Network (ERN) Rare Liver Youth Panel participated in the workshop. The specific objectives of this year's 5th Workshop were: (1) To further improve diagnostics. (2) Initiate clinical trials including knowledge transfer on drugs from extrahepatic immune-mediated diseases, including B cell-depleting CAR T cells. (3) Utilisation of multi-omics approaches to improve the understanding of disease pathogenesis. (4) Application of machine learning-based approaches established in oncology or transplantation medicine to improve diagnosis and outcome prediction in AIH.

Autoimmune hepatitis (AIH) is a chronic inflammatory autoimmune disease with either acute or chronic presentation. Previous scoring systems have primarily focused on chronic hepatitis, but none have been validated in an acute setting of pediatric patients. This study aimed to: 1) summarize the clinicopathologic characteristics of pediatric AIH patients; 2) assess if the modified Hepatic Activity Index (mHAI) can be used in both acute and chronic presentations of pediatric AIH; 3) evaluate the association of initial mHAI scores with treatment response at various endpoints. Thirty-one pediatric AIH patients were categorized into acute and chronic presentation groups. Biopsies were reviewed using the mHAI grading and staging system. AIH treatment endpoints were analyzed: 4 weeks (response vs. non-response), 6 months (complete vs. insufficient response), and approximately 12 months (histological remission vs. non-remission). Patients with acute AIH had higher mean mHAI scores and more prominent interface activity. Those achieving complete response at 6 months had significantly higher mean mHAI scores compared to those with an insufficient response. Notably, patients demonstrating fibrosis reversal at the 1-year follow-up often had higher initial mHAI scores. The mHAI can be used to evaluate acute and chronic presentations of pediatric AIH. Acute pediatric AIH has a higher mHAI score with more severe activity. The patients with a higher mHAI have a greater likelihood of achieving a complete response to treatment at 6 months and subsequent improvement in fibrosis status.

Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver. This inflammation is accompanied by elevated IgG and autoantibody levels. Historically, treatment consists of steroids with the addition of azathioprine, which results in remission in approximately 80% of patients. Despite significant advancements in our understanding of the immune system over the past two decades, few modifications have been made to treatment algorithms, which have remained largely unchanged since they were first proposed more than 40 years ago. This review summarized the various treatment options currently available as well as our experiences using them. Although steroids are the standard treatment for induction therapy, other medications may be considered. Cyclosporin A, a calcineurin inhibitor that decreases T cell activation, has proven effective for induction of remission, but its long-term side effects limit its appeal for maintenance. Tacrolimus, a drug belonging to the same family, has been used in patients with refractory diseases with fewer side effects. Sirolimus and everolimus have interesting effects on regulatory T cell populations and may become viable options in the future. Mycophenolate mofetil is not effective for induction but is a valid alternative for patients who are intolerant to azathioprine. B cell-depleting drugs, such as rituximab and belimumab, have been successfully used in refractory cases and are useful in both the short and long term. Other promising treatments include anti-tumor necrosis factors, Janus kinases inhibitors, and chimeric antigen receptor T cell therapy. This growing armamentarium allows us to imagine a more tailored approach to the treatment of autoimmune hepatitis in the near future.

The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria.

The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance.

In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH.

Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Pediatric autoimmune hepatitis has an incidence of 0.23/100.000 children in North America, with a bleak prognosis if left untreated. Steroids are the therapy of choice but are not always effective. B cell depletion is a safe and effective therapy that allows for a steroid-sparing protocol, especially in patients who do not tolerate side effects.

We retrospectively reviewed rituximab-treated patients between 2017 and 2022. Demographics, previous treatments, reasons for B cell depletion, response, and adverse effects were noted.

Six patients with a mean age of 10.2 years were included. All patients had comorbidities that rendered treatment with steroids unsuccessful or undesirable. Rituximab was started at a mean follow-up of 8 months. After 6 months, the mean alanine transaminase and aspartate transaminase levels decreased from 575 IU/L and 342 IU/L, respectively, to 28 IU/L (p = 0.02) and 36 IU/L (p = 0.008), respectively. Mean γ-glutamyl transpeptidase decreased from 105 to 25 IU/L (p = 0.01). Immunoglobulin G levels were normalized in all patients (p = 0.01). No severe adverse events were observed. One patient had persistent hypogammaglobulinemia, and another had lymphopenia.

B-cell depletion is an effective and safe treatment for autoimmune liver diseases and should be included as an option, particularly for relapsing patients in whom steroids are undesirable or have shown nonadherence.

Prothrombin time (PT) is a key parameter for assessing the severity of liver disease. We present the case of a 37-year-old woman with severe acute liver injury due to autoimmune hepatitis. Although prednisolone drastically improved her hepatocyte function, her PT did not recover to the reference range. A review of her medical records revealed that the patient had normal transaminase levels and prolonged PT 2 years previously. Further examinations of her coagulopathy revealed that she had low factor VII activity, suggesting a diagnosis of factor VII deficiency. Our experience suggests that altered coagulopathy should be considered in cases of liver injury with an extraordinary PT.

Autoimmune hepatitis (AIH) is a severe hepatopathy characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological appearance of interface hepatitis. Liver damage in AIH is initiated by the presentation of a liver autoantigen to uncommitted Th0 lymphocytes, followed by a cascade of effector immune responses culminating with the production of inflammatory cytokines, activation of cytotoxic cells and subsequent hepatocyte injury. B cells actively participate in AIH liver damage by presenting autoantigens to uncommitted T lymphocytes. B cells also undergo maturation into plasma cells that are responsible for production of immunoglobulin G and autoantibodies, which mediate antibody dependent cell cytotoxicity. Perpetuation of effector immunity with consequent progression of liver damage is permitted by impairment in regulatory T cells (Tregs), a lymphocyte subset central to the maintenance of immune homeostasis. Treg impairment in AIH is multifactorial, deriving from numerical decrease, reduced suppressive function, poor response to IL-2 and less stable phenotype. In this review, we discuss the role of B and T lymphocytes in the pathogenesis of AIH. Immunotherapeutic strategies that could limit inflammation and halt disease progression while reconstituting tolerance to liver autoantigens are also reviewed and discussed.

Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.

Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study aims to evaluate the efficacy of using corticosteroids (prednisolone and azathioprine) as a combination therapy in treating AIH. This study aims to synthesize and analyze existing evidence to inform clinical practices concerning the overall clinical efficacy of this treatment approach in managing AIH. A comprehensive search was conducted across multiple online databases and search engines, including PubMed, Google Scholar, ScienceDirect, Medline, and Embase. RevMan 5.4 software was used for meta-analysis, with forest plots created for each outcome. Thirteen studies were included in this systematic review and meta-analysis. The results indicate that the combination of prednisolone and azathioprine for treating AIH leads to less recurrence and better disease control.

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management.

Autoimmune hepatitis is an immune-mediated inflammatory condition of the liver of undetermined cause that affects both sexes, all ages, races, and ethnicities. Its clinical presentation can be very broad, from having an asymptomatic and silent course to presenting as acute hepatitis, cirrhosis, and acute liver failure potentially requiring liver transplantation. The diagnosis is based on histological abnormalities (interface hepatitis), characteristic clinical and laboratory findings (increased aspartate aminotransferase, alanine aminotransferase, and serum IgG concentration), and the presence of one or more characteristic autoantibodies. The large heterogeneity of these clinical, biochemical, and histological findings can sometimes make a timely and proper diagnosis a difficult task. Treatment seeks to achieve remission of the disease and prevent further progression of liver disease. First-line therapy includes high-dose corticosteroids, which are later tapered to decrease side effects, and azathioprine. In the presence of azathioprine intolerance or a poor response to the standard of care, second-line therapy needs to be considered, including mycophenolate mofetil. AIH remains a diagnostic and therapeutic challenge, and a further understanding of the pathophysiological pathways of the disease and the implementation of randomized controlled trials are needed.

Autoimmune hepatitis (AIH) is a chronic, relapsing and remitting, immune-mediated liver disease that progresses to cirrhosis if left untreated. A significant number of patients may present with acute hepatitis or acute liver failure, which are often misdiagnosed as toxic liver injury. AIH shows a preponderance in young women but may be seen in children and the elderly. Diagnosis requires the integration of clinical, biochemical, and serologic parameters, along with supportive liver histology and exclusion of other causes of liver disease. Liver biopsy is a prerequisite for diagnosis of AIH, to assess severity and stage of disease, exclude other entities, and recognize any concurrent morbidities. No single biomarker or histologic feature is pathognomonic for AIH. The diagnostic and histologic criteria have undergone several modifications since the original scoring system was proposed by the International Autoimmune Hepatitis Group (IAIHG) in 1993. Recently, the IAIHG has proposed consensus recommendations for histologic criteria, relevant for both acute and chronic AIH. This review article will describe the evolving diagnostic criteria for AIH, with their limitations and utility, and with an emphasis on the role of liver histology in the diagnosis and management of AIH.

Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population.

Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied.

Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients.

Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.

The histological criteria in the 1999 and 2008 scoring systems proposed by the International Autoimmune Hepatitis Group (IAIHG) have their inherent limitations in diagnosing autoimmune hepatitis (AIH). In this study, we evaluated the histology components of four scoring systems (1. revised original scoring system ["1999 IAIHG"], 2. simplified scoring system ["2008 IAIHG"], 3. modified histologic criteria ["2017 UCSF"], and 4. a new histologic criteria proposed by the International AIH Pathology Group ["2022 IAHPG"]) in AIH patients.

Medical records and liver biopsies were retrospectively reviewed for 68 patients from two independent medical institutions, diagnosed with AIH based on the 1999 IAIHG system between 2006 and 2016. The histological features were reviewed in detail, and the four histological scoring systems were compared.

Out of the 68 patients, 56 (82.4%) patients met the "probable" or "definite" AIH criteria of the 2008 IAIHG system, and the proportion of histologic score 2 (maximum) was 40/68 (58.8%). By applying the 2017 UCSF criteria, the number of histology score 2 increased to 60/68 (88.2%), and "probable" or "definite" AIH cases increased to 61/68 (89.7%). Finally, applying the 2022 IAHPG histology score resulted in the highest number of cases with histologic score 2 (64/68; 94.1%) and with a diagnosis of "probable" or "definite" AIH (62/68; 91.2%).

The recently proposed UCSF/IAHPG histological criteria increased the histology score of AIH. Substituting the histology component of the 2008 IAIHG system with the 2022 IAHPG criteria increased the sensitivity for diagnosing AIH (≥"Probable AIH") from 82.4% to 91.2%.

There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis.

From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model.

A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation.

ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

Autoimmune liver diseases (AILD) represent a spectrum of related yet distinct immune-mediated disorders. The literature on the prevalence of these AILDs in Indian population is scarce. This study aims to assess the prevalence and clinicopathological spectrum of various AILDs especially the overlap syndrome.

A 10-year (2011-2020) cross-sectional, retrospective observational study of histological proven cases of AILD was conducted. Clinical, demographic, and laboratory parameters were retrieved. Two pathologists independently reviewed the liver biopsies and reassessed 18 histopathological parameters.

During the study period, 17664 liver biopsies were received, out of which 1060 (6%) biopsies of AILD were identified. After exclusion, we had 721 cases which revealed a distribution of autoimmune hepatitis (AIH)-64.7%, primary biliary cholangitis (PBC)-14.8%, primary sclerosing cholangitis (PSC)-7.6%, overlap AIH-PBC 11%, and overlap AIH-PSC 1.7%. AIH patients had significantly higher prevalence for severe lobular inflammation (27%, P ≤ 0.001), several lobular plasma cells (37%, P ≤ 0.001), central perivenulitis (30%, P ≤ 0.001), hepatic rosettes (51%, P ≤ 0.001), and necrosis (35.5%, P ≤ 0.001), while PBC patients had significantly higher frequency of florid duct lesions (11.2%, P ≤ 0.001), duct loss (83.17%, P ≤ 0.001), bile duct damage (76.6%, P ≤ 0.001), and periportal copper deposits (19.6%, P ≤ 0.001). Overlap AIH-PBC group had the highest proportion of severe portal inflammation (27.5%, P ≤ 0.001), prominent portal plasma cells (75%, P ≤ 0.001), moderate interface activity (53.7%, P ≤ 0.001), Mallory-Denk bodies (27.5%, P ≤ 0.001), and periportal cholate stasis (25%, P ≤ 0.001).

Prevalence of biopsy-proven AILDs in our study cohort is 6%. AIH (64.7%) is the most common AILD followed by PBC (14.8%). Overlap syndrome (AIH-PBC) showed prevalence of 11%.

Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022.

We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term "autoimmune hepatitis" in combination with "incidence," "prevalence," or "trend." Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I2 statistic. The study protocol was registered with PROSPERO, CRD42023430138.

A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45°). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970-1999; 9.95 [4.77-15.13], I2 = 95·58% versus 2015-2022; 27.91 [24.86-30.96], I2 = 99·32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias.

AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa.

National Research Foundation of Korea.

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by immune-mediated destruction of hepatocytes, leading to inflammation and fibrosis. In recent years, significant advances have been made in understanding the pathogenesis, epidemiology, diagnosis, and treatment of AIH. This comprehensive narrative review aims to provide an up-to-date overview of these advances. The review begins by outlining the historical background of AIH, dating back to its initial recognition in the 1940s, and highlights the evolution of diagnostic criteria and classification based on autoantibody profiles. The epidemiology of AIH is explored, discussing its varying prevalence across different regions and the role of genetic predisposition, viral infections, and drug exposure as risk factors. Furthermore, the review delves into the pathogenesis of AIH, focusing on the dysregulated immune response, involvement of T cells, and potential contribution of the gut microbiome. Clinical presentation, diagnostic criteria, and liver biopsy as crucial tools for diagnosis are also discussed. Regarding management, the review provides an in-depth analysis of the standard first-line treatments involving glucocorticoids and azathioprine, as well as alternative therapies for non-responsive cases. Additionally, emerging second and third-line treatment options are examined. In conclusion, this narrative review highlights the complexity of AIH and underscores the importance of early diagnosis and individualized treatment approaches to improve patient outcomes. Further research and clinical trials are needed to optimize AIH management and ensure a better long-term prognosis for affected individuals.

Autoimmune hepatitis (AIH) is a rare autoimmune liver disease that is characterised by a chronic inflammatory immune reaction directed against hepatocytes. The disease results in a substantial reduction in quality of life and potentially leads to liver-related complications or death. The International Autoimmune Hepatitis Group (IAIHG) initiated a series of research workshops to uncover the scientific gaps and opportunities in AIH. This review summarises the results of the latest workshop in Maastricht in 2022 and reviews the current challenges in adult AIH, particularly in relation to four important aspects of AIH: diagnostics; new immunomodulatory therapies; clinical trial design; and unmet clinical needs. This review also summarises the progress made since the AIH workshop in 2017. Patients and patient representatives were actively involved in the parallel working groups alongside clinicians and researchers. Despite 40 years of experience with diagnosing and treating AIH, false diagnoses occur and treatment is still based on nonselective immunosuppression. In addition to the need for more specific diagnostic tests, prognostic markers and tailor-based treatments, a major unmet clinical need was identified in areas of care delivery and health-related quality of life.

Autoimmune hepatitis (AIH) is a relatively rare liver disease with varying worldwide incidence of from 0.7 to 2 per 100,000 people. It is characterized by the presence of auto-antibodies. However, an average of 10% of AIH cases have AIH symptoms and pathology but lack autoimmune serology. For such seronegative AIH (snAIH) cases, there is currently no established diagnostic algorithm for diagnosis. and improper or delayed diagnosis of snAIH can lead to no or inappropriate treatment that results in progression to fulminant hepatitis or cirrhosis. This review aims to review the current literature and to present an update of seronegative autoimmune hepatitis, including its pathophysiology, clinical presentation, methods of diagnosis, and treatment in order to increase awareness and emphasize the necessity for timely management.

The treatment response criteria in autoimmune hepatitis (AIH) have been recently updated. This study aimed to assess treatment responses in 39 (16 males) patients with AIH confirmed by histology. Prednisone added to azathioprine or mycophenolate was the most frequent first-line treatment. Serum alanine aminotransferase (ALT) levels were periodically checked for a median of 45 months. Eight (20.5%) patients presented 4 weeks non-response (NR). Baseline lower multiples of ALT above the upper normal limit (UNL) (p = 0.005), Ishak liver fibrosis score > 3 (p = 0.029), and less frequent confluent necrosis > 2 (p < 0.001) were independent predictors of NR. 24 (61.5%) patients achieved complete biochemical response (CBR) at six months. Ishak liver fibrosis score ≤ 3 (p < 0.001), lobular eosinophilic infiltrate (p < 0.001), and ≥50% decrease in serum ALT levels at week 4 (p < 0.001) were independent predictors of CBR. In addition, the GLUCRE score, derived from the multiplication of serum creatinine (mg/dL) and glucose (mg/dL) levels, were identified. A baseline GLUCRE value > 100 strongly predicted CBR failure (p = 0.003) at a follow-up greater than 12 months. In conclusion, the absence of cirrhosis and a ≥50% UNL decrease in serum ALT levels were independent predictors for CBR. A baseline GLUCRE score may help identify patients maintaining longer CBR.

Many hepatologic pathologies mimic autoimmune hepatitis (AIH). Researchers developed the International Autoimmune Hepatitis Group (IAIHG) scoring system to compensate for the lack of specific diagnostic tests for AIH. The scoring system was not designed with pediatric patients in mind, so there are limits to its pediatric use. Additionally, there is limited information on the value of a liver biopsy in conjunction with its use.

In this retrospective study, we evaluated the effect of liver biopsy scores on the IAIHG scoring system in patients that were 0-18 years old with suspected AIH. We also analyzed demographic data and laboratory values associated with a final AIH diagnosis.

We found that interface hepatitis and predominant plasma cells found during the biopsy were significantly associated with a final AIH diagnosis. We also found that abnormal laboratory values were associated with an AIH diagnosis. We found that IAIHG scores calculated post-liver biopsy showed a greater area under the receiver operating characteristic curve (AUROC) of 0.95, which was compared to 0.88 for the scores calculated before a liver biopsy. Including biopsy metrics lowered the optimized cutoff score and test specificity.

Incorporating liver histopathological features improved the performance of the IAIHG scoring system. Further studies to identify other potential elements in liver histology may improve the performance metrics of the IAIHG test in the pediatric population.

All the diagnostic criteria of autoimmune hepatitis (AIH) include histopathology. However, some patients may delay getting this examination due to concerns about the risks of liver biopsy. Therefore, we aimed to develop a predictive model of AIH diagnostic that does not require a liver biopsy. We collected demographic, blood, and liver histological data of unknown liver injury patients. First, we conducted a retrospective cohort study in two independent adult cohorts. In the training cohort (n = 127), we used logistic regression to develop a nomogram according to the Akaike information criterion. Second, we validated the model in a separate cohort (n = 125) using the receiver operating characteristic curve, decision curve analysis, and calibration plot to externally evaluate the performance of this model. We calculated the optimal cutoff value of diagnosis using Youden's index and presented the sensitivity, specificity, and accuracy to evaluate the model in the validation cohort compared with the 2008 International Autoimmune Hepatitis Group simplified scoring system. In the training cohort, we developed a model to predict the risk of AIH using four risk factors-The percentage of gamma globulin, fibrinogen, age, and AIH-related autoantibodies. In the validation cohort, the areas under the curve for the validation cohort were 0.796. The calibration plot suggested that the model had an acceptable accuracy (p > 0.05). The decision curve analysis suggested that the model had great clinical utility if the value of probability was 0.45. Based on the cutoff value, the model had a sensitivity of 68.75%, a specificity of 76.62%, and an accuracy of 73.60% in the validation cohort. While we diagnosed the validated population by using the 2008 diagnostic criteria, the sensitivity of prediction results was 77.77%, the specificity was 89.61% and the accuracy was 83.20%. Our new model can predict AIH without a liver biopsy. It is an objective, simple and reliable method that can effectively be applied in the clinic.

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease with an uncertain cause. The diagnosis of AIH is based on the characteristic clinical and laboratory findings (elevated liver enzyme and hypergammaglobulinemia), the presence of characteristic autoantibodies, and compatible histological abnormalities. AIH lacks a signature diagnostic marker, and the diagnosis requires the exclusion of other diseases (viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced liver injury, Wilson's disease, and hereditary hemochromatosis). Therefore, collaboration between the clinical physician, laboratory medicine experts, and pathologists is important for a diagnosis. In December 2022, the Korean Association for the Study of the Liver (KASL) clinical practice guidelines were established. This review article summarizes the diagnosis part of these guidelines.

Autoimmune hepatitis is an inflammatory disease of the liver of unknown cause that may progress to liver cirrhosis and end stage liver failure if diagnosis is overlooked and treatment delayed. The clinical presentation is often that of acute hepatitis, sometimes very severe; less frequently, it can be insidious or completely asymptomatic. The disease can affect people of any age and is more common in women; its incidence and prevalence seem to be on the rise worldwide. An abnormal immune response targeting liver autoantigens and inducing persistent and self-perpetuating liver inflammation is the pathogenic mechanism of the disease. A specific set of autoantibodies, increased IgG concentrations, and histological demonstration of interface hepatitis and periportal necrosis are the diagnostic hallmarks of autoimmune hepatitis. Prompt response to treatment with corticosteroids and other immunomodulatory drugs is almost universal and supports the diagnosis. The aims of treatment are to induce and maintain long term remission of liver inflammation. Treatment can often even reverse liver fibrosis, thus preventing progression to advanced cirrhosis and its complications. Most patients need lifelong maintenance therapy, and repeated follow-up in experienced hands improves the quality of care and quality of life for affected patients.

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.

This study investigated serum microRNAs (miRNAs/miRs) in autoimmune hepatitis (AIH) and the relationship of these molecules with diagnostic and relapse markers.

Initially, extracellular vesicle-encapsulated miRNAs (EV-miRNAs) in serum with altered expression in AIH relative to healthy control (HC) samples were identified using microarray analysis. To validate the microarray results, the expression levels of selected EV-miRNAs were determined.

Among the 2569 mature miRNAs evaluated in the microarray, EV-miR-557 discriminated patients with AIH from healthy controls (HCs). Validation by digital polymerase chain reaction indicated that serum EV-miR-557 levels were higher in patients with AIH (7.75 copies/μl) than in patients with non-alcoholic steatohepatitis (1.60 copies/μl; p < 0.001), patients with primary biliary cholangitis (2.16 copies/μl; p < 0.005), and HCs (1.86 copies/μl; p < 0.005). The area under the receiver operating characteristic curve values for the probability of AIH using serum EV-miR-557 between the AIH and non-alcoholic steatohepatitis, AIH and primary biliary cholangitis, and AIH and HC groups were 0.81, 0.78, and 0.79, respectively. In addition, serum EV-miR-557 levels >7.69 copies/μl were associated with a significantly higher risk of relapse in patients with AIH (7-year incidence rate: 11.1 vs. 35.4%, log-rank test, p < 0.05). Interestingly, gene expression analysis revealed that increased miR-557 expression following transient transfection of peripheral blood mononuclear cells with a miR-557 mimic resulted in enhanced expression of proinflammatory cytokine-related genes such as interleukin-6, interferon-γ, and tumor necrosis factor. Moreover, miR-557 induced significant tumor necrosis factor-α production (mean: 313.5 vs. 10 642.3 pg/ml, p < 0.05).

EV-miR-557 may play an important role as a potential biomarker of AIH and may be a promising therapeutic target for AIH.

Diagnostic histological criteria for autoimmune hepatitis (AIH) have not been clearly established. Previously published criteria focused mainly on chronic AIH, in which inflammatory changes mainly occur in portal/periportal regions and may not be applicable to acute presentation of AIH, in which inflammatory changes are typically predominantly lobular in location. International consensus criteria for the diagnosis and assessment of disease severity in both acute and chronic AIH are thus urgently needed.

Seventeen expert liver pathologists convened at an international workshop and subsequently used a modified Delphi panel approach to establish consensus criteria for the histopathological diagnosis of AIH.

The consensus view is that liver biopsy should remain standard for diagnosing AIH. AIH is considered likely, if there is a predominantly portal lymphoplasmacytic hepatitis with more than mild interface activity and/or more than mild lobular hepatitis in the absence of histological features suggestive of another liver disease. AIH is also considered likely if there is predominantly lobular hepatitis with or without centrilobular necroinflammation and at least one of the following features: portal lymphoplasmacytic hepatitis, interface hepatitis or portal-based fibrosis, in the absence of histological features suggestive of another liver disease. Emperipolesis and hepatocellular rosettes are not regarded as being specific for AIH.

The criteria proposed in this consensus statement provide a uniform approach to the histological diagnosis of AIH, which is relevant for patients with an acute as well as a chronic presentation and to more accurately reflect the current understanding of liver pathology in AIH.

Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment.

A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis.

The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term 'complete biochemical response' defined as 'normalization of serum transaminases and IgG below the upper limit of normal' be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as '<50% decrease of serum transaminases within 4 weeks after initiation of treatment'. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for 'any adverse event possibly related to treatment leading to potential drug discontinuation'.

These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints.

Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting.

Sclerosing cholangitis (SC) is a rare chronic disorder characterised by inflammation and progressive obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts. Diagnosis is based on cholangiogram showing bile duct dilatation, narrowing and obliteration of the biliary tree, and histologically, on the presence of inflammatory bile duct damage leading to periductal fibrosis. In children the most common SC is associated with strong autoimmune features, overlapping with those of autoimmune hepatitis (AIH); this form is known as autoimmune sclerosing cholangitis, ASC. Conversely, primary SC (PSC), a condition in which the term "primary" indicates that aetiology and pathogenesis are unknown, is rare in paediatrics. Secondary SC (SSC) defines a cholangiopathy associated with an identifiable aetiology such as immunodeficiencies, infections or haematological disorders. ASC and PSC are strongly associated with inflammatory bowel disease (IBD). ASC responds biochemically well to immunosuppressive drugs and ursodeoxycholic acid (UDCA). Primary forms are exclusively managed with oral UDCA, while in the secondary forms the medical treatment depends on the underlying aetiology. Despite treatment, SC often progresses to biliary cirrhosis and end-stage liver disease requiring liver transplantation. The disease can recur after transplant. Better understanding of pathogenic mechanisms and better treatment modalities are needed to improve the prognosis of this invalidating hepatic disorder.

Autoimmune hepatitis (AIH) is a T-cell mediated, inflammatory liver disease affecting all ages and characterized by female preponderance, elevated serum transaminase and immunoglobulin G levels, positive circulating autoantibodies, and presence of interface hepatitis at liver histology. AIH type 1, affecting both adults and children, is defined by positive anti-nuclear and/or anti-smooth muscle antibodies, while type 2 AIH, affecting mostly children, is defined by positive anti-liver-kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody. While the autoantigens of type 2 AIH are well defined, being the cytochrome P4502D6 (CYP2D6) and the formiminotransferase cyclodeaminase (FTCD), in type 1 AIH they remain to be identified. AIH-1 predisposition is conferred by possession of the MHC class II HLA DRB1*03 at all ages, while DRB1*04 predisposes to late onset disease; AIH-2 is associated with possession of DRB1*07 and DRB1*03. The majority of patients responds well to standard immunosuppressive treatment, based on steroid and azathioprine; second- and third-line drugs should be considered in case of intolerance or insufficient response. This review offers a comprehensive overview of pathophysiological and clinical aspects of AIH.

Autoimmune hepatitis (AIH) is a liver disease characterised by necrotico-inflammatory lesions of hepatocytes, the presence of specific autoantibodies and response to corticosteroid treatment. AIH must be considered in any patient with acute or chronic liver disease. As there is no pathognomonic sign of AIH, the diagnosis is based on a combination of clinical, biological, immunological and histological findings, after excluding other causes of liver disease. The clinical and biological presentation of AIH is variable and AIH can be associated with an autoimmune biliary disease, primary biliary cholangitis or primary sclerosing cholangitis in an overlap syndrome. For these reasons, diagnosis of AIH can be challenging. Even if liver histology remains essential in the diagnosis of AIH, non-invasive tests can be used at different steps of the management of AIH: diagnosis of AIH, notably diagnosis of an overlap syndrome, assessment of severity of AIH, searching for extra-hepatic disease frequently associated to AIH, evaluation of response to therapy, decision of treatment withdrawal. This review aims to provide practical guidelines for the use of non-invasive tests for the diagnosis and the follow-up of AIH.