Autoimmune Hepatitis and Obstetrical Outcomes: A Nationwide Assessment.

INTRODUCTION: Previous research identified AIH as linked to unfavorable obstetrical outcomes in a US nationwide retrospective study from 2012-2016. Our aim is to update the literature and strengthen the AIH-pregnancy outcomes relationship. METHODS: Using the National Inpatient Sample database in the US, from 2016 to 2020, we compared pregnant females with a diagnosis of AIH to those with and without other chronic liver diseases (CLD), using ICD-10-CM codes. Baseline characteristics were analyzed using T-test and Chi-Square, and multivariate regression was used to estimate the differences in maternal outcomes adjusted for age, race, insurance status, geographical location, hospital characteristics, and comorbid conditions. RESULTS: Out of 19,392,328 hospitalizations for pregnant females ≥ 18 years old from 2016 to 2020, 1095 had AIH, 179,655 had CLD, and 19,206,696 had no CLD. No mortality was observed among individuals with AIH. When compared to individuals without CLD, AIH was associated with an 82% increase in the odds of preterm delivery (AIH: 8% vs. Without CLD: 5%, adjusted Odds Ratio = 1.82, 95% CI 1.06-3.14), with no significant differences in gestational diabetes mellitus, hypertensive complications, and postpartum hemorrhage, and a 0.6 day longer hospital stay. Furthermore, there were no significant differences in outcomes between AIH and CLD. CONCLUSIONS: Our study reinforces the association of AIH with adverse obstetrical outcomes (e.g., preterm delivery), however, we found that there is no difference in GDM and hypertensive complications, as suggested in prior studies. Therefore, further investigations are needed to clarify the association between AIH and these obstetrical complications.

Epidemiology, clinical features and management of autoimmune hepatitis in Switzerland: a retrospective and prospective cohort study.

BACKGROUND AND AIMS: The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data. RESULTS: A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes). CONCLUSION: Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

[Assessment of the possible impact of hepatitis viruses on the development and course of autoimmune liver diseases].

BACKGROUND: Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown. AIM: To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD. MATERIALS AND METHODS: A single-center case-control study included 139 patients with AILD: autoimmune hepatitis - AIH (n=46), primary biliary cholangitis - PBS (n=74), primary sclerosing cholangitis - PSC (n=19). Median age 56 years, IQR 48-65 years. 125 patients - without liver disease - control group (median age 55 years, IQR 46-65 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy - 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5). RESULTS: Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p<0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.481-4.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.633-5.542] and OR 2.515, 95% CI [1.242-5.093]). In patients with severe liver fibrosis (F3-F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0-F2 [85% vs 65%; p=0.008]. CONCLUSION: In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.

LiverMultiScan as an alternative to liver biopsy to monitor autoimmune hepatitis in the National Health Service in England: an economic evaluation.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic progressive liver disease, managed with corticosteroids and immunosuppressants and monitored using a combination of liver biochemistry and histology. Liver biopsy (gold standard) is invasive, costly and has risk of complications. Non-invasive imaging using multiparametric magnetic resonance (mpMR) can detect the presence and extent of hepatic fibroinflammation in a risk-free manner. OBJECTIVE: To conduct early economic modelling to assess the affordability of using mpMR as an alternative to liver biopsy. METHODS: Medical test costs associated with following 100 patients over a 5-year time horizon were assessed from a National Health Service payor perspective using tariff costs and average biopsy-related adverse events costs. Sensitivity analyses modelling the cost consequences of increasing the frequency of mpMR monitoring within the fixed cost of liver biopsy were performed. RESULTS: Per 100 moderate/severe AIH patients receiving an annual mpMR scan (in place of biopsy), early economic modelling showed minimum cost savings of £232 333. Per 100 mild/moderate AIH patients receiving three mpMR scans over 5 years estimated minimum cost savings were £139 400. One-way sensitivity analyses showed increasing the frequency of mpMR scans from 5 to 10 over 5 years in moderate/severe AIH patients results in a cost saving of £121 926.20. In patients with mild/moderate AIH, an increase from 3 to 6 mpMR scans over 5 years could save £73 155.72. In a minimalistic approach, the use of 5 mpMR scans was still cost saving (£5770.48) if they were to replace two biopsies over the 5-year period for all patients with moderate/severe or mild/moderate AIH. CONCLUSIONS: Integration of mpMR scans in AIH patient pathways leads to significant cost savings when liver biopsy frequency is either reduced or eliminated, in addition to improved patient experience and clinician acceptability as well as providing detailed phenotyping to improve patient outcomes. TRIAL REGISTRATION: NCT03979053.

Measurement of liver and spleen stiffness as complementary methods for assessment of liver fibrosis in autoimmune hepatitis.

BACKGROUND AND AIMS: Liver stiffness measurements (LSM), commonly performed by transient elastography (TE) or two-dimensional shear wave elastography (2D-SWE), are used to quantify liver fibrosis. Active hepatitis, a hallmark of autoimmune hepatitis (AIH), could bias LSM. This bias might be overcome by measurement spleen 2D-SWE. Here, we compare liver and spleen 2D-SWE to TE and liver biopsy (LB) in prospectively recruited patients with AIH. METHODS: We analysed liver and spleen 2D-SWE in relation to liver TE in 90 patients treated ≥ 6 months for AIH. Liver and spleen 2D-SWE were also compared to LB in 63 individuals with AIH. Finally, we evaluated these tools in 220 patients with AIH and during 18 months follow-up. RESULTS: Liver 2D-SWE correlated with surrogate markers of active hepatitis (ALT and IgG, both P < .001) but there was no link between spleen 2D-SWE and ALT. Liver 2D-SWE, but not spleen 2D-SWE, was associated with histopathological inflammatory score (P < .01). When compared to LB, the optimal cut-offs for detecting cirrhosis by liver and spleen 2D-SWE were 16.1 kPa (AUROC 0.93) and 29.8 kPa (AUROC 0.95), respectively. In patients with active hepatitis the combined diagnostic approach including liver and spleen 2D-SWE had significantly better AUROC for detecting cirrhosis than liver 2D-SWE alone. CONCLUSIONS: Liver and spleen 2D-SWE are reliable complementary methods for the diagnosis of advanced fibrosis in AIH. Spleen 2D-SWE seems to be less biased by inflammation and could facilitate fibrosis assessment in therapy-naïve patients or in the presence of active hepatitis.

Assessment of EN-RAGE, sRAGE and EN-RAGE/sRAGE as potential biomarkers in patients with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is a liver disease characterized by the autoimmune-induced injury of hepatocytes which can lead to cirrhosis and hepatic failure. The diagnosis and disease management of AIH patients remain challenging due to the diversity of clinical phenotypes and the presence of confounders such as alcohol and viruses. Recently, EN-RAGE and sRAGEs have been implicated in inflammatory-immune response. Nonetheless, their natural behaviour and relationship to disease activity as well as clinical predictive values in AIH development or therapy-induced remission have not been reported. METHODS: Sixty-seven AIH patients and thirty gender- and age-matched healthy controls (HC) were enrolled. The serum concentrations of EN-RAGE, sRAGE and their ratio (EN-RAGE/sRAGE) in these subjects were measured by ELISA. Besides, the correlations of three parameters with clinical features and therapeutic response were analyzed, respectively. Furthermore, their potential predictive values for monitoring the AIH progression and therapeutic response were also evaluated. RESULTS: Higher serum EN-RAGE, lower sRAGE and higher EN-RAGE/sRAGE value were observed in AIH patients. EN-RAGE and sRAGE as well as EN-RAGE/sRAGE were correlated with liver necroinflammation parameters, cirrhosis occurrence and therapeutic response. In addition, we identified that EN-RAGE/sRAGE, EN-RAGE and sRAGE had valuable predicting power for AIH patients, AIH patients with normal ALT and cirrhosis incidence, respectively. More importantly, EN-RAGE/sRAGE also exerted predicting power for the remission in AIH patients. CONCLUSIONS: AIH patients rendered distinct patterns of serum EN-RAGE, sRAGE or EN-RAGE/sRAGE compared to healthy controls. Moreover, these three parameters exhibited potentials as novel biomarkers for AIH diagnosis and prognosis evaluation.

Second-line and third-line therapy for autoimmune hepatitis: A position statement from the European Reference Network on Hepatological Diseases and the International Autoimmune Hepatitis Group.

Most patients with autoimmune hepatitis respond well to standard immunosuppressive therapy with steroids and azathioprine, and while untreated disease is usually fatal, patients who respond well to therapy have an excellent prognosis. However, insufficient response to standard therapy or intolerable side effects requiring dose adaptions or treatment changes occur in 10-20% of patients. While there is fairly good agreement on second-line treatment options, there is very wide variation in the indication and use of possible third-line therapies. Herein, the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) and the International Autoimmune Hepatitis Group (IAIHG) outline a treatment algorithm for both children and adults that should help to standardise treatment approaches, in order to improve patient care and to enable the comparison of treatment results between scientific publications.

Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature.

BACKGROUND: Abnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years. CASE SUMMARY: We present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications. CONCLUSION: This report underscores the emergence of autoimmune hepatitis in the context of HIV infection.

Racial disparities in presentation and outcomes of paediatric autoimmune hepatitis.

BACKGROUND & AIMS: Most studies on autoimmune hepatitis (AIH) in children are in predominantly Caucasian cohorts. Paediatric AIH in African Americans (AA) is understudied, with a dearth of clinical predictors of outcome, often leading to serious complications and even mortality. The aim of the study was to define disease presentation, progression, response to therapy and outcomes in paediatric AIH in a well-defined, large, single centre, demographically diverse population. METHODS: We conducted a review of patients with AIH who were followed at this tertiary liver transplant centre. Clinical and laboratory covariates were assessed with regard to disease presentation, progression and outcomes in AA vs Non-AA children. RESULTS: African Americans patients constituted 42% of this cohort. At 1-year follow-up, AA children were receiving significantly higher doses of steroids compared to non-AA. More AA presented with end-stage liver disease (ESLD) with high immunoglobulin G and GGT:platelet ratio. After adjusting for other risk factor variables like gender, age at presentation and ESLD, AA children were at 4.5 times higher risk for significant outcome liver transplant/death within the first 12 months of presentation. Post-transplant, recurrent AIH was seen in 50% of AA vs 8% in non-AA. CONCLUSIONS: African American patients with AIH are more likely to present with ESLD and have an increased early risk for transplantation with high likelihood of disease recurrence post-transplantation. Studies are needed to delineate factors such as inherent biology, genetics and access to care. Early referral and tailored immunosuppressive regimens are required for AA patients with AIH.

Population-based prevalence, incidence, and disease burden of autoimmune hepatitis in South Korea.

BACKGROUND AND AIM: Little is known about population-based epidemiology and disease burden of autoimmune hepatitis (AIH). The aim of this study was to investigate the prevalence, incidence, comorbidity and direct medical cost of AIH in South Korea. METHODS: The data was from the nationwide, population-based National Health Insurance Service claims database and the Rare Intractable Disease registration program. Age and gender-specific prevalence rates were calculated, and data on comorbidity, diagnostic tests, prescribed drugs, and medical costs were retrieved for patients registered under the disease code K75.4 (AIH) from 2009 to 2013. RESULTS: A total of 4,085 patients with AIH were identified between 2009 and 2013 with a female-to-male ratio of 6.4. The age-adjusted prevalence rate was 4.82/100,000 persons and gender adjusted prevalence rates were 8.35 in females and 1.30 in males. The age-adjusted calculated incidence rate was 1.07/100,000 persons (gender-adjusted 1.83 in females and 0.31 in males). Ascites, variceal bleeding, and hepatocellular carcinoma were found in 1.4%, 1.3%, and 2.2% of the patients, respectively. Forty-six patients (1.1%) underwent liver transplantation during the study period. Case-fatality was 2.18%. Corticosteroid and azathioprine were prescribed in 44.1% and 38.0% of prevalent patients with AIH in 2013, respectively. The nationwide total direct medical cost was less than 4.0 million USD, and the average cost for each patient was 1,174 USD in 2013. CONCLUSION: This is the first report on the nationwide epidemiology of AIH in Korea, and it showed a lower prevalence than that of Western countries with considerable disease burden.

Challenges in the Standardization of Autoantibody Testing: a Comprehensive Review.

Standardization and harmonization are complementary tools to achieve higher testing quality in laboratory medicine. Both are of great relevance and are strongly needed in autoimmune diagnostics, due to the impressive advance in basic research and technological development observed in this diagnostic field in recent years that has led to the introduction of many new tests and new analytical methods. It is, therefore, essential that this strong innovative thrust is translated into clinical practice in a coordinated way to avoid confusion and the risk of potentially harmful errors for the patient. However, while standardization of antibody assays is a very complex task, harmonization of procedures and behaviors is a more feasible target and should necessarily include all the phases of the total testing process-in the pre-analytical phase, appropriateness of test requests, harmonization of autoantibody terminology, and adoption of uniform nomenclature for laboratory tests; in the analytical phase, harmonization of measurements, and sharing of test profiles and diagnostic algorithms; and in the post-analytical phase, harmonization of data reporting, and criteria for interpreting immunoserological results, especially harmonization of units, reference intervals, decision limits, and definition and notification of critical values. We here provide and discuss some examples of harmonization initiatives related to anti-nuclear antibodies, TSH receptor, and anti-thyroid peroxidase antibodies and to antibodies associated with autoimmune hepatitis and with celiac disease. These initiatives could be the starting steps to achieve a wider consensus and a closer interaction among stakeholders in the path of autoimmune diagnostics harmonization to enhance clinical effectiveness and provide greater patient safety.

Assessment of the histopathological key features in autoimmune hepatitis.

AIMS: In this study, we aimed to evaluate the use of typical histological features of both the revised original (1999) and simplified (2008) criteria in the diagnosis of autoimmune hepatitis (AIH) in clinical practice. METHODS AND RESULTS: We performed a detailed histopathological evaluation of the pretreatment biopsies of 63 AIH patients, and used biopsies of 62 untreated chronic viral hepatitis patients [hepatitis B (n = 21) or hepatitis C (n = 41)] as a reference cohort. Biopsies were systematically reviewed for inflammation, fibrosis and the presence of interface hepatitis, plasma cells, rosettes and emperipolesis with a well-defined assessment method. AIH biopsies showed more interface hepatitis (87% versus 63%, P = 0.002), more plasma cell-rich infiltrates (48% versus 27%, P = 0.02), more rosettes (49% versus 23%, P = 0.004) and more emperipolesis (78% versus 50%, P = 0.001) than chronic viral hepatitis biopsies. Emperipolesis (P = 0.01) and rosettes (P < 0.01) were superior to plasma cells and interface hepatitis as independent predictors for AIH. Moderate to severe lymphocytic cholangitis was found in 28% of AIH patients. CONCLUSIONS: Emperipolesis and rosette formation are superior histological predictors of AIH than the classic hallmark features of interface hepatitis and plasma cells. In addition, moderate to severe lymphocytic cholangitis does not preclude the diagnosis of AIH.

Noninvasive markers in the assessment and management of autoimmune liver diseases.

Historically, liver biopsy has been used to determine the etiology of liver disease, the degree of inflammation, the stage of liver fibrosis, and the response to treatments. In the last decade, the advent of noninvasive tests has improved the diagnosis and management of autoimmune liver diseases. For example, serum markers can identify hepatic inflammation, whereas ultrasound and MRI can diagnose liver fibrosis. Physicians now have a much larger repertoire of diagnostic tests to assess the liver parenchyma compared with liver biopsy alone. In some rare cases, noninvasive tests may provide an alternative to liver biopsy. In general, however, these noninvasive tests complement liver biopsy and provide quick, accurate, and reliable adjunctive data.

Autoimmune hepatitis in diverse ethnic populations and geographical regions.

Autoimmune hepatitis has diverse clinical phenotypes and outcomes in ethnic groups within a country and between countries, and these differences may reflect genetic predispositions, indigenous etiological agents, pharmacogenomic mechanisms and socioeconomic reasons. In the USA, African-American patients have cirrhosis more commonly, treatment failure more frequently and higher mortality than white American patients. Survival is poorest in Asian-American patients. Autoimmune hepatitis in other countries is frequently associated with genetic predispositions that may favor susceptibility to indigenous etiological agents. Cholestatic features influence treatment response; acute-on-chronic liver disease increases mortality and socioeconomic and cultural factors affect prognosis. Ethnic-based deviations from classical phenotypes and the frequency of late-stage disease can complicate the diagnosis and management of autoimmune hepatitis in non-white populations.

Usefulness of the measurement of azathioprine metabolites in the assessment of non-adherence.

Azathioprine is a thiopurine immunosuppressive antimetabolite used to chronically treat inflammatory bowel disease and autoimmune hepatitis. Azathioprine treatment is a long-term therapy and therefore it is at risk for non-adherence, which is considered an important determinant of treatment inefficacy. Measurement of 6-thioguanine and 6-methylmercaptopurine nucleotides has been recently suggested as a screener for non-adherence detection. We describe four young patients in which non-adherence to azathioprine therapy was detected only through the measurement of drug metabolite concentrations, and the criterion for non-adherence was undetectable metabolite levels. After the identification of non-adherence, patients and their families were approached and the importance of a correct drug administration was thoroughly enlightened and discussed; this allowed obtaining a full remission in all subjects. Our observations support the use of undetectable metabolite levels as indicators of non-adherence to therapy in azathioprine treated patients. The additional level of medical supervision given by this assay allows getting a better adherence to medical treatment, which results in an improvement in the response to therapy; these benefits may justify the costs associated with the assay.

[ALT screening for chronic liver diseases: scrutinizing the evidence]. / ALT als Screeningparameter für Lebererkrankungen: eine kritische Evaluation der Evidenz.

Elevated serum amino-transferase levels may be associated with liver injury. Testing for aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is part of many routine screening approaches. The aim of this manuscript was to scrutinize the evidence for using ALT testing as a primary screening parameter for liver diseases. We conclude that (i) elevated serum ALT levels indicate a high specificity and a reasonable sensitivity liver injury, (ii) 10 - 25 % of German adults have elevated ALT levels, (iii) ALT values are increased in the majority but not all patients with acute and chronic liver disease (iv) elevated ALT-values are associated with an increased risk of liver-specific mortality, (v) elevated ALT values are also a risk factor for non-hepatic diseases including diabetes mellitus type 2, metabolic syndrome, cardiovascular diseases and malignancies, (vi) many liver diseases identified by an ALT screening can be treated successfully including prevention of development of clinical endpoints, (vii) an ALT-screening is very likely to be cost-effective although studies are needed for Germany to support this conclusion.

Scoring systems for the diagnosis of autoimmune hepatitis: past, present, and future.

The diagnosis of autoimmune hepatitis (AIH) can be challenging due to the variable clinical and laboratory findings. The original diagnostic criteria published in 1993 by the International Autoimmune Hepatitis Group (IAIHG) were revised in 1999 in an attempt to standardize the diagnosis. However, these criteria are complex and can be cumbersome in clinical practice. In 2008, simplified diagnostic criteria were reported to facilitate the bedside diagnosis of AIH. The scoring systems have been evaluated in several retrospective case series and tested for their ability to reliably diagnose and exclude AIH. However, the scoring systems did not fare as well in patients with concomitant cholestatic disease, fatty liver disease, fulminant hepatitis, and pediatric patients. Both positive and negative predictive values are low in these patients. Prospective studies are needed to compare the two scoring systems to determine which (if not all) patients require liver biopsy and which patients would benefit from immunotherapy.

[Incidence and prevalence of autoimmune hepatitis in the area of the Hospital de Sagunto (Spain)]. / Incidencia y prevalencia de hepatitis autoinmune en el área sanitaria del Hospital de Sagunto.

Thirteen cases of autoimmune hepatitis (AIH) were diagnosed from 1990 to 2003 in the area of the Hospital de Sagunto (Valencia, Spain), which attends a population of 112,003 inhabitants aged more than 14 years (54,622 males and 57,381 females). The diagnostic criteria of the International Autoimmune Hepatitis Group were used and patients who, despite having a probable diagnosis of AIH, presented hepatitis C virus infection were excluded. The diagnosis was probable in one patient and definitive in 12. All patients, 11 females and two males aged 45.9 12.2 years (range: 28-66), were classified as AIH type 1. Among the population aged more than 14 years, the mean annual incidence of AIH was 0.83 cases/100,000 inhabitants (95% CI, 0.44-1.42) (range: 0-2.68), showing a significant trend to increase (b = 0.132; p = 0.019). The incidence was higher in women than in men (RR = 5.24; 95% CI, 1.16-23.62). The mean annual incidence was 1.37 (95% CI, 0.68-2.46) (range: 0-3,49) in women and was 0.26 (95% CI, 0.02-0.96) (range: 0-1.83) in men. By age, the maximum mean annual incidence was observed in the group aged 55-64 years (1.6 cases/100,000 inhabitants). The prevalence of AIH in September 2003 was 11.61 cases/100,000 inhabitants aged more than 14 years (95% CI, 6.78-19.86). The prevalence was 3.66 (95% CI, 1-13.35) in men and was 19.17 (95% CI, 10.70-34.33) in women.