Objective: To analyze the clinical features and prognosis of acute severe autoimmune hepatitis (AIH). Methods: A retrospective analysis of the clinical data of patients with acute severe AIH admitted to our hospital from 2008 to 2019 was divided into acute AIH (A-AIH) and chronic acute AIH (AC-AIH) according to the presence or absence of liver diseases. Patients' general condition, liver biochemistry, immunology, histological features of liver, hormonal therapies prognosis and related factors were analyzed. Results: A total of 41 cases [39 females, age (54.24 ± 10.55) years] were collected. Alanine aminotransferase (ALT) and total bilirubin (TBil) were significantly increased, and the international normalized ratio (INR) was > 1.5. Acute lobular inflammation was the feature of acute and severe AIH in the histology of liver. The serum IgG level was (28.36 ± 8.35) g / L. The positive rate of antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA) was 82.9%, and 17.1%, respectively. Over 70% of acute severe AIHs were AC-AIH. The duration of onset of AC-AIH was > 8 weeks, while most A-AIHs < 8 weeks, and the differences between the two groups were statistically significant (P = 0.001). The mortality rate within 30 days after hormonal treatment was 19.5%. There were statistically significant differences in TBil, Model for End-Stage Liver Disease (MELD) score and leukocyte count between the death and survival group. Conclusion: The mortality rate in acute severe AIH is high, and most of them have the basis of chronic liver disease. Serum IgG level, autoantibodies and acute lobular inflammation are important factors for diagnosis. The prognosis of hormonal therapy is related to the patients' condition and course of disease.
Adult ; Autoantibodies ; End Stage Liver Disease ; Female ; Hepatitis, Autoimmune/diagnosis* ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index

autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.]]>
Diagnosis ; Flow Cytometry ; Hepatitis A ; Hepatitis ; Hepatitis, Autoimmune ; Humans ; Inflammation Mediators ; Liver Failure ; Liver Transplantation ; Necrosis ; T-Lymphocytes, Regulatory

Autoimmune hepatitis (AIH) is a chronic disease that may lead to cirrhosis. The immunopathogenesis of AIH is not fully understood and it mainly involves T-cell mediated mechanism. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that promotes T cell response and its polymorphism may serve as a severity marker of AIH. No previous study has considered investigating MIF polymorphism in children with AIH.METHODS: Forty-two children with definite diagnosis of AIH were enrolled along with 100 age and sex matched controls. All participants were tested for polymorphism at -173GC (rs755622) of MIF gene. All patients received the standard protocol of steroid plus azathioprine to achieve remission. Liver biopsy was performed at time of diagnosis for all patients and only 18 of them underwent a second biopsy after treatment.RESULTS: No statistically significant differences in the frequency of the genotypes GG and GC or in allele distribution were found in both patient and control groups (p=0.590, 0.640 respectively). Initial alanine aminotransferase (ALT) levels at the time of presentation was significantly higher in the GC group than GG group (p=0.020). GC genotype significantly correlated with disease relapse (r=0.41, p=0.007). Regression of necroinflammation and the fibrosis score in the second liver biopsy was statistically significant in the GG group (p < 0.0001, p=0.010 respectively).CONCLUSION: MIF -173GC polymorphism is associated with clinically significant markers of pediatric AIH, including increased initial serum ALT levels, may help predict necroinflammatory/fibrosis regression effectively, following immunosuppressive treatment.]]>
Alanine Transaminase ; Alleles ; Azathioprine ; Biopsy ; Child ; Chronic Disease ; Diagnosis ; Fibrosis ; Genotype ; Hepatitis, Autoimmune ; Humans ; Liver ; Macrophages ; Recurrence ; T-Lymphocytes

PURPOSE: Classical criteria for diagnosis of autoimmune hepatitis (AIH) are intended as research tool and are difficult to apply at patient's bedside. We aimed to study the accuracy of simplified criteria and the concordance with the expert diagnosis based on the original criteria. METHODS: A cohort of children under study for liver disorder was selected through consecutive sampling to obtain the prevalence of AIH within the group of differential diagnoses. AIH was defined, based on classical criteria, through committee review of medical reports. Validity indicators of the simplified criteria were obtained in an intention to diagnose approach. Optimal cut-off and the area under the receiver operating characteristic (ROC) curve were calculated. RESULTS: Out of 212 cases reviewed, 47.2% were AIH. For the optimal cut-off (6 points), the simplified criteria showed a sensitivity of 72.0% and a specificity of 96.4%, with a 94.7% positive and a 79.4% negative predictive value. The area under the ROC curve was 94.3%. There was a good agreement in the pre-treatment concordance between the classical and the simplified criteria (kappa index, 0.775). CONCLUSION: Simplified criteria provide a moderate sensitivity for the diagnosis of AIH, but may help in indicating treatment in cases under suspicion with 6 or more points.
Child* ; Cohort Studies ; Diagnosis* ; Diagnosis, Differential ; Hepatitis, Autoimmune* ; Humans ; Intention ; Liver ; Prevalence ; ROC Curve ; Sensitivity and Specificity

Autoimmune liver diseases including autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are rare diseases. The aim of this review is to examine the epidemiology and clinical characteristics of AIH and PBC in South Korea. There were 4,085 patients registered as AIH in the Rare Intractable Disease Registry of Korea between 2009-2013, with a median age of 56 years and female-to male ratio of 6.4. The age-adjusted incidence and prevalence of AIH were 1.07/100,000/year and 4.82/100,000 persons, respectively. Among the patients, 1.1% underwent liver transplantation, and case fatality was 2.18%. Liver cirrhosis at diagnosis was accompanied in 23%; liver biopsy was performed in 75.2%, and prednisolone therapy or prednisolone and azathioprine combination therapy was done in 73% with a remission rate of 86%. There were 2,824 patients with PBC (≥20 years) registered in Korea between 2009-2013 with a median age of 57 years and female-to male ratio of 6.2. The age-adjusted incidence and prevalence of PBC were 0.86/100,000/year and 4.75/100,000 persons, respectively. Among the patients, 2.5% underwent liver transplantation, and case fatality was 2.2% with a 5-year transplantation-free survival of 95.4%. Ursodeoxycholic acid (UDCA) was prescribed in 90% of the patients with a UDCA inadequate response rate of 30%. In conclusion, AIH and PBC are rare but mostly treatable diseases if diagnosed in the early stages. However, scarce data, low awareness, delayed diagnosis and non-availability of 2nd line therapeutics are important issues to be solved. Therefore, governmental support for research and drug development and nationwide cooperative studies are warranted.
Azathioprine ; Biopsy ; Cholangitis ; Delayed Diagnosis ; Diagnosis ; Epidemiology* ; Hepatitis, Autoimmune ; Humans ; Incidence ; Korea* ; Liver Cirrhosis ; Liver Diseases* ; Liver Transplantation ; Liver* ; Male ; Prednisolone ; Prevalence ; Rare Diseases ; Ursodeoxycholic Acid

Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
Anti-Inflammatory Agents/*therapeutic use ; Autoantibodies/*blood ; Azathioprine/therapeutic use ; Biomarkers/blood ; Diagnosis, Differential ; Drug Therapy, Combination ; Hepatitis, Autoimmune/*diagnosis/*drug therapy ; Humans ; Immunosuppressive Agents/*therapeutic use ; Prednisolone/therapeutic use ; Prednisone/therapeutic use

The differential diagnosis of systemic lupus erythematosus (SLE) and autoimmune hepatitis (AIH) is difficult due to the resemblance of these two disorders. However, the accurate diagnosis is important for prognosis and treatment that are different from each other. We report a case of AIH-SLE overlap syndrome which tapering of prednisone and azathioprine therapy deteriorated the condition of a patient due to flare up of SLE. The patient was a 28-year-old woman diagnosed as AIH. After administrations of prednisone and azathioprine, her condition was improved. During dose reduction, she was admitted to our hospital as fever and dyspnea. She diagnosed as lupus nephritis. After high dose treatment with corticosteroids and azathioprine, she recovered. Once the diagnosis of autoimmune disease such as SLE or AIH has been made, clinicians should also be fully aware of concomitant other autoimmune disease.
Adrenal Cortex Hormones ; Adult ; Autoimmune Diseases ; Azathioprine ; Diagnosis ; Diagnosis, Differential ; Dyspnea ; Female ; Fever ; Hepatitis, Autoimmune ; Humans ; Lupus Erythematosus, Systemic ; Lupus Nephritis ; Prednisone ; Prognosis

Interferon-alpha (IFN-alpha) is an important therapeutic agent for hepatitis C virus (HCV) infection, but has various side effects including thyroiditis. We report a case of interferon-induced non-autoimmune hypothyroidism followed by autoimmune-medicated Graves' disease. A 59-year-old woman was diagnosed with chronic active hepatitis C; she had been treated with IFN-alpha and ribavirin for 24 weeks. Before starting the IFN-alpha, her thyroid function was normal and she was negative for autoantibodies. Severe hypothyroidism developed 5 weeks after halting the IFN-alpha, with the Graves' disease phase arising at 32 weeks. For accurate diagnosis and appropriate treatment of thyroid dysfunction during treatment with IFN-alpha, we need to understand and consider rare cases of multiphasic disorder involving both non-autoimmune and autoimmune thyroiditis induced by IFN-alpha.
Autoantibodies ; Diagnosis ; Female ; Graves Disease* ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Hepatitis, Chronic ; Humans ; Hypothyroidism* ; Interferon-alpha* ; Interferons ; Middle Aged ; Ribavirin ; Thyroid Gland ; Thyroiditis ; Thyroiditis, Autoimmune

BACKGROUND/AIMS: Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone. METHODS: This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes. RESULTS: The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups. CONCLUSIONS: The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.
Adult ; Aged ; Cohort Studies ; Drug Therapy, Combination ; Female ; Hepatitis, Autoimmune/complications/*diagnosis ; Humans ; Liver/metabolism/pathology ; Liver Cirrhosis, Biliary/complications/*diagnosis/drug therapy ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Steroids/therapeutic use ; Treatment Outcome ; Ursodeoxycholic Acid/therapeutic use

Smooth muscle antibodies (SMAs) are diagnostic markers for the serological diagnosis of type 1 autoimmune hepatitis. SMA that is restricted to staining of the stomach muscle and blood vessel walls was referred to as "SMA-V". In addition, SMAs are classified into the peritubular (SMA-T) and glomerular (SMA-G) patterns. SMAs are occasionally present in patients with malignancies, but have not yet been reported in thyroid cancer. We came across the first case of SMA positivity in a patient with papillary thyroid carcinoma (PTC). A 31-yr-old male was admitted to our hospital for evaluation of incidentally detected thyroid cancer. He had been diagnosed with PTC based on pathological results following fine-needle aspiration biopsy. The patient underwent total thyroidectomy followed by radio-iodine treatment. The serum levels of AST and ALT were increased before radiotherapy. Tests were conducted for the evaluation of liver disease. SMA was positive at a titer of 1:320, showing positive results for the vessel walls but negative results for the glomerulus and tubules in the kidney (SMA-V pattern). The association of SMA with malignancies and the classification of SMA immunofluorescent subtypes have been previously reported. However, these studies have not clearly established the ability of SMA subtype to predict a specific disease. Therefore, evaluation of an association of SMA pattern with specific diseases in SMA-positive patients may provide additional and useful information for the rapid diagnosis and accurate treatment of patients with autoimmune diseases or malignancies. This case report could serve as a great resource for further studies on SMA.
Antibodies ; Autoimmune Diseases ; Biopsy, Fine-Needle ; Blood Vessels ; Classification ; Diagnosis ; Hepatitis, Autoimmune ; Humans ; Kidney ; Liver Diseases ; Male ; Muscle, Smooth* ; Radiotherapy ; Stomach ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy