Autoimmune Hepatitis: Serum Autoantibodies in Clinical Practice

Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued by the International Autoimmune Hepatitis Group. They also allow the distinction between type 1 AIH, characterized by positive anti-nuclear and/or anti-smooth muscle antibody, and type 2 AIH, characterized by positive anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody. Anti-soluble liver antigen is the only AIH-specific autoantibody, and is found in 20–30% of both type 1 and type 2 AIH. Anti-neutrophil cytoplasmic antibody is frequently positive in type 1 AIH, being associated also with inflammatory bowel disease and with primary/autoimmune sclerosing cholangitis. The reference method for autoantibody testing remains indirect immunofluorescence on triple tissue (rodent liver, kidney and stomach), allowing both the detection of the majority of liver-relevant reactivities, including those autoantibodies whose molecular target antigens are unknown. Of note, the current knowledge of the clinical significance of autoantibodies relies on studies based on this technique. However, immunofluorescence requires trained laboratory personnel, is observer-dependent, and lacks standardization, leading to ongoing attempts at replacing this method with automated assays, the sensitivity, and specificity of which, however, require further studies before they can be used as a reliable alternative to immunofluorescence; currently, they may be used as complementary to immunofluorescence.

Clinical characteristics and treatment outcomes of acute severe autoimmune hepatitis

Background and aim Acute severe autoimmune hepatitis (AS-AIH) is a rare cause of acute liver failure (ALF), which is often neglected and delayed in treatment. The purpose of this study was to analyze the clinical characteristics and therapeutic effects of AS-AIH. Methods Retrospective analysis was performed. AIH was diagnosed according to the International Autoimmune Hepatitis Group (IAIHG) criteria revised in 1999. AS-AIH was defined as an acute presentation (onset of symptoms to presentation of ≤ 26 weeks) and INR of ≥ 1.5, and no histologic evidence of cirrhosis. Results Twelve patients were diagnosed as AS-AIH. At baseline, median immunoglobulin G was 28.35 g/L (range, 11.4–49.2). Ten (83.3%) patients were antinuclear antibodies and/or anti-smooth muscle antibodies positive. The prominent histologic characteristics were lobular necrosis/inflammation (91.7%) and plasma cell infiltration (100%). All patients received corticosteroid therapy. Death occurred in 2 (16.7%) patients within 30 days resulted from ALF. The average interval between the onset of symptoms and initiation of corticosteroid therapy in deceased patients was 65 days, compared with 19 days for survivors. Conclusions AS-AIH is an uncommon disease with poor outcomes. Patients with acute severe hepatitis of unknown cause should be minded the possibility of AS-AIH and corticosteroids should be considered as soon as possible.

Prognosis of Probable Autoimmune Hepatitis Patients in a Retrospective Cohort Study

Background: Autoimmune hepatitis (AIH) is an idiopathic inflammatory liver disease with genetic susceptibility and unknown environmental triggers, which results in failures of physiologic immunotolerance and destruction of the liver tissues. The gold standard for diagnosis is the International Autoimmune Hepatitis Group (IAIHG) scoring system: the disease is classified as definite or probable according to the scores. However, conventional research on probable AIH has focused on the Caucasian population and there is little data pertaining to the Asian population. Therefore, this study aimed to assess and compare the prognosis of Japanese patients with probable and definite AIH. Methods: Patients with probable and definite AIH diagnosed based on IAIHG scores between 1987 and 2018 were enrolled in this retrospective study. Results: Seventy-two patients with definite AIH and 49 patients with probable AIH were evaluated in the study. Univariate analysis revealed age, fibrosis stage 4, and the fibrosis-4 index were prognostic factors for overall survival. Multivariate analysis indicated that age and liver cirrhosis significantly affected the overall survival. When the cut off albumin-bilirubin score was set appropriately, cirrhosis was differentially diagnosed using albumin-bilirubin score with 100% sensitivity and 70.5% specificity. Classification of probable or definite disease did not alter overall survival with statistical significance. Conclusions: Our findings suggest that probable AIH should be managed as definite AIH is managed in Japanese population. The albumin-bilirubin score helps identify liver cirrhosis and is a prognostic biomarker for overall survival.

Seronegative Lupus- A Wolf in Sheep’s Skin

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory multisystem autoimmune disease. Most of the SLE cases are seropositive, but rare (5%) seronegative SLE cases can also present with complications. Hepatic involvement SLE is multifactorial like hepatotoxic drugs, steatohepatitis, viral hepatitis and Autoimmune Hepatitis (AIH). However, the differentiation between lupus-related hepatitis and AIH remains a challenge to the clinician because of many similar features. It is very difficult to differentiate whether hepatitis is due to autoimmune involvement or purely lupus related on the basis of clinical and biochemical parameters. The patient must fulfill ACR criteria for SLE and International Autoimmune Hepatitis Group (IAIHG) criteria for AIH. Histological diagnosis is considered to be definative in differentiating SLE-related hepatitis and AIH. The cardiac manifestations of SLE are multiple with pericardial disease being the most common. While pericardial effusion is rarely haemodynamically significant, the occurrence of subsequent constrictive pericarditis is even less frequent with only occasional reports in the literature. Authors described a case of a 17-year-old female with Antinuclear Antibody (ANA) negative active SLE (seronegative) with AIH and constrictive pericarditis. The patient responded well to the conservative management initially but later developed drug induced myelosuppression and bilateral pneumonia and succumbed.

Typical features of liver Histology in autoimmune hepatitish

Autoimmune hepatitis is a chronic progressive liver disease which may present as acute hepatitis, chronic hepatitis or even cirrhosis. We report a case of 67-year-old female with diabetic mellitus and hyperlipidemia present with progressive fatigue for one year. Her liver function tests showed hepatocellular injury pattern, elevated serum IgG level and positive ANA 1:320 in homogeneous pattern. Her abdominal ultrasound revealed normal liver parenchyma and no bile duct dilatation. The liver biopsy showed interface hepatitis, lymphoplasmacytic infiltration, bridging necrosis, emperipolesis and hepatic rosettes. The diagnosis autoimmune hepatitis was made according to The Simplified Diagnosis Criteria and The Revised Original Scoring System of the International Autoimmune Hepatitis Group. Her clinical and laboratory were improved after received prednisolone and azathioprine. Figure 1 พยาธิสภาพของชิ้นเนื้อตับย้อมด้วย hematoxylin และ eosin (H&E) รูป A และ B: Interface hepatitis (ลูกศรแดง), Cluster of plasma cells infiltration (หัวลูกศรดำ) รูป C: Hepatic rosette formation (*),Emperipolesis (หัวลูกศรดำ)

Seronegative Autoimmune Hepatitis A Clinically Challenging Difficult Diagnosis

Autoimmune hepatitis (AIH) is a complex liver disease of unknown cause which results in immune-mediated liver injury with varied clinical presentations. Seronegative AIH follows a similar course to autoantibody-positive disease and diagnosis may be challenging. There are no single serologic tests of sufficient diagnostic specificity, and delay in appropriate treatment may lead to progression of the liver disease and liver failure. The revised conventional diagnostic criteria (RDC) scoring for AIH is complex and not routinely used in the clinical practice. The more recent simplified diagnostic criteria (SDC) scoring proposed by International Autoimmune Hepatitis Group in 2008 has wider application in routine practice facilitating the diagnosis of AIH with a specificity and sensitivity of ~90%. In this report, we describe a case of seronegative autoimmune hepatitis diagnosed using RDC. SDC score calculated in our case was 4 and was not diagnostic for AIH. We subsequently used the complex revised diagnostic criteria for definitive diagnosis. Some of the patients previously diagnosed as cryptogenic active hepatitis of unknown etiology probably had an unrecognized diagnosis of seronegative autoimmune hepatitis. SDC scoring may not be applicable in patients with seronegative autoimmune hepatitis. These patients should be reassessed by using RDC.