Elsevier

Autoimmunity Reviews

Volume 13, Issues 4–5, April–May 2014, Pages 435-440
Autoimmunity Reviews

Review
Diagnostic criteria of autoimmune hepatitis

https://doi.org/10.1016/j.autrev.2013.11.009Get rights and content

Abstract

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder characterised by female preponderance, elevated transaminase and immunoglobulin G levels, seropositivity for autoantibodies and interface hepatitis. Presentation is highly variable, therefore AIH should be considered during the diagnostic workup of any increase in liver enzyme levels. A set of inclusion and exclusion criteria for the diagnosis of AIH have been established by the International Autoimmune Hepatitis Group (IAIHG). There are two main types of AIH: type 1, positive for anti-nuclear (ANA) and/or anti-smooth muscle antibodies (SMAs) and type 2, defined by the presence of anti-liver kidney microsomal antibody type 1 (LKM-1) and/or anti-liver cytosol type 1 (LC-1) autoantibodies. The central role of autoantibodies in the diagnosis of AIH has led the IAIHG to produce a consensus statement detailing appropriate and effective methods for their detection. Autoantibodies should be tested by indirect immunofluorescence at an initial dilution of 1/40 in adults and 1/10 in children on a freshly prepared rodent substrate that includes kidney, liver and stomach sections to allow for the simultaneous detection of all reactivities relevant to AIH. Anti-LKM-1 is often confused with anti-mitochondrial antibody (AMA) if rodent kidney is used as the sole immunofluorescence substrate. The identification of the molecular targets of anti-LKM-1 and AMA has led to the establishment of immuno-assays based on the use of the recombinant or purified autoantigens. Perinuclear anti-nuclear neutrophil antibody (p-ANNA) is an additional marker of AIH-1; anti soluble liver antigen (SLA) antibodies are specific for autoimmune liver disease, can be present in AIH-1 and AIH-2 and are associated with a more severe clinical course. Anti-SLA are detectable by ELISA or radio-immuno-assays, but not by immunofluorescence. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival.

Introduction

Autoimmune hepatitis (AIH), a progressive inflammatory hepatopathy and important cause of end-stage liver disease, was first described in a group of young women in 1950 by the Swedish professor Jan Waldenström. The patients were afflicted by a severe form of un-resolving hepatitis characterised by markedly elevated serum immunoglobulin levels [1]. The observation that a proportion of patients in similar cohorts were positive for lupus erythematosus cells and anti-nuclear autoantibodies (ANA), led to the hypothesis that a loss of immune tolerance was at the basis of this condition [2].

The most typical features of AIH are female preponderance, hypergammaglobulinaemia, seropositivity for circulating autoantibodies and a picture of interface hepatitis on histology [3]. AIH responds to immunosuppressive treatment in the majority of cases. Treatment should be instituted promptly upon diagnosis. If left untreated, AIH usually progresses to liver failure requiring transplantation. Two types of AIH are distinguished according to serological profile: type 1 AIH (AIH-1) patients are positive for ANA and/or anti-smooth muscle antibody (SMA), and type 2 AIH (AIH-2) patients are defined by the positivity for anti-liver kidney microsomal type 1 antibody (anti-LKM-1) and/or for anti-liver cytosol type 1 antibody (anti-LC-1) [4].

Section snippets

Epidemiology

AIH occurs globally, affecting children and adults of all ages [5], [6] and both sexes, although it is more commonly found in females [7].

Estimates of the prevalence of AIH were mired by a lack of standardization before the introduction of the International Autoimmune Hepatitis Group (IAIHG) Scoring System in the early 1990s [8], [9]. Moreover, early studies did not exclude patients with hepatitis C virus infection. The first study to utilize the IAIHG Scoring System reported a prevalence of

Clinical presentation and natural history

The mode of presentation of AIH is diverse and highly variable [12], although the majority of adult patients manifest with an insidious onset characterised by progressive fatigue, relapsing jaundice, amenorrhea, weight loss and occasionally arthralgia [13]. Complications of portal hypertension, such as gastrointestinal bleeding or hypersplenism can sometimes be apparent [14]. Approximately 25% of patients are completely asymptomatic and are diagnosed after incidental discovery of abnormal liver

Scoring systems

The diagnosis of AIH is based on the presence of elevated serum transaminase and IgG levels, autoantibody seropositivity and histological evidence of interface hepatitis.

This tenet has been factored into the IAIHG diagnostic criteria for AIH [8], [9], which were originally developed for use in the research setting. This scoring system incorporates a number of positive and negative scores, enabling the researcher to grade clinical, laboratory and histological features of AIH. The score has also

Treatment

With the exception of fulminant presentation with encephalopathy, AIH responds to immunosuppressive treatment whatever the degree of liver impairment [20].

Standard treatment, consisting of prednisolone alone or in combination with azathioprine, induces remission (i.e. normal transaminases and IgG levels) in around 80% of the patients, including those with cirrhosis [20], [32]. Once achieved, remission can be maintained with azathioprine alone [20].

In treatment failure, other drugs have been

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