Consensus Recommendations for Histological Criteria of Autoimmune Hepatitis From the International AIH Pathology Group

Results of a Workshop on AIH Histology hosted by the European Reference Network on Hepatological Diseases and the European Society of Pathology

Ansgar W. Lohse; Marcial Sebode; Prithi S. Bhathal; Andrew D. Clouston; Hans P. Dienes; Dhanpat Jain; Annette S. H. Gouw; Maha Guindi; Sanjay Kakar; David E. Kleiner; Till Krech; Carolin Lackner; Thomas Longerich; Romil Saxena; Luigi Terracciano; Kay Washington; Sören Weidemann; Stefan G. Hübscher; Dina Tiniakos

Disclosures

Liver International. 2022;42(5):1058-1069. 

In This Article

Abstract and Introduction

Abstract

Background & Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Introduction

Autoimmune hepatitis (AIH) is a rare disease but is being diagnosed with increasing frequency around the world.[1] The clinical picture is very heterogeneous. The disease can start in infancy, but can also manifest in the 8th or 9th decade of life for the first time.[2–4] Similarly, the disease can manifest as asymptomatic mild disease coming to medical attention because of raised liver enzymes on a routine blood test, or present with an acute hepatitis or even acute liver failure.[5] Up to one third of all AIH patients have cirrhosis at the time of initial diagnosis because the disease had a subclinical, undetected course.[1] The wide spectrum of clinical presentations in combination with lack of specific or sensitive laboratory markers makes the diagnosis of AIH challenging even for experts, and has led to the use of scores to help in making the diagnosis.[2,3,6] Liver histology represents a central component of these scores, thus liver biopsy is considered mandatory in the diagnostic work-up of AIH in most guidelines published by international scientific societies.[4,7–9] There is no diagnostic biomarker for AIH and histopathology plays a key role in designating the diagnosis of AIH as definite, probable or unlikely. However, the histological criteria for making a diagnosis of AIH are largely based on old studies, and have neither been prospectively validated, nor agreed upon by international consensus.

AIH was initially described as a chronic disease. Indeed, the disease was called chronic AIH as part of the spectrum of chronic active hepatitis until 1993.[2] Inflammatory changes in the context of chronic AIH are characterized by predominantly portal-based lymphoplasmacytic inflammation associated with varying degrees of interface hepatitis (previously referred to as "piecemeal necrosis"). These early studies largely provided the basis for the histological criteria used in diagnostic scores.[3,6] Patients with an acute presentation of AIH typically have predominantly lobular-based inflammation which may be associated with centrilobular necrosis (central perivenulitis) and may lack the typical portal/periportal histological features of chronic hepatitis.[10–15] The scoring systems proposed for the histological diagnosis of chronic AIH are consequently inadequate in the setting of acute AIH. Such cases are often misclassified as drug-induced or toxic acute liver injury and the diagnosis of AIH may not be considered in the histopathological evaluation. As AIH patients would particularly benefit from the rapid institution of immunosuppressive treatment, recognition and accurate diagnosis of AIH presenting as acute hepatitis is of paramount importance.[16] Furthermore, recent evidence suggests that histological features such as hepatocellular rosettes and emperipolesis, which were considered to be necessary for classifying a case as 'typical' AIH according to the 2008 simplified diagnostic criteria, can also be found in other inflammatory liver diseases such as viral hepatitis, primary biliary cholangitis (PBC) or drug-induced liver injury (DILI).[17–19] Hepatocyte rosettes are indicative of hepatocellular regeneration in the context of severe liver cell damage rather than pointing to a specific aetiology, while the pathophysiology of emperipolesis remains unclear. The aim of this study was to develop international consensus criteria for the diagnosis of AIH and for the assessment of disease severity in AIH, which could be applied to both acute and chronic presentations of the disease.

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