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Review
. 2023 Sep;79(3):853-866.
doi: 10.1016/j.jhep.2023.04.033. Epub 2023 May 8.

Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report

Raúl J Andrade  1 , Guruprasad P Aithal  2 , Ynto S de Boer  3 , Rodrigo Liberal  4 , Alexander Gerbes  5 , Arie Regev  6 , Benedetta Terziroli Beretta-Piccoli  7 , Christoph Schramm  8 , David E Kleiner  9 , Eleonora De Martin  10 , Gerd A Kullak-Ublick  11 , Guido Stirnimann  12 , Harshad Devarbhavi  13 , John M Vierling  14 , Michael P Manns  15 , Marcial Sebode  16 , Maria Carlota Londoño  17 , Mark Avigan  18 , Mercedes Robles-Diaz  19 , Miren García-Cortes  19 , Edmond Atallah  2 , Michael Heneghan  20 , Naga Chalasani  21 , Palak J Trivedi  22 , Paul H Hayashi  23 , Richard Taubert  24 , Robert J Fontana  25 , Sabine Weber  5 , Ye Htun Oo  26 , Yoh Zen  27 , Anna Licata  28 , M Isabel Lucena  29 , Giorgina Mieli-Vergani  30 , Diego Vergani  30 , Einar S Björnsson  31 ; IAIHG and EASL DHILI Consortium
Affiliations
Review

Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report

Raúl J Andrade et al. J Hepatol. 2023 Sep.

Abstract

Drug-induced liver injury (DILI) can mimic almost all other liver disorders. A phenotype increasingly ascribed to drugs is autoimmune-like hepatitis (ALH). This article summarises the major topics discussed at a joint International Conference held between the Drug-Induced Liver Injury consortium and the International Autoimmune Hepatitis Group. DI-ALH is a liver injury with laboratory and/or histological features that may be indistinguishable from those of autoimmune hepatitis (AIH). Previous studies have revealed that patients with DI-ALH and those with idiopathic AIH have very similar clinical, biochemical, immunological and histological features. Differentiating DI-ALH from AIH is important as patients with DI-ALH rarely require long-term immunosuppression and the condition often resolves spontaneously after withdrawal of the implicated drug, whereas patients with AIH mostly require long-term immunosuppression. Therefore, revision of the diagnosis on long-term follow-up may be necessary in some cases. More than 40 different drugs including nitrofurantoin, methyldopa, hydralazine, minocycline, infliximab, herbal and dietary supplements (such as Khat and Tinospora cordifolia) have been implicated in DI-ALH. Understanding of DI-ALH is limited by the lack of specific markers of the disease that could allow for a precise diagnosis, while there is similarly no single feature which is diagnostic of AIH. We propose a management algorithm for patients with liver injury and an autoimmune phenotype. There is an urgent need to prospectively evaluate patients with DI-ALH systematically to enable definitive characterisation of this condition.

Keywords: AIH; DI-ALH; DILI; Drug-induced autoimmune-like hepatitis; Liver injury; autoimmune hepatitis; diagnosis; drug-induced liver injury; epidemiology; hepatotoxicity; management; outcome.

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Conflict of interest statement

Conflict of interest

The authors have no conflict of interest to disclose in relation with this topic. Arie Regev is employee of Eli Lilly, but has no conflict of interest in relation to this topic.

Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Fig. 1.
Fig. 1.. Liver biopsy findings in DI-ALH.
(A) A biopsy of minocycline-related DI-ALH shows a chronic hepatitis pattern of injury with predominantly portal based inflammation and periportal fibrosis. Interface hepatitis is noted (arrows). (B) Higher magnification shows plasma cells aggregated at the interface. (C) A biopsy of nitrofurantoin-related DI-ALH demonstrates an acute hepatitis pattern of injury with predominantly lobular inflammation and perivenular confluent necrosis (arrow). (D) High magnification shows enlarged hepatocytes with cytoplasmic vacuolation, multinucleation and emperipolesis, against the background of lymphoplasmacytic infiltration. DI-ALH, drug-induced autoimmune-like hepatitis.
Fig. 2.
Fig. 2.. Overlap between drug-induced liver injury, drug-induced autoimmune-like hepatitis, and idiopathic autoimmune hepatitis.
Limited number of patients with drug-induced autoimmune-like hepatitis progress to chronicity and evolve a disease phenotype more like that of idiopathic autoimmune hepatitis.
Fig. 3.
Fig. 3.. An algorithm to approach suspected DI-ALH in clinical practice.
*Alternatively, in mild cases associated with specific drugs known to induce this phenotype (i.e. infliximab), which show clinical/biochemical improvement following drug withdrawal, a liver biopsy is not always necessary. DI-ALH, drug-induced autoimmune-like hepatitis.
See this image and copyright information in PMC

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