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

Andrade, Raúl J.; Aithal, Guruprasad P.; Boer, Ynto S. de; Liberal, Rodrigo; Gerbes, Alexander L.; Regev, Arie; Beretta‐Piccoli, Benedetta Terziroli; Schramm, Christoph; Kleiner, David E.; Martin, Eléonora De; Kullak‐Ublick, Gerd A.; Stirnimann, Guido; Devarbhavi, Harshad; Vierling, John M.; Manns, Michael P.; Sebode, Marcial; Londoño, María Carlota; Avigan, Mark; Robles‐Díaz, Mercedes; García‐Cortés, Miren; Atallah, Edmond; Heneghan, Michael A.; Chalasani, Naga; Trivedi, Palak; Hayashi, Paul H.; Taubert, Richard; Fontana, Robert J.; Weber, Sabine; Oo, Ye Htun; Zen, Yoh; Licata, Anna; Lucena, M. Isabel; Mieli‐Vergani, Giorgina; Vergani, Diego; Bjõrnsson, Einar

doi:10.1016/j.jhep.2023.04.033

Cited by 56 publications

(57 citation statements)

References 85 publications

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“…8 Due to the lack of pathognomonic features and the absence of specific diagnostic criteria, distinguishing between AIH and DILI with autoimmune features is a diagnostic dilemma, and no harmonized definition of this clinical pattern of DILI has been reached. 9 In a recently held expert opinion conference, 10 the term drug-induced autoimmunelike hepatitis (DI-ALH) was endorsed by experts in both DILI and AIH.…”

Section: Introductionmentioning

confidence: 99%

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries

García‐Cortés

Ortega‐Alonso

Matilla-Cabello

et al. 2023

Liver International

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Background & aims: Idiosyncratic drug-induced liver injury (DILI) with autoimmune features is a liver condition with laboratory and histological characteristics similar to those of idiopathic autoimmune hepatitis (AIH), which despite being increasingly reported, remains largely undefined. We aimed to describe in-depth the features of this entity in a large series of patients from two prospective DILI registries.

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Section: Introductionmentioning

confidence: 99%

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries

García‐Cortés

Ortega‐Alonso

Matilla-Cabello

et al. 2023

Liver International

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“…Third, human leukocyte antigens were tested in only two patients; therefore, we could not determine whether genetic predisposition would affect the risk of DI‐ALH after pulse steroid therapy. Fourth, there has been no consensus on the diagnostic criteria for DI‐ALH 9 . Although simplified IAIHG criteria 37 are often used for diagnosis of DI‐ALH, 38 these criteria seemed not appropriate, because elevated immunoglobulin G levels and high titers of autoantibodies were not found in our patients.…”

Section: Discussionmentioning

confidence: 89%

“…Autoimmune hepatitis (AIH) is an inflammatory liver disease of autoimmune mechanism that may progress to end‐stage liver failure if appropriate treatment is delayed 1 . Among the complicated pathogenesis of AIH, exposure to drugs, such as minocycline, nitrofurantoin, and infliximab, can be a trigger, 2–5 and this phenotype of AIH is referred to by various terms, including drug‐induced AIH, drug‐induced AIH‐like injury, immune‐mediated drug‐induced liver injury, and drug‐induced liver injury with autoimmune features 6–9 . Recently, the Drug‐Induced Liver Injury consortium and International Autoimmune Hepatitis Group (IAIHG) held a joint international conference, where drug‐induced autoimmune‐like hepatitis (DI‐ALH) was chosen as the preferred term for this condition 9 .…”

Section: Introductionmentioning

confidence: 99%

“…1 Among the complicated pathogenesis of AIH, exposure to drugs, such as minocycline, nitrofurantoin, and infliximab, can be a trigger, [2][3][4][5] and this phenotype of AIH is referred to by various terms, including drug-induced AIH, druginduced AIH-like injury, immune-mediated drug-induced liver injury, and drug-induced liver injury with autoimmune features. [6][7][8][9] Recently, the Drug-Induced Liver Injury consortium and International Autoimmune Hepatitis Group (IAIHG) held a joint international conference, where drug-induced autoimmune-like hepatitis (DI-ALH) was chosen as the preferred term for this condition. 9 Even though corticosteroids are the mainstay of treatment of AIH, 6 methylprednisolone, a synthetic glucocorticoid, is also a cause of DI-ALH.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] Recently, the Drug-Induced Liver Injury consortium and International Autoimmune Hepatitis Group (IAIHG) held a joint international conference, where drug-induced autoimmune-like hepatitis (DI-ALH) was chosen as the preferred term for this condition. 9 Even though corticosteroids are the mainstay of treatment of AIH, 6 methylprednisolone, a synthetic glucocorticoid, is also a cause of DI-ALH. 9 Reported cases of methylprednisolone-induced liver injury occurred mostly after pulse therapy; that is, short-course intravenous administration of high-dose methylprednisolone, 10 probably due to an immune rebound phenomenon after rapid and strong immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

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Long‐term outcomes of drug‐induced autoimmune‐like hepatitis after pulse steroid therapy

Ueno

Tanaka

Kayahara

et al. 2023

Hepatology Research

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AimPulse steroid therapy occasionally causes drug‐induced autoimmune‐like hepatitis (DI‐ALH), but the long‐term outcome of treated patients is not well known. In this study, we investigated the long‐term outcomes of DI‐ALH due to pulse steroid therapy.MethodsWe retrospectively reviewed the medical records of 405 patients treated with pulse high‐dose methylprednisolone in Kurashiki Central Hospital. The frequency and clinicopathological characteristics of acute liver injury that occurred within 3 months after the therapy were analyzed. The diagnosis of DI‐ALH was made according to the revised international autoimmune hepatitis group criteria.ResultsAmong the 405 patients treated with methylprednisolone, 61 (15.1%) had acute liver injury after the pulse steroid therapy, and DI‐ALH was diagnosed in five patients (1.2%). Absence of oral prednisolone tapering after the pulse steroid therapy was a significant risk factor for the subsequent development of DI‐ALH (odds ratio 11.9; p = 0.017). One patient was treated with 3 days of intravenous methylprednisolone followed by oral prednisolone. Two patients were treated with glycyrrhizin followed by oral prednisolone due to ineffectiveness of glycyrrhizin. Remission was achieved with glycyrrhizin alone, and spontaneous remission without drug therapy occurred in one patient each. During the median follow‐up period of 34 months, no relapse was evident in all the patients without maintenance therapy.ConclusionsPulse steroid therapy can cause DI‐ALH, especially when subsequent prednisolone is not tapered. Prednisolone is effective for DI‐ALH due to pulse steroid therapy, and can be safely withdrawn once remission is achieved.

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Acute onset nitrofurantoin‐induced autoimmune hepatitis after urinary tract infection treatment

Chaudhary,

Khan,

Sohail

et al. 2024

Clinical Case Reports

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Key Clinical MessageThis case signifies the importance of recognizing DIAIH within the context of antibiotic therapy, especially in older adults and even shortly after common drug exposures for treating UTI.AbstractVarious drugs can induce immune‐mediated liver damage and in rare instances may lead to autoimmune hepatitis. Here we report an 84‐year‐old woman who developed autoimmune hepatitis less than 3 weeks after treatment for urinary tract infection with the antibiotic nitrofurantoin. She presented with jaundice, right upper quadrant abdominal pain, nausea, and vomiting. In the absence of a history of an autoimmune disorder or elevated liver enzymes in the past; elevated liver enzymes after a short course of Nitrofurantoin and the presence of smooth muscle antibodies strongly suggested autoimmune hepatitis, which was confirmed through biopsy sample analysis. The patient scored 7 points on the Naranjo adverse reaction probability scale. The patient's rapid recovery within 1 month of prednisone therapy supports the association of liver damage with nitrofurantoin use.

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

Cited by 56 publications

References 85 publications

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries

Long‐term outcomes of drug‐induced autoimmune‐like hepatitis after pulse steroid therapy

Acute onset nitrofurantoin‐induced autoimmune hepatitis after urinary tract infection treatment

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