Natural history and outcomes in drug‐induced autoimmune hepatitis

Yeong, T.; Lim, Kok Haw Jonathan; Goubet, Stephanie; Parnell, Nick; Verma, Sumita

doi:10.1111/hepr.12532

Cited by 29 publications

(26 citation statements)

References 33 publications

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“…In DIAIH, successful discontinuation of immunosuppressive therapy has been reported, without relapses 44. Contrarily, the rate of relapse has been reported by others to be similar for both idiopathic AIH and DIAIH 48. It must be noted that, the latter report included a significant number of statin-induced DIAIH cases, while patients with nitrofurantoin-induced DIAIH are less likely to relapse than other DIAIH patients after discontinuation of immunosuppression.…”

Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 78%

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Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

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Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by high levels of aminotransferases and autoantibodies, hypergammaglobulinemia, and interface hepatitis. AIH affects all races and all ages worldwide, regardless of sex, although a preponderance of females is a constant finding. The etiology of AIH has not been completely elucidated, but immunogenetic background and environmental parameters may contribute to its development. The most important genetic factor is human leukocyte antigens (HLAs), especially HLA-DR, whereas the role of environmental factors is not completely understood. Immunologically, disruption of the immune tolerance to autologous liver antigens may be a trigger of AIH. The diagnosis of classical AIH is fairly easy, though not without pitfalls. In contrast, the diagnosis of atypical AIH poses great challenges. There is confusion as to the definition of the disease entity and its boundaries in the diagnosis of overlap syndrome, drug-induced autoimmune hepatitis, and AIH with concomitant nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C. Centrilobular zonal necrosis is now included in the histological spectrum of AIH. However, the definition and the significance of AIH presenting with centrilobular zonal necrosis have not been examined extensively. In ~20% of AIH patients who are treated for the first time with standard therapy, remission is not achieved. The development of more effective and better tolerated novel therapies is an urgent need. In this review, we discuss the current challenges and the future prospects in relation to the diagnosis and treatment of AIH, which have been attracting considerable recent attention.

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Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 78%

“…However, the clinical and histopathological features of DIAIH are sometimes quite similar to those of AIH 47. Response to corticosteroids is similar for both DIAIH and AIH 48. There is disagreement as to whether recurrence after discontinuation of corticosteroids occurs in DIAIH.…”

Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 99%

Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

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“…The former may only need a short course of steroids, whereas the latter, which is often indistinguishable from idiopathic AIH, often requires prolonged courses of steroids and/or additional immunosuppression. [46][47][48][49] As already stated, differentiating DILI from 'drug-induced' AIH can often be difficult and in such situations, after careful assessment of risks and benefits, a trial of corticosteroids may be warranted. Although ursodeoxycholic acid is often used in cholestatic DILI, its use remains non-evidence based.…”

Section: Management Of Dilimentioning

confidence: 99%

Drug-induced liver injury

2016

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Drug-induced liver injury (DILI) remains the most common cause of acute liver failure (ALF) in the western world. Excluding paracetamol overdose, nearly all DILI encountered in the clinical setting is idiosyncratic in nature because affected individuals represent only a small proportion of those treated with such drugs. In many cases, the mechanism for idiosyncrasy is immune-mediation and is often identifi ed by genetic risk determined by human leukocyte antigen variants. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests. Antibiotics are the class of drugs most frequently associated with idiosyncratic DILI, although recent studies indicate that herbal and dietary supplements are an increasingly recognised cause. It is imperative that upon development of DILI the culprit drug be discontinued, especially in the presence of elevated transaminases (aspartate aminotransferase/alanine aminotransferase ratio ≥5 times the upper limit of normal) and/or jaundice. Risk factors for the development ALF include hepatocellular DILI and female gender, the treatment being supportive with some benefi t of N-acetylcysteine in the early stages. In view of the poor transplant-free survival in idiosyncratic DILI, early consideration for liver transplant is mandatory. KEYWORDS : Autoimmune hepatitis , cholestasis , drug-induced acute liver failure , herbal and dietary supplements , hepatocellular DILI , hepatotoxicity IntroductionAt a regulatory level, drug-induced liver injury (DILI) is the commonest reason for withdrawing drugs from the market and/or issuing warnings and modification of use.1 DILI is classified as either predictable or unpredictable (idiosyncratic). 2The former tends to be dose-related, has a short latency (days), is due to direct toxicity of the drug or its metabolite, and is ABSTRACT Drug-induced liver injuryreproducible in animal models (eg paracetamol overdose). 3The vast majority of DILI, however, is idiosyncratic or unpredictable -it is unexpected based on the pharmacological actions of the drug and in most cases routine animal toxicology fails to identify the risk of subsequent clinical toxicity. 4 This review shall largely focus on idiosyncratic DILI .

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“…Equally important, this drug is known for severe and at times irreversible adverse effects, the most feared among them being pulmonary fibrosis and hepatitis [4,5]. Yet the actual incidence of these events remains opaque: almost all descriptions of severe toxicity are single case reports and so possibly result from, and drive, a significant publication bias.…”

Section: Introductionmentioning

confidence: 99%