Features of Autoimmune Hepatitis in Patients With Drug-induced Liver Injury

Boer, Ynto S. de; Kosinski, Andrzej S.; Urban, Thomas; Zhao, Zhen; Long, Norton E.; Chalasani, Naga; Kleiner, David E.; Hoofnagle, Jay H.

doi:10.1016/j.cgh.2016.05.043

Cited by 158 publications

(197 citation statements)

References 32 publications

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“…This abnormality spontaneously improves with recovery from liver damage and is not associated with HLA-DR3 or DR4 49. Therefore, the immunopathological settings of DIAIH are quite different from those of idiopathic AIH.…”

Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 93%

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: 93%

Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

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“…It should be noted that, in the context of DILI, a patient presenting with “acute hepatitis” may show a chronic hepatitis pattern of inflammation. For example, both minocycline 20,21 and the statins 22,23 may show portal predominant inflammation similar to chronic viral hepatitis, yet present with an acute onset of aminotransferase elevations and jaundice. Other features, including microgranulomas and mild to moderate steatosis may be present without affecting the categorization as either acute or chronic hepatitis.…”

Section: Characteristic Patterns Of Injurymentioning

confidence: 99%

“…In fact, even in the absence of suspected DILI, a liver biopsy is often performed to confirm the clinical suspicion of AIH. Drug-induced AIH (DIAIH) has been reported in association with a number of drugs and also has been the subject of larger clinical studies 20,63 . Drugs that have been associated with an AIH-like syndrome include nitrofurantoin, minocycline, hydralazine, methyldopa and the statins.…”

Section: Difficult Differentialsmentioning

confidence: 99%

“…Both groups responded similarly to corticosteroid therapy, although the DIAIH patients could be weaned from steroids more successfully than the AIH patients. A study from the DILIN analyzed cases of DILI from patients taking drugs typically associated with DIAIH, including nitrofurantoin, minocycline, hydralazine and methyldopa 20 . Clinical features of AIH were found in most of the cases of nitrofurantoin and minocycline and about half of the cases of hydralazine and methyldopa injury.…”

Section: Difficult Differentialsmentioning

confidence: 99%

“…Some drugs however, may cause injury even after many months to years of exposure. In particular, the agents associated with autoimmune hepatitis-like reactions, such as nitrofurantoin, minocycline and the statins, fall into this category 20,22 . The injury may also not be recognized until weeks after the drug has been stopped.…”

Section: Final Analysis and Consultative Opinionmentioning

confidence: 99%

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Drug-induced Liver Injury

Kleiner

2017

Gastroenterology Clinics of North America

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Biopsies of suspected drug-induced liver injury pose a particular challenge to the pathologist that requires a careful and systematic approach. The initial evaluation should be as objective as possible, setting aside consideration of the medical history. Histological changes are catalogued with attention to the hepatic architecture, noting the intensity and character of inflammation, cholestasis, apoptosis and necrosis. Bile ducts, portal vessels, hepatocytes, sinusoidal lining cells and vessels are each examined for evidence of injury. The assessment culminates with the determination of the overall pattern of injury. Armed with this information, the pathologist correlates the findings with the patient’s medical and pharmacological history. Drug induced liver injury is always a diagnosis of exclusion, so the emphasis should be on identification of potential competing causes of injury. If alternate etiologies of injury can be eliminated, the histological injury pattern can be compared to the known patterns of injury of suspect medications. The histological changes can also shed light on the potential mechanism of injury in situations where the suspect agents are new and do not yet have reports of hepatotoxicity. The pathological findings, the histological differential diagnosis and expert interpretation are part of a complete biopsy assessment and provide information that is of greatest value in patient management.

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