Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis

Foureau, David M.; Walling, Tracy L.; Maddukuri, Vinaya C.; Anderson, William E.; Culbreath, Katherine; Kleiner, David E.; Ahrens, Will; Jacobs, Carl; Watkins, Paul B.; Fontana, Robert J.; Chalasani, Naga; Talwalkar, Jayant A.; Lee, William M.; Stolz, Andrew; Serrano, José; Bonkovsky, Herbert L.

doi:10.1111/cei.12558

Cited by 89 publications

(81 citation statements)

References 28 publications

(29 reference statements)

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“…The prominent histological features indicated above are also present in many other acute or chronic liver diseases 60 63 74 75. However, when occurring in combination, they may favour a diagnosis of AIH.…”

Section: Discussionmentioning

confidence: 92%

Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

et al. 2017

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The acute presentation of AIH represents the entire histological spectrum of acute hepatitis and chronic hepatitis with various activity grades and fibrosis stages that clinically correspond to acute-onset AIH and acute exacerbation of classic AIH, respectively. Although there are no pathognomonic features for the pathological diagnosis, the prominent presence of lobular and perivenular necroinflammatory activity, pigmented macrophages and cobblestone appearance of hepatocytes in addition to the classic AIH features, such as plasma cell infiltration and emperipolesis, are useful for the pathological diagnosis of the acute presentation of AIH.

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Section: Discussionmentioning

confidence: 92%

Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

et al. 2017

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“…In recent work from DILIN, we have shown that AC and other agents associated with immuno-allergic injury cause hepatitis with infiltration of portal triads by many T cells, most of which are CD8+ cytotoxic T cells [19]. These and other findings suggest that the pathogenesis of the liver injury is primarily an immune-mediated attack on cholangiocytes or perhaps on the apical pole of hepatocytes.…”

Section: Discussionmentioning

confidence: 94%

Amoxicillin–Clavulanate-Induced Liver Injury

et al. 2016

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Background and Aims Amoxicillin–clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. Methods Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. Results One hundred and seventeen subjects with AC-DILI were identified from the cohort (n = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents (n = 479). Those with AC-DILI were older (60 vs. 48 years, P < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. Conclusion AC-DILI causes a moderately severe, mixed hepatocellular–cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

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“…Similarly, studies of lymphocyte subsets in liver tissue samples have demonstrated that DILI subjects are less likely to have Natural killer cells, CD4+ T-Helper, and B-cells compared to patients with acute viral hepatitis (61). The predominance of CD8 + cytotoxic T-cells in the livers of idiosyncratic DILI patients is consistent with the hypothesis that the intrahepatic generation of neo-antigens from the drug or its metabolite may lead to the recruitment and activation of T-lymphocytes that can initiate or perpetuate the liver injury (62).…”

Section: Inferences Of Dili Pathogenesis From Liver Histologymentioning

confidence: 99%

Pathogenesis of Idiosyncratic Drug-Induced Liver Injury and Clinical Perspectives

2014

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Idiosyncratic drug-induced liver injury (DILI) is a rare disease that develops independently of drug dose, or route or duration, of administration. Furthermore, idiosyncratic DILI is not a single disease entity, but rather a spectrum of rare diseases with varying clinical, histologic, and laboratory features. The pathogenesis of DILI is not fully understood. Standardization of the DILI nomenclature and methods to assess causality, along with the information provided by the LiverTox website, will harmonize and accelerate DILI research. Studies of new serum biomarkers such as glutamate dehydrogenase, high-mobility group box-1 protein, and microRNA-122 could provide information for use in diagnosis and prognosis, and provide important insights into mechanisms of DILI pathogenesis. Single nucleotide polymorphisms in the HLA region have been associated idiosyncratic hepatotoxicity attributed to flucloxacillin, ximelagatran, lapatanib, and amoxicillin- clavulanate. However, genome-wide association studies of pooled cases have not associated any genetic factors with idiosyncratic DILI. Whole-genome and whole-exome sequencing analyses are underway to study DILI cases attributed to a single medication. Serum proteomic, transcriptome, and metabolome, along with intestinal microbiome, analyses will increase our understanding of the mechanisms of this disorder. Further improvements to in vitro and in vivo test systems should advance our understanding of the causes, risk factors, and mechanisms of idiosyncratic DILI.

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Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis

Cited by 89 publications

References 28 publications

Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients

Amoxicillin–Clavulanate-Induced Liver Injury

Pathogenesis of Idiosyncratic Drug-Induced Liver Injury and Clinical Perspectives

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