Dataset Information

Histopathological Features of Drug-Induced Liver Injury Secondary to Osimertinib.

ABSTRACT: In the past few years, a better understanding of the genomic alterations in lung cancer has facilitated a targeted therapy. Lung adenocarcinomas with epidermal growth factor receptor mutations have a good response to tyrosine kinase inhibitors (TKIs). Osimertinib is a third-generation TKI approved by the Food and Drug Administration (FDA). Drug-induced liver injury is a well-known adverse effect of TKIs as a group and reported to show an autoimmune hepatitis-like picture. However, little is known about the histopathologic changes with osimertinib. We present a case of drug-induced liver injury secondary to osimertinib and discuss the histopathologic findings.

SUBMITTER: Gonzalez I

PROVIDER: S-EPMC6657992 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Histopathological Features of Drug-Induced Liver Injury Secondary to Osimertinib.

González Iván I Chatterjee Deyali D

ACG case reports journal 20190225 2

In the past few years, a better understanding of the genomic alterations in lung cancer has facilitated a targeted therapy. Lung adenocarcinomas with epidermal growth factor receptor mutations have a good response to tyrosine kinase inhibitors (TKIs). Osimertinib is a third-generation TKI approved by the Food and Drug Administration (FDA). Drug-induced liver injury is a well-known adverse effect of TKIs as a group and reported to show an autoimmune hepatitis-like picture. However, little is know ...[more]

PMID: 31616716

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Project description:Background & aimsDrug-induced liver injury (DILI) has features similar to those of other liver diseases including autoimmune hepatitis (AIH). We aimed to characterize the clinical and autoimmune features of liver injury caused by nitrofurantoin, minocycline, methyldopa, or hydralazine.MethodsWe analyzed data from 88 cases of DILI attributed to nitrofurantoin, minocycline, methyldopa, or hydralazine included in the Drug-Induced Liver Injury Network prospective study from 2004 through 2014. Sera were collected from patients at baseline and follow-up examination and tested for levels of immunoglobulin G (IgG), antibodies to nuclear antigen (ANA), smooth muscle (SMA), and soluble liver antigen (SLA). An autoimmune score was derived on the basis of increases in levels of IgG, ANA, SMA, and SLA (assigned values of 0, 1+, or 2+). AIH-associated HLA-DRB1*03:01 and HLA-DRB1*04:01 allele frequencies were compared with those of the general population (controls).ResultsOf the 88 cases, 80 were women (91%), 74% had hepatocellular injury, and 25% had severe injury. At the onset of DILI, 39% of cases had increased levels of IgG, 72% had increased levels of ANA, 60% had increased levels of SMA, and none had increases in SLA. A phenotype of autoimmunity (autoimmune score ≥2) was observed in 82% of cases attributed to nitrofurantoin and 73% of cases attributed to minocycline (73%) but only 55% of cases attributed to methyldopa and 43% of cases attributed to hydralazine (P = .16 for nitrofurantoin and minocycline vs methyldopa and hydralazine). We observed a decrease in numbers of serum samples positive for ANA (P = .01) or SMA (P < .001) and in autoimmune scores (P < .001) between DILI onset and follow-up. Similar percentages of patients with DILI had HLA-DRB1*03:01 (15%) and HLA-DRB1*04:01 (9%) as controls (12% and 9%, respectively).ConclusionsIn analysis of data from the DILIN prospective study, we found that most cases of DILI attributed to nitrofurantoin or minocycline and about half of cases that were due to methyldopa and hydralazine have a phenotype of autoimmunity similar to AIH. These features decrease with recovery of the injury and are not associated with the typical HLA alleles found in patients with idiopathic AIH.

Project description:Background & aimsThe Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study.MethodsIn an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI.ResultsAmong 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P < .001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared with those without liver disease (6.7% vs 1.5%; P = .006). Forty-one cases with latency ≤7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died.ConclusionsMortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality.

Dataset Information

Histopathological Features of Drug-Induced Liver Injury Secondary to Osimertinib.

Publications

Histopathological Features of Drug-Induced Liver Injury Secondary to Osimertinib.

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