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Hepatitis e virus detection in liver tissue from patients with suspected drug-induced liver injury.

ABSTRACT: Hepatitis E virus (HEV) infection is increasingly recognized as a cause of acute hepatitis in the industrialized world. We aimed to determine the frequency of acute HEV infection in cases of suspected drug-induced liver injury (DILI), mainly a diagnosis of exclusion. To this aim, formalin-fixed paraffin-embedded (FFPE) liver tissues of all cases routinely processed in our institute during a 2?1/2?years period in which DILI was among the differential diagnoses (157 liver biopsies, 1 liver explant) were subjected to semi-nested RT-PCR for the detection of HEV RNA. Histopathology was re-evaluated on all cases tested positive. HEV RNA was detectable in 3 of 158 cases (2%) tested, comprising autochthonic as well as travel-related infections with genotypes 1, 3, and 4 each found once, respectively. Histopathologic findings comprised one case with subtotal hepatic necrosis and two cases of acute (cholestatic) hepatitis not distinguishable from acute hepatitis of other etiology. Thus, the overall frequency of acute HEV infection as determined by detection of HEV RNA in liver tissue is substantially increased in patients with suspected DILI compared to the healthy population, emphasizing the need to actively look for HEV infection in cases of suspected DILI. Molecular testing for HEV RNA in routinely processed FFPE liver tissues can be applied to cases with undetermined HEV status.

SUBMITTER: Chijioke O

PROVIDER: S-EPMC4378310 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Hepatitis e virus detection in liver tissue from patients with suspected drug-induced liver injury.

Chijioke Obinna O Bawohl Marion M Springer Erik E Weber Achim A

Frontiers in medicine 20150330

Hepatitis E virus (HEV) infection is increasingly recognized as a cause of acute hepatitis in the industrialized world. We aimed to determine the frequency of acute HEV infection in cases of suspected drug-induced liver injury (DILI), mainly a diagnosis of exclusion. To this aim, formalin-fixed paraffin-embedded (FFPE) liver tissues of all cases routinely processed in our institute during a 2 1/2 years period in which DILI was among the differential diagnoses (157 liver biopsies, 1 liver explant ...[more]

PMID: 25870858

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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.

Dataset Information

Hepatitis e virus detection in liver tissue from patients with suspected drug-induced liver injury.

Publications

Hepatitis e virus detection in liver tissue from patients with suspected drug-induced liver injury.

Similar Datasets

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