title: Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury.
abstract: OBJECTIVE
  The diagnosis of drug-induced liver injury relies on exclusion of other causes, including viral hepatitis A, B, and C. Hepatitis E virus (HEV) infection has been proposed as another cause of suspected drug-induced liver disease. We assessed the frequency of HEV infection among patients with drug-induced liver injury in the United States.
  
  
  METHODS
  The Drug-Induced Liver Injury Network (DILIN) is a prospective study of patients with suspected drug-induced liver injury; clinical information and biological samples are collected to investigate pathogenesis and disease progression. We analyzed serum samples, collected from patients enrolled in DILIN, for immunoglobulin (Ig) G and IgM against HEV; selected samples were tested for HEV RNA.
  
  
  RESULTS
  Among 318 patients with suspected drug-induced liver injury, 50 (16%) tested positive for anti-HEV IgG and 9 (3%) for anti-HEV IgM. The samples that contained anti-HEV IgM (collected 2 to 24 weeks after onset of symptoms) included 4 that tested positive for HEV RNA genotype 3. Samples from the 6-month follow-up visit were available from 4 patients; they were negative for anti-HEV IgM, but levels of anti-HEV IgG increased with time. Patients who had anti-HEV IgM were mostly older men (89%; mean age, 67 years), and 2 were human immunodeficiency virus positive. Clinical reassessment of the 9 patients with anti-HEV IgM indicated that acute hepatitis E was the most likely diagnosis for 7 and might be the primary diagnosis for 2.
  
  
  CONCLUSIONS
  HEV infection contributes to a small but important proportion of cases of acute liver injury that are suspected to be drug induced. Serologic testing for HEV infection should be performed, particularly if clinical features are compatible with acute viral hepatitis.
authors.affiliation: Department of Transplantation, California Pacific Medical Center, San Francisco, California, USA. davernt@sutterhealth.org
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Davern
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Paul H
authors.initials: PH
authors.lastname: Hayashi
authors.forename: Petr
authors.initials: P
authors.lastname: Protiva
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Engle
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.forename: Suzanne U
authors.initials: SU
authors.lastname: Emerson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Jiezhun
authors.initials: J
authors.lastname: Gu
authors.forename: Jose
authors.initials: J
authors.lastname: Serrano
authors.forename: Jay H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000208:Acute Disease; D055371:Acute Lung Injury / Q000097:blood / Q000453:epidemiology* / Q000209:etiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D003937:Diagnosis, Differential; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology*; D016752:Hepatitis E virus / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011446:Prospective Studies; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
chemical_list: D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M