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Diagnostic Testing for Acute Hepatitis

Educational Objective
To understand how to interpret the results of diagnostic tests and apply them clinically.
1 Credit CME

An 18-year-old man from India who emigrated to the United States 4 weeks earlier presented with fever, malaise, and anorexia for 4 days. The patient reported ingesting no prescription, over-the-counter, or herbal medications; alcohol; or illicit drugs. On physical examination, he was afebrile and had scleral icterus and a palpable liver edge. Initial laboratory test results showed a white blood cell count of 3.9 × 103/μL and elevations in total bilirubin (5.6 mg/dL), direct bilirubin (3.6 mg/dL), alkaline phosphatase (240 U/L), aspartate aminotransferase (3322 U/L), and alanine aminotransferase (6114 U/L). His platelet count was 126 000 × 109/μL and prothrombin time was 17 seconds. Testing for viral hepatitis was performed (Table). Antinuclear, antismooth muscle, and liver/kidney microsomal antibodies were not detected. Immunoglobulin G (1294 mg/dL) and ceruloplasmin (22 mg/dL) levels were normal. Right upper quadrant ultrasonography demonstrated a liver span of 16 cm, a common bile duct measuring 0.3 cm, and patent hepatic vasculature.

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B. Anti–hepatitis E virus (HEV) IgM testing

Annually, an estimated 20 million cases of hepatitis E virus (HEV) occur worldwide.1 HEV is endemic in resource-limited countries and is typically caused by transmission of genotypes 1 or 2 via fecal-contaminated water.1 HEV accounts for many acute hepatitis cases in India.2 However, in resource-rich countries, HEV is rare; typically caused by genotypes 3 and 4; and results from ingestion of undercooked pig, boar, or deer meat.1 The annual estimated incidence in the United States from 1998 to 1994 was 0.7% per 1000 persons.3 HEV is typically self-limited and asymptomatic, but has a mortality rate of up to 20% in pregnant women and can lead to chronic infections in immunosuppressed individuals (eg, solid organ or bone marrow transplant recipients, individuals with HIV).1,3

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Article Information

Corresponding Author: Adam E. Mikolajczyk, MD, Division of Gastroenterology and Hepatology, University of Illinois at Chicago, 840 S Wood St, 1034 CSB, MC 716, Chicago, IL 60612 (amikolaj@uic.edu).

Published Online: February 13, 2020. doi:10.1001/jama.2019.21895

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for providing permission to share his information.

References
1.
Hovartis  T, Schukze zur Wiesch  J, Lutehetmann  M, Lohse  AW, Pischke  S.  The clinical perspective on hepatitis E.  Viruses. 2019;11(7):617. doi:10.3390/v11070617PubMedGoogle ScholarCrossref
2.
Aggarwal  R, Gandhi  S.  The Global Prevalence of Hepatitis E Virus Infection and Susceptibility: a Systematic Review. Geneva, Switzerland: World Health Organization; 2010.
3.
Kamar  N, Dalton  HR, Abravanel  F, Izopet  J.  Hepatitis E virus infection.  Clin Microbiol Rev. 2014;27(1):116-138. doi:10.1128/CMR.00057-13PubMedGoogle ScholarCrossref
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Aggarwal  R.  Diagnosis of hepatitis E.  Nat Rev Gastroenterol Hepatol. 2013;10(1):24-33. doi:10.1038/nrgastro.2012.187PubMedGoogle ScholarCrossref
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Drobeniuc  J, Meng  J, Reuter  G,  et al.  Serologic assays specific to immunoglobulin M antibodies against hepatitis E virus: pangenotypic evaluation of performances.  Clin Infect Dis. 2010;51(3):e24-e27. doi:10.1086/654801PubMedGoogle ScholarCrossref
6.
Wu  WC, Su  CW, Yang  JY, Lin  SF, Chen  JY, Wu  JC.  Application of serologic assays for diagnosing acute hepatitis E in national surveillance of a nonendemic area.  J Med Virol. 2014;86(4):720-728. doi:10.1002/jmv.23785PubMedGoogle ScholarCrossref
7.
Huang  S, Zhang  X, Jiang  H,  et al.  Profile of acute infectious markers in sporadic hepatitis E.  PLoS One. 2010;5(10):e13560. doi:10.1371/journal.pone.0013560PubMedGoogle Scholar
8.
McGivern  DR, Lin  HS, Wang  J,  et al.  Prevalence and impact of hepatitis E virus infection among persons with chronic hepatitis B living in the US and Canada.  Open Forum Infect Dis. 2019;6(5):ofz175. doi:10.1093/ofid/ofz175PubMedGoogle Scholar
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Singh  NJ, Kumari  A, Catanzaro  R, Marotta  F.  Prevalence of hepatitis E and hepatitis B dual infection in North India (Delhi).  Acta Biomed. 2012;83(3):197-201.PubMedGoogle Scholar
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European Association for the Study of the Liver.  EASL Clinical Practice Guidelines on hepatitis E virus infection.  J Hepatol. 2018;68(6):1256-1271. doi:10.1016/j.jhep.2018.03.005PubMedGoogle ScholarCrossref
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