eMedicine Specialties > Gastroenterology > Liver

Hepatitis E: Differential Diagnoses & Workup

Author: Jonathan M Schwartz, MD, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Sciences University
Coauthor(s): Kenneth Ingram, PAC, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University; Kenneth D Flora, MD, Adjunct Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University; Consulting Staff, Department of Gastroenterology, The Oregon Clinic
Contributor Information and Disclosures

Updated: Nov 11, 2008

Differential Diagnoses

Hepatitis A
Isoniazid Hepatotoxicity
Hepatitis B
Recurrent Pyogenic Cholangitis
Hepatitis C
Hepatitis D
Hepatitis, Viral

Workup

Laboratory Studies

  • A study involving human volunteers and nonhuman primates determined the typical serological course of HEV.
    • Two humans ingested the virus and demonstrated liver enzyme elevations within 4-6 weeks that persisted for as long as 90 days.
    • The virus was detectable in their stool approximately 1 month after ingestion and remained for another 2-4 weeks.
  • Western blot and enzyme immunoassays detect anti-HEV antibodies by using the antigenic domains from ORF-2 and ORF-3. Assays of ORF-2 are more sensitive.
    • Testing to detect anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG) differentiates acute and chronic infection.
    • The IgM titer falls rapidly after infection, becoming virtually undetectable within 6 months.
    • Anti-HEV IgG persists for longer than 6 months, although its actual duration of positivity is unknown.
    • IgG anti-HEV appears to afford protection against reinfection.
    • HEV IgG AB testing is available through the Centers for Disease Control and Prevention (CDC).
  • Serum, liver, and stool samples can be tested for HEV RNA with a polymerase chain reaction assay. These tests are not available commercially.
  • Aminotransferase levels (AST, ALT) are elevated several days before the onset of symptoms but generally return to normal within 1-2 months after the peak severity of the disease has passed.
    • Elevations can be associated with underlying liver disease or exposure to other hepatotoxins.
    • Whether the magnitude of elevation correlates with the histological severity is not clear.
  • Serum bilirubin elevations occur in both the total and direct fractions.
    • Hemolysis is unusual.
    • In most cases, bilirubin levels take longer to return to normal than aminotransferase levels.
  • Many patients develop a mild leukocytosis.
    • If associated with fever, bacteremia should be suspected.
    • More commonly, WBC counts are decreased. Differential counts may show atypical cells and lymphocytosis.

Imaging Studies

  • Abdominal radiographs have no role in evaluating acute viral hepatitis unless the physical examination suggests a perforated viscus.
  • Abdominal ultrasonography is recommended.
    • It helps rule out biliary obstruction in cases with significant nausea, vomiting, or fever.
    • It can demonstrate the presence of an enlarged liver; echo texture is heterogeneous and coarsened.
    • It can demonstrate splenomegaly, if present.

Other Tests

  • Perform blood cultures if the patient is febrile and hypotensive with an elevated WBC count.
  • Determine serum acetaminophen levels if overdose is suspected.

Procedures

  • Liver biopsy usually is not necessary.
  • Typical pathological findings are included in Histological Findings.

Histologic Findings

The pathology picture is cholestatic, with stasis of canalicular bile and marked proliferation of intralobular bile ductules. The cholestasis is most notable within the centroacinar regions. Parenchymal changes are less severe and include swollen hepatocytes, foam cells, and acidophil bodies. Inflammatory infiltrate of mononuclear cells is present, resulting in expanded portal areas and possible piecemeal necrosis.

More on Hepatitis E

Overview: Hepatitis E
Differential Diagnoses & Workup: Hepatitis E
Treatment & Medication: Hepatitis E
Follow-up: Hepatitis E
References
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References

  1. Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. Feb 21 2008;358(8):811-7. [Medline].

  2. Shrestha MP, Scott RM, Joshi DM, et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. Mar 1 2007;356(9):895-903. [Medline].

  3. Favorov MO, Fields HA, Purdy MA, et al. Serologic identification of hepatitis E virus infections in epidemic and endemic settings. J Med Virol. Apr 1992;36(4):246-50. [Medline].

  4. Fields HA, Favorov MO, Margolis HS. Hepatitis E virus: a review. J Clin Immunoassay. 1993;16:215-23.

  5. Ghabrah TM, Tsarev S, Yarbough PO, et al. Comparison of tests for antibody to hepatitis E virus. J Med Virol. Jun 1998;55(2):134-7. [Medline].

  6. Harrison TJ. Hepatitis E virus -- an update. Liver. Jun 1999;19(3):171-6. [Medline].

  7. Mast EE, Krawczynski K. Hepatitis E: an overview. Annu Rev Med. 1996;47:257-66. [Medline].

  8. Purdy MA, Krawczynski K. Hepatitis E. Gastroenterol Clin North Am. Sep 1994;23(3):537-46. [Medline].

  9. Skidmore SJ. Factors in spread of hepatitis E. Lancet. Sep 25 1999;354(9184):1049-50. [Medline].

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Further Reading

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Keywords

hepatitis E, hepatitis E virus, HEV, Caliciviridae family, anti-HEV antibodies

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Contributor Information and Disclosures

Author

Jonathan M Schwartz, MD, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Sciences University
Jonathan M Schwartz, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and American Hepato-Pancreato-Biliary Association
Disclosure: Nothing to disclose.

Coauthor(s)

Kenneth Ingram, PAC, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University
Disclosure: Nothing to disclose.

Kenneth D Flora, MD, Adjunct Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University; Consulting Staff, Department of Gastroenterology, The Oregon Clinic
Kenneth D Flora, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, and American Gastroenterological Association
Disclosure: Nothing to disclose.

Medical Editor

David Eric Bernstein, MD, Chief, Section of Hepatology, North Shore University Hospital, Director, Associate Professor, Department of Internal Medicine, Division of Hepatology, New York University School of Medicine
David Eric Bernstein, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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