Hepatitis E Workup
- Author: Sandeep Mukherjee, MB, BCh, MPH, FRCPC; Chief Editor: Julian Katz, MD more...
Imaging Studies
Abdominal radiography has 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 also 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.
Serum, liver, and stool samples can be tested for HEV RNA with a polymerase chain reaction assay. These tests are not available commercially.
Basic Laboratory Studies
Many patients develop a mild leukocytosis. If associated with fever, bacteremia should be suspected. More commonly, white blood cell (WBC) counts are decreased. Differential counts may show atypical cells and lymphocytosis.
Serum aminotransferase (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) levels are elevated several days before the onset of symptoms. They increase rapidly and peak within 4-6 weeks of onset 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 histologic 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.
Serologic Testing
A study involving human volunteers and nonhuman primates determined the typical serologic course of hepatitis E virus (HEV) infection. 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. Viral excretion in stool commonly persists for at least 14 days from onset.
Western blot and enzyme immunoassays detect anti-HEV antibodies by using the antigenic domains from ORF-2[10] and ORF-3. Assays of ORF-2 are more sensitive.[11]
Testing to detect anti-HEV immunoglobulin M (IgM) and immunoglobulin G (IgG) differentiates acute infection from 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. Anti-HEV IgG appears to afford protection against reinfection. Testing for this immunoglobulin is available through the Centers for Disease Control and Prevention (CDC).
Tissue Analysis and Histologic Findings
Liver biopsy usually is not necessary.
The typical pathologic 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.
Mast EE, Krawczynski K. Hepatitis E: an overview. Annu Rev Med. 1996;47:257-66. [Medline].
Purdy MA, Krawczynski K. Hepatitis E. Gastroenterol Clin North Am. Sep 1994;23(3):537-46. [Medline].
Fields HA, Favorov MO, Margolis HS. Hepatitis E virus: a review. J Clin Immunoassay. 1993;16:215-23.
Harrison TJ. Hepatitis E virus -- an update. Liver. Jun 1999;19(3):171-6. [Medline].
Skidmore SJ. Factors in spread of hepatitis E. Lancet. Sep 25 1999;354(9184):1049-50. [Medline].
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].
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].
Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. Sep 11 2010;376(9744):895-902. [Medline].
Legrand-Abravanel F, Kamar N, Sandres-Saune K, et al. Hepatitis E virus infection without reactivation in solid-organ transplant recipients, France. Emerg Infect Dis. Jan 2011;17(1):30-7. [Medline].
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].
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].

