Hepatitis E Workup

  • Author: Prospere Remy, MD; Chief Editor: BS Anand, MD  more...
Updated: Jul 14, 2016

Imaging Studies

Abdominal radiography has no role in evaluating acute viral hepatitis unless clinically indicated.

Abdominal ultrasonography is recommended. It helps to rule out extra hepatic causes of biliary obstruction, which may coexist with the presence of hepatitis E virus (HEV) infection. It may also demonstrate the presence of an enlarged liver and the presence of advanced liver disease, such as splenomegaly, ascites, or hepatofugal flow of the portal venous system.


Basic Laboratory Studies

Elevation in the serum aminotransferase levels is the laboratory hallmark of acute viral hepatitis. Serum alanine aminotransferase (ALT) level is usually higher than the serum aspartate aminotransferase (AST) level. The levels of aminotransferases may range from 10 times the upper limit of normal to more than 20 times the upper limit of normal. 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. The serum alkaline phosphatase level may be normal or slightly increased (< 3 times upper limit of normal). Serum bilirubin level usually ranges from 5-20 mg/dL, depending on the extent of hepatocyte damage. The patient may develop leukopenia with neutropenia or lymphopenia. Prolonged prothrombin time, decreased serum albumin, and very high bilirubin are signs of impending hepatic failure requiring referral to a liver transplantation center.

Perform blood cultures if the patient is febrile and hypotensive with an elevated white blood cell (WBC) count.

Obtain serum acetaminophen levels if overdose is suspected.


Serologic Testing

Acute hepatitis E virus (HEV) infection is diagnosed in immunocompetent individuals based on the detection of anti-HEV immunoglobulin M (IgM). The anti-HEV IgM usually starts rising 4 weeks after infection and remains detectable for 2 months after the onset of illness.[32]

The test for the presence of anti-HEV IgM is performed by detection of specific IgM antibodies directed against a range of recombinant viral antigens by enzyme immunoassay or rapid immunochromatography kits.[33] However, comparative studies show that these tests differ substantially in their accuracy.[34, 35] Therefore, users should ensure that a test is used that has been validated in their population.[32] Confirmation of acute cases detected in this way is either by molecular techniques, detecting rising reactivity in a specific immunoglobulin G (IgG) assay, or positivity in immunoblot IgM assays.[36]

A study comparing two rapid immunochromatography kits with three commercial anti-HEV ELISA assays and one real-time polymerase chain reaction (RT-PCR) assay showed that the sensitivity of Wantai Rapid and Assure Rapid tests was 96.1% and 92.6%, respectively; the specificity of both rapid tests was 100%.[37] Therefore, anti-HEV IgM rapid assays may be used as a first-line test in primary healthcare settings, particularly for patients with chronic liver disease or pregnant women who urgently need an antiviral treatment.[37]

After exposure, viral RNA can be detected just before the onset of clinical symptoms in both blood and stool samples. HEV RNA does not persist for long, becoming undetectable in blood about 3 weeks after the onset of symptoms. The virus is shed in stool for a further 2 weeks.[38, 39] The window of detectable RNA is, therefore, narrow, and if patients present late in their illness, an undetectable HEV RNA result does not exclude recent infection.[32] However, immunocompromised individuals (such as patients with autoimmune hepatitis who receive immunosuppressant agents) should always be tested for HEV RNA if there is suspicion that they are infected because seroconversion could be delayed in these patients.[40]

Detection of elevated reactivity in a specific IgG assay indicates the presence of acute hepatitis E. However, the determination of immunity or previous exposure to HEV by detection of IgG antibodies is problematic. Available enzyme immunoassays use different antigens and vary in their effectiveness.[41, 42] The detection cutoff for some commercial assays may be close to the protective antibody concentration[43, 44] ; therefore, they might not reliably detect protective concentrations of anti-HEV IgG.


Tissue Analysis and Histologic Findings

Liver biopsy usually is not necessary.

Biopsies from acute fulminant hepatitis E show varying degrees of hepatocyte necrosis and mixed portal and lobular inflammation, accompanied by bile ductular proliferation, lymphocytic cholangitis, Kupffer cell prominence, cholestasis, apoptotic bodies, pseudo-rosette formation, steatosis, and plasma cells in the portal tracts.[45]

Compared with the epidemic type of acute hepatitis E virus (HEV) infection, liver biopsy from patients with autochthonous HEV infection show preferential localization of polymorphs at the portal-hepatocyte interface, and that of lymphocytes and plasma cells centrally in portal tracts.[46] Hepatocyte necrosis is reported to be located in the perivenular acinar zone 3 in patients with autochthonous HEV infection. The histology of epidemic cases of HEV infection show less intense portal and acinar inflammation, no cholangiolitis, and no geographical distribution of the portal inflammatory infiltrate. Significant steatosis, megamitochondria, and Mallory bodies are not present in autochthonous cases.

Contributor Information and Disclosures

Prospere Remy, MD Assistant Professor of Medicine, Albert Einstein College of Medicine; Attending Physician, Department of Internal Medicine, Bronx-Lebanon Hospital Center

Prospere Remy, MD is a member of the following medical societies: American College of Physicians, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.


David Widjaja, MD Gastroenterological Consultant, Medistra Hospital, Jakarta, Indonesia

David Widjaja, MD is a member of the following medical societies: American Society for Gastrointestinal Endoscopy, Indonesian Medical Association

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.


David Eric Bernstein, MD Director of Hepatology, North Shore University Hospital; Professor of Clinical Medicine, Albert Einstein College 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.

Kenneth D Flora, MD Adjunct Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University School of Medicine; 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.

Kenneth Ingram, PAC Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Science University School of Medicine

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Jonathan M Schwartz, MD Associate Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Sciences University School of Medicine

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.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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