Hepatitis viruses A, B, and C cause 95% of viral hepatitis cases in the U.S. Less common hepatitis viruses include D, E, and G (HGV or GBV-C). Generally, patients meeting the indications for testing should be screened for hepatitis A, B, and C concurrently, unless a specific exposure is known.
Quick Answers for Clinicians
Diagnosis
Indications for Testing
- New onset of jaundice, anorexia, or dark urine
- Known or suspected exposure to hepatitis virus
Laboratory Testing
- Viral hepatitis information for health professionals (CDC)
- Screen for hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) infections concurrently unless specific exposure is known
- Panel testing includes HAV IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody
- Positive HAV antibodies indicate acute HAV
- Positive HBV antibodies and surface antigen indicate acute HBV or chronic hepatitis
- Repeat surface antigen testing and consider HBV DNA testing if nonacute presentation
- Positive HCV antibodies indicate acute HCV or chronic HCV
- High and low positives should be followed by RNA quantitative testing
- Hepatitis E virus (HEV) testing – if patient is from a high-risk area and hepatitis screening tests are negative
- Hepatitis delta virus (HDV) testing – if patient with known chronic hepatitis manifests acute hepatitis
- For further evaluation of hepatitis, refer to specific hepatitis algorithms in ARUP Consult
Differential Diagnosis
- Virus
- Cytomegalovirus
- Epstein-Barr virus
- Herpes simplex virus
- Varicella-zoster virus
- Hepatitis A, B, C, D, E, or G
- Toxin exposure
- Alcohol
- Tetrachloride
- Nonalcoholic steatohepatitis
- Drug-induced hepatitis
- Acetaminophen
- Antiseizure medications
- Isoniazid (Nydrazid)
- Oral contraceptives
- Rifampin (Rifadin)
- Sulfonamides
- Autoimmune disease
- Systemic lupus erythematosus
- Primary biliary cirrhosis
- Sclerosing cholangitis
- Autoimmune hepatitis
- Bacterial infection
- Sepsis
- Leptospira spp
- Coxiella burnetii (Q-fever)
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Treponema pallidum (secondary syphilis)
- Rickettsia typhi (typhus fever)
- Granulomatous disease
- Mycobacterium tuberculosis
- Sarcoidosis
- Hereditary disease/disorder
- Wilson disease
- Hemochromatosis
- Alpha-1-antitrypsin deficiency
- Ischemia
- Parasitic infection
- Liver trematodes
- Toxocara spp
Background
Epidemiology
- Transmission – variable according to virus
- HAV, HEV – fecal-oral
- HBV, HCV, HDV, HGV – intravenous (IV) drug abuse, sexual transmission, blood transfusions
Organism
- Diverse group of viruses that share a common ability to cause inflammation and necrosis of the liver
- Virus may persist in a chronic state (HBV, HCV, HDV)
- May cause the development of cirrhosis
- Patients may remain chronic carriers
Risk Factors
- HAV – child daycare settings
- HBV and HCV
- Sexual transmission via infected partner
- HIV
- IV drug abusers
- Infection from blood products (patients with hemophilia)
- HDV
- IV drug abuse
- Travel to endemic area (Amazon basin, Mediterranean basin, Middle East, South Pacific, Asia, Sub-Saharan Africa)
- HEV – travel to endemic area (Central Asia, Middle East, parts of South America, Africa)
Clinical Presentation
- May be difficult to diagnose clinically
- Frequently asymptomatic – may have only mild increase in aminotransferases
- Mild symptoms – malaise, fever, chills, decreased appetite
- Similar symptoms among viral hepatitis types
- Jaundice not a predominant symptom in most patients
- Complication – acute liver failure
Prevention
- Chronic hepatitis is a public health concern in terms of transmission and because it can lead to the development of cirrhosis and hepatocellular carcinoma
- Vaccines are available to immunize against HAV and HBV
ARUP Laboratory Tests
Initial screening for hepatobiliary inflammation
Quantitative Enzymatic/Quantitative Spectrophotometry
Preferred test to evaluate viral etiology in patients with acute hepatitis
Not recommended for screening asymptomatic patients
Qualitative Chemiluminescent Immunoassay/Quantitative Transcription Mediated Amplification
Components: HAV IgM, HBV core antibody IgM, HBV surface antigen with reflex to confirmation, and HCV antibody with reflex to HCV by quantitative NAAT
Order to evaluate viral etiology in patients with acute hepatitis
Not recommended for screening asymptomatic patients
Qualitative Chemiluminescent Immunoassay
Components: HAV IgM, HBV core antibody IgM, HBV surface antigen with reflex to confirmation, and HCV antibody
Preferred single test to confirm hepatitis C virus (HCV) infection following positive HCV antibody screen
Quantitative Transcription Mediated Amplification
Confirm and quantify presence of HDV
Quantitative Polymerase Chain Reaction
Recommended for determining exposure to HEV
Qualitative Enzyme-Linked Immunosorbent Assay
Preferred test for diagnosing acute HEV infection
Qualitative Enzyme-Linked Immunosorbent Assay
Confirm and quantify presence of HEV
Negative result (less than 3.3 log IU/mL or less than 1,800 IU/mL) does not rule out presence of PCR inhibitors in patient specimen or HEV RNA concentrations below level of detection of the test
Inhibition may also lead to underestimation of viral quantitation
Quantitative Polymerase Chain Reaction
Diagnose acute hepatitis A virus infection
For panel test that includes HAV IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody, refer to acute hepatitis panel with reflex to confirmation
Qualitative Chemiluminescent Immunoassay
Can be ordered as part of acute hepatitis panel which includes HAV IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody to determine if patient has acute HBV infection
Refer to acute hepatitis panel with reflex to confirmation
Qualitative Chemiluminescent Immunoassay
Can be ordered as part of acute hepatitis panel which includes HAV IgM, HBV core antibody IgM, HBV surface antigen, and HCV antibody
Refer to acute hepatitis panel with reflex to confirmation
Qualitative Chemiluminescent Immunoassay
Preferred single screening test for one-time screening of population born between 1945 and 1965 and individuals at risk for HCV
Positive results require confirmation by molecular testing (eg, HCV by quantitative PCR or HCV quantitative PCR with reflex to HCV genotype by sequencing)
Qualitative Chemiluminescent Immunoassay
Stand-alone antibody testing is recommended
Refer to IgM hepatitis E antibody testing for acute disease or IgG hepatitis E antibody testing for exposure evaluation
Qualitative Enzyme-Linked Immunosorbent Assay
Medical Experts
Hillyard

Slev

References
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Denk H. What is expected from the pathologist in the diagnosis of viral hepatitis? Virchows Arch. 2011;458(4):377-392.
Panel includes albumin; alkaline phosphatase (ALP); aspartate aminotransferase (AST); alanine aminotransferase (ALT); bilirubin, direct; protein, total; and bilirubin, total