Viral Hepatitis

Indications for Testing

Laboratory testing for viral hepatitis is used to ^, , , :

• Screen individuals for hepatitis virus infection (e.g., prenatal screening for HBV, HDV in individuals with confirmed HBV infections, and HCV)
• Evaluate symptoms of hepatitis (e.g., anorexia, dark urine, jaundice)
• Follow up on a known or suspected exposure to hepatitis virus
• Inform treatment planning

Laboratory Testing

Hepatitis A

HAV is a vaccine-preventable disease transmitted through the fecal-oral route. HAV causes acute, self-limiting disease that may be asymptomatic or severe with symptoms such as abdominal pain, anorexia, fever, malaise, and nausea. Jaundice may present within a few days of symptom onset. 

HAV is diagnosed using both clinical and laboratory criteria. HAV immunoglobulin M (IgM) antibody testing is the primary test used in diagnosis.  More detailed information about hepatitis A diagnosis may be found in the CDC’s case definition for acute hepatitis A.  A total assay should be used to assess immunization status or exposure. 

Hepatitis B

HBV is a vaccine-preventable disease that may be acute or chronic. Chronic infection is often asymptomatic until the onset of cirrhosis or end-stage liver disease. Transmission of HBV generally occurs through contact with the blood or bodily fluids of an infected person. Vertical transmission from mother to child often leads to chronic infection. Children are more likely to develop chronic, asymptomatic disease, whereas adults are more likely to develop acute, self-limiting disease.  For more detailed information, refer to the CDC’s case definitions for acute and chronic HBV infection. 

No single test is sufficient to diagnose a current HBV infection (whether acute or chronic) and stage the disease, therefore, simultaneous testing for multiple markers is usually necessary. The following table details common HBV markers and their indications.

Screening and Testing for HBV Infection

The CDC recommends all adults 18 years and older be screened for HBV at least once in their life and all pregnant individuals be screened during each pregnancy.  Additional testing is recommended for populations considered at risk for HBV infection, including men who have sex with men (MSM), individuals experiencing homelessness, and individuals who will undergo immunosuppressive therapy. The current recommendation for screening all individuals for HBV infection is to use a triple panel that includes HBsAg, anti-HBs, and total anti-HBc tests. 

Use of multiple HBV markers interpreted together is necessary to determine a patient’s HBV status. Initial diagnostic testing should include HBsAg, anti-HBs, and total anti-HBc testing. 

 The following table details the expected HBV test results for HBV markers in various clinical situations.

Monitoring Chronic HBV

The recommended tests for monitoring chronic HBV infection are HBsAg, HBeAg, total anti-HBs, HBeAb, HBV DNA, and alanine aminotransferase (ALT).  The frequency of monitoring depends on the clinical situation; refer to guidance from the American Association for the Study of Liver Diseases (AASLD) for more information.  HBV genotyping and HBsAg quantification are not routinely recommended.  Resistance testing in treatment naïve patients is not recommended. 

Hepatitis C

HCV may occur acutely, but more than 85% of cases progress to chronic HCV infection.  Acute and chronic disease are commonly asymptomatic. Transmission of HCV is parenteral.  Detailed information about acute and chronic HCV infections can be found in the CDC’s case definitions. ^, 

Screening

Serology is the recommended screening test to detect HCV antibodies. All adults 18 to 79 years of age are recommended to be screened at least once. ^,  More frequent screening is recommended in populations considered at high risk for HCV infections, such as those with continued injection drug use. Refer to the AASLD and Infectious Diseases Society of America for screening recommendations in high-risk populations. 

Diagnosis

Serology to detect anti-HCV antibodies is the first-line test to diagnose HCV infection.  If serology returns a positive result, HCV RNA testing can differentiate between current, chronic, and previous infections. ^, 

Treatment Determination and/or Monitoring

Quantitative HCV RNA testing is recommended before treatment initiation. Depending on the treatment type, HCV genotype and subtype testing is also recommended.  Within six months before starting treatment, a CBC, international normalized ratio (INR), estimated glomerular filtration rate (eGFR), and a hepatic function panel (i.e., serum albumin, total and direct bilirubin, alanine aminotransferase [ATL], and alkaline phosphate levels) are recommended.  A quantitative HCV RNA test should be used 12 or more weeks after therapy to determine efficacy. 

Hepatitis Delta

Hepatitis D, also known as delta, only occurs in patients who are also infected with HBV. If HBV and HDV are acquired concurrently (coinfection), the majority of individuals will clear both HBV and HDV spontaneously. If HDV is acquired in a patient already infected with HBV (superinfection), the likelihood of progression to chronic HDV is 90%. Superinfection with HDV results in the most severe form of viral liver disease, with most progressing to cirrhosis and hepatocellular carcinoma (HCC) rapidly. Testing for HDV should be considered in any person who is positive for HBsAg  or any HBsAg-positive person experiencing disease exacerbation or considered high risk for HDV infection.  Total HDV antibody testing is recommended for screening and diagnosis (HDV IgM and HDV antigen are not recommended), and quantitative HDV RNA testing can confirm active infection.   Quantitative HDV RNA testing can also be used to monitor HDV therapy. 

Hepatitis E

Symptomatic HEV cases may have a clinical presentation that is indistinguishable from cases caused by other hepatitis viruses. Most HEV infections are mild and self-limiting, although HEV-1 infections may be serious in pregnant individuals.  Because HEV can lead to chronic infection in solid organ transplant patients who are undergoing immunosuppressive therapy, HEV also poses a significant risk in this population. 

Testing for HEV should be informed by patient history (e.g., past travel to endemic areas). In areas with low HEV prevalence, such as the United States, testing should be considered in persons who have undergone solid organ transplantation and in individuals who exhibit symptoms of viral hepatitis but have tested negative for other hepatitis viruses.  Serologic testing for IgM antibodies indicates current or recent infection and is diagnostic for HEV infection.  Serial detection of HEV RNA may suggest chronic infection.