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Laboratory Tests and Ancillaries
Hepatitis B is usually characterized by the presence of hepatitis
B surface antigen (HBsAg) which suggests infectivity. Anti-HBs is produced
following a resolved infection and is the only hepatitis B virus antibody
marker present after immunization. Persistence of HBsAg for at least 6 months indicates
chronic infection.
The hepatitis B core antibody (anti-HBc) is the first antibody to
appear in the serum and is a marker of natural immunity. Its presence indicates
an immune response against the hepatitis B virus within the liver cells and is
a specific marker of acute hepatitis B infection. The presence of anti-HBc IgM
is diagnostic for acute hepatitis B virus infection but may occur during a
flare of chronic hepatitis B. Hepatitis B e antigen (HBeAg) is a marker of
active viral replication. This may be negative at the time that the patient is
evaluated for acute hepatitis B since viral replication may have already ceased.
Hepatitis B virus DNA tests for hepatitis B virus and aids in the evaluation of
treatment efficacy with antiviral agents.
New biomarkers of hepatitis B virus infection include the viral
cccDNA, hepatitis B core-related antigen (HBcrAG), and circulating hepatitis B
virus RNA. Viral cccDNA is a key genomic form that causes the persistence of
infection and was shown to persist in the liver of infected patients even after
long-term nucleos(t)ide analog therapy and even after HBsAg loss and
seroconversion. It is used in clinical trials evaluating treatment concepts to
cure hepatitis B virus infection. Quantitative HBsAg concentrations which are highest
among HBeAg-positive individuals and low concentrations (<1,000 IU/mL) in
HBeAg-negative infection in individuals with an HBV DNA concentration of
<2,000 IU/mL and normal serum aminotransferases indicate improved outcome.
HBcrAG is composed of several antigens that were expressed from
pre-core or core gene and quantification may give additional information
regarding the translational activity of the hepatitis B virus infection beyond
HBsAg quantification. It might also be helpful in defining the phase of chronic
hepatitis B virus infection, especially in HBe-negative patients, as well as predicting
the long-term HCC risk.
There are ten hepatitis B virus genotypes (A-J) that play a role
in the development of liver disease and response to treatment with Interferon.
However, it is not recommended for routine testing nor for follow-up of chronic
hepatitis B patients.
Depending on the local health services, persons born in hyperendemic
areas, men who have sex with men (MSM), intravenous drug users, dialysis
patients, human immunodeficiency virus (HIV)-positive individuals, pregnant
women and family members, household members and sexual contacts of hepatitis B
virus-infected persons, blood or organ donors, healthcare workers, and patients
needing chemotherapy should be tested for chronic hepatitis B virus infection.
Individuals who are seronegative should be vaccinated against hepatitis
B virus. If the patient turned out to be anti-HBc positive only, the patient
may have had a past resolved hepatitis B virus infection or a false-positive
test, and that vaccination may be given if the patient is from an endemic area.
HBsAg-positive patients should be evaluated to assess the progression of liver
disease and the need for antiviral therapy. Anti-HBs-positive patients have
developed natural immunity and do not need to be vaccinated.
Patients with chronic hepatitis B should also be tested for
coinfection with hepatitis C virus, hepatitis D virus, and HIV if they are at
risk for these infections.
Hepatitis B_DiagnosisTests to Rule Out Other Viral Hepatitis*
Hepatitis D virus (HDV) is confirmed by positive immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-HDV virus antibody followed by HDV RNA test. Hepatitis D occurs as a coinfection with hepatitis B, hence, patients who are positive for HBsAg presenting with severe symptoms or acute exacerbations should be tested for hepatitis D virus infection. Hepatitis D virus genotype should be determined, if possible, in all hepatitis D virus-infected persons prior to treatment. The predominant genotypes worldwide are genotype 1 in North America, Europe, the Middle East, and North Africa; genotypes 2 and 4 in East Asia; genotype 3 in Amazon Basin in South America; and genotypes 5, 6, 7, and 8 for West and Central Africa.
To test for hepatitis A virus (HAV), anti-HAV IgM should be done. Nucleic acid amplification test (NAAT) for HAV RNA may be considered. To test for hepatitis C virus (HCV), anti-HCV antibody, HCV RNA test, or HCV core antigen may be considered. To test for hepatitis E virus (HEV), IgM anti-HEV, and IgG anti-HEV in combination with HEV RNA may be done. NAAT for HEV RNA may be considered.
*Please see Hepatitis A and E and Hepatitis C disease management charts for further information
Other Recommended Lab Tests in Patients Suspected of Viral Hepatitis
Liver function tests (LFTs) such as aspartate aminotransferase (AST) and ALT, serum bilirubin, and alkaline phosphatase (ALP) are recommended tests for patients suspected of viral hepatitis. Complete blood count (CBC) with platelets, prothrombin time (PT), international normalized ratio (INR), and renal function tests may likewise be performed. Noninvasive tests such as the aminotransferase/platelet ratio index (APRI) or fibrosis-4 (FIB-4) may be used to assess the degree of hepatic fibrosis when resources are limited prior to initiating HCV therapy. APRI is the preferred non-invasive test to assess for presence of significant fibrosis or cirrhosis for adults. Transient elastography (FibroScan®) may be an option for patients with contraindications to liver biopsy. Significant fibrosis is defined as an APRI score of >0.5 or transient elastography value of >7.0 kPa. While cirrhosis is based on clinical criteria (decompensated cirrhosis as evidenced by portal hypertension [eg ascites, variceal hemorrhage, hepatic encephalopathy], coagulopathy, or liver insufficiency [jaundice]; other clinical features of advanced liver disease or cirrhosis including hepatomegaly, splenomegaly, pruritus, fatigue, arthralgia, palmar erythema, or edema) or an APRI score of >1.0 or transient elastography value of >12.5 kPa.
Lastly, alpha-fetoprotein (AFP) measurement for periodic surveillance of HCC and endoscopy for varices in patients with cirrhosis is recommended.
Imaging
Ultrasound of the liver helps identify HCC and subclinical ascites.