At a Glance

Hepatitis B virus (HBV) can cause either acute or chronic hepatitis.

Asia: All countries

Africa: All countries

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South Pacific Islands: All countries

Middle East (except Cyprus and Israel)

European Mediterranean: Malta and Spain

The Arctic (indigenous populations of Alaska, Canada, and Greenland)

South America: Ecuador, Guyana, Suriname, Venezuela, and Amazon regions of Bolivia, Brazil, Colombia, and Peru

Eastern Europe: All countries except Hungary

Caribbean: Antigua and Barbuda, Dominica, Granada, Haiti, Jamaica, St. Kitts and Nevis, St. Lucia, and Turks and Caicos

Central America: Guatemala and Honduras

Other groups recommended for screening include:

U.S. born persons not vaccinated as infants whose parents were born in regions with high HBV endemicity (≥8%)

household and sexual contacts of HBsAg-positive persons

persons who have ever injected drugs

persons with multiple sexual partners or history of sexually transmitted disease

men who have sex with men

inmates of correctional facilities

individuals with chronically elevated ALT or AST

individuals infected with hepatitis C virus (HCV) or HIV

patients undergoing renal dialysis

all pregnant women

persons needing immunosuppressive therapy

Roughly 70% of infected patients have subclinical or anicteric acute infections. The signs and symptoms of acute symptomatic hepatitis B may include fever, chills, fatigue, myalgias, anorexia, nausea, vomiting, jaundice, and right upper quadrant pain or discomfort. Symptoms and jaundice decline over a few months, but constitutional symptoms may last for some time after normalization of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Progression to chronic hepatitis B after acute infection is age-dependent; 90% of infants progress, but less than 5% of adults progress.

Chronic hepatitis B is usually asymptomatic until significant hepatic damage has occurred, so screening of persons at risk is recommended. The American Association for the Study of Liver Diseases (AASLD) Practice Guidelines for Management of Chronic Hepatitis B provides a significant list of those who should be screened.

Individuals born in the following areas of high or intermediate prevalence rates for HBV, including immigrants and adopted children, should be screened.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Markers of liver damage are typical: elevated serum aminotransferases, serum total and direct bilirubin, and alkaline phosphatase. In chronic HBV, some patients with significant ongoing hepatitis have normal-range ALT/AST. The degree of liver damage in the later stages correlates with markers of hepatic dysfunction, such as low albumin and elevated International Normalized Ratio (INR).

For diagnosis of acute HBV, the primary markers are hepatitis B surface antigen (HBsAg) and hepatitis B core IgM antibody (HBc IgM).

HBsAg appears in serum 1110 weeks after exposure, becoming detectable prior to symptoms or elevated transaminases. In patients who recover from acute infection without progressing to chronic HBV, HBsAg declines to undetectable levels in 4-6 months. Persistence of HBsAg for more than 6 months suggests chronic infection and a possible need for further intervention.

HBc IgM is the only serological marker of HBV infection during the “window period” between the disappearance of HBsAg and the appearance of anti-HBs. Thus, HBcIgM is usually regarded as a marker of acute HBV infection. However, IgM anti-HBc can be detected for up to 2 years after the acute phase of infection and can also increase back to detectable levels during exacerbations of chronic HBV, confusing the diagnostic picture, particularly in endemic areas in which many patients presenting with HBsAg-positive acute hepatitis may actually have an exacerbation of chronic HBV.

For diagnosis and assessment of chronic HBV, a panel of tests is useful: HBsAg, hepatitis B surface antibody (HBsAb), and hepatitis B core total antibody (HBcAb). The core total antibody is the single most useful marker of exposure to HBV; the core antigen is not part of the HBV vaccine, so HBcAb is negative in immunized, uninfected persons.

For assessment of HBV immune status due to immunization, HBsAb is the test of choice. Immunized patients will be positive for HBsAb but negative for all other markers. A positive vaccine response is defined as an antibody level of 10 IU/ml 1-2 months after completion of the primary vaccination series. Because roughly 95% of recipients respond to the vaccine, it is unnecessary to monitor vaccine response, except in persons expected to have an ongoing significant risk of exposure.

For assessment of HBV disease activity in seropositive patients, the critical markers are HBsAb, HBsAg, HBeAb, and HBeAg. The persistence of HBsAg more than 6 months after primary infection implies chronic HBV; conversely, the rise of HBsAb after acute infection implies control of the HBV and low risk of ongoing hepatic disease. In HBsAg positive patients, hepatitis B e antibody (HBeAb) is a good prognostic factor, whereas hepatitis B e antigen (HBeAg) is a poor prognostic factor. Hepatitis B viral load testing by DNA (HBV DNA) provides further prognostic information to guide therapy (Table 1).

Table 1
Test Application and Interpretation
Elevated liver indicators; aspartate aminotransferase (AST) alanine aminotransferase (ALT), bilirubins, alkaline phosphatase These markers of hepatic injury are not specific to HBV but indicate hepatitis is present.
HBsAg Surface antigen is associated with acute hepatitis B and with active chronic disease.
HBsAb Surface antibody is associated with clearance of primary HBV infection and with successful immunization.
HBcIgM Core IgM is a marker of acute hepatitis B and occasionally of exacerbations of chronic disease, particularly in endemic areas.
HBcAb Core (total) antibody is the most reliable marker of HBV infection history; it is not produced by immunization, and although some chronically infected patients lose HBsAb, core antibody usually persists. Isolated positivity for HBcAb may be seen in persons with long-distant, cleared primary infections, but may also be false-positive serology, particularly in low-risk populations.
HBeAg The e markers are of prognostic value in HBsAg(+) chronically infected patients. The persistence of e Ag is a poor prognostic sign, indicating an increased risk of progressive liver disease. HBe Ab/Ag status affects treatment strategy.
HBeAb The e markers are of prognostic value in HBsAg(+) chronically infected patients. The development of e Ab is a good prognostic sign, indicating a decreased risk of progressive liver disease. HBe Ab/Ag status affects treatment strategy.
HBV DNA / viral load This marker is valuable primarily for staging and therapeutic decisions.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Because the HBV vaccine contains surface antigen, recently-vaccinated persons can be HBsAg positive without being infected.

All serological tests, and particularly IgM assays, have some false positives in uninfected persons; this is particularly likely when low-risk individuals are tested. Follow-up testing in 1-3 months is recommended.

What Lab Results Are Absolutely Confirmatory?

Although HBV DNA testing is sometimes used to confirm serological testing, molecular diagnostic tests are also subject to false-positive results and HBV DNA is not recommended as a diagnostic procedure.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

HBV-infected patients should be screened for diseases with similar sexual and blood-borne routes of transmission and for infections that can exacerbate the course of HBV, including HIV, HCV, and hepatitis A virus (HAV); patients not immune to HAV should be immunized.

In addition, hepatocellular carcinoma is a known complication of chronic HBV infection. Groups for whom every six-month ultrasonographic screening is definitely indicated include:

Asian male HBV carriers 40 years of age or older

Asian female HBV carriers 50 years of age or older

HBV carriers with family history of hepatocellular carcinoma (HCC) African/North American blacks with HBV

Cirrhotic HBV carriers

Treatment is recommended for patients with acute liver failure or complicated cirrhosis and any detectable viral load, cirrhosis, or advanced fibrosis with high HBV viral load (>2000 IU/ml), or reactivation disease after chemotherapy or immunosuppression. Patients with active disease without advanced fibrosis or cirrhosis (chronic hepatitis) may be candidates for the following treatment:

HBeAg-positive patients: Offer treatment to those with HBV DNA greater than 20,000 IU/mL and ALT greater than 2 times the upper limit of normal (ULN) in patients without cirrhosis, but delay for 3-6 months after a new diagnosis to see if active disease will spontaneously remit.

HBeAg-negative patients: Offer treatment to those with ALT greater than 2 times ULN and HBV DNA greater than 2000 IU/mL.

Patients for whom immediate therapy is not routinely indicated include patients with normal serum ALT or little activity on liver biopsy, regardless of HBV viral load.

Patients not being treated should be monitored with serum ALT every 3 months of the first year, and then every 6 months thereafter, more frequently if ALT rises above normal or if patient is immunosuppressed.