Applied Evidence

Chronic hepatitis B infection: A workshop consensus statement and algorithm

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Here, presented with an evidence-based algorithm, are workshop consensus recommendations on whom to screen for hepatitis B and when to pursue further evaluation and management.




Screen patients at risk of contracting hepatits B virus (HBV), especially those from HBV-endemic regions of the world, by testing for hepatitis B surface antigen and antibody (HBsAg and anti-HBs). A

Vaccinate all infants, children, and adolescents following guidelines of the Centers for Disease Control and Prevention and American Academy of Pediatrics, as well as at-risk adults whose screening results are negative for both HBsAg and anti-HBs. A

Provide periodic monitoring for patients who are HBsAg-positive. While these patients may appear asymptomatic, they are infected with HBV and require further evaluation. A

Consult a specialist experienced in treating hepatitis if active liver disease is suspected in patients with chronic HBV infection who present with elevated alanine aminotransferase and HBV DNA >2,000 IU/mL. B

Screening for hepatitis B virus (HBV) infection is simple and relatively inexpensive. Yet it is underused in everyday practice, leaving some HBV-positive patients unaware and at risk for serious health consequences, including cirrhosis, liver failure, and hepatocellular carcinoma (HCC).1 In addition, many primary care providers do not follow existing guidelines for HBV screening and management.2 Yet they are often the first, and sometimes the only, clinicians that infected individuals will see.

Why chronic HBV is still a problem. Although the incidence of acute HBV infection has declined significantly as a result of universal infant vaccination in the United States, chronic infections are still prevalent in this country due to such factors as immigration from areas where HBV is endemic, perinatal transmission, transmission among household contacts, and risky behaviors. In most adolescents and adults, HBV infection leads to acute hepatitis from which they fully recover; chronic infection ensues in only 5% to 10% of cases. However, 90% of infants and 25% to 50% of children younger than 5 years who become infected with HBV go on to develop lifelong infection. Most people with chronic HBV infection do not exhibit any signs of clinical illness, which makes screening all the more important—particularly since effective antiviral treatments are available.1,3

To help primary care providers address the issues of screening for HBV, the Hepatitis B Foundation convened a workshop of prominent primary care practitioners and specialists in hepatitis and liver diseases. The workshop panel reviewed evidence-based guidelines and reports from the American Association for the Study of Liver Diseases (AASLD), the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the Institute of Medicine (IOM), as well as a recent Hepatitis B Foundation publication on HBV screening and management in children and other relevant publications.1-5 The resultant algorithm and consensus recommendations presented here can assist primary care providers in applying evidence-based guidelines for HBV infection to everyday practice.

3 phases of HBV infection: What screening results mean

Hepatitis B surface antigen (HBsAg) that is persistently detectable in a patient’s serum for more than 6 months signifies chronic HBV infection.1,3,4 The 3 immunologic phases of chronic HBV infection—immune tolerant, immune active, and inactive carrier—are determined by serum levels of alanine aminotransferase (ALT) and HBV DNA, and the presence or absence of hepatitis B e antigen (HBeAg) (TABLE 1).6

All individuals with chronic HBV infection are initially HBeAg positive. Those in the immune tolerant phase also have high levels of circulating virus, indicated by HBV DNA levels. However, the body does not mount an immune response to the virus; there is no active liver disease, and the serum ALT level is normal.

When the immune system recognizes HBV as foreign, the patient enters the immune active phase, wherein liver inflammation and fibrosis can develop and ALT is correspondingly elevated. HBV antibody (anti-HBe) may be present.

In nearly all patients, HBeAg seroconversion to HBeAg-negative/anti-HBe-positive status occurs spontaneously or as a result of antiviral treatment. After seroconversion, most patients enter the HBsAg inactive carrier phase, in which a strong cellular immune response is able to suppress, but not eliminate, the virus. This phase typically features low or undetectable serum levels of HBV DNA and normal ALT levels. Over time, liver inflammation and fibrosis improve, and the risk of cirrhosis and HCC declines.7

However, some patients do not enter the inactive phase after HBeAg seroconversion. They instead continue to exhibit active viral replication and liver disease due to the emergence of one or more HBeAg-negative viral mutants. Moreover, in as many as 20% of those who enter the inactive HBsAg carrier state, infection will reactivate and possibly return the patient to HBeAg-positive status. HBV infection is a dynamic condition: Individuals can go from active disease to the inactive phase and then have reactivation of liver disease at any point during their lifetime. Thus, patients require lifelong monitoring of their chronic infection.8 .


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