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Management of Hepatitis B Infection

Stefan Zeuzem, MD
Program Director
Harry L. A. Janssen, MD, PhD
Milan J. Sonneveld, MD, PhD, MSc
Released: June 17, 2019

Monitoring of Patients Who Are Not Candidates for Therapy

Patients who are not candidates for immediate initiation of therapy should be closely monitored, and it should be appreciated that there is a risk of HCC and progression to cirrhosis in this population.[10] According to the AASLD, HBeAg-positive patients with high HBV DNA (typically > 1 million IU/mL) but normal ALT levels, no fibrosis, and minimal inflammation (ie, so-called immune-tolerant patients) should have their ALT levels measured at least every 6 months and should be regularly tested for the presence of HBeAg (approximately every 6-12 months).[3] In HBeAg-negative patients with HBV DNA < 2000 IU/mL and normal ALT (ie, so-called inactive chronic hepatitis B), ALT and HBV DNA levels should be reassessed every 3 months during the first year, with subsequent biannual to annual assessments.[3]

Although AASLD guidance maintains use of the “immune-tolerant” classification, terminology from the EASL has been updated (Table 2). For HBeAg-positive patients, EASL now uses the term “chronic infection” for what was previously described as immune tolerant and the term “chronic hepatitis” for the disease phase previously described as immune reactive.

Table 2. Updated EASL Terminology for Classification of Patients With HBV[4]


According to EASL guidelines, patients with HBeAg-positive chronic HBV infection who do not meet indications for immediate treatment should undergo noninvasive testing for liver fibrosis every 12 months, HBV DNA level every 6-12 months, and ALT at least every 3 months.[4] Recommendations for HBeAg-negative patients differ by HBV DNA level. In patients with HBV DNA ≥ 2000 IU/mL, ALT should be tested every 3 months for 1 year and biannually thereafter, with HBV DNA level and liver fibrosis annually. In patients with HBV DNA < 2000 IU/mL, ALT should be assessed every 6-12 months and HBV DNA level and fibrosis testing should be assessed every 2-3 years.

Patients with low levels of serum HBV DNA (< 2000 IU/mL) and HBsAg (< 1000 IU/mL) may require less frequent monitoring due to a very low probability of disease reactivation.[4,11]

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