Version July 2025
| HBeAg | HBV DNA (PCR) | ALT | Treatment strategy |
| Patients without cirrhosis* | |||
| + | >20,000 international units/mL | ≤2 × ULN¶ | Treatment is not recommended, because current treatment has low efficacy in inducing HBeAg seroconversion. Treatment may be considered in older patients (>40 years) and in those with family history of HCC. Patients should be monitoredΔ and treatment considered if ALT becomes elevated >2 × ULN, liver biopsy shows moderate/severe inflammation or fibrosis◊ (eg, METAVIR score ≥F2), and/or noninvasive testing suggests moderate/severe fibrosis. |
| + | >20,000 international units/mL | >2 × ULN¶ | Observe for 3 to 6 months if compensated and treat if no spontaneous HBeAg loss. Immediate treatment if severe hepatitis flare (eg, icteric or clinical decompensation). ETV, TAF, TDF, or PegIFN alfa are preferred for initial therapy.§¥ End-point of treatment – Seroconversion from HBeAg to anti-HBe.‡ Duration of therapy:
|
| – | >2000 international units/mL | >2 × ULN¶ or 1 to 2 × ULN¶ if liver biopsy shows moderate/severe necroinflammation or significant fibrosis◊ (eg, METAVIR score ≥F2) or non-invasive testing shows significant fibrosis | ETV, TAF, TDF, or PegIFN alfa are preferred for initial therapy.§¥ End-point of treatment – HBsAg loss. Duration of therapy:
|
| – | ≤2000 international units/mL | ≤ULN¶ | Monitor and treat if HBV DNA and ALT increase as described above. |
| Patients with cirrhosis* | |||
| +/– | Detectable | Any ALT | Compensated:
Decompensated:
|
| +/– | Undetectable | Any ALT | Compensated: Observe, recheck HBV DNA during follow-up, evaluate for other causes of cirrhosis if HBV DNA remains undetectable. Decompensated: Refer for liver transplant, recheck HBV DNA during follow-up, evaluate for other causes of cirrhosis. |
ALT: alanine aminotransferase; anti-HBe: antibody to hepatitis B e antigen; ETV: entecavir; HBeAg: Hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; PegIFN alfa: pegylated interferon alfa; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil fumarate; ULN: upper limit of normal.
* Based upon findings on noninvasive testing or liver biopsy performed during the initial evaluation. Patients with advanced fibrosis determined by noninvasive methods should be evaluated using a second method, and if results are concordant, consider managing the same way as patients with cirrhosis.
¶ The American Association for the Study of Liver Diseases (AASLD) recommends using an ALT >35 U/L for men and >25 U/L for women as the upper limit of normal (ULN) rather than local laboratory values.
Δ Refer to UpToDate topic on "Hepatitis B virus: Overview of management" for a discussion of monitoring.
◊ Refer to UpToDate topic on "Hepatitis B virus: Overview of management" for a discussion of indications for biopsy.
§ Adefovir, lamivudine, and telbivudine are not recommended due to a high rate of resistance after the first year and/or weak antiviral activity.
¥ Refer to UpToDate topic on "Hepatitis B virus: Overview of management" for a discussion of which agent to use.
‡ Up to 50% of patients who achieve HBeAg seroconversion can experience a virologic relapse after discontinuing treatment with oral agents. Thus, some providers prefer to treat until HBsAg-loss.
† For most patients, antiviral therapy should be continued indefinitely. However, treatment discontinuation may be considered in persons without cirrhosis who have demonstrated loss of HBsAg and in selected patients who have had undetectable serum HBV DNA for >3 years and agree to close monitoring after stopping treatment. Persons who stop antiviral therapy should be monitored every month for the first 6 months. Refer to the UpToDate topic on management of hepatitis B virus infection for a detailed discussion of the risks and benefits of stopping antiviral therapy in this setting.
** This includes HBeAg-positive adults with cirrhosis who seroconvert to anti-HBe on therapy.Adapted from: Lok ASF, McMahon BJ. AASLD Practice Guidelines: Chronic Hepatitis B: Update 2009. Hepatology 2009; 50:1-36.
Updated with information from: