Monitoring

In patients who don’t meet the local criteria for treatment with antiviral therapy, the aim of monitoring is to identify a change in clinical status that indicates progression to disease state that requires treatment. The aim of monitoring in those who have received antiviral therapy is to evaluate treatment response, adverse effects, and disease progression or reactivation.[2][29]​​​​​​​[191]

Guidelines for monitoring vary, but typically involve the following serological markers:[2][29] 

  • HBV DNA

  • Alanine aminotransferase (ALT)

  • Hepatitis B surface antigen (HBsAg)

  • Hepatitis B e antigen (HBeAg)

  • Antibody to HBeAg (anti-HBe)

Patients not currently on treatment

  • Monitoring recommendations for patients not currently on treatment after initial diagnosis may vary across guidelines.

  • The European Association for the Study of the Liver (EASL) recommends monitoring the following in newly diagnosed individuals for the first year post-diagnosis:​​[29]

    • HBV DNA and ALT levels: every 3-6 months for the first year after diagnosis, or until treatment is initiated (can be extended to every 6-12 months after this initial phase)

    • HBsAg: every 12 months (quantitative is preferred, but qualitative is the minimum requirement)

    • HBeAg and anti-HBe (in patients who are HBeAg-positive): every 12 months or when HBV DNA or ALT levels change significantly

    • Liver fibrosis progression: using non-invasive methods, with the frequency and interval determined by factors such as disease phase and presence of comorbidities.

  • Further monitoring after the first year post-diagnosis is based on the phase of infection.​​[29]

  • The American Association for the Study of Liver Diseases (AASLD) recommends monitoring based on the phase of disease.[2]

    • Immune-tolerant chronic hepatitis B virus (HBV) infection HBeAg-positive, high HBV DNA, and persistently normal ALT level): monitor ALT every 3-6 months. Monitor more frequently, along with a HBV DNA level, if ALT level becomes elevated. Check HBeAg status every 6-12 months. Consider starting antiviral therapy in patients with compensated liver disease who remain HBeAg-positive with a HBV DNA level >20,000 IU/mL; after a 3-6 month period of elevated ALT level greater than 2 times the upper limit of normal. Consider liver biopsy (or alternative non-invasive tests) in patients with persistent borderline normal, or slightly elevated, ALT level, particularly in patients >40 years of age who have been infected from a young age. Initiate antiviral therapy in patients with moderate to severe inflammation and/or fibrosis.

    • Immune-inactive chronic HBV infection (HBeAg-negative, normal ALT, and HBV DNA <2000 IU/mL): monitor ALT and HBV DNA levels every 3 months during the first year to confirm patient is in the inactive phase, then every 6-12 months thereafter. Monitor more frequently (i.e., every 3-6 months) if ALT level becomes elevated. If ALT elevation is persistent or recurrent, evaluate the patient for other causes of liver disease. If HBV DNA is >2000 IU/mL, assess disease severity with liver biopsy (or non-invasive methods), and initiate treatment in patients with moderate to severe inflammation or significant fibrosis. Evaluate for HBsAg loss annually.

    • Resolved chronic HBV infection: includes patients who have achieved HBsAg loss spontaneously or with therapy (also known as functional cure). Routine monitoring of ALT and HBV DNA are not required. However, surveillance for hepatocellular carcinoma (HCC) should continue if the person has cirrhosis, a first-degree family member with HCC, or a long duration of infection (i.e., >40 years for males and >50 years for females who have been infected from a young age).

Patients on treatment

  • ​Monitoring recommendations for patients on treatment may vary across guidelines.

  • The European Association for the Study of the Liver (EASL) recommends monitoring the following:​​[29]

    • HBV DNA and ALT levels: every 3-6 months during treatment until there is a virological response (can be extended to every 6-12 months once a virological response is achieved)

    • HBsAg: every 12 months

    • HBeAg and anti-HBe (in patients who are HBeAg-positive): every 12 months

    • Liver fibrosis progression: using non-invasive methods every 12-14 months

    • Renal function: assess at baseline and monitor regularly during treatment

  • In addition to this, the American Association for the Study of Liver Diseases (AASLD) recommends monitoring the following:[2]

    • Lactic acid level: if there is a clinical concern for lactic acidosis (e.g., use of entecavir or tenofovir in patients with decompensated cirrhosis)

    • Bone density study: at baseline and during treatment (patients receiving tenofovir disoproxil with a history of fracture or risks for osteopenia)

    • Full blood count (FBC): every 1-3 months (patients receiving peginterferon alfa)

    • Thyroid-stimulating hormone: every 3 months (patients receiving peginterferon alfa).

  • The AASLD recommends monitoring patients who stop treatment every 3 months for at least 1 year for viremia, ALT flares, seroconversion, and clinical decompensation. Monitoring frequency and duration may differ in special patient populations (e.g., pregnant women, co-infections, patients with cirrhosis).[2]

Screening for HCC

  • Treatment with antivirals does not eliminate the risk of HCC and surveillance for HCC should continue in at-risk patients, regardless of HBsAg loss. Individual risk assessment can be enhanced by using HCC risk scores.[2][29]

  • All patients who are HBsAg-positive with cirrhosis or at high risk for HCC (e.g., Asian or black men aged >40 years, Asian women aged >50 years, people with a first-degree family member with a history of HCC, people with hepatitis D infection) should be screened with an abdominal ultrasound, with or without alpha-fetoprotein (AFP), every 6 months. In areas where ultrasound is not readily available, screen with AFP every 6 months.[2][29]

  • If abdominal ultrasound cannot provide reliable information, other imaging modalities may be used (e.g., computed tomography, magnetic resonance imaging).[29]

  • Routine surveillance for patients with occult HBV infection is not recommended unless the patient has additional risk factors (e.g., cirrhosis, co-infections, metabolic liver disease).[29]

Patients who come off long-term tenofovir disoproxil treatment can remain in a low replicative state (i.e., low HBV DNA and normal ALT), but there is approximately a 30% risk of ALT elevation, so patients should be closely monitored.[192]

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