AGA releases updated guidelines on hepatitis B reactivation in patients on immunosuppressive drugs

The American Gastroenterological Association (AGA) has unveiled an updated clinical practice guideline in Gastroenterology addressing the prevention and management of hepatitis B virus reactivation (HBVr) in patients on immunosuppressive drugs. The use of immunosuppressive drugs has increased significantly since 2013, according to data gathered via the National Health Interview Survey.

New tailored risk assessments can help health care providers and patients navigate challenges posed by the newer immunosuppressive therapies used for oncology, rheumatology, and gastrointestinal diseases. As the number of immunosuppressive drugs has grown, so has the number of patients referred to gastroenterologists with hepatitis B reactivation, which can lead to acute liver failure.

For patients at high risk of hepatitis B reactivation, AGA recommends preventive antiviral medication. Reactivated HBV can lead to liver damage, hospitalization, and even death. These risks are higher than any potential side effects of antiviral medicines. For at-risk patients who do not initiate prophylactic antiviral medication, a commitment to close monitoring by both patients and providers is essential to prevent missed reactivation. Antiviral treatments are readily available in the U.S.

Both current HBV-positive patients and those with previous HBV exposure, including those with immunity to HBV, are at risk of virus reactivation while on immunosuppressive drugs.

Screening for hepatitis B virus is the first crucial step for patients starting immunosuppressive medications, noted guideline authors. In March 2023, the U.S. Center for Disease Control and Prevention recommended universal HBV screening and testing for all adults in the United States at least once in their lifetime. It should include a "triple" panel of HBsAg, antibodies to HBV surface Ag (anti-HBs), and HBV total core Ag (anti-HBc). Those with positive anti-HBc are at risk for HBVr.

AGA's guidance is based on a patient's HBV infection status. Patients are further grouped into low, medium, and high reactivation risk based on which immunosuppressive medication they take.

Risk categories for HBV-positive patients (chronic hepatitis B: positive HBsAg)

High Risk:

• Patients on anthracycline derivatives, anti-tumor necrosis factor (TNF) agents, or anti-interleukin-6 (IL-6) therapies.
• Patients receiving B cell-depleting agents (E.g., rituximab), chimeric antigen receptor (CAR)-T cell therapies, or cytokine/integrin inhibitors.
• Patients receiving tyrosine kinase inhibitor (TKI) therapies or Janus kinase (JAK) inhibitors.
• Patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE)
• HCV co-infected patients undergoing direct-acting antiviral (DAA) therapy.
• Patients on high doses of corticosteroids for one month or more.

Moderate Risk:

• Patients treated with anti-T cell therapies.
• Patients on low-dose corticosteroids for four or more weeks.

Low Risk:

• Patients on low, moderate, or high doses of corticosteroids for one week or less.
• Patients receiving intra-articular corticosteroid therapies.

Risk categories for patients without chronic hepatitis B but previously exposed to HBV (negative HBsAg, positive anti-HBc [total or IgG]; anti-HBs can be negative or positive)

High Risk:

• Patients receiving rituximab.

Moderate Risk:

• Patients on anthracycline derivatives, anti-IL-6 therapies, anti-T cell therapies, or CAR-T cell therapies.
• Patients treated with cytokine/integrin inhibitors, TKI therapies, or JAK inhibitors
• Patients undergoing TACE.
• Patients on moderate to high doses of corticosteroids for one month or more.

Low Risk:

• Patients on immune checkpoint inhibitors or anti-TNF therapies.
• Patients with HCV co-infection undergoing DAA therapy.
• Patients on low or moderate doses of corticosteroids for four or more weeks or any dose for less than one week.
• Patients receiving intra-articular corticosteroid therapies.

Understanding HBVr

For individuals who have had hepatitis B, the virus can sometimes become active again later in life, a process known as hepatitis B reactivation. HBVr can cause significant liver damage, including acute liver failure in severe cases, the need for a liver transplant, and even death.

Certain groups with chronic hepatitis B or prior exposure to hepatitis B are at increased risk of HBVr, particularly those taking medications that suppress the immune system. These medications include:

• Chemotherapy and biologic therapies for cancer treatment.
• Immunosuppressive medications for inflammatory conditions such as inflammatory bowel disease, rheumatologic diseases such as rheumatoid arthritis, and dermatologic conditions such as psoriasis.

• Transplant medications for solid organ or bone marrow recipients.
• Corticosteroids, especially when used for extended periods (more than a few weeks and/or high dose).
• Hepatitis C treatments with DAA.
• Patients with HIV infection.

By understanding these risks, health care providers can take proactive steps to prevent HBVr in vulnerable patients.