It’s Back Again: New Guidance on HBV Reactivation With Immunosuppressive Therapy

Hepatitis due to hepatitis B virus (HBV) reactivation is increasingly recognized as a cause of liver-related morbidity and mortality in the Asia-Pacific region. HBV reactivation is characterized by an abrupt reappearance or rise of HBV DNA in the serum of a patient with previously inactive or resolved HBV infection. Furthermore, HBV reactivation is often accompanied by a flare of hepatitis, which might result in acute-on-chronic liver failure and death.

Role of Immunosuppressive Therapy
Although HBV reactivation can be spontaneous, its clinical relevance is mainly related to the use of immunosuppressive therapies in patients with cancer, transplant recipients, and patients who benefit from immunomodulatory therapy. Until 2020, numerous clinical guidelines included recommendations on how to reduce the occurrence of HBV reactivation related to the use of immunosuppressive therapies. In 2021, the Asian-Pacific Association for the Study of the Liver (APASL) developed a clinical practice guideline specifically addressing HBV reactivation related to the use of immunosuppressive therapy.

Barriers to Prevention
The key steps to prevent HBV reactivation are to screen patients for HBV prior to starting immunosuppressive therapy and to start preemptive anti-HBV nucleos(t)ide analogs in high-risk settings.

Nevertheless, there are barriers to these preventive steps, so hepatitis due to HBV reactivation leading to acute-on-chronic liver failure remains a major health threat in the Asia-Pacific region, where HBV infection is endemic.

The major barriers to HBV reactivation prevention appear to be the nonadherence of healthcare professionals to clinical guideline recommendations for HBV screening prior to immunosuppressive therapy initiation. This is further compounded by the recent rapid expansion of new immunosuppressive agents such as tyrosine kinase inhibitors used for oncologic and rheumatologic indications, immune checkpoint inhibitors used in the treatment of various cancers, and tumor necrosis factor inhibitors used for many autoimmune diseases.

Hepatitis C Coinfection
In the past few years, in patients coinfected with chronic hepatitis C and HBV, HBV reactivation has also been reported during and after treatment with direct-acting antiviral agents. Direct-acting antivirals are highly effective at hepatitis C virus eradication in coinfected patients but are more likely to induce HBV reactivation than interferon-based therapy. This can occur even in patients with undetectable levels of HBV DNA.

New Guideline
In 2021, The APASL published a clinical practice guideline aiming to assist healthcare professionals in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage HBV reactivation. To develop the guideline, all publications related to HBV reactivation with the use of immunosuppressive therapies since 1975 were reviewed and advice from key opinion leaders in 21 member countries/administrative regions of APASL were collected and synchronized. Immunosuppressive agents were risk-stratified by their individual reported rates of HBV reactivation.

The recommendations remain the same for HBsAg-positive patients in whom preemptive nucleos(t)ide analogs should be started. The main changes affect patients who are HBsAg-negative but anti-HBc–positive. With the evolving data during the past few years better elucidating the risk of HBV reactivation in HBsAg-negative but anti-HBc–positive patients, preemptive use of nucleos(t)ide analogs are now recommended for these patients in the moderate-risk and high-risk groups.

In addition, liver fibrosis assessment was included in the algorithm, as patients with advanced fibrosis and cirrhosis run a higher risk of mortality and morbidity with HBV reactivation. New data on HBV reactivation within patients coinfected with HBV and hepatitis C virus treated with direct-acting antivirals are also included.

New guidelines specific to HBV reactivation will provide guidance to healthcare professionals emphasizing the importance of screening for HBV prior to initiation of immunosuppressive therapy. You can learn more as expert faculty interpret key APASL guideline recommendations to address common misunderstandings in the management of patients with HBV infection.

Your Thoughts
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