Updated guidelines for preventing and treating hepatitis B virus reactivation

Updated guidelines for preventing and treating hepatitis B virus reactivation

New recommendations address advances in immunosuppressive therapies and emphasize antiviral prophylaxis for high-risk patients.

In a recently published study inGastroenterologyResearchers are updating clinical practice guidelines to prevent and monitor hepatitis B virus (HBV) reactivation.

What is HBV reactivation?

HBV reactivation (HBVR) occurs when HBV activity is no longer suppressed by the immune system in people who are positive for either HBV surface antigen (HBSAG) or HBV core antibody (anti-HBC). The most common cause of HBVR is prolonged immunosuppression due to medications, particularly B cell depleting agents such as rituximab, or disease. HBSAG positivity also confers a higher risk of HBVR than past-resolved HBV infection.

A measurable baseline risk is defined as HBVR prophylaxis. “”

Need for updated guidelines

The American Gastroenterology Association's (AGA) first guideline on HBVR prevention and management was published in 2014 and focused on immunocompromised patients. Since then, many new immunosuppressive drugs and interventions have been approved for clinical use, some of which include immune checkpoint inhibitors (ICIs), anti-interleukin (IL) therapies, chimeric antigen receptor T cell (CAR-T) therapies, and Janus kinase (JAK) inhibitors.

In these recent advances, clinicians need to update current guidelines to provide evidence-based recommendations on the appropriate use of antiviral and surveillance strategies for HBVR. These guidelines are particularly important for frontline healthcare professionals who encounter HBV patients in their practice, patients exposed to HBVR risk factors, and policy makers.

The Grading Recommendation Assessment, Development and Evaluation (GRADE) approach was used to formulate these recommendations. Following a systematic review of existing evidence, these new recommendations were based on balance of impact/adverse effects with considerations of patient values, costs and healthcare equity.

Risk categories

Previous guidelines categorized patients as low, moderate, and high risk with less than 1%, 1-10%, respectively. over 10% risk. The greatest variability in decision making was in the moderate risk category.

To formulate the updated guidelines, patients were given a survey to understand their treatment preferences and values, such as: Data from randomized controlled trials (RCTs) comparing two alternative treatment approaches were also used to determine the relative risk of different outcomes.

An 82% lower risk of HBVR was associated with antiviral prophylaxis, while a 77% lower risk of hepatitis flareup was attributed to HBVR. However, the baseline risk determines the size of the actual effect, which could ultimately influence the final decision on antiviral use.

Exposures were also considered and classified according to the risk of HBVR to patients when used as individual medications. Low-dose corticosteroids in HBSAG-negative anti-HBC-positive individuals are typically high risk compared to the high risk used with moderate to high doses for four or more weeks in HBSAG-positive individuals. Immune checkpoint inhibitors and anti-TNF therapy were also associated with low risk unless the person is HBSAG positive.

Strong vs. conditional recommendations

Strong recommendations were based on the observation that most people wanted the recommended option. Comparatively, conditional recommendations implied that most would prefer the recommended course of action.

For clinicians, the strongly recommended course of action would be agreed upon by most patients without the need for extensive discussion, although the opposite is often true with conditional recommendations that are more dependent on the patient's values ​​and risk aversion. For policymakers, strong policy recommendations would be appropriate, while conditional recommendations require additional participation and performance measures.

Four recommendations

Antiviral prophylaxis is clearly recommended for those at high risk of HBVR. These medications should be started before starting the risk-associated medication and continued for six months after it is stopped. For B cell depletion therapy, antivirals should be continued for 12 months.

As with high risks, the antivirals selected must not be susceptible to the development of resistance. Patients who are concerned about the use and cost of these medications, and who are less risk-averse, may elect to be monitored.

Patients at low risk of reactivation can be monitored regularly without prophylaxis under certain conditions. Monitoring is required at one to three month intervals and should include assessment of HBV viral load and alanine aminotransferase (ALT) levels. However, risk-averse people and those who are not concerned about their cost or use may choose to use antiviruses.

All people at risk for HBV should be tested, regardless of their risk level. This recommendation is based on screening advice from the United States Centers for Disease Control and Prevention (CDC), which targets all adults with testing for HBSAG, anti-HBSAG, and anti-HBC. If either HBSAG or anti-HBC is positive, the patient should be tested for the presence of viral DNA.

Conclusions

The updated guidelines prescribe best practices for the management of HBVR based on the patient's risk level. However, cost-effectiveness analyzes are required for each risk category because out-of-pocket costs may limit their use and exacerbate health care disparities.

In the future, an online database of HBV serologic results could provide important information that may impact baseline risk establishment. By avoiding the need to depend on biological plausibility and expert consensus, this would allow for more precise risk categorization.

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