Clinical Context

Hepatitis B virus (HBV) in the setting of cancer may be particularly dangerous, and previous guidelines from the American Society of Clinical Oncology (ASCO) have described recommendations for screening patients with cancer for HBV. In 2010, ASCO recommended screening only patients who had risk factors for HBV or who were candidates for highly immunosuppressive therapies such as rituximab or stem cell transplantation. In 2015, this recommendation was modified to include HBV testing before the initiation of anti-CD20 therapy, but was largely unchanged otherwise.

However, the current report describes more recent research in which 21% of patients with newly diagnosed cancer were positive for HBV infection on screening yet had no traditional risk factors such as multiple sexual partners or a history of intravenous drug use. This calls into question the practice of screening for HBV on the basis of risk factors. The current guideline from ASCO calls for broad testing for HBV among patients being considered for anticancer therapy.

Study Synopsis and Perspective

All patients with cancer who are candidates for systemic anticancer therapy should be screened for HBV before or at the start of therapy, according to an updated provisional clinical opinion (PCO) from ASCO.

"This is a new approach [that] will actively take system changes...but it will ultimately be safer for patients, and that is crucial," commented Jessica P. Hwang, MD, MPH, cochair of the ASCO HBV Screening Expert Panel and the first author on the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr Hwang told Medscape Medical News.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy in those with chronic HBV receiving any systemic anticancer treatment and in those with past HBV receiving any therapies posing an HBV reactivation risk.

"Hepatitis B reactivation can cause really terrible outcomes like organ failure and even death," Dr Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

"This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring," she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.^[1]

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening in patients with cancer, say the authors.

ASCO PCOs are developed "to provide timely clinical guidance" based on emerging practice-changing information. This is the second update to follow the initial HBV screening PCO published in 2010.^[2] In the absence of clear consensus resulting from limited data, the original PCO called for a risk-based approach to screening; a 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or stem cell transplantation and to those with risk factors for HBV exposure.^[3]

The current update provides "a clinically pragmatic approach to HBV screening and management" based on the latest findings, say the authors. This includes findings from a multicenter prospective cohort study of more than 3000 patients showing that 21% of patients with chronic HBV had no known risk factors for the infection and another large prospective observational cohort study, led by Dr Hwang, of more than 2100 patients with cancer in which approximately 90% had 1 or more significant risk factors for HBV infection, making selective screening "inefficient and impractical."^[1,4,5]

"The results of these 2 studies suggest that a universal screening approach, its potential harms (eg, patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment," the authors comment.

The screening recommended in the PCO requires 3 tests: hepatitis B surface antigen (HBsAg), core antibody (anti-HBc) total immunoglobulin or immunoglobulin G, and antibody to HBsAg (anti-HBs) tests.

Anticancer therapy should not be delayed pending the results, they said.

Planning for monitoring and long-term prophylaxis for chronic HBV should involve a clinician experienced in HBV management, the authors write. Management in those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than receiving prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they agreed.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management in these patients should follow relevant national HBV guidelines, they noted.

Challenges in Implementing Universal HBV Screening

The expert panel acknowledged the challenges associated with implementation of universal HBV screening as recommended in their report, and noted that electronic health record-based approaches that use alerts to prompt screening have demonstrated success. In 1 study of high-risk primary care patients, an electronic health record alert system significantly increased testing rates (odds ratio, 2.64 vs a control group without alerts), and another study that used a simple "sticky-note" alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.^[6,7]

In a cancer population, a "comprehensive set of multimodal interventions," including pharmacy staff checks for screening before anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.^[8]

A study of 965 patients in Taiwan also showed that a computer-assisted reminder system that prompted for testing before ordering anticancer therapy increased screening from 8% to 86%, but was less effective for improving the rates of antiviral prophylaxis in those testing HBV-positive, particularly among clinicians treating patients with nonhematologic malignancies.

"Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in [electronic health record] systems," the panel writes, noting that "[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation."

The panel also identified a research gap related to HBV reactivation risks "for the growing list of agents that deplete or modulate B cells" and noted a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary depending on the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective in patients with hematologic malignancies and high HBV reactivation risk, but are less consistent in patients with solid tumors and lower reactivation risk, they explained.

Dr Hwang told Medscape Medical News that not 1 of the more than 2100 patients in her HBV screening cohort study encountered issues with getting insurance payment for their HBV screening.

"That's a really strong statement that insurance payers are accepting of this kind of preventative service," she said.

Expert panel cochair Andrew Artz, MD, commented that there is now a greater acceptance of the need for HBV screening across medical specialties.

"There's growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment," Dr Artz told Medscape Medical News.

Dr Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is in part a result of the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies, and more lines of therapy, could mean greater risk, he explained, adding that testing is easy and universal screening is the simplest approach to determining who needs it.

"There's no question we will have to change practice," Dr Artz said in an interview. "But this is easier than the previous approach that essentially wasn't being followed because it was too difficult to follow and patients were being missed."

In fact, most clinicians will appreciate having an approach that's easier to follow, Dr Artz predicted.

If there is a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas with a paucity of subspecialists, oncologists will have to "take some ownership of the issue" as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as "strong," with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as "moderate." All were based on "informal consensus," with the exception of the key recommendation for universal HBV screening, using 3 specific tests, which was "evidence-based."

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr Artz received research funding from Miltenyi Biotec. All expert panel members' disclosures are available in the PCO update.

J Clin Oncol. Published online July 27, 2020.

Clinical Implications

• The current recommendations from ASCO suggest that all patients anticipating systemic anticancer therapy should be screened with HBsAg, anti-HBc, and anti-HBs.
• Patients with chronic HBV infection should be treated with an antiviral regimen during systemic cancer therapy and for 1 year after the end of cancer therapy. Patients with past HBV infection receiving anti-CD20 antibodies or stem cell transplantation should also receive antiviral treatment, but patients with past HBV infection receiving other forms of chemotherapy can be monitored for HBV reactivation without antiviral therapy.
• Implications for the Healthcare Team: The current guidelines take a more proactive approach to identify cases of HBV infection among patients with cancer. The entire healthcare team should be engaged in making the follow-up of these guidelines a priority.

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