Oncologists should consider screening all patients with cancer for the hepatitis B virus (HBV) prior to starting systemic anticancer therapy, with a focus on tests that use the hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antihepatitis B surface antibody. This is according to a new ASCO provisional clinical update to an HBV screening and management guideline published in the Journal of Clinical Oncology.1
Previous research has indicated that up to 90% of patients with cancer have at least one risk factor for HBV infection.2 This research found that the prevalence rates of chronic HBV infection and past HBV infection were 0.3% and 6.0%, respectively. Current knowledge states that HBV reactivation often occurs during immunosuppression, placing patients with cancer (particularly those who have a history of HBV infection) at prime risk of reactivation.3,4 Cancer treatments—such as chemotherapies, immunosuppressive agents, and biologic therapies—can lower the immune system, ultimately reactivate the virus, and result in increased morbidity in patients with cancer. The trouble is that many patients with cancer are not being screened for HBV infection prior to receipt of anticancer therapy. To mitigate the risk of increased morbidity in these patients, many experts are calling for increased use of universal testing to identify infection early and/or prevent HBV reactivation.
Jessica P. Hwang, MD, MPH
Guideline Co-Chair Jessica P. Hwang, MD, MPH, of The University of Texas MD Anderson Cancer Center, told the ASCO Daily News that the most important update in this Provisional Clinical Opinion is the recommendation of universal screening of HBV infection in patients with cancer who anticipate systemic anticancer therapy. Randomized trials have found that universal screening for HBV, particularly HBsAg testing, could be increased by having alerts in the electronic health record. In contrast to universal screening, the implementation of risk-based screening may be more of a challenge, primarily because of the gap in knowledge among clinicians on the risk factors for HBV infection and/or the lack of time afforded to clinicians to conduct such assessments.
Assessment of HBV Reactivation Risk
Despite this challenge, the update does recommend the use of HBV reactivation risk assessment in patients with cancer with chronic HBV (ie, HBsAg-positive) or a history of HBV (ie, HBsAg-negative and anti–HBc-positive) infection. Non-cancer HBV monitoring and guideline-based treatment are both recommended for patients who are treated with hormonal therapy alone, as hormonal therapy by itself is not known to increase the risk of HBV reactivation to a substantial degree.
Treatment with anti-CD20 monoclonal antibodies or stem cell transplantation, however, may increase the risk of HBV reactivation. Dr. Hwang said systematic management of chronic HBV with antiviral prophylaxis during and up to 12 months after anticancer therapy is recommended.
She noted that antiviral prophylaxis is recommended for most patients with chronic HBV who are HBsAg-positive as well as for select patients with past HBV infection who are HBsAg-negative and anti–HBc-positive who are also receiving anticancer therapies that are considered to pose a significant risk of HBV reactivation. A total of three antivirals—entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide—are recommended for HBV infection due to their high levels of potency.
In patients with cancer and an HBV infection, the update recommends obtaining HBV DNA at baseline and every 6 months during antiviral therapy. The use of anti-HBs are also recommended as part of the screening panel. Patients who have negative anti-HBs may be at increased risk of HBV reactivation compared with patients with a positive anti-HBs.
The updated guideline also stated that an alternative to the use of both HBsAg and anti-HBc tests for screening would be to use HBsAg testing in all patients with cancer, irrespective of therapy. Testing with anti-HBc could be reserved for patients who receive cancer treatment that has proved to confer an increased risk of HBV reactivation and would invariably need monitoring and/or subsequent treatment with antiviral therapy.
Andrew S. Artz, MD, MS
“Antiviral therapy and monitoring for HBV reactivation may need to be continued even after the completion of anticancer therapy,” said Guideline Co-Chair Andrew S. Artz, MD, MS, of the City of Hope Comprehensive Cancer Center. He added that patients with a history of HBV who currently receive systemic anticancer therapies that do not increase the risk of viral reactivation could be carefully monitored with HBsAg and alanine aminotransferase, with initiation of antiviral therapy at the first indication of HBV reactivation. At the moment HBV reactivation is observed, clinicians should initiate antiviral therapy, according to the guideline.
Coordination of Care
Dr. Artz also emphasized that care should be coordinated with a clinician who has expertise in treating patients with chronic HBV, as these clinicians can help identify the best HBV monitoring strategy and long-term antiviral treatment following anticancer therapy. Additionally, a clinician experienced in HBV management could help monitor withdrawal flares and assess advanced liver disease, including cirrhosis and liver cancer. Dr. Hwang agreed with the sentiments raised by Dr. Artz, adding that oncologists should participate collaboratively with clinicians experienced in the management of HBV who can offer patient-tailored hepatitis B recommendations.
Dr. Hwang added that this update represents an opportunity to streamline hepatitis B screening to ensure safety in the administration of anticancer therapies. “Systems could be developed in clinical practice to incorporate routine hepatitis B testing prior to starting systemic anticancer therapy,” she said. “Further, this update will help guide clinicians on subsequent monitoring and antiviral therapies for patients with chronic or previous hepatitis B.”
DISCLOSURE: Dr. Hwang has received institutional research funding from Gilead Sciences and Merck Sharp & Dohme and has other financial relationships with Asian Health Foundation. Dr. Artz has received research funding from Miltenyi Biotec.
1. Hwang JP, Feld JJ, Hammond SP, et al: Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. July 27, 2020 (early release online).
2. Hwang JP, Lok AS, Fisch MJ, et al: Models to predict hepatitis B virus infection among patients with cancer undergoing systemic anticancer therapy: A prospective cohort study. J Clin Oncol 36:959-967, 2018.
3. Loomba R, Liang TJ: Hepatitis B reactivation associated with immune suppressive and biological modifier therapies: Current concepts, management strategies, and future directions. Gastroenterology 152:1297-1309, 2017.
4. Tavakolpour S, Alavian SM, Sali S: Hepatitis B reactivation during immunosuppressive therapy or cancer chemotherapy, management, and prevention: A comprehensive review. Hepat Mon 16:e35810, 2016.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, July 29, 2020. All rights reserved.