SUMMARY: Immunosuppressive chemotherapy drugs can potentially cause the immune system to lose control over hepatitis B virus, but HBV screening is not required for all patients about to start cancer treatment, according to a controversial provisional clinical opinion from the American Society of Clinical Oncology (ASCO) published in the July 1, 2010 Journal of Clinical Oncology. Clinicians may, however, test individuals at risk for infection or known to have been exposed to HBV.
By Liz Highleyman
The immune system is able to naturally suppress HBV in many people with normal immune and others are apparently cured with successful antiviral treatment. But a low level of virus can remain in the body and become active -- or reactivate -- if the immune system is weakened, for example due to HIV infection or use of immunosuppressive drugs to treat cancer.
The U.S. Centers for Disease Control and Prevention (CDC) in 2008 recommended routine hepatitis B screening-- that is, testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and hepatitis B surface antibodies (anti-HBs) -- for "persons receiving cytotoxic or immunosuppressive therapy" such as chemotherapy for malignancies.
The ASCO opinion takes a less aggressive approach due to lack of data showing benefits of routine testing.
"The evidence is insufficient to determine the net benefits and harms of routine screening for chronic HBV infection in individuals with cancer who are about to receive cytotoxic or immunosuppressive therapy or who are already receiving therapy," the opinion states.
"Individuals with cancer who undergo certain cytotoxic or immunosuppressive therapies and have HBV infection or prior exposure to HBV may be at elevated risk of liver failure from HBV reactivation," the statement continues. "As such, HBV screening requires clinical judgment. Physicians may consider screening patients belonging to groups at heightened risk for chronic HBV infection or if highly immunosuppressive therapy is planned."
Highly immunosuppressive treatments include bone marrow stem cell transplants and chemotherapy regimens that include rituximab (Rituxan).
If screening is deemed appropriate for an individual patient, the opinion recommends testing for HBsAg as a serologic marker for HBV infection. "In some populations, testing for anti-HBc should also be considered," according to the statement. However, "[t]here is no evidence to support serologic testing for anti-HBs in this context."
When evidence of chronic HBV infection is detected, "antiviral therapy before and throughout the course of chemotherapy may be considered to reduce the risk of HBV reactivation, although evidence from controlled trials of this approach is limited," the opinion adds. But "[s]creening and/or treating HBV infection should not delay the initiation of chemotherapy."
The ASCO opinion is subject to controversy. In addition to the CDC, the American Association for the Study of Liver Diseases (AASLD) and Memorial Sloan-Kettering Cancer Center also recommend routine HBV screening before immunosuppressive chemotherapy.
A retrospective review from Memorial Sloan Kettering Cancer Center, presented by Emmy Ludwig at the 2010 ASCO annual meeting last month, found 23 documented cases of HBV reactivation in cancer patients on immunosuppressive therapy in the prior 3 years at that center, resulting in 19 hospitalizations, 4 deaths, 4 clinically significant delays in cancer treatment, and 1 liver transplant. But in the nearly 1 year since HBV screening was implemented, with entecavir (Baraclude) treatment for those who test positive, there have been no cases of reactivation.
7/13/10
References
AS Artz, MR Somerfield, J Feld, and others. American Society of Clinical Oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. Journal of Clinical Oncology 28(19): 3199-3202 (Abstract). July 1, 2010.
RB Mendelsohn, S Nagula, Y Taur, E Ludwig, and others. Reactivation of chronic hepatitis B virus in cancer patients receiving immunosuppression: The case for screening. American Society of Clinical Oncology Annual Meeting. Chicago, June 4-8, 2010. Abstract 9088.
Other Source
Zosia Chustecka. Screening Cancer Patients for Hepatitis B: Should it Be Routine? Medscape (http://www.medscape.com/). June 24, 2010.
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