Screening Cancer Patients for Hepatitis B: Should it Be Routine?

Zosia Chustecka

June 24, 2010

June 24, 2010 — Chemotherapy and immunosuppressive drugs, including high-dose steroids, can cause the reactivation of hepatitis B in people who are carrying the virus, with potentially fatal results.

Hence, cancer patients who are about to undergo such treatment should be screened for hepatitis B virus (HBV), and treated prophylactically with an antiviral if they are found to be positive, according to a new protocol recently put into place at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City.

The new protocol was outlined at the recent American Society of Clinical Oncology (ASCO) 2010 Annual Meeting (abstract 9009) by Emmy Ludwig MD, an MSKCC gastroenterologist, who explained that it was set up after a retrospective review found deaths from liver failure, resulting from hepatitis B activation, in patients who had potentially been cured of their cancer.

This new protocol is in line with recommendations issued in 2008 by the Centers for Disease Control and Prevention, together with the American Association for the Study of Liver Diseases, which recommends screening for HBV in several groups of people, including those about to undergo immunosuppressive therapy.

But this is directly at odds with a new provisional clinical opinion just issued by ASCO, which concludes that there is no need to screen all cancer patients prior to chemotherapy and immunosuppressive drugs, only those considered to be at high risk.

The ASCO provisional opinion, published online June 1 in the Journal of Clinical Oncology, states that 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."

Instead of being carried out routinely, it suggests that HBV screening in cancer patients requires "clinical judgment." Physicians can consider screening patients belonging to groups at heightened risk for chronic HBV infections if highly immunosuppressive therapy is planned, the document states.

At the meeting, Dr. Ludwig said she was "surprised" by this.

New Protocol at MSKCC

The new protocol at MSKCC, introduced just over a year ago, recommends screening all patients who will receive anticancer therapy, including hormonal therapy and high-dose steroids (equivalent to a cumulative dose of prednisolone of >80 mg).

The cases who died were cured patients.

The action was prompted by a retrospective review of the MSKCC experience, which found 23 documented cases of hepatitis B reactivation in cancer patients on immunosuppressive therapy in the previous 3 years. Four patients died, 3 of whom had solid tumors. "The cases who died were cured patients — one was a 35-year-old with early breast cancer," Dr. Ludwig said. Nineteen patients were hospitalized, 1 required a liver transplant, and 4 had a "clinically significant delay" in treatment with curative chemotherapy or surgery, she said.

"Two of these patients were only on steroids," she noted.

"We think this is a vast underestimation," she said, and her team suspects that many more cases, maybe even hundreds of cases, went undocumented.

Under the new protocol, cancer patients are screened for hepatitis surface antigen (HBsAg), which indicates a chronic infection, and also for hepatitis B core antibody (HBcAb), which indicates a previous infection. If either or both are positive, then patients also undergo a reflexive HBV DNA polymerase chain reaction (PCR).

Patients who test positive for HBsAg and for HBV DNA PCR are started on prophylactic antiviral therapy with entecavir 0.5 mg orally once daily, which is continued throughout their cancer therapy and for 6 months after it ends.

Patients who test negative for HBsAg and for HBV DNA PCR but test positive for HBcAb are not given prophylactic antiviral therapy, but are followed and retested with PCR every 3 months, unless they are slated for a bone marrow transplant or rituximab therapy, in which case they receive entecavir.

This protocol has been in place for just under a year, and so far there have been no cases of reactivation, Dr. Ludwig noted. She also said that there have been no adverse reactions reported with entecavir: "We have seen absolutely no toxicity."

In the time that the protocol has been in place, just more than half of the cancer patients have been screened (1720 of 3309 patients, 53%).

This is another thing to add to very busy oncologists' lives.

This is an increase in what was happening previously, when about 10% of cancer patients were screened for HBV, she noted, but added that "this is another thing to add to very busy oncologists' lives, and some people have responded better than others."

Of the 1720 cancer patients who were screened, 18 patients (1.1%) tested positive for HBsAg, of whom 91% had solid tumors and 46% were Asian.

There were also 155 patients (9.2%) who tested positive for HBcAb, of whom 76% had solid tumors and 19% were Asian.

Profiling patients by country of birth, cancer diagnosis, or planned treatment will miss a lot of patients who test positive, Dr. Ludwig said.

"The screening is straightforward, and the most exciting thing is that prophylaxis has been 100% effective," she concluded.

Inability to Select High-Risk Patients

In a discussion of this presentation, Sandra Wong, MD, MS, from the University of Michigan in Ann Arbor, said that the finding that 91% of patients who tested positive for HBsAg had solid tumors was "a very surprising and unanticipated result."

Dr. Wong, who was a coauthor of the recent ASCO Provisional Clinical Opinion that recommended screening for HBV only for high-risk patients, rather than routinely, pointed out that "this experience highlights the inability to select high-risk patients for screening for HBV."

She commended the MSKCC team for putting this protocol in place, but added that the short experience so far "limits interpretation, especially as prophylaxis will be continued for 6 months after cancer treatment and the protocol has been in place for less than a year."

There is no doubt that increased awareness of this issue is important.

"There is no doubt that increased awareness of this issue is important," Dr. Wong concluded. "There may be a lot of benefit, but it is not based on strong evidence at this time"

In addition, Dr. Wong raised a question about the choice of antiviral for prophylaxis. "Lamivudine is really the accepted drug and has been used in many randomized trials, although entecavir is being increasingly used," she said.

Dr. Ludwig explained that her team chose entecavir because of documented cases of resistance with lamivudine.

In another presentation at the meeting, Gretchen Genevieve Kimmick, MD, from Duke University in Durham, North Carolina, included this work in her overview of Highlights of the Day. She noted that she had found, in a review publication, data to show that prophylaxis with lamivudine had a "number needed to treat to prevent reactivation of HBV of only 3, so it is certainly worth considering."

Dr. Ludwig and Dr. Wong have disclosed no relevant financial relationships.

J Clin Oncol. Published online June 1, 2010. Abstract