Nick Mulcahy
March 17, 2011 (Hollywood, Florida) — Every cancer patient undergoing chemotherapy should be tested for hepatitis B virus (HBV) infection, said a presenter here at the National Comprehensive Cancer Network (NCCN) 16th Annual Conference.
Chemotherapy and its related immunosuppression can cause a reactivation of HBV – "a potentially fatal and preventable disease," said Emmy Ludwig, MD, from Memorial Sloan-Kettering Cancer Center in New York City.
"Reactivation may complicate cancer therapy," said Dr. Ludwig, explaining that delays in treatment can result.
Testing allows infected patients — those with chronic infection or past exposure — to be treated with prophylactic antiviral oral therapy, which is an "extremely effective" means of preventing reactivation, she said. Dr. Ludwig also told the NCCN audience that 5% to 40% of reactivation cases will die of liver failure.
Currently, cancer patients treated with rituximab are routinely screened for HBV, said Dr. Ludwig. In 2004, the US Food and Drug Administration issued a warning that there was a risk for HBV-reactivation-related fatal fulminant hepatitis with rituximab.
However, the need to screen for HBV is often associated only with "high-risk" groups, said Dr. Ludwig, especially natives of Asia. But "profiling patients by country of birth misses patients — about half of them," she said.
Furthermore, she said that the HBV problem is "enormous" and that an estimated one third of the world has been "exposed" to HBV, meaning that they have a core antibody (HBcAb+), and that about 350 million people have chronic infection, meaning that they have a surface antigen (HBsAg+).
In the United States, an estimated 15 million people (5% of population) have been exposed and about 1 million have chronic infection.
Interestingly, the NCCN does not recommend universal testing for patients undergoing chemotherapy.
Instead, the NCCN says in its Prevention and Treatment of Cancer-Related Infections guideline, that, "in patients undergoing intensive immunosuppressive therapy, evaluation of HBV surface antigen, core antibody, and surface antibody should be considered at baseline." Patients with a surface antibody only (HBsAb+) are effectively immunized against HBV, noted Dr. Ludwig.
The NCCN also recommends evaluation in hematopoietic stem cell transplantation recipients and donors.
However, at least 2 NCCN institutions routinely test all chemotherapy patients for HBV. Memorial Sloan-Kettering does, said Dr. Ludwig. Their testing protocol was outlined at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.
Stanford Comprehensive Cancer Center in Palo Alto, California, also tests for HBV, Robert Carlson, MD, told Medscape Medical News. Dr. Carlson is a breast cancer expert from Stanford who attended the NCCN meeting.
Another meeting attendee, Suzanne Cole, MD, from Charleston, West Virginia, was inspired by Dr. Ludwig's presentation. "I plan to personally screen all patients I am placing on chemotherapy for hepatitis B," she told Medscape Medical News.
"It is not difficult or expensive to screen for patients at risk for reactivation — I currently screen everyone who receives rituximab chemotherapy for hepatitis B," she added.
Dr. Cole also said that her group at the Charleston Area Medical Center might perform an observational study "to see how many patients we identify at risk for hep B reactivation."
"I hope we see more data emerge on the true risk of hepatitis B reactivation during chemotherapy," she said.
Dr. Ludwig said that the hepatitis C virus (HCV) is not comparable to the B virus with regard to activation. Immunosuppression from chemotherapy can increase HCV RNA levels, but related flares are "rare" and are "not preventable," she said.
Limited Data
The NCCN guideline says that the data are "limited" in support of antiviral therapy for active HBV infection in the context of cancer treatment.
Dr. Ludwig said that the data in support of prophylaxis have "major limitations." She cited a systematic review of 14 studies (2 randomized controlled trials, 8 prospective cohort studies, 4 retrospective cohort studies). Despite various shortcomings, the data collectively indicated that none of the patients in the studies receiving prophylactic lamivudine developed HBV‐related hepatic failure (0 of 108 patients vs 21 of 162 patients who received placebo).
The options for HBV treatment include lamivudine (which is no longer in favor because of drug-resistant viral mutations that occur with long-term therapy), entecavir (which is used at Memorial Sloan-Kettering), adefovir, tenofovir, and telbivudine.
Also, prevention is better than treatment after reactivation, according to the results of one study, said Dr. Ludwig.
In that study, 30 HBsAg+ lymphoma patients were randomized to either lamivudine treatment before chemotherapy (prophylaxis) or lamivudine treatment during chemotherapy if HBV DNA polymerase chain reaction levels increased. There was no HBV reactivation in the prophylaxis group, but in the delayed treatment group, 53% reactivated. Furthermore, there was no HBV acute hepatitis or liver failure in the prophylaxis group, whereas there was 47% in the delayed treatment group.
"Screening and prophylaxis appear to work," said Dr. Ludwig.
A number of organizations endorse universal screening for immunosuppressive therapy. The list includes the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, the American Gastroenterology Association, the World Gastroenterology Organization, the Asian‐Pacific Association for the Study of the Liver, the American College of Rheumatology, the Infectious Disease Society of America, the French Society of Rheumatology, and the Centers for Disease Control and Prevention.
ASCO does not recommend universal screening and says that randomized controlled trials are needed to establish reactivation rates and HBV-related complications, said Dr. Ludwig.
Dr. Ludwig argued that such trials might not be possible, that "other evidence of effectiveness is good," and that the potential benefits are "large."
"There are no randomized controlled trials to show that parachutes work," she argued.
Since instituting screening at Memorial Sloan-Kettering in 2006, the center has had only 3 reactivations, all of which were related to a failure to adhere to the treatment, said Dr. Ludwig.
National Comprehensive Cancer Network (NCCN) 16th Annual Conference. Presented March 10, 2011.
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