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Hepatitis B screening low, missing at-risk patients
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The prevalence of hepatitis B screening to prevent a flare in disease in patients initiating chemotherapy is suboptimal and still misses patients at high risk for hepatitis B reactivation, according to data from two single-institution studies presented at the 2010 ASCO Annual Meeting.
Screening for hepatitis B can prevent virus reactivation, which is a well-recognized complication that occurs after chemotherapy. More than 5% of cancer patients who have hepatitis B reactivation die from liver failure, according to Emmy Ludwig, MD, assistant attending physician at Memorial Sloan-Kettering Cancer Center. In addition, risk for reactivation persists for at least 6 months after immunosuppression ends, and prophylaxis to prevent reactivation is effective and easily administered, Ludwig said.
Despite still suboptimal screening rates, "hepatitis B screening is gaining momentum in oncology and public health communities,” said Jessica P. Hwang, MD, MPH, assistant professor, department of general internal medicine at The University of Texas M.D. Anderson Cancer Center.
In 2008, the CDC issued a recommendation that called for routine screening for hepatitis B in all patients undergoing cytotoxic or immunosuppressive therapy. Earlier this year, ASCO published a provisional clinical opinion to address hepatitis B screening in cancer patients. Its recommendations differed slightly from the CDC’s.
“ASCO advised physicians to screen patients who are either at high risk for hepatitis B or who are planning to have therapies that are highly immunosuppressive, such as hematologic stem cell transplantation or regimens containing rituximab [Rituxan, Genentech],” Hwang said.
Despite these recommendations, widespread compliance has been slow to gain traction, and more research is needed to better define the benefits of more routine screening policies.
Screening by cancer type
The first study examining hepatitis B screening was conducted by Hwang and colleagues at M.D. Anderson Cancer Center. The retrospective, cross-sectional study examined newly diagnosed adult cancer patients who had undergone chemotherapy between January 2004 and September 2007. The researchers defined the proportion of these patients who had undergone screening for the hepatitis B virus using hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (anti-HBc) 2 months before or 1 month after their first chemotherapy (n=12,340).
Analyses were conducted to examine differences in the prevalence of screening and test positivity between solid and hematologic malignances.
Of the patients who had undergone chemotherapy, 18% had been screened with HBsAg (2% positive) and 17% had been screened with anti-HBc (8% positive).
“Rates of screening were significantly lower for patients with solid tumors as compared with patients with hematologic malignancies,” Hwang said. “However, despite the lower rates of screening, the solid tumor patients who were screened had significantly higher rates of positive test results.”
The researchers also conducted a subgroup analysis to examine the rate of hepatitis B screening among patients at high risk for the virus by looking at ICD-9 diagnosis codes in billing databases before the date of the first screening test, Hwang said. Further, they looked at tumor registry data to examine ethnic groups that may be at increased risk for hepatitis B.
“Overall, patients with hepatitis C, general hepatitis and other liver disease had a significantly increased rate of screening than patients who did not have these diagnoses,” Hwang said.
However, when examining the Asian population — used as a surrogate for coming from a high prevalence area — the rates of screening were low and did not significantly differ by ethnicity. Yet, as anticipated, Asian patients had significantly higher rates of having a positive HBsAg (26% vs. 1% in non-Asians).
These same prevalence trends were found when examining solid tumor patients.
In contrast, in hematologic malignancy patients, screening did not significantly differ by known hepatitis B risk factors. In hematologic malignancy patients, rates of screening and positive HBsAg were also higher among Asians as compared with non-Asians, according to Hwang.
In all, about 20% of patients undergoing chemotherapy were previously screened for hepatitis B virus.
“Although patients with liver-related risk factors had higher rates of screening, the rates were still suboptimal,” Hwang said.
Immunosuppressive therapy
In the second study, Ludwig and colleagues at Memorial Sloan-Kettering Cancer Center reported the results of a study that examined the prevalence of HBsAg and hepatitis B virus core antibody (HBcAb) positivity in the first 6 months of a hepatitis B screening program in patients initiating immunosuppressive therapy.
The researchers had previously identified 22 patients who had hepatitis B virus reactivation. Four patients died, 19 were hospitalized, one required a liver transplant and four had clinically significant delays in their cancer treatment or surgery. No association was identified linking the reactivation with a particular malignancy or medication. Therefore, Memorial Sloan-Kettering Cancer Center established a standard to screen patients initiating immunosuppressive therapy for hepatitis B. The recommendation for prophylaxis of patients was based on planned treatment and risk group.
During the first 6 months of the program, 3,343 patients (48%) were screened for hepatitis B before first chemotherapy intervention; 4.8% were tested after first chemotherapy intervention and 43.6% were not tested. In all, 1,720 patients were screened. If patients were positive for HBsAg or HBcAb, hepatitis B DNA by polymerase chain reaction (HBV PCR) was measured.
Of the screened patients, 1.1% were positive for HBsAg (83.3% of whom had evidence of positive HBV PCR) and 9.2% were HBsAg negative but HBcAb positive (2.6% of these patients were HBV PCR positive; see Table).
“Of real concern are the four patients who were HBsAg negative but HBcAb positive — who had evidence of HBV replication,” Ludwig said “This group is thought to be large; in some studies, up to 20% of patients with HBcAb who lack HBsAb still replicate virus.”
In addition, the researchers found that “profiling” by country of birth, cancer diagnosis or planned treatment missed a substantial number of patients.
Finally, in this program, prophylactic treatment with a nucleoside antiviral agent was 100% effective in preventing HBV reactivation, Ludwig said.
Moving forward, although additional research is needed on the optimal timing, duration and type of antiviral prophylaxis, the ultimate goal is zero reactivation cases, she added. – by Leah Lawrence
Table: Serology Profile Results Among Hepatitis B Virus Screened Patients (n=1,720) |
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There are unclear benefits and harms to routine screening for hepatitis B in patients undergoing cytotoxic or immunosuppressive therapy. Current practice should be guided by awareness and clinical judgment. More research is necessary to determine prevalence rates, risk factors for reactivation and strategies for prophylactic treatment.
– Sandra Wong, MD
Assistant Professor,
Division of Surgical Oncology,
University of Michigan Health Systems
For more information:
- Hwang J. #9008.
- Ludwig E. #9009. Both presented at: the 2010 ASCO Annual Meeting; June 4-8; Chicago.