NEW YORK – While nowadays there is less likelihood that the hepatitis B virus causes rheumatic disease, major changes in epidemiology and drug therapy, especially the use of immunosuppressives, have made reactivation of the virus during the course of rheumatic disease treatment a major public health concern, according to Dr. Leonard H. Calabrese.
"HBV reactivation has been well known in cancer and transplantation but is now really coming to the fore in autoimmune and autoinflammatory diseases. It may be mild (asymptomatic viremia) or severe (fulminant liver failure and death) and has been observed in patients with both chronic infection or resolved disease. While it is largely preventable, unfortunately many physicians who regularly prescribe immunosuppressive therapies – including rheumatologists, oncologists, gastroenterologists, and dermatologists – do not recognize this potential," Dr. Calabrese said at a meeting sponsored by New York University.
Dr. Leonard H. Calabrese
The major risk of HBV is not during but after immunosuppression, when reactivation leading to severe or fatal hepatitis can occur. Reactivations have been reported rarely with low-dose prednisone and methotrexate, as well as all tumor necrosis factor (TNF) inhibitors, rituximab, abatacept, and infliximab, prompting a black box warning for many biologics, said Dr. Calabrese, director of the Fasenmyer Center for Clinical Immunology at the Cleveland Clinic.
In a retrospective study of 257 patients with positive HBV markers who were treated with TNF-targeted therapies, 39% with chronic infections (as indicated by the presence of HB surface antigens) developed HBV reactivation. Five developed acute liver failure, and four died (Medicine 2011;90:359-71). "This is not a trivial risk," Dr. Calabrese said.
Yet many rheumatologists do not screen for HBV prior to prescribing immunosuppressive therapy, he said. Dr. Calabrese cited a 2010 survey of rheumatologists that found that only 42% routinely screen for HBV before a patient begins nonbiologic disease-modifying antirheumatic drug therapy and 69% screen before prescribing a biologic DMARD. Seven percent of rheumatologists reported witnessing a reactivation event (Arthritis Care Res. 2010;62:704-11).
Of the three serologic markers for HBV (the hepatitis B surface antigen [HBsAg], the total hepatitis B core antibody [anti-HBc]), and the hepatitis B surface antibody (anti-HBsAb), Dr. Calabrese said he prefers HBsAg. "If you remember anything from this talk, remember that all patients with hepatitis B surface antigen need to be tended to before beginning any rheumatic therapy," he said. All positive tests should be followed up with HBV DNA testing.
Although all patients with a history of HBV are at some risk for HBV reactivation, with or without the presence of serologic markers, Dr. Calabrese outlined the relative risks of HBV reactivation as indicated by serologic findings. Those at highest risk are patients with chronic HBV infection (HBsAg positive, high level of HBV DNA), followed by inactive carriers (HBsAg positive, some HBV DNA) and those with resolved HBV (HBsAg negative, anti-HBc positive, anti-HBsAb positive). Those at lowest risk have resolved HBV (anti-HBc alone).
Rheumatologists should also be aware of the increased chance of HBV reactivation in high-risk populations. While in urban areas HBV is known to be associated with drug abuse, there is also a heightened risk in immigrants, especially those from Asia. Asian Americans are 2.7 times more likely to develop hepatocellular carcinoma. According to Dr. Calabrese, in mainland China there are an estimated 1 million people with rheumatologic problems who manifest chronic HBsAg positivity. "This is a global health problem," he noted.
Dr. Calabrese recommended that preemptive therapeutic measures be taken for all HBsAg-positive and HBV DNA–positive patients, including possible lifelong antiviral medication, and then these patients can be treated for their rheumatologic issues. Those who test positive for anti-HBc should be carefully monitored. "There should not be a patient with spondylitis, rheumatoid arthritis, lupus, or vasculitis who is getting less than effective therapy because they have chronic HBV," he said.
Dr. Calabrese reported no relevant financial disclosures.