Be Alert for Hepatitis B Virus Reactivation

VBCR - April 2015, Volume 4, No 2 - NCRA 2015 Meeting
Alice Goodman

Hepatitis B virus (HBV) reactivation is a serious and potentially lethal complication of HBV infection, and the risk is increased in patients on immunosuppressive therapy, especially anti–tumor necrosis factor (TNF) inhibitors or TNF-like antirheumatic drugs used by patients with rheumatoid arthritis (RA) and other rheumatic diseases. This syndrome, which can occur in patients with active as well as “resolved” HBV infection, is largely preventable. Unfortunately many physicians who regularly prescribe immunosuppressive drugs are not aware of the potential for HBV reactivation.

At the 2015 annual meeting of the North Carolina Rheumatology Association, Leonard Calabrese, MD, updated attendees about HBV infection and how best to manage patients with rheumatologic disease coinfected with HBV. Calabrese is Professor of Medicine at the Cleveland Clinic Lerner College of Medicine, and R. J. Fasenmyer Chair of Clinical Immunology, Department of Rheumatic and Immunologic Disease, Cleveland Clinic, Ohio.

Chronic HBV accounts for 1.25 million cases in the United States. “HBV is de-emerging as a cause of rheumatic disease, while HCV [hepatitis C virus] is increasing,” noted Calabrese. “However, major changes in epidemiology and drug therapy make HBV reactivation a major concern.”

Extrahepatic complications of HBV, which can include arthralgia, arthritis, arthritis dermatitis, polyarteritis nodosa, and, less commonly, nephropathy and aplastic anemia, occur in less than 1% of HBV-infected patients. Reactivation of HBV following immunosuppressive therapy is a far more worrisome complication.

“HBV reactivation can lead to severe/fatal hepatitis. This is well reported to occur in rheumatoid arthritis and other conditions with conventional or biologic therapy,” Calabrese stated.

Definitions are important: HBV reactivation refers to abrupt, marked increases in HBV replication (HBV-DNA levels), usually accompanied by elevations in serum aminotransferase levels. Reverse seroconversion refers to reappearance of hepatitis B surface antigen (HBsAg) in a person who was HBsAg negative, hepatitis B core antibody (anti-HBc) positive. Recovered hepatitis B refers to seropositivity for anti-HBc without detectable HBsAg, with or without hepatitis B surface antibody (anti-HBs). Current HBV infection refers to seropositivity for HBsAg.

Drugs associated with HBV reactivation include corticosteroids, conventional chemotherapy, and injectable or infused biologic therapy (eg, anti-CD20, anti-TNF, abatacept, tocilizumab, and tofacitinib).

As HBV reactivation emerges as a major concern, various medical societies are developing guidelines. The American College of Rheumatology (ACR) 2012 Guidelines recommend screening high-risk patients for HBV before they receive methotrexate or leflunomide in order to mitigate the risk of HBV reactivation; testing for HBsAg is also recommended.

“All patients with a past history of HBV are at some finite risk of reactivation, regardless of presence or absence of serologic markers. The highest risk is among those with chronic HBV infection who are HBsAg positive and have high HBV-DNA viral load,” Calabrese said.

A reasonable strategy in HBV-infected patients requiring immunosuppression is to screen high-risk patients and to screen all patients going on immunosuppressive therapy for HBV infection, testing for the following: HBsAg, anti-HBc, and anti-HBs. Calabrese recommended following up by testing the HBV-DNA viral load in all positive cases.

He also advised preemptive therapy in all patients who are HBsAg positive and HBV-DNA positive, and careful monitoring in all isolated anti-HBc with drugs and a higher barrier to resistance. All patients who are candidates for antiviral therapy should be referred to hepatology experts, he added.

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