SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) – The ACR guidelines for hepatitis B virus screening prior to starting immunosuppressive therapy are sorely in need of an overhaul, Leonard H. Calabrese, MD, asserted at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

“We need to do better,” declared Dr. Calabrese, professor of medicine and head of the section of clinical immunology at the Cleveland Clinic.

The current ACR guidelines on hepatitis B virus (HBV) screening in rheumatoid arthritis patients ( Arthritis Rheumatol. 2016 Jan;68[1]:1-26 ) are unchanged since 2008. The recommendation is for selective screening confined to patients who are going to go on methotrexate or leflunomide or who state they have an HBV risk factor.

That approach is wholly inadequate for the prevention of iatrogenic HBV reactivation, a known complication of immunosuppressive therapy. And this is a potentially fatal yet preventable condition, the rheumatologist stressed.

He recommended that his fellow rheumatologists skip the ACR guidance and instead do what he does, which is to follow the American Association for the Study of Liver Diseases (AASLD) guidelines that have been in place for the past 8 years ( Hepatology. 2009 Sep;50[3]:661-2 ).

The AASLD screening algorithm is simple and straightforward: Screen everyone who is going to go on any form of immunosuppressive therapy or cancer therapy by testing for hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies (anti-HBc).

The highest-risk group for HBV reactivation are patients who are HBsAg positive. They have an active infection and should be referred to a hepatologist for antiviral therapy. Depending upon the patient’s HBV DNA level and liver function test results, the antiviral therapy will be started either prior to or simultaneously with the immunosuppressive therapy.

The AASLD guidelines rank immunosuppressive agents in terms of their associated risk of HBV reactivation based upon the best available evidence. It’s a tricky business. Patients with a history of HBV are excluded from clinical trials of immunosuppressants, so the evidence is sketchy.

Nevertheless, the consensus is that among HBsAg-positive patients the risk associated with methotrexate and other antimetabolites is considered low. The tumor necrosis factor inhibitors are deemed to pose a moderate risk, as does cyclosporine. The risk of other cytokine inhibitors, including ustekinumab (Stelara) and abatacept (Orencia), is uncertain, but thought to be moderate to high. The use of corticosteroids at more than 20 mg/day for longer than 4 weeks is considered high-risk therapy. And rituximab (Rituxan), which carries a black box warning regarding HBV reactivation, is rated very-high-risk, as is cancer chemotherapy and hematopoietic stem cell transplantation.

An HBV screen that comes back HBsAg negative but anti-HBc positive indicates past HBV infection. This places a patient at intermediate risk for reactivation during immunosuppressive therapy. If Dr. Calabrese plans to put that patient on rituximab, he’ll make a referral to a hepatologist for consideration of antiviral therapy. If he’s going to use any other form of immunosuppressive therapy in a patient who is HBsAg negative/anti-HBc positive, he tests for HBV DNA every 1-3 months while the patient is on treatment. If HBV DNA becomes detectable, it’s time to start antiviral therapy.

No further action is required if a rheumatology patient’s HBV screen comes back negative for both HBsAg and anti-HBc.

“There are six approved drugs for HBV. They don’t have the power of the direct-acting antiviral agents used for hepatitis C. Cures are very infrequent. But lifelong viral suppression is readily achievable with these drugs, which are well tolerated and have low potential for drug-drug interactions. If patients have undetectable HBV DNA on antiviral therapy, I believe we can treat them with any of our rheumatologic regimens, including rituximab,” Dr. Calabrese said.

He reported having no financial conflicts of interest regarding his presentation.


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