THU0146 Clinical analysis of hepatitis B virus reactivation associated with non-biological disease-modifying antirheumatic drug(s) in patients with rheumatoid arthritis

Abstract

Background Hepatitis B virus (HBV) reactivation, which refers to the abrupt rise in HBV replication in patients with inactive or resolved hepatitis B and is triggered typically by immunosuppressive chemotherapy in patients with cancer, can also occur in patients with RA undergoing DMARDs therapy, especially in endemic areas of HBV infection such as China. However, most related publications until now are based on case reports or case series. Objectives To investigate the clinical features of HBV reactivation associated with non-biological DMARDs therapy in a cohort of Chinese RA patients. Methods The follow-up records of 18 Chinese RA patients with positive serum HBsAg treated with non-biological DMARDs from March 2006 to September 2011 were analyzed. A multiple regression model was developed by stepwise method to screen the risk factor(s) for HBV reactivation from gender, age, non-biological DMARDs including glucocorticoid, MTX, leflunomide (LEF), HCQ, SSZ,and preventive antiviral therapy. Results 1. Among 18 patients, 15 (83%) were females and mean age was (47±12) years, with 2 to 61 months’ follow-up. Baseline load of HBV-DNA was determined in 11 patients and four (36%) was positive (≥103 copies/mL). Transaminases and bilirubins were normal before DMARDs therapy in all patients. All patients took combination therapy of non-biological DMARDs without biologic agents during follow-up. Glucocorticoid (equivalent to prednisone 10mg/d, except one overlapped with lupus and one complicated with rheumatoid vasculitis) was taken in 13 patients, and MTX 10∼20mg/week in sixteen, LEF 10∼20mg/d in ten, HCQ 0.2∼0.4g/d in five and SSZ 1.5∼2g/d in four. 2. Seven of 18 patients (39%) developed HBV reactivation 4 to 38 months after non-biological DMARDs therapy, of whom six cases showed more than 10-fold rise than baseline HBV-DNA and the other one showed reversion from negative to positive HBsAg. Five of 7 patients (71%) with HBV reactivation developed active hepatitis, of whom three (43%) with jaundice (one died of acute hepatic failure, one developed decompensated cirrhosis and one recovered), the other two (29%) without jaundice who recovered after therapy. 3. The multiple regression analysis showed LEF (p<0.001) and glucocorticoid (p=0.002) were risk factors for HBV reactivation in RA patients, in which LEF alone could explain 48% risk of HBV reactivation and the combination of LEF and glucocorticoid explain 70%. HBV reactivation occurred in all six patients with combination therapy of LEF and glucocorticoid. 4. Two patients with baseline HBV-DNA ≥105 copies/mL received preventive antiviral drug before DMARDs therapy, and the load of HBV-DNA decreased to 103∼104 copies/mL with normal liver function for more than one year. Conclusions Chinese RA patients should screen HBV infection including the load of HBV-DNA before non-biological DMARDs therapy. LEF, especially with glucocorticoid, should be used cautiously or even be avoided for RA patients with positive HBsAg and/or positive HBV-DNA. HBV reactivation and liver functio...