Dear editor,

We are writing in response to 'Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumor necrosis factor alpha therapy' by Lan, et al[1]. We performed a similar retrospective study in the rheumatoid arthritis and the spondyloarthritis patients comorbid with chronic hepatitis B treated by anti-tumor necrosis factor alpha (anti-TNF- alpha). Our study was slightly different from Lan's in that none of our patients receive preemptive antiviral therapy. We reviewed a total 220 patients who had been treated with etanercept or adalimumab from January 2002 to November 2010 in Chung Shan Medical University Hospital, Taiwan. We monitored the serum aminotransferase (ALT) levels, hepatitis serologic status including HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV core IgG antibody (HBcAb), and HBV DNA. The endpoints were the biochemical flare defined by persistent twofold elevation of ALT from normal upper limit in >/=2 consecutive tests and the virological flare defined by HBV DNA viral load increased by one log10IU/mL compared with the baseline.

Among those 220 patients, 23 (10.45%) patients had chronic hepatitis B (HBsAg+) without preemptive antiviral therapy. Twelve were excluded due to missing data. Of these remaining 11 patients, 7 (63.6%) had virological flares but none of them had biochemical flare. Six of 7 (85.7%) HBV flares occurred within 6 months after initiating TNF blockers. On contrary to Lan, et al[1], our patients experienced no biological flare and had lower viral load at baseline (HBV DNA 475.36+/-777 IU/mL). Three similarities were observed in both studies. Firstly, in the study of Lan, 62.5% (5 of 8) HBsAg (+) patients without preemptive antiviral therapy developed reactivations of hepatitis B while our data showed 63.6% (7 of 11) of patients had virological reactivations. Secondly, those with HBV reactivation in both studies had good clinical outcome after antiviral treatment. Thirdly, most of the patients developed reactivations (85.7% vs 100% in Lan, et al) within the first 6 months after initiating anti-TNF- alpha.

All patients with rheumatic diseases who plan to receive biological treatment should undergo the baseline screening tests for HBV including HBsAg, anti-HBs, anti-HBc and HBV DNA. Antiviral treatment should be initiated before the biological treatment in patients with active hepatitis[2]. According to the clinical practice guideline of the European Association for the Study of the Liver (EASL), immunotolerant patients with persistently normal ALT levels and a high HBV DNA level do not require immediate liver biopsy or therapy[2]. However, there is no guideline for patients treated with anti-TNF agents. The cost of preemptive antiviral therapy was high[3] and the time of discontinuation of antiviral therapy was still unclear. Moreover, long-term antiviral treatment increases the risk of drug resistance through viral mutations[2,4]. Careful and close follow-up of ALT and HBV DNA is essential, especially in the first 6 months of anti-TNF-alpha. Immediate initiation of antiviral therapy when reactivation once detected is a good strategy for management.

References

1 Lan JL, Chen YM, et al. Kinetics of viral loads and risk of hepatitis B virus reactivation in hepatitis B core antibody-positive rheumatoid arthritis patients undergoing anti-tumour necrosis factor alpha therapy. Ann Rheum Dis 2011;70:1719-1725.

2 European Association For The Study Of The Liver. EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009;50:227-242.

3 Colombo GL, Gaeta GB, et al. A cost-effectiveness analysis of different therapies in patients with chronic hepatitis B in Italy. Clinicoecon Outcomes Res 2011;3:37-46.

4 Kim SS, Cheong JY, et al. Current Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B. Gut Liver 2011;5(3):278-87

Conflict of Interest:

None declared