Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine.
A primary non-response to oral drugs against hepatitis B virus (HBV) is a generally-accepted criterion for interrupting treatment. We investigated whether the concept of primary non-response suggested by current American (AASLD) and European (EASL) guidelines is appropriate for treatment with entecavir (ETV).The study included 1,254 treatment-naïve patients who had pretreatment HBV DNA levels of >2,000 IU/mL and received ETV 0.5mg/day for over 6 months. "Primary non-response" was defined as a <2 log drop in HBV DNA after 6 months of therapy by AASLD and as a <1 log drop after 3 months by EASL. The cumulative probability of virological response (VR; HBV DNA of <15 IU/mL) was compared in patients with and without primary non-response. Median time to achieve VR was significantly shorter in primary responders by AASLD than non-responders (12 vs. 24 months; P=0.004), but the cumulative probability of achieving a VR at 54 months was similar in the two groups (95.8% vs. 100%). Time to achieve a VR and cumulative probability of VR over time did not differ between primary responders and non-responders by EASL. On-treatment virological breakthrough occurred in 18 patients with a cumulative rate of 4.6% at 72 months. ETV resistance was detected in 13 of these 18 patients (72.2%), who were all classified as primary responder according to both guidelines. Conclusions: Long-term ETV therapy generally leads to a VR in treatment-naïve patients, although the time to achieve it is delayed in primary non-responders. The current recommendation to change therapy in primary non-responders needs to be modified to reflect drug differences in antiviral potency and resistance risk.