Safety and adherence to the long-term treatment with nucleoside and nucleotide analogues in patients with chronic hepatitis B

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To evaluate the safety, the persistence and adherence rates of the long-term nucleos(t)ide analogs treatment in patients with chronic hepatitis B (CHB)

Material and methods

One hundred and one patients with CHB who were treated with telbivudine, tenofovir disoproxil fumarate (TDF), or entecavir for at least 3 years were enrolled in the study. We assessed the renal (serum creatinine [sCr], eGFR by Cockcroft-Gault [eGFR]) and muscle (serum CPK level) safety parameters and the other adverse events. Persistence was defined as continuing acquisition of medication during follow-up, while adherence was defined as the percentage of days during which patients took medication


TDF treated patients showed increase in median serum creatinine level (14 μmol/l, +12,2% from baseline, p=0.0034) and median decrease in eGFR (12,3 ml/min, -13,5% from baseline, p=0.008) during 5-year follow-up. Telbivudine treated patients showed median increase in eGFR (6,2 ml/min, +5,9% from baseline, p=0.023) during 8-year follow-up. There were no changes in sCr or eGFR in entecavir treated patients during 8-year follow-up. Five (21,7%) telbivudine treated patients developed myalgia and myopathy. Treatment was discontinued in 3 of 5 patients. No clinically significant increase in CPK level or myopathy developed in entecavir or TDF treated patients. The mean persistence rate was 78%. It was higher among entecavir treated patients (89%) compared with that in tenofovir (76%) or telbivudine (48%) treated patients. The adherence rate was better in tenofovir (92%) and entecavir (91%) treated patients then in telbivudine (70%) treated patients.


Entecavir and tenofovir were safe and were associated with the higher persistence and adherence rates during long-term treatment in patients with CHB. Renal safety parameters should be monitored in tenofovir treated patients

Key words

Chronic hepatitis B, entecavir, tenovofir, telbivudin, safety.