CLINICAL OUTCOMES AFTER ADEFOVIR DISCONTINUATION IN LAMIVUDINE-RESISTANT CHRONIC HEPATITIS B PATIENTS

Abstract

Background/Aim: Sustained response rate after adefovir (ADV)discontinuation has been reported up to 66% in nucleos(t)ide treatment naïve patients. But, it is not known whether the viral response is sustained after ADV discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients receiving ADV. Our aim was to analyze the clinical outcomes after ADV discontinuation in LMV-R CHB patients.

Patients and Methods: One hundred twenty LMV-R CHB pts receiving ADV monotherapy were analyzed retrospectively. Among them, 39 patients discontinued ADV treatment. Indication of ADV treatment cessation was undetectable HBV DNA which was documented on 2 separate occasions at least 6 months apart. In HBeAg positive patients, HBeAg seroconversion was confirmed two times. All of them received additional ADV for at least 12 months after the confirmation of undetectable HBV-DNA. After the exclusion of 20 patients who did not met treatment cessation,19 pts were included for analyze. LFT and HBV DNA (CobasTaqMan PCR assay, <70 copies/ml), HBeAg and anti-HBe antibody were measured every 3 months. Virological relapse was defined as re-detection of HBV-DNA. Arbitrary, virological relapse–high level (VR-H) was defined as re-detection of HBV-DNA higher than 105 copies/ml. Biochemical relapse was re-elevation of AST/ALT.

Results: ADV treatment baseline characteristics as follows as; mean ages were 37 years old, 10 were HBeAg (+). ADV treatment and additional therapy were given for 33 (median, range 11-47) and 18 months, respectively. They were followed up 11 (range 3-26) months after ADV cessation. During that period, 18/19 pts (95%) experienced viral relapse. VR-H was observed in 6 pts (32%). But, 12 of 18 patients (68%) showed serum HBV-DNA level less than 105 cps/ml. Biochemical relapses were observed only in 4 of 6 VR-H patient. 1 patient in VR-H experienced HBeAg reversion. Factors associated with VR-H such as age, sex, ALT, cirrhosis, baseline HBV-DNA, treatment and additional duration of ADV were analyzed. Only one factor associated with VR-H was HBV-DNA level above 104 cps/ml after 3rd month of ADV cessation. (80% vs 23%, p=0.047).

Summary/Conclusion: During the short term follow-up of ADV discontinuation, most patients(68%) showed viral relapse. But, most patients with VR maintained normal ALT and HBV-DNA level less than 105 cps/ml. Although the clinical significance of viral load less than 105 cps/ml was not known, ADV treatment cessation can be considered in selected patients. Long-term follow up and adequate number of patients were needed for the study.