On-treatment monitoring of adefovir therapy in chronic hepatitis B: virologic response can be assessed at 24 weeks.
Patients with chronic hepatitis B (CHB) who will and those who will not respond to adefovir (ADV) monotherapy need to be identified at an early stage in order to adjust treatment and prevent future development of antiviral resistance. In a single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median follow-up of 122 (24-185) weeks, 42 (55%) patients achieved virologic response (VR), defined as HBV-DNA levels <10(3) copies/mL, and 10 patients (13%) developed genotypic ADV resistance. Independent baseline predictors of VR were HBeAg negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24-7.19; P = 0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05-1.18; P = 0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41-0.75; P < 0.001). HBV-DNA at week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48. Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54; 95% CI 1.39-30.9; P = 0.018), and not achieving VR during treatment (HR 6.60; 95% CI 1.35-32.4; P = 0.008). Patients without VR at week 24 already demonstrated a trend towards the emergence of ADV resistance (P = 0.07). HBV-DNA at week 24 was a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant mutations developed more frequently in patients without VR at week 24. Therefore, our study suggests that virologic response to ADV therapy can be assessed at 24 weeks, instead of the generally recommended 48 weeks.
Reijnders
J G P
JG
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
Leemans
W F
WF
Hansen
B E
BE
Pas
S D
SD
de Man
R A
RA
Schutten
M
M
Janssen
H L A
HL
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine