[A clinical study of adefovir dipivoxil in treating lamivudine refractory HBeAg-positive chronic hepatitis B].
OBJECTIVE
To evaluate the efficacy and safety of adefovir dipivoxil (ADV) in treating patients with lamivudine (LAM) refractory HBeAg-positive chronic hepatitis B.


METHODS
It is a randomized, double-blind, placebo-controlled, multicenter study. 226 eligible patients with HBeAg-positive chronic hepatitis B were randomized (randomization ratio was 2:1) into two groups. One group received ADV 10 mg/d and LAM 100 mg/d for 12 weeks and followed by ADV 10 mg/d for 36 weeks (ADV + LAM-->ADV group); the other received placebo and LAM 100 mg/d for 12 weeks and followed by ADV 10 mg/d for 36 weeks (placebo + LAM-->ADV group). The primary efficacy measure was virological response. The secondary efficacy measure was serological response (HBeAg loss rate and HBeAg seroconversion rate) and ALT normalization rate.


RESULTS
After 12 weeks of therapy, mean reduction of HBV DNA level, the percentage of patients with HBV DNA lower than 5 l g copies/ml and the percentage of patients with HBV DNA level decrease of more than 2 l g copies/ml in patients of ADV + LAM-->ADV group were significantly higher than those in patients of placebo + LAM-->ADV group (2.69 lg copies/ml vs. 1.06 lg copies/ml, 92.7% vs. 33.3%, 78.1% vs. 27.8%), all the P values were 0.00. HBV DNA undetectable (<3l g copies/ml) rate and serological response (HBeAg loss rate and HBeAg seroconversion rate) in patients of ADV + LAM-->ADV group was slightly higher than those in patients of placebo + LAM-->ADV group (12.2% vs 5.6%, 5.1% vs 0, 4.9% vs 0), but did not reach statistical significance. Much more patients in both treatment arms achieved virological response, serological response and ALT normalization after another 36 weeks of therapy. The overall safety profile of ADV was similar to that of placebo. rtN236T and rtA181V mutation was not found in this 48-week study.


CONCLUSIONS
ADV is an effective and well-tolerated treatment option for patients with LAM refractory HBeAg-positive chronic hepatitis B.
Zhao
Hong
H
Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.
Zhang
Yue-xin
YX
Chen
Xin-yue
XY
Wang
Lei
L
Tang
Xiao-ping
XP
Si
Chong-wen
CW
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil