Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.
OBJECTIVE
Treatment with adefovir dipivoxil for 48 weeks resulted in clinical improvement in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B that was lost when treatment was discontinued. We investigated the efficacy, safety, and resistance profile of adefovir dipivoxil treatment for up to 240 weeks.


METHODS
HBeAg-negative patients were treated double blind with placebo or adefovir dipivoxil 10 mg once daily for 48 weeks, followed by adefovir dipivoxil from week 49 to 96. At week 97, 125 patients enrolled in a 144-week, open-label phase. Patients received adefovir dipivoxil for up to 192 or 240 weeks.


RESULTS
Serum hepatitis B virus (HBV) DNA levels were less than 1000 copies per milliliter in 67% of patients, and alanine aminotransferase (ALT) levels normalized in 69% after 240 weeks. After 192 or 240 weeks of treatment, over 83% of patients had improvement in necroinflammation, and over 73% had improvement in fibrosis. Ishak fibrosis scores improved compared with baseline in 35%, 55%, and 71% of patients after 48, 192, and 240 weeks of adefovir dipivoxil, respectively. After 240 weeks, the cumulative probability of HBV polymerase mutations was 29%, but the cumulative probability of mutations with virologic resistance was 20% and of mutations, virologic resistance, and ALT elevations was 11%. Slight elevations in creatinine were confirmed in 4 (3%) patients.


CONCLUSIONS
Treatment with adefovir dipivoxil for up to 240 weeks was well tolerated and produced significant, increasing improvement in hepatic fibrosis, durable suppression of HBV replication, normalization of liver enzymes, and delayed development of resistance.
Hadziyannis
Stephanos J
SJ
Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece. hadziyannis@ath.forthnet.gr
Tassopoulos
Nicolaos C
NC
Heathcote
E Jenny
EJ
Chang
Ting-Tsung
TT
Kitis
George
G
Rizzetto
Mario
M
Marcellin
Patrick
P
Lim
Seng Gee
SG
Goodman
Zachary
Z
Ma
Jia
J
Brosgart
Carol L
CL
Borroto-Esoda
Katyna
K
Arterburn
Sarah
S
Chuck
Steven L
SL
D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil