Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir.
OBJECTIVE
Little is known about the biochemical and virological effects of stopping long-term nucleos(t)ide analogue therapy for hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB).


METHODS
We performed a cohort observational study, following 33 HBeAg-negative patients with CHB, undetectable serum HBV DNA, and normal levels of aminotransferases after long-term (4 or 5 years) treatment with adefovir dipivoxil (ADV). All patients were followed for 5.5 years; follow-up visits included measurements of serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), and HBV DNA monthly for the first 6 months and every 3-6 months thereafter. Various factors were measured at baseline, the end of treatment (EOT), and following treatment to identify those associated with clearance of HBsAg.


RESULTS
During the first few months of the postdiscontinuation period, all patients experienced virological and 25 (76%) had biochemical relapse. During the follow-up period, 18 patients (55%) who had discontinued antiviral therapy achieved sustained response (HBV DNA level <2000 IU/L, persistently normal level of ALT). Among these, 13 (72%) cleared HBsAg. Fifteen patients (45%) with virological and/or biochemical relapse were re-treated with oral antiviral agents (11 during the first 18 months and 4 after the third year), without evidence of liver decompensation; only 1 lost HBsAg (6%). Higher pretreatment and EOT levels of ALT, no previous treatment with interferon, and lower level of HBsAg at the EOT were significantly associated with HBsAg clearance based on multivariate analysis.


CONCLUSIONS
In HBeAg-negative patients with CHB, it is safe and effective to discontinue ADV therapy after 4 or 5 years; 55% of patients have sustained responses, and 39% of patients lose HBsAg.
Department of Medicine and Hepatology, Henry Dunant Hospital, National and Kapodistrian University of Athens, Athens, Greece; Molecular Biology Laboratory of the Liver Unit at the Evgenidion Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: hadziyannis@ath.forthnet.gr.
Stephanos J
SJ
Hadziyannis
Department of Medicine and Hepatology, Henry Dunant Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Vassilios
V
Sevastianos
Department of Medicine and Hepatology, Henry Dunant Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Irene
I
Rapti
2nd Academic Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Dimitrios
D
Vassilopoulos
2nd Academic Department of Medicine, Hippokration Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Emilia
E
Hadziyannis
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D063065:Organophosphonates / Q000008:administration & dosage*; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D063065:Organophosphonates; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil