Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase.
OBJECTIVE
Interferon (IFN) induced hepatitis B e antigen (HBeAg) seroconversion is durable in 80-90% of chronic hepatitis B patients. Preliminary reports on the durability of HBeAg seroconversion following lamivudine are contradictory. We investigated the durability of response following IFN, lamivudine, or IFN-lamivudine combination therapy in a meta-analysis of individual patient data.


METHODS
Twenty four centres included 130 patients in total with an HBeAg seroconversion (HBeAg negative, antibodies to hepatitis B e antigen positive) at the end of antiviral therapy: 59 with lamivudine, 49 with interferon, and 22 with combination therapy. Relapse was defined as confirmed reappearance of HBeAg.


RESULTS
The three year cumulative HBeAg relapse rate by the Kaplan-Meier method was 54% for lamivudine, 32% for IFN, and 23% for combination therapy (p=0.01). Cox regression analysis identified pretreatment hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), sex, and therapy as independent predictive factors of post-treatment relapse; Asian race, previous therapy, centre, and type of study were not predictive of relapse. The relative HBeAg relapse risk of lamivudine compared with IFN therapy was 4.6 and that of combination therapy to IFN therapy 0.7 (p(overall)=0.01).


CONCLUSIONS
The durability of HBeAg seroconversion following lamivudine treatment was significantly lower than that following IFN or IFN-lamivudine combination therapy. The risk of relapse after HBeAg seroconversion was also related to pretreatment levels of serum ALT and HBV DNA, but independent of Asian race.
van Nunen
A B
AB
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Centre Rotterdam, the Netherlands.
Hansen
B E
BE
Suh
D J
DJ
Löhr
H F
HF
Chemello
L
L
Fontaine
H
H
Heathcote
J
J
Song
B C
BC
Janssen
H L A
HL
de Man
R A
RA
Schalm
S W
SW
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D051263:D-Alanine Transaminase; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D007372:Interferons; D000410:Alanine Transaminase; D051263:D-Alanine Transaminase