Significance of viral load, core promoter/precore mutations and specific sequences of polymerase gene in HBV-infected patients on 3-year lamivudine treatment.
BACKGROUND
Comprehensive study on viral factors predicting treatment responsiveness to lamivudine is lacking.


OBJECTIVE
To define the significance of various viral factors and changes of viral population with lamivudine treatment.


METHODS
Hepatitis B virus (HBV) DNA levels at baseline, week 24, 52 and year 3 were measured in 80 patients on continuous lamivudine therapy for 3 years. Genotypes, core promoter/precore mutations, YMDD mutations, polymorphic sequence of polymerase gene (rt91 I/L, rt256S/C) were determined at baseline, week 12, 24 and 52. YMDD mutations were also determined at year 3.


RESULTS
High alanine aminotransferase levels and presence of core promoter/ precore mutations at baseline were associated with higher chance of achieving HBV DNA <1,000 copies/ml (good response) and higher rate of hepatitis Be antigen (HBeAg) seroconversion at week 52. Achieving HBV DNA levels <1,000 copies/mi at week 24 as well as baseline core promoter/precore mutations were associated with higher chance of achieving good response, higher rate of HBeAg seroconversion and lower rate of YMDD mutations at year 3. Lamivudine reversed core promoter mutations to wild type in 25% of patients. All 5 patients with rt256C had poor HBV DNA response, persistent HBeAg and YMDD mutations by year 3. There was no difference in treatment response between patients with genotype B and C.


CONCLUSIONS
Achieving HBV DNA levels <1,000 copies/ml at 24 week is the best target for short- and long-term treatment efficacy. Core promoter and precore mutations were associated with better treatment outcome, and rt256C polymorphism in the polymerase gene with poor response.
Yuen
Man-Fung
MF
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong. mfyuen@hkucc.hku.hk
Sablon
Erwin
E
Libbrecht
Evelien
E
Van De Velde
Hilde
H
Wong
Danny Ka-Ho
DK
Fung
James
J
Wong
Benjamin Chun-Yu
BC
Lai
Ching-Lung
CL
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000097:blood; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D011498:Protein Precursors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase; D004259:DNA-Directed DNA Polymerase