In vivo dynamics and pathogenicity of wild-type and resistant Hepatitis B virus during long-term lamivudine monotherapy -: a clinical note

被引:10
作者
Zöllner, B
Stoehr, A
Plettenberg, A
Feucht, HH
Schröter, M
Schäfer, P
Laufs, R
机构
[1] Univ Hamburg, Hosp Eppendorf, Inst Med Microbiol & Immunol, D-20246 Hamburg, Germany
[2] Gen Hosp St Georg, Infect Outpatient Dept, D-20099 Hamburg, Germany
关键词
HBV; lamivudine; resistance; turnover;
D O I
10.1016/S1386-6532(00)00092-5
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background: Genotypic resistance of Hepatitis B virus (HBV) against lamivudine evolves within months after onset of therapy. Objectives: To determine the longitudinal order in which resistance mutations appear and to compare the kinetics and pathogenicity of wild-type and resistant HBV. Study design: In a longitudinal study, consecutive samples were drawn over a period of 28 months from a patient with chronic hepatitis B, and resistance mutations were followed by sequencing a part of the polymerase region of HBV. These data were compared with HBV copy numbers, HBsAg and ALT levels, and results of consecutive liver biopsies. Results: After 21 weeks of treatment, a silent mutation at codon 528 (CTG to TTG) occurred. Significant genotypic resistance was detectable after 68 weeks, indicated by a substitution of isoleucine for methionine at residue 552 (M552I). Nineteen weeks later, the virus exhibited additional resistance-associated mutations (L528N and I552V). The resulting high-level resistance was reflected by an increase of serum HBV copies of 4.7 log(10). The turnover of wild-type and resistant HBV was 2.6 x 10(6) and 1.8 x 10(6) virions/day, respectively. HBsAg and ALT levels were lower within the period when resistant HBV was detectable. During treatment the progress of liver fibrosis was arrested. Conclusions: The in vivo replicative capacities and dynamics of wild-type and resistant HBV were similar. However, resistant HBV seemed to exhibit reduced pathogenicity. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:183 / 188
页数:6
相关论文
共 16 条
[1]   Identification and characterization of mutations in hepatitis B virus resistant to lamivudine [J].
Allen, MI ;
Deslauriers, M ;
Andrews, CW ;
Tipples, GA ;
Walters, KA ;
Tyrrell, DLJ ;
Brown, N ;
Condreay, LD .
HEPATOLOGY, 1998, 27 (06) :1670-1677
[2]   Hepatitis-B-virus resistance to lamivudine given for recurrent infection after orthotopic liver transplantation [J].
Bartholomew, MM ;
Jansen, RW ;
Jeffers, LJ ;
Reddy, KR ;
Johnson, LC ;
Bunzendahl, H ;
Condreay, LD ;
Tzakis, AG ;
Schiff, ER ;
Brown, NA .
LANCET, 1997, 349 (9044) :20-22
[3]   EFFICACY OF LAMIVUDINE ON REPLICATION OF HEPATITIS-B VIRUS IN HIV-INFECTED PATIENTS [J].
BENHAMOU, Y ;
DOHIN, E ;
LUNELFABIANI, F ;
POYNARD, T ;
HURAUX, JM ;
KATLAMA, C ;
OPOLON, P ;
GENTILINI, M .
LANCET, 1995, 345 (8946) :396-397
[4]   Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy [J].
Chayama, K ;
Suzuki, Y ;
Kobayashi, M ;
Kobayashi, M ;
Tsubota, A ;
Hashimoto, M ;
Miyano, Y ;
Koike, H ;
Kobayashi, M ;
Koida, I ;
Arase, Y ;
Saitoh, S ;
Murashima, N ;
Ikeda, K ;
Kumada, H .
HEPATOLOGY, 1998, 27 (06) :1711-1716
[5]   A PRELIMINARY TRIAL OF LAMIVUDINE FOR CHRONIC HEPATITIS-B INFECTION [J].
DIENSTAG, JL ;
PERRILLO, RP ;
SCHIFF, ER ;
BARTHOLOMEW, M ;
VICARY, C ;
RUBIN, M .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (25) :1657-1661
[6]   Role of additional mutations outside the YMDD motif of hepatitis B virus polymerase in L(-)SddC (3TC) resistance [J].
Fu, L ;
Cheng, YC .
BIOCHEMICAL PHARMACOLOGY, 1998, 55 (10) :1567-1572
[7]   Quantitative detection of hepatitis B virus DNA in two international reference plasma preparations [J].
Heermann, KH ;
Gerlich, WH ;
Chudy, M ;
Schaefer, S ;
Thomssen, R .
JOURNAL OF CLINICAL MICROBIOLOGY, 1999, 37 (01) :68-73
[8]   Clinical impact of lamivudine resistance in chronic hepatitis B [J].
Honkoop, P ;
de Man, RA ;
Niesters, HGM ;
Schalm, SW .
JOURNAL OF HEPATOLOGY, 1998, 29 (03) :510-511
[9]   GENOTYPIC AND PHENOTYPIC CHARACTERIZATION OF HIV-1 ISOLATED FROM PATIENTS RECEIVING (-)-2',3'-DIDEOXY-3'-THIACYTIDINE [J].
KAVLICK, MF ;
SHIRASAKA, T ;
KOJIMA, E ;
PLUDA, JM ;
HUI, F ;
YARCHOAN, R ;
MITSUYA, H .
ANTIVIRAL RESEARCH, 1995, 28 (02) :133-146
[10]   Hepatitis B virus mutants associated with 3TC and Famciclovir administration are replication defective [J].
Melegari, M ;
Scaglioni, PP ;
Wands, JR .
HEPATOLOGY, 1998, 27 (02) :628-633