title: Virological and biochemical relapse according to YMDD motif mutant type during long-term lamivudine monotherapy.
abstract: Whether the type of lamivudine-resistant virus in hepatitis B virus (HBV) influences the clinical outcome, it is not completely understood. We evaluated the serial changes in YMDD motif mutant in 60 Japanese genotype C-HBV patients who received long-term lamivudine monotherapy. YIDD or YVDD alone tended to stop shifting to the mixed type (YVDD and YIDD) within 12 months after the detection of mutant virus. Hence, the characteristics, virological relapse (DNA breakthrough) and biochemical relapse (breakthrough hepatitis) of 49 patients, who could be classified into three types (continuous YVDD, continuous YIDD, and the mixed type), were investigated. YVDD and YIDD type tended to have the opposite background with regard to age, histology, and viral load. The mixed and YIDD types tended to have similar backgrounds, except for viral load. In the mixed type, both the HBeAg-positive rate and viral load as risk factors for emergence of the mutant tended to be high. Mutant virus, DNA breakthrough and breakthrough hepatitis emerged significantly earlier in the mixed type than the two other types. The incidence of severe breakthrough hepatitis accompanied by icteric flare-up tended to be higher in the mixed type than the other types. Our results suggest that the YMDD motif mutant type might emerge from different backgrounds and modulate the virological and biochemical relapse after the emergence. Large-scale studies of each mutant type should be conducted in the future to confirm these findings.
authors.affiliation: Department of Gastroenterology and Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Marie
authors.initials: M
authors.lastname: Matsuda
authors.forename: Junko
authors.initials: J
authors.lastname: Sato
authors.forename: Kimiko
authors.initials: K
authors.lastname: Takagi
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Someya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015684:Gene Products, pol / Q000737:chemistry / Q000235:genetics; D005814:Genes, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D019259:Lamivudine