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Clinical course of virologic breakthrough after emergence of YMDD mutations in HBeAg-positive chronic hepatitis B.

 Do Young Kim  ;  Sang Hoon Ahn  ;  Hyun Woong Lee  ;  Jun Yong Park  ;  Seung Up Kim  ;  Yong Han Paik  ;  Kwan Sik Lee  ;  Kwang-Hyub Han  ;  Chae Yoon Chon 
 INTERVIROLOGY, Vol.51(4) : 293-298, 2008 
Journal Title
Issue Date
Adult ; Aged ; Alanine Transaminase/blood ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use* ; DNA, Viral/blood ; Drug Resistance, Viral* ; Female ; Hepatitis B virus/drug effects* ; Hepatitis B virus/genetics* ; Hepatitis B virus/isolation & purification ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B, Chronic/physiopathology ; Hepatitis B, Chronic/virology* ; Humans ; Lamivudine/pharmacology ; Lamivudine/therapeutic use* ; Male ; Middle Aged ; Mutation, Missense* ; Viral Load
Lamivudine ; Chronic hepatitis B ; Virologic breakthrough ; Clinical breakthrough
OBJECTIVE: High rate of resistance to lamivudine is a major problem in treating chronic hepatitis B (CHB) patients. We investigated the course of virologic breakthrough (VB) after emergence of YMDD mutants in CHB patients receiving lamivudine.

METHODS: Ninety-three consecutive HBeAg-positive CHB patients treated with lamivudine (100 mg/day) who developed YMDD mutants and VB were enrolled. The clinical breakthrough (CB) was defined by elevation of alanine aminotransferase (ALT) >2 times the upper limit of normal.

RESULTS: The median age was 47 years, and genotype of hepatitis B virus (HBV) was all C. The median duration of lamivudine administration was 39 months, and median pre-lamivudine ALT and HBV DNA were 165 IU/l and 1.2 x 10(8) copies/ml. In all patients, CB concurred with VB or appeared some months following VB. When patients were divided into two groups according to time sequence of two breakthroughs - group 1 (VB followed by CB, n = 68) and group 2 (concurrent VB and CB, n = 25)--there was no difference in patient and virologic characteristics between the two groups. The median time from VB to CB was 8 months in group 1.

CONCLUSION: VB might eventually progress to CB in HBeAg-positive patients harboring YMDD mutants with high pretreatment ALT and HBV DNA.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Paik, Yong Han(백용한)
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Chon, Chae Yoon(전재윤)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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