PMID- 15338371
OWN - NLM
STAT- MEDLINE
DCOM- 20050128
LR  - 20131121
IS  - 0944-1174 (Print)
IS  - 0944-1174 (Linking)
VI  - 39
IP  - 8
DP  - 2004 Aug
TI  - Prognostic indicators of breakthrough hepatitis during lamivudine monotherapy for 
      chronic hepatitis B virus infection.
PG  - 769-75
AB  - BACKGROUND: Breakthrough hepatitis (BTH), defined as a flare of transaminases 
      alanine aminotransferase [ALT]) can occur during lamivudine monotherapy for 
      hepatitis B virus (HBV) infection. There have been many reports of 
      lamivudine-resistant mutations within the C domain of the viral reverse 
      transcriptase; however, the appearance of these mutants is not necessarily 
      correlated with BTH during lamivudine therapy. METHODS AND RESULTS: Entire serial 
      HBV genomic sequences before and during lamivudine therapy for 4 patients with 
      BTH and 1 patient without BTH were analyzed and showed changes in the pre-S 
      region. These changes may be associated with ALT flares. Further investigation in 
      a cohort of 36 patients with a median treatment period of 25 months showed that 
      21 patients had a rise in HBV-DNA titer, of whom 18 had BTH. Univariate 
      statistical analyses showed that possible prognostic indicators for the 
      occurrence of BTH were pre-S deletions ( P = 0.03) and L180M/M204L mutations ( P 
      = 0.04). By multivariate Cox regression analyses, significant variables were 
      pre-S deletions (hazard ratio, 0.17; 95% confidence internal (CI), 0.044-0.66) 
      and precore mutations (hazard ratio, 5.70; 95% CI, 1.74-18.71) prior to the 
      commencement of lamivudine monotherapy. Interestingly, BTH occurred after the 
      selection of the wild-type species in the pre-S region during lamivudine 
      monotherapy. CONCLUSIONS: These results suggest that patients with HBV pre-S 
      deletion mutants should be monitored carefully during lamivudine therapy.
FAU - Tanaka, Yasuhito
AU  - Tanaka Y
AD  - Department of Clinical Molecular Informative Medicine, Nagoya City University 
      Medical School Graduate School of Sciences, Kawasumi 1, Mizuho, 467-8601 Nagoya, 
      Japan.
FAU - Yeo, Anthony E T
AU  - Yeo AE
FAU - Orito, Etsuro
AU  - Orito E
FAU - Ito, Kiyoaki
AU  - Ito K
FAU - Hirashima, Noboru
AU  - Hirashima N
FAU - Ide, Tatsuya
AU  - Ide T
FAU - Sata, Michio
AU  - Sata M
FAU - Mizokami, Masashi
AU  - Mizokami M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - J Gastroenterol
JT  - Journal of gastroenterology
JID - 9430794
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Protein Precursors)
RN  - 0 (presurface protein 2, hepatitis B surface antigen)
RN  - 2T8Q726O95 (Lamivudine)
SB  - IM
CIN - J Gastroenterol. 2004 Aug;39(8):813-4. PMID: 15338383
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence/genetics
MH  - Antiviral Agents/*therapeutic use
MH  - Chromosome Deletion
MH  - DNA Mutational Analysis
MH  - DNA, Viral/blood
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Resistance, Viral/genetics
MH  - Female
MH  - Hepacivirus/*drug effects/genetics
MH  - Hepatitis B Surface Antigens/genetics
MH  - Hepatitis B, Chronic/*drug therapy/virology
MH  - Humans
MH  - Lamivudine/*therapeutic use
MH  - *Liver Function Tests
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Protein Precursors/genetics
MH  - Regression Analysis
EDAT- 2004/09/01 05:00
MHDA- 2005/01/29 09:00
CRDT- 2004/09/01 05:00
PHST- 2003/09/17 00:00 [received]
PHST- 2003/12/16 00:00 [accepted]
PHST- 2004/09/01 05:00 [pubmed]
PHST- 2005/01/29 09:00 [medline]
PHST- 2004/09/01 05:00 [entrez]
AID - 10.1007/s00535-003-1387-1 [doi]
PST - ppublish
SO  - J Gastroenterol. 2004 Aug;39(8):769-75. doi: 10.1007/s00535-003-1387-1.