PMID- 14762859
OWN - NLM
STAT- MEDLINE
DCOM- 20040528
LR  - 20081121
IS  - 1527-6465 (Print)
IS  - 1527-6465 (Linking)
VI  - 10
IP  - 2
DP  - 2004 Feb
TI  - Genetic variability of hepatitis C virus NS3 protein in human leukocyte 
      antigen-A2 liver transplant recipients with recurrent hepatitis C.
PG  - 217-27
AB  - The association between the severity of chronic hepatitis C and the variability 
      of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge 
      few data are available to date regarding T-cell epitope coding regions in 
      transplant patients. In the current study, we identified 21 human leukocyte 
      antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 
      immunosuppressed liver transplant recipients, and 7 immunocompetent controls. 
      Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of 
      fibrosis progression were determined. Genetic distances of HCV isolates and 
      variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and 
      NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression 
      of fibrosis. Isolates from transplant patients with fast progression were found 
      to be more divergent (P =.03), had a higher mean value of synonymous (dS) 
      variations (P =.02), and some were differentiated in a phylogenetic tree, 
      compared with isolates from patients with slow progression. The HLA-A2-restricted 
      NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from 
      the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% 
      variation). A shift in the viral peptide was not detected in a subset of 
      transplant patients, but was evident in two of three nontransplant patients with 
      follow-up. There was no correlation noted between a particular amino acid 
      variation and fibrosis progression (slow or fast) in either transplant or 
      nontransplant patients. The results of the current study suggest that 1) there 
      may be different HCV-1b strains in our geographic area, 2) immunosuppression 
      appears to have little effect in amino acid variation at the HCV NS3-1406 
      epitope, and 3) variations over time might be more frequent in 
      nonimmunosuppressed patients.
FAU - Lopez-Labrador, F Xavier
AU  - Lopez-Labrador FX
AD  - Microbiology, Hospital Universitari La Fe and Centro de Investigacion, Valencia, 
      Spain. fxlopez@teleline.es
FAU - Berenguer, Marina
AU  - Berenguer M
FAU - Sempere, Amparo
AU  - Sempere A
FAU - Prieto, Martin
AU  - Prieto M
FAU - Sirera, Rafael
AU  - Sirera R
FAU - Gonzalez-Molina, Andres
AU  - Gonzalez-Molina A
FAU - Ortiz, Vicente
AU  - Ortiz V
FAU - Marty, Maria Luisa
AU  - Marty ML
FAU - Berenguer, Joaquin
AU  - Berenguer J
FAU - Gobernado, Miguel
AU  - Gobernado M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Liver Transpl
JT  - Liver transplantation : official publication of the American Association for the 
      Study of Liver Diseases and the International Liver Transplantation Society
JID - 100909185
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (NS3 protein, hepatitis C virus)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Female
MH  - *Genetic Variation
MH  - HLA-A2 Antigen/*analysis
MH  - Hepatitis C
MH  - Humans
MH  - *Liver Transplantation
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Phylogeny
MH  - Recurrence
MH  - Viral Nonstructural Proteins/*genetics
EDAT- 2004/02/06 05:00
MHDA- 2004/05/29 05:00
CRDT- 2004/02/06 05:00
PHST- 2004/02/06 05:00 [pubmed]
PHST- 2004/05/29 05:00 [medline]
PHST- 2004/02/06 05:00 [entrez]
AID - 10.1002/lt.20066 [doi]
PST - ppublish
SO  - Liver Transpl. 2004 Feb;10(2):217-27. doi: 10.1002/lt.20066.