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Titolo:
EVIDENCE FOR SELECTION OF HEPATITIS-B MUTANTS AFTER LIVER-TRANSPLANTATION THROUGH PERIPHERAL-BLOOD MONONUCLEAR CELL INFECTION
Autore:
BRIND A; JIANG JJ; SAMUEL D; GIGOU M; FERAY C; BRECHOT C; KREMSDORF D;
Indirizzi:
CHU NECKER,INSERM U370,156 RUE VAUGIRARD F-75730 PARIS 15 FRANCE CHU NECKER,INSERM U370 F-75730 PARIS 15 FRANCE HOP PAUL BROUSSE,HEPATO BILARY CTR VILLEJUIF FRANCE HOP NECKER ENFANTS MALAD,LIVER UNIT PARIS FRANCE
Titolo Testata:
Journal of hepatology
fascicolo: 2, volume: 26, anno: 1997,
pagine: 228 - 235
SICI:
0168-8278(1997)26:2<228:EFSOHM>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBROSING CHOLESTATIC HEPATITIS; CHRONIC HBV INFECTION; VIRUS PRECORE MUTANT; E-ANTIGEN; PRE-C; NUCLEOTIDE-SEQUENCE; NEGATIVE PATIENTS; ESCAPE MUTANT; DNA; CARRIERS;
Keywords:
HEPATITIS B VIRUS; PBMC; REINFECTION; TRANSPLANTATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
38
Recensione:
Indirizzi per estratti:
Citazione:
A. Brind et al., "EVIDENCE FOR SELECTION OF HEPATITIS-B MUTANTS AFTER LIVER-TRANSPLANTATION THROUGH PERIPHERAL-BLOOD MONONUCLEAR CELL INFECTION", Journal of hepatology, 26(2), 1997, pp. 228-235

Abstract

Background/Aims: Despite anti-HBs immunoglobulin therapy, hepatitis Bvirus (HBV) infection recurs in a high proportion of patients transplanted for HBsAg positive and serum HBV DNA negative chronic liver disease, The contribution of HBV genetic variability to disease recurrencehas not been yet thoroughly addressed, We have therefore undertaken adetailed comparison of preS/S and preC/C sequences in two selected patients with recurrence of HBsAg and HBV DIVA after transplantation. Methods: PreS/S and preC/C regions were amplified by PCR from the serum,peripheral blood mononuclear cell (PBMC) and liver tissues of two patients transplanted for end stage HBV-related cirrhosis, Samples were taken both pre- and post-transplantation, HBV-sequences from four to nine clones were determined and compared. Results: A mixing of differentHBV DNA molecules was observed within and between serum, liver and PBMC samples, Sequences from both patients showed mutations in the preC region which abolished HBeAg secretion, and in the preS2 initiation codon which prevented preS2 envelope protein production, In addition, for both patients, deletions in the preS2 domain (3 and 21 base pairs) led to the expression of modified preS1 envelope protein. For one patient, the predominant HBs protein sequence found in the PBMC before transplantation showed four specific mutations, One of these mutations wasin the ''a'' determinant (codon 144, asparagine to glycine change) ofthe major envelope protein, These mutations were not detected, as predominant mutations, in the liver and serum pre-orthotopic liver transplant samples. In contrast, after liver transplantation, this was the major form identified in serum, liver and PBMC. Conclusions: Our results have shown the selection of different HBV DNA molecules in liver andmononuclear cells, In addition, they provide direct evidence for the role of PBMC in the infection of liver grafts and support the hypothesis that infection of PBMC might lead to selection of HBV variants which would escape immune therapy Finally, we provide in vivo evidence forreinfection of the liver by HBV particles lacking preS2 envelope protein expression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 08:20:00