Host and viral determinants of the outcome of exposure to HCV infection genotype 4: a large longitudinal study.
Am J Gastroenterol
; 109(2): 199-211, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24445571
ABSTRACT
OBJECTIVES:
The objective of this study was to characterize the factors that influence the outcome of exposure to hepatitis C virus (HCV) genotype 4 (HCV-G4) and the course of recent infection.METHODS:
In this longitudinal study, we prospectively assessed the clinical, genetic, virological, and immunological parameters and retrospectively determined single-nucleotide polymorphisms at interleukin-28B (IL-28B) rs12979860 in a well-characterized large cohort recently exposed to HCV-G4.RESULTS:
A total of 136 subjects with acute HCV (new viremia, seroconversion, and HCV-specific T-cell responses) were identified. Forty-eight subjects (35%) had spontaneous viral clearance and 88 subjects developed chronic HCV of which 42 subjects were treated with pegylated interferon monotherapy, with a sustained virologic response (SVR) rate of 88%. Twenty-six subjects developed HCV-specific T-cell immune responses without detectable viremia or seroconversion. IL-28B-CC (odds ratio (OR) 14.22; P<0.0001), multispecific T-cell responses (OR=11.66; P<0.0001), >300 IU/l alanine aminotransferase (ALT) decline within 4 weeks (OR=6.83; P<0.0001), jaundice (OR=3.54; P=0.001), female gender (OR=2.39; P=0.007), and >2.5 log10 HCV-RNA drop within 8 weeks (OR=2.48; P=0.016) were independently associated with spontaneous clearance. ALT normalization and undetectable HCV-RNA predicted SVR. Exposed apparently uninfected participants had a higher frequency of IL-28B-CC than patients with unresolved acute HCV (P<0.001). IL-28B-CC was associated with multispecific T-cell response (r(2)=0.0.835; P<0.001).CONCLUSIONS:
IL-28B-CC genotype, multispecific HCV T-cell responses, rapid decline in ALT, and viral load predict spontaneous clearance and response to acute HCV-G 4 therapy. IL-28B-CC genotype correlates with developing early multispecific T-cell responses. These findings have important implications for predicting the outcome of HCV exposure and acute infection and identifying patients likely to benefit from therapy.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Viremia
/
Interleucinas
/
Hepatite C
/
Hepacivirus
Tipo de estudo:
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
País/Região como assunto:
Africa
Idioma:
En
Revista:
Am J Gastroenterol
Ano de publicação:
2014
Tipo de documento:
Article