RESUMEN
BACKGROUND: Fibrosis progression in hepatitis C virus (HCV)-infected patients varies greatly between individuals. Chemokines recruit immune cells to the infected liver and may thus play a role in the fibrosis process. AIM: To investigate plasma levels of a diverse chemokine panel in relation to liver fibrosis. METHODS: African-American and Caucasian HCV genotype 1 infected patients were treated with peginterferon (pegIFN) and ribavirin (RBV) for 48 weeks (VIRAHEP-C cohort). Plasma levels of 13 cytokines were studied at baseline (n = 386). Subsequently, GROα levels were assessed in a sub cohort (n = 99) at baseline, and at 4 and 12 weeks after start of pegIFN/RBV treatment. RESULTS: Increased severity of fibrosis (Ishak fibrosis score 0-2 vs. 3-6) was associated with increased plasma IP-10 (CXCL10) and IL-8 (CXCL8) levels, and decreased plasma levels of the chemokine growth-related oncogene (GRO, CXCL1-3). Plasma GRO levels were also positively correlated with platelet counts, and were higher in African-American as compared to Caucasian patients. In response to pegIFN/RBV treatment, GROα levels increased in Caucasian but not African-American patients from week 4 onwards. CONCLUSIONS: The association with severity of fibrosis and platelet count positions plasma GRO as a potential biomarker for liver fibrosis in HCV-infected patients. The secretion of GRO by platelets may explain the correlation between GRO plasma level and platelet count. The ethnic difference in GRO levels both pre-treatment and in response to pegIFN/RBV might be driven by a genetic polymorphism in GROα associated with higher plasma levels and more common in the African-American population.
Asunto(s)
Antivirales/uso terapéutico , Quimiocinas/sangre , Hepatitis C/complicaciones , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Recuento de Plaquetas , Ribavirina/uso terapéutico , Adulto , Negro o Afroamericano/genética , Anciano , Biomarcadores , Quimiocina CXCL1 , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Humanos , Interferón alfa-2 , Interleucina-8 , Interleucinas , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Polimorfismo Genético , Proteínas Recombinantes , Población Blanca/genética , Adulto JovenRESUMEN
The gastrointestinal mucosa is a major lymphoid tissue reservoir for human immunodeficiency virus (HIV) replication. Genotypic and phenotypic resistance patterns of HIV type 1 (HIV-1) RNA isolated from colonic mucosa were compared with those from the plasma and peripheral blood mononuclear cells (PBMC) of 7 patients. Genotyping was performed using full-sequence analysis, and phenotyping was performed using a recombinant virus assay. Mutations in the reverse-transcriptase (kappa=.84) and protease (kappa=.73) genes were highly concordant among compartments. Similarly, phenotypic resistance patterns were highly concordant among compartments (intraclass correlation coefficient,.91). In 5 instances among 3 patients, a different genotypic result was observed between plasma and the other tissue compartments. Mixtures of wild-type and mutated HIV-1 RNA were present in the mucosa and PBMC but not in the plasma. Despite significant concordance among compartments, mucosal- and PBMC-derived viral RNA showed instances of discordance with plasma-derived virus that may suggest compartmentalization of virus.