L'IMPATTO DEL POLIMORFISMO GENETICO IL 28B SUL TRATTAMENTO ANTIVIRALE CON INTERFERONE PEGHILATO E RIBAVIRINA IN PAZIENTI CON EPATITE CRONICA C GENOTIPO 4 [Tesi di dottorato]
Università degli Studi di Milano, 2012-01-31

Background. Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to Peg-Interferon (PegIFN) and Ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too, is unknown. Aim To investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. Methods. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver Centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Results. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis ) 103 were included in the final analysis, since 5 discontinued treatment for non virologic reasons and 4 did not consent to genetic testing. Twenty four (23%) were genotype CC, 65 (63%) CT and 14 (14%) TT. Overall 50 (49%) achieved an SVR, 21 (88%) CC patients vs 29 (37%) CT/TT (p<0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% vs 23, 29% p = 0.08), while also showing lower relapse rates [0% (0/21) vs 36% (16/45) p=0.0013]. In non-RVR patients, SVR rated were higher in CC than CT/TT patients [9(75%) vs. 13(23%)p=0.001]. By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 11.1 (95% confidence interval 3.04 – 40.57 (p <0.0001). Conclusions. The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients, since it is the strongest predictor of an SVR to PegIFN/ Rbv therapy.

diritti: info:eu-repo/semantics/restrictedAccess
tutor: M. Colombo
COLOMBO, MASSIMO GIUSEPPE
Settore MED/12 - - Gastroenterologia


Tesi di dottorato. | Lingua: Italiano. | Paese: | BID: TD16000586