OBJECTIVE: The aim of this study was to assess the influence of host genetic factors on response to combination therapy for chronic hepatitis C infection. METHODS: Patients with biopsy-proved chronic hepatitis C infection were treated with interferon alone (n = 143) or combined therapy of interferon + ribavarin (n = 105; 46 treatment naïve, 59 relapsers). Human leukocyte antigen (HLA) class I was determined by microlymphocytotoxicity and class II by polymerase chain reaction-single specific oligonucleotide. The two biallelic tumor necrosis factor-alpha promoter polymorphisms were studied by a polymerase chain reaction-amplification refractory mutation system. Other variables measured were viral genotype, hepatitis C virus RNA load, liver function tests, and ferritin concentration. RESULTS: Univariate analysis indicated that patients bearing HLA B44+, DRB1*03, infected by genotype non-1, with higher concentrations of transaminases and shorter duration of infection showed a higher sustained response (SR) rate than those on combination therapy. HLA class II and TNF-alpha promoter polymorphisms were not related to SR. In multivariate analysis, non-1 genotype (OR 2.42, 95% CI 1.12-5.55, p = 0.026) and HLA B44+ (OR 4.84, 95% CI 1.3-17.8, p = 0.017) were the independent variables associated with SR. However, HLA B44+ was not associated with SR in patients treated with interferon alone. CONCLUSIONS: HLA class I B44 is related to a higher rate of SR in combination therapy but not in interferon monotherapy, whereas HLA class II, tumor necrosis factor-alpha -238A or -308A seem not to influence response to the antiviral therapy. These findings may be of value in therapy selection for hepatitis C-infected patients.
OBJECTIVE: The aim of this study was to assess the influence of host genetic factors on response to combination therapy for chronic hepatitis C infection. METHODS:Patients with biopsy-proved chronic hepatitis C infection were treated with interferon alone (n = 143) or combined therapy of interferon + ribavarin (n = 105; 46 treatment naïve, 59 relapsers). Human leukocyte antigen (HLA) class I was determined by microlymphocytotoxicity and class II by polymerase chain reaction-single specific oligonucleotide. The two biallelic tumor necrosis factor-alpha promoter polymorphisms were studied by a polymerase chain reaction-amplification refractory mutation system. Other variables measured were viral genotype, hepatitis C virus RNA load, liver function tests, and ferritin concentration. RESULTS: Univariate analysis indicated that patients bearing HLA B44+, DRB1*03, infected by genotype non-1, with higher concentrations of transaminases and shorter duration of infection showed a higher sustained response (SR) rate than those on combination therapy. HLA class II and TNF-alpha promoter polymorphisms were not related to SR. In multivariate analysis, non-1 genotype (OR 2.42, 95% CI 1.12-5.55, p = 0.026) and HLA B44+ (OR 4.84, 95% CI 1.3-17.8, p = 0.017) were the independent variables associated with SR. However, HLA B44+ was not associated with SR in patients treated with interferon alone. CONCLUSIONS: HLA class I B44 is related to a higher rate of SR in combination therapy but not in interferon monotherapy, whereas HLA class II, tumor necrosis factor-alpha -238A or -308A seem not to influence response to the antiviral therapy. These findings may be of value in therapy selection for hepatitis C-infectedpatients.
Authors: Ivo Ivić; Nikola Bradarić; Neira Puizina-Ivić; Dragan Ledina; Boris Luksić; Roko Martinić Journal: Croat Med J Date: 2007-12 Impact factor: 1.351
Authors: M Romero-Gómez; M A Montes-Cano; M A Otero-Fernández; B Torres; D Sánchez-Muñoz; F Aguilar; N Barroso; L Gómez-Izquierdo; V M Castellano-Megias; A Núñez-Roldán; J Aguilar-Reina; M F González-Escribano Journal: Gut Date: 2004-03 Impact factor: 23.059
Authors: James D Porter; Jennifer Watson; Lee R Roberts; Simren K Gill; Helen Groves; Jaideep Dhariwal; Mark H Almond; Ernie Wong; Ross P Walton; Lyn H Jones; John Tregoning; Iain Kilty; Sebastian L Johnston; Michael R Edwards Journal: J Antimicrob Chemother Date: 2016-07-25 Impact factor: 5.790