Study’s Purpose: Viral and host factors influence Sustained Virological Response (SVR) to standard of care (SOC) in HCV chronic hepatitis. The primary aim of this prospective multicentre cohort study was to report data on SVR and adherence to SOC in daily practice. Secondary aims were to evaluate the influence on SVR of viral (HCV genotypes and serum HCV-RNA levels), genetic (sex, frequency of T/T, G/T and G/G alleles of IL28B rs8099860 Single Nucleotide Polymorphisms) and metabolic (body mass index, visceral obesity, HOMA) factors. Patients and Methods: 670 naïve patients with HCV infection (362 G1, 175 G2, 100 G3, 33 G4) were enrolled and treated with SOC in 12 Italian Centers. The rate of SVR was evaluated by intention to treat analysis. Associations between variables and SVR were assessed by multivariate logistic regression analysis. Results: Overall SVR rates were 43% in G1, 81.1% in G2, 69% in G3 and 39.4% in G4 patients (p<0.001). Analysis by gender was done in the 362 G1 patients. In 163 females age < 50 years (p=0.001), waist circumference < 88 cm (p=0.013), ALT values (p=0.044), presence of type 2 diabetes (p=0.020) and C/C alleles of rs8099860 SNP (p=0.004) were associated with SVR. At multivariate analysis only age < 50 years (OR 2.17, CI95% 1.03–4.57, P=0.041) and C/C alleles (OR 3.74, CI95% 1.63–8.56, p=0.002) were independently associated with SVR. Including RVR as independent variable did not enhance the predictability of SVR (OR 1.12; CI95% 0.98-1.28; p=0.11). In 199 males waist circumference < 102 cm (p=0.063), HCV-RNA levels < 400.000 IU/mL (p=0.007) and C/C alleles (p<0.001) were associated with SVR. At multivariate analysis waist circumference < 102 cm (OR 2.33, CI95% 1.07–5.12, p=0.034), HCV-RNA levels < 400.000 IU/mL (OR 2.66, CI 95% 1.29–5.51, p=0.008) and C/C alleles (OR 6.02, CI95% 2.94–12.32, p<0.001) remained independently associated with SVR. Again, including RVR as independent variable did not enhance the predictability of SVR (OR 1.060; CI 95% 0.94- 1.20; p = 0.336). Combining variables independently associated with SVR the likelihood of SVR ranges from 26.7% to 82.3% for women and from 17.6% to 85.7% for men. Conclusions: In genotype 1 infection, RVR to SOC is strongly dependent from factors affecting sensitivity to IFN such as IL28b polymorphisms and viral load. The relevance of host-related factors such as age and overweight is remarkably different between women and men. The age cutoff found significant in women may relate to menopause (Villa E, et al. Gastroenterology. 2011;140:818-29). Gender-related differences in response should be kept into account when evaluating the need for DAAs in addition to SOC.
Gender specific determinants of response in HCV genotype 1 to current SOC with PEG IFN and ribavirin in a practice cohort.
FATTOVICH, Giovanna;
2011-01-01
Abstract
Study’s Purpose: Viral and host factors influence Sustained Virological Response (SVR) to standard of care (SOC) in HCV chronic hepatitis. The primary aim of this prospective multicentre cohort study was to report data on SVR and adherence to SOC in daily practice. Secondary aims were to evaluate the influence on SVR of viral (HCV genotypes and serum HCV-RNA levels), genetic (sex, frequency of T/T, G/T and G/G alleles of IL28B rs8099860 Single Nucleotide Polymorphisms) and metabolic (body mass index, visceral obesity, HOMA) factors. Patients and Methods: 670 naïve patients with HCV infection (362 G1, 175 G2, 100 G3, 33 G4) were enrolled and treated with SOC in 12 Italian Centers. The rate of SVR was evaluated by intention to treat analysis. Associations between variables and SVR were assessed by multivariate logistic regression analysis. Results: Overall SVR rates were 43% in G1, 81.1% in G2, 69% in G3 and 39.4% in G4 patients (p<0.001). Analysis by gender was done in the 362 G1 patients. In 163 females age < 50 years (p=0.001), waist circumference < 88 cm (p=0.013), ALT values (p=0.044), presence of type 2 diabetes (p=0.020) and C/C alleles of rs8099860 SNP (p=0.004) were associated with SVR. At multivariate analysis only age < 50 years (OR 2.17, CI95% 1.03–4.57, P=0.041) and C/C alleles (OR 3.74, CI95% 1.63–8.56, p=0.002) were independently associated with SVR. Including RVR as independent variable did not enhance the predictability of SVR (OR 1.12; CI95% 0.98-1.28; p=0.11). In 199 males waist circumference < 102 cm (p=0.063), HCV-RNA levels < 400.000 IU/mL (p=0.007) and C/C alleles (p<0.001) were associated with SVR. At multivariate analysis waist circumference < 102 cm (OR 2.33, CI95% 1.07–5.12, p=0.034), HCV-RNA levels < 400.000 IU/mL (OR 2.66, CI 95% 1.29–5.51, p=0.008) and C/C alleles (OR 6.02, CI95% 2.94–12.32, p<0.001) remained independently associated with SVR. Again, including RVR as independent variable did not enhance the predictability of SVR (OR 1.060; CI 95% 0.94- 1.20; p = 0.336). Combining variables independently associated with SVR the likelihood of SVR ranges from 26.7% to 82.3% for women and from 17.6% to 85.7% for men. Conclusions: In genotype 1 infection, RVR to SOC is strongly dependent from factors affecting sensitivity to IFN such as IL28b polymorphisms and viral load. The relevance of host-related factors such as age and overweight is remarkably different between women and men. The age cutoff found significant in women may relate to menopause (Villa E, et al. Gastroenterology. 2011;140:818-29). Gender-related differences in response should be kept into account when evaluating the need for DAAs in addition to SOC.
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