TY - JOUR
T1 - Interferon lambda-3 is not associated with clinical outcome in patients with HCV-induced compensated cirrhosis
T2 - A long-term cohort study
AU - Bruno, Savino
AU - Thompson, Alex J.
AU - Critelli, Rosina
AU - Crosignani, Andrea
AU - Rossi, Sonia
AU - De Lisi, Stefania
AU - Cariani, Elisabetta
AU - Zermiani, Paola
AU - Vaira, Valentina
AU - Boccaccio, Vincenzo
AU - Maisonneuve, Patrick
AU - Villa, Erica
PY - 2015
Y1 - 2015
N2 - Background: Interferon Lambda-3 (IFN-λ3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-λ3 genotype influences liver disease progression remains unclear. Methods: We determined IFN-λ3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-λ3 genotype and clinical outcome. Results: IFN-λ3 was determined in 264 patients (52% males, mean age 57 ± 8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p <0.0001). Univariate and multivariate analyses found no association between IFN-λ3 (CC vs. non-CC genotype) and disease progression. Conclusion: IFN-λ3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease.
AB - Background: Interferon Lambda-3 (IFN-λ3) gene polymorphism is associated with spontaneous clearance of hepatitis C virus (HCV) and response to IFN-based therapy (IFN). However, very few data are available about its value in predicting sustained virologic response (SVR) in patients with cirrhosis, and whether IFN-λ3 genotype influences liver disease progression remains unclear. Methods: We determined IFN-λ3 genotype by PCR in a cohort of patients with compensated HCV-related cirrhosis, enrolled between 1989 and 1992. Person-years follow-up was calculated for each individual from the date of enrolment to the development of first episode of decompensation, HCC, liver transplant, death or end of follow-up. The follow-up of patients who achieved SVR was censored at the time of IFN initiation. Kaplan-Meier curves and Cox regression analyses were used to assess the association between IFN-λ3 genotype and clinical outcome. Results: IFN-λ3 was determined in 264 patients (52% males, mean age 57 ± 8 years, 67% HCV genotype (G)1, while CC, CT and TT genotypes were 36%, 50% and 14%, respectively. During a median follow-up of 14.8 years, 149 (56%) patients received IFN. Overall, SVR was achieved in 31 (21%) patients, 40% among those with CC genotype (22% in G1 and 61% in G2, respectively) compared to 10% and 13% among patients with CT and TT genotypes (p <0.0001). Univariate and multivariate analyses found no association between IFN-λ3 (CC vs. non-CC genotype) and disease progression. Conclusion: IFN-λ3 determination is fundamental for allocating cirrhotic patients to be treated with IFN, while it has no value in predicting the outcome of the disease.
KW - IFN-based therapy
KW - IFN-λ3 polymorphism
KW - Outcome of compensated cirrhosis
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U2 - 10.1016/j.antiviral.2014.11.002
DO - 10.1016/j.antiviral.2014.11.002
M3 - Article
C2 - 25446338
AN - SCOPUS:84913534851
VL - 113
SP - 27
EP - 32
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -