Background & Aims : Homozygosity for the Patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M polymorphism (p.148M/M) has been associated with steatosis, fibrosis progression, and hepatocellular carcinoma in chronic hepatitis C (CHC) patients, but the effect on treatment outcome is still controversial. Aim of this study was to evaluate the effect of p.148M/M on the rate of sustained virological response (SVR) and viral kinetics in CHC patients who underwent standard of care (SOC) antiviral therapy with peg-interferon and ribavirin, stratified according to viral genotype (genotype 2 (gen2) vs. others), and severity of fibrosis (Metavir < or > 2). Patients: 602 naïve consecutive patients from two tertiary referral centers in Milan and one in Vienna, for whom DNA samples and liver biopsy were available. Mean age 50.8±12 years, 39% were females, 61% gen1, 17% gen2, 6% gen3, 16% gen4, 30% had advanced fibrosis, 33% were IL28B rs12979860 CC. Results: p.148M/M was detected in 49 patients (8%), and was associated with advanced fibrosis (21/49, 43% vs. 158/553, 28%; p=0.049), but not with demographic, anthropometric, and virological parameters. The p.148M/M genotype was not significantly associated with SVR in the whole series (25/49, 51% vs. 326/553, 59%; p=0.29), but it was associated with a lower SVR rate in non-gen2 patients with advanced fibrosis (4/18, 22% vs. 64/135, 48%; p=0.047). In these subjects, p.148M/M was also associated with a lower rate of complete early viral response (5/18, 28% vs. 80/135, 59%; p=0.021). SVR was not influenced by p.148M/M in gen2 patients and in patients without advanced fibrosis. In non-gen2 patients, SVR was independently associated with younger age, absence of advanced fibrosis, IL28B CC genotype, completion of adequate dose treatment (≥80/80/80%), and p.148M/M (OR 0.70, 95% c.i 0.46-1.0). Conclusions: PNPLA3 genotype seems to represent a negative prognostic factor for antiviral treatment outcome independently of the effect on fibrosis progression, but only in a very selected subgroup of difficult-to-cure CHC patients (3% in this series). However, whether it also influences the outcome of triple therapies with direct antiviral agents needs to be evaluated in future studies

Effect of the PNPLA3 I148M polymorphism on the outcome of peg-interferon plus ribavirin treatment in chronic hepatitis C

A. M. Aghemo
2011-01-01

Abstract

Background & Aims : Homozygosity for the Patatin-like phospholipase domain-containing 3 (PNPLA3) p.I148M polymorphism (p.148M/M) has been associated with steatosis, fibrosis progression, and hepatocellular carcinoma in chronic hepatitis C (CHC) patients, but the effect on treatment outcome is still controversial. Aim of this study was to evaluate the effect of p.148M/M on the rate of sustained virological response (SVR) and viral kinetics in CHC patients who underwent standard of care (SOC) antiviral therapy with peg-interferon and ribavirin, stratified according to viral genotype (genotype 2 (gen2) vs. others), and severity of fibrosis (Metavir < or > 2). Patients: 602 naïve consecutive patients from two tertiary referral centers in Milan and one in Vienna, for whom DNA samples and liver biopsy were available. Mean age 50.8±12 years, 39% were females, 61% gen1, 17% gen2, 6% gen3, 16% gen4, 30% had advanced fibrosis, 33% were IL28B rs12979860 CC. Results: p.148M/M was detected in 49 patients (8%), and was associated with advanced fibrosis (21/49, 43% vs. 158/553, 28%; p=0.049), but not with demographic, anthropometric, and virological parameters. The p.148M/M genotype was not significantly associated with SVR in the whole series (25/49, 51% vs. 326/553, 59%; p=0.29), but it was associated with a lower SVR rate in non-gen2 patients with advanced fibrosis (4/18, 22% vs. 64/135, 48%; p=0.047). In these subjects, p.148M/M was also associated with a lower rate of complete early viral response (5/18, 28% vs. 80/135, 59%; p=0.021). SVR was not influenced by p.148M/M in gen2 patients and in patients without advanced fibrosis. In non-gen2 patients, SVR was independently associated with younger age, absence of advanced fibrosis, IL28B CC genotype, completion of adequate dose treatment (≥80/80/80%), and p.148M/M (OR 0.70, 95% c.i 0.46-1.0). Conclusions: PNPLA3 genotype seems to represent a negative prognostic factor for antiviral treatment outcome independently of the effect on fibrosis progression, but only in a very selected subgroup of difficult-to-cure CHC patients (3% in this series). However, whether it also influences the outcome of triple therapies with direct antiviral agents needs to be evaluated in future studies
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/13091
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