Implications of PNPLA3 polymorphism in chronic hepatitis C patients receiving peginterferon plus ribavirin

Authors

  • L. Valenti,

    Corresponding author
    • Department of Internal Medicine, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • A. Aghemo,

    1. A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • A. F. Stättermayer,

    1. Internal Medicine, Department of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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  • P. Maggioni,

    1. Department of Internal Medicine, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • S. De Nicola,

    1. A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • B. M. Motta,

    1. Department of Internal Medicine, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • M. G. Rumi,

    1. A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
    2. Division of Hepatology, Ospedale San Giuseppe IRCCS Multimedica, Università degli Studi di Milano, Milan, Italy
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  • P. Dongiovanni,

    1. Department of Internal Medicine, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • P. Ferenci,

    1. Internal Medicine, Department of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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  • M. Colombo,

    1. A.M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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  • S. Fargion

    1. Department of Internal Medicine, Università degli Studi, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
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Correspondence to:

Dr L. Valenti, Metabolic liver diseases research center, Department of Internal Medicine, Università degli Studi di Milano, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, pad. Granelli, via F Sforza 35, 20122, Milano, Italy.

E-mail: luca.valenti@unimi.it

Summary

Background

Homozygosity for the PNPLA3 p.I148M polymorphism influences steatosis and fibrogenesis in chronic hepatitis C (CHC).

Aim

To evaluate the effect of p.148M/M on sustained virological response (SVR) and viral kinetics in patients who underwent antiviral therapy with peg-interferon and ribavirin, stratified according to viral genotype and fibrosis severity, and secondarily, the interaction with interleukin-28B (IL28B) genotype on liver damage.

Methods

In this observational study, we considered 602 treatment-naïve consecutive patients from tertiary referral centres in Milan and Vienna [61% genotype 1 (G1), 30% advanced fibrosis, 33% IL28B rs12979860 CC].

Results

The p.148M/M genotype, detected in 8% of patients, did not influence SVR in the overall series (= 0.29), but it was associated with SVR (3/17, 17% vs. 56/121, 46%; P = 0.034) and complete early viral response (4/17, 23% vs. 68/121, 56%; P = 0.018) in G1/4 patients with advanced fibrosis. After adjustment for age, viral load, IL28BCC genotype, treatment dose, and steatosis, p.148M/M remained a predictor of SVR in G1/4 patients with advanced fibrosis (OR 0.23, 95% CI 0.04–0.87). The p.148M/M genotype was associated with more advanced fibrosis in the overall series (P = 0.049), whereas the rs12979860 IL28BCC genotype only in patients negative for p.148M/M (P = 0.017), independently of age, BMI and alanine transaminase levels (OR 1.51, 95% CI 1.01–2.27).

Conclusions

PNPLA3 p.148M/M genotype was negatively associated with SVR and early viral kinetics independently of steatosis, albeit only in difficult-to-cure G1/4 patients with advanced fibrosis, whereas stratification for the p.148M/M PNPLA3 genotype unmasked an association between IL28BCC genotype and more severe liver fibrosis.

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