Patatin-like phospholipase domain-containing 3 I148M affects liver steatosis in patients with chronic hepatitis B

Authors

  • Mauro Viganò,

    1. Hepatology Unit, Ospedale San Giuseppe, Università degli Studi di Milano, Milano, Italy
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    • These authors contributed equally.

  • Luca Valenti,

    Corresponding author
    • Internal Medicine 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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    • These authors contributed equally.

  • Pietro Lampertico,

    1. Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Floriana Facchetti,

    1. Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Benedetta Maria Motta,

    1. Internal Medicine 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Roberta D'Ambrosio,

    1. Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Solange Romagnoli,

    1. Pathology Unit, Department of Health Sciences, San Paolo Hospital, Università degli Studi di Milano, Milan, Italy
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  • Paola Dongiovanni,

    1. Internal Medicine 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Benedetta Donati,

    1. Internal Medicine 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Silvia Fargion,

    1. Internal Medicine 1B, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Massimo Colombo

    1. Centro A.M. e A. Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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  • Potential conflict of interest: Mauro Viganò has worked in a speaking and teaching capacity for Bristol-Myers Squibb, Roche, and Gilead Sciences. Massimo Colombo has been awarded grant and research support from MSD, Roche, Bristol-Myers Squibb, and Gilead Sciences, has served on the advisory committees of MSD, Roche, Novartis, Bayer, Bristol-Myers Squibb, Gilead Sciences, Tibotec, and Vertex, and has worked in a speaking and teaching capacity for Tibotec, MSD, Roche, Novartis, Bayer, Bristol-Myers Squibb, Gilead Sciences, and Vertex. Pietro Lampertico has served on the advisory board/speaker bureau for Bristol-Myers Squibb, Roche, Gilead Sciences, and GlaxoSmithKline.

Address reprint requests to: Luca Valenti, M.D., Ph.D., Fondazione IRCCS Ca' Granda–Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35, 20122 Milan, Italy. E-mail: luca.valenti@unimi.it; fax: 00390250320296.

Abstract

Steatosis is a common histopathological feature of chronic hepatitis B (CHB) and has been associated with severity of liver disease. Recently, the rs738409 I148M patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism has been demonstrated to influence steatosis susceptibility and fibrosis progression in patients with different liver diseases, but no data are yet available for CHB. The aim of this study was to evaluate whether PNPLA3 I148M influences steatosis susceptibility in a large series of patients with CHB. We enrolled 235 treatment-naïve CHB patients consecutively examined by percutaneous liver biopsy. In ≥2-cm-long liver tissue cores, steatosis and fibrosis were staged by Kleiner and METAVIR scores, respectively. The I148M polymorphism was determined by Taqman assays. Steatosis was present in 146 (62%) patients, of whom 24 (10%) had severe (>33% of hepatocytes) steatosis. Steatosis was independently associated with age (odds ratio [OR]: 2.67; confidence interval [CI]: 1.50-4.92; for age ≥50 years), body mass index (BMI; OR, 2.84; CI, 1.30-6.76; for BMI ≥27.5 kg/m2), diabetes or impaired fasting glucose (OR, 4.45; CI, 1.10-30.0), and PNPLA3 148M allele (OR, 1.62; CI, 1.00-7.00; for each 148M allele). Independent predictors of severe steatosis were BMI (OR, 3.60; CI, 1.39-9.22; for BMI ≥27.5 kg/m2) and PNPLA3 148M allele (OR, 6.03; CI, 1.23-5.0; for each 148M allele). PNPLA3 148M alleles were associated with a progressive increase in severe steatosis in patients with acquired cofactors, such severe overweight and a history of alcohol intake (P = 0.005). Conclusion: In CHB patients, the PNPLA3 I148M polymorphism influences susceptibility to steatosis and, in particular, when associated with severe overweight and alcohol intake, severe steatosis. (Hepatology 2013;58:1245–1252)

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