Background & Aims: Aim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival. Methods: we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data. Results: Homozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5-9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1-3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20-39 vs. 45, 95% c.i. 38-52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32-64 vs. 55, 95% c.i. 43-67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12-2.78). Conclusions: PNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival.

PNPLA3 I148M Polymorphism, Clinical Presentation, and Survival in Patients with Hepatocellular Carcinoma / L. Valenti, B. Motta, G. Soardo, M. Iavarone, B. Donati, A. Sangiovanni, A. Carnelutti, P. Dongiovanni, R. Rametta, C. Bertelli, F. Facchetti, M. Colombo, S. Fargion, A. Fracanzani. - In: PLOS ONE. - ISSN 1932-6203. - 8:10(2013 Oct 14), pp. e75982.1-e75982.8. [10.1371/journal.pone.0075982]

PNPLA3 I148M Polymorphism, Clinical Presentation, and Survival in Patients with Hepatocellular Carcinoma

L. Valenti
Primo
;
B. Motta
Secondo
;
M. Iavarone;B. Donati;P. Dongiovanni;R. Rametta;C. Bertelli;F. Facchetti;M. Colombo;S. Fargion
Penultimo
;
A. Fracanzani
Ultimo
2013

Abstract

Background & Aims: Aim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival. Methods: we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data. Results: Homozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5-9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1-3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20-39 vs. 45, 95% c.i. 38-52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32-64 vs. 55, 95% c.i. 43-67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12-2.78). Conclusions: PNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival.
hepatocellular carcinoma; liver diseases; homozygosity; cirrhosis; etiology; alleles; genetics of disease; fatty liver
Settore MED/09 - Medicina Interna
14-ott-2013
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/230598
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