PNPLA3 I148M polymorphism, clinical presentation, and survival in patients with hepatocellular carcinoma.
<h4>Background & aims</h4>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.<h4>Methods</h4>we considered 460 consecutive HCC pa...
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| Autores principales: | , , , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/dcbc63d1da6c40f7a2e76c9c1c7a8ecb |
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| Sumario: | <h4>Background & aims</h4>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.<h4>Methods</h4>we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data.<h4>Results</h4>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).<h4>Conclusions</h4>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. |
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