Background & Aims: Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients. Methods: One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested. Results: Seventy-four (46.2%) patients had IL28B rs12979860 CC polymorphism, compared with 72 (45%) and 14 (8.8%) with TC and TT variants, respectively. PNPLA3 rs738409 CC polymorphism was present in 47 (29.4%) patients, compared with 79 (49.4%) and 34 (21.3%) with CG and GG variants, respectively. Multivariate logistic regression analysis showed that age (OR 1.043, 95% CI 1.012-1.075, p = 0.007), triglycerides (OR 1.005, 95% CI 1.000-1.010, p = 0.04), hyperuricemia (OR 5.027, 95% CI 1.839-13.742, p = 0.002), IL28B rs12979860 TT/TC (OR 0.219, 95% CI 0.101-0.472, p <0.001), and steatosis grade (OR 1.704, 95% CI 1.048-2.773, p = 0.03) were independently linked to moderate-severe lobular inflammation. Finally, IL28B rs12979860 CC was associated with severe fibrosis (F3-F4) on univariate analysis, even if only older age (OR 1.064, 95% CI 1.026-1.104, p = 0.001), high HOMA (OR 1.213, 95% CI 1.068-1.377, p = 0.003), and lobular inflammation (OR 3.181, 95% CI 1.438-7.036, p = 0.004), remained associated in multivariate logistic regression analysis. Conclusions: In NAFLD patients, IL28B rs12979860 CC genotype, together with PNPLA3 rs738409 GG, is associated with the severity of liver damage. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Petta, S., Grimaudo, S., Cammà, C., Cabibi, D., Di Marco, V., Licata, G., et al. (2012). IL28B and PNPLA3 Polymorphisms Affect Histological Liver Damage in Patients with Non-alcoholic Fatty Liver Disease. JOURNAL OF HEPATOLOGY, 56, 1356-1362.

IL28B and PNPLA3 Polymorphisms Affect Histological Liver Damage in Patients with Non-alcoholic Fatty Liver Disease.

PETTA, Salvatore;GRIMAUDO, Stefania;CAMMA', Calogero;CABIBI, Daniela;DI MARCO, Vito;LICATA, Giusalba;PIPITONE, Rosaria Maria;CRAXI, Antonio
2012-01-01

Abstract

Background & Aims: Genetic background may affect liver damage in patients with non-alcoholic fatty liver disease (NAFLD). The main outcomes of the study were to assess whether IL28B rs12979860 and rs8099917 polymorphisms, together with PNPLA3 rs738409 C>G polymorphism, are associated with lobular inflammation and fibrosis, in NAFLD patients. Methods: One hundred sixty consecutive NAFLD patients were assessed by liver biopsy (Kleiner score); anthropometric, and biochemical and metabolic features were included. IL28B rs12979860 C>T, IL28B rs8099917 G>C, and PNPLA3 rs738409 C>G single nucleotide polymorphisms were tested. Results: Seventy-four (46.2%) patients had IL28B rs12979860 CC polymorphism, compared with 72 (45%) and 14 (8.8%) with TC and TT variants, respectively. PNPLA3 rs738409 CC polymorphism was present in 47 (29.4%) patients, compared with 79 (49.4%) and 34 (21.3%) with CG and GG variants, respectively. Multivariate logistic regression analysis showed that age (OR 1.043, 95% CI 1.012-1.075, p = 0.007), triglycerides (OR 1.005, 95% CI 1.000-1.010, p = 0.04), hyperuricemia (OR 5.027, 95% CI 1.839-13.742, p = 0.002), IL28B rs12979860 TT/TC (OR 0.219, 95% CI 0.101-0.472, p <0.001), and steatosis grade (OR 1.704, 95% CI 1.048-2.773, p = 0.03) were independently linked to moderate-severe lobular inflammation. Finally, IL28B rs12979860 CC was associated with severe fibrosis (F3-F4) on univariate analysis, even if only older age (OR 1.064, 95% CI 1.026-1.104, p = 0.001), high HOMA (OR 1.213, 95% CI 1.068-1.377, p = 0.003), and lobular inflammation (OR 3.181, 95% CI 1.438-7.036, p = 0.004), remained associated in multivariate logistic regression analysis. Conclusions: In NAFLD patients, IL28B rs12979860 CC genotype, together with PNPLA3 rs738409 GG, is associated with the severity of liver damage. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
2012
Settore MED/12 - Gastroenterologia
Settore MED/08 - Anatomia Patologica
Petta, S., Grimaudo, S., Cammà, C., Cabibi, D., Di Marco, V., Licata, G., et al. (2012). IL28B and PNPLA3 Polymorphisms Affect Histological Liver Damage in Patients with Non-alcoholic Fatty Liver Disease. JOURNAL OF HEPATOLOGY, 56, 1356-1362.
File in questo prodotto:
File Dimensione Formato  
IL28B AND PNPLA3 IN NAFLD.pdf

Solo gestori archvio

Dimensione 676.26 kB
Formato Adobe PDF
676.26 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/61945
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 81
  • ???jsp.display-item.citation.isi??? 79
social impact