UNLABELLED: Interleukin (IL)28B polymorphisms are associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to therapy. Whether IL28B genotype affects fibrosis progression or clinical outcome is unclear. Our aim was to study the relationship between IL28B genotype and both histological and clinical outcomes in patients with chronic hepatitis C (CHC). Hepatic fibrosis was scored using the Ishak (0-6) scale; progression was defined as a 2-point increase in Ishak score between biopsies. Multiple logistic and Cox regressions were used to identify variables associated with fibrosis progression. In all, 1,483 patients were included in a baseline cross-sectional analysis, from which 276 were eligible for a paired biopsy analysis (median time between biopsies 4 years), and 400 for a clinical outcome analysis. At baseline biopsy, patients with IL28B CC genotype had significantly higher portal inflammation (2.4 versus 2.2) and alanine aminotransferase (ALT) levels (133 versus 105 U/L; P < 0.05 for all). In the paired biopsy analysis, there was no difference in the frequency of fibrosis progression between patients with IL28B CC and non-CC genotypes (17% versus 23%). In logistic regression, only higher baseline alkaline phosphatase, lower platelets, and greater hepatic steatosis were associated with fibrosis progression. Patients with IL28B CC were twice as likely to develop adverse clinical outcomes compared to non-CC (32% versus 16%; P = 0.007). CONCLUSION: IL28B CC genotype was associated with greater hepatic necroinflammation, higher ALT, and worse clinical outcomes in CHC patients. This suggests that IL28B CC is associated with a state of enhanced immunity that, on the one hand, can promote viral clearance, but alternately can increase necroinflammation and hepatic decompensation without enhancing fibrosis progression.
UNLABELLED: Interleukin (IL)28B polymorphisms are associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to therapy. Whether IL28B genotype affects fibrosis progression or clinical outcome is unclear. Our aim was to study the relationship between IL28B genotype and both histological and clinical outcomes in patients with chronic hepatitis C (CHC). Hepatic fibrosis was scored using the Ishak (0-6) scale; progression was defined as a 2-point increase in Ishak score between biopsies. Multiple logistic and Cox regressions were used to identify variables associated with fibrosis progression. In all, 1,483 patients were included in a baseline cross-sectional analysis, from which 276 were eligible for a paired biopsy analysis (median time between biopsies 4 years), and 400 for a clinical outcome analysis. At baseline biopsy, patients with IL28B CC genotype had significantly higher portal inflammation (2.4 versus 2.2) and alanine aminotransferase (ALT) levels (133 versus 105 U/L; P < 0.05 for all). In the paired biopsy analysis, there was no difference in the frequency of fibrosis progression between patients with IL28B CC and non-CC genotypes (17% versus 23%). In logistic regression, only higher baseline alkaline phosphatase, lower platelets, and greater hepatic steatosis were associated with fibrosis progression. Patients with IL28B CC were twice as likely to develop adverse clinical outcomes compared to non-CC (32% versus 16%; P = 0.007). CONCLUSION:IL28B CC genotype was associated with greater hepatic necroinflammation, higher ALT, and worse clinical outcomes in CHCpatients. This suggests that IL28B CC is associated with a state of enhanced immunity that, on the one hand, can promote viral clearance, but alternately can increase necroinflammation and hepatic decompensation without enhancing fibrosis progression.
Authors: Francesco Marabita; Alessio Aghemo; Stella De Nicola; Maria G Rumi; Cristina Cheroni; Rossana Scavelli; Marco Crimi; Roberta Soffredini; Sergio Abrignani; Raffaele De Francesco; Massimo Colombo Journal: Hepatology Date: 2011-08-19 Impact factor: 17.425
Authors: Hans L Tillmann; Keyur Patel; Andrew J Muir; Cynthia D Guy; Josephine H Li; Xiang Qian Lao; Alexander Thompson; Paul J Clark; Stephen D Gardner; John G McHutchison; Jeanette J McCarthy Journal: J Hepatol Date: 2011-04-14 Impact factor: 25.083
Authors: Ludmila Prokunina-Olsson; Brian Muchmore; Wei Tang; Ruth M Pfeiffer; Heiyoung Park; Harold Dickensheets; Dianna Hergott; Patricia Porter-Gill; Adam Mumy; Indu Kohaar; Sabrina Chen; Nathan Brand; McAnthony Tarway; Luyang Liu; Faruk Sheikh; Jacquie Astemborski; Herbert L Bonkovsky; Brian R Edlin; Charles D Howell; Timothy R Morgan; David L Thomas; Barbara Rehermann; Raymond P Donnelly; Thomas R O'Brien Journal: Nat Genet Date: 2013-01-06 Impact factor: 38.330
Authors: L Nosotti; A Petrelli; D Genovese; S Catone; C Argentini; S Vella; A Rossi; G Costanzo; A Fortino; L Chessa; L Miglioresi; C Mirisola Journal: J Immigr Minor Health Date: 2017-08
Authors: Brad R Rosenberg; Catherine A Freije; Naoko Imanaka; Spencer T Chen; Jennifer L Eitson; Rachel Caron; Skyler A Uhl; Marija Zeremski; Andrew Talal; Ira M Jacobson; Charles M Rice; John W Schoggins Journal: J Infect Dis Date: 2018-01-30 Impact factor: 5.226
Authors: Emilie Estrabaud; Martine Lapalus; Philippe Broët; Kevin Appourchaux; Simon De Muynck; Olivier Lada; Michelle Martinot-Peignoux; Ivan Bièche; Dominique Valla; Pierre Bedossa; Patrick Marcellin; Michel Vidaud; Tarik Asselah Journal: J Virol Date: 2014-03-26 Impact factor: 5.103
Authors: Jessica L Mueller; Lindsay Y King; Kara B Johnson; Tian Gao; Lauren D Nephew; Darshan Kothari; Mary Ann Simpson; Hui Zheng; Lan Wei; Kathleen E Corey; Joseph Misdraji; Joon Hyoek Lee; M Valerie Lin; Neliswa A Gogela; Bryan C Fuchs; Kenneth K Tanabe; Fredric D Gordon; Michael P Curry; Raymond T Chung Journal: Clin Transplant Date: 2016-03-01 Impact factor: 2.863