{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T13:40:12Z","timestamp":1769262012901,"version":"3.49.0"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T00:00:00Z","timestamp":1398384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients. Materials and Methods: Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as &lt;5% or \u22655%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in  151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients  (CC vs. CT\/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT\/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients  (CC vs. CT\/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3-F4  (CC vs. CT\/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23\u20138.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.<\/jats:p>","DOI":"10.3390\/ijms15057213","type":"journal-article","created":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T05:15:00Z","timestamp":1398662100000},"page":"7213-7224","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent"],"prefix":"10.3390","volume":"15","author":[{"given":"Roberta","family":"D'Ambrosio","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessio","family":"Aghemo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"De Francesco","sequence":"additional","affiliation":[{"name":"INGM, Istituto Nazionale Genetica Molecolare Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Rumi","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Ospedale San Giuseppe IRCCS Multimedica,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Galmozzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stella","family":"De Nicola","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Cheroni","sequence":"additional","affiliation":[{"name":"INGM, Istituto Nazionale Genetica Molecolare Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Clark","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University, Durham, NC 27715, USA"},{"name":"Kirby Institute for Infection and Immunity in Society, University of South Wales,  Kensington 2033, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Ronchi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Lampertico","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Colombo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Ospedale Maggiore Policlinico,  Universit\u00e0 degli Studi di Milano, Milan 20100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nature08463","article-title":"Genetic variation in IL28B and spontaneous clearance of hepatitis C virus","volume":"461","author":"Thomas","year":"2009","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2009.12.056","article-title":"Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: A genome-wide association study","volume":"138","author":"Rauch","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nature08309","article-title":"Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance","volume":"461","author":"Ge","year":"2009","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/ng.447","article-title":"IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy","volume":"41","author":"Suppiah","year":"2009","journal-title":"Nat. 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Hepatol"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1002\/hep.26506","article-title":"Association of IL28B genotype with fibrosis progression and clinical outcomes in patients with chronic hepatitis C: A longitudinal analysis","volume":"58","author":"Noureddin","year":"2013","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/hep.25606","article-title":"A morphometrical and immunoistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis","volume":"56","author":"Aghemo","year":"2012","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1002\/hep.24556","article-title":"Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C","volume":"54","author":"bambha","year":"2011","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1002\/hep.25647","article-title":"Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response","volume":"56","author":"Naggie","year":"2012","journal-title":"Hepatology"},{"key":"ref_14","first-page":"1220A","article-title":"Genome wide-association study identifies IL28B polymorphism to be associated with baseline ALT and hepatic necro-inflammatory activity in chronic hepatitis C patients enrolled in the IDEAL study","volume":"52","author":"Thompson","year":"2010","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rembeck, K., Alsio, A., Christensen, P.B., F\u00e4rkkil\u00e4, M., Langeland, N., Buhl, M.R., Pedersen, C., M\u00f8rch, K., Westin, J., and Lindh, M. (2012). Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3. PLoS One, 7.","DOI":"10.1371\/journal.pone.0029370"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/hep.24678","article-title":"IL28B alleles associated with poor HCV clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes","volume":"55","author":"Bochud","year":"2012","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/hep.25631","article-title":"Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in agenotype-specific manner","volume":"56","author":"Check","year":"2012","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jhep.2009.05.016","article-title":"Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C","volume":"51","author":"Bochud","year":"2009","journal-title":"J. Hepatol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.jhep.2011.03.015","article-title":"Beneficial IL28B genotype associated with lower frequency of hepatic Steatosis in patients with chronic hepatitis C","volume":"55","author":"Tillmann","year":"2011","journal-title":"J. Hepatol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/hep.20535","article-title":"Sources of variability in histological scoring of chronic viral hepatitis","volume":"41","author":"Rousselet","year":"2005","journal-title":"Hepatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1053\/j.gastro.2009.08.071","article-title":"Randomized study of peginterferon-alpha2a plus ribavirin and peginterferon-alpha2b plus ribavirin in chronic hepatitis C","volume":"138","author":"Rumi","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Aghemo, A., Prati, G.M., Rumi, M.G., Soffredini, R., D\u2019Ambrosio, R., Orsi, E., de Nicola, S., Degasperi, E., Grancini, V., and Colombo, M. (2012). Sustained virological response prevents the development of insulin resistance in patients with chronic hepatitis C. Hepatology, 56.","DOI":"10.1002\/hep.25867"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/hep.1840200104","article-title":"Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C","volume":"20","author":"Bedossa","year":"1994","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/hep.510240201","article-title":"An alghoritm for the grading of activity in chronic hepatitis C","volume":"24","author":"Bedossa","year":"1996","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","article-title":"Histological grading and staging of chronic hepatitis","volume":"22","author":"Ishak","year":"1995","journal-title":"J. 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