{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:06:22Z","timestamp":1791187582520,"version":"4.1.0"},"reference-count":17,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":549,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Pretreatment up-regulation of hepatic interferon (IFN)-stimulated genes (ISGs) has a stronger association with the treatment-resistant interleukin (IL)28B minor genotype (MI; TG\/GG at rs8099917) than with the treatment-sensitive IL28B major genotype (MA; TT at rs8099917). We compared the expression of ISGs in the liver and blood of 146 patients with chronic hepatitis C who received pegylated IFN and ribavirin combination therapy. Gene expression profiles in the liver and blood of 85 patients were analyzed using an Affymetrix GeneChip (Affymetrix, Santa Clara, CA). ISG expression was correlated between the liver and blood of the MA patients, whereas no correlation was observed in the MI patients. This loss of correlation was the result of the impaired infiltration of immune cells into the liver lobules of MI patients, as demonstrated by regional gene expression analysis in liver lobules and portal areas using laser capture microdissection and immunohistochemical staining. Despite having lower levels of immune cells, hepatic ISGs were up-regulated in the liver of MI patients and they were found to be regulated by multiple factors, namely, IL28A\/B, IFN-\u03bb4, and wingless-related MMTV integration site 5A (WNT5A). Interestingly, WNT5A induced the expression of ISGs, but also increased hepatitis C virus replication by inducing the expression of the stress granule protein, GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1), in the Huh-7 cell line. In the liver, the expression of WNT5A and its receptor, frizzled family receptor 5, was significantly correlated with G3BP1. <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>: Immune cells were lost and induced the expression of other inflammatory mediators, such as WNT5A, in the liver of IL28B minor genotype patients. This might be related to the high level of hepatic ISG expression in these patients and the treatment-resistant phenotype of the IL28B minor genotype. (HEPATOLOGY 2014;59:828\u2013838)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26788","type":"journal-article","created":{"date-parts":[[2014,1,27]],"date-time":"2014-01-27T15:34:40Z","timestamp":1390836880000},"page":"828-838","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":35,"title":["Hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis C patients with different interleukin-28B genotypes"],"prefix":"10.1097","volume":"59","author":[{"given":"Masao","family":"Honda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Shirasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Shimakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akito","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Horii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniaki","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikari","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Murai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikiko","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eishiro","family":"Mizukoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-15-20250207","doi-asserted-by":"crossref","first-page":"24172428","DOI":"10.1056\/NEJMoa1013086","article-title":"Telaprevir for retreatment of HCV infection.","volume":"364","author":"Zeuzem","year":"2011","journal-title":"N Engl J Med"},{"key":"R3-15-20250207","doi-asserted-by":"crossref","first-page":"399401","DOI":"10.1038\/nature08309","article-title":"Genetic variation in IL28B predicts hepatitis C treatmentinduced viral clearance.","volume":"461","author":"Ge","year":"2009","journal-title":"Nature"},{"key":"R4-15-20250207","doi-asserted-by":"crossref","first-page":"11001104","DOI":"10.1038\/ng.447","article-title":"IL28B is associated with response to chronic hepatitis C interferonalpha and ribavirin therapy.","volume":"41","author":"Suppiah","year":"2009","journal-title":"Nat Genet"},{"key":"R5-15-20250207","doi-asserted-by":"crossref","first-page":"11051109","DOI":"10.1038\/ng.449","article-title":"Genomewide association of IL28B with response to pegylated interferonalpha and ribavirin therapy for chronic hepatitis C.","volume":"41","author":"Tanaka","year":"2009","journal-title":"Nat Genet"},{"key":"R6-15-20250207","doi-asserted-by":"crossref","first-page":"499509","DOI":"10.1053\/j.gastro.2010.04.049","article-title":"Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C.","volume":"139","author":"Honda","year":"2010","journal-title":"Gastroenterology"},{"key":"R7-15-20250207","doi-asserted-by":"crossref","first-page":"817826","DOI":"10.1016\/j.jhep.2010.04.036","article-title":"Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C.","volume":"53","author":"Honda","year":"2010","journal-title":"J Hepatol"},{"key":"R8-15-20250207","first-page":"164171","article-title":"A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus.","volume":"45","author":"ProkuninaOlsson","year":"2013","journal-title":"Nat Genet"},{"key":"R9-15-20250207","first-page":"791796","article-title":"Production of infectious hepatitis C virus in tissue culture from a cloned viral genome.","volume":"11","author":"Wakita","year":"2005","journal-title":"Nat Med"},{"key":"R10-15-20250207","doi-asserted-by":"crossref","first-page":"1104311056","DOI":"10.1128\/JVI.07101-11","article-title":"Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress.","volume":"86","author":"Garaigorta","year":"2012","journal-title":"J Virol"},{"key":"R11-15-20250207","doi-asserted-by":"crossref","first-page":"23102320","DOI":"10.1242\/jcs.084046","article-title":"Arginine methylation of G3BP1 in response to Wnt3a regulates betacatenin mRNA.","volume":"124","author":"Bikkavilli","year":"2011","journal-title":"J Cell Sci"},{"key":"R12-15-20250207","first-page":"70347039","article-title":"Interferon signaling and treatment outcome in chronic hepatitis C.","volume":"105","author":"SarasinFilipowicz","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R13-15-20250207","doi-asserted-by":"crossref","first-page":"14371444","DOI":"10.1053\/j.gastro.2005.01.059","article-title":"Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection.","volume":"128","author":"Chen","year":"2005","journal-title":"Gastroenterology"},{"key":"R14-15-20250207","doi-asserted-by":"crossref","first-page":"777784","DOI":"10.1084\/jem.185.4.777","article-title":"A novel migration pathway for rat dendritic cells from the blood: hepatic sinusoidslymph translocation.","volume":"185","author":"Kudo","year":"1997","journal-title":"J Exp Med"},{"key":"R16-15-20250207","doi-asserted-by":"crossref","first-page":"15231530","DOI":"10.1002\/hep.23509","article-title":"Systemic and intrahepatic interferongammainducible protein 10 kDa predicts the firstphase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.","volume":"51","author":"Askarieh","year":"2010","journal-title":"Hepatology"},{"key":"R17-15-20250207","doi-asserted-by":"crossref","first-page":"e5354","DOI":"10.1371\/journal.pone.0005354","article-title":"Wnt5a exhibits layerspecific expression in adult skin, is upregulated in psoriasis, and synergizes with type 1 interferon.","volume":"4","author":"Romanowska","year":"2009","journal-title":"PLoS One"},{"key":"R18-15-20250207","doi-asserted-by":"crossref","first-page":"12551267","DOI":"10.1016\/j.cell.2009.12.018","article-title":"A physical and regulatory map of hostinfluenza interactions reveals pathways in H1N1 infection.","volume":"139","author":"Shapira","year":"2009","journal-title":"Cell"},{"key":"R19-15-20250207","doi-asserted-by":"crossref","first-page":"581593","DOI":"10.1038\/nri2360","article-title":"WNT signalling in the immune system: WNT is spreading its wings.","volume":"8","author":"Staal","year":"2008","journal-title":"Nat Rev Immunol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.26788","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201403000-00015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T16:56:55Z","timestamp":1738947415000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201403000-00015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.26788","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2014,3]]}}}