{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:03:51Z","timestamp":1753877031515,"version":"3.41.2"},"reference-count":40,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,9,13]],"date-time":"2019-09-13T00:00:00Z","timestamp":1568332800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870404","81670518","81170392"],"award-info":[{"award-number":["81870404","81670518","81170392"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Project on the Integration of Industry, Education and Research of Guangzhou, China","award":["201604020155"],"award-info":[{"award-number":["201604020155"]}]},{"name":"Science and Technology Program of Guangdong province","award":["2013B021800290","2014A020212118","2017A020215015"],"award-info":[{"award-number":["2013B021800290","2014A020212118","2017A020215015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Keratin 8 and 18 (K8\/K18) are the exclusively expressed keratins intermediate filaments pair in hepatocytes that protect against liver injuries and viral infection. We aimed to explore the genetic link between keratin variants and chronic hepatitis B virus (CHB) infection in a large cohort from a high-epidemic area.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Genomic deoxyribonucleic acid was isolated from patients, and Sanger sequencing was applied to analyze variations in exon regions of K8\/18. Biochemical and functional analysis of novel mutations was also performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The 713 participants comprised 173 healthy controls and 540 patients, which covered chronic hepatitis (n = 174), decompensated cirrhosis (n = 192), and primary liver carcinoma (n = 174). The frequency of mutations in K8\/18 was significantly higher among patients than among controls (8.15% vs 0.58%, P &lt; .001). Significant differences were found between the chronic hepatitis subgroup and controls in multiple comparisons (6.32% vs 0.58%, P = .006). All 21 missense mutations (3.89%) were detected in the keratin 8 (K8), including 4 novel conserved missense variants (R469C, R469H, A447V, and K483T). Multivariate logistic regression analysis demonstrated a higher risk of acute-on-chronic liver failure (ACLF) and missense variants (odds ratio = 4.38, P = .035). Transfection of these variants caused keratin network disruption in vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Novel K8 cytoskeleton-disrupting variants predispose toward ACLF in CHB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiz467","type":"journal-article","created":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T11:51:56Z","timestamp":1568202716000},"source":"Crossref","is-referenced-by-count":1,"title":["Keratin 8 Mutations Were Associated With Susceptibility to Chronic Hepatitis B and Related Progression"],"prefix":"10.1093","author":[{"given":"Junzhao","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minrui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaorong","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bihui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,9,13]]},"reference":[{"key":"2019102404291281300_CIT0001","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD guidelines for treatment of chronic hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"2019102404291281300_CIT0002","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/S1473-3099(15)00218-2","article-title":"Seroepidemiology of hepatitis B virus infection in 2 million men aged 21-49 years in rural China: a population-based, cross-sectional study","volume":"16","author":"Liu","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"2019102404291281300_CIT0003","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1016\/S0140-6736(18)31865-8","article-title":"Chronic hepatitis B virus 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