{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:13:07Z","timestamp":1791245587211,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T00:00:00Z","timestamp":1543536000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastroenterol"],"published-print":{"date-parts":[[2019,5]]},"DOI":"10.1007\/s00535-018-01533-x","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T08:02:30Z","timestamp":1543564950000},"page":"427-436","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Independent and additive effects of PNPLA3 and TM6SF2 polymorphisms on the development of non-B, non-C hepatocellular carcinoma"],"prefix":"10.1007","volume":"54","author":[{"given":"Maneerat","family":"Raksayot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natthaya","family":"Chuaypen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apichaya","family":"Khlaiphuengsin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nutcha","family":"Pinjaroen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sombat","family":"Treeprasertsuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Poovorawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pisit","family":"Tangkijvanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,30]]},"reference":[{"key":"1533_CR1","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1016\/S0140-6736(11)61347-0","volume":"379","author":"A Forner","year":"2012","unstructured":"Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245\u201355.","journal-title":"Lancet"},{"issue":"1264\u201373","key":"1533_CR2","first-page":"e1","volume":"142","author":"HB El-Serag","year":"2012","unstructured":"El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(1264\u201373):e1.","journal-title":"Gastroenterology"},{"key":"1533_CR3","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s005350050248","volume":"34","author":"P Tangkijvanich","year":"1999","unstructured":"Tangkijvanich P, Hirsch P, Theamboonlers A, et al. Association of hepatitis viruses with hepatocellular carcinoma in Thailand. J Gastroenterol. 1999;34:227\u201333.","journal-title":"J Gastroenterol"},{"key":"1533_CR4","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1053\/j.gastro.2005.11.017","volume":"130","author":"CP Day","year":"2006","unstructured":"Day CP. From fat to inflammation. Gastroenterology. 2006;130:207\u201310.","journal-title":"Gastroenterology"},{"key":"1533_CR5","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.jhep.2017.06.003","volume":"67","author":"JG Fan","year":"2017","unstructured":"Fan JG, Kim SU, Wong VW. New trends on obesity and NAFLD in Asia. J Hepatol. 2017;67:862\u201373.","journal-title":"J Hepatol"},{"key":"1533_CR6","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.jhep.2012.02.035","volume":"57","author":"P Nahon","year":"2012","unstructured":"Nahon P, Zucman-Rossi J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J Hepatol. 2012;57:663\u201374.","journal-title":"J Hepatol"},{"key":"1533_CR7","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1038\/ng.257","volume":"40","author":"S Romeo","year":"2008","unstructured":"Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461\u20135.","journal-title":"Nat Genet"},{"issue":"1728\u201344","key":"1533_CR8","first-page":"e7","volume":"150","author":"QM Anstee","year":"2016","unstructured":"Anstee QM, Seth D, Day CP. Genetic factors that affect risk of alcoholic and nonalcoholic fatty liver disease. Gastroenterology. 2016;150(1728\u201344):e7.","journal-title":"Gastroenterology"},{"key":"1533_CR9","doi-asserted-by":"publisher","first-page":"e1001324","DOI":"10.1371\/journal.pgen.1001324","volume":"7","author":"EK Speliotes","year":"2011","unstructured":"Speliotes EK, Yerges-Armstrong LM, Wu J, et al. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7:e1001324.","journal-title":"PLoS Genet"},{"key":"1533_CR10","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/ng.2901","volume":"46","author":"J Kozlitina","year":"2014","unstructured":"Kozlitina J, Smagris E, Stender S, et al. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2014;46:352\u20136.","journal-title":"Nat Genet"},{"key":"1533_CR11","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1038\/ng.3417","volume":"47","author":"S Buch","year":"2015","unstructured":"Buch S, Stickel F, Trepo E, et al. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nat Genet. 2015;47:1443\u20138.","journal-title":"Nat Genet"},{"issue":"1219\u201330","key":"1533_CR12","first-page":"e6","volume":"150","author":"RM Mancina","year":"2016","unstructured":"Mancina RM, Dongiovanni P, Petta S, et al. The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of european descent. Gastroenterology. 2016;150(1219\u201330):e6.","journal-title":"Gastroenterology"},{"key":"1533_CR13","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1002\/hep.24199","volume":"53","author":"J Bruix","year":"2011","unstructured":"Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020\u20132.","journal-title":"Hepatology"},{"key":"1533_CR14","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/jnci\/djn134","volume":"100","author":"JM Llovet","year":"2008","unstructured":"Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100:698\u2013711.","journal-title":"J Natl Cancer Inst"},{"key":"1533_CR15","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.7314\/APJCP.2013.14.5.2865","volume":"14","author":"W Sopipong","year":"2013","unstructured":"Sopipong W, Tangkijvanich P, Payungporn S, et al. The KIF1B (rs17401966) single nucleotide polymorphism is not associated with the development of HBV-related hepatocellular carcinoma in Thai patients. Asian Pac J Cancer Prev. 2013;14:2865\u20139.","journal-title":"Asian Pac J Cancer Prev"},{"key":"1533_CR16","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.bpg.2014.08.006","volume":"28","author":"JC Nault","year":"2014","unstructured":"Nault JC. Pathogenesis of hepatocellular carcinoma according to aetiology. Best Pract Res Clin Gastroenterol. 2014;28:937\u201347.","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"1533_CR17","doi-asserted-by":"publisher","first-page":"48968","DOI":"10.1074\/jbc.M407841200","volume":"279","author":"CM Jenkins","year":"2004","unstructured":"Jenkins CM, Mancuso DJ, Yan W, et al. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem. 2004;279:48968\u201375.","journal-title":"J Biol Chem"},{"key":"1533_CR18","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.bbalip.2013.12.006","volume":"1841","author":"P Pingitore","year":"2014","unstructured":"Pingitore P, Pirazzi C, Mancina RM, et al. Recombinant PNPLA3 protein shows triglyceride hydrolase activity and its I148\u00a0M mutation results in loss of function. Biochim Biophys Acta. 2014;1841:574\u201380.","journal-title":"Biochim Biophys Acta"},{"key":"1533_CR19","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1002\/hep.29041","volume":"65","author":"FV Bruschi","year":"2017","unstructured":"Bruschi FV, Claudel T, Tardelli M, et al. The PNPLA3 I148\u00a0M variant modulates the fibrogenic phenotype of human hepatic stellate cells. Hepatology. 2017;65:1875\u201390.","journal-title":"Hepatology"},{"key":"1533_CR20","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/hep.27242","volume":"61","author":"E Smagris","year":"2015","unstructured":"Smagris E, BasuRay S, Li J, et al. Pnpla3I148\u00a0M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis. Hepatology. 2015;61:108\u201318.","journal-title":"Hepatology"},{"key":"1533_CR21","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.jhep.2016.03.011","volume":"65","author":"E Trepo","year":"2016","unstructured":"Trepo E, Romeo S, Zucman-Rossi J, et al. PNPLA3 gene in liver diseases. J Hepatol. 2016;65:399\u2013412.","journal-title":"J Hepatol"},{"key":"1533_CR22","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/ajg.2013.476","volume":"109","author":"AG Singal","year":"2014","unstructured":"Singal AG, Manjunath H, Yopp AC, et al. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. Am J Gastroenterol. 2014;109:325\u201334.","journal-title":"Am J Gastroenterol"},{"key":"1533_CR23","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1002\/hep.26767","volume":"59","author":"E Trepo","year":"2014","unstructured":"Trepo E, Nahon P, Bontempi G, et al. Association between the PNPLA3 (rs738409 C\u2009>\u2009G) variant and hepatocellular carcinoma: evidence from a meta-analysis of individual participant data. Hepatology. 2014;59:2170\u20137.","journal-title":"Hepatology"},{"key":"1533_CR24","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1111\/hepr.12840","volume":"47","author":"Y Seko","year":"2017","unstructured":"Seko Y, Sumida Y, Tanaka S, et al. Development of hepatocellular carcinoma in Japanese patients with biopsy-proven non-alcoholic fatty liver disease: association between PNPLA3 genotype and hepatocarcinogenesis\/fibrosis progression. Hepatol Res. 2017;47:1083\u201392.","journal-title":"Hepatol Res"},{"key":"1533_CR25","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1007\/s00535-015-1116-6","volume":"51","author":"M Ueyama","year":"2016","unstructured":"Ueyama M, Nishida N, Korenaga M, et al. The impact of PNPLA3 and JAZF1 on hepatocellular carcinoma in non-viral hepatitis patients with type 2 diabetes mellitus. J Gastroenterol. 2016;51:370\u20139.","journal-title":"J Gastroenterol"},{"key":"1533_CR26","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1111\/liv.12695","volume":"35","author":"WP Brouwer","year":"2015","unstructured":"Brouwer WP, van der Meer AJ, Boonstra A, et al. The impact of PNPLA3 (rs738409 C\u2009>\u2009G) polymorphisms on liver histology and long-term clinical outcome in chronic hepatitis B patients. Liver Int. 2015;35:438\u201347.","journal-title":"Liver Int"},{"key":"1533_CR27","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1111\/jgh.13536","volume":"32","author":"AW Chan","year":"2017","unstructured":"Chan AW, Wong GL, Chan HY, et al. Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B. J Gastroenterol Hepatol. 2017;32:667\u201376.","journal-title":"J Gastroenterol Hepatol"},{"key":"1533_CR28","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1080\/00365521.2017.1334088","volume":"52","author":"X Gao","year":"2017","unstructured":"Gao X, Liu W, Yang L, et al. Association between PNPLA3 gene polymorphisms and risk of hepatitis B virus-related hepatocellular carcinoma in Han population in China: a case-control study. Scand J Gastroenterol. 2017;52:1120\u20137.","journal-title":"Scand J Gastroenterol"},{"key":"1533_CR29","doi-asserted-by":"publisher","first-page":"8913","DOI":"10.1073\/pnas.1323785111","volume":"111","author":"H Mahdessian","year":"2014","unstructured":"Mahdessian H, Taxiarchis A, Popov S, et al. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content. Proc Natl Acad Sci USA. 2014;111:8913\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1533_CR30","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1002\/hep.28142","volume":"62","author":"CJ Pirola","year":"2015","unstructured":"Pirola CJ, Sookoian S. The dual and opposite role of the TM6SF2-rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver: a meta-analysis. Hepatology. 2015;62:1742\u201356.","journal-title":"Hepatology"},{"key":"1533_CR31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.dld.2015.09.009","volume":"48","author":"E Falleti","year":"2016","unstructured":"Falleti E, Cussigh A, Cmet S, et al. PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis. Dig Liver Dis. 2016;48:69\u201375.","journal-title":"Dig Liver Dis"},{"key":"1533_CR32","doi-asserted-by":"publisher","first-page":"4309","DOI":"10.1038\/ncomms5309","volume":"5","author":"YL Liu","year":"2014","unstructured":"Liu YL, Reeves HL, Burt AD, et al. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease. Nat Commun. 2014;5:4309.","journal-title":"Nat Commun"},{"key":"1533_CR33","first-page":"1277","volume":"6","author":"BK Koo","year":"2017","unstructured":"Koo BK, Joo SK, Kim D, et al. Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2017;6:1277\u201385.","journal-title":"J Gastroenterol Hepatol"},{"key":"1533_CR34","first-page":"140","volume":"7","author":"X Wang","year":"2016","unstructured":"Wang X, Liu Z, Wang K, et al. Additive effects of the risk alleles of PNPLA3 and TM6SF2 on non-alcoholic fatty liver disease (NAFLD) in a Chinese Population. Front Genet. 2016;7:140.","journal-title":"Front Genet"},{"key":"1533_CR35","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1053\/j.gastro.2016.01.006","volume":"150","author":"N Goossens","year":"2016","unstructured":"Goossens N, Hoshida Y. Is hepatocellular cancer the same disease in alcoholic and nonalcoholic fatty liver diseases? Gastroenterology. 2016;150:1710\u20137.","journal-title":"Gastroenterology"},{"key":"1533_CR36","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s00535-012-0647-3","volume":"48","author":"Y Takeuchi","year":"2013","unstructured":"Takeuchi Y, Ikeda F, Moritou Y, et al. The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis. J Gastroenterol. 2013;48:405\u201312.","journal-title":"J Gastroenterol"},{"key":"1533_CR37","doi-asserted-by":"publisher","first-page":"e75982","DOI":"10.1371\/journal.pone.0075982","volume":"8","author":"L Valenti","year":"2013","unstructured":"Valenti L, Motta BM, Soardo G, et al. PNPLA3 I148M polymorphism, clinical presentation, and survival in patients with hepatocellular carcinoma. PLoS One. 2013;8:e75982.","journal-title":"PLoS One"},{"key":"1533_CR38","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1016\/j.bbamem.2013.10.003","volume":"1838","author":"K D\u2019Souza","year":"2014","unstructured":"D\u2019Souza K, Epand RM. Enrichment of phosphatidylinositols with specific acyl chains. Biochim Biophys Acta. 2014;1838:1501\u20138.","journal-title":"Biochim Biophys Acta"},{"key":"1533_CR39","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1016\/j.jhep.2016.07.045","volume":"65","author":"PK Luukkonen","year":"2016","unstructured":"Luukkonen PK, Zhou Y, Hyotylainen T, et al. The MBOAT7 variant rs641738 alters hepatic phosphatidylinositols and increases severity of non-alcoholic fatty liver disease in humans. J Hepatol. 2016;65:1263\u20135.","journal-title":"J Hepatol"},{"key":"1533_CR40","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.jhep.2014.06.006","volume":"61","author":"HD Nischalke","year":"2014","unstructured":"Nischalke HD, Lutz P, Kramer B, et al. A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease. J Hepatol. 2014;61:1073\u20139.","journal-title":"J Hepatol"}],"container-title":["Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-018-01533-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00535-018-01533-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-018-01533-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T10:31:09Z","timestamp":1576492269000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00535-018-01533-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,30]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["1533"],"URL":"https:\/\/doi.org\/10.1007\/s00535-018-01533-x","relation":{},"ISSN":["0944-1174","1435-5922"],"issn-type":[{"value":"0944-1174","type":"print"},{"value":"1435-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,30]]},"assertion":[{"value":"4 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}