{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:45:36Z","timestamp":1791229536053,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is a common and fatal cancer. People with HCC report higher odds of comorbidity compared with people without HCC. To explore the association between HCC and medical comorbidity, we used routinely collected clinical data and applied a network perspective. In the network perspective, we used correlation analysis and community detection tests that described direct relationships among comorbidities. We collected 14,891 patients with HCC living in Jilin Province, China, between 2016 and 2018. Cirrhosis was the most common comorbidity of HCC. Hypertension and renal cysts were more common in male patients, while chronic viral hepatitis C, hypersplenism, hypoproteinemia, anemia and coronary heart disease were more common in female patients. The proportion of chronic diseases in comorbidities increased with age. The main comorbidity patterns of HCC were: HCC, cirrhosis, chronic viral hepatitis B, portal hypertension, ascites and other common complications of cirrhosis; HCC, hypertension, diabetes mellitus, coronary heart disease and cerebral infarction; and HCC, hypoproteinemia, electrolyte disorders, gastrointestinal hemorrhage and hemorrhagic anemia. Our findings provide comprehensive information on comorbidity patterns of HCC, which may be used for the prevention and management of liver cancer.<\/jats:p>","DOI":"10.3390\/ijerph17093108","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:23:45Z","timestamp":1588166625000},"page":"3108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Patterns of Comorbidity in Hepatocellular Carcinoma: A Network Perspective"],"prefix":"10.3390","volume":"17","author":[{"given":"Xiao-Min","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Medical Informatics, School of Public Health, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, School of Public Health, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, School of Public Health, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics, School of Public Health, Jilin University, Changchun 130021, China"},{"name":"Cancer Systems Biology Center, Jilin University, Changchun 130033, China"},{"name":"College of Computer Science and Technology, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/cncr.28509","article-title":"Annual Report to the Nation on the status of cancer, 1975\u20132010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer","volume":"120","author":"Edwards","year":"2014","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1111\/ajco.12130","article-title":"Identifying important comorbidity among cancer populations using administrative data: Prevalence and impact on survival","volume":"12","author":"Sarfati","year":"2016","journal-title":"Asia Pac. J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7251","DOI":"10.7314\/APJCP.2013.14.12.7251","article-title":"Attributable causes of liver cancer mortality and incidence in China","volume":"14","author":"Fan","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1001\/jamaoncol.2017.3055","article-title":"The Burden of Primary Liver Cancer and Underlying Etiologies from 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015","volume":"3","author":"Akinyemiju","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1183\/09031936.00059814","article-title":"Number 2 in the series \u201cMultimorbidity and the lung\u201d: Ageing and the epidemiology of multimorbidity","volume":"44","author":"Divo","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0140-6736(12)60240-2","article-title":"Epidemiology of multimorbidity and implications for health care, research, and medical education: A cross-sectional study","volume":"380","author":"Barnett","year":"2012","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3322\/caac.21342","article-title":"The impact of comorbidity on cancer and its treatment","volume":"66","author":"Sarfati","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2147\/CLEP.S47150","article-title":"The impact of comorbidity on cancer survival: A review","volume":"5","author":"Sogaard","year":"2013","journal-title":"Clin. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s41687-018-0057-2","article-title":"The relationship between comorbidity medication adherence and health related quality of life among patients with cancer","volume":"2","author":"Drzayich","year":"2018","journal-title":"J. Patient Rep. Outcomes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.canlet.2008.10.040","article-title":"Liver cancer: Descriptive epidemiology and risk factors other than HBV and HCV infection","volume":"286","author":"Chuang","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_11","first-page":"3685","article-title":"Increased cancer rates in patients with chronic hepatitis C","volume":"40","author":"Nyberg","year":"2020","journal-title":"Liver Int. Off. J. Int. Assoc. Study Liver"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ninio, L., Nissani, A., Meirson, T., Domovitz, T., Genna, A., Twafra, S., Srikanth, K.D., Dabour, R., Avraham, E., and Davidovich, A. (2019). Hepatitis C virus enhances the invasiveness of hepatocellular carcinoma via EGFR-mediated invadopodia formation and activation. Cells, 8.","DOI":"10.3390\/cells8111395"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1634\/theoncologist.2012-0065","article-title":"Diabetes mellitus is associated with increased mortality in patients receiving curative therapy for hepatocellular carcinoma","volume":"17","author":"Shau","year":"2012","journal-title":"Oncologist"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1002\/hep.29660","article-title":"Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies","volume":"67","author":"Simon","year":"2018","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.aohep.2019.07.004","article-title":"Obesity and liver cancer","volume":"18","author":"Saitta","year":"2019","journal-title":"Ann. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Thun, M.J., Linet, M.S., Cerhan, J.R., Haiman, C.A., and Schottenfeld, D. (2018). Liver cancer. Cancer Epidemiology and Prevention, Oxford University Press. [4th ed.].","DOI":"10.1093\/oso\/9780190238667.001.0001"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1177\/1745691616639283","article-title":"A complex network perspective on clinical science","volume":"11","author":"Hofmann","year":"2016","journal-title":"Perspect. Psychol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/wps.20375","article-title":"A network theory of mental disorders","volume":"16","author":"Borsboom","year":"2017","journal-title":"World Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: A network-based approach to human disease","volume":"12","author":"Gulbahce","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00127-016-1319-z","article-title":"Mental disorders as networks of problems: A review of recent insights","volume":"52","author":"Fried","year":"2017","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol."},{"key":"ref_21","unstructured":"World Health Organization (1992). ICD-10: International Statistical Classification of Diseases and Related Health Problems 10th Revision, World Health Organization."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Guo, M., Yu, Y., Wen, T., Zhang, X., Liu, B., Zhang, J., Zhang, R., Zhang, Y., and Zhou, X. (2019). Analysis of disease comorbidity patterns in a large-scale China population. BMC Med. Genom., 12.","DOI":"10.1186\/s12920-019-0629-x"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.archger.2016.09.001","article-title":"Multimorbidity in the community-dwelling elderly in urban China","volume":"68","author":"Gu","year":"2017","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1532-5415.2008.02109.x","article-title":"Patterns of chronic multimorbidity in the elderly population","volume":"57","author":"Marengoni","year":"2009","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bastian, M., Heymann, S., and Jacomy, M. (2009, January 17\u201320). Gephi: An open source software for exploring and manipulating networks. Proceedings of the International AAAI Conference on Weblogs and Social Media, San Jose, CA, USA.","DOI":"10.1609\/icwsm.v3i1.13937"},{"key":"ref_26","first-page":"P1000","article-title":"Fast unfolding of communities in large networks","volume":"10","author":"Blondel","year":"2008","journal-title":"J. Stat. Mech. Theory Exp."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/MEG.0b013e3282f4489f","article-title":"Liver cirrhosis, other liver diseases, pancreatitis and subsequent cancer: Record linkage study","volume":"20","author":"Goldacre","year":"2008","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/bjc.2012.193","article-title":"Risk of liver cancer among US male veterans with cirrhosis, 1969\u20131996","volume":"107","author":"Persson","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/apt.15082","article-title":"HECAM-FibroFrance Group. LCR1 and LCR2, two multi-analyte blood tests to assess liver cancer risk in patients without or with cirrhosis","volume":"49","author":"Poynard","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ando.2013.02.008","article-title":"Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: Which clinical arguments?","volume":"74","author":"Rosmorduc","year":"2013","journal-title":"Ann. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"678","DOI":"10.4254\/wjh.v11.i9.678","article-title":"Cirrhotic patients and older people","volume":"11","author":"Carrier","year":"2019","journal-title":"World J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.3748\/wjg.v20.i23.7223","article-title":"Comorbidity in cirrhosis","volume":"20","author":"Jepsen","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","article-title":"Current concepts: Hepatocellular carcinoma","volume":"365","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/bjs.4776","article-title":"Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism","volume":"92","author":"Chen","year":"2005","journal-title":"Br. J. Surg."},{"key":"ref_35","unstructured":"Ministry of Health of the People\u2019s Republic of China (2011). Practice guidelines for diagnosis and treatment of primary hepatic carcinoma (v.2011). J. Clin. Hepatol., 11, 22\u201340."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.humpath.2009.06.021","article-title":"End-stage nonalcoholic fatty liver disease: Evaluation of pathomorphologic features and relationship to cryptogenic cirrhosis from study of explant livers in a living donor liver transplant program","volume":"41","author":"Nayak","year":"2010","journal-title":"Hum. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5651","DOI":"10.1002\/cncr.24687","article-title":"Metabolic syndrome and hepatocellular carcinoma: Two growing epidemics with a potential link","volume":"115","author":"Siegel","year":"2009","journal-title":"Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.canep.2011.03.007","article-title":"Metabolic syndrome and incidence of liver and breast cancers in Japan","volume":"36","author":"Osaki","year":"2012","journal-title":"Cancer Epidemiol."},{"key":"ref_39","first-page":"718","article-title":"Genes and molecular mechanisms affecting the correlation between liver cancer and diabetes mellitus","volume":"26","author":"Yang","year":"2018","journal-title":"Zhonghua gan zang bing za zhi Chin. J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.31557\/APJCP.2018.19.11.3301","article-title":"Clinical outcome and predictive factors of variceal bleeding in patients with hepatocellular carcinoma in Thailand","volume":"19","author":"Kerdsuknirun","year":"2018","journal-title":"Asian Pac. J. Cancer Prev."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/9\/3108\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:09:26Z","timestamp":1760364566000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/9\/3108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,29]]},"references-count":40,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijerph17093108"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17093108","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,29]]}}}