{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:44:51Z","timestamp":1787028291788,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T00:00:00Z","timestamp":1466121600000},"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>Hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC) in China. At present, there still are 9.3 million chronic HBV-infected Chinese. Numerous studies have explored the association between possible factors and hepatocellular carcinoma risk, however, the results remains inconsistent. Therefore, we did this pooled analysis so as to get a precise result. Here, we took the chronic HBV-infected Chinese as the object. We systematically searched for studies evaluating whether the proposed factors changed HCC risk in PubMed, Chinese National Knowledge Infrastructure, VIP database and Wanfang data. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by Review Manager 5.0 and publication bias was determined by Begg\u2019s test and Egger\u2019s test. In total, 3165 cases and 10,896 controls from 27 studies were included in this meta-analysis. Our results showed that pooled OR with 95% CI for each of the factors investigated were: non-antiviral treatment 2.70 (2.01, 3.62), high HBV DNA levels 2.61 (1.73, 3.94), alcohol consumption 2.19 (1.53, 3.13), a family history of HCC 3.58 (2.53, 5.06) and male gender 2.14 (1.68, 2.73), respectively. Our meta-analysis supports that high HBV DNA levels, non-antiviral treatment, alcohol consumption, a family history of HCC and male gender contributed to the risk of hepatocellular carcinoma in chronic HBV-infected Chinese from currently available evidence. Given the high prevalence of the non-antiviral treatment and alcohol drinking, behavior interventions for the two factors should be tackled first.<\/jats:p>","DOI":"10.3390\/ijerph13060604","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T10:09:24Z","timestamp":1466158164000},"page":"604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Analysis of Risk Factors Associated with the Development of Hepatocellular Carcinoma in Chronic HBV-Infected Chinese: A Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiang","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Statistics, Purdue University, West Lafayette, IN 47907, USA"},{"name":"School of Statistics, Renmin University of China, Beijing 100872, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongdi","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofeng","family":"Cai","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-8845","authenticated-orcid":false,"given":"Zhenggang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengting","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.3748\/wjg.14.4300","article-title":"Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis","volume":"14","author":"Gomaa","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global cancer statistics, 2002","volume":"55","author":"Parkin","year":"2005","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cld.2004.12.009","article-title":"Epidemiology of hepatocellular carcinoma","volume":"9","author":"Bosch","year":"2005","journal-title":"Clin. Liver Dis."},{"key":"ref_4","first-page":"587","article-title":"Analysis and prediction of liver cancer incidence in China","volume":"46","author":"Zhang","year":"2012","journal-title":"Zhonghua Yu Fang Yi Xue Za Zhi"},{"key":"ref_5","unstructured":"Stewart, B.W., and Wild, C. (2014). World Cancer Report 2014, World Health Organization."},{"key":"ref_6","first-page":"700","article-title":"Study on microcystins-LR pollution situation of Taihu rim","volume":"3","author":"Zhang","year":"2012","journal-title":"J. Food Saf. Q."},{"key":"ref_7","unstructured":"Shandong Lu Hua Group, Co., Ltd. (2008). Squeezing methods of oil production and technology of getting rid of aflatoxin. Food Saf. Guide, 1, 81\u201383."},{"key":"ref_8","first-page":"82","article-title":"The role of Chinese herbal medicine in the elimination of aflatoxin","volume":"4","author":"Zhang","year":"1995","journal-title":"Food Storage"},{"key":"ref_9","first-page":"405","article-title":"Heavy alcohol consumption can enhance risk of hepatocellular carcinoma associated with hepatitis B virus infection","volume":"12","author":"Huang","year":"2005","journal-title":"J. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.vaccine.2013.08.012","article-title":"Reprint of: Epidemiological serosurvey of Hepatitis B in China\u2014Declining HBV prevalence due to Hepatitis B vaccination","volume":"31","author":"Liang","year":"2013","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1086\/599332","article-title":"Evaluation of the impact of hepatitis B vaccination among children born during 1992\u20132005 in China","volume":"200","author":"Liang","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chang, M.H. (2014). Viruses and Human Cancer, Springer.","DOI":"10.1007\/978-3-642-38965-8"},{"key":"ref_13","first-page":"166","article-title":"A study on the long-term outcome of hepatitis B e antigen-negative chronic hepatitis B compared with that of hepatitis B e antigen-positive chronic hepatitis B","volume":"25","author":"Wu","year":"2007","journal-title":"Chin. J. Infect. Dis."},{"key":"ref_14","first-page":"1832","article-title":"The prospective study of the clinical features and outcome of HBeAg-negative and HBeAg-positive cirrhosis in patients with chronic type B hepatitis","volume":"87","author":"Ma","year":"2007","journal-title":"Chin. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/hep.1840130303","article-title":"Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma","volume":"13","author":"Chen","year":"1991","journal-title":"Hepatology"},{"key":"ref_16","first-page":"46","article-title":"The effect of lamivudine treatment on the prognosis of patients with hepatitis B related decompensative liver diseases","volume":"26","author":"Yang","year":"2008","journal-title":"Chin. J. Infect. Dis."},{"key":"ref_17","first-page":"280","article-title":"The Impact of Alcohol Drinking Habit and HBsAg on the Risk of Hepatocellular Carcinoma in Taixing City","volume":"13","author":"Cao","year":"2004","journal-title":"Bull. Chin. Cancer"},{"key":"ref_18","first-page":"709","article-title":"The Study on the Interactions between HBsAg and Various Risk Factors in Primary Hepatocellular Carcinoma in Taixing Area","volume":"12","author":"Ding","year":"2001","journal-title":"Bull. Chin. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1056\/NEJM200211213472119","article-title":"Hepatitis B e antigen and the risk of hepatocellular carcinoma","volume":"347","author":"Geier","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1093\/jnci\/dji043","article-title":"Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: A prospective study in men","volume":"97","author":"Yu","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1086\/502978","article-title":"Role of hepatitis B viral load and basal core promoter mutation in hepatocellular carcinoma in hepatitis B carriers","volume":"193","author":"Liu","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_22","first-page":"72","article-title":"Clinical characteristics of 1829 cases of HBeAg positive chronic hepatitis B","volume":"3","author":"Li","year":"2009","journal-title":"J. Kunming Med. Univ."},{"key":"ref_23","first-page":"5246","article-title":"Hepatitis B virus and cigarette smoking: Risk factors for hepatocellular carcinoma in Hong Kong","volume":"42","author":"Lam","year":"1982","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.3748\/wjg.14.3059","article-title":"A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong, China","volume":"14","author":"Liu","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_25","first-page":"370","article-title":"Mutiviate Regression Analysis of Risk Factors for HBV-related Primary Liver Cancer","volume":"30","author":"Gao","year":"2014","journal-title":"J. Clin. Hepatol."},{"key":"ref_26","first-page":"1157","article-title":"A case-control study on risk factors of primary hepatocellular cancer in Guizhou","volume":"43","author":"Zhao","year":"2014","journal-title":"Chongqing Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jhep.2006.08.021","article-title":"Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma","volume":"46","author":"Lin","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_28","first-page":"1874","article-title":"Relationship between serum hepatitis B virus DNA load and hepatocellular carcinoma in Qidong, China: A cohort follow-up study of 14 years","volume":"92","author":"Sun","year":"2012","journal-title":"Natl. Med. J. China"},{"key":"ref_29","first-page":"20","article-title":"Relationship analysis between hepoatocelluar carcinoma incidence and hepatitis B e antigen expression in chronic hepatitis B patients with long-term treatment of nucleoside analogues therapy","volume":"36","author":"Chen","year":"2013","journal-title":"Chin. J. Postgrad. Med."},{"key":"ref_30","first-page":"591","article-title":"The Effects of Long-term Antiviral Therapy on the Prognosis of patients with Hepatitis B-induced Cirrhosis","volume":"18","author":"Lu","year":"2013","journal-title":"Chin. Hepatol."},{"key":"ref_31","first-page":"84","article-title":"Priming effects of alcohol on the risk factors of hepatocellular carcinoma in chronic hepatitis B","volume":"16","author":"Liu","year":"2011","journal-title":"Chin. Hepatol."},{"key":"ref_32","first-page":"930","article-title":"A prospective study of the relationship between serum hepatitis B virus DNA and the risk of primary liver cancer","volume":"17","author":"Chen","year":"2009","journal-title":"Chin. J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1743-422X-9-16","article-title":"High hepatitis B virus load is associated with hepatocellular carcinomas development in Chinese chronic hepatitis B patients: A case control study","volume":"9","author":"Zhou","year":"2012","journal-title":"Virol. J."},{"key":"ref_34","first-page":"458","article-title":"Patients with chronic hepatitis B liver factors occurring nucleoside analogues 10 antiretroviral therapy","volume":"16","author":"Zhang","year":"2013","journal-title":"J. Clin. Hepatol."},{"key":"ref_35","first-page":"608","article-title":"A serological investigation on relationship between the infection rate of HBV and the PHC","volume":"9","author":"Mao","year":"2002","journal-title":"Pract. Prev. Med."},{"key":"ref_36","first-page":"399","article-title":"Evaluation of Risk Factors of Primary Hepatic Carcinoma Due to Hepatitis B Cirrhosis","volume":"28","author":"Shi","year":"2013","journal-title":"Pract. J. Cancer"},{"key":"ref_37","first-page":"54","article-title":"Analysis of risk factors for hepatitis B liver cirrhosis complicated with primary cancer","volume":"51","author":"Yang","year":"2013","journal-title":"China Mod. Dr."},{"key":"ref_38","first-page":"1218","article-title":"Risk factors for hepatocellular carcinomas in patients with liver cirrhosis","volume":"47","author":"Chen","year":"2012","journal-title":"Acta Univ. Anhui"},{"key":"ref_39","first-page":"279","article-title":"Long-term follow-up of Japanese patients with chronic hepatitis B treated with interferon-\u03b1","volume":"16","author":"Truong","year":"2005","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","first-page":"452","article-title":"Long-term effect of interferon therapy on incidence of cirrhosis and hepatocellular carcinoma in Thai patients with chronic hepatitis B","volume":"32","author":"Tangkijvanich","year":"2001","journal-title":"Southeast Asian J. Trop Med. Public Health"},{"key":"ref_41","unstructured":"Key Documents. Available online: http:\/\/www.prisma-statement.org\/."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.ejca.2012.02.009","article-title":"Population attributable risk of aflatoxin-related liver cancer: Systematic review and meta-analysis","volume":"48","author":"Liu","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"ref_43","unstructured":"Chinese Anti-Cancer Associationand the Professional Committee of Liver Cancer Clinical Oncology Collaboration Committee, and China HCC Medical Association Hepatology Study Group (2009). Diagnosis and treatment of primary liver cancer experts from standardization knowledge. J. Clin. Oncol., 14, 259\u2013269."},{"key":"ref_44","unstructured":"Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association (2011). The guideline of prevention and treatment for chronic hepatitis B (2010 version). Zhonghua Liu Xing Bing Xue Za Zhi, 32, 405\u2013415."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"Dersimonian","year":"1986","journal-title":"Controll. Clin. Trials"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/S0895-4356(01)00377-8","article-title":"Funnel plots for detecting bias in meta-analysis: Guidelines on choice of axis","volume":"54","author":"Sterne","year":"2001","journal-title":"J. Clin. Epidemiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S1383-5742(00)00027-2","article-title":"Primary prevention of hepatocellular carcinoma in developing countries","volume":"462","author":"Wild","year":"2000","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_49","unstructured":"Monto, A., and Wright, T.L. (2001). Seminars in Oncology, Elsevier."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.mrrev.2008.01.005","article-title":"Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: Possibilities for prevention","volume":"659","author":"Anwar","year":"2008","journal-title":"Mutat. Res.\/Rev. Mutat. Res."},{"key":"ref_51","first-page":"101","article-title":"Comparative Analysis of Aetiology Clustering of Hepatocellular Carcinoma between Two Families with High Mortality of Hepatoceilular Carcinoma Discovered Recently in Guangxi Region","volume":"38","author":"Zang","year":"2011","journal-title":"Tumor"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1196\/annals.1441.025","article-title":"Drug addiction in China","volume":"1141","author":"Lu","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_53","unstructured":"Jiang, Y., and Qin, C.Y. The Association of Cigarette Smoking with PDCD4 in Hepatocellular Carcinoma. Available online: http:\/\/kns.chkd.cnki.net\/kcms\/detail\/detail.aspx?recid=&FileName=2009248620.nh&DbName=CDMH9911&DbCode=CDMH&uid=WEEvREcwSlJHSldTTEYzUk1zUTdMT2dib1lwNzdyVy9yOFZvVUIxeXRnQko5Zm5XM1UxRUNobk1lZzFOc0ltRXpBPT0=$9A4hF_YAuvQ5obgVAqNKPCYcEjKensW4IQMovwHtwkF4VYPoHbKxJw!!."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.3748\/wjg.14.1652","article-title":"Natural history of hepatitis-related hepatocellular carcinoma","volume":"14","author":"But","year":"2008","journal-title":"World J. Gastroenterol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/13\/6\/604\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:25:40Z","timestamp":1760210740000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/13\/6\/604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,17]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["ijerph13060604"],"URL":"https:\/\/doi.org\/10.3390\/ijerph13060604","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,17]]}}}