title: Risk Factors for Hepatocellular Carcinoma in Cirrhotic Patients with Chronic Hepatitis B.
abstract: OBJECTIVE
  To investigate the clinical and genetic risk factors associated with hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB).
  
  
  METHODS
  Nine hundred forty-nine Chinese Han patients with CHB were studied, including noncirrhotic patients without HCC (N = 234), cirrhotic patients without (N = 281) and with HCC (N = 434). Patients were genotyped for 10 candidate single nucleotide polymorphisms (SNPs) by the polymerase chain reaction (PCR)-ligase detection reaction (LDR) method.
  
  
  RESULTS
  By multivariate logistic regression analysis adjusted for Child-Pugh scores, noneffective antiviral treatment, drinking history, family history of HCC, and age ≥50 years old were associated with HCC risk (odds ratio [OR] = 5.923, 2.456, 2.241, 1.955, respectively). Sixty-two of 170 cirrhotic patients who achieved sustained virological suppression by antiviral treatment developed HCC, with fatty liver disease, family history of HCC, and family history of hepatitis B virus (HBV) infection as the risk factors (OR = 11.646, 3.339, 2.537, respectively). The SNPs associated with HCC risk in patients with cirrhosis and CHB were rs11536889 in TLR4 and rs2853744 in SPP1. Polymorphisms of TLR4 rs2149356, AP3S2 rs2290351, STXBP5L rs2169302, MLEC rs7976497, and SOCS3 rs4969168 were associated with HCC risk in specific stratified analyses with gender, age, and drinking history in the cirrhotic patients.
  
  
  CONCLUSIONS
  Inadequate antiviral treatment, family history of HCC, drinking history, and age ≥50 years old are risk factors for HCC. Sustained suppression of HBV does not eliminate the risk of HCC. Specific host genetic factors may impact HCC development in Han Chinese cirrhotic patients with CHB, including SNPs in TLR4, SPP1, AP3S2, STXBP5L, MLEC, and SOCS3, which warrant further validation in additional cohorts.
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Peng
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Yi-Rong
authors.initials: YR
authors.lastname: Cao
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Zeng
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Cheng
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Wang
authors.affiliation: 2 Division of Liver Diseases, Icahn School of Medicine at Mount Sinai , New York, New York.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
authors.affiliation: 3 Celera Corporation, Alameda, California.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sninsky
authors.affiliation: 1 Division of Digestive Diseases, Zhong Shan Hospital, Fu Dan University , Shanghai, China .
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Guo
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005260:Female; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors