title: Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B.
abstract: OBJECTIVE
  We aimed to identify determinants of hepatocellular carcinoma (HCC) in cirrhotic patients who received nucleos(t)ide analogues for chronic hepatitis B (CHB).
  
  
  METHODS
  This retrospective-prospective study screened all patients (n = 1630) who received antiviral therapy for CHB between 1 September 2007 and 31 March 2013 at the E-Da Hospital and enrolled 210 consecutive cirrhotic patients with pretreatment viral DNA >2000 IU/mL. Those who developed HCC within 3 months of treatment were excluded. All participants were observed until occurrence of HCC, death or 1 January 2014. The incidence and determinants of HCC were estimated using competing risk analyses adjusted for mortality.
  
  
  RESULTS
  Thirty-five (16.7%) patients developed HCC during a median follow-up of 25.2 months (IQR, 16.3-37.3 months), with a cumulative incidence of 24.1% (95% CI, 16.3%-32.0%) at 5 years. Multivariate-adjusted analyses identified age >55 years [adjusted hazard ratio (HR), 2.19; 95% CI, 1.03-4.66], male gender (adjusted HR, 3.07; 95% CI, 1.05-9.02), model for end-stage liver disease (MELD) score >12 points (adjusted HR, 2.16; 95% CI, 1.10-4.23) and diabetes mellitus (DM; adjusted HR, 3.49; 95% CI, 1.54-7.91) as independent risk factors after adjusting for multiple covariates, including antidiabetes medication. A scoring formula that used information on age, gender, MELD score, DM and antidiabetes regimen significantly discriminated patients at high or low risk of HCC, with sensitivity and specificity of 82.9% and 62.3%, respectively.
  
  
  CONCLUSIONS
  Age, gender, hepatic dysfunction, DM and medication for DM are baseline factors that stratify the risk of HCC in cirrhotic patients who receive nucleos(t)ide analogues for CHB.
authors.affiliation: Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chi-Yang
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Tai
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Gin-Ho
authors.initials: GH
authors.lastname: Lo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Daw-Shyong
authors.initials: DS
authors.lastname: Perng
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan moleinray@gmail.com.
authors.forename: Lein-Ray
authors.initials: LR
authors.lastname: Mo
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides
keywords: antiviral therapy; diabetes mellitus; hepatitis B virus; liver cirrhosis; risk stratification