title: Association between nucleoside analogues and risk of hepatitis B virus–related hepatocellular carcinoma recurrence following liver resection.
abstract: BACKGROUND
  Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection.
  
  
  OBJECTIVE
  To investigate the association between nucleoside analogue use and risk of tumor recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery.
  
  
  METHODS
  A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010.
  
  
  METHODS
  The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality.
  
  
  RESULTS
  The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765 [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%]; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89).
  
  
  CONCLUSIONS
  Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan. chun@vghtc.gov.tw
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Wu
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Hsiu J
authors.initials: HJ
authors.lastname: Ho
authors.forename: Yao-Chun
authors.initials: YC
authors.lastname: Hsu
authors.forename: Ken N
authors.initials: KN
authors.lastname: Kuo
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology*; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009705:Nucleosides / Q000627:therapeutic use; D015995:Prevalence; D012306:Risk; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides