Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection

Chun Ying Wu, Yi Ju Chen, Hsiu J. Ho, Yao Chun Hsu, Ken N. Kuo, Ming Shiang Wu, Jaw Town Lin

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730 Citations (Scopus)

Abstract

Context: 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. Design, Setting, and Participants: 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. Main Outcome Measures: 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). Conclusion: Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.

Original languageEnglish
Pages (from-to)1906-1913
Number of pages8
JournalJAMA
Volume308
Issue number18
DOIs
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • General Medicine

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