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Nonsteroidal Anti-inflammatory Drugs Are Associated With Reduced Risk of Early Hepatocellular Carcinoma Recurrence After Curative Liver Resection: A Nationwide Cohort Study

Yeh, Chun-Chieh MD*,†,‡; Lin, Jaw-Town MD§,¶,‖; Jeng, Long-Bin MD†,‡; Ho, Hsiu J. PhD§; Yang, Horng-Ren MD†,‡; Wu, Ming-Shiang MD**; Kuo, Ken N. MD††; Wu, Chun-Ying MD, PhD, MPH‡‡,§§,¶¶,‖‖

doi: 10.1097/SLA.0000000000000746
Original Articles

Purpose: The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in reducing the risk of various de novo cancers has been reported; however, its role in reducing hepatocellular carcinoma (HCC) recurrence after liver resection still remains unknown.

Methods: We have conducted a nationwide cohort study by recruiting all patients with a newly diagnosed HCC who had received curative liver resection as their initial treatment. The use of NSAIDs and the risk of early HCC recurrence have been examined by multivariate and stratified analyses. To avoid immortal time bias, the use of NSAIDs has been treated as a time-dependent variable in Cox proportional hazard ratio models.

Results: Between January 1997 and December 2010, a total of 15,574 HCC patients who had received liver resection were enrolled in this study. The 1-, 3-, and 5-year overall survival rates were 90.4%, 73.2%, and 59.8%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 80.5%, 59.4%, and 50.2%, respectively. NSAID use (hazard ratio, 0.81; 95% confidence interval, 0.73–0.90) and minor liver resection (hazard ratio, 0.83; 95% confidence interval, 0.78–0.89) were independently associated with a reduced risk of early HCC recurrence after liver resection. In the stratified analyses, NSAID usage was universally associated with reduced risks in most subgroups, particularly for those aged younger than 65 years, male, with underlying diabetes mellitus and receiving major liver resection.

Conclusions: The use of NSAIDs can be associated with a reduced risk of early HCC recurrence within 2 years after curative liver resection, regardless of patients' age, extent of liver resection, viral hepatitis status, underlying diabetes, and liver cirrhosis.

Early use of nonsteroidal anti-inflammatory drugs is associated with a reduced risk of early recurrent hepatocellular carcinoma after liver resection, irrespective of patients' age, extent of liver resection, viral hepatitis status, underlying diabetes, and liver cirrhosis.

*Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan

Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan

School of Medicine, China Medical University, Taichung, Taiwan

§School of Medicine, Fu Jen Catholic University, Taipei, Taiwan

Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan

Center for Health Policy Research and Development, National Health Research Institutes, Miaoli, Taiwan

**Division of Gastroenterology, National Taiwan University Hospital, Taipei, Taiwan

††Center for Evidence-Based Medicine Taipei Medical University, Taipei, Taiwan

‡‡Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan

§§Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

¶¶Department of Public Health, China Medical University, Taichung, Taiwan; and

‖‖Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan.

Reprints: Chun-Ying Wu, MD, MPH, PhD, Division of Gastroenterology, Taichung Veterans General Hospital, 1650, Sec 4, Taiwan Ave, Taichung 407, Taiwan. E-mail: chun@vghtc.gov.tw.

Disclosure: Supported in part by National Health Research Institute (grant no. PH-100-PP-54, PH-101-PP-23) and Taichung Veterans General Hospital (grant no. TCVGH-1003303C), Taiwan. All authors have nothing to disclose, including any potential financial, professional, or personal conflicts that are relevant to the manuscript. There is no study sponsor involved in the study design, collection, analysis, and interpretation of the data.

This study has been based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health, and managed by the National Health Research Institutes. The interpretations and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or the National Health Research Institutes.

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