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Association between proton pump inhibitor use and mortality in patients with hepatocellular carcinoma receiving tyrosine kinase inhibitor
  1. Chun-Ying Wu1,2,
  2. Hsiu J Ho1,
  3. Chen-Yi Wu3,
  4. Yi-Ju Chen4,
  5. Teng-Tu Lee5,
  6. Yao-Chun Hsu6,
  7. Jaw-Town Lin7
  1. 1Institute of Biomedical Informatics, School of Medicine, National Yang-Ming University, Taipei, Taiwan
  2. 2Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
  3. 3Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
  4. 4Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
  5. 5Division of Gastroenterology & Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan
  6. 6Division of Gastroenterology, E-Da Hospital, Yanchao, Kaohsiung, Taiwan
  7. 7Digestive Medicine Center, China Medical University, Taichung, Taiwan
  1. Correspondence to Professor Chun-Ying Wu, Institute of Biomedical Informatics, School of Medicine, National Yang-Ming University, Taipei, Taiwan; dr.wu.taiwan{at}

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We read with great interest the recent work by Xu et al,1 and Wang et al,2 on the role of sorafenib in the treatment of hepatocellular carcinoma (HCC). Tyrosine kinase inhibitors (TKIs) are standard therapy for advanced stage HCC.3 However, the effectiveness of TKIs is less than ideal and studies are trying to discover methods to improve their effectiveness.1 2 Most orally administrated TKIs are weak bases and their absorption may be impaired by proton pump inhibitors (PPIs) due to suppression of intragastric acidity.4 5 Concomitant PPI use is found associated with increased overall mortality in patients with lung cancer,6 7 but not known in patients with HCC.

We conducted a nationwide cohort study based on Taiwan’s National Health Insurance Research Database (NHIRD).8 9 In the NHIRD, we identified all hospitalised patients with HCC admitted with a primary diagnosis of HCC (International Classification of Diseases (ICD)-9 code: 155.0 and ICD-10 code: C22) and validated by inclusion in the Registry for Catastrophic …

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  • Contributors Chun-YW and HJH had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design; drafting of the manuscript; study supervision: Chun-YW. Acquisition, analysis or interpretation of data: Chun-YW, HJH and Chen-YW. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: HJH and Chun-YW. Obtained funding: Chun-YW, HJH, Chen-YW and Y-JC. Administrative, technical or material support: Chun-YW, T-YL and Y-CH.

  • Funding This work was supported in part by National Yang-Ming University (E107F-M01-0503), the Handa Pharmaceuticals (YM108C058) and Ministry of Science and Technology (MOST 109-2327-B-010-003-), Taiwan.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

  • Patient consent for publication Not required.

  • Ethics approval Taipei Veterans General Hospital IRB approved (2020-03-007AC).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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