Letter to the editor: Association between proton pump inhibitor use and biliary tract cancer risk: A Swedish population‐based cohort study
Authors: Hamood Ur Rehman Chaudhry, Ahmad Hayat, Anees Ahmad
Journal: Hepatology (2022)

To the editor, With great enthusiasm, we read the article "Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population‐Based Cohort Study" by Kamal et al.[1] It was propitious to read this manuscript, and the authors' endeavors are to be admired. We agree with the utmost conclusion that long‐term utilization of proton pump inhibitors (PPIs) is significantly associated with biliary tree cancers. However, we deem it compulsory to state additional points that would augment the excellence of this article and add to former knowledge. Firstly, historic cohort study design is of significant concern to the study's validity because of the risk of reporting bias and imprecise substantiation. For clarification, a 2006 study conducted by Cahan et al.[2] had a 1‐month prospective follow‐up that augmented their results. The authors were also able to elucidate interim PPI effects on the biliary tree along with long‐term usage.[2] With great regard, the authors should also have explained the definite stature of gallbladder dysfunction due to this therapy. Likewise, gallbladder ejection fraction was one of the parameters in outlining the importance of preevaluation of gallbladder function before starting this medication.[2] By explaining the established diagnostic techniques, an accurate estimation of biliary tree functional status could be given. For this purpose,[2] hepatobiliary iminodiacetic acid scan, an effective diagnostic tool, is preferred in most cases. The authors have clearly explained the risks of infection due to long‐term usage of PPI; however, they could not report a specific class of organisms involved in it. For instance, a 2014 study explained various tiny entities involved in oral flora, gastrointestinal tract, and environmental factors such as Staphylococcus aureus.[3] In addition, as they are entrenched, PPIs are involved in various changes in the body, such as PH and hormonal changes.[4] The authors should have described those changes associated with other significant gastrointestinal cancers. For representation,[4] different abdominal tumors, such as pancreatic cancers, biliary ductal cancer, ampulla cancer, and metastatic cancers, along with their specific locations, were explained, which will help find an association between PPI use and other accompanying cancers. As accepted, biliary tract obstruction is associated with worsening of the liver's physiology; authors should have delineated laboratory parameters involved in deciphering the functional status of the liver. Aspartate aminotransferase and alanine aminotransferase were significantly elevated in PPI and control groups.[4] Several drugs, when taken together, can cause serious drug interactions; hence, we believe that various other drugs that participants were taking should have been annotated. For example, aspirin, statin, and metformin usage was reported along with PPI in a study by Xiong et al.[5] These authors were also able to particularize different types of PPI, such as lansoprazole and rabeprazole, which were also documented.[5] Finally, new studies should be carried out to find specific risks and associations between PPI and biliary tract dysfunction, setting specific criteria and indications for PPI use in the future. CONFLICTS OF INTEREST Nothing to report.