Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study
(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/11/10/2865 |
| _version_ | 1797498881213202432 |
|---|---|
| author | Soungmun Kim Seogsong Jeong Sun Jae Park Jooyoung Chang Seulggie Choi Yoosun Cho Joseph C. Ahn Gyeongsil Lee Joung Sik Son Sang Min Park |
| author_facet | Soungmun Kim Seogsong Jeong Sun Jae Park Jooyoung Chang Seulggie Choi Yoosun Cho Joseph C. Ahn Gyeongsil Lee Joung Sik Son Sang Min Park |
| author_sort | Soungmun Kim |
| collection | DOAJ |
| description | (1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91–1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73–1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63–1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings. |
| first_indexed | 2024-03-10T03:39:38Z |
| format | Article |
| id | doaj.art-70e4a2bf05734d94b8e699476d17c393 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T03:39:38Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-70e4a2bf05734d94b8e699476d17c3932023-11-23T11:36:02ZengMDPI AGJournal of Clinical Medicine2077-03832022-05-011110286510.3390/jcm11102865Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort StudySoungmun Kim0Seogsong Jeong1Sun Jae Park2Jooyoung Chang3Seulggie Choi4Yoosun Cho5Joseph C. Ahn6Gyeongsil Lee7Joung Sik Son8Sang Min Park9Graduate School of Data Science, Seoul National University, Seoul 08826, KoreaDepartment of Biomedical Informatics, CHA University School of Medicine, Seongnam 13488, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaTotal Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USADepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang 14068, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91–1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73–1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63–1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.https://www.mdpi.com/2077-0383/11/10/2865epidemiologypharmacoepidemiologyproton pump inhibitorhepatocellular carcinomaliver cirrhosischronic liver diseases |
| spellingShingle | Soungmun Kim Seogsong Jeong Sun Jae Park Jooyoung Chang Seulggie Choi Yoosun Cho Joseph C. Ahn Gyeongsil Lee Joung Sik Son Sang Min Park Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study Journal of Clinical Medicine epidemiology pharmacoepidemiology proton pump inhibitor hepatocellular carcinoma liver cirrhosis chronic liver diseases |
| title | Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study |
| title_full | Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study |
| title_fullStr | Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study |
| title_full_unstemmed | Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study |
| title_short | Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study |
| title_sort | association between proton pump inhibitor use and risk of hepatocellular carcinoma a korean nationally representative cohort study |
| topic | epidemiology pharmacoepidemiology proton pump inhibitor hepatocellular carcinoma liver cirrhosis chronic liver diseases |
| url | https://www.mdpi.com/2077-0383/11/10/2865 |
| work_keys_str_mv | AT soungmunkim associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT seogsongjeong associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT sunjaepark associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT jooyoungchang associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT seulggiechoi associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT yoosuncho associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT josephcahn associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT gyeongsillee associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT joungsikson associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy AT sangminpark associationbetweenprotonpumpinhibitoruseandriskofhepatocellularcarcinomaakoreannationallyrepresentativecohortstudy |