Dataset Information

Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.

ABSTRACT:

Background

Epidemiological studies investigating the use of proton pump inhibitors (PPI) on the risk of liver cancer and/or mortality among persons with chronic liver disease (CLD) have reported conflicting results. We conducted a systematic review and meta-analysis to determine the impact of PPI use on liver cancer and/or death among patients with CLD.

Methods

The core databases including MEDLINE, EMBASE, and Cochrane library were searched through January 2020. We included studies, evaluating the association between PPIs and liver cancer or mortality among patients with CLD including randomized controlled, nonrandomized controlled, and observational studies. We used inverse-variance random-effects models to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for liver cancer or mortality.

Results

Eleven studies including 173,894 patients were selected. In three studies, individuals with CLD who used PPIs had a 67% greater risk of developing hepatocellular carcinoma (HCC) compared to nonusers (RR, 1.67; 95% CI, 1.12-2.50; I² = 92%). Combining data from the eight studies relating PPI to overall mortality, we observed a 57% increased risk of mortality in PPI users with CLD compared to CLD nonusers (RR: 1.57; 95% CI, 1.24-1.99; I² = 69%).

Conclusion

PPI use was associated with an increased risk of HCC and mortality in patients with CLD suggesting that PPI prescriptions in patients with CLD should be considered carefully.

SUBMITTER: Song HJ

PROVIDER: S-EPMC7244371 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.

Song Hyun Jin HJ Jiang Xinyi X Henry Linda L Nguyen Mindie H MH Park Haesuk H

European journal of clinical pharmacology 20200314 6

<h4>Background</h4>Epidemiological studies investigating the use of proton pump inhibitors (PPI) on the risk of liver cancer and/or mortality among persons with chronic liver disease (CLD) have reported conflicting results. We conducted a systematic review and meta-analysis to determine the impact of PPI use on liver cancer and/or death among patients with CLD.<h4>Methods</h4>The core databases including MEDLINE, EMBASE, and Cochrane library were searched through January 2020. We included studie ...[more]

PMID: 32172363

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Project description:Background: Proton pump inhibitors (PPI) are generally considered to be one of the well-established prescription drug classes and are commonly used to treat most acid-related diseases. However, a growing body of literature showing an association between gastric and colorectal cancer risk and PPI use continues to raise concerns about the safety of PPI use. Therefore, we aimed to investigate the association between proton pump inhibitor use and risk of gastric and colorectal cancer. Methods: We collected relevant articles using PubMed, Embase, Web of Science and Cochrane library from 1 January 1990 to 21 March 2022. The pooled effect sizes were calculated based on the random-effects model. The study was registered with PROSPERO (CRD42022351332). Results: A total of 24 studies (n = 8,066,349) were included in the final analysis in the screening articles. Compared with non-PPI users, PPI users had a significantly higher risk of gastric cancer (RR = 1.82, 95% CI: 1.46–2.29), but not colorectal cancer (RR = 1.22, 95% CI: 0.95–1.55). Subgroup analysis showed that there was a significant positive correlation between the use of PPI and the risk of non-cardiac cancer (RR = 2.75, 95% CI: 2.09–3.62). There was a significant trend between the duration dependent effect of PPI use and the risk of gastric cancer (<1 year RR = 1.56, 95% CI: 1.30–1.86; 1–3 years RR = 1.75, 95% CI: 1.28–2.37; >3 years RR = 2.32, 95% CI: 1.15–4.66), but not colorectal cancer (≤1 year RR = 1.00, 95% CI: 0.78–1.28; >1 year RR = 1.18, 95% CI: 0.91–1.54; ≥5 years RR = 1.06, 95% CI: 0.95–1.17). Conclusion: We found that PPI use increased gastric cancer risk, but not colorectal cancer risk. This result may be biased due to confounding factors. More prospective studies are needed to further validate and support our findings. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351332], identifier [CRD42022351332].

Project description:Proton pump inhibitors (PPIs) were primarily approved for short-term use (2 to 8 weeks). However, PPI use continues to expand. Widely believed to be safe, we reviewed emerging evidence on increased mortality with PPI long-term use. Our 2016 systematic PPI drug class review found that mortality was not reported as an outcome in randomized controlled trials (RCTs) that directly compared different PPIs. We sought more recent and comprehensive data on PPI harm outcomes from research syntheses as a follow-on. A search was conducted from January 2014 to January 2020. We searched MEDLINE, EMBASE, and Cochrane Central for evidence from systematic reviews (SRs) and primary studies reporting all-cause mortality in adults treated with a PPI for any indication (duration >12 weeks) compared to patients without PPI treatment (no use, placebo, or H2RA use). Two independent investigators assessed study eligibility, synthesized evidence, and assessed the quality of the included studies. Data on all-cause mortality were sought, analyzed, critically examined, and interpreted herein. From 1304 articles, one SR was identified that reported on all-cause mortality. The SRs pooled three observational studies with data to 1 year: odds ratio, 95% confidence interval (CI) 1.53-1.84. A RCT, the COMPASS (Cardiovascular Outcomes for People Using Anticoagulant Strategies) RCT with data to 3 years: hazard ratio (HR) 1.03, 95% CI 0.92-1.15. The US Veterans Affairs cohort study using a large national dataset with data to 10 years found a HR of 1.17, 95% CI (1.10-1.24) and (NNH) of 22. The most common causes of death were from cardiovascular and chronic kidney diseases, with an excess death of 15 and 4 per 1000 patients, respectively, over the 10-year period. Harms arising from real-world medication use are best evaluated using a pharmacovigilance "convergence of proof" approach using data from a variety of sources and various study designs. Given that most PPI indications for use recommended a treatment duration of less than 12 weeks, it seems clear that PPIs were significantly overused in older patients. The median exposure time to PPI ranged from 1 to 4.6 years. Signals of serious harms including increased mortality with long-term PPI use are reported in observational studies. The COMPASS trial findings are not inconsistent with contemporaneous findings from observational studies. The COMPASS RCT was unlikely to detect an increase in mortality given the trial was not powered to detect this outcome. The potential increase in mortality in older patients associated with prolonged PPI exposure needs to be conveyed to health professionals. Clinicians and patients may be able to reverse the relentless expansion of long-term PPI exposure by reviewing indications and considering potential harms as well as benefits.

Dataset Information

Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.

Background

Methods

Results

Conclusion

Publications

Proton pump inhibitors and risk of liver cancer and mortality in patients with chronic liver disease: a systematic review and meta-analysis.

Similar Datasets

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