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Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis

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An Invited Commentary to this article was published on 15 November 2023

Abstract

Background/Aims

Proton pump inhibitors (PPIs) are frequently prescribed to cirrhotic patients, but there is limited longitudinal evidence regarding their effects. This study aimed to assess the impact of PPIs on adverse events in cirrhotic patients.

Methods

A comprehensive search was conducted using the Medline and Embase databases to identify relevant articles. Pooled hazard ratios (HRs) using DerSimonian and Laird random-effects model were calculated to evaluate the risk of adverse events such as long-term mortality, hepatic decompensation, hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), and overall infection in cirrhotic patients with PPI use.

Results

The analysis included 28 studies with 260,854 cirrhotic patients. The prevalence of PPI use among cirrhotic patients was 55.93%. The use of PPIs was not significantly associated with short-term mortality in cirrhotic patients. However, long-term mortality (HR 1.321, 95% CI 1.103–1.581, P = 0.002), decompensation (HR 1.646, 95% CI 1.477–1.835, P < 0.001), HE (HR 1.968, 95% CI 1.372–2.822, P < 0.001), SBP (HR 1.751, 95% CI 1.649–1.859, P < 0.001), and infection (HR 1.370, 95% CI 1.148–1.634, P < 0.001) were significantly associated with PPI use. Sensitivity analysis with prospective studies yielded similar results.

Conclusion

PPIs should be reserved for appropriate indications at lowest effective dose for cirrhotic patients due to the potential harm.

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Data availability

All articles in this manuscript are available from Medline and Embase.

Abbreviations

CI:

Confidence interval

HE:

Hepatic encephalopathy

HR:

Hazard ratio

PPI:

Proton pump inhibitor

PRISMA:

Preferred reporting items for systematic review and meta-analyses

SBP:

Spontaneous bacterial peritonitis

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Acknowledgments

All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted. No writing assistance was obtained in the preparation of the manuscript. The manuscript, including related data, figures and tables has not been previously published and that the manuscript is not under consideration elsewhere.

Funding

No funding was required for this study.

Author information

Author notes

  1. Zhen Yu Wong, Jia Hong Koh, and Mark Muthiah have contributed equally to this work and share first authorship.

  2. Cheng Han Ng and Margaret Teng have contributed equally to this work and share last authorship.

Authors and Affiliations

  1. Nottingham City Hospital, Nottingham University Hospitals NHS Trust, Nottingham, UK

    Zhen Yu Wong & Kai Qi Ou

  2. Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore

    Jia Hong Koh, Mark Muthiah, Benjamin Koh, Elden Yen Hng Ong, Christen En Ya Ong, Wen Hui Lim, Darren Jun Hao Tan, Yujun Wong, Benjamin Nah, Daniel Q. Huang, Cheng Han Ng & Margaret Teng

  3. Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore

    Jia Hong Koh, Mark Muthiah, Douglas Chee, Kewin Tien Ho Siah, Yujun Wong, Benjamin Nah, Daniel Q. Huang & Margaret Teng

  4. Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA

    Daniel Q. Huang

  5. National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore

    Jia Hong Koh, Mark Muthiah, Benjamin Nah & Daniel Q. Huang

  6. Houston Research Institute, Houston, TX, USA

    Mazen Noureddin

  7. Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand

    Apichat Kaewdech

  8. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA

    Karn Wijarnpreecha

  9. Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India

    Anand V. Kulkarni

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  1. Zhen Yu Wong
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Contributions

All authors approve the final version of the manuscript, including the authorship list and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Conceptualization—CHN, MN, MM, MT. Data curation—ZYW, BK, JHK, CHN. Formal analysis—ZYW, BK, JHK, CHN. Supervision—JHK, CHN, MN, MM, MT. Validation—DC, KTHS, YW, DQH, AK, KW, AVK, BN. Writing, original draft—ZYW, BK, JHK, CHN, EYHO, CEYO, KQO, ASPT, JQ, WHL, DJHT. Writing, review, and editing—CHN, JHK, DC, KTHS, YW, DQH, AK, KW, AVK, BN, MN, MM, MT. All authors have read and approved the final version of the manuscript for submission.

Corresponding author

Correspondence to Cheng Han Ng.

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The study was conducted in accordance with the Declaration of Helsinki. The study was exempt from IRB review as no confidential patient information was involved.

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Wong, Z.Y., Koh, J.H., Muthiah, M. et al. Proton Pump Inhibitors Increases Longitudinal Risk of Mortality, Decompensation, and Infection in Cirrhosis: A Meta-Analysis. Dig Dis Sci 69, 289–297 (2024). https://doi.org/10.1007/s10620-023-08150-6

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