Association of proton pump inhibitors with risk of hepatic encephalopathy in advanced liver disease: A meta-analysis.

Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Internet ISSN: 2219-2840 (Electronic) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE

Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group
Original Publication: Beijing : WJG Press, c1998-

Hepatic Encephalopathy/*epidemiology ; Liver Cirrhosis/*complications ; Proton Pump Inhibitors/*adverse effects; Disease Progression ; Hepatic Encephalopathy/etiology ; Humans ; Liver Cirrhosis/pathology ; Observational Studies as Topic ; Prognosis ; Randomized Controlled Trials as Topic ; Risk Assessment ; Risk Factors

Background: Several studies have explored the association between the use of proton pump inhibitors (PPIs) and the risk of developing hepatic encephalopathy (HE) in patients with advanced liver disease. However, the evidence-based conclusions are controversial. We hypothesized that using PPIs may increase the risk of HE in patients with advanced liver disease. If confirmed, clinicians must strictly adhere to the indications for PPI treatment in this population.
Aim: To evaluate the pooled risk of HE in patients with advanced liver disease who use PPIs.
Methods: Three electronic databases (PubMed, EMBASE, and the Cochrane Library) were searched from the date of database inception through January 8, 2019 to identify comparative studies evaluating the association between PPI use and the risk of HE. Data from the included studies were extracted. The random-effects model was used for pooling risk estimates and the corresponding 95% confidence intervals (CIs). Subgroup and sensitivity analyses were also performed.
Results: In total, 4342 patients from five case-control studies and 188053 patients from four cohort studies were included in this analysis. In patients with advanced liver disease, PPI use was associated with an elevated risk of developing HE, with significant heterogeneity. The pooled odds ratio for case-control studies was 2.58 (95%CI: 1.68-3.94, I ² = 72%). The pooled RR for cohort studies was 1.67 (95%CI: 1.30-2.14, I ² = 67%). The results of the subgroup analyses suggested that the heterogeneity may be the result of differences in the study designs and the definitions of PPI use. The sensitivity and subgroup analyses did not alter our findings.
Conclusion: In patients with advanced liver disease, PPI use is associated with an elevated risk of HE. Future large prospective studies are needed to confirm this association.
Competing Interests: Conflict-of-interest statement: The authors have no potential conflicts of interest to disclose.

Aliment Pharmacol Ther. 1999 Aug;13 Suppl 3:27-36. (PMID: 10491726)
JAMA. 2000 Apr 19;283(15):2008-12. (PMID: 10789670)
Am J Med. 2001 Oct 15;111(6):469-73. (PMID: 11690573)
Lancet. 2002 Feb 2;359(9304):431-4. (PMID: 11844534)
Gut. 2006 Feb;55(2):152-7. (PMID: 15872000)
Eur J Gastroenterol Hepatol. 2008 Jun;20(6):512-8. (PMID: 18467910)
Med Sci Monit. 2008 Sep;14(9):CR468-72. (PMID: 18758417)
Int J Public Health. 2008;53(3):165-7. (PMID: 19127890)
Gut. 2010 Jul;59(7):874-81. (PMID: 20581234)
J Hepatol. 2010 Nov;53(5):849-55. (PMID: 20675008)
Nat Rev Gastroenterol Hepatol. 2010 Sep;7(9):515-25. (PMID: 20703237)
Eur J Clin Invest. 2012 Jul;42(7):760-7. (PMID: 22288900)
Aliment Pharmacol Ther. 2012 Nov;36(9):866-74. (PMID: 22966967)
Clin Gastroenterol Hepatol. 2013 May;11(5):483-90. (PMID: 23270866)
Aliment Pharmacol Ther. 2013 Nov;38(9):1129-37. (PMID: 24099474)
Curr Opin Endocrinol Diabetes Obes. 2014 Feb;21(1):3-8. (PMID: 24310148)
Gut Microbes. 2014 May-Jun;5(3):397-403. (PMID: 24690956)
Hepat Mon. 2014 Apr 07;14(4):e16258. (PMID: 24748895)
Intern Med. 2014;53(10):1037-42. (PMID: 24827481)
Liver Int. 2015 Feb;35(2):362-9. (PMID: 24836902)
Hepatology. 2014 Aug;60(2):715-35. (PMID: 25042402)
J Hepatol. 2015 Feb;62(2):437-47. (PMID: 25218789)
Am J Physiol Gastrointest Liver Physiol. 2014 Nov 15;307(10):G951-7. (PMID: 25258407)
Aliment Pharmacol Ther. 2015 Mar;41(5):459-66. (PMID: 25523381)
Gut. 2016 May;65(5):740-8. (PMID: 26657899)
Gut. 2016 May;65(5):749-56. (PMID: 26719299)
Clin Gastroenterol Hepatol. 2016 Dec;14(12):1706-1719.e5. (PMID: 27211501)
Hepatology. 2016 Oct;64(4):1265-72. (PMID: 27474889)
Gastroenterology. 2017 Jan;152(1):134-141. (PMID: 27639806)
Aliment Pharmacol Ther. 2016 Dec;44(11-12):1213-1223. (PMID: 27774677)
N Engl J Med. 2016 Oct 27;375(17):1660-1670. (PMID: 27783916)
Aliment Pharmacol Ther. 2017 Jan;45(2):378-379. (PMID: 27933687)
Medicine (Baltimore). 2017 Apr;96(17):e6723. (PMID: 28445288)
Gut. 2018 Oct;67(10):1870-1880. (PMID: 28847867)
Arq Gastroenterol. 2018 Jan-Mar;55(1):28-32. (PMID: 29561973)
Liver Int. 2018 Sep;38(9):1602-1613. (PMID: 29675988)
Br J Clin Pharmacol. 2018 Aug;84(8):1806-1820. (PMID: 29688583)
United European Gastroenterol J. 2018 Oct;6(8):1179-1187. (PMID: 30288280)
Hepatology. 2018 Oct 5;:null. (PMID: 30289992)
United European Gastroenterol J. 2018 Nov;6(9):1380-1390. (PMID: 30386611)
Aliment Pharmacol Ther. 1996 Aug;10(4):557-61. (PMID: 8853759)
BMJ. 1998 Mar 28;316(7136):989-91. (PMID: 9550961)

Keywords: Cirrhosis; Hepatic encephalopathy; Meta-analysis; Proton pump inhibitors; Systematic review

0 (Proton Pump Inhibitors)

Date Created: 20190619 Date Completed: 20191216 Latest Revision: 20200225

20221213

PMC6558434

10.3748/wjg.v25.i21.2683

31210719