Safety of Proton Pump Inhibitors in Patients with Cirrhosis: A Systematic Literature Review
Keamanan Proton Pump Inhibitor pada Pasien Sirosis: Kajian Literatur Sistematik
Keywords:
Keamanan, Proton Pump Inhibitor, Sirosis
Abstract
Abstract. Drug safety is a very important concept in therapy, especially regarding the risk of Adverse Drug Reactions (ADRs). Proton Pump Inhibitors (PPIs) are one of the most widely prescribed drugs in the world with diverse indications such as gastritis, GERD, and peptic ulcers. However, the side effects of PPIs in cirrhosis are still a concern. This study aims to review the safety of PPI use in cirrhotic patients through a systematic literature review method. The results showed that the safety of PPI use in cirrhotic patients is associated with an increased risk of PPI side effects, worsening of the disease, and causing new diseases. However, further research is needed to evaluate mechanisms and strategies to prevent the risk of PPI side effects in cirrhotic patients.
Abstrak. Kemanan obat merupakan konsep yang sangat penting dalam terapi, terutama terkait resiko Adverse Drug Reactions (ADRs). Proton Pump Inhibitor (PPI) merupakan salah satu obat yang paling banyak diresepkan di dunia dengan indikasi yang beragam seperti gastritis, GERD, dan tukak lambung. Namun, efek samping PPI pada sirosis masih menjadi perhatian. Penelitian ini bertujuan untuk meninjau keamanan penggunaan PPI pada pasien sirosis melalui metode kajian literatur sistematik. Hasil penelitian menunjukkan keamanan penggunaan PPI pada pasien sirosis berhubungan dengan peningkatan resiko efek samping PPI, perburukan penyakit, hingga menimbulkan penyakit baru. Namun, diperlukan penelitian lebih lanjut untuk mengevaluasi mekanisme dan strategi pencegahan resiko efek samping PPI pada pasien sirosis.
References
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[2] A. Rumi, R. Aulia, and R. Tandah, “Identifikasi Kejadian Adrverse Drug Reactions pada Penggunaan Amlodipin di Instalasi Rawat Jalan RSUD Undata Identifiaction of Adverse Drug Reactions on The Use of Amlodiphine in Outpatient Installations at Undata Hospital,” Majalah Farmaseutik, vol. 19, no. 3, p. 2023, doi: 10.22146/farmaseutik.v19i3.77852.
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[4] C. Tosetti and I. Nanni, “Use of proton pump inhibitors in general practice,” World J Gastrointest Pharmacol Ther, vol. 8, no. 3, p. 180, 2017, doi: 10.4292/wjgpt.v8.i3.180.
[5] D. S. Strand, D. Kim, and D. A. Peura, “25 years of proton pump inhibitors: A comprehensive review,” Jan. 01, 2017, Joe Bok Chung. doi: 10.5009/gnl15502.
[6] J. S. Bajaj et al., “Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis,” Am J Gastroenterol, vol. 113, no. 8, pp. 1177–1186, Aug. 2018, doi: 10.1038/S41395-018-0085-9.
[7] I. B. Lázaro-Pacheco, A. I. Servín-Caamaño, J. L. Pérez-Hernández, G. Rojas-Loureiro, L. Servín-Abad, and F. Higuera-De La Tijera, “Inibidores de bomba protônica aumentam o risco geral de desenvolver infecções bacterianas em pacientes com cirrose,” Arq Gastroenterol, vol. 55, no. 1, pp. 28–32, Jan. 2018, doi: 10.1590/s0004-2803.201800000-09.
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[9] G. Dam, H. Vilstrup, H. Watson, and P. Jepsen, “Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites,” Hepatology, vol. 64, no. 4, pp. 1265–1272, Oct. 2016, doi: 10.1002/hep.28737.
[10] M. Ratelle, B. Pharm, S. Perreault, J.-P. Villeneuve, and L. Tremblay, “association between proton pump inhibitor use and spontaneous bacterial peritonitis in cirrhotic patients with ascites,” 2014.
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[12] Y. C. Kuan, K. W. Huang, C. L. Lin, J. C. Luo, and C. H. Kao, “Short-term proton pump inhibitor use and hepatic encephalopathy risk in patients with decompensated cirrhosis,” J Clin Med, vol. 8, no. 8, Aug. 2019, doi: 10.3390/jcm8081108.
[13] C. F. Tsai et al., “Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study,” Gastroenterology, vol. 152, no. 1, pp. 134–141, Jan. 2017, doi: 10.1053/j.gastro.2016.09.007.
[14] M. A. De Roza et al., “Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis,” World J Gastroenterol, vol. 25, no. 33, pp. 4933–4944, Sep. 2019, doi: 10.3748/wjg.v25.i33.4933.
[15] A. Minalyan, L. Gabrielyan, D. Scott, J. Jacobs, and J. R. Pisegna, “The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors,” Curr Gastroenterol Rep, vol. 19, no. 8, Aug. 2017, doi: 10.1007/S11894-017-0577-6.
[16] J. S. Bajaj et al., “Systems biology analysis of omeprazole therapy in cirrhosis demonstrates significant shifts in gut microbiota composition and function,” Am J Physiol Gastrointest Liver Physiol, vol. 307, no. 10, pp. G951–G957, Nov. 2014, doi: 10.1152/AJPGI.00268.2014.
[17] M. A. Jackson et al., “Proton pump inhibitors alter the composition of the gut microbiota,” Gut, vol. 65, no. 5, pp. 749–756, May 2016, doi: 10.1136/GUTJNL-2015-310861.
[18] A. Tsuda et al., “Influence of Proton-Pump Inhibitors on the Luminal Microbiota in the Gastrointestinal Tract,” Clin Transl Gastroenterol, vol. 6, no. 6, Jun. 2015, doi: 10.1038/CTG.2015.20.
[19] G. C. Du Moulin, J. Hedley-Whyte, D. G. Paterson, and A. Lisbon, “Aspiration of gastric bacteria in antacid-treated patients: a frequent cause of postoperative colonisation of the airway,” Lancet, vol. 1, no. 8266, pp. 242–245, Jan. 1982, doi: 10.1016/S0140-6736(82)90974-6.
[20] S. E. Gulmez, A. Holm, H. Frederiksen, T. G. Jensen, C. Pedersen, and J. Hallas, “Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study,” Arch Intern Med, vol. 167, no. 9, pp. 950–955, May 2007, doi: 10.1001/ARCHINTE.167.9.950.
[21] R. Rosen, L. Hu, J. Amirault, U. Khatwa, D. V. Ward, and A. Onderdonk, “16S community profiling identifies proton pump inhibitor related differences in gastric, lung, and oropharyngeal microflora,” J Pediatr, vol. 166, no. 4, pp. 917–923, 2015, doi: 10.1016/J.JPEDS.2014.12.067.
[22] G. Garcia-Tsao and R. Wiest, “Gut microflora in the pathogenesis of the complications of cirrhosis,” Best Pract Res Clin Gastroenterol, vol. 18, no. 2, pp. 353–372, Apr. 2004, doi: 10.1016/j.bpg.2003.10.005.
[23] T. Kanno et al., “Gastric acid reduction leads to an alteration in lower intestinal microflora,” Biochem Biophys Res Commun, vol. 381, no. 4, pp. 666–670, Apr. 2009, doi: 10.1016/J.BBRC.2009.02.109.
[24] A. R. Bonnel, C. Bunchorntavakul, and K. R. Reddy, “Immune dysfunction and infections in patients with cirrhosis,” Clin Gastroenterol Hepatol, vol. 9, no. 9, pp. 727–738, Sep. 2011, doi: 10.1016/J.CGH.2011.02.031.
[25] L. Christou, G. Pappas, and M. E. Falagas, “Bacterial infection-related morbidity and mortality in cirrhosis,” Am J Gastroenterol, vol. 102, no. 7, pp. 1510–1517, Jul. 2007, doi: 10.1111/J.1572-0241.2007.01286.X.
[26] A. F. Goddard and R. C. Spiller, “The effect of omeprazole on gastric juice viscosity, pH and bacterial counts,” Aliment Pharmacol Ther, vol. 10, no. 1, pp. 105–109, 1996, doi: 10.1111/J.1365-2036.1996.TB00183.X.
[27] M. Sanaka, T. Yamamoto, and Y. Kuyama, “Effects of proton pump inhibitors on gastric emptying: a systematic review,” Dig Dis Sci, vol. 55, no. 9, pp. 2431–2440, Sep. 2010, doi: 10.1007/S10620-009-1076-X.
[28] H. P. Parkman et al., “Effect of gastric acid suppressants on human gastric motility,” Gut, vol. 42, no. 2, pp. 243–250, 1998, doi: 10.1136/GUT.42.2.243.
[29] R. R. Kedika, R. F. Souza, and S. J. Spechler, “Potential anti-inflammatory effects of proton pump inhibitors: a review and discussion of the clinical implications,” Dig Dis Sci, vol. 54, no. 11, pp. 2312–2317, Nov. 2009, doi: 10.1007/S10620-009-0951-9.
[30] M. T. Noor and P. Manoria, “Immune Dysfunction in Cirrhosis,” J Clin Transl Hepatol, vol. 5, no. 1, pp. 50–58, 2017, doi: 10.14218/JCTH.2016.00056.
[31] J. Zhu et al., “Association of proton pump inhibitors with the risk of hepatic encephalopathy during hospitalization for liver cirrhosis,” United European Gastroenterol J, vol. 6, no. 8, pp. 1179–1187, Oct. 2018, doi: 10.1177/2050640618773564.
[32] Y. C. Kuan, K. W. Huang, C. L. Lin, J. C. Luo, and C. H. Kao, “Short-term proton pump inhibitor use and hepatic encephalopathy risk in patients with decompensated cirrhosis,” J Clin Med, vol. 8, no. 8, Aug. 2019, doi: 10.3390/jcm8081108.
[33] A. Gupta et al., “Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy,” J Hepatol, vol. 53, no. 5, pp. 849–855, Nov. 2010, doi: 10.1016/J.JHEP.2010.05.017.
[34] C. Pande, A. Kumar, and S. K. Sarin, “Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease,” Aliment Pharmacol Ther, vol. 29, no. 12, pp. 1273–1281, Jun. 2009, doi: 10.1111/J.1365-2036.2009.03994.X.
[35] S. Balata et al., “Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis,” Hepatology, vol. 37, no. 4, pp. 931–939, Apr. 2003, doi: 10.1053/jhep.2003.50156.
[36] P. J. Parekh and L. A. Balart, “Ammonia and Its Role in the Pathogenesis of Hepatic Encephalopathy,” Clin Liver Dis, vol. 19, no. 3, pp. 529–537, Aug. 2015, doi: 10.1016/J.CLD.2015.05.002.
[37] F. Imhann et al., “Proton pump inhibitors affect the gut microbiome,” Gut, vol. 65, no. 5, pp. 740–748, May 2016, doi: 10.1136/GUTJNL-2015-310376.
[38] L. G. van Vlerken et al., “Bacterial infections in cirrhosis: role of proton pump inhibitors and intestinal permeability,” Eur J Clin Invest, vol. 42, no. 7, pp. 760–767, Jul. 2012, doi: 10.1111/J.1365-2362.2011.02643.X.
[39] A. J. Richardson, N. McKain, and R. J. Wallace, “Ammonia production by human faecal bacteria, and the enumeration, isolation and characterization of bacteria capable of growth on peptides and amino acids,” BMC Microbiol, vol. 13, no. 1, pp. 1–8, Jan. 2013, doi: 10.1186/1471-2180-13-6/TABLES/3.
[40] Y. X. Yang and D. C. Metz, “Safety of proton pump inhibitor exposure,” Gastroenterology, vol. 139, no. 4, pp. 1115–1127, 2010, doi: 10.1053/J.GASTRO.2010.08.023.
[41] R. A. Weersink et al., “Safe use of proton pump inhibitors in patients with cirrhosis,” Br J Clin Pharmacol, vol. 84, no. 8, pp. 1806–1820, Aug. 2018, doi: 10.1111/BCP.13615.
[42] F. Lodato et al., “Proton pump inhibitors in cirrhosis: Tradition or evidence based practice?,” World Journal of Gastroenterology : WJG, vol. 14, no. 19, p. 2980, May 2008, doi: 10.3748/WJG.14.2980.
[43] G. Dultz, A. Piiper, S. Zeuzem, B. Kronenberger, and O. Waidmann, “Proton pump inhibitor treatment is associated with the severity of liver disease and increased mortality in patients with cirrhosis,” Aliment Pharmacol Ther, vol. 41, no. 5, pp. 459–466, Mar. 2015, doi: 10.1111/APT.13061.
Published
2025-01-30
Section
Articles
