Proton pump inhibitor use and spontaneous bacterial peritonitis in cirrhosis: An undesirable association?
Authors: Suelen A. da Silva Miozzo, Cristiane Valle Tovo, Jorge Alberto John, Angelo Alves de Mattos
Journal: Journal of Hepatology (2015)

Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: A multicenter prospective studyJournal of HepatologyVol. 62Issue 5PreviewRetrospective studies show an association between proton pump inhibitor (PPI) therapy and spontaneous bacterial peritonitis (SBP). We investigate the relationship between PPI and SBP in decompensated cirrhotic patients in a large nationwide prospective study. Full-Text PDF It is well known that bacterial infections in cirrhotic patients are associated with significant morbidity and mortality, determining a poor short- and long-term prognosis and a low survival rate [[1]Jalan R. Fernandez J. Wiest R. Schnabl B. Moreau R. Angeli P. et al.Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013.J Hepatol. 2014; 60: 1310-1324Abstract Full Text Full Text PDF PubMed Scopus (613) Google Scholar]. In a recent issue, Terg et al. [[2]Terg R. Casciato P. Garbe C. Cartier M. Stieben T. Mendizabal M. et al.Study Group of Cirrhosis Complications of the Argentine Association for the Study of Liver Disease. Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study.J Hepatol. 2015; 62: 1056-1060Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar] published their experience on the association between proton pump inhibitor (PPI) use and spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. They found that, among 770 hospitalized cirrhotic patients, SBP was diagnosed in 95 (24.7%) out of 394 patients with ascites and that there was no significant difference in the rate of PPI consumption between patients with SBP and those with ascites, but not with SBP (46% vs. 42%, p >0.05). Moreover, a high percentage of cirrhotic patients were taking a PPI without any documented indication (42%). When we evaluated the incidence of SBP in 1030 cirrhotic patients and its effect on survival [[3]Coral G. Mattos A.A. Damo D.F. Viégas A.C. Prevalência e Prognóstico da Peritonite Bacteriana Espontânea. Experiência em Pacientes internados em um hospital geral de Porto Alegre, RS, Brasil, (1991–2000).Arq Gastroenterol. 2002; 39: 158-162Crossref PubMed Google Scholar], it was evident that SBP was a common complication in patients with cirrhosis and ascites (11.1%) and that it determined a poor prognosis (21.9% mortality rate). We are currently performing a prospective study assessing the incidence of SBP among cirrhotic outpatients using PPIs. Among 582 cirrhotic patients followed-up for a median time of 5 years, 258 patients developed ascites and were evaluated (Table 1). Among these, 151 were using PPIs (58.5%). SBP developed in 34 of the 151 patients who were using PPIs (22.5%) and in 23 of the 107 patients who were not using PPIs (21.5%, p = 0.176). In order to evaluate risk factors for the development of SBP, a multivariate analysis was performed and showed that only the Child-Turcotte-Pugh score was independently associated with the incidence of SBP in cirrhotic outpatients [odds ratio of 2.09, 95% confidence interval of 1.07–4.07; p = 0.029]. To the best of our knowledge, there is only one study that evaluated the incidence of SBP in a prospective cohort of cirrhotic outpatients using PPIs and did not find a difference between patients who used PPIs and those who did not [[4]van Vlerken L.G. Huisman E.J. van Hoek B. Renooij W. de Rooij F.W. Siersema P.D. et al.Bacterial infections in cirrhosis: role of proton pump inhibitors and intestinal permeability.Eur J Clin Invest. 2012; 42: 760-767Crossref PubMed Scopus (45) Google Scholar]. Nevertheless, in that study, the incidence of SBP was evaluated in a small group with only 84 cirrhotic patients, of which 29 had ascites, and SBP was diagnosed in nine patients.Table 1Characteristics of the 258 patients with cirrhosis and ascites.SD, standard deviation; n, number of patients; HCV, hepatitis C virus; CTP, Child-Turcotte-Pugh score; MELD, model for end stage liver disease.aStudent's t test, bFisher's exact test. Open table in a new tab SD, standard deviation; n, number of patients; HCV, hepatitis C virus; CTP, Child-Turcotte-Pugh score; MELD, model for end stage liver disease. aStudent's t test, bFisher's exact test. Even though most studies describe an association between the development of SBP and the use of PPIs, their results seem to be limited by their retrospective character. We share the understanding of Terg et al. [[2]Terg R. Casciato P. Garbe C. Cartier M. Stieben T. Mendizabal M. et al.Study Group of Cirrhosis Complications of the Argentine Association for the Study of Liver Disease. Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study.J Hepatol. 2015; 62: 1056-1060Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar], since, despite the indiscriminate use of PPIs in cirrhotic patients, our experience, prospectively evaluating cirrhotic outpatients, showed no significant difference in the incidence of SBP between the group of cirrhotics with ascites who used PPIs and the group who did not. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. AA Mattos and CV Tovo were responsible for the conception and design; JA John and SAS Miozzo collected and analyzed data; SAS Miozzo wrote the manuscript; AA Mattos and CV Tovo critically reviewed intellectual content; all authors reviewed the manuscript and approved its final version for publication.