Elsevier

Journal of Hepatology

Volume 62, Issue 5, May 2015, Pages 1056-1060
Journal of Hepatology

Research Article
Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: A multicenter prospective study

https://doi.org/10.1016/j.jhep.2014.11.036Get rights and content

Background & Aim

Retrospective 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.

Methods

Seven hundred seventy patients with a diagnosis of decompensated cirrhosis were admitted consecutively in 23 hospitals in Argentina from March 2011 to April 2012; the patients were carefully investigated for PPI consumption in the previous 3 months. In total, 251 patients were excluded because of active gastrointestinal hemorrhage, antibiotic use during the preceding weeks, HIV-positive status and immunosuppressive therapy.

Results

Two hundred twenty-six out of 519 patients (43.5%) had received PPI therapy within the last 3 months. In 135 patients, PPIs were administered for longer than 2 weeks. A bacterial infection was shown in 255 patients (49.1%). SBP was diagnosed in 95 patients out of 394 patients with ascites (24.7%). There was no significant difference in the rate of PPI consumption between the infected and the non-infected patients (44.3% vs. 42.8%) or between the SBP patients and the patients with ascites without SBP (46% vs. 42%). In the SBP patients, the duration of PPI administration did not influence the rate of SBP occurrence. The type of bacteria and the origin of SBP infection were similar in the patients with and without PPI.

Conclusion

In the current large, multicenter, prospective study, PPI therapy, specifically evaluated at admission of consecutive cirrhotic patients, was not associated with a higher risk of SBP.

Introduction

Proton pump inhibitors (PPIs) have been associated with a modest increased risk of spine and total fractures in 130,487 postmenopausal women (risk factor 1.25 [1], [2]), with a significant increase in the rate of Clostridium difficile infections and recurrences in hospitalized patients [3] and with an increased risk of community- and nosocomially-acquired pneumonia [4].

Recent retrospective studies show controversial results regarding an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients taking PPIs [5], [6], [7], [8], [9], [10], [11].

These studies had a similar design, which might constitute a source of error: (1) the studies were retrospective reviews of the list of medications taken by the cirrhotic hospitalized patients, and most were performed in a single center; (2) patients with documented PPI ingestion were considered PPI users, and those with an absence of data were considered PPI non-users; and (3) the inclusion criteria were heterogeneous.

Difficulties in data collection are clearly shown by the high number of medical records invalidated for the final analysis in these studies.

A retrospective analysis may lead to a false estimation of patients taking PPIs because this issue was not specifically investigated at admission.

Total PPI sales in Argentina represent approximately 169 million dollars annually and because SBP represents one of the most frequent causes of bacterial infection in decompensated cirrhotic patients, the impact of the potential increase in SBP in cirrhotic patients taking PPIs should be urgently clarified.

The aim of the study was to investigate the relationship between PPI therapy and the development of SBP in decompensated cirrhotic patients in a nationwide multicenter, prospective study.

Section snippets

Patients and methods

We prospectively collected and analyzed the data of 770 patients with decompensated cirrhosis who were consecutively hospitalized in 23 hospitals in Argentina from March 2011 to April 2012.

All of the patients were specifically asked about PPI consumption in the 3 months prior to hospitalization and were classified as PPI users or non-users.

The inclusion criteria were as follows: A diagnosis of cirrhosis established either with a liver biopsy or by a combination of physical, endoscopic,

Results

A total of 521 patients were included in the study. There were 255 patients with bacterial infections and 264 without bacterial infections. Only the MELD score (19 ± 7 vs. 17 ± 6) and the serum albumin (2.53 ± 0.54 vs. 2.69 ± 0.62 gr/dl) were significantly different in the infected patients compared with the non-infected patients.

A history of PPI consumption was found in 114 (44.3%) of the infected patients and in 112 (42.8%) of the non-infected patients (n.s.).

The causes of the bacterial infection were

Discussion

The use of a PPI, which is a potent gastric acid suppressor, is widespread around the world, and these drugs represent a very important source of sales in the pharmaceutical markets. In many countries, including Argentina, PPIs do not require a prescription, and the majority of individuals taking a PPI do not have a clear indication for the drug.

Recent studies have introduced concerns regarding the increased risk of bacterial infections, typically SBP, in patients with cirrhosis [5], [6], [7],

Members of the Study Group for Cirrhosis Complications

Fernando Gruz, Fundación Favaloro, Buenos Aires. Carlos Guma, Hospital HIGA Eva Perón, Buenos Aires. Hugo Faimboim, Hospital Muñiz, Buenos Aires. Ezequiel Ridruejo, CEMIC, Buenos Aires, Diana Gibelli, Silvia Mengarelli S, Hospital San Roque, Córdoba, Adriana Spiraquis A, Hospital Militar, Rodolfo Carbonetti, Sanatorio Parque, Tucumán. Fernando Ross, Hospital Milstein, Buenos Aires. Oscar Laudano, Hospital Bocalandro, Buenos Aires, Bernardo Frider, Hospital Argerich, Buenos Aires Jose Allevato,

Financial support

The study was supported in part, by the Argentine Association for the Study of Liver Disease (AAEEH).

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

References (26)

  • E.J. Choi et al.

    Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites

    Scand J Gastroenterol

    (2011)
  • J. Bajaj et al.

    Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis

    Aliment Pharmacol Ther

    (2012)
  • M. De Vos et al.

    Role of proton pump inhibitors in the occurrence and the prognosis of spontaneous bacterial peritonitis in cirrhotic patients with ascites

    Liver Int

    (2013)
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