Proton Pump Inhibitor Use and Association with Spontaneous Bacterial                     Peritonitis in Patients with Cirrhosis and Ascites

Siple, Jolene; Morey, Jessica M; Gutman, Tracy E; Weinberg, Kathy L; Collins, Peggie D

doi:10.1345/aph.1r174

Cited by 15 publications

(14 citation statements)

References 24 publications

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“…The potential clinical consequences could be increased incidences of enteric infections [ 4 ], including Clostridium difficile enterocolitis, and pulmonary infections [ 7 ]. Some specific subsets of patients could sustain a particularly high risk of suffering these complications, including cirrhotics with ascites [ 16 , 17 ] and hospitalized patients on antibiotic therapy [ 6 ]. CKD may also represent a high risk setting, because the intestinal barrier and the microbiota of these patients are frequently altered [ 18 ], and treatment with IGAS could further complicate these disorders.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

et al. 2016

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BackgroundEvidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD).MethodObservational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time-dependent analyses and, when appropriate, competing risk analyses.Main resultsThe clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08–2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other.ConclusionsTreatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

et al. 2016

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“…In cirrhotic patients, the main reason for inadequate PPI use was previous variceal bleeding (Kalaitzakis and Björnsson, 2008). Although clinical guidelines recommended PPI administration prior to endoscopic variceal ligation, this is not reasonable for continuous long-term PPI therapy (Garcia-Tsao et al, 2007;Siple et al, 2012). Acid secretion is constitutively reduced during cirrhosis, so there is no sufficient evidence to support PPI use for prophylaxis of peptic complications in patients with portal hypertension or esophageal varices (Merli et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We used a meta-analysis approach to investigate the association between proton pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to identify eligible studies. We included studies that compared cirrhotic patients who did or did not use PPIs. The primary outcome was SBP, and the secondary outcome was overall bacterial infection. Results were pooled using random-effect models. This process led to identification of 12 journal articles and 5 conference abstracts. The pooled data showed that PPI use in patients with cirrhosis and ascites was significantly associated with an increased risk of SBP [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I 2 = 85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P < 0.05; I 2 = 0). Subgroup analysis revealed that journal articles and studies reporting adjusted effect estimates demonstrated that PPI users had a significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I 2 = 29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I 2 = 67%, respectively). In conclusion, PPI use increased the risk of SBP and overall bacterial infection in patients with cirrhosis and ascites. PPIs should be administered after careful assessment of the indications in cirrhotic patients. Future well-designed prospective studies are warranted to clarify the dose relationships and to compare infection risks associated with different classes of PPIs.

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“…It should be noted that the studies about the effect of PPIs on bacterial translocation were limited to animal studies. Recently published studies have suggested that PPIs could increase the risk of SBP in patients with cirrhosis (11, 12, 16, 25, 26). The use of PPIs increases the gastric pH, bacterial translocation, facilitates the growth of the gut microflora, and alters various immunomodulatory and anti-inflammatory effects (12, 27).…”

Section: Discussionmentioning

confidence: 99%

“…Previous case control studies have found an increased risk of GI infections in patients taking PPIs (10). Some studies have reported that PPI therapy is associated with spontaneous bacterial peritonitis (SBP) in patients with advanced cirrhosis (11, 12). Increased ammonia-producing enteric bacteria in patients is shown to be a risk factor for HE (13).…”

Section: Introductionmentioning

confidence: 99%

“…Numerous studies have been published concerning the prognostic factors in ACLF (15), but there is little information regarding the factors predictive of development of HE. Nevertheless, it has been recently hypothesized that PPI therapy may increase the intestinal bacterial overgrowth (11, 16), which produces more toxic substances in colon.…”

Section: Introductionmentioning

confidence: 99%

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Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure

Lin

Zuo

2014

Hepat Mon

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Background:Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections.Objectives:The aim of this study was to assess whether PPI use in ACLF is associated with HE.Patients and Methods:A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE.Results:In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003).Conclusions:The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF.

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Proton Pump Inhibitor Use and Association with Spontaneous Bacterial Peritonitis in Patients with Cirrhosis and Ascites

Cited by 15 publications

References 24 publications

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis

Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis

Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure

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