META-ANALYSYS AND SYSTEMATIC REVIEW Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: A meta-analysis Abhishek Deshpande,* 1 Vinay Pasupuleti,* 1 Priyaleela Thota, † Chaitanya Pant, †† Sulaiman Mapara, ¶ Sohaib Hassan, ‡ David D K Rolston, ‡‡ Thomas J Sferra** and Adrian V Hernandez § *Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, Departments of † Hospital Medicine, ‡ Internal Medicine and § Quantitative Health Sciences, Cleveland Clinic, ¶ Department of Internal Medicine, St. Vincent Charity Medical Center, **Department of Pediatrics, Case Western Reserve University, Rainbow Babies and Children’s Hospital, Cleveland, Ohio, †† Department of Pediatrics, Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, and ‡‡ Department of Internal Medicine, Geisinger Medical Center, Danville, Pennsylvania, USA Key words H2 receptor antagonist, meta-analysis, proton pump inhibitor, spontaneous bacterial peritonitis. Accepted for publication 24 October 2012. Correspondence Dr Abhishek Deshpande, Case Western Reserve University, Department of Medicine, Division of Infectious Diseases, 10900 Euclid Avenue, BRB 10 West, Cleveland, OH 44106-4984, USA. Email: abhishekdp@gmail.com Conflicts of interest: Nothing to declare for all authors. Financial Support: None. 1 Contributed equally to this study. Author Contributions: Conception and design: AD, VP, CP, AVH Analysis and interpretation of data: AD, VP, AVH, TJS, DDKR Drafting of the article: AD, VP, PT, CP, SM, SH, DDKR, TJS, AVH Critical revision of the article for important intellectual content: AD, VP, PT, CP, SM, SH, DDKR, TJS, AVH Final approval of the article: AD, VP, PT, CP, SM, SH, DDKR, TJS, AVH Statistical expertise: AVH Collection and assembly of data: AD, VP, PT, CP, SM, SH, DDKR, TJS, AVH Abstract Background and Aim: Proton pump inhibitors (PPI) and H2-receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are con- flicting reports regarding the role of acid-suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP). The aim of this meta- analysis was to evaluate the association between acid-suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis. Methods: We searched MEDLINE and four other databases for subject headings and text words related to SBP and acid-suppressive therapy. All observational studies that investi- gated the risk of SBP associated with PPI/H2RA therapy and utilized SBP as an endpoint were considered eligible. Data from the identified studies were combined by means of a random-effects model and odds ratios (ORs) were calculated. Results: Eight studies (n = 3815 patients) met inclusion criteria. The risk of hospitalized cirrhotic patients developing SBP increased when using acid-suppressive therapy. The risk was greater with PPI therapy (n = 3815; OR 3.15, 95% confidence interval 2.09–4.74) as compared to those on H2RA therapy (n = 562; OR 1.71, 95% confidence interval 0.97– 3.01). Conclusions: Pharmacologic acid suppression was associated with a greater risk of SBP in hospitalized patients with cirrhosis. Cirrhotic patients receiving a PPI have approxi- mately three times the risk of developing SBP compared with those not receiving this medication. Prospective studies may help clarify this relationship and shed light on the mechanism(s) by which acid-suppressive therapy increases the risk of SBP in hospitalized patients with cirrhosis. Introduction Spontaneous bacterial peritonitis (SBP) is a frequent complication in cirrhotic patients with ascites and is associated with significant morbidity and increased mortality. 1–3 In hospitalized patients with cirrhosis, SBP accounts for 10–30% of all reported bacterial infections. 1–3 While the mechanism of SBP is unknown, evidence suggests that patients with cirrhosis are predisposed to gastrointes- tinal bacterial overgrowth resulting from increased intestinal permeability, altered intestinal motility, and medication-induced doi:10.1111/jgh.12065 235 Journal of Gastroenterology and Hepatology 28 (2013) 235–242 © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd