DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20190338

Proton pump inhibitor: a risk factor for spontaneous bacterial peritonitis in Indian cirrhotics decompensated with ascites

Akash Rajender, Priyanka Choudhary, Saumya Mathur, Rajat Bhargava, Shalini Upadhyay, Subhash Nepalia

Abstract


Background: Spontaneous bacterial peritonitis (SBP) is common complication of cirrhosis caused by bacterial translocation. Bacterial colonization and overgrowth may occur in GI tract on suppression of gastric acid secretion. Beta-blockers have been postulated to reduce intestinal permeability. There is no significant Indian study to evaluate association of PPI with SBP in cirrhotic ascites. We aimed to assess the effect of PPI in cirrhotic patients decompensated with ascites.

Methods: A retrospective case control study (January 2016 to April 2018), evaluated subjects with cirrhosis and ascites. Two study groups of cirrhotic subjects with and without SBP were formed. In each of the two study groups, 143 subjects, were enrolled by matching for age, year of admission, Child-Pugh-Turcotte (CTP) class after considering the inclusion and exclusion criteria. PPI use and various other correlates were compared in both study groups. SPSS ver 24.0 was used for statistical analysis.

Results: About 69.23% subjects were using PPI prior to admission in SBP group, which was significant compared to only 31.47% in cirrhotics without SBP (p 0.003). On multivariate analysis PPI use was an independent risk factor for SBP (OR 2.24, 95% CI: 1.01-4.24; p value 0.033) and beta blocker use was protective (OR 0.58; 95% CI: 0.4-0.8; p 0.001).

Conclusions: PPI use doubles the risk of development of SBP in cirrhotics decompensated with ascites. In contrast, Beta blockers use significantly lowers the risk of SBP.

Keywords


Ascites, Cirrhosis, PPI, SBP

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References


Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30:890-5.

Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis. 2008;28:26-42.

Scarpellini E, Valenza V, Gabrielli M, Lauritano EC, Perotti G, Merra G, et al. Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed?. Am J Gastroenterol. 2010 Feb;105(2):323.

Chang CS, Chen CH, Lien HC, Yeh HZ. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 1998;28:1187-90.

Rimola A, Soto R, Bory F, Arroyo V, Piera C, Rodes J. Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis. Hepatology. 1984;4:538.

Fiuza C, Salcedo M, Clemente G, Tellado J. In vivo neutrophil dysfunction in cirrhotic patients with advanced liver disease. J Infect Dis. 2000;182:526-33.

Such J, Guarner C, Enriquez J, Rodriguez JL, Seres I, Vilardell F. Low C3 in cirrhotic ascites predisposes to spontaneous bacterial peritonitis. J Hepatol. 1988;6:80-4.

Morillas RM, Planas R. Spontaneous bacterial peritonitis and other infections in cirrhosis. Humana Press: Totowa, NJ; 2005.

Lodato F, Azzaroli F, Di Girolamo M, Feletti V, Cecinato P, Lisotti A, et al. Proton pump inhibitors in cirrhosis: tradition or evidence based practice?. WJG. 2008 May 21;14(19):2980.

Deshpande N, Sharanya V, VV RK, Murthy HV, Sasikala M, Banerjee R, et al. Rapid and ultra-rapid metabolizers with CYP2C19* 17 polymorphism do not respond to standard therapy with proton pump inhibitors. Meta gene. 2016 Sep 30;9:159-64.

Kudzi W, Dodoo A, Mills J. Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population. BMC Med Genet. 2009;10(1):124.

He N, Yan F, Huang S, Wang W, Xiao Z, Liu Z. CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population. Eur J Clin Pharmacol. 2002;58(1):15-18.

Sugimoto K, Uno T, Yamazaki H, Tateishi T. Limited frequency of the CYP2C19*17 allele and its minor role in a Japanese population. Br J Clin Pharmacol. 2008;65(3):437-9.

Campbell MS, Obstein K, Reddy KR, Yang YX. Association between proton pump inhibitor use and spontaneous bacterial peritonitis. Dig Dis Sci. 2008;53:394-8.

Bajaj JS, Zadvornova Y, Heuman DM, Hafeezullah M, Hoffmann RG, Sanyal AJ, et al. Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol. 2009;104:1130-4.

Goel GA, Deshpande A, Lopez R, Hall GS, van Duin D, Carey WD. Increased rate of spontaneous bacterial peritonitis among cirrhotic patients receiving pharmacologic acid suppression. Clin Gastroenterol Hepatol. 2012;10:422-7.

Choi EJ, Lee HJ, Kim KO, Lee SH, Eun JR, Jang BI, et al. Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites. Scand J Gastroenterol. 2011;46:616-20.

de Vos M, De Vroey B, Garcia BG, Roy C, Kidd F, Henrion J, 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;33:1316-23.

Deshpande A, Pasupuleti V, Thota P. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: A meta-analysis. J Gastroenterol Hepatol. 2013;28:235-4.

Yoshida N, Yoshikawa T, Tanaka Y, Fujita N, Kassai K, Naito Y, et al. A new mechanism for anti‐inflammatory actions of proton pump inhibitors–inhibitory effects on neutrophil-endothelial cell interactions. Alimentary Pharmacol Therapeut. 2000 Feb 1;14:74-81.

Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxböck F, Graninger W. Omeprazole treatment diminishes intra-and extracellular neutrophil reactive oxygen production and bactericidal activity. Crit Care Med. 2002 May 1;30(5):1118-22.

Sánchez E, Such J, Chiva MT, Soriano G, Llovet T, Merce J, et al. Development of an experimental model of induced bacterial peritonitis in cirrhotic rats with or without ascites. The American J Gastroenterol. 2007 Jun;102(6):1230.

Chang CS, Chen GH, Lien HC, Yeh HZ. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 1998 Nov;28(5):1187-90.

Kedika RR, Souza RF, Spechler SJ. Potential anti-inflammatory effects of proton pump inhibitors: a review and discussion of the clinical implications. Dig Dis Sci. 2009;54:2312-7.

Reiberger T, Ferlitsch A, Payer BA, Mandorfer M, Heinisch BB, Hayden H, et al. Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis. J Hepatol. 2013;58:911-21.

Senzolo M, Cholongitas E, Burra P, Leandro G, Thalheimer U, Patch D, et al. β‐Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta‐analysis. Liver International. 2009 Sep;29(8):1189-93.

Lebrec D, Poynard T, Hillon P, Benhamou JP. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a controlled study. N Engl J Med. 1981;305:1371-4.

Lo GH, Chen WC, Lin CK, Tsai WL, Chan HH, Chen TA, et al. Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding. Hepatol. 2008;48:580-7.

Cholongitas E, Papatheodoridis GV, Manesis EK, Burroughs AK, Archimandritis AJ. Spontaneous bacterial peritonitis in cirrhotic patients: Is prophylactic propranolol therapy beneficial? J Gastroenterol Hepatol. 2006;21:581-7.