Proton Pump Inhibitor Treatment Is Associated With the Severity of Liver Disease and Increased Mortality in Patients With Cirrhosis

G. Dultz; A. Piiper; S. Zeuzem; B. Kronenberger; O. Waidmann


Aliment Pharmacol Ther. 2015;41(5):459-466. 

In This Article

Abstract and Introduction


Background Proton pump inhibitors (PPI) are widely used in patients with liver diseases. Within the last years, there have been concerns about the PPI use as they may promote infections in patients with cirrhosis.

Aim As there are sparse data of the prognostic relevance of PPI treatment, to perform a prospective study investigating the relation of PPI treatment and overall survival (OS) in cirrhotic individuals.

Methods Patients with cirrhosis were enrolled and followed prospectively. The primary end point was OS. PPI treatment and additional clinical and laboratory data were assessed at the day of the study inclusion. The time until the end point death was assessed and the individual risks were calculated with Cox regression analyses.

Results A total of 272 patients were included and 213 individuals (78.3%) were on PPI treatment. In multivariate logistic regression analysis, PPI treatment was associated with higher MELD scores (P = 0.027) and ascites (P = 0.039). In a multivariate Cox regression model, PPI use was an independent predictor of mortality (hazard ratio 2.330, 95% confidence interval 1.264–4.296, P = 0.007) in addition to the model of end-stage liver disease (MELD) score, hepatocellular carcinoma and hepatic decompensation.

Conclusions PPI use is an independent risk factor for mortality in patients with cirrhosis. Although a causative role for increased mortality in patients taking PPI is still missing, the prescription of PPI in cirrhotics should be considered carefully taking into account its potential adverse effects.


Cirrhosis is the consequence of different chronic liver diseases characterised by hepatic cell death, inflammation and fibrotic conversion of the liver.[1] Compensated cirrhosis often only slightly worsens patients' general condition. However, if decompensation of cirrhosis occurs and cirrhosis related complications are arising, morbidity and mortality are increasing rapidly.[2,3] A common complication of cirrhosis is gastrointestinal bleeding including acute bleeding from varices or ulcers and chronic blood loss from portal hypertensive gastropathy (PGH) or gastric vascular ectasia (GAVE) syndrome. Acute bleeding from varices is managed using vasoconstrictors, antibiotics and endoscopic ligation or sclerotherapy.[4] In such patients proton pump inhibitors (PPI) reduce the risk of death irrespective of concomitant endoscopic hemostasis.[5] Patients undergoing endoscopic band ligation benefit from PPI treatment as PPI reduce the size of post-banding ulcers.[6] However, there is evidence that PPI may have adverse effects in patients with cirrhosis. PPI intake favours bacterial infections including spontaneous bacterial peritonitis (SBP),[7–10] but there are conflicting data if PPI worsen the prognosis of patients with SBP.[11,12] Furthermore, even in noncirrhotic patients PPI usage may increase the risk of bacterial infections including pneumonia or Clostridium difficile colitis.[13,14] Multi-drug resistant (MDR) bacteria are a severe and increasing healthcare challenge.[15] As PPI may facilitate bacterial colonisation of the upper gastrointestinal tract and the small bowel, cirrhotic patients receiving acid suppression therapy might also be at an increased risk of being colonised with MDR bacteria. Studies in mice have shown a higher susceptibility to colonisation with Vancomycin-resistant Enterococcus faecium (VRE) or resistant Klebsiella pneumoniae in animals receiving PPI.[16] However, there is only little data concerning a possible relation between acid suppression with PPI and colonisation with MDR bacteria in humans. In a cohort of cirrhotic patients awaiting liver transplantation VRE colonisation was associated with antibiotic treatment and PPI treatment.[17] However, beneath the indicated studies there is little data concerning the relation between PPI intake and infectious complications, colonisation with MDR bacteria and overall mortality of cirrhotic patients. Therefore, we performed a prospective mono centre study in a German university hospital investigating the relation of PPI treatment and overall mortality in cirrhotic individuals.