Treatment With Proton Pump Inhibitors Is Associated With Increased Mortality in Patients With Pyogenic Liver Abscess

D. Bettinger; D. Martin; S. Rieg; M. Schultheiss; N. Buettner; R. Thimme; T. Boettler


Aliment Pharmacol Ther. 2018;47(6):801-808. 

In This Article

Abstract and Introduction


Background Proton pump inhibitors (PPI) are often used in patients with gastro-esophageal reflux and peptic ulcer disease. A higher risk for infectious diseases and for pyogenic liver abscess has been reported in patients with prolonged PPI intake. Although many patients have ongoing PPI treatment after diagnosis of liver abscess, there are no data available that focus on the prognostic impact of PPI treatment in these patients.

Aim To analyse the effect of PPI treatment on mortality in patients with pyogenic liver abscesses.

Methods Between January 2005 and March 2017, one hundred and eighty-one patients with pyogenic liver abscess were retrospectively included in this analysis. Medical records including PPI treatment, microbiological and imaging data were reviewed. The primary endpoint was index mortality and predictive factors were analysed using uni- and multivariate logistic regression models.

Results One hundred patients with pyogenic liver abscess (55.2%) were treated with PPI compared to 81 patients (44.8%) without PPI treatment. In both patient cohorts, enterococcus spp. and streptococcus of the anginous group were the most common pathogens identified. Patients with PPI treatment had significantly higher index mortality compared to patients without PPI treatment (30.0% vs 11.1%, P = 0.003). After adjusting for comorbidities PPI remained an independent predictive factor with an OR of 2.56 (1.01–6.46, P = 0.036).

Conclusions PPI treatment is associated with higher index mortality in patients with pyogenic liver abscess. Therefore, critical evaluation of the indication for PPI treatment is particularly important in patients at high risk for pyogenic liver abscess.


Proton pump inhibitors (PPI) lead to reduced gastric acid prodution as the H+/K+-adenosine triphosphatase in parietal cells is irreversibly blocked.[1] This is the rationale for their regular use in patients with gastroesophageal reflex disease (GERD) and peptic ulcer disease. Apart from these well-defined indications, the Food and Drug Adminstration (FDA) recommends PPI therapy for patients with Zollinger-Ellison syndrome, for healing and maintenance of erosive oesophagitis and for risk reduction in patients with regular need for treatment with non-steroidal antiinflammatory drugs (NSAIDS) as well as in combination with antibiotics for treatment of helicobacter pylori infection.[2] PPIs are generally well tolerated as they have few adverse events such as flatulence, headache, diarrhoea and abdominal pain which are often self-limiting.[1] In contrast to these well-defined indications, PPIs are also used for treatment of unspecific abdominal pain and discomfort, often as over-the-counter drugs without any medical consultation. This leads to an increasing and often inappropriate use of PPIs which are currently among the most commonly used drugs.[3] However, during the last years, there have been several reports revealing negative long-term effects of PPI treatment. Their use was associated with development of pneumonia caused by reduced gastric acidity which may facilitate bacterial overgrowth leading to pneumonia due to microaspiration.[1] In addition, an association of PPI treatment with an increased risk for C. difficile infection, hepatic encephalopathy[4] and spontaneous bacterial peritonitis in patients with liver cirrhosis have been reported.[5] Furthermore, some analyses found associations of PPI use with an increased risk for dementia,[6,7] myopathy[8–10] and acute kidney injury.[11,12] Recently, two population-based case-control studies demonstrated a strong association of PPI treatment with the development of pyogenic liver abscesses.[13,14] Since many patients who are hospitalised for pyogenic liver abscess have ongoing PPI treatment and since previous studies have shown an increased mortality in patients with ongoing PPI treatment in infectious diseases,[5] we set out to analyse the prognostic effect of PPI treatment in patients with newly diagnosed pyogenic liver abscess.