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Proton pump inhibitors linked to higher mortality for patients with cirrhosis

Patients with cirrhosis had a greater risk for mortality while using proton pump inhibitor treatment, according to new study results.

Researchers at the Goethe University Hospital in Germany studied the relation of proton pump inhibitor (PPI) treatment and overall survival in patients with cirrhosis to address concerns associated with PPIs and infections.

“Proton pump inhibitors are considered to facilitate bacterial overgrowth of the gastrointestinal tract and thereby may promote infections leading to worsening of liver function,” the researchers wrote.

The prospective monocentric study included 272 patients older than 18 years with cirrhosis who were treated between May 2009 and June 2011.

Seventy-eight percent of the patients had PPI treatments, such as omeprazole, esomeprazole or pantoprazole. Of those patients, 89 were given PPI treatment for recent gastrointestinal bleeding, recent endoscopic ligation of varices, severe reflux or peptic ulcer disease.  The rest of the patients were given PPI treatment symptomatically for epigastric pain or abdominal discomfort.

Patients were observed up until death, last moment of contact, or if they received a liver transplant. Median follow-up time was 266 days, ranging from 1 day to 1,382 days.

According to a univariate analysis, patients with PPI treatment were likely to have a higher mortality (HR=2.33; 95% CI, 1.264-4.296). Other mortality predictors included infectious complications (HR=2.704; 95% CI, 1.759-4.158), hepatocellular carcinoma (HR=2.542; 95% CI, 1.557-4.149) and MELD score (HR=1.102; 95% CI 1.067-1.138).

A multivariate analysis that had been adjusted for the severity of cirrhosis showed that PPI treatment was an independent factor associated with mortality (HR=2.363; 95% CI 1.26-4.43).  Hepatic decompensation (HR=2.211; 95% CI, 1.208-4.045), HCC (HR=4.971; 95% CI, 2.909-8.497), and the MELD score (HR=1.097; 95% CI, 1.059-1.137) were negative prognostic factors, as well.

“Interestingly, PPI use was a stronger predictor of mortality in multivariate Cox regression analysis than the presence of infections,” the researchers wrote.

In other results, there was no suggestion that patients who used PPI treatment for specific vs. symptomatic reasons were at higher risk for mortality (HR=1.49; 95% CI, 0.946-2.37).  There was no association with age, gender or etiology of cirrhosis in OS.

“Although a causative role for PPI in the increased mortality cannot and should not be deduced from our observations, we advise a careful use of PPI in cirrhotics given by the potential adverse effects of PPI, especially when they are used apart from hard indications for symptomatic treatment of abdominal symptoms,” the researchers wrote.

Disclosure: The researchers report no relevant financial disclosures.