PPI use tied to higher risk of hepatic encephalopathy in cirrhotic patients

Last Updated: 2016-09-22

By Reuters Staff

NEW YORK (Reuters Health) - Patients with cirrhosis who are treated with a proton pump inhibitor (PPI) face an increased risk of hepatic encephalopathy, and the risk rises in a dose-dependent fashion, a large study from Taiwan has found.

"It is therefore important for healthcare providers to carefully consider prolonged PPI use by patients with cirrhosis," conclude Dr. Ching-Liang Lu and colleagues from National Yang-Ming University School of Medicine in Taipei in their paper in Gastroenterology, online September 14.

Hepatic encephalopathy (HE), they explain, is a serious complication of cirrhosis and is associated with gut microbial imbalance. PPIs, which are often prescribed to patients with cirrhosis, can contribute to small bowel bacterial overgrowth.

To see whether PPI use predisposes cirrhotic patients to HE, the researchers did a matched case-control study using the Taiwan National Health Insurance database. The study included 2,332 mostly male patients with cirrhosis, half with and half without an occurrence of HE.

They defined PPI use as >30 cumulative defined daily doses (cDDDs) and non-PPI use as 30 cDDDs or less.

Roughly 38% patients with HE and 21% without HE were on a PPI. Prolonged PPI use was more frequently identified in cirrhotic patients with HE occurrence than in their peers without HE.

"All 4 models after logistic regression demonstrated a consistent dose-dependent relationships between PPI use and HE risk," the team reports.

The adjusted odd ratios were 1.41, 1.51 and 3.01 for patients with 30 to 120 cDDDs, 120 to 365 cDDDs, and >365 cDDDs, respectively, compared with PPI non-users (all p<0.05).

Stratified by each individual PPI, the use of pantoprazole, lansoprazole, omeprazole and esomeprazole, but not rabeprazole, were associated with an increased risk of developing HE.

The small sample size of rabeprazole users might explain this finding, the researchers say, adding, "Another possibility is the metabolic and pharmacokinetic differences among different PPIs."

They say that to their knowledge, "this is the first study showing a dose-response relationship between PPI use and the risk of HE occurrence in cirrhotic patients after controlling for the confounding effects of age, sex, income, level of urbanization, medical comorbidities, and using psychotropic medicine during the follow-up."

Given that PPI therapy is common in cirrhotic patients, the authors suggest that it is "important to periodically review the appropriateness of prolonged PPI use in cirrhotic patients," especially those at high risk of developing HE.

Dr. Lu did not respond to request for comment by press time.

The study had no commercial funding and the authors have no disclosures.

SOURCE: http://bit.ly/2co9SxU

Gastroenterol 2016.