What is the role of Proton Pump Inhibitors (PPI) in cirrhosis?

From the Guidelines

Proton pump inhibitors (PPIs) should be avoided in patients with cirrhosis unless there is a clear and formal indication, due to the increased risk of hepatic encephalopathy and other complications. The use of PPIs in cirrhosis has been associated with an increased incidence of hepatic encephalopathy (HE) by promoting microbial proliferation and dysbiosis in the small intestine, leading to the formation of ammonia and bacterial endotoxins 1. This is supported by a recent cohort study that found an increased risk for covert HE and development of overt HE in cirrhotic patients with long-term use of PPIs 1.

Key Considerations

• PPIs should only be prescribed when there are clear indications such as gastroesophageal reflux disease, peptic ulcer disease, or for prevention of variceal bleeding in combination with endoscopic therapy.
• Common PPIs include omeprazole (20-40mg daily), pantoprazole (40mg daily), and esomeprazole (20-40mg daily), but treatment duration should be limited to the shortest period necessary to manage the condition.
• Patients with cirrhosis may require dose adjustments, particularly those with Child-Pugh C cirrhosis, where reducing the dose by 50% may be appropriate.
• Regular reassessment of the need for continued PPI therapy is essential, with consideration of step-down therapy or discontinuation when possible to minimize the risks associated with long-term PPI use 1.

Risks Associated with PPI Use

• Increased risk of spontaneous bacterial peritonitis
• Increased risk of Clostridium difficile infection
• Increased risk of hepatic encephalopathy
• PPI-induced changes in gut microbiota and increased intestinal permeability, which can promote bacterial translocation 1.

It is essential to weigh the benefits and risks of PPI use in patients with cirrhosis and to consider alternative treatments when possible, in order to minimize the risk of complications and improve patient outcomes 1.

From the Research

Proton Pump Inhibitors (PPIs) in Cirrhosis

• PPIs are commonly prescribed for gastric disorders, but their use in patients with liver cirrhosis is associated with an increased risk of spontaneous bacterial peritonitis and increased mortality rates 2, 3, 4, 5.
• A retrospective study found that 50.2% of cirrhotic patients were prescribed PPIs during hospitalization, and 39.7% were prescribed PPIs at discharge, with 47.4% of inpatients and 34.7% at discharge having no valid indication for PPI administration 2.
• The most common reason for PPI prescription during hospital stays was gastritis, followed by antiplatelet use in high-risk patients, ulcers, and upper gastrointestinal bleeding 2.
• The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy, and should be carefully considered 6, 3, 4, 5.
• A systematic review and meta-analysis found a statistically significant association between SBP and PPIs use, with a pooled odds ratio of 1.80 (95% CI of 1.41 to 2.31) 5.
• Subgroup analysis involving cohort studies found a weaker association between SBP and PPIs use, with an odds ratio of 1.55 (95% CI of 1.16 to 2.06) 5.
• The use of PPIs in patients with liver cirrhosis should be guided by clinical guidelines, and patients should be carefully monitored for signs of spontaneous bacterial peritonitis and hepatic encephalopathy 2, 6, 4.
• Esomeprazole, omeprazole, and rabeprazole were classified as having 'no additional risks known' in patients with cirrhosis, while pantoprazole and lansoprazole were classified as unsafe due to increased exposure 6.
• The maximum dose of omeprazole and rabeprazole should be reduced in patients with Child-Turcotte-Pugh (CTP) A and B cirrhosis, and esomeprazole should be used at a maximum dosage of 20 mg per day in patients with CTP C cirrhosis 6.