Are Proton Pump Inhibitors (PPIs) avoided in patients with liver cirrhosis?

PPIs Should Be Used With Caution and Restricted to Clear Indications in Liver Cirrhosis

PPIs are not strictly avoided in liver cirrhosis, but their use should be restricted to patients with clear, appropriate gastrointestinal indications and used at the lowest effective dose for the shortest duration necessary, as long-term PPI therapy significantly increases the risk of spontaneous bacterial peritonitis, hepatic encephalopathy, and other infections. 1

Key Guideline Recommendations

When PPIs Should Be Used

• PPIs are appropriate for short-term use after endoscopic variceal ligation (EVL) to reduce post-banding ulcer size and bleeding risk 1
• Clear gastrointestinal indications include active peptic ulcer disease, upper gastrointestinal bleeding from non-variceal sources, severe erosive esophagitis, and antiplatelet therapy in high-risk patients 2, 3
• PPIs have NOT shown efficacy for managing acute variceal hemorrhage itself 1

When PPIs Should Be Avoided or Discontinued

• Long-term PPI use increases the risk of spontaneous bacterial peritonitis (SBP) with an adjusted hazard ratio of 1.72 (95% CI 1.10-2.69) 4
• PPIs increase hepatic encephalopathy risk with an adjusted hazard ratio of 1.36 for any HE and 1.88 for overt HE 4
• In hospitalized patients with cirrhosis and ACLF, PPIs should be stopped unless there is a clear and current indication 1
• The EASL guidelines explicitly state that PPI use should be restricted to those with clear indication since they may increase SBP risk 1

Mechanism of Harm

PPIs increase infection risk through multiple pathways:

• Gastric pH elevation promotes intestinal bacterial overgrowth and dysbiosis, facilitating bacterial translocation from the gut 5, 3, 4
• This bacterial translocation is the proposed mechanism for both increased SBP and hepatic encephalopathy in cirrhotic patients 4
• PPIs can worsen hyponatremia through SIADH-like effects, which further increases hepatic encephalopathy risk 5, 6

Clinical Evidence of Harm

Real-world data demonstrates widespread inappropriate use:

• In one study, 50% of hospitalized cirrhotic patients received PPIs, but 47% had no valid indication 2
• At discharge, 40% were prescribed PPIs with 35% having no appropriate indication 2
• A New Zealand study found only 31% of cirrhotic patients on PPIs had a clear indication, yet PPI use was associated with higher liver-related events (OR 2.9) and infections (OR 2.4) 7

Practical Management Algorithm

Step 1: Assess Current PPI Use

• Review all cirrhotic patients for PPI indication at every hospitalization and clinic visit 1
• Common inappropriate indications include: portal hypertensive gastropathy alone, corticosteroid use alone, anticoagulant use alone 2

Step 2: Discontinue When Appropriate

• Stop PPIs immediately if no clear indication exists 1
• Consider H2-receptor antagonists as alternatives when acid suppression is needed but PPI risks outweigh benefits 6

Step 3: When PPI Use Is Necessary

For patients with Child-Pugh A or B cirrhosis:

• Use esomeprazole, omeprazole, or rabeprazole as these have the most favorable pharmacokinetic profiles 8
• Reduce maximum dose of omeprazole and rabeprazole compared to standard dosing 8

For patients with Child-Pugh C cirrhosis:

• Use only esomeprazole at a maximum of 20 mg per day 8
• Avoid pantoprazole and lansoprazole due to 4-8 fold increased drug exposure 8

Step 4: Monitoring

• Monitor for development of infections, particularly SBP, during PPI therapy 1, 3, 4
• Watch for worsening hepatic encephalopathy 1, 4
• Periodically reassess the need for continued therapy and discontinue as soon as the indication resolves 3

Common Pitfalls to Avoid

• Continuing PPIs indefinitely after EVL: PPIs should only be used short-term post-procedure 1
• Prescribing PPIs for portal hypertensive gastropathy: This is not an appropriate indication 2
• Using high-dose or unfavorable PPIs in advanced cirrhosis: Stick to esomeprazole 20 mg daily maximum in Child-Pugh C 8
• Failing to document clear indications: This leads to inappropriate continuation at discharge 2
• Ignoring the dose-response relationship: Higher doses and longer duration increase adverse outcomes 3, 7

The bottom line: PPIs are not absolutely contraindicated in cirrhosis, but their risks substantially outweigh benefits when used without appropriate indication, making judicious prescribing essential for patient safety. 1, 2, 3, 7