Can Proton Pump Inhibitors (PPIs) cause elevated liver enzymes, specifically hepatocellular injury or cholestasis?

From the Guidelines

Proton pump inhibitors can indeed have an impact on liver health, although the provided evidence does not directly address the elevation of liver enzymes, it highlights the potential for increased risk of hepatic encephalopathy (HE) in patients with cirrhosis due to the use of PPIs. The study published in Liver International in 2023 1 discusses the diagnosis and management of hepatic encephalopathy and notes that proton pump inhibitors increase the incidence of HE by promoting microbial proliferation and dysbiosis in the small intestine. This leads to the formation of products such as ammonia and bacterial endotoxins, which can cause systemic inflammation and potentially affect liver function.

Key points to consider include:

• The potential for PPIs to increase intestinal membrane permeability and bacterial translocation, which could underlie systemic inflammation and impact liver health.
• The association between PPI dose and the risk for HE, as observed in retrospective studies.
• The recommendation to systematically re-evaluate the benefit–risk balance and appropriateness of PPI prescriptions in patients with cirrhosis, suggesting a cautious approach to PPI use in this population.

While the direct effect of PPIs on liver enzymes is not explicitly addressed in the provided evidence, the information suggests that PPIs should be used judiciously, especially in patients with pre-existing liver conditions, due to their potential to contribute to complications such as hepatic encephalopathy. Monitoring liver function and carefully weighing the benefits against the risks of PPI therapy is crucial, particularly in vulnerable populations like those with cirrhosis, as indicated by the study 1.

From the Research

Proton Pump Inhibitors and Liver Enzymes

• The provided studies do not directly address the question of whether proton pump inhibitors (PPIs) can elevate liver enzymes 2, 3, 4, 5, 6.
• However, the studies suggest that PPIs can have adverse effects on the liver, including an increased risk of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatocellular carcinoma 3, 4, 6.
• One study found that PPIs can alter the composition and function of the intestinal microflora, leading to small intestinal bacterial overgrowth and bacterial translocation, which can have adverse effects on the liver 3.
• Another study found that PPIs are associated with an increased risk of liver abscess and increased mortality in patients with chronic liver disease 3.
• A meta-analysis found that PPIs are associated with a significant increase in the risk of hepatic encephalopathy, spontaneous bacterial peritonitis, and mortality in patients with chronic liver disease 4.
• A systematic review and meta-analysis found that PPIs are associated with an increased risk of hepatocellular carcinoma and mortality in patients with chronic liver disease 6.

Mechanism of Action

• PPIs work by reducing gastric acid secretion, which can lead to changes in the gut microbiome and increase the risk of adverse effects on the liver 3, 5.
• The mechanism of action of PPIs is different from that of H2-receptor antagonists, which can also reduce gastric acid secretion but have a different effect on the gut microbiome 5.

Clinical Implications

• The use of PPIs in patients with chronic liver disease should be carefully considered, as they may be associated with an increased risk of adverse effects on the liver 3, 4, 6.
• Clinicians should be aware of the potential risks and benefits of PPIs in patients with liver disease and consider alternative treatments when possible 3, 4, 6.