Background
- Proton pump inhibitors (PPI) are among the most common medications used in the US.
- Many patients (estimated at 63% in some studies) do not have a clear indication for PPI use.
- Recent literature supports association between PPI use and infection, hepatic decompensation, and liver-related mortality in patients with cirrhosis.
Figure 1. Relative hazard of severe infection, infection subtypes, and decompensation associated with PPI exposure in multivariable IPTW Cox regression models. SST/MSK – skin soft tissue/musculoskeletal. Mahmud et al. 2022.
- Adverse effects in patients with cirrhosis likely driven by alterations to the gut microbiome leading to bacterial translocation and impaired metabolism given hepatic impairment.
- A recent retrospective review at Northwestern and its affiliate hospitals found that only 58.2% of patients with cirrhosis on PPIs had an “appropriate” indication as defined by societal guidelines.
- Despite the evidence suggesting the adverse effects of PPIs in patients with cirrhosis, these patients are at higher risk of developing problems like GERD, peptic ulcer disease, and H. pylori.
What should we do?
- PPIs should not be avoided in cirrhosis but use should be limited to appropriate indications at lowest dose.
- Perform a thorough med rec on patients with cirrhosis and de-escalate PPI therapy if not indicated by societal guidelines.
- Stay posted for an upcoming Epic-based intervention to help address this!
| Indications | |||||
|---|---|---|---|---|---|
| Definitely indicated for long-term use (>8 wk) | Conditionally indicated for long-term use | Not indicated for long-term use | Definitely indicated for acute/short-term use (≤8 wk) | Conditionally indicated for acute/short-term use | Not indicated for acute/short-term use |
| Barrett’s esophagus Clinically significant (LA Classification grade C/D) erosive esophagitis Esophageal strictures from GERD (ie, peptic strictures) Zollinger-Ellison syndrome Eosinophilic esophagitis Gastroprotection in users of ASA/nonsteroidal anti-inflammatory drug at high risk for GI bleeding Prevention of progression of idiopathic pulmonary fibrosis |
PPI-responsive endoscopy-negative reflux disease, with recurrence on PPI cessation PPI-responsive functional dyspepsia, with recurrence on PPI cessation PPI-responsive upper airway symptoms ascribed to laryngopharyngeal reflux, with recurrence on PPI cessation Refractory steatorrhea in chronic pancreatic insufficiency with enzyme replacement Secondary prevention of gastric and duodenal peptic ulcers with no concomitant antiplatelet drugs |
Symptoms of nonerosive reflux disease with no sustained response to high-dose PPI therapy Functional dyspepsia with no sustained response to PPI therapy Steroid therapy in the absence of ASA/nonsteroidal anti-inflammatory drug therapy Prevention of recurrent upper GI bleeding from causes other than: Peptic ulcer disease, including gastric and duodenal erosions Erosive esophagitis |
Helicobacter pylori eradication Stress ulcer prophylaxis for ICU patients with risk factors Uninvestigated GERD/dyspepsia Treatment of NSAID-related gastric and duodenal peptic ulcers |
Initial or on-demand treatment of endoscopy-negative reflux disease Initial treatment of functional dyspepsia Uninvestigated dyspepsia Ulcer prevention after sclerotherapy or band ligation treatment of esophageal varices Prevention of rebleeding from Mallory-Weiss tears |
Empiric treatment of laryngopharyngeal symptomatology Acute undifferentiated abdominal pain Acute nausea and vomiting not believed to be related to GERD/esophagitis Any isolated lower GI symptomatology |
Table 1. Indications for Proton Pump Inhibitor Use. Targownik et al. 2022. ASA, aspirin; ICU, intensive care unit; LA, Los Angeles.
References
- Mahmud N, Serper M, Taddei TH, Kaplan DE. The Association Between Proton Pump Inhibitor Exposure and Key Liver-Related Outcomes in Patients With Cirrhosis: A Veterans Affairs Cohort Study. Gastroenterology. 2022 Jul 1;163(1):257-269.e6.
- Bajaj JS, Acharya C, Fagan A, White MB, Gavis E, Heuman DM, et al. Proton Pump Inhibitor Initiation and Withdrawal affects Gut Microbiota and Readmission Risk in Cirrhosis. Am J Gastroenterol. 2018 Aug;113(8):1177–86.
- Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022 Apr 1;162(4):1334–42.