Published online Jun 27, 2019. doi: 10.4254/wjh.v11.i6.522
Peer-review started: January 17, 2019
First decision: March 5, 2019
Revised: April 26, 2019
Accepted: June 17, 2019
Article in press: June 17, 2019
Published online: June 27, 2019
Proton pump inhibitors (PPIs) are a recent hot topic in both internal medicine and gas-troenterology, mostly because of their widespread use. Studies are quickly demonstrating that these medications may not come without risk, as recent studies have demonstrated a clear association between PPI and conditions like osteoporosis, pneumonia, Clostridium difficile, and some even postulate an association with dementia. While many effects of PPIs are still in question, it has also been shown that PPIs work by acid suppression, which can disrupt the gut microbiome. Patients with cirrhosis are at risk to develop hepatic encephalopathy (HE), primarily through ammonia produced by typical gut flora, and could subsequently be at risk for changes in this condition if the microbiome is altered in any way.
The main topic we are trying to address is whether PPI overuse can lead to additional effects aside from those previously mentioned and described in the literature. One particularly vulnerable population is those with cirrhosis, as ammonia production is affected by the gut microbiome. Solving this problem would allow future therapeutics to focus on the gut-liver-microbiome axis to prevent or lessen the severity of HE.
The main objective we want to demonstrate is the effect of PPI on the degree of HE. We hope to draw an association between PPIs and HE to encourage further prospective research studies on the side effects of PPIs, the gut microbiome in relation to HE, and to further aid in hospital outcomes for patients with cirrhosis.
This is a retrospective analysis of patients with liver cirrhosis who were admitted with an ICD-9 and/or ICD-9 diagnosis of HE. Once these patients were identified, a chart analysis was performed to determine if these patients were on a PPI for > 30 d prior to their hospital admission. Those who were on a PPI for > 30 d were compared to patients who were not on a PPI at all in relation to their hospital stay. A linear regression model was applied to all patients to confirm the absence of any confounding variables.
During our analysis, we found that patients on a PPI who were admitted with HE subsequently had a significantly longer hospital stay, significantly worse grade of HE, and a larger percentage of those had intensive care unit (commonly known as ICU) admissions during their hospital stay. These findings suggest that patients should be assessed for the need for PPIs at every visit. This also points to the gap in knowledge between PPI and HE, especially if future research is able to demonstrate changes in the gut microbiome in patients on PPIs.
In summary, in this retrospective medical chart review, PPI use was shown to be associated with worsened HE, greater length of hospital stays, and higher rate of ICU admissions in cirrhotic patients. To our knowledge, this is the first study that demonstrated that PPI use is associated with worse grades of HE, whereas prior studies by Tsai et al and Hung et al demonstrated higher risk of HE and overall higher mortality, respectively, in an Asian population. We propose that PPI use might affect cirrhotic patients by altering gastric pH, leading to the proliferation of gut micro-biome, thereby increasing ammonia production and bacterial translation. Considering the recent increased prevalence of PPIs, this study provides clinically relevant information regarding their potential risks in the cirrhotic population.
As a retrospective review, our study is limited by incomplete data collection and uneven distribution of PPI user and non-user groups. However, the observation that PPI users experience worsen HE and longer hospital stays is clinically important. Future randomized-controlled studies will help confirm this observation and guide clinicians in a shift away from the use of PPI in cirrhotic patients.