Liver

This page looks at research of whether Liver Disease is related to PPI usage.

Studies are shown below in chronological order.


N.B. Summary & conclusions to follow.

13 December 2016 The Impact of Proton Pump Inhibitor Therapy on Patients With Liver Disease "There was no statistically significant difference in survival between patients who were prescribed a PPI at assessment and those who were not.

Conclusion: Associations between PPI use, encephalopathy and higher MELD scores imply caution should be exercised in prescribing gastric acid suppressants to patients with cirrhosis, particularly in the absence of clear indications." (Alimentary pharmacology & therapeutics)


May 2017 Risk of progression of Barrett's esophagus in patients with cirrhosis. "Cirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients." (world Journal of Gastroenterology)


10 October 2017 Popular Acid Reflux Drugs Promote Chronic Liver Disease "The researchers concluded that there is an association between PPI use among people who abuse alcohol and risk of liver disease. However, they can't yet rule out the possibility that there could be other unidentified factors that differ between patients that do and do not take PPIs, which might confound the relationship between PPI use and liver disease." (Genetic Engineering & Biotechnology News)


23 October 2017 Nonalcoholic Fatty Liver Disease Is Associated with Increased Risk of Reflux Esophagitis. "In this large cohort of Korean men and women, participants with NAFLD exhibited increased incidence of reflux esophagitis independent of possible confounders, suggesting that NAFLD contributes to the development of reflux esophagitis." (Digestive Diseases & Sciences)


12 November 2017 Nonalcoholic Fatty Liver Disease and the Development of Reflux Esophagitis: A Cohort Study. "NAFLD is not independently associated with the risk of the development of reflux esophagitis, but rather reflux esophagitis is primarily the consequence of increased BMI commonly associated with NAFLD" (Journal of Gastroenterology and hepatology)


December 2017 Association between gastroesophageal reflux disease and nonalcoholic fatty liver disease: A meta-analysis. "A significantly increased risk of NAFLD among patients with GERD was observed in this meta-analysis." (Saudi Journal of gastroenterology)


9 May 2018 Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies. "In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. Ever use of PPIs was associated with increased liver cancer risk. ... Whether this association is causal or reflects residual confounding or reverse causation requires additional research." (Alimentary Pharmacology & Therapeutics"


2 August 2018 Proton Pump Inhibitor and Histamine–2 Receptor Antagonist Use and Risk of Liver Cancer in Two Population–Based Studies "We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research." (Alimentary Pharmacology & Therapeutics)


March 2019 The Dark Side of the Long-Term Use of Proton Pump Inhibitors in Chronic Liver Disease "In recent years, several observational studies have raised concern regarding the potential long-term side effects of PPIs, including acute and chronic kidney disease, hypomagnesemia, cardiovascular events, bone fractures, dementia, and infections such as Clostridium difficile colitis, bacterial pneumonia, and spontaneous bacterial peritonitis (SBP). ... However, as pointed out by most studies, correlation does not imply causation. Furthermore, even if the risk of overall infections may be higher, there does not appear to be a signal for increased mortality associated with PPI use." (Portuguese Journal of Gastroenterology)

https://pubmed.ncbi.nlm.nih.gov/31170742/

6 June 2019 [Proton pump inhibitors in patients with liver cirrhosis - a survey among hepatologists in Germany] "PPI are frequently prescribed among patients with liver cirrhosis in Germany. Prescribers are aware of an unclear risk-benefit ratio. Further prospective data are urgently needed to increase evidence regarding indication and duration of PPI therapy in patients with cirrhosis." (Zeitschrift für Gastroenterologie)


24 July 2019 Non alcoholic fatty liver disease increases the risk of gastroesophageal reflux disease: A systematic review and meta-analysis "NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD." (European Journal of clinical investigation) GERD not PPI


7 September 2019 Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis "PPI use in decompensated cirrhosis is associated with increased risk of mortality and hepatic decompensation. Longer PPI exposure with cDDD [cumulative defined daily dose] > 90 increases the risk of mortality." (World Journal of Gastroenterology)


2019 Proton Pump Inhibitors "Side effects of PPIs are uncommon, usually mild, and include nausea, abdominal discomfort, constipation, flatulence and diarrhea. Less common side effects include myopathy, arthralgias, headaches and skin rash. Rare instance of acute liver injury have been reported with most of the PPIs. In view of the wide scale use of the PPIs, clinically apparent liver injury is exceedingly rare. " (LiverTox)



17 April 2020 Proton pump inhibitors in chronic liver disease: accomplice or bystander? "In the post-hoc analysis of a recently published randomized double blinded controlled trial of 17,598 PPI vs. non-PPI user (median follow-up of 3.01 years) that looked at the cardiovascular events as the primary outcome, it showed that all the alleged PPI-related adverse effects, except enteric infections, were not significantly different between PPI users and non-PPI users" (Hepatology International)