Be careful with proton pump inhibitors, warns Peter Jepsen, medical specialist in liver diseases and senior researcher at Aarhus University. A newly published study shows that the altered acidic balance in the stomach can create an intestinal flora that advances liver damage.

2017.10.16 | Nanna Jespersgård

"We believe that many Danes receive proton pump inhibitors solely because of discomfort in the stomach, bile and/or heartburn.", says Peter Jepsen.

"Physicians ought to be more cautious with prescriptions for the type of gastric acid suppressants known as acid pump, or proton pump, inhibitors."

This is according to Peter Jepsen, medical specialist in liver diseases and senior researcher at the Department of Clinical Epidemiology, after he has been involved in mapping some of the unintended consequences of proton pump inhibitors in a new study.

The study, published in Nature Communications, shows that consumption of proton pump inhibitors can contribute to development of liver cirrhosis.

Peter Jepsen points to the fact that a wide range of medical specialities have turned their attention to the importance of intestinal flora in the development of disease. Most recently in the form of extensive discussion of the relationship between intestinal flora and diabetes – and now with liver cirrhosis added to the list of diseases where intestinal flora has an influence.

"Medicine containing acid or proton pump inhibitors that are known under names such as Lansoprazole and Pantoloc, are characterised by the fact that they alter the pH value in the stomach, which is what you want to achieve with the medicine. The problem is that the altered acidic balance provides better conditions for some of the bacteria that turn out to advance liver damage," says Peter Jepsen. 

Both animal and human studies

The Danish part of the study included all 4,830 Danes registered with a hospital diagnosis of hazardous alcohol consumption. No less than 21 per cent of them used proton pump inhibitors, and these people had a greater risk of developing cirrhosis of the liver than those who did not use them.

The analysis of Danish registry data was included as part of a predominantly American study carried out in collaboration between the Department of Clinical Epidemiology and the Department of Hepatology and Gastroenterology at Aarhus University Hospital and a research group at the University of California San Diego. The study builds primarily on animal studies that have clarified how the reduction in gastric acidity causes intestinal overgrowth of Enterococcus. These bacteria travel in the blood from the intestines to the liver, where they can contribute to the development of liver disease.

Bile or stomach ulcers?

Around one in ten people in Denmark takusee proton pump inhibitors, and only three per cent of the medicine is bought over-the-counter, meaning that general practitioners and hospital doctors in Denmark are mostly responsible for its use.

The problem with the proton pump inhibitors is reinforced by the fact that many of the prescriptions are likely given on an insufficient basis. Peter Jepsen and his fellow researchers therefore urge all physicians to restrict proton pump inhibitors for the treatment and prevention of ulcers and the treatment of severe reflux oesophagitis – a condition in which gastric acid from the stomach leaks back up to the oesophagus.

"We believe that many Danes receive proton pump inhibitors solely because of discomfort in the stomach, bile and/or heartburn. These people may be offered a four-week course of treatment with proton pump inhibitors, and if the treatment does not have an effect it should be terminated. If it has an effect it should be adjusted to the lowest effective dose and treatment breaks ought to be introduced to reassess the effect," says Peter Jepsen.

"Our message is not that ulcer medicine such as proton pump inhibitors should be done away with; rather, it is that in each individual case the physician ought to be able to explain to him or herself and to the patient why proton pump inhibitors are the right choice."

The research results – more information 

• Facts about the type of study: Translational research, register-based cohort study.
• Partners from Denmark and abroad: Project manager: Bernd Schnabl, University of California San Diego. Danish partners: Professor Henrik Toft Sørensen, Department of Clinical Epidemiology, Professor Hendrik Vilstrup, Department of Hepatology and Gastroenterology, Aarhus University Hospital.
• The Danish analysis has not received any earmarked funding, but is based on data already collected for other purposes. 
• The scientific article on which the press coverage is based on, is published in Nature Communications: https://www.nature.com/articles/s41467-017-00796-x

Contact

Specialty Registrar, Senior Researcher, PhD Peter Jepsen
Aarhus University, Department of Clinical Medicine, Department of Clinical Epidemiology
Aarhus University Hospital, Department of Hepatology and Gastroenterology.
Email: pj@clin.au.dk
Mobile: (+45) 2425 2944