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Blocking stomach acid may promote chronic liver disease (2017-11-08)

A new study found that the proton pump inhibitors (PPIs), blocking stomach acid can lead to an overgrowth of intestinal bacteria that likely contributes to liver inflammation and damage.
The findings suggest that some widely used acid reflux (heartburn) medications may worsen chronic liver disease.

In mice, some common acid reflux medications promote growth of Enterococcus bacteria, shown here artificially glowing red, in the intestines. These bacteria can move to the liver and affect its function. UC San Diego Health.

The liver has many important functions, including helping to digest food and process and distribute nutrients.

A healthy liver is necessary for survival.
The liver can regenerate after being damaged. However, repeated or long-lasting injury can cause scar tissue to form.

Scarring of the liver may lead to cirrhosis, a condition in which the liver is unable to function normally.

Liver cirrhosis is a leading cause of death worldwide.

Many conditions can contribute to the development of cirrhosis, including obesity, which is associated with non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH), a form of NAFLD in which you also have inflammation and liver cell damage.

But alcohol misuse accounts for about half of cirrhosis-related deaths.

Changes in your gut’s microorganisms, or microbiota, can affect the progression of liver disease.

Misusing alcohol alters the microbes in your gut.
So can a commonly used class of heartburn medication called proton pump inhibitors (PPIs), which block stomach acid secretion.

PPIs are often used by people who have chronic liver disease, however, the impact of these medications on liver disease progression has been unknown.

To investigate whether blocking stomach acid affects chronic liver disease, a team led by Dr. Bernd Schnabl at the University of California San Diego School of Medicine looked at PPIs in mouse models of three types of liver disease—alcohol-induced liver disease, NAFLD, and NASH—and in humans.

The team blocked stomach acid in the mice either by genetically deleting the gene that controls stomach acid secretion or by administering the PPI omeprazole (Prilosec).

Liver conditions in all three disease models were worsened when the mice lacked stomach acid.

The researchers found that mice lacking stomach acid had higher levels of intestinal bacteria as well as imbalances among the microbes.

In particular, the mice had increased levels of Enterococcus in their guts.

Further experiments suggested that these bacteria can reach the liver, where they can cause liver inflammation and damage.

In a previous study (Link...) researchers examined data of 188,323 exposed to ASMs (proton pump inhibitors PPIs, and H2 receptor antagonists H2RA) and 376,646 who were not exposed to ASMs between 1999 and 2013.

Compared to people who didn’t use the drugs, those who did were at higher risk for a severe form of diarrhea caused by the Clostridium difficile bacteria.
Their odds of this infection were 1.4 times higher when they were hospitalized and 1.7 times higher when they weren’t in the hospital.

In addition, PPI users had a 4.5 times greater risk of getting Campylobacter infections, a common form of food poisoning, if they were hospitalized and a 3.7 times higher risk when they weren’t hospitalized.

Researchers also tested for Salmonella, Shigella and Escherichia coli, but didn’t find an association between PPIs and these infections.

In the new study the team looked at whether also people taking PPIs have increased levels of Enterococcus in their guts.

They collected fecal samples from healthy people before and after PPI treatment.

After two weeks, those taking the PPI treatment also had a higher number of Enterococcus.

The researchers next investigated whether there might be a link between PPIs and the development of alcoholic liver disease.

They looked at 4,830 patients with a diagnosis of alcohol use disorder.

Among these, 36% had been using PPIs.
The analysis showed that PPI use increased the 10-year risk of developing liver disease (20.7% for active users; 16.1% for previous users; 12.4% for those who had never used PPIs).

Proton pump inhibitors (PPIs) have also been shown to be potentially involved in cognitive decline  in a study of the German Center for Neurodegenerative Diseases in Bonn, Germany (Link...)

“Our findings indicate that the recent rise in use of [stomach] acid-suppressing medications might have contributed to the increased incidence of chronic liver disease,” Schnabl says, “We believe clinicians should consider withholding medications that suppress [stomach] acid unless there is a strong medical indication.”

See also
Heartburn pills tied to bacterial gastroenteritis (2017-01-22)

Popular heartburn pills known as proton pump inhibitors (PPIs) tied to greater mortality (2017-07-24)

For more information
Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus.
Llorente C, Jepsen P, Inamine T, Wang L, Bluemel S, Wang HJ, Loomba R, Bajaj JS, Schubert ML, Sikaroodi M, Gillevet PM, Xu J, Kisseleva T, Ho SB, DePew J, Du X, Sørensen HT, Vilstrup H, Nelson KE, Brenner DA, Fouts DE, Schnabl B. Nat Commun. 2017 Oct 16;8(1):837. doi: 10.1038/s41467-017-00796-x. PMID: 29038503.

NIH U.S. National Institutes of Health