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Is Liver Cancer a Risk of Acid-Suppressing Drugs?

Proton pump inhibitors (PPIs) like Nexium and Prilosec can prevent heartburn and heal ulcers. But they do have some frightening side effects and might even promote liver cancer.
Is Liver Cancer a Risk of Acid-Suppressing Drugs?
A woman holds the liver. Pain in the abdomen. Cirrhosis of the liver. Sore point highlighted in red. Closeup. Isolated.

Not again! We are sick and tired or reading about another potentially serious side effect of proton pump inhibitors (PPIs). Over the last few decades the list of very worrisome adverse reactions has grown substantially. Now, a group of researchers in Taiwan have reported a possible relationship between long-term PPI use and liver cancer (hepatocellular carcinoma abbreviated HCC). That is not welcome news.

PPIs Are Super Popular:

There was a time when people swallowed antacids when they had heartburn. Old timers would put a little baking soda (sodium bicarbonate) in a glass of water, stir and swallow. It was cheap and fast. Then along came drugs like Alka-Seltzer, Tums, Rolaids, Maalox and Mylanta. They were available over the counter and were very popular.

Then came the H2 antagonists. They suppressed acid somewhat. In their day they were very high on the doctors’ hit parade of most popular drugs. We’re talking about cimetidine (Tagamet), famotidine (Pepcid) and ranitidine (Zantac). When the patents expired on these prescription drugs, they went over the counter and lost their luster with physicians.

Enter proton pump inhibitors. Drugs like omeprazole (Prilosec) and esomeprazole (Nexium) became doctors’ favorites. It took no time at all for these acid suppressing drugs to become the go-to treatment for digestive upset. People were prescribed PPIs for acid reflux, heartburn, indigestion, stomach ulcers and just about anything else affecting the upper GI tract.

People taking nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis, strains and sprains are often told to take a PPI to protect the stomach from damage. The hope is that suppressing acid will prevent NSAID-caused lesions from turning into dangerous ulcers.

In 2015 (the most recent data we have), roughly 25 million people received a prescription for a PPI, adding up to more than 117 million prescriptions. That does not include use of over-the-counter drugs such as esomeprazole (Nexium 24HR), lansoprazole (Prevacid 24HR) and omeprazole (Prilosec OTC).

How Safe Are PPIs?

Such acid-suppressing drugs have long been considered among the safest medications in the pharmacy. That is why the FDA decided 15 years ago that Prilosec could be sold without a prescription.

Physicians are beginning to worry about over-utilization of these drugs, however (Therapeutic Advances in Gastroenterology, July 2012). There is growing evidence that long-term use of PPIs may carry some serious safety problems that weren’t anticipated when the drugs were first launched.


Stomach acid is strong, and it kills many types of bacteria. When acid is suppressed, people may develop infections. Higher rates of both pneumonia and Clostridium difficile, an intestinal infection, are linked to PPI use. In addition, these drugs can change the balance of bacteria in the digestive tract (Digestive Disease and Sciences, online, May 24, 2018).  This disruption in the ecology of the intestines may in part contribute to these infections (Gut, May, 2016).

Nutritional Deficiencies:

Other unexpected complications of prolonged use of PPIs include nutritional deficiencies. Changing the pH of the stomach may lead to lower levels of magnesium, iron, zinc, calcium and vitamin B12. As a result, users may have an increased risk of osteoporosis and fractures (Osteoporosis International, April 2013).

Kidney Disease:

Another serious adverse reaction associated with these potent acid-suppressing drugs is kidney disease. There is growing evidence that long-term use of PPIs can damage the kidneys (Nephrologie & Therapeutique, April, 2018).  Clinicians have been encouraged to monitor kidney function of patients on prolonged PPI therapy.

Heart Problems:

More controversial is the link between these acid-suppressing drugs and cardiovascular health. Researchers have reported a connection between PPIs and heart attacks (PLoS One, June 10, 2015).  Other investigators have found no such risk, however (Gastroenterology, March, 2018).

Strokes, Dementia and Liver Cancer:

People taking anti-platelet drugs to prevent blood clots (clopidogrel, prasugrel, ticlopidine) may be at increased risk of both heart attacks and strokes if they also take PPIs (Stroke, Feb. 2018). Other controversial complications include reports of dementia, Alzheimer disease and liver cancer (Alimentary Pharmacology & Therapeutics, July 2018).

Although such research is scary, it should not discourage people from taking PPIs when they are essential. But doctors are being encouraged to prescribe such drugs only when absolutely necessary. We hope that people who take OTC acid-suppressing drugs without medical supervision are equally cautious.

It’s Hard to Stop PPIs:

People who get into a PPI habit often find it hard to stop cold turkey. That’s because of something called rebound hyperacidity.

When you suppress acid formation in the stomach with PPIs, the body tries to compensate. It attempts to make acid but is thwarted by the medicine. Once the acid-suppressing drug is stopped, however, the stomach starts churning out lots of acid. This can lead to unbearable heartburn that can last days or weeks.

When symptoms return with a vengeance, many people reach for their PPI. This can lead to a vicious cycle. It’s hardly any wonder that some people remain on PPIs for years or even decades.

Liver cancer is probably a relatively low risk of long-term PPI use. And for some, the benefits of the drugs outweighs the danger. For others, though, it would be wise to discuss the pros and cons of PPIs with a physician. Liver cancer is challenging. Even a small increased risk would be worrisome.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
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