PPIs and Liver Cancer Risk: A Complex Relationship

PPIs and Liver Cancer: What You Need to Know About the Risks

Mira Elwood in Health & Wellness December 2025 • 4 min read.

"Are your heartburn meds increasing your risk? Unpacking the latest research on PPIs and hepatocellular carcinoma."

Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide, primarily used to treat acid reflux, heartburn, and ulcers. These drugs, available both over-the-counter and by prescription, provide relief by reducing the amount of acid produced in the stomach.

However, as with many medications, concerns about potential long-term side effects continue to emerge. Recent studies have sparked debate over a possible association between PPI use and an increased risk of hepatocellular carcinoma (HCC), the most common type of liver cancer.

This article dives into the science behind these claims, examining the latest research, identifying potential risk factors, and offering practical guidance for individuals who rely on PPIs for managing their digestive health. Our goal is to provide a balanced perspective, helping you make informed decisions about your health in consultation with your healthcare provider.

The PPI-Liver Cancer Connection: What the Studies Say

PPIs and Liver Cancer Risk: A Complex Relationship

Several studies have explored the potential link between PPI use and the development of HCC. One study, by Shao et al., published in Alimentary Pharmacology & Therapeutics, found an association between PPIs and an increased risk of liver cancer. This prompted further investigation into the topic.

However, other research paints a more complex picture. A case-control study conducted in Taiwan by Lai et al. yielded different results, highlighting the challenges in drawing definitive conclusions about this potential association.

Study Design Matters: The conflicting results often stem from differences in study design, including cohort studies versus case-control studies. Each approach has its strengths and limitations, particularly when assessing long-term effects.
Time-Related Biases: Some studies may be affected by time-related biases, such as 'immortal time bias' or 'time-window bias,' which can skew the results. These biases occur when the opportunity for events (like cancer diagnosis) isn't comparable between groups or when the length of follow-up varies.
Population Differences: The prevalence of viral hepatitis (B and C) varies across populations, influencing HCC rates. In regions with high rates of viral hepatitis, like Taiwan, the primary drivers of HCC may differ from those in regions with lower rates.

It's important to remember that correlation doesn't equal causation. While some studies suggest an association, it doesn't necessarily mean that PPIs directly cause liver cancer. Other factors, such as lifestyle choices, genetics, and underlying health conditions, can also play a significant role.

Making Informed Decisions About PPI Use

The evolving research on PPIs and liver cancer risk underscores the importance of informed decision-making. If you're currently taking PPIs, especially for long-term management of acid reflux or other conditions, it's wise to discuss your concerns with your doctor. Together, you can weigh the benefits and potential risks based on your individual health profile and explore alternative strategies if necessary. Regular check-ups and open communication with your healthcare provider are key to ensuring your overall well-being.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1111/apt.14935, Alternate LINK

Title: Letter: Cohort Study Examining The Association Between Proton Pump Inhibitors Therapy And Risk Of Hepatocellular Carcinoma In Taiwan-Authors’ Reply

Subject: Pharmacology (medical)

Journal: Alimentary Pharmacology & Therapeutics

Publisher: Wiley

Authors: Yu-Hsuan Joni Shao, Szu-Yuan Wu

Published: 2018-08-21

Everything You Need To Know

What are Proton Pump Inhibitors (PPIs), and what do they do?

Proton Pump Inhibitors (PPIs) are medications frequently prescribed to treat conditions like acid reflux, heartburn, and ulcers. These drugs work by reducing the amount of acid produced in the stomach, offering relief from these conditions. They are available both over-the-counter and by prescription. The widespread use of PPIs makes understanding their potential long-term effects, such as the risk of hepatocellular carcinoma (HCC), crucial for individuals managing digestive health.

What does the research say about the link between PPIs and liver cancer?

Several studies have investigated the association between Proton Pump Inhibitors (PPIs) and the risk of liver cancer, specifically hepatocellular carcinoma (HCC). One study, by Shao et al., indicated an increased risk. However, a case-control study by Lai et al. presented different results. These conflicting findings emphasize the complexities of research in this area. It is important to note that these studies focus on correlation, not causation. The results show an association, not necessarily a direct causal link between PPI use and liver cancer.

Why do different studies on PPIs and liver cancer sometimes have conflicting results?

The conflicting results in studies examining the link between Proton Pump Inhibitors (PPIs) and liver cancer can be attributed to several factors. Study design is a key factor, with differences between cohort studies and case-control studies leading to varying conclusions. Additionally, time-related biases, such as 'immortal time bias' and 'time-window bias,' can skew results by affecting the comparability of event opportunities or follow-up durations among study groups. Population differences, especially in the prevalence of viral hepatitis (B and C), also influence hepatocellular carcinoma (HCC) rates, potentially impacting the generalizability of findings across different regions.

What are some crucial considerations for people taking PPIs long-term?

For individuals using Proton Pump Inhibitors (PPIs) long-term, it is vital to consider the evolving research on the potential risks, especially the connection with hepatocellular carcinoma (HCC). It is recommended to discuss concerns with a healthcare provider to assess the benefits and risks based on individual health profiles. Regular check-ups and open communication are key to monitoring overall well-being. Exploring alternative strategies and understanding individual risk factors are essential components of informed decision-making.

How can I make informed decisions about using PPIs if I am concerned about liver cancer risk?

To make informed decisions about using Proton Pump Inhibitors (PPIs) if you are concerned about the potential risk of liver cancer, consult with your healthcare provider. Discuss your individual health profile, including any pre-existing conditions, family history, and lifestyle factors. Consider the benefits of PPIs against the potential risks, especially the link to hepatocellular carcinoma (HCC). Explore alternative treatment options and discuss strategies for managing your digestive health. Regular monitoring, check-ups, and open communication with your healthcare provider are crucial for making well-informed decisions about your health.