Proton Pump Inhibitors linked to liver disease, researchers find

Last updated: February 7, 2026Reviewed date: February 7, 2026Reading time: 4 min read

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Proton Pump Inhibitors linked to liver disease, researchers find?Researchers have found evidence that use of proton pump inhibitors (PPIs) may cause changes to gut bacteria that can promote liver disease. They also showed a link between liver damage from alcohol abuse and use of PPIs. Through a...

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Proton Pump Inhibitors linked to liver disease, researchers find?Researchers have found evidence that use of proton pump inhibitors (PPIs) may cause changes to gut bacteria that can promote liver disease.

They also showed a link between liver damage from alcohol abuse and use of PPIs.

Through a series of experiments in mice and humans, the team from University of California San Diego School of Medicine found that the absence of gastric acid promotes the growth of Enterococcus bacteria in the intestine.

The bacteria can then move to the liver, where they exacerbate infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation and worsen chronic liver disease, the researchers said.

In mouse models that mimic human alcoholic liver disease, the researchers used either genetic engineering or a PPI to block gastric acid production, then analysed stool samples to look at the gut microbiome.

The increase in Enterococcus bacteria in the mice with acid suppression were found to increase the progression of alcohol-induced liver disease, non-alcoholic fatty liver disease (NAFLD) and steatohepatitis.

In a separate study of 4,830 patients with a diagnosis of chronic alcohol abuse — 1,024 active PPI users, 745 were previous users, and 3061 who had never used PPIs — the researchers also found a link between PPI intake and increased stool concentrations of Enterococcus.

They also reported that the rate of liver disease in people who chronically abuse alcohol was 8.3% higher for those who actively use PPIs compared with those who never used the medicines.

Study leader Bernd Schnabl, associate professor of gastroenterology, said: “Our stomachs produce gastric acid to kill ingested microbes, and taking a medication to suppress gastric acid secretion can change the composition of the gut microbiome.

“Our findings indicate that the recent rise in use of gastric acid-suppressing medications might have contributed to the increased incidence of chronic liver disease.

“We believe clinicians should consider withholding medications that suppress gastric acid unless there is a strong medical indication.”

Collected

References

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^[2] Ford AC & Moayyedi P. Dyspepsia. The BMJ 2013;347:f5059. doi: 10.1136/bmj.f5059

^[3] Graham DY & Fischbach L. Helicobacter pylori treatment in the era of increasing bacterial infections. সহজ বাংলা: ব্যাকটেরিয়ার সংক্রমণের ওষুধ।" data-rx-term="antibiotic" data-rx-definition="An antibiotic is a medicine used to treat bacterial infections. সহজ বাংলা: ব্যাকটেরিয়ার সংক্রমণের ওষুধ।">antibiotic resistance. Gut 2010;59:1143–1153. doi: 10.1136/gut.2009.192757

^[4] Laine L. GI risk and risk factors of NSAIDs. J Cardiovasc Pharmacol 2006;47:S60–66. PMID: 16785831

^[5] Fitzgerald RC, di Pietro M, Ragunath K et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut 2014;63:7–42. doi: 10.1136/gutjnl-2013-305372

^[6] Forgacs I & Loganayagam A. Overprescribing proton pump inhibitors. The BMJ 2008;336:2–3. doi: 10.1136/bmj.39406.449456.BE

^[7] Neumann I, Letelier LM, Rada G et al. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Cochrane Database Syst Rev 2013;(6):CD007999. doi: 10.1002/14651858.CD007999

^[8] Hollingworth S, Duncan EL & Martin JH. Marked increase in proton pump inhibitors use in Australia. Pharmacoepidemiol Drug Saf 2010;19:1019–1024. doi: 10.1002/pds.1969

^[9] Haastrup P, Paulsen MS, Zwisler JE et al. Rapidly increasing prescribing of proton pump inhibitors in primary care despite interventions: a nationwide observational study. Eur J Gen Pract 2014;20:290–293. doi: 10.3109/13814788.2014.905535

^[10] McGowan B, Bennett K, Barry M et al. The utilisation and expenditure of medicines for the prophylaxis and treatment of fracture risk. সহজ বাংলা: হাড় দুর্বল হয়ে ভাঙার ঝুঁকি বেশি।" data-rx-term="osteoporosis" data-rx-definition="Osteoporosis means weak, fragile bones with higher fracture risk. সহজ বাংলা: হাড় দুর্বল হয়ে ভাঙার ঝুঁকি বেশি।">osteoporosis. Ir Med J 2008;101:38–41. PMID: 18450246

^[11] Ribolsi M, Savarino E, De Bortoli N et al. Reflux pattern and role of impedance-pH variables in predicting PPI response in patients with suspected GERD-related chronic cough. Aliment Pharmacol Ther 2014;40:966–973. doi: 10.1111/apt.12919

^[12] Schepisi R, Fusco S, Sganga F et al. Inappropriate use of proton pump inhibitors in elderly patients discharged from acute care hospitals. J Nutr Health Aging 2016;20:665–670. doi: 10.1007/s12603-015-0642-5

^[13] Haastrup PF, Rasmussen S, Hansen JM et al. General practice variation when initiating long-term prescribing of proton pump inhibitors: a nationwide cohort study. BMC Fam Pract 2016;17:57. doi: 10.1186/s12875-016-0460-9

^[14] Haastrup PF, Paulsen MS, Christensen RD et al. Medical and non-medical predictors of initiating long-term use of proton pump inhibitors: a nationwide cohort study of first-time users during a 10-year period. Aliment Pharmacol Ther 2016;44:78–87. doi: 10.1111/apt.13649

^[15] van den Bemt PM, Chaaouit N, van Lieshout EM et al. Noncompliance with guidelines on proton pump inhibitor prescription as gastroprotection in hospitalized surgical patients who are prescribed NSAIDs. Eur J Gastroenterol Hepatol 2016. doi: 10.1097/MEG.0000000000000634

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Safety note: This is not a prescription or diagnosis. For severe symptoms, pregnancy danger signs, children with serious illness, chest pain, breathing difficulty, stroke-like weakness, or major injury, seek urgent care.

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What to tell the doctor

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Questions to ask

What is the most likely cause of my symptoms?
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Which tests are necessary now, and which can wait?
How should I take medicines safely and what side effects should I watch for?
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Tests to discuss

Vital signs: temperature, pulse, blood pressure, oxygen saturation
Basic physical examination by a clinician
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Safe first steps

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For rural patients and family caregivers

Patient health record and symptom diary

Write your symptoms, medicines already taken, test results, and questions before visiting a doctor. This note stays on your device unless you print or copy it.

Doctor to discuss: Doctor / qualified healthcare provider

Tests to discuss with doctor

Basic vital signs: temperature, pulse, blood pressure, oxygen level if needed
Relevant blood, urine, imaging, or specialist tests only after clinical assessment

Questions to ask

What is the most likely cause of my symptoms?
Which warning signs mean I should go to emergency care?
Which tests are really needed now?
Which medicines are safe for my age, pregnancy status, allergy, kidney/liver/stomach condition, and current medicines?

Emergency warning signs such as chest pain, severe breathing difficulty, sudden weakness, confusion, severe dehydration, major injury, or loss of bladder/bowel control need urgent medical care. Do not wait for online information.

Go to emergency care if you notice:

Severe or rapidly worsening symptoms
Breathing difficulty, chest pain, fainting, confusion, severe weakness, major injury, or severe dehydration

Doctor / service to discuss: Qualified healthcare provider; specialist depends on symptoms and examination.

Step 1
Check danger signs first
If danger signs are present, seek emergency care and do not wait for online information.
Step 2
Record the symptom story
Write when symptoms started, severity, medicines already taken, allergies, pregnancy status, and test results.
Step 3
Visit a qualified clinician
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Step 4
Do only useful tests
Do tests after clinical assessment. Avoid unnecessary tests, random antibiotics, or repeated medicines without diagnosis.
Step 5
Follow up and return early if worse
If symptoms worsen, new warning signs appear, or treatment is not helping, return for review quickly.

Rural patient practical tips

Take a written symptom diary and all previous prescriptions/test reports.
Do not hide medicines already taken, even herbal or over-the-counter medicines.
Ask which warning signs mean urgent referral to hospital.

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