What are the causes of elevated Carbohydrate Antigen 19-9 (CA 19.9)?

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Last updated: March 22, 2025View editorial policy

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From the Guidelines

Elevated Carbohydrate Antigen 19-9 (CA 19-9) levels can be caused by various malignant and benign conditions, including pancreatic cancer, biliary tract cancers, colorectal cancer, gastric cancer, and benign conditions such as pancreatitis, cholangitis, and liver cirrhosis, as supported by the most recent study 1. The causes of elevated CA 19-9 levels are diverse and can be attributed to both malignant and benign conditions.

  • Malignant causes include:
    • Pancreatic cancer
    • Biliary tract cancers (cholangiocarcinoma, gallbladder cancer)
    • Colorectal cancer
    • Gastric cancer
    • Ovarian and lung cancers
  • Benign causes include:
    • Pancreatitis (both acute and chronic)
    • Cholangitis
    • Cholecystitis
    • Liver cirrhosis
    • Inflammatory bowel diseases like ulcerative colitis and Crohn's disease
    • Non-gastrointestinal conditions such as endometriosis, pneumonia, and pleural effusions It is essential to note that approximately 5-10% of the population cannot produce CA 19-9 due to genetic factors (Lewis antigen-negative individuals), which can lead to false negatives 1. The degree of elevation often correlates with disease severity, with malignancies typically causing higher elevations than benign conditions, though there is significant overlap 1. In clinical practice, it is crucial to interpret CA 19-9 levels in the context of the patient's overall clinical presentation and medical history, and to consider further diagnostic testing and evaluation by an experienced multidisciplinary team when CCA is suspected, as recommended by the most recent guidelines 1.

From the Research

Causes of Elevated Carbohydrate Antigen 19-9 (CA 19.9)

Elevated CA 19.9 levels can be caused by various conditions, including:

  • Malignant diseases such as pancreatic, gastric, and hepatobiliary cancers 2, 3, 4
  • Benign diseases of the hepatobiliary system, including cholangitis, cholestasis, and choledocholithiasis 2, 5, 6
  • Other benign conditions such as pneumonia, pleural effusion, renal failure, and systemic lupus erythematosus (SLE) 4
  • Non-malignant and non-cholestatic diseases, as seen in a study where 10 patients with elevated CA 19-9 levels had no evidence of malignant disease 3
  • Xanthogranulomatous cholecystitis, a rare benign condition that can cause significantly elevated CA 19-9 levels 6

Benign Conditions Associated with Elevated CA 19-9

Some benign conditions that can cause elevated CA 19-9 levels include:

  • Cholangitis, which can cause elevated CA 19-9 levels, especially in patients with choledocholithiasis 5
  • Cholestasis, which can also cause elevated CA 19-9 levels 2
  • Choledocholithiasis, which can cause elevated CA 19-9 levels, especially in patients with cholangitis 5
  • Pulmonary fibrosis, diabetes, non-ulcer dyspepsia, obesity, acute diarrhea, colon diverticula, and gastric ulcer, which were seen in a study of 10 patients with elevated CA 19-9 levels and no evidence of malignant disease 3

Importance of Clinical Context

It is essential to interpret elevated CA 19-9 levels in the context of the patient's clinical presentation, as elevated levels can be found in both malignant and benign conditions 2, 4, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Persistent elevation of serum CA 19-9 with no evidence of malignant disease.

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2009

Research

The clinical significance of elevated levels of serum CA 19-9.

The Medical journal of Malaysia, 2003

Research

Relationship of CA 19-9 with choledocholithiasis and cholangitis.

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 2011

Research

[Elevated CA19-9 levels; not always cancer].

Nederlands tijdschrift voor geneeskunde, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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