Chronic Hepatitis C Linked to Higher Pancreatic Cancer Risk: JAMA

Written By :  Medha Baranwal
Medically Reviewed By :  Dr. Kamal Kant Kohli
Published On 2025-11-27 15:15 GMT   |   Update On 2025-11-27 15:16 GMT
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USA: A large cohort study of over 6 million U.S. veterans, chronic hepatitis C virus infection significantly increases the risk of pancreatic ductal adenocarcinoma (PDAC). Even prior exposure to HCV—without chronic infection—was associated with a smaller but elevated risk. Because VA patients differ from the general population, external validation of these findings is necessary.

The study, published in
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JAMA Network Open
by Rachel N. Levinson and colleagues from Yale School of Medicine, offers one of the most comprehensive evaluations to date of the relationship between hepatitis C and pancreatic cancer. While HCV is known to be an oncovirus linked to several malignancies, its role in PDAC has remained unclear. This research sought to fill that gap and also examined whether different HCV genotypes carry distinct risks.
The retrospective cohort analysis drew on data from the Veterans Health Administration (VA), including individuals who had undergone HCV testing between 2001 and 2020. A total of 6,330,856 veterans were included, with a median age of 61.6 years. Among them, 246,218 had chronic HCV infection, and another 209,492 showed evidence of prior exposure without chronic disease. All participants were followed for at least 18 months after their initial VA visit.
The study led to the following findings:
  • A total of 33,451 individuals developed PDAC during the study period.
  • People with chronic HCV were diagnosed with PDAC at younger ages (median 65 years) compared with those without HCV (median 72.4 years).
  • After adjustment for demographic and clinical factors, chronic HCV infection was associated with a 76% higher risk of PDAC (adjusted HR 1.76).
  • Individuals with prior HCV exposure, but no chronic infection, still showed an 18% increased risk of developing PDAC.
  • Risk varied by viral genotype, with genotype 3 showing the highest risk (aHR 2.02).
  • Genotype 1 also carried a significantly elevated risk (aHR 1.75).
  • Genotype 2 was associated with a lower, but still meaningful, increased risk (aHR 1.35).
The authors emphasized that chronic HCV appears to be a potentially modifiable risk factor for pancreatic cancer, underscoring the importance of timely diagnosis and antiviral treatment. They also highlighted the need for continued scientific exploration into the mechanisms by which persistent viral infection may contribute to pancreatic carcinogenesis.
However, the study has limitations. Its largely male VA population may limit broader applicability, and factors such as military exposures, socioeconomic differences, and healthcare access were not fully captured. Misclassification of metastatic disease and possible surveillance bias from more frequent imaging in chronic HCV patients also remain concerns. Even so, sensitivity analyses confirmed the consistency of the results.
The study provides strong evidence that chronic HCV infection increases the likelihood of developing PDAC, with certain genotypes posing even higher risks. The authors call for future research examining how direct-acting antiviral therapy may reduce this risk and unravel the biological pathways linking HCV to pancreatic cancer.
Reference:
Levinson RN, Bushman R, Tate JP, et al. Pancreatic Ductal Adenocarcinoma After Hepatitis C Infection. JAMA Netw Open. 2025;8(11):e2543701. doi:10.1001/jamanetworkopen.2025.43701


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Article Source : JAMA Network Open

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