Yale Study Finds Association Between Chronic Hepatitis C and Pancreatic Cancer

Chronic hepatitis C virus (HCV) is linked to pancreatic cancer in a study of over 6 million US veterans. The findings were published in JAMA Network Open by researchers from Yale School of Medicine in New Haven, Connecticut.¹

Pancreatic ductal adenocarcinoma (PDAC) is the most common, aggressive type of pancreatic cancer, accounting for over 80% of all diagnoses. PDAC is a silent disease, often diagnosed by the time patients progress to advanced stages of disease when cancers are most difficult to treat. As of 2025, the 5-year survival rate for patients with PDAC is 13%. PDAC is the third leading cause of US cancer deaths, representing a significant need for better prevention and improved treatments.^2,3

PDAC is associated with multiple risk factors such as smoking, alcohol use, diabetes, obesity, history of chronic pancreatitis, and family history; however, hereditary risk factors for PDAC account for only 10% of all cases.^1,2,4

HCV is an oncovirus with established associations with various cancers including hepatocellular carcinoma, non-Hodgkin lymphoma, non-melanoma non-epithelial skin cancers, diffuse large B-cell lymphoma, and others. Now, emerging research shows HCV could also be a risk factor for PDAC.

“Several previous observations suggest that [HCV] may be a risk factor for PDAC,” the researchers wrote. “Increased HCV antigens have been found in pancreatic acinar cells. Pancreatic enzyme levels increase with worsening HCV-associated liver disease, suggesting a link between HCV and pancreatic inflammation, an established risk factor for PDAC progression.”

The Yale team performed a retrospective, national, population-based cohort study of 6,330,856 US veterans (5,841,571 men [92.3%]; median age, 61.6 years [49.9-70.1]) across Veterans Health Administration (VA) sites, of whom 246,218 (3.9%) had chronic HCV and 209,492 (3.3%) were exposed. Eligibility criteria included veterans with HCV testing documented in the VA or VA-linked Medicare with at least 1 inpatient or outpatient visit between October 1, 2001, and September 30, 2020.

Cox proportional hazards regression, adjusted for demographic and clinical confounders, were used to determine an association between HCV status and PDAC. The team categorized HCV status as chronic HCV, exposure to HCV, or no chronic HCV infection.

Among the 33,451 individuals in the study who developed PDAC—representing 0.5% of the full cohort—those with HCV infection were diagnosed at a significantly younger age than those without the virus. The median age at PDAC diagnosis was 65.0 years (IQR, 59.9–69.6) for individuals with HCV, compared with 72.4 years (IQR, 66.7–79.0) among those without HCV.

The analysis showed that HCV was consistently associated with a higher risk of developing PDAC. Compared with individuals who had no history of HCV infection, those with chronic HCV infection had a 76% higher risk of incident PDAC (adjusted hazard ratio [aHR], 1.76; 95% CI, 1.67–1.86). Even individuals with evidence of past HCV exposure and without confirmed chronic infection faced an elevated risk (aHR, 1.18; 95% CI, 1.11–1.25).

Notably, the research team found that risk also varied by viral genotype. HCV genotype 3 was linked to the highest risk of PDAC (aHR, 2.02; 95% CI, 1.67–2.45), followed by genotype 1 (aHR, 1.75; 95% CI, 1.64–1.87). Genotype 2 carried a more modest but still statistically significant increase in risk (aHR, 1.35; 95% CI, 1.14–1.60) compared with individuals without HCV infection.

Overall, the findings suggest that both chronic HCV infection and prior exposure meaningfully increase the likelihood of PDAC, with certain genotypes—particularly genotype 3—conferring the greatest risk.

Further research is needed to more firmly establish these findings as the study had some limitations, particularly a population limited to male veterans. The researchers suggest that preventing and treating HCV can reduce PDAC risk.

“Our findings suggest an independent association between chronic HCV infection and PDAC,” the team wrote. “Although future studies are needed to determine whether HCV treatment with [direct-acting antiviral] therapy partially or completely mitigates the observed PDAC risk, it is important to emphasize that untreated HCV is modifiable.”

REFERENCES

1. Levinson RN, Bushman R, Tate JP, et al. Pancreatic ductal adenocarcinoma after hepatitis C infection. JAMA Netw Open. November 14, 2025. doi:10.1001/jamanetworkopen.2025.43701

2. Pancreatic Ductal Adenocarcinoma Study. National Cancer Institute Center for Cancer Genomics. Accessed December 2, 2025. https://www.cancer.gov/ccg/research/genome-sequencing/tcga/studied-cancers/pancreatic-ductal-adenocarcinoma-study#:~:text=What%20is%20pancreatic%20cancer?,methods%20to%20deconvolute%20the%20data

3. Pancreatic cancer diagnoses and mortality rates climb; five-year survival rate for pancreatic cancer stalls at 13%. Pancreatic Cancer Action Network. January 16, 2025. Accessed December 2, 2025. https://pancan.org/press-releases/pancreatic-cancer-diagnoses-and-mortality-rates-climb-five-year-survival-rate-for-pancreatic-cancer-stalls-at-13/

4. Study shows link between Hepatitis C virus, multiple cancers. Baylor College of Medicine. January 26, 2017. Accessed December 2, 2025. https://www.bcm.edu/news/link-between-hepatitis-c-virus-cancers#:~:text=Your%20medical%20provider%20can%20give%20guidance%20on,Pancreas%20cancer%20*%20Non%2Dmelanoma%20non%2Depithelial%20skin%20cancers