Chronic HCV infection increases pancreatic ductal carcinoma risk

medwireNews: Chronic hepatitis C virus (HCV) infection doubles the risk for pancreatic ductal carcinoma (PDAC) relative to people without HCV, a study in US veterans concludes.

“In non-VA health settings in both the US and globally, costs and access to HCV testing and treatment are major barriers. Our study lends additional support for HCV treatment initiatives,” write Louise Wang (Yale School of Medicine, New Haven, Connecticut, USA) and colleagues in JAMA Network Open.

Data on 6,330,856 veterans in the Veterans Health Administration were assessed. Eligible participants had at least one inpatient or outpatient visit between October 2001 and September 2020, and the patients were followed up for at least 18 months.

The participants were at least 20 years old (median of 61.6 years), 92.3% were men, and 65.2% were non-Hispanic White.

A total of 3.9% had chronic HCV infection, indicated by a positive antibody and a positive viral load (>600 IU/mL or >600 copies/mL), positive genotype, or history of HCV treatment. A total of 3.3% were exposed to HCV, as indicated by a positive antibody only and negative viral loads.

HCV linked to earlier and increased PDAC risk

A total of 0.5% of the participants developed PDAC, with the median time to diagnosis being 3.9 years. Participants with chronic HCV had the highest age-adjusted PDAC incidence rate, with 107.69 cases per 100,000 person–years versus 67.97 and 51.92 cases per 100,000 person–years among participants exposed to HCV and without HCV, respectively.

Those with chronic HCV were diagnosed with PDAC at a younger age than those exposed to HCV infection and those without HCV infection (median=65.0, 68.5 and 72.4 years, respectively). The median time to death among patients with PDAC was similar across the groups, however, at 0.29, 0.31, and 0.32 years for those with chronic HCV, exposure to HCV and no infection, respectively.

After adjusting for demographic variables including age, sex, and race and ethnicity, patients with chronic HCV infection or HCV exposure continued to be more likely than uninfected individuals to develop PDAC, with respective adjusted hazard ratios (aHRs) of 1.76 and 1.18.

The factors with the strongest links to PDAC development included age, pancreatic cysts and pancreatitis, and male sex.

Although all HCV genotypes were associated with an increased risk for PDAC compared with no HCV infection, the incidence of PDAC was higher among those with HCV genotype 3 (61.1%) or 1 (6.4%) than those with genotype 2 (9.3%) or other genotypes (4–6 mixed; 1.0%). The aHRs for PDAC according to HCV genotype relative to no HCV were a corresponding 2.02, 1.75, 1.35, and 2.18.

“It is unknown whether this association is due to inherent differences in the pathogenicity of HCV genotypes or unmeasured confounding,” the researchers say.

Mechanisms and implications

The mechanisms linking HCV and PDAC are unclear and may include “chronic inflammatory changes and/or viral replication in the pancreas,” the investigators comment, advocating for more translational investigations of these potential mechanisms.

“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,” the researchers say, whereas most clinical risk factors linked to PDAC are either unmodifiable, such as age, or hard to treat, such as smoking or obesity.

In an invited commentary, En Cheng and colleagues, from the Albert Einstein College of Medicine in New York, USA, write that the study “provides encouraging evidence that targeting HCV infections may be a future study direction to lower pancreatic cancer risk.”

They remark that HCV screening rates remain low due to barriers including low socioeconomic status, lack of health insurance, limited healthcare coverage, lack of awareness about HCV infection, and social stigma.

To address these issues, the commentators suggest “helping uninsured and underinsured patients find health resources, implementing electronic medical record-based screening alerts, improving access through point-of-care testing and mobile clinics, and providing education materials to increase awareness and combat stigma.”

They conclude: “Of particular interest related to this study, future studies should investigate whether HCV screening and treatment may be associated with lower risk of pancreatic cancer.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature

JAMA Netw Open 2025; 8: e2543701
JAMA Netw Open 2025; 8: e2543710