A retrospective, national, population-based cohort study of 6.3 million veterans, which was published in JAMA Network Open, found that individuals with chronic hepatitis C virus developed pancreatic ductal adenocarcinoma at younger ages and had a higher risk compared with those without the infection. According to Levinson et al, risk also varied by virus genotype.
“These findings suggest that chronic hepatitis C virus is a potentially modifiable risk factor for pancreatic cancer,” the investigators commented.
Study Details
The investigators focused on 6,330,856 veterans (male: n = 5,841,571 [92.3%]; median age = 61.6 years) who underwent hepatitis C virus testing, with records in the Veterans Health Administration (VA) or VA-linked Medicare systems, and who had at least one inpatient or outpatient visit between October 2001 and September 2020. After this visit, patients were followed up for at least 18 months.
The association between hepatitis C virus status and pancreatic ductal adenocarcinoma was assessed using Cox proportional hazards regression, with adjustments for demographic and clinical confounders. The analysis was substratified by hepatitis C virus genotype.
Key Findings
A total of 246,218 (3.9%) and 209,492 (3.3%) individuals had chronic hepatitis C virus and were exposed, respectively. In the 33,451 who developed pancreatic ductal adenocarcinoma (0.5%), the age at diagnosis was younger among those with vs without hepatitis C virus infection (median age = 65.0 vs 72.4 years).
Compared with no hepatitis C virus infection, chronic infection (adjusted hazard ratio [HR] = 1.76, 95% confidence interval [CI] = 1.67–1.86) and exposure (adjusted HR = 1.18, 95% CI = 1.11–1.25) were found to be associated with an increased risk of incident pancreatic ductal adenocarcinoma. All hepatitis C virus genotypes appeared to be associated with an increased risk of pancreatic ductal adenocarcinoma, with hazards in the following order: other or mixed genotype (adjusted HR = 2.18, 95% CI = 1.43–3.31), genotype 3 (adjusted HR = 2.02, 95% CI = 1.67–2.45), genotype 1 (adjusted HR = 1.75, 95% CI = 1.64–1.87), and genotype 2 (adjusted HR = 1.35, 95% CI = 1.14–1.60).
“In this cohort study of veterans, chronic hepatitis C virus infection was associated with a 1.8-fold higher risk of pancreatic ductal adenocarcinoma diagnosis, and hepatitis C virus genotypes 3 and 1 had greater pancreatic ductal adenocarcinoma risk than genotype 2,” the investigators wrote.
They concluded, “Future work should focus on the impact of direct-acting antiviral treatment for hepatitis C virus on risk mitigation of pancreatic ductal adenocarcinoma and mechanisms of pancreatic ductal adenocarcinoma carcinogenesis related to chronic hepatitis C virus infection.”
Louise Wang, MD, MSCE, of Yale School of Medicine, New Haven, Connecticut, is the corresponding author of the article in JAMA Network Open.
Disclosure: The study was funded by the Veterans Health Administration and Yale School of Medicine. For full disclosures of the study authors, visit jamanetwork.com.
