Chronic Hepatitis C Linked to Increased Risk of Pancreatic Cancer, New Study Shows

A new study from Yale School of Medicine researchers found a positive link between chronic hepatitis C and pancreatic cancer. The study, which was published in JAMA Network Open, revealed that individuals with chronic hepatitis C virus (HCV) infection have a 1.8-fold increased risk of pancreatic cancer compared to those who test negative for the virus. In comparison, well-known risk factors, like diabetes or active smoking, increased the likelihood of pancreatic cancer by 1.2- or 1.3-fold.

“These findings suggest that chronic HCV is a strong, potentially modifiable risk factor for pancreatic cancer, even after adjusting for other risk factors, like tobacco smoking, liver disease, and alcohol use,” says Louise Wang, MD, assistant professor of medicine (digestive diseases) and senior author of the paper. “Pancreatic cancer is the third leading cause of cancer deaths in the United States, making it critical to explore any strategy that could help reduce the risk of pancreatic cancer and enhance early detection.”

The retrospective cohort study included approximately 6.3 million individuals who received HCV testing through the Veterans Health Administration (VA). Wang and her colleagues analyzed objective longitudinal data from each patient, such as documented evidence of a positive viral load, genotype, or treatment for hepatitis C. Unlike traditional study designs that look at a specific point in time, the researchers randomized each patient’s index date to capture the random risk a veteran would have when they walk into a clinic.

“Pancreatic cancer is not common, so having access to extensive databases like the one at the VA is invaluable in identifying risk factors that may help the medical community connect higher-risk individuals to targeted screening and surveillance,” says Wang. “I’m very grateful for the generous investment from the VA that allows us to conduct projects like this that will inform patient care across the country.”

There are some limitations to using VA data, as the population is predominantly male. Additionally, since all individuals included in the study had access to similar health care provided through the VA, the study may not fully account for the influence of access to health care and/or socioeconomic status.

The study also found that individuals exposed to hepatitis C, but who did not develop a chronic infection, had a slightly increased risk of pancreatic cancer. Wang notes that future investigations will investigate whether treatment of HCV mitigates some of the risk of exposure to the virus. Modern HCV treatment includes an 8- 12-week regimen of direct-acting antivirals, which have an approximately 95% cure rate.

“The VA has focused on screening every veteran for HCV, and as a result, more than 75% of veterans receiving care at the VA have undergone this screening,” says Wang. “I hope this research encourages broader HCV screenings across the general population to help mitigate the risk of liver-based cancers, pancreatic cancers, and possibly other types of hepatobiliary cancers.”

In addition, the study found that individuals with certain genetic variations of hepatitis C, namely genotype 1 and 3, have a slightly increased risk compared with genotype 2. Genotype 1 is the most common genotype in the U.S. Wang says additional research is needed to understand if this is a true biological risk or if it results from other unmeasured factors.

Wang and her colleagues are also investigating if other electronic health record (EHR)-based biomarkers, like laboratory information, body mass index, or medications, correlate with subtle changes that could signal pancreatic cancer up to five years prior to eventual diagnosis. They aim to build predictive models in large EHR databases such as the VA and EPIC Cosmos to better understand the risk of pancreatic cancer and the series of events that lead to its development.

“Most people with pancreatic cancer are not diagnosed until the disease has progressed to advanced stages,” Wang says. “If we can better understand a person’s risk for the disease, we can enhance early detection and help improve patient outcomes.”

The paper’s first author is Rachel Levinson, MD, a former Yale medical student who is now a resident at Brigham and Women’s Hospital. Other study authors include: Ryan Bushman, MS; Janet P. Tate, MPH, ScD; Melissa Skanderson, MSW; Catherine Mezzacappa, MD, MPH; Lesley S. Park, PhD, MPH; Cynthia A. Brandt, MD, MPH; Kevin M. Schuster, MD, MPH; Gyanprakash A. Ketwaroo, MD, MSc; Yu-Xiao Yang, MD, MSCE; and Amy C. Justice, MD, PhD.

Digestive Diseases, one of 10 sections in the Yale Department of Internal Medicine, is committed to advancing the science and practice of gastroenterology and hepatology through extensive laboratory and clinical research, comprehensive training for future leaders in liver and gastrointestinal disorders, and the delivery of state-of-the-art patient care. To learn more, visit Digestive Diseases.