A new study by Carle Illinois College of Medicine (CI MED) researchers sheds new light on the typical age at which the most common form of liver cancer occurs and on how early-onset disease responds to treatment. The research delivers the most comprehensive Western analysis to date of hepatocellular carcinoma (HCC) trends and is the first to establish a data-driven definition of early-onset HCC (eHCC). The results could lay the groundwork for more tailored screening and treatment strategies for liver cancers in younger adults.
HCC is an aggressive disease that accounts for about 90% of all cancers that begin in the liver. The five-year survival rate is about 18%. HCC can be hard to detect in its early stages before symptoms develop.
“Innovation in oncology starts with asking the right clinical questions,” said Dr. Claudius Conrad, senior author of the study, surgical oncologist, and CI MED’s Associate Dean of Research and Innovation. “We wanted to understand why early-onset HCC behaves differently and how we can give these younger patients the best possible outcomes.”
New insight into the epidemiology of liver cancer
CI MED researchers found that the overall incidence of HCC rose between 2010 and 2019, but interestingly, the proportion of cases in people under 50 declined — from 6.4% (2010–2014) to 4.1% (2015–2019). This diverges sharply from the growing rates of colorectal cancers in young adults and prompted a deeper investigation into the clinical behavior and risk factors associated with eHCC.
“The fact that early-onset HCC is declining even as other GI cancers rise speaks to the success of prevention—but also to the danger of clinical complacency,” Conrad said. “We must still identify and treat the patients who fall through the cracks.”
Defining early-onset HCC
Typically, HCC is diagnosed later in life. In analyzing more than 200,000 patient records, the team became the first to validate an age cut-off of under 50 years old as early-onset HCC, while defining the age range of typical onset (tHCC) as 50 and over. “Defining eHCC as occurring younger than age 50 years could have significant implications for future early-detection guidelines,” CI MED student and lead author Daniel Cheah said. Diagnosing liver cancer early is one factor that can improve patient survival rates.
Surgical opportunity in young patients
Despite often being diagnosed at more advanced stages, the research team found that younger patients with HCC have better outcomes after surgical resection. The research emphasizes the urgency of identifying surgical candidates early—especially among those with tumors at stage T3 or below.
“Surgery remains the most powerful tool we have for curing HCC,” Conrad emphasized. “When we catch early-onset cases in time, the liver's regenerative capacity and overall fitness in younger patients allows us to be aggressive and successful.”
Social and clinical factors
A history of viral hepatitis, liver cirrhosis, excess alcohol use, smoking, and obesity are all known risk factors for developing HCC at any time of life. But Cheah says his team’s analysis also found that social factors may play a role in early development. “Patients who are of minority race, uninsured, lower income, and greater distance from treatment centers are more likely to develop early-onset HCC. In the future, these social determinants combined with a deeper understanding of the specific tumor biology and epigenetics [how the patient’s environment and behaviors affect how genes work] of early-onset HCC could be the basis for effective screening for early-onset HCC,” Cheah said.
Co-author and CI MED student Kathryn Tsai says the next steps for researchers include delving further into the immunobiology underpinnings and the demographics that affect eHCC incidence. “In future studies, we hope to measure and characterize the dynamic changes of eHCC at molecular, multi-omic, and clinical levels,” Tsai said.
“Our discoveries for eHCC could have vast implications on treatment paradigms for neoadjuvant [pre-surgery] immunotherapy, an emerging, rapidly developing therapy that utilizes a patient’s own immune system to recognize and attack cancer cells,” Tsai said.
“This study is just the beginning,” Conrad said. “We are entering an era where liver cancer treatment will not only be age-aware, but biology-specific and potentially curable in ways we couldn’t have imagined a decade ago.”
Editor’s note: The international research team includes CI MED and Carle Health clinical experts, faculty members, and medical students. The study, “Are More Young, Western Patients Also Developing Hepatocellular Carcinoma?” is published in the Annals of Surgical Oncology, the leading journal in the field of surgical oncology. The research was authored by a team of CI MED students and faculty, including Daniel Cheah, Kathryn Tsai, and Helen Kemprecos with senior guidance from Drs. Mark Cohen and Claudius Conrad. https://doi.org/10.1245/s10434-025-17042-0
Researchers also authored the following reflection on their findings: https://link.springer.com/article/10.1245/s10434-025-17189-w