At the annual American College of Gastroenterology (ACG) meeting in 2015, Allison Kasmari, M.D., internal medicine resident, Penn State Health Milton S. Hershey Medical Center, presented findings on behalf of a group of researchers, including Amy Welch, M.D., Thomas Riley, M.D., and Thomas McGarrity, M.D., demonstrating a significantly increased risk (35 percent) of hepatocellular carcinoma (HCC) among individuals with type II diabetes mellitus (DM) and hypertension (23 percent). Based on a retrospective review (2008-2012) of 7,473 patients with HCC using MarketScan, a U.S. insurance claims database, the largest increase in HCC risk (458 percent) was seen among patients with the triple combination of DM, hypertension and hepatitis C virus (HCV), compared to age-matched controls without such diseases (Table). The abstract findings were ranked among the top 10 from a total of more than 2,500 abstracts presented at the ACG meeting and were also featured on Medscape and in an ACG SmartBrief.
Based on prior reports indicating a link between DM and HCC risk,1,2 the researchers, also evaluated HCC risk with medications commonly used to treat DM and components of the metabolic syndrome. Insulin was associated with an increased risk of HCC, while metformin and cholesterol-lowering drugs were significantly protective, and sulfonylureas were neutral, suggesting that tight glycemic control and lipid reduction may mitigate some of the added risk of developing HCC with DM or metabolic syndrome. Dr. Riley adds, “These data confirm the importance of achieving good control of DM and the metabolic syndrome at the primary care level.”
Dr. Welch explains, “Successful treatment of HCC is linked to early detection, so it is important to identify key risk factors beyond known risks, like cirrhosis or hepatitis B virus.” Dr. Riley notes, “Currently, only patients with cirrhosis (any cause) or chronic hepatitis B infection are routinely screened for HCC. The findings raise the question of whether the HCC screening algorithm needs to evolve, to include other patient populations like those with HCV without cirrhosis, metabolic syndrome or diabetes.” Both Drs. Welch and Riley acknowledge that prospective, controlled, large-scale investigations are needed to properly define clinical features that may serve as thresholds where HCC case detection is improved.
“I hope our findings will be a call-to-action, challenging other researchers to join in an effort to identify criteria and clinical thresholds needed to develop a cost-effective HCC screening protocol,” Dr. Riley adds. “It’s impractical to screen every patient with type II DM or some feature of metabolic syndrome.” The benefit of early HCC detection must balance with costs and personal burden of screening. Further prospective work is needed to define the potential rate of accurate HCC case detection among the populations of patients with DM and various features of the metabolic syndrome, drilling down on specific patient and clinical features linked to HCC development.
Thomas R. Riley, III, M.D.
Professor of Medicine
Medical Director, Liver Transplantation
FELLOWSHIP: Gastroenterology and hepatology, University of Pittsburgh–University Health Center of Pittsburgh, Pittsburgh, Pa.
RESIDENCY: Internal medicine, University of Utah Hospital and Clinics, Salt Lake City, Utah
MEDICAL SCHOOL: The Ohio State University College of Medicine, Columbus, Ohio
Amy Welch, M.D., MSN, MSc
FELLOWSHIP: Gastroenterology, Penn State Health Milton S. Hershey Medical Center, Hershey, Pa.
RESIDENCY: Internal medicine, Penn State Health Hershey Medical Center, Hershey, Pa.
MEDICAL SCHOOL: Saba University College of Medicine, Dutch Caribbean, Netherlands
- Lai, S-W. Chen, P-C., Liao, K-F. Muo, C-H. Lin, C-C. Sung, F-C. 2012. Risk of Hepatocellular Carcinoma in Diabetic Patients and Risk Reduction Associated With Anti-Diabetic Therapy: A Population-Based Cohort Study. Am J Gastroenterol 107:46–52.
- El-Serag, H-B. Richardson, P-A. Everhart, J-E. 2001. The role of diabetes in hepatocellular carcinoma: a case-control study among United States veterans. Am J Gastroenterol. 96:2462–2467.