Diabetes Mellitus and Metabolic Syndrome—Independent Risk Factors for Hepatocellular Carcinoma

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.

Odds Ratio of Hepatocellular Carcinoma, Cases vs. Controls

MarketScan database 2008-2012, 56 million patients annually. Cases N=7,473; controls N=22,110; excluded were cases with hepatitis B, cirrhosis, alcoholic liver damage and nonalcoholic fatty liver disease and steatohepatitis, alpha-1 antitrypsin deficiency, autoimmune hepatitis and Wilson’s disease.

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.

View the ACG meeting presentation on these findings.

Thomas R. Riley, III, M.D.Thomas R. Riley, III, M.D.
Professor of Medicine
Medical Director, Liver Transplantation
PHONE: 717-531-6261
E-MAIL: triley@hmc.psu.edu
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

Connect with Thomas R. Riley, III, M.D. on Doximity

Amy Welch, M.D., MSN, MSc Amy Welch, M.D., MSN, MSc
Gastroenterology Fellow
PHONE: 717-531-6261
E-MAIL: awelch@hmc.psu.edu
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

Connect with Amy Welch, M.D. on Doximity


  1. 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.
  2. 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.

Leave a comment

Filed under Disorders, Treatments

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s