title: Independent of Cirrhosis, Hepatocellular Carcinoma Risk Is Increased with Diabetes and Metabolic Syndrome.
abstract: Hepatocellular carcinoma is the most common primary liver malignancy, commonly a sequelae of hepatitis C infection, but can complicate cirrhosis of any cause. Whether metabolic syndrome and its components, type II diabetes, hypertension, and hyperlipidemia increase the risk of hepatocellular carcinoma independent of cirrhosis is unknown.
  
  
  
  A retrospective cohort study was conducted using the MarketScan insurance claims database from 2008-2012. Individuals with hepatocellular carcinoma aged 19-64 years and age and sex-matched controls were included. Multivariate analysis of hepatocellular carcinoma risk factors was performed.
  
  
  
  Hepatitis C (odds ratio [OR] 2.102) was the largest risk factor for hepatocellular carcinoma. Other independent risk factors were type II diabetes (OR 1.353) and hypertension (OR 1.229). Hyperlipidemia was protective against hepatocellular carcinoma (OR 0.885). The largest risk increase occurred with hypertension with type II diabetes and hepatitis C (OR 4.580), although hypertension and type II diabetes without hepatitis C still incurred additional risk (OR 3.399). Type II diabetes and hyperlipidemia had a similar risk if hepatitis C was present (OR 2.319) or not (OR 2.395). Metformin (OR 0.706) and cholesterol medications (OR 0.645) were protective in diabetics. Insulin (OR 1.640) increased the risk of hepatocellular carcinoma compared with the general type II diabetes population.
  
  
  
  In the absence of cirrhosis, type II diabetes and hypertension were independent risk factors for hepatocellular carcinoma. Hyperlipidemia and medical management of type II diabetes with metformin and cholesterol medication appeared to reduce the incidence of hepatocellular carcinoma. In contrast, insulin was associated with a higher risk of hepatocellular carcinoma.
authors.affiliation: Department of Internal Medicine, Penn State Hershey Medical Center, College of Medicine, Pa. Electronic address: akasmari@pennstatehealth.psu.edu.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Kasmari
authors.affiliation: Division of Gastroenterology and Hepatology, Penn State Hershey Medical Center, College of Medicine, Pa.
authors.forename: Amy
authors.initials: A
authors.lastname: Welch
authors.affiliation: Department of Public Health Sciences, Penn State Hershey Medical Center, College of Medicine, Pa.
authors.forename: Guodong
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Public Health Sciences, Penn State Hershey Medical Center, College of Medicine, Pa.
authors.forename: Doug
authors.initials: D
authors.lastname: Leslie
authors.affiliation: Division of Gastroenterology and Hepatology, Penn State Hershey Medical Center, College of Medicine, Pa.
authors.forename: Thomas
authors.initials: T
authors.lastname: McGarrity
authors.affiliation: Division of Gastroenterology and Hepatology, Penn State Hershey Medical Center, College of Medicine, Pa.
authors.forename: Thomas
authors.initials: T
authors.lastname: Riley
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000453:epidemiology*; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology*; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000453:epidemiology; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D006973:Hypertension / Q000150:complications / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications / Q000453:epidemiology; D008113:Liver Neoplasms / Q000150:complications / Q000453:epidemiology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000453:epidemiology*; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Diabetes; Hepatocellular carcinoma; Metabolic syndrome