Brandon G. Smaglo, MD; Suzanne Graef, MSc


July 26, 2013

Diabetes and the Risk for Liver Cancer

Editor's Note: Is diabetes an independent risk factor for hepatocellular carcinoma (HCC)? Brandon G. Smaglo, MD, for Medscape spoke to Suzanne Graef, MSc,Clinical Fellow,School of Medicine and Dentistry, The University of Birmingham, United Kingdom, who presented a study[1] at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO®) that sought to answer this question.

Medscape: Why did you and your colleagues want to investigate whether cancer of the liver, which is so difficult to pinpoint, is related to diabetes?

Dr. Graef: Two factors generated this thought process: nonalcoholic fatty liver disease and the metabolic syndrome. These conditions are big problems in the western world and, in fact, are overtaking standard risk factors -- such as hepatitis C infection and alcohol intake -- in the prevalence of liver disease. If we can find preventive measures or effective intervention strategies for this population that lead to an increase in survival, that would be a huge benefit. In the management of diabetes, a lot of data have been generated on the possible beneficial effects of metformin,[2,3,4] as well as the possible detrimental effects of insulin.[5,6]

Medscape: Are you thinking that down the road, we might find that treating individuals with a drug such as metformin could reduce the incidence of HCC? Is that in the scope of consideration?

Dr. Graef: It has been suggested. We know that the benefits of metformin are not limited to the effects on glucose and metabolism.[7] Metformin also has an impact on cellular metabolism, which may be beneficial in terms of preventing HCC. It is worth looking at.

Medscape: Tell us about your study.

Dr. Graef: This study aimed to examine whether diabetes was an independent risk factor for the development of HCC and to assess the impact of diabetes on overall survival.[1]The secondary aim was to examine whether the type of treatment received for diabetes had an impact on overall survival in HCC.

Data were prospectively accrued as part of an ethically approved biomarker study, and patients were entered into the study. A total of 724 patients with HCC and a control group comprising 340 patients with chronic liver disease were entered into this study between 2007 and 2012. Data were collected on a range of baseline characteristics and comorbidities, including known risk factors for HCC, and patients were followed up for the full 5-year period.

The odds ratio for HCC in diabetic vs nondiabetic patients was calculated. Univariate and multivariate analysis was then performed using logistic regression to demonstrate the independent risk factors for HCC. Cox proportional hazards analysis was used to estimate the hazard ratio for death in HCC patients with and without diabetes and for the impact of variation in diabetic treatments.

Medscape: What did you discover? What is the association between diabetes and HCC?

Dr. Graef: We found that the prevalence of diabetes was significantly higher in the population with HCC (39%) compared with the chronic liver disease group (10.3%). Definitively, patients with diabetes had an increased risk for developing HCC, independent of any other liver disease. Even if they had hepatitis C infection, hepatitis B infection, or alcohol excess, diabetes still increased the risk for developing HCC.

With respect to treatment, this finding is quite useful in hypothesis-generation, but we can't take too much away from this without doing further study because the numbers are small. However, the data seem to show that metformin had a beneficial effect on overall survival.

Medscape: What about variables relating to how diabetes was controlled -- for example, patients with well-regulated A1c levels vs those with poorly controlled disease?

Dr. Graef: We don't have complete data on A1c control. The difficulty with this patient cohort is that their diabetes was often managed elsewhere, and we lack complete data on their treatments.


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