Impact of pre-existing diabetes mellitus on survival from hepatocellular carcinoma in the United States: A population based study Open Access

Tian, Yao (2015)

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Background: The prognosis of hepatocellular carcinoma (HCC) is dismal, and the impact of pre-existing Diabetes Mellitus (DM) on HCC survival is still disputable. Our study aim is to investigate the impact of pre-existing DM on the survival of patients with HCC and further explore whether the impact varies among HCC patients with/without hepatitis in the U.S.

Methods: We identified 6,789 HCC patients from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000 through 2009. At least two separate claims in the three year window prior to HCC diagnosis were required to confirm a diagnosis of DM. Patients with only one claim in the window were classified as possible DM while those with no claims were classified as no pre-existing DM. The outcome in this study was survival time, and it was defined as the time in months from diagnosis until death from HCC or censoring. Multivariable modeling of survival was performed using Cox proportional hazards models to examine the association between DM and HCC survival, and interaction between DM and hepatitis was examined using the likelihood ratio (LR) test based on full and reduced multivariable Cox models. The primary analysis was conducted excluding the possible DM group and a sensitivity analysis was conducted to reexamine the association between DM and survival incorporating the individuals with possible DM.

Results: In primary analysis, there were 3,262 HCC patients classified with pre-existing DM and 2,910 patients without pre-existing DM. After adjusting for demographic and clinical variables, DM was associated with increased risk of death from HCC (hazard ratio=1.118, 95% confidence interval: 1.060, 1.180). No statistically significant interaction was observed between DM and hepatitis status. Results from the sensitivity analysis were similar to the primary analysis.

Conclusion: Pre-existing DM was associated with increased risk of death for HCC patients diagnosed after 68 years old in the Medicare population. No significant interaction between chronic hepatitis B/C infection and pre-existing DM on HCC survival was observed in this population.

Table of Contents

List of Tables. i

List of Figures. ii

Chapter I: Background. 1

1. Overview of Hepatocellular Carcinoma Epidemiology. 2

2. Risk Factors for Hepatocellular Carcinoma Incidence and Survival. 4

3. The Role of Diabetes Mellitus on Hepatocellular Carcinoma Survival. 9

4. Diabetes Mellitus, Hepatitis and Hepatocellular Carcinoma. 11

5. Reference. 13

Chapter II: Manuscript. 21

1. Abstract. 21

2. Introduction. 23

3. Methods. 24

4. Results. 28

5. Discussion. 31

6. Reference. 38

7. Tables. 43

8. Figures/Figure Legends. 50

Chapter III: Summary and Future Directions. 52

Appendices. 53

Supplemental Table1: International Classification of Diseases, 9th Revision, and Current Procedural Terminology codes for Treatments in the Study. 53

Emory Institutional Review Board Approval Information. 54

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