Impact of diabetes mellitus on risk of major vessel invasion and distant metastasis in hepatocellular carcinoma.
174 Background: Diabetes mellitus (DM) is identified as a negative prognostic indicator in hepatocellular carcinoma (HCC), though the basis for this is unknown. Methods: We conducted a retrospective review of 279 advanced and 191 transplanted HCC patients diagnosed between 1998 and 2008. Logistic regression analyses were conducted to assess the effect of clinical DM on clinical outcomes including distant metastasis and vascular invasion. Results: Eighty- four of 191 (44%) transplanted patients had DM at time of transplantation and 97 of 279 (34%) nontransplanted patients had DM at the time of diagnosis. The presence of DM was associated with an older age at time of diagnosis and a higher prevalence of hepatitis C virus (HCV) and nonalcoholic steatohepatitis (NASH). Also 30% (30/97) of diabetics compared to only 9.3% (17/182) of nondiabetics (p<0.0001) among the cohort with advanced disease had distant metastasis at the time of initial diagnosis, and this difference remained significant when adjusting for CLIP stage, age, and etiologic risk factors in a multivariate logistic regression analysis (OR=8.3, p<0.0001). The association of DM with invasive disease was echoed among early stage transplanted HCC patients in whom histologically confirmed macrovascular invasion was higher among patients with DM compared to those without (20.5% vs. 9.5%, p=0.032). The association of DM with increased risk of macrovascular invasion remained significant in a multivariate logistic regression analysis when adjusting for tumor size, number of nodules, age, obesity and etiologic risk factors (OR=3.2, p=0.025). Conclusions: DM was associated with significantly higher incidence of histological macrovascular invasion in a large cohort of HCC patients receiving liver transplantation and a significantly higher rate of distant metastatic disease at diagnosis in a large cohort of HCC patients with advanced disease. No significant financial relationships to disclose.