The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrence rates of 10–15%. We undertook this pilot study to examine the use of sorafenib as adjuvant therapy in high-risk LT recipients. Methods. We prospectively enrolled patients transplanted for HCC into a treatment protocol utilizing sorafenib if their explant examination showed evidence of viable tumor exceeding Milan criteria. We utilized as historical controls patients transplanted previously, whose explant tumor characteristics exceeded Milan criteria, but who were not “preemptively” treated with sorafenib. Wilcoxon two-sample test and Fisher’s exact test were used to compare survival and recurrence rates between the two groups. Results. Seven patients were treated with sorafenib and compared to 12 historical “controls.” Two of 7 treated patients suffered from HCC recurrence. Of the comparison group, 9 experienced HCC recurrence and all succumbed to disease. Dose reduction improved tolerance of drug. The overall rate of HCC recurrence was decreased in the adjuvant therapy group compared to historical controls (29% versus 75%, ). Disease free 1-year survival for the treated versus untreated group was 100% versus 66%, respectively. Conclusion. Adjuvant use of sorafenib is safe and decreases risk of HCC recurrence in high-risk LT recipients. 1. Introduction Hepatocellular carcinoma (HCC) accounts for more than a million new cases each year worldwide and is the third leading cause of cancer-related death worldwide. Its incidence in the United States has shown a dramatic rise over the past few decades [1] and is expected to increase in the coming years. Liver transplantation (LT) is in many cases the ideal therapy for HCC, providing not only oncologic resection but also replacement of a diseased organ. An important study by Mazzaferro and colleagues demonstrated that if LT was limited to those with early HCC, long-term post-LT survival was excellent [2]. Based on this study and others, LT has become the standard of care for those HCC that satisfy the eponymous Milan criteria (a single tumor under 5？cm, or ≤3 tumors each under 3？cm, without evidence of metastatic disease/vascular invasion) on radiological imaging. However, despite advances in imaging techniques, almost 20% of HCCs are “understaged” on pre-LT radiological studies [3] and are found on explant to exceed Milan criteria, an established risk factor for post-LT HCC recurrence. Specific predictors of post-LT recurrence are tumor size, multifocality, and vascular invasion. The efficacy of liver
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