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Microscopic vascular invasion by hepatocellular carcinoma in liver transplant patients

Brian I Carr, Volkan Ince, Harika Gozukara Bag, Veysel Ersan, Sertac Usta and Sezai Yilmaz

Background: A characteristic of Hepatocellular Carcinoma (HCC) is to invade the portal venous system in the liver as a means of spread within the liver and systemically. The ensuing Portal Vein Thrombosis (PVT) is a poor prognosis parameter and often diagnosed radiologically pre-treatment. More limited Microvascular Portal Invasion (microPVI) is typically diagnosed on examination of tumors removed after treatment by resection or transplant. The biological characteristics and subsets of PVI are incompletely characterized. Aims: To examine HCC patients with and without microPVI to understand the clinical relationships to other tumor and clinical characteristics and to survival. Methods: A cohort of 270 liver transplant patients with HCC without macroscopic PVT that were available to us was examined. Patients with (165) and without (105) microPVI were compared for survival and clinical features. Results: The mean survival of patients with and without microPVI was significantly different: 86.6 versus 110.5 months, p=0.007. The microPVI+ patients differed from microPVI- patients in having a significantly larger number of tumor nodules, tumor size and higher serum levels of both Alpha-Fetoprotein (AFP) and almost significant for higher Gamma-Glutamyl Transpeptidase (GGT, p=0.053). Survival in microPVI+ patients related significantly to serum GGT (p=0.006) but not to AFP levels. The incidence of microPVI increased with increase in tumor size and survival decreased significantly with increase in tumor size for microPVI patients. Increase in tumor size was also associated with significantly higher serum GGT levels in patients who were microPVI+, but not in those who were microPVI. Furthermore, patients with microPVI who had prolonged survival significantly differed from those with shorter survival in respect only to tumor size and serum GGT levels. Conclusion: These findings draw attention to a group of patients with microPVI who have long survival and to the usefulness of serum GGT levels in their evaluation and prognosis.