Total tumor volume (TTV) has been proposed as a more accurate means of selecting patients for liver transplantation (LT) due to hepatocellular carcinoma (HCC). We aim to analyze the role of TTV in a population with a short waiting time on list. Methods: Analysis of a prospective database of patients submitted to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC), UCSF (University of California San Francisco), and “Up to Seven” criteria were calculated both with preoperative imaging exams and histological data. Results: The study population consisted of 231 out of patients. Median waiting time on list was 62.5 days. MC included 187 patients, while TTV ≤115 cm3 included 214. Microvascular invasion (HR 2.601, 95% CI 1.529–4.426), MC (HR 1.666, 95% CI 0.990–2.804), UCSF criteria (HR 2.995, 95% CI 1.875–4.875), TTV ≤115 cm3 (HR 2.898, 95% CI 1.398–6.007), and “Up to Seven” criteria (HR 2.139, 95% CI 1.353–3.383) proved to be independent factors for prognosis for disease-free survival. Conclusions: TTV ≤115 cm3 may be a useful tool to properly identify the best HCC candidates for LT in a population with a short waiting time on list. TTV gives more patients the opportunity of undergoing LT while maintaining similar rates of tumor recurrence and patient survival.

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