The percentage of patients who underwent successful downstaging in the previously mentioned series ranged between 24 % and 70 % (Table 2). The proportion of patients who were downstaged and then transplanted ranged from 23 % to 100 %. The average wait period from initiation of downstaging to OLT ranged between 2 and 11 months. Recurrence-free survival after downstaging and OLT was approximately 65 % at 5 years in most of the series. The overall survival rate ranged from 79 % to 90 % and from 55 % to 94 % at 3 and 5 years, respectively. Four studies (DeLuna et al. 2009; Chapman et al. 2008; Otto et al. 2006; Lei et al. 2013) did not report any significant difference in overall or disease-free survival in patients who were transplanted after downstaging and those who received transplant directly. Chapman et al. reported on 76 patients with stage III/IV HCC who received TACE as a downstaging modality before OLT. 18 patients were downstaged to within the MILAN criteria and of those 17 patients underwent OLT. 94 % of patients were alive at a median of 19.6 month. Only one patient sustained a recurrence in the lungs that was resected and was alive 63 months after OLT. They concluded that patients with advanced HCC that are successfully downstaged have excellent midterm and disease-free survival after OLT and are similar to stage II HCC (Chapman et al. 2008).

Yao et al. reported on 61 patients with HCC who did not meet traditional criteria for transplantation. Patients were treated with TACE, RFA, ethanol injection, or a combination of those modalities. Patients were considered to be eligible for OLT if after treatment they had either one tumor greater than 5 cm but less than 8 cm or two to three tumors with one lesion greater than 3 cm but less than 5 cm and total tumor diameter not exceeding 8 cm or four to five lesions with none greater than 3 cm with a total tumor diameter not exceeding 8 cm. All patients had to be observed for 3 months before OLT. 43 patients (70 %) were successfully downstaged. Of those, 35 patients (81 %) underwent LT. The posttransplant 1- and 4-year survival was 96 % and 92 %, respectively. At a follow-up period of 25 months, no patients had posttransplant recurrence. The authors concluded that in selected patients downstaging of HCC can be achieved and is associated with excellent posttransplantation outcomes (Yao et al. 2008).

Along the same line of thought, DeLuna et al. in 2009 studied 122 patients with HCC who received transarterial chemo-infusion either as a bridge or as a downstaging modality before OLT. 27 patients did not meet the MILAN criteria and were considered for downstaging with TACI. 17 patients (63 %) were successfully downstaged to meet the MILAN criteria. Of those, 15 patients (88 %) underwent LT. The overall survival after LT was 79 % at 3 years. There was no difference in post LT outcomes between patients who originally met the MILAN criteria and those who did not. No factors associated with downstaging were identified in this series (DeLuna et al. 2009).

In an attempt to identify factors that successfully predict downstaging in patients with advanced HCC, Barakat et al. studied 32 patients with advanced HCC who underwent locoregional therapy as a method of downstaging including TACE, radioembolization, RFA, or a combination of those modalities. 18 (56 %) patients were successfully downstaged and 14 (78 %) of them were transplanted. 92 % and 75 % of the patients were alive at 1 and 2 years, respectively, after OLT. After a median follow-up period of 35 months, only 2 patients had tumor recurrence after OLT. He concluded that the only factor that predicts successful downstaging and improved outcome in patients with advanced HCC on both univariate and multivariate analyses is the presence of non-infiltrative expanding type of HCC (Barakat et al. 2010). Similarly, Bova et al. attempted to identify factors that predict successful downstaging. He studied 227 patients who received intra-arterial chemotherapy for treatment of HCC. He was able to identify 80 patients who originally did not meet criteria for transplantation. He excluded patients with infiltrative-type HCC, hypovascular HCC, and portal vein thrombosis. 48 patients were included in the final analysis. Reduction in the number and size of viable tumors within the MILAN criteria and presence of serum AFP level of 100 ng/ml for 6 months were considered as criteria for successful downstaging. 19 (39 %) patients were successfully downstaged, of which 9 (47 %) underwent LT. At a median follow-up of 40 months, 8 of the 9 patients did not have HCC recurrence. When identifying factors that were associated with successful downstaging, only a serum AFP level of 100 ng/ml and a high 3-year calculated survival using the “Metroticket” calculator were good predictors of response after intra-arterial chemotherapy in patients with advanced HCC (Bova et al. 2013).