Baseline Demographics of patients
Among the 107 HCC patients with PVTT, 48 patients received pretransplant downstaging therapy for HCC with 15 (31%) patients had well response on radiology. Patient, tumor and pretransplant treatment characteristics are shown in Table 1. To summarize, the median age was 49 years [interquartile range (IQR) 42–56], and 97% were male. Hepatitis B virus (HBV) infection was the underlying liver disease. The median pre-transplant AFP was 602.6 (IQR 30.8-13719) ng/ml. The pre-transplant systematic inflammatory index such as NLR, PLR and CRP were 4.9 (IQR 3.4-8.5), 153 (IQR 94-234) and 18 (IQR 6.1-38.8) mg/L, respectively. The majority of patients (89.6%) received TACE, with 66.7% receiving TACE alone and 22.9% receiving TACE and systematic therapies (sorafenib, lenvatinib or PD-1 antibody). Only 10.4% of patients received other treatments (thermal ablation, radiotherapy, lenvatinib or PD-1 antibody) without TACE. Concerning the pathology of extracted liver, 47 (43.9%) patients had poorly differentiated HCC, 88 (82.2%) patients had multifocal tumor, 45 (42.1%) patients had Vp4-PVTT and 80 (74.8%) patients had total tumor size larger than 8 cm.
Univariate and Multivariate Analysis of Predictors of Well Response to Downstaging Therapy
Among the 48 HCC patients received pretransplant downstaging therapy, 15 (31%) patients had well response on radiology and 33 (69%) patients had poor response to pretransplant downstaging therapy. Univariate predictors of well response to downstaging are shown in Table 2. In summary, patients were less likely to achieve well response to downstaging with pre-transplant AFP ≥1000ng/mL (OR 0.184, 95% CI, 0.044-0.778, P=0.021), pre-transplant PLR ≥120 (OR 0.208, 95% CI, 0.054-0.799, P=0.022), total tumor size larger than 8 cm (OR 0.254, 95% CI, 0.066-0.976, P=0.046); or poorly differentiated HCC (OR 0.110, 95% CI, 0.013-0.939, P=0.044). Patients who received multiple combined downstaging therapies (TACE, thermal ablation, tyrosine kinase inhibitors or PD-1 antibody) were more likely to achieve well response (OR 6.400, 95% CI, 1.593-25.717, P=0.009).
Multivariate modeling identified independent factors associated with well response, as shown in Table 2. poorly differentiated HCC (OR 0.06, 95% CI, 0.005-0.693, P=0.024) was independent risk factor associated with well response, and multiple combined downstaging therapies (OR 10.884, 95% CI, 1.909-62.047, P=0.007) was independent favorable factor associated with well response.
Posttransplant HCC Recurrence and Overall Survival
Survival outcomes are shown in Figure 1. Compared with poor response or non-downstaged patients, patients who achieved well response to downstage had significantly superior 1-, 2-, and 3-year recurrence-free survival (72%, 72%, and 72% vs 30.4%, 22.6%, and 22.6%; P = 0.002; Fig. 1A) and overall survival (100%, 90.9%, and 90.9% vs 66.3%, 47.7%, and 47.7%; P = 0.008; Fig. 1B).
As shown in table 3, by the univariate analysis, pre-transplant AFP ≥1000 ng/mL, NLR ≥7, PLR ≥120, CRP ≥10mg/L, maximum or total tumor size >8cm, poorly differentiated tumor and Vp4-PVTT were risk factors for both HCC recurrence and inferior overall survival. In addition, tumor necrosis >50% after downstaging and multiple combined downstaging therapies were both favorable factors for superior recurrence-free survival and overall survival.
In the multivariate analysis, pre-transplant AFP ≥1000 ng/mL was independent risk factors for post-LT HCC recurrence (HR 3.032, 95% CI, 1.303-7.057, P=0.010) and overall survival (HR 3.287, 95% CI, 1.154-9.368, P=0.026). In addition, tumor necrosis >50% after downstaging was associated with superior recurrence-free survival (HR 0.311, 95% CI, 0.102-0.954, P=0.041) and overall survival (HR 0.116, 95% CI, 0.015-0.889, P=0.038) (Table 4).