Patients’ Characteristics
The study totally enrolled 1651 HCC patients initially treated with hepatectomy according to inclusion and exclusion criteria. The baseline characteristics of all enrolled patients were shown in Table 1. There were 1448 male (87.7%) and 203 female (12.3%). There were 157 patients in PH group and 1494 patients in non-PH group. There were 1198 patients (72.6%) developed recurrence and 1009 patients (61.1%)died during follow-up. There were 1545 patients (93.6%) with HBV infection and 989 patients (59.9%) with cirrhosis. The mean tumor size was 8.05 cm, and 542 patients (32.8%) had multiple tumors. According to Edmonson-Steiner stage, there were 42 stage I patients (2.5%), 1123 stage II patients (68.0%), 472 stage III patients (28.6%) and 14 stage IV patients (0.8%). PH group patients had lower level of albumin (ALB) (38.08 vs. 40.16 g/L, p < 0.001), alanine aminotransferase (ALT) (48.5 vs.56.8 U/L, p=0.01), white blood cells (WBC) (4.68 vs. 6.84, p < 0.001), tumor size (6.35 vs. 8.23 cm, p < 0.001), hemoglobin (HB) (130.9 VS. 137.8 g/L, p < 0.001). PH group patients had longer prothrombin time (PT) (13.58 vs. 12.75 s, p < 0.001), more intraoperative bleeding (1138.5 vs. 820.7 ml, p=0.05), higher rate of transfusion (72/157, 45.9% vs. 446/1494, 27.1%, p < 0.001), higher rate of Child-Pugh classification B (21/157, 13.4% vs. 18/1494, 1.2%, p=0.03). Patients with PH were older than non-PH patients (52.1 vs. 49.6, p=0.003). Both groups had similar rate of HBV infection (p=0.59), similar tumor number (p=0.28), similar capsulation (p=0.55), similar micro/macro venous invasion (p=0.33/0.29), similar Edmonson-Steiner stage (p=0.21).
Survival Analysis of Total 1651 Patients
The PH group had a similar OS (p=0.29, Fig.1) compared with non-PH group after initial hepatectomy. The 6-month, 1-, 3-, 5-, and 6-year OS rate in non-PH group and PH group were 87.1%, 76.1%, 49.2%, 39.4%, 35.8% and 84.1%, 72.6%, 49%, 34.1%, 31.6%. The PH group had a similar RFS (p=0.83, Fig.2) compared with non-PH group after initial hepatectomy. The 6-month, 1-, 2-, 3, and 5-year RFS rate in non-PH group and PH group were 58%, 46.1%, 36.3%, 31.7%, 26.2% and 64.5%, 47%, 35.6%, 32.8%, 24.7%.
Multivariate Analysis for OS and RFS
Univariate analysis showed that age, gender, tumor size, multiple, macro venous invasion, MVI, organ invasion, lymphatic metastasis, preoperative AFP, Child-Pugh classification, capsulation, Edmonson-Steiner stage, ALT, aspartate aminotransferase (AST) and intraoperative bleeding were significantly associated with OS. PH was not an independent protective factor for OS (hazard ratio [HR]=0.982, 95% CI 0.792-1.217, p=0.87) by multivariate analysis (Table 2). Tumor size (>5 cm) (p < 0.001), tumor number (multiple) (p < 0.001), macro venous invasion (p < 0.001), MVI (p < 0.001), lymphatic metastasis (p < 0.001), preoperative AFP (>400 ng/ml) (p=0.005), Child-Pugh classification (B) (p=0.05), non-capsulation (p=0.003), ALT (>40 U/L) (p=0.002), AST (>37 U/L) (p < 0.001), intraoperative bleeding(>400 ml) (p < 0.001) were identified as independent risk factors for OS.
Univariate analysis revealed that age, gender, tumor size, multiple, macro venous invasion, MVI, organ invasion, lymphatic metastasis, preoperative AFP, Child-Pugh classification, capsulation, Edmonson-Steiner stage, ALT, AST and intraoperative bleeding were significantly associated with RFS. PH was not an independent protective factor for RFS (HR=0.923, 95% CI 0.756-1.126, p=0.43) by multivariate analysis (Table 3). Age (>55 years) (p=0.04), gender (female) (p=0.05), tumor size (>5 cm) (p < 0.001), tumor number (multiple) (p < 0.001), macro venous invasion (p < 0.001), MVI (p < 0.001), lymphatic metastasis (p < 0.001), preoperative AFP (>400 ng/ml) (p=0.005), non-capsulation (p=0.004), AST (>37 U/L) (p < 0.001), intraoperative bleeding(>400 ml) (p < 0.001) were independent risk factors for RFS.
Survival Analysis After PSM Processing
After PSM processing, the baseline characteristics were highly comparable for both groups (133 patients in each group) (Table 4). The PH group had a similar OS (p=0.81, Fig.3) compared with non-PH group after initial hepatectomy. The 6-month, 1-, 3-, 5-, and 6-year OS rate in non-PH group and PH group were 81.2%, 73.6%, 45.7%, 38.7%, 36% and 84.2%, 71.4%, 48.9%, 35.3%, 32.2%. The PH group had a similar RFS (p=0.65, Fig.4) compared with non-PH group after initial hepatectomy. The 6-month, 1-, 2-, 3, and 5-year RFS rate in non-PH group and PH group were 53.4%, 44.7%, 33.7%, 28.9%, 23.1% and 63.6%, 45.3%, 34.1%, 30.9%, 24%.
Multivariate Analysis for OS and RFS After PSM Processing
Tumor size, multiple, macro venous invasion, MVI, organ invasion, lymphatic metastasis, preoperative AFP, capsulation, Edmonson-Steiner stage, ALT, AST and intraoperative bleeding were significantly associated with OS by univariate analysis. While multivariate analysis identified tumor size (>5 cm) (p=0.02), macro venous invasion (p < 0.001), AST (>37 U/L) (p =0.008) as independent risk factors for OS. Organ invasion and lymphatic metastasis presented as marginally significant with OS (multivariate analysis: p= 0.07, p= 0.08).
Tumor size, multiple, macro venous invasion, MVI, organ invasion, lymphatic metastasis, preoperative AFP, Child-Pugh classification, capsulation, Edmonson-Steiner stage, ALT, AST and intraoperative bleeding were significantly associated with RFS by univariate analysis. Multivariate analysis identified tumor size (>5 cm) (p=0.04), macro venous invasion (p < 0.001), lymphatic metastasis (p= 0.001) as independent risk factors for RFS. Organ invasion presented as marginally significant with RFS (multivariate analysis: p= 0.06).Importantly, multivariate analysis presented that PH were not an independent risk factor for OS (HR=1.061, 95% CI 0.771-1.46, p=0.71) and RFS (HR=0.986, 95% CI 0.736-1.322, p=0.93).