Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.

Hepatocellular carcinoma (HCC) is a common type of cancer that ranks first in cancer-associated death worldwide. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) are the key components of the pyrimidine pathway, which promotes cancer development. However, the function of CAD in HCC needs to be clarified. In this study, the clinical and transcriptome data of 424 TCGA-derived HCC cases were analyzed. The results demonstrated that high CAD expression was associated with poor prognosis in HCC patients. The effect of CAD on HCC was then investigated comprehensively using GO annotation analysis, KEGG enrichment analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT algorithm. The results showed that CAD expression was correlated with immune checkpoint inhibitors and immune cell infiltration. In addition, low CAD levels in HCC patients predicted increased sensitivity to anti-CTLA4 and PD1, while HCC patients with high CAD expression exhibited high sensitivity to chemotherapeutic and molecular-targeted agents, including gemcitabine, paclitaxel, and sorafenib. Finally, the results from clinical sample suggested that CAD expression increased remarkably in HCC compared with non-cancerous tissues. Loss of function experiments demonstrated that CAD knockdown could significantly inhibit HCC cell growth and migration both in vitro and in vivo. Collectively, the results indicated that CAD is a potential oncogene during HCC metastasis and progression. Therefore, CAD is recommended as a candidate marker and target for HCC prediction and treatment.

A new scoring system for predicting the outcome of hepatocellular carcinoma patients without microvascular invasion-a large-scale multicentre study.

BACKGROUND: The prognosis of HCC patients without MVI (so called M0) is highly heterogeneous and the need for adjuvant therapy is still controversial. METHODS: Patients with HCC with M0 who underwent liver resection (LR) or liver transplantation (LT) as an initial therapy were included. The Eastern Hepatobiliary Surgery Hospital (EHBH)-M0 score was developed from a retrospective cohort to form the training cohort. The classification which was developed using multivariate cox regression analysis was externally validated. RESULTS: The score was developed using the following factors: α-fetoprotein level, tumour diameter, liver cirrhosis, total bilirubin, albumin and aspartate aminotransferase. The score differentiated two groups of M0 patients (≤3, >3 points) with distinct long-term prognoses outcomes (median overall survival (OS), 98.0 vs. 46.0 months; p < 0.001). The predictive accuracy of the score was greater than the other commonly used staging systems for HCC. And for M0 patients with a higher score underwent LR. Adjuvant transcatheter arterial chemoembolization (TACE) was effective to prolong OS. CONCLUSIONS: The EHBH M0 scoring system was more accurate in predicting the prognosis of HCC patients with M0 after LR or LT. Adjuvant therapy is recommended for HCC patients who have a higher score.

An inferior vena cava-priority approach in laparoscopic isolated hepatic caudate lobectomy.

PURPOSE: Laparoscopic isolated caudate lobectomy is still a challenging operation for surgeons. The access route of the operation plays a vital role during laparoscopic caudate lobectomy. There are few references regarding this technique. Here, we introduce a preferred inferior vena cava (IVC) approach in laparoscopic caudate lobectomy. METHODS: Twenty-one consecutive patients with caudate hepatic tumours between June 2016 and December 2021 were included in this study. All of them received laparoscopic caudate lobectomy involving an IVC priority approach. The IVC priority approach refers to prioritizing the dissection of the IVC from the liver parenchyma before proceeding with the conventional left or right approach. It emphasizes the importance of the IVC dissection during process. Clinical data, intraoperative parameters and postoperative results were evaluated. Sixteen patients were performed pure IVC priority approach, while 5 patients underwent a combined approach. We subsequently compared the intraoperative and postoperative between the two groups. RESULTS: All 21 patients were treated with laparoscopic technology. The operative time was 190.95 ± 92.65 min. The average estimated blood loss was 251.43 ± 247.45 ml, and four patients needed blood transfusions during the perioperative period. The average duration of hospital stay was 8.43 ± 2.64 (range from 6.0 to 16.0) days. Patients who underwent the pure inferior vena cava (IVC) approach required a shorter hepatic pedicle clamping time (26 vs. 55 min, respectively; P < 0.001) and operation time (150 vs. 380 min, respectively; P = 0.002) than those who underwent the combined approach. Hospitalization (7.0 vs. 9.0 days, respectively; P = 0.006) was shorter in the pure IVC group than in the combined group. CONCLUSIONS: Laparoscopic caudate lobectomy with an IVC priority approach is safe and feasible for patients with caudate hepatic tumours.

A new chemotherapy strategy for advanced hepatocellular carcinoma with exrahepatic metastasis: predictors of long-term survival.

The prognosis of hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM) is extremely poor. This study aimed to identify prognostic factors for systemic chemotherapy of HCC with EHM. Eighty-five patients who received systemic chemotherapy for HCC with EHM between May 2014 and October 2021 were retrospectively evaluated. Patient demographic data and characteristics of hepatic tumors and EHM were assessed to identify factors that were significantly associated with prognosis. Of the 85 patients, 68 (80.0%) had pulmonary metastasis, 11 (12.9%) had abdominal lymph node metastasis, 7 (8.2%) had abdominal metastasis, and 4 (4.7%) had bone metastasis. The median overall survival (OS) was 17.0 months, and the median progression-free survival (PFS) was 5.1 months. Univariate analysis of OS showed that synchronous EHM-HCC, serum albumin level<35 g/l and number of hepatic tumors>1 were significantly associated with poorer OS. The results of the multivariate analysis indicated that the serum albumin level and number of hepatic tumors were independent prognostic factors. Subgroup analysis of patients with 0, 1, or 2 of these independent prognostic factors showed that the median OS was 24.0 months, 16.2 months and 7.7 months and that the ORR was 38.3%, 22.6% and 0, respectively. Systemic chemotherapy is beneficial for well-selected HCC patients with EHM. The number of hepatic tumors and serum albumin level were independent risk factors for prognosis, and the number of risk factors significantly influenced OS. Therefore, these factors need to be considered before administering systemic chemotherapy for HCC patients with EHM.

Combined FOLFOX4 with all-trans retinoic acid versus FOLFOX4 with placebo in treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a randomized, double-blind comparative study.

The majority of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage. Currently, there are only a few therapeutic methods available for patients with advanced HCC and extrahepatic metastasis (EHM). Systemic chemotherapy, such as FOLFOX4 (infusions of fluorouracil, leucovorin, and oxaliplatin), has been reported for treating advanced HCC with EHM, but its effectiveness is very poor. In this randomized, double-blind, placebo-controlled study, we aimed to assess the efficacy and safety of FOLFOX4 with all-trans-retinoic acid (ATRA) as a palliative treatment for HCC patients with EHM, compared to FOLFOX4 with a placebo. The primary endpoint was overall survival (OS), and subsequently, an exploratory model was developed based on bioinformatics to predict the efficacy of FOLFOX4-ATRA treatment. A total of 108 patients were randomly assigned in a 1:1 ratio to receive either FOLFOX4-ATRA or FOLFOX4-placebo. The intention-to-treat (ITT) population showed a median OS of 16.2 months for the FOLFOX4-ATRA group, compared with 10.7 months for the FOLFOX4-placebo group (HR 0.56, 95% CI 0.33-0.93; p = 0.025). The median progression-free survival (PFS) was 7.1 months for the FOLFOX4-ATRA group and 4.2 months for the FOLFOX4-placebo group (HR 0.62, 95% CI 0.41-0.94; p = 0.024). A panel of proteins with unique upregulation during complete response (CR) (SOD3, TTR, SSC5D, GP5, IGKV1D-33) and partial response (PR) (TGFB1, GSS, IGHV5-10-1) effectively predicted CR and PR in patients treated with FOLFOX4-ATRA, as compared to FOLFOX4-placebo. The results suggest that FOLFOX4-ATRA is a safe and effective treatment for patients with advanced HCC and EHM in eastern China.

Efficacy and safety of transarterial chemoembolization plus antiangiogenic- targeted therapy and immune checkpoint inhibitors for unresectable hepatocellular carcinoma with portal vein tumor thrombus in the real world.

Purpose: This study aimed to assess the efficacy and safety of a triple therapy that comprises transarterial chemoembolization (TACE), antiangiogenic-targeted therapy, and programmed death-1 (PD-1) inhibitors in a real-world cohort of patients with unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Methods: Consecutive patients treated with TACE combined with antiangiogenic therapy and PD-1 inhibitors at the Eastern Hepatobiliary Surgery Hospital between June 2019 and May 2021 were enrolled. The baseline characteristics and treatment course of the patients were recorded. The tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and HCC-specific modified RECIST (mRECIST). The overall survival (OS) and progression-free survival (PFS) of the patients were analyzed using the Kaplan-Meier method. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: As of the data cutoff on 30 August 2021, the median follow-up time was 10.0 (3.9-28.4) months. A total of 39 eligible patients were included. The objective response rate (ORR) and the disease control rate (DCR) were 35.9% and 74.4% according to the RECIST 1.1, and 48.7% and 84.6% according to mRECIST criteria, respectively. The median OS and PFS were 14.0 and 9.2 months, respectively. Moreover, 34 (87.2%) patients experienced at least one treatment-related AE and 8 (20.5%) patients experienced grade 3/4 treatment-related AEs. The most common treatment- and laboratory-related AEs were hypertension (46.2%) and decreased albumin (53.8%), respectively. No treatment-related mortality occurred during the study period. Conclusions: TACE combined with antiangiogenic-targeted therapy and immune checkpoint inhibitors may have promising anticancer activity in unresectable HCC patients with PVTT. AEs were manageable, with no unexpected overlapping toxicities.

A novel chemotherapy strategy for advanced hepatocellular carcinoma: a multicenter retrospective study.

BACKGROUND: Chemotherapy is a common treatment for advanced hepatocellular carcinoma, but the effect is not satisfactory. The study aimed to retrospectively evaluate the effects of adding all-trans-retinoic acid (ATRA) to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) for advanced hepatocellular carcinoma (HCC). METHODS: We extracted the data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, and Zhejiang Sian International Hospital and retrospectively compared for overall survival. The Cox proportional hazards model was used to calculate the hazard ratios for overall survival and disease progression after controlling for age, sex, and disease stage. RESULTS: From July 2013 to July 2018, 111 patients with HCC were included in this study. The median survival duration was 14.8 months in the ATRA plus FOLFOX4 group and 8.2 months in the FOLFOX4 only group ( P  < 0.001). The ATRA plus FOLFOX4 group had a significantly longer median time to progression compared with the FOLFOX4 group (3.6 months vs. 1.8 months, P  < 0.001). Hazard ratios for overall survival and disease progression were 0.465 (95% confidence interval: 0.298-0.726; P  = 0.001) and 0.474 (0.314-0.717; P  < 0.001) after adjusting for potential confounders, respectively. CONCLUSION: ATRA plus FOLFOX4 significantly improves the overall survival and time to disease progression in patients with advanced HCC.

A Double Suspension Technique for Laparoscopic Isolated Caudate Lobectomy.

Background: Laparoscopic isolated caudate lobectomy is still a challenging procedure for hepatobiliary surgeons because of its deep location and narrow operating space. Hilar exposure and adequate operation space play an important role during laparoscopic caudate lobectomy. Very few references are available on this technique, and in this study, we present a new suspension technique to assist laparoscopic caudate lobectomy. Materials and Methods: The data of patients with caudate hepatic tumors who underwent laparoscopic isolated caudate lobectomy with or without the double suspension technique at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. Results: A total of 25 patients underwent laparoscopic isolated caudate lobectomy at Eastern Hepatobiliary Surgery Hospital between June 2016 and March 2022. Eight patients had perioperative complications, and no patient died within 30 days after surgery. There were no significant differences between the two groups in terms of conversion rate (8.3% versus 7.7%; P = .954), complication rate (25.0% versus 38.5%; P = .480), length of stay (8.0 [6.0-11.0] days versus 9.0 [6.0-19.0] days; P = .098), and postoperative liver function changes. Patients who underwent resection in the suspension group had shorter operation time (154.9 ± 44.3 minutes versus 224 ± 86.3 minutes; P = .018), inferior vena cava dissection time (30.1 ± 5.4 minutes versus 44.8 ± 7.4 minutes; P < .001), and less bleeding (125.0 [20-800.0] mL versus 350 [80-850.0] mL, P = .011). Conclusions: This double suspension technique is a safe and feasible method to assist laparoscopic caudate lobectomy. It provides clear exposure and adequate surgical space, thereby shortening the operation time and reducing intraoperative blood loss.

Guidelines for Diagnosis and Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus in China (2021 Edition).

Portal vein tumor thrombus (PVTT) is very common and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the guideline in 2016 and revised in 2018. Over the past several years, many new evidences for the treatment of PVTT become available, especially for the advent of new targeted drugs and immune checkpoint inhibitors which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association revised the 2018 version of the guideline to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.

All-Trans-Retinoic Acid Plus Oxaliplatin/Fluorouracil/Leucovorin for Advanced Hepatocellular Carcinoma with Pulmonary Metastasis: A Multicenter Retrospective Study.

Aim: To study the impact of All-trans-retinoic acid (ATRA) plus FOLFOX4 compared to FOLFOX4 alone in patients with advanced hepatocellular carcinoma (HCC) with pulmonary metastasis. Methods: The data of patients with advanced HCC who underwent systemic chemotherapy using FOLFOX4 or ATRA plus FOLFOX4 at the Eastern Hepatobiliary Surgery Hospital, First Hospital of Jilin University, Zhejiang Sian International Hospital and Fujian Cancer Hospital were retrospectively analyzed. The survival outcomes in the 2 groups were compared. Results: From May 2014 to July 2020, 66 patients were suitable to enter into this study. The median survival (14.0 vs 8.0 months, p=0.012), and the median time to progression in the ATRA plus FOLFOX4 group were both significantly longer than those in the FOLFOX4 group (8.7 vs 3.2 months, p=0.002). The 6 month-, 1 year- and 2 year- overall survival rates were also significantly better in the ATRA plus FOLFOX4 group (100.0%, 64.7% and 20.5%; respectively) than the FOLFOX4 group (59.4%, 21.9%, and 12.5%, respectively; p<0.001). Leukocytopenia, fatigue, anorexia, nausea, were the most common acute toxicities, but these were mostly NCI CTCAE Grade 1 or 2. There was no significant difference in adverse events between the two groups. Conclusion: ATRA plus FOLFOX4 significantly improved the survival outcomes in patients with advanced HCC with pulmonary metastasis.

Recurrence hazard rate in patients with hepatocellular carcinoma and bile duct tumor thrombus: a multicenter observational study.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) bile duct tumor thrombus (BDTT) have a high rate of postoperative recurrence. We aimed to describe the patterns and kinetics of recurrence in BDTT patients and provide management options accordingly. METHODS: This retrospective study included 311 HCC patients with BDTT who underwent surgery from 2009 to 2017 at five centers in China. The hazard rate of recurrence was calculated using the hazard function. RESULTS: The hazard rate of intrahepatic recurrence was higher than that of extrahepatic recurrence (0.0588 vs. 0.0301), and both showed a decreasing trend, and the intrahepatic recurrence and extrahepatic recurrence risk decreased to a lower level after 40 and 20 months, respectively. Patients who underwent anatomic resection had a consistently lower hazard rate of recurrence than patients who underwent nonanatomic resection, whereas patients who received postoperative adjuvant transarterial chemoembolization (TACE) mainly had a lower hazard rate of recurrence in the first year than patients who did not. CONCLUSION: The follow-up of BDTT patients should be at least 40 months because of its high rate of recurrence, in parallel with the need for vigilance for extrahepatic recurrence within 20 months. Anatomic hepatectomy and adjuvant TACE are recommended to improve BDTT patient outcomes.

Prognostic Comparison Between Liver Resection and Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Patients With Bile Duct Tumor Thrombus: A Propensity-Score Matching Analysis.

Background: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The aim of this study is to evaluate the long-term prognosis of liver resection (LR) versus transcatheter arterial chemoembolization (TACE) in these patients. Methods: Data from HCC patients with BDTT who underwent liver resection and TACE were analyzed respectively. Propensity score matching (PSM) analysis was performed in these patients. Results: A total of 145 HCC patients with BDTT were divided into two groups: the LR group (n = 105) and the TACE group (n = 40). The median OS in the LR group was 8.0 months longer than that in the TACE group before PSM (21.0 vs. 13.0 months, P <0.001) and 9.0 months longer after PSM (20.0 vs. 11.0 months, P <0.001). The median DFS in the LR group was 3.5 months longer than that in the TACE group before PSM (7.0 vs. 3.5 months, P = 0.007) and 5 months longer after PSM (7.0 vs. 2.0 months, P = 0.007). Conclusion: If surgery is technically feasible, liver resection provides better prognosis for HCC patients with BDTT compared with TACE.

Impact of Bile Duct Tumor Thrombus on the Long-Term Surgical Outcomes of Hepatocellular Carcinoma Patients: A Propensity Score Matching Analysis.

BACKGROUND: Hepatectomy with tumor thrombectomy is the preferred treatment option for hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT); however, the impact of BDTT on their prognosis is unclear. OBJECTIVE: We aimed to investigate the long-term surgical outcomes of HCC patients with BDTT. METHODS: The data of HCC patients with and without BDTT who underwent hepatectomy were retrospectively reviewed and the long-term outcomes were compared. For propensity score matching (PSM) analysis, patients were matched in a 1:1 ratio. Subgroup analysis was conducted according to the American Joint Committee on Cancer (AJCC) staging system. RESULTS: Before PSM, HCC patients with BDTT had more advanced tumor stages and adverse clinicopathological features. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the non-BDTT group before PSM (RFS, p < 0.001; OS, p < 0.001), while after PSM, the BDTT group had significantly poorer RFS (p = 0.025). There was no difference in OS between the groups (p = 0.588). Subgroup analysis showed that RFS and OS in AJCC stage I-II patients were significantly poorer in the BDTT group; no differences were found in the AJCC stage III group before or after PSM. When the presence of BDTT was recommended to increase the AJCC staging system by one stage in AJCC stage I-II patients, the predictive ability for RFS and OS was higher. CONCLUSIONS: BDTT was associated with significantly poorer long-term surgical outcomes in AJCC stage I-II patients. A modified AJCC staging system including BDTT status in stage I-II might have a better prognostic ability.

Postoperative adjuvant transarterial chemoembolization improves outcomes of hepatocellular carcinoma associated with bile duct tumor thrombus: a propensity score matching analysis.

BACKGROUND: Surgical resection is the primary treatment for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT). This study was conducted to investigate the efficacy of postoperative adjuvant TACE (PA-TACE) in patients with HCC and BDTT. METHODS: Data from patients who underwent surgery for HCC with BDTT at two medical centers were retrospectively analyzed. The survival outcomes of patients who were treated by hepatic resection followed by PA-TACE were compared with those of patients who underwent surgery alone. Propensity score matching (PSM) analysis was performed with a 1:1 ratio. RESULTS: Of the 308 consecutively enrolled HCC patients with BDTT who underwent surgical resection, 134 underwent PA-TACE whereas 174 underwent surgery alone. From the initial cohort, PSM matched 106 pairs of patients. The OS and DFS rates were significantly better for the PA-TACE group than the surgery alone group (for OS: before PSM, P = 0.026; after PSM, P = 0.039; for DFS: before PSM, P = 0.010; after PSM, P = 0.013). CONCLUSION: PA-TACE was associated with better survival outcomes than surgery alone for patients with HCC and BDTT. Prospective clinical trials are warranted to validate the beneficial effect of PA-TACE on HCC patients associated with BDTT.

Chinese Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021 Edition).

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. Summary: In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the "Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)" based on current clinical studies and clinical medication experience for reference in China. Key Messages: The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.

Efficacy and Safety of Transarterial Chemoembolization for the Treatment of Unresectable Hepatocellular Carcinoma Associated with Bile Duct Tumor Thrombus: A Real-World Retrospective Cohort Study.

BACKGROUND: The occurrence of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The aim of the study was to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) for patients with unresectable HCC with BDTT. METHODS: This retrospective study was conducted on newly diagnosed HCC and BDTT patients who were initially treated with TACE or conservative management (CM) from 2009 to 2018. Survival outcomes of patients treated with TACE were compared with those of patients given CM. Multivariate analyses were performed to identify independent prognostic factors related to survival. RESULTS: Out of 100 patients included in this study, 40 patients underwent TACE, while the remaining 60 received CM. The median survival time of the TACE group was 8.0 months longer than that of the CM group (13.0 versus 5.0 months, P < 0.001). The 6-, 12-, 18-, 24-month overall survival (OS) rates were 90.0%, 52.5%, 22.5%, and 12.5%, respectively, for the TACE group compared with 26.7%, 8.3%, 5.0%, and 3.3%, respectively, for the CM group. Multivariate analyses showed that treatment allocation (hazard ratio [HR], 0.421; 95% confidence interval [CI], 0.243-0.730; P = 0.002), Child-Pugh status (HR, 2.529; 95% CI, 1.300-4.920; P = 0.006) and total bilirubin level (HR, 1.007; 95% CI, 1.004-1.009; P < 0.001) on first admission were independent predictors of OS. There was no procedure-related mortality within one month after TACE treatment. CONCLUSION: TACE is a safe and effective treatment method that may improve the OS of patients with unresectable HCC with BDTT.

Typing of biliary tumor thrombus influences the prognoses of patients with hepatocellular carcinoma.

OBJECTIVE: To establish a new classification of biliary tumor thrombus (BTT). METHODS: Overall survival of patients with BTT was first used to determine whether it correlated with current hepatocellular carcinoma staging systems. Univariate and multivariate analyses were used to determine factors affecting the overall survival (OS) to form the basis of our new classification for BTT. RESULTS: All 6 international staging systems showed overlapping survival curves. Univariate followed by multivariate analyses showed that total bilirubin and intrahepatic/extrahepatic BTT were significant risk factors of OS. Based on these data, a new BTT classification was defined as: Type I: intrahepatic BTT; and Type II: extrahepatic BTT involving a common bile duct or common hepatic duct. Type I was further subdivided into type Ia: BTT involving a second-order intrahepatic duct or above, and type Ib: BTT involving a first-order intrahepatic duct. Type II was further subdivided into type IIa and type IIb using a cut-off total bilirubin (TB) > 300 µmol/L. The numbers (percentages) of patients with types I and II BTT were 69 (34.2%) and 133 (65.8%), respectively. The median OS of type I patients was significantly higher than that of type II patients (37.5 months vs. 23.2 months; P = 0.002). Using subgroup analyses, OS outcomes were significantly different between the subgroups of type IIb and type IIa, although there was no significant difference between the type Ia and type Ib subgroups (P = 0.07). CONCLUSIONS: A new BTT classification was established to predict prognoses of HCC patients with BTT who underwent liver resection.