Background: Immunotherapy has revolutionized hepatocellular carcinoma (HCC) treatment, increasingly being incorporated into various stages of treatment, including preoperative therapy. However, preoperative immunotherapy alters both physiological status and tumor biology, potentially impacting the perioperative risk. We aimed to explore the association between the implementation details of preoperative immunotherapy and perioperative risk. Methods: This study retrospectively enrolled HCC patients who received immune checkpoint inhibitor (ICI)-based immunotherapy prior to radical surgery. A comprehensive dataset encompassing baseline characteristics and immunotherapy-specific parameters was collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors, followed by validation through machine learning algorithms to evaluate the predictive performance of the derived determinants. Results: This multicenter retrospective study enrolled 303 HCC patients who received preoperative immunotherapy across 26 participating centers. Based on specified perioperative risk stratification criteria, 182 patients (60.07%) were stratified into the low-risk cohort, while 121 patients (39.93%) constituted the high-risk cohort. Multivariate logistic regression analysis identified several independent risk factors of elevated perioperative risk: ICI duration exceeding four cycles [odds ratio (OR), 2.00; 95% confidence interval (CI) 1.20-3.32]; the occurrence of grade >= 3 immune-related adverse events (irAEs) (OR, 2.36; 95% CI: 1.13-4.92); the presence of major vein thrombus (OR, 2.05; 95% CI: 1.25-3.38); multiple tumor nodules (OR, 1.74; 95% CI: 1.02-2.98); and maximal tumor diameter >5 cm (OR, 2.02; 95% CI: 1.10-3.73). Subgroup analyses consistently demonstrated these associations. Machine learning algorithms quantified feature importance for perioperative risk predictors, with extended ICIs duration (mean importance rank =2.88) and grade >= 3 irAEs (mean importance rank =2.38) emerging as top-ranked variables. Conclusions: This multicenter retrospective study reveals ICIs duration and high-grade irAEs were associated with elevated perioperative risk in HCC patients undergoing preoperative immunotherapy, providing actionable insights for optimizing perioperative management protocols.

The advanced lung cancer inflammation index (ALI), which integrates nutritional and inflammatory indicators, has been associated with outcomes in several malignancies. This study evaluates the predictive efficacy of ALI in patients undergoing curative-intent surgery for intrahepatic cholangiocarcinoma (ICC). Patients undergoing curative-intent resection for ICC from a multi-institutional database were stratified into low- and high-ALI groups, with propensity score matching (PSM) applied to reduce baseline differences. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression models identified independent factors associated with overall survival (OS), and P values were adjusted using the Benjamini–Hochberg false discovery rate (FDR) method. The cohort was randomly split into training (n = 464) and validation (n = 227) datasets to construct and validate an ALI-based dynamic online nomogram. Prognostic performance was assessed using the concordance index (C-index), time-dependent ROC curves, and decision curve analysis (DCA). A total of 691 patients were included, of whom 194 (28.1

BACKGROUND:To investigate the preoperative factors influencing textbook outcomes (TO) in Intrahepatic cholangiocarcinoma (ICC) patients and evaluate the feasibility of an interpretable machine learning model for preoperative prediction of TO, we developed a machine learning model for preoperative prediction of TO and used the SHapley Additive exPlanations (SHAP) technique to illustrate the prediction process. AIM:To analyze the factors influencing textbook outcomes before surgery and to establish interpretable machine learning models for preoperative prediction. METHODS:A total of 376 patients diagnosed with ICC were retrospectively collected from four major medical institutions in China, covering the period from 2011 to 2017. Logistic regression analysis was conducted to identify preoperative variables associated with achieving TO. Based on these variables, an EXtreme Gradient Boosting (XGBoost) machine learning prediction model was constructed using the XGBoost package. The SHAP (package: Shapviz) algorithm was employed to visualize each variable's contribution to the model's predictions. Kaplan-Meier survival analysis was performed to compare the prognostic differences between the TO-achieving and non-TO-achieving groups. RESULTS:Among 376 patients, 287 were included in the training group and 89 in the validation group. Logistic regression identified the following preoperative variables influencing TO: Child-Pugh classification, Eastern Cooperative Oncology Group (ECOG) score, hepatitis B, and tumor size. The XGBoost prediction model demonstrated high accuracy in internal validation (AUC = 0.8825) and external validation (AUC = 0.8346). Survival analysis revealed that the disease-free survival rates for patients achieving TO at 1, 2, and 3 years were 64.2%, 56.8%, and 43.4%, respectively. CONCLUSION:Child-Pugh classification, ECOG score, hepatitis B, and tumor size are preoperative predictors of TO. In both the training group and the validation group, the machine learning model had certain effectiveness in predicting TO before surgery. The SHAP algorithm provided intuitive visualization of the machine learning prediction process, enhancing its interpretability.

Background: The conversion therapy for advanced hepatocellular carcinoma (HCC) shows promise with a triple therapy approach that combines interventional therapy, immune checkpoint inhibitors, and molecular targeted therapy (primarily small-molecule TKIs and the large-molecule bevacizumab). This combination has achieved the highest objective response rates (ORR) along with acceptable safety profiles. The aim of this study was to compare the clinical efficacy of lenvatinib versus bevacizumab, when combined with immune checkpoint inhibitors and interventional triple therapy, as first-line treatments for Chinese patients with unresectable HCC (uHCC). Method: This retrospective multicenter study involved 371 consecutive patients from 21 centers in China, observed between April 2017 and December 2023. The study focused on patients with uHCC at Chinese liver cancer stages IIb to IIIb (Barcelona Clinic Liver Cancer stage B or C) who received lenvatinib or bevacizumab combined with anti-PD-1/L1 and interventional therapy (including TACE and/or HAIC) as first-line treatment. Of the 371 patients, 258 received lenvatinib-based triple therapy, while 113 received bevacizumab-based triple therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). To balance baseline clinical characteristics, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied. Subgroup analysis was also performed based on different clinicopathological characteristics of the enrolled uHCC patients. Results: The median OS in the lenvatinib group was significantly longer than in the bevacizumab group, both before (36.0 vs. 27.9 months; hazard ratio [HR]: 0.536; 95% confidence interval [CI]: 0.344–0.835; p = 0.0016) and after PSM (HR: 0.524; 95% CI: 0.305–0.900; p = 0.01), as well as after IPTW (HR: 0.549; 95% CI: 0.331–0.908; p = 0.01). Before adjustment, PFS in the lenvatinib group was also significantly longer than in the bevacizumab group (20.0 vs. 12.1 months; HR: 0.649; 95% CI: 0.457–0.922; p = 0.0078). However, after PSM (HR: 0.808; 95% CI: 0.535–1.222; p = 0.33) and IPTW, there was no significant difference in PFS between the two groups. Multivariate analysis showed that lenvatinib-based triple therapy was independently associated with improved OS compared to bevacizumab-based triple therapy. Subgroup analysis indicated that patients with age ≤65 years, no history of hepatitis B virus infection, Barcelona Clinic Liver Cancer stage C (BCLC-C), ALT levels ≤40 U/L, platelets ≥100 × 109/L, or log 10 AFP ≥1.40 benefited more from lenvatinib-based triple therapy. Conclusion: Lenvatinib-based triple therapy tends to prolong OS compared to bevacizumab, although the PFS was similar between the two groups. Patients aged ≤65 years, without a history of hepatitis B virus infection, with BCLC-C stage, ALT ≤40 U/L, platelets ≥100 × 109/L, or log 10 AFP ≥1.40 are likely to benefit more from lenvatinib-based triple therapy.

OBJECTIVE:The impact of nucleos(t)ide analogues (NAs) therapy on the long-term outcomes in chronic HBV infection individuals outside 2025 European Association for the Study of the Liver (EASL) strongly recommended treatment indications remains uncertain. We aimed to assess the association between NAs therapy and the risks of cirrhosis and hepatocellular carcinoma (HCC) in Chinese chronic HBV infection individuals outside these criteria. DESIGN:We analysed data from 30 784 chronic HBV infection individuals across 12 centres in China. We categorised individuals outside 2025 EASL strongly recommended treatment criteria into four groups: (1) hepatitis B e antigen (HBeAg)-positive, high replicative (age <30, HBV DNA ≥8 log₁₀IU/mL, normal alanine aminotransferase (ALT), no/mild fibrosis, no family history of liver cancer); (2) HBeAg-positive, impending phase transition (typically age ≥30, HBV DNA ≥6 log₁₀IU/mL, normal ALT, no advanced fibrosis); (3) HBeAg-negative, low replicative (HBV DNA <3.3 log₁₀IU/mL, normal ALT, no/mild fibrosis); (4) HBeAg-negative, high replicative, low-risk (HBV DNA 3.3-4.3 log₁₀IU/mL, normal ALT, no/mild fibrosis). The primary endpoints were the incidence of cirrhosis and HCC. RESULTS:Up to 5 years of follow-up (117 814 person-years), we documented 635 incident cirrhosis and 164 HCC cases. In multivariable analyses, NA therapy significantly reduced risks of cirrhosis (HR 0.18, 95% CI 0.11 to 0.32) and HCC (HR 0.03, 95% CI 0.01 to 0.21) in Group 1, and cirrhosis (HR 0.50, 95% CI 0.41 to 0.61) and HCC (HR 0.25, 95% CI 0.16 to 0.41) in Group 2. No significant associations were observed in Groups 3 and 4. Findings were consistent in propensity score matching analyses. CONCLUSION:NAs therapy was associated with reduced risks of cirrhosis and HCC in HBeAg-positive individuals with high replicative or impending phase transition phenotypes, supporting the expansion of chronic HBV infection treatment criteria.

BACKGROUND:Conversion therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) offers the potential for curative resection in unresectable hepatocellular carcinoma (HCC). However, early recurrence (≤2 years) after conversion liver resection remains a major concern. This study aimed to develop and validate online preoperative and postoperative risk scores to predict early recurrence in patients undergoing conversion liver resection. METHODS:A total of 203 patients with initially unresectable HCC who underwent conversion liver resection following TKI and ICI therapy across 28 academic centers were analyzed. Independent predictors of early recurrence were identified using Cox proportional hazards analyses, and risk scores were developed and validated using the C-index, time-dependent AUC (tdAUC), and calibration curves. RESULTS:Preoperative risk score model included the neutrophil-to-lymphocyte ratio (NLR) ≥ 1.39, multiple tumors, absence of radiographic response, and no alpha-fetoprotein (AFP) response. Postoperative risk score model included NLR ≥1.39, multiple tumors, no AFP response, active macrovascular invasion, and incomplete pathological response. The preoperative risk score had a C-index of 0.699 (training) and 0.681 (validation), while the postoperative risk score had a C-index of 0.739 (training) and 0.706 (validation). Both models demonstrated good predictive accuracy through tdAUC and calibration curves. Decision tree analysis stratified patients into distinct risk categories with significant differences in 2-year recurrence rates. All risk score models are available online for clinical use. CONCLUSION:Online preoperative and postoperative risk scores provide valuable tools for predicting early recurrence in HCC patients after conversion liver resection, aiding in surgical decision-making and postoperative management.

Background:The prevalence of hepatocellular carcinoma (HCC) among older patients is rising due to the aging population. This study aimed to compare the efficacy and safety of targeted therapy alone versus its combination with immunotherapy in older patients (≥ 65 years old) with unresectable HCC (uHCC). Methods:We retrospectively analyzed 158 patients aged ≥ 65 diagnosed with uHCC who received targeted therapy alone or in combination with immunotherapy from the CLEAP database between March 2019 and July 2023. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety assessments for adverse events (AEs). Results:The ORR was 3.6% in the targeted monotherapy group compared to 29.4% in the combination therapy group, while the DCRs were 53.6% and 54.9%, respectively. Survival analysis indicated a median PFS of 7.3 months for monotherapy versus 13.2 months for combination therapy (P = 0.137) and a median OS of 16.0 months versus 20.0 months, respectively (P = 0.140). AEs occurred in 44.6% of the monotherapy group and 58.8% in the combination therapy group, with 20.5% in the combination group withdrawing due to adverse reactions, significantly higher than in monotherapy group. Conclusion:Among older patients with uHCC, the combination therapy demonstrated higher ORR and longer PFS and OS, although it had higher incidences of AEs and drug withdrawal.

BACKGROUND The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.

Background: The application of Pringle maneuver (PM) during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion, but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma (HCC) remains controversial. We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC. Methods: Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified. Using two propensity score methods [propensity score matching (PSM) and inverse probability of treatment weight (IPTW)], cumulative recurrence rate and cancer-specific mortality (CSM) were compared between the patients in the PM and non-PM groups. Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors. Results: Of the 2,798 included patients, 2,404 and 394 did and did not adopt PM (the PM and non-PM groups), respectively. The rates of intraoperative blood transfusion, postoperative 30-day mortality and morbidity were comparable between the two groups (all P>0.05). In the PSM cohort by the 1:3 ratio, compared to 382 patients in the non-PM group, 1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM (63.9% and 39.1% vs. 55.3% and 31.6%, both P<0.05). Similar results were also yielded in the entire cohort and the IPTW cohort. Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts (HR, 0.82 and 0.77 in the adjusted entire cohort, HR 0.80 and 0.73 in the PSM cohort, and HR 0.80 and 0.76 in the IPTW cohort, respectively). Conclusions: The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20 similar to 25%.

Abstract Aims Portal venous pressure frequently increases after a major hepatectomy. We aimed to assess the outcomes of patients with hepatocellular carcinoma (HCC) with different post‐hepatectomy portal pressure statuses and the predictive factors correlated with prognosis and post‐hepatectomy portal hypertension (PHPH). Methods Data from consecutive patients who underwent curative‐intent hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University between January 2008 and December 2016 were retrospectively analyzed. Patients were followed up until March 1, 2022. PHPH was defined as new‐onset portal hypertension (PH) in patients without preoperative PH within 1 month of hepatectomy. Patients were classified into two groups according to the presence or absence of PHPH: non‐PH and PHPH. The clinicopathological characteristics were compared between the two groups. Univariate and multivariate analyses were used to identify independent risk factors for early and late recurrence of HCC, overall survival (OS), and PHPH. Results Disease‐free survival rates were significantly higher in the non‐PH group (n = 1068) than those in the PHPH group (n = 423) (62.0%, 39.0%, and 31.0% vs. 46.2%, 24.5%, and 19.3% at 1, 3, and 5 years, respectively; all p < 0.001). The 1‐, 3‐, and 5‐year OS rates were 91.0%, 66.4%, and 51.4% in the non‐PH group and 80.0%, 48.9%, and 32.6% in the PHPH group, respectively (all p < 0.001). Multivariate analysis revealed that PHPH was independently associated with early recurrence of HCC and poor OS (hazard ratio [HR] 1.476, 95% confidence interval [CI] 1.279–1.704, p < 0.001 and HR 1.601, 95% CI 1.383–1.853, p < 0.001, respectively). Furthermore, hepatitis B virus infection, cirrhosis, preoperative alanine aminotransferase > 40 U/L, and major hepatectomy were identified as independent risk factors for PHPH. Conclusions PHPH was associated with early recurrence of HCC and poor OS but not with late recurrence. Therefore, PHPH may be an attractive target for therapeutic interventions and follow‐up surveillance to improve prognosis.

Abstract Background Radical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients. Methods Data of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared. Results Two hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child–Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05. Conclusion Surgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.

The impact of hepatic resection type on long-term oncological prognosis of patients with early-stage hepatocellular carcinoma (HCC) has not been systematically investigated. We sought to determine risk factors, recurrence patterns, and survival outcomes after anatomical resection (AR) versus non-anatomical resection (NAR) for early-stage HCC. From a prospectively collected multicenter database, consecutive patients undergoing curative hepatectomy for early-stage HCC were identified. Recurrence patterns, overall survival (OS), recurrence-free survival (RFS), and risk factors were investigated in patients undergoing AR versus NAR using propensity score matching (PSM), subgroup analysis, and COX regression analysis. A total of 3585 patients with early-stage HCC were enrolled, including 1287 and 2298 in the AR and NAR groups, respectively. After PSM, the OS and RFS of patients in the AR group were 58.8

Background: Liver transplantation (LT) is the only effective therapy for end-stage liver diseases, but some patients usually present with serious infection and immune rejection. Those with immune rejection require long-term administration of immunosuppressants, leading to serious adverse effects. Mesenchymal stem cells (MSCs) have various advantages in immune regulation and are promising drugs most likely to replace immunosuppressants. Summary: This study summarized the application of MSCs monotherapy, its combination with immunosuppressants, MSCs genetic modification, and MSCs derivative therapy (cell-free therapy) in LT. This may deepen the understanding of immunomodulatory role of MSCs and promote the application of MSCs in immune rejection treatment after LT. Key messages: MSCs could attenuate ischemia-reperfusion injury and immune rejection. There is no consensus on the effects of types and concentrations of immunosuppressants on MSCs. Although genetically modified MSCs have contributed to better outcomes to some extent, the best modification is still unclear. Besides, multiple clinical complications developed frequently after LT. Unfortunately, there are still few studies on the polygenic modification of MSCs for the simultaneous treatment of these complications. Therefore, more studies should be performed to investigate the potency of multi-gene modified MSCs in treating complications after LT. Additionally, MSC derivatives mainly include exosomes, extracellular vesicles, and conditioned medium. Despite therapeutic effects, these three therapies still have some limitations such as heterogeneity between generations and that they cannot be quantified accurately.

Background:Systemic therapy is the standard care of unresectable hepatocellular carcinoma (uHCC), while transcatheter intra-arterial therapies (TRITs) were also widely applied to uHCC patients in Chinese practice. However, the benefit of additional TRIT in these patients is unclear. This study investigated the survival benefit of concurrent TRIT and systemic therapy used as first-line treatment for patients with uHCC. Methods:This real-world, multi-center retrospective study included consecutive patients treated at 11 centers accross China between September 2018 and April 2022. Eligible patients had uHCC of China liver cancer stages IIb to IIIb (Barcelona clinic liver cancer B or C stage), and received first-line systemic therapy with or without concurrent TRIT. Of 289 patients included, 146 received combination therapy and 143 received systemic therapy alone. The overall survival (OS), as primary outcomes, was compared between patients who received systemic therapy plus TRIT (combination group) or systemic therapy alone (systemic-only group) using survival analysis and Cox regression. Imbalances in baseline clinical features between the two groups were adjusted through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Moreover, subgroup analysis was conducted based on the different tumor characteristics of enrolled uHCC patients. Results:The median OS was significantly longer in the combination group than the systemic-only group before adjustment [not reached vs. 23.9 months; hazard ratio (HR), 0.561; 95% confidence interval (CI), 0.366 to 0.861; P = 0.008], after PSM (HR, 0.612; 95% CI, 0.390 to 0.958; P = 0.031) and after IPTW (HR, 0.539; 95% CI, 0.116 to 0.961; P = 0.008). Subgroup analyses suggested the benefit of combining TRIT with systemic therapy was greatest in patients with liver tumors exceeding the up-to-seven criteria, with an absence of extrahepatic metastasis, or with alfa-fetoprotein ≥ 400 ng/ml. Conclusion:Concurrent TRIT with systemic therapy was associated with improved survival compared with systemic therapy alone as first-line treatment for uHCC, especially for patients with high-intrahepatic tumor load and no extrahepatic metastasis.

BACKGROUND:Hepatic pedicle clamping (HPC) is frequently utilized during hepatectomy to reduce intraoperative bleeding and diminish the need for intraoperative blood transfusion (IBT). The long-term prognostic implications of HPC following hepatectomy for hepatocellular carcinoma (HCC) remain under debate. This study aims to elucidate the association between HPC and oncologic outcomes after HCC resection, stratified by whether IBT was administered.PATIENTS AND METHODS:Prospectively collected data on patients with HCC who underwent curative resection from a multicenter database was studied. Patients were stratified into two cohorts on the basis of whether IBT was administered. The impact of HPC on long-term overall survival (OS) and recurrence-free survival (RFS) between the two cohorts was assessed by univariable and multivariable Cox regression analyses.RESULTS:Of 3362 patients, 535 received IBT. In the IBT cohort, using or not using HPC showed no significant difference in OS and RFS outcomes (5-year OS and RFS rates 27.9% vs. 24.6% and 13.8% vs. 12.0%, P = 0.810 and 0.530). However, in the non-IBT cohort of 2827 patients, the HPC subgroup demonstrated significantly decreased OS (5-year 45.9% vs. 56.5%, P < 0.001) and RFS (5-year 24.7% vs. 33.3%, P < 0.001) when compared with the subgroup without HPC. Multivariable Cox regression analysis identified HPC as an independent risk factor of OS and RFS [hazard ratios (HR) 1.16 and 1.12, P = 0.024 and 0.044, respectively] among patients who did not receive IBT.CONCLUSIONS:The impact of HPC on the oncological outcomes following hepatectomy for patients with HCC differed significantly whether IBT was administered, and HPC adversely impacted on long-term survival for patients without receiving IBT during hepatectomy.

Background and Aims:Hepatectomy is an effective treatment for selected patients with large hepatocellular carcinoma (HCC). This study aimed to develop a nomogram incorporating non-tumoral liver volume (non-TLV) and liver function markers to predict the patients' overall survival (OS) and disease-free survival (DFS).Methods:Data of 198 consecutive large HCC patients who underwent hepatectomy at the Zhongshan Hospital Xiamen University were collected. Another 68 patients from the Mengchao Hepatobiliary Surgery Hospital served as an external validation cohort. The nomograms were developed based on the independent prognostic factors screened by multivariate Cox regression analyses. Concordance index (C-index), calibration curves, and time-dependent receiver operating characteristic (ROC) curves were used to measure the discrimination and predictive accuracy of the models.Results:High HBV DNA level, low non-TLV/ICG, vascular invasion, and a poorly differentiated tumor were confirmed as independent risk factors for both OS and DFS. The model established in this study predicted 5-year post-operative survival and DFS in good agreement with the actual observation confirmed by the calibration curves. The C-indexes of the nomograms in predicting OS and DFS were 0.812 and 0.823 in the training cohort, 0.821 and 0.846 in the internal validation cohort, and 0.724 and 0.755 in the external validation cohort. The areas under the ROC curves (AUCs) of nomograms for predicted OS and DFS at 1, 3, and 5 year were 0.85, 0.86, 0.83 and 0.76, 0.76, 0.63, respectively.Conclusions:Nomograms with non-TLV/ICG predicted the prognosis of single large HCC patients accurately and effectively.

BackgroundThis study aimed to analyze the biomarkers that may reliably indicate rejection or tolerance and the mechanism that underlie the induction and maintenance of liver transplantation (LT) tolerance related to immunosuppressant or mesenchymal stem cells (MSCs).MethodsLT models of Lewis-Lewis and F344-Lewis rats were established. Lewis-Lewis rats model served as a control (Syn). F344-Lewis rats were treated with immunosuppressant alone (Allo+IS) or in combination with MSCs (Allo+IS+MSCs). Intrahepatic cell composition particularly immune cells was compared between the groups by single-cell sequencing. Analysis of subclusters, KEGG pathway analysis, and pseudotime trajectory analysis were performed to explore the potential immunoregulatory mechanisms of immunosuppressant alone or combined with MSCs.ResultsImmunosuppressants alone or combined with MSCs increases the liver tolerance, to a certain extent. Single-cell sequencing identified intrahepatic cell composition signature, including cell subpopulations of B cells, cholangiocytes, endothelial cells, erythrocytes, hepatic stellate cells, hepatocytes, mononuclear phagocytes, neutrophils, T cells, and plasmacytoid dendritic cells. Immunosuppressant particularly its combination with MSCs altered the landscape of intrahepatic cells in transplanted livers, as well as gene expression patterns in immune cells. MSCs may be included in the differentiation of T cells, classical monocytes, and non-classical monocytes.ConclusionThese findings provided novel insights for better understanding the heterogeneity and biological functions of intrahepatic immune cells after LT treated by IS alone or in combination with MSCs. The identified markers of immune cells may serve as the immunotherapeutic targets for MSC treatment of liver transplant rejection.

Background and objectives Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC. Methods One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA). Results The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69–0.85) and 0.76 (95% CI: 0.66–0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. Conclusions Our model demonstrated favorable performance in predicting VER in cHCC patients.

Primary liver cancer is one of the most common and fatal malignant tumors, and surgical treatment is the most important radical treatment method, but there is still a high postoperative recurrence rate and poor prognosis. In recent years, emerging techniques represented by artificial intelligence have achieved rapid innovation and are gradually integrated into the whole process of the diagnosis and treatment of primary liver cancer. Promoting the implementation of artificial intelligence in the surgical treatment of primary liver cancer is of great significance to the high-quality development of precision liver surgery. At present, researchers have extensively explored the application of artificial intelligence in treatment decision-making, preoperative evaluation, surgical implementation, postoperative management, and adjuvant therapy for primary liver cancer. This article reviews the advances in the application of artificial intelligence in the surgical treatment of primary liver cancer, so as to accelerate the application of artificial intelligence in clinical diagnosis and treatment, improve clinical service ability, and ultimately improve patients’ prognosis.

Abstract Background and Objectives Previous studies have reported that the microvascular invasion three‐tiered grading (MiVI‐TTG) scheme is a better prognostic predictor than the two‐tiered microvascular invasion (MiVI) grading scheme in hepatocellular carcinoma. This study aims to explore the prognostic significance of MiVI‐TTG in patients undergoing liver resection for combined hepatocellular‐cholangiocarcinoma (cHCC) and to explore the risk factors for MiVI in cHCC. Methods This research included 208 patients graded as M0, M1, or M2 using the MiVI‐TTG scheme. Predictive performance was assessed by Cox regression analysis, Kaplan–Meier curve with Log rank test, Harrell's c‐index, and time‐dependent areas under the receiver operating characteristic curve (tdAUC). The clinical utility of the two schemes was evaluated by decision cure analysis (DCA). The risk factors for MiVI were evaluated using logistic regression analysis. Results Among 208 cHCC patients, the proportions of M0, M1 and M2 were 38.9%, 36.5%, and 24.5%, respectively. Patients with severe MiVI status had worse recurrence‐free survival and overall survival (OS) based on Kaplan–Meier analysis. M1, M2, and MiVI‐positive were independent risk factors for early recurrence, while M2 and MiVI‐positive were associated with overall survival (OS). MiVI‐TTG had a larger c‐index, tdAUC, and net benefit rate than the two‐tiered MiVI grading scheme for predicting recurrence free survival and OS. AFP≥400 ng/ml was the independent risk factor for MiVI, and satellite nodules were independent risk factors for M2. Conclusions MiVI‐TTG has a greater prognostic value than the two‐tiered MiVI grading scheme in patients undergoing hepatic resection for cHCC.