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Background: Microvascular invasion (MVI) is well established as a negative prognostic factor for hepatocelluar carcinoma (HCC). However, its prognostic value in different subgroups of Barcelona Clinical Liver Cancer (BCLC) stages remains to be elucidated., Methods: Four hundred fifty-eight MVI-negative and 204 MVI-positive patients who underwent hepatectomy were retrospectively analyzed. After propensity score matching (PSM) analysis, 187 pairs of matched patients were generated. Long-term survival was compared by the Kaplan-Meier method., Results: Patients with MVI commonly had more advanced tumors. All the patients with MVI had significantly worse survival rate compared to the patients without MVI before and after PSM(p < 0.001). In the subgroup analysis, BCLC stage A HCC patients without MVI had better prognosis than those with MVI before and after PSM (p < 0.001 and p = 0.024). For BCLC stage B HCCs, long-term survival was significantly better for patients without MVI before PSM(p = 0.001). However, the overall survival (OS) rate was comparable between both groups after PSM (p = 0.682), although MVI-positive group had a higher rate of recurrence (p = 0.011).. Surgery type, satellite lesions, tumor size, and serum ALT level were statistically significant factors associated with survival in MVI-positive group. Tumor number, tumor size and neutrophil to lymphocyte ratio (NLR) were predictors of survival in MVI-negative group., Conclusions: Its prognostic value in different subgroups of BCLC stages differed. MVI is an independent predictor of prognosis in patients with BCLC stage A. For BCLC stage B HCCs, MVI-positive group had poor prognosis through more advanced HCCs.

Aims: To determine the relationship between microvascular invasion (MVI) and the clinical features of hepatocellular carcinoma (HCC) and provide a method to evaluate MVI status by neutral network analysis. Methods: The patients were divided into two groups (MVI-positive group and MVI-negative group). Univariate analysis and multivariate logistic regression analysis were carried out to identify the independent risk factors for MVI positivity. Neural network analysis was used to analyze the different importance of the risk factors in MVI prediction. Results: We enrolled 1697 patients in this study. We found that the independent prognostic factors were age, NEU, multiple tumors, AFP level and tumor diameter. By neural network analysis, we proposed that the level of AFP was the most important risk factor for HCC in predicting MVI status (the AUC was 0.704). However, age was the most important risk factor for early-stage HCC with a single tumor (the AUC was 0.605). Conclusion: Through the neutral network analysis, we could conclude that the level of AFP is the most important risk factor for MVI-positive patients and the age is the most important risk factor for early-stage HCC with a single tumor. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) remains a global health challenge with a low early diagnosis rate and high mortality. The Rab GTPase (RAB) family plays an essential role in the occurrence and progression of HCC. Nonetheless, a comprehensive and systematic investigation of the RAB family has yet to be performed in HCC. We comprehensively assessed the expression landscape and prognostic significance of the RAB family in HCC and systematically correlated these RAB family genes with tumor microenvironment (TME) characteristics. Then, three RAB subtypes with distinct TME characteristics were determined. Using a machine learning algorithm, we further established a RAB score to quantify TME features and immune responses of individual tumors. Moreover, to better evaluate patient prognosis, we established a RAB risk score as an independent prognostic factor for patients with HCC. The risk models were validated in independent HCC cohorts and distinct HCC subgroups, and their complementary advantages guided clinical practice. Furthermore, we further confirmed that the knockdown of RAB13, a pivotal gene in risk models, suppressed HCC cell proliferation and metastasis by inhibiting the PI3K/AKT signaling pathway, CDK1/CDK4 expression, and epithelial-mesenchymal transition. In addition, RAB13 inhibited the activation of JAK2/STAT3 signaling and the expression of IRF1/IRF4. More importantly, we confirmed that RAB13 knockdown enhanced GPX4-dependent ferroptosis vulnerability, highlighting RAB13 as a potential therapeutic target. Overall, this work revealed that the RAB family played an integral role in forming HCC heterogeneity and complexity. RAB family-based integrative analysis contributed to enhancing our understanding of the TME and guided more effective immunotherapy and prognostic evaluation. [ABSTRACT FROM AUTHOR]

Background: An elevated preoperative aspartate aminotransferase‐to‐lymphocyte ratio index (ALRI) may predict poor survival in various cancers. However, the prognostic value of aminotransferase‐to‐lymphocyte ratio index (ALRI) in patients with hepatocellular carcinoma (HCC) remains to be determined. Materials and methods: A retrospective cohort study was conducted among 983 patients with HCC in our hospital from February 2007 to March 2016. A propensity‐score matching (PSM) was performed to correct the selection bias and confounding factors. The risk of death and recurrence was plotted over aminotransferase‐to‐lymphocyte ratio index (ALRI) using the locally weighted scatterplot smoothing (LOWESS)‐smoothed fit curve. Time‐dependent receiver operating characteristic (ROC) and Kaplan–Meier method analysis was utilized to the role of aminotransferase‐to‐lymphocyte ratio index (ALRI) in HCC. Multivariate analysis was conducted to identify independent prognostic factors associated with overall survival (OS) and recurrence‐free survival (RFS). Results: With the increase of aminotransferase‐to‐lymphocyte ratio index (ALRI), the risk of recurrence and death in HCC patients increases. In time‐dependent ROC analysis, the AUC of aminotransferase‐to‐lymphocyte ratio index (ALRI) for predicting 1‐, 3‐ and 5‐year OS were 0.668 (95% CI: 0.596‐0.740), 0.605 (95% CI: 0.560‐0.649) and 0.613 (95% CI: 0.570‐0.656), respective. The AUC of aminotransferase‐to‐lymphocyte ratio index (ALRI) for predicting 1‐, 3‐ and 5‐year RFS were 0.598 (95% CI: 0.555‐0.641), 0.590 (95% CI: 0.552‐0.628) and 0.604 (95% CI: 0.562‐0.646), respectively. HCC patients with high aminotransferase‐to‐lymphocyte ratio index (ALRI) had a poor overall survival. Moreover, cox regression analysis revealed that aminotransferase‐to‐lymphocyte ratio index (ALRI) was an independent factor affecting the prognosis of HCC patients. Conclusions: Elevated preoperative aminotransferase‐to‐lymphocyte ratio index (ALRI) is a noninvasive, simple, and effective predictor in the prognosis of patients with HCC. [ABSTRACT FROM AUTHOR]

Background: Although numerous scoring models are available to predict the prognosis of patients undergoing liver transplantation (LT), the field lacks a simple model for quick prediction of the short-term survival of patients after LT in the event that the donor's information is not available in advance.Methods: A total of 1495 adult patients underwent LT in the present study. Three-quarters of recipients were randomly selected into the test set (n = 1121), while the remaining 25% formed the validation set (n = 374). Univariate and multivariate analysis and machine-learning techniques were applied to evaluate possible influencing factors. To further simplify the model, a weighted-scoring system was designed considering each influencing factor and its importance in an artificial neural network (ANN).Results: In the test set, multivariate analysis identified creatinine, age, and total bilirubin as independent risk factors, while albumin was an independent protective factor. Logistic regression analysis showed the C-statistic to be 0.650, while ANN indicated this to be 0.698. We simplified the model to obtain the final scoring model, for which the C-statistic was 0.636, and defined four risk grades. The 90-day mortality rates corresponding to the four risk levels were 6.2%, 11.8%, 24.0%, and 34.9%, respectively. In the validation set, the C-statistic value of the original model was 0.668 and that of the simplified model was 0.647.Conclusion: We developed a simple scoring system for the preliminary prediction of the postoperative 90-day mortality of adult LT based on preoperative characteristics of LT recipients. [ABSTRACT FROM AUTHOR]

The relationship between age and the prognosis of patients with hepatocellular carcinoma (HCC) has been widely investigated. However, few studies have focused on the influence of patient age on the prognosis of HCC with microvascular invasion (MVI). Patients with histologically confirmed HCC with MVI who underwent hepatectomy between 2008 and 2016 were retrospectively enrolled in this study and allocated to younger (young group) and older age groups (old group) according to age< or ≥60 years. A propensity score matching analysis was performed, and prognostic factors evaluated by Kaplan–Meier curves and Cox proportional hazards regression. Intraoperative and postoperative characteristics were compared between the two groups. A total of 374 patients were enrolled in this study. There were 84 patients in each group after a 1 : 1 propensity score matching analysis. The rates of both disease-free survival (DFS) and overall survival (OS) differed significantly between the age groups. By univariate and multivariate analyses, age < 60 years was significantly associated with DFS (hazard ratio, 1.590; 95% CI, 1.135–2.228) and OS (hazard ratio, 1.837; 95% CI, 1.259–2.680). There were no significant differences in intraoperative or postoperative characteristics between the two age groups. In patients with histologically confirmed HCC with MVI, the prognosis is poorer for those aged younger than 60 years than for those aged 60 years or older. Hepatectomy can be safely performed in selected older patients. [ABSTRACT FROM AUTHOR]

Aim: As high gamma-glutamyltransferase level or low albumin had negative impacts on the prognosis of hepatocellular carcinoma (HCC), the prognostic role of albumin to gamma-glutamyltransferase ratio (AGR) in HCC patients after hepatectomy remains unclear. Methods: Between January 2007 and December 2015, 1143 HCC patients after hepatectomy were reviewed from a prospectively maintained database in West China Hospital. All qualified patients (n = 959) were classified as training set (year 2007–2012, n = 480) and validation set (year 2012–2017, n = 479). A time-dependent receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance. Result: AGR = 0.5 was identified as the best cut-off point to predict recurrence free survival (RFS) and overall survival (OS) in the training set. Low AGR was related to poor tumor characteristics and high systemic inflammation. Based on the multivariate analysis, high AGR was an independent predictor for better RFS and OS with an hazard ratio of 0.696 and 0.673. The high AGR group had better RFS and OS than the low AGR group in the training set as well as the validation set. The AGR-based score (AGR-PLR) could stratify HCC patients into three subgroups with different prognosis in the training and validation set. Patients with score 1 had a worse prognosis than those with AGR-PLR score 0, but better than those with AGR-PLR score 2. The predictive accuracy of the AGR-PLR score appeared superior to that of the AGR or PLR alone. Conclusions: we firstly reported that AGR ≤ 0.5 was an independently prognostic factor in HCC after hepatectomy. The AGR-PLR score could further improve the discriminatory ability of prognosis. [ABSTRACT FROM AUTHOR]

Background: There is little information regarding the role of preoperative serum albumin (ALB) in intrahepatic cholangiocarcinoma (ICC) patients who underwent liver resection. Methods: Clinicopathological characteristics and survival rate of 91 ICC patients who underwent surgery between 2009 and 2013 were included in this study. The optimal cut-off for ALB were determined by plotting the receiver operating characteristics curves of ALB in predicting overall survival (OS) and utilizing the Youden index. Long-term outcome was calculated by Kaplan-meire method. Results: The pathological characteristics were similar in both groups. The 1- and 3-year disease-free survival (DFS) rates between the high ALB group and the lower ALB group were 62.7 vs. 25.5% and 27.0 vs. 11.1% respectively (p < 0.001). The 1- and 3-year OS rates between the high ALB group and the lower ALB group were 78.4 vs. 57.5% and 42.6 vs. 6.7% respectively (p < 0.001). The ALB level as continuous variable in multivariate analysis remained a favorable factor for DFS and OS (p < 0.05). Furthermore, ALB could distinguish the prognoses in non-cirrhotic patients. Multivariate analysis showed other pathological risk factors like lymph node involvement, positive surgical margin, satellite lesions, and carbohydrate antigen 19-9 were associated with DFS and OS (p < 0.05 for all). Conclusions: A higher preoperative serum ALB level is associated with better long-term survival in ICC patients. [ABSTRACT FROM AUTHOR]

Aim: The role of tumor differentiation in the prognosis of hepatocellular carcinoma (HCC) after hepatectomy remains controversial. The present study aimed to classify the impact of tumor differentiation on solitary hepatitis B viral (HBV)-associated HCC using propensity score matching analysis.Methods: Between January 2009 and March 2015, the data of 721 HCC patients in West China Hospital were prospectively collected and analyzed. Propensity matching analysis was applied to overcome the imbalance in baseline characteristics. Survival analysis was performed using the Kaplan-Meier method. Risk factors were identified by the Cox proportional hazards model.Results: All HCC patients were classified into the moderately well-differentiated HCCs group (group A, n = 442, 61.3%) or poorly differentiated HCCs group (group B, n = 279, 38.7%). Patients with poorly differentiated HCCs commonly had a larger tumor size, more advanced tumors, and a higher alpha-fetoprotein (AFP) level. Patients with poorly differentiated HCCs had a poorer recurrence-free survival and overall survival before and after propensity score matching analysis. Poorly differentiated tumors, positive serum hepatitis B viral e antigen, positive hepatitis B virus deoxyribonucleic acid load, tumor size, microvascular invasion, and AFP > 400 ng/ml were risk factors of a poor outcome.Conclusions: Our propensity model provided strong evidence that a poorly differentiated tumor had a negative impact on the recurrence and long-term survival of solitary HBV-associated HCCs after curative hepatectomy. Antiviral therapy might improve their prognosis. [ABSTRACT FROM AUTHOR]

Objective: The optimal treatment strategy for patients with recurrent hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the outcomes of salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) with respect to the time to recurrence after initial curative resection.Methods: Between 2007 and 2016, 756 patients underwent curative hepatectomy for HCC in accordance with the Milan criteria. Among them, 152 experienced an intrahepatic recurrence and underwent SLT (n = 36) and RR/RFA (n = 116). Clinical data, overall survival (OS), and disease-free survival (DFS) (including subgroup analyses) according to the time to recurrence were statistically compared between the 2 groups, and prognostic factors were identified.Results: The DFS of the patients who underwent SLT was much better than that of the patients who underwent RR/RFA (P = 0.002), particularly those with late recurrence (more than 12 months, P = 0.004). The time to recurrence from initial hepatectomy was found to be an independent predictor of OS and DFS.Conclusions: SLT, rather than re-resection or RFA, should be the preferred treatment option for patients with late recurrence. [ABSTRACT FROM AUTHOR]

Background: The proportion of the both serum hepatitis B surface antigen and hepatitis C antibody negative hepatocellular carcinoma (NBNC HCC) patients are tended to increase recently. We investigated the characteristics and surgical outcome for those patients after liver resection.Methods: Four hundred and thirty-five NBNC patients were involved in our study. According to the results of the HBcAb in the serum, those patients were divided into HBcAb-positive subgroup (n = 328) and HBcAb-negative subgroup (n = 107). Based on the multivariate risk factors, the nomogram was constructed for predicting the possibility for over survival (OS) rate.Results: For all of the NBNC HCC patients, the median OS was 57 months with 5-year OS rate 54.0%. The positive HBcAb NBNC patients were associating with a better liver function (p = 0.026), higher AFP (p < 0.001) and more proportion of micro-vascular invasion (p = 0.001). Multivariate analysis revealed that worse liver function (Child-Pugh B, HR = 1.93; 95% CI: 1.23-3.04), vascular invasion (MIVI vs negative, HR = 1.86; 95% CI: 1.21-2.86, MAVI vs negative, HR = 2.05; 95% CI: 1.37-3.06), poorer ES differentiation (HR = 2.34; 95% CI: 1.67-3.30) and larger tumor size (HR = 1.10; 95% CI: 1.06-1.15) were associated with the worse OS.Conclusion: We established a novel prognostic nomogram to predict the OS of NBNC HCC patients after liver resection. The prognosis of NBNC HCC was mainly determined by tumor stage and liver function not by the previous etiologies. [ABSTRACT FROM AUTHOR]

The impact of the tumor location on the outcome after hepatic resection (HR) in multifocal hepatocellular carcinoma (HCC) is still poorly understood. The aim of this study was to compare the short- and long-term outcomes of HR patients with multifocal tumors meeting the Milan criteria and tumors located in the same or different sections. A total of 219 consecutive HR patients with multifocal tumors meeting the Milan criteria were divided into group SS (n = 97; same section) and group DS (n = 122; different sections) according to their anatomical location (Couinaud's segmentation). The prognostic predictors were evaluated, and a subgroup analysis was performed. The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates were significantly higher in group SS than group DS. The subgroup analysis showed that patients with two tumors in the same section and patients undergoing en bloc resection had better OS and RFS. A multivariate analysis revealed that tumors located in different sections and macrovascular invasion were independent predictors of poor prognosis. In HCC patients with multifocal tumors meeting the Milan criteria, tumors located in the same hepatic section may lead to better long-term survival and lower HCC recurrence rates than tumors in different sections after HR. [ABSTRACT FROM AUTHOR]

• IRF4 played a critical role in the tumour immune microenvironment of HCC. • The IRF4 risk score predicted prognosis in HCC patients. • The IRF4 risk score predicted the response to immunotherapy in HCC patients. • IRF4 inhibited proliferation and metastasis and was positively correlated with PD-1 expression in HCC tissues. • IRF4 suppressed the JAK2/STAT3 signalling pathways and EMT signalling activity. Hepatocellular carcinoma (HCC) remains a global health challenge due to high recurrence and metastasis rates. The interferon regulatory factor (IRF) family plays an essential role in the tumour immune microenvironment. However, an IRF family-based score that can predict prognosis and response to immunotherapy in HCC patients has not been adequately investigated. Here, we comprehensively evaluated the expression landscape and prognostic significance of IRF family genes as well as their relationship with the immune microenvironment. We further screened IRF4-associated genes to construct a signature and explored their biological features. Then, we established an IRF4 risk score consisting of nine IRF4-associated genes. Importantly, we demonstrated significant differences in the prognostic stratification and immune characteristics of HCC patients with different IRF4 risk scores. The predictive capability of the IRF4 risk score was validated in different HCC subgroups and independent HCC cohorts. Moreover, immunohistochemical analysis of our HCC cohort revealed a positive correlation between IRF4 and PD-1 expression. In vitro experiments demonstrated that the overexpression of IRF4 inhibited the proliferation and migration capacity of HCC cells by restricting the JAK2/STAT3 signalling pathway and epithelial-mesenchymal transition. Overall, our study identified a novel IRF4 risk score that could serve as a robust prognostic biomarker and provide therapeutic benefits for immunotherapy in HCC patients, which may be helpful for clinical decision-making for HCC patients. [ABSTRACT FROM AUTHOR]