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Recent studies suggest that circular RNA (circRNA)‐mediated post‐translational modification of RNA‐binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi‐omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif‐containing 21 to reduce the proteasome‐mediated degradation of NCL via K48‐linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient‐derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi‐omics landscape of circRNA‐mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target. [ABSTRACT FROM AUTHOR]

This article discusses a study on the use of liver transplantation as a treatment option for patients with advanced hepatocellular carcinoma (HCC) after successful downstaging with lenvatinib, transcatheter arterial chemoembolization (TACE), and camrelizumab. The study found that three patients who underwent liver transplantation had positive outcomes with stable graft function, no tumor recurrence or metastasis, and promising results. The article highlights the potential benefits of combination therapy and calls for further research to provide more evidence. The document also provides supplementary material and author contributions for the study, which was funded by the National Natural Science Foundation of China and the Key Research and Development Program of Sichuan Province. The authors disclose potential conflicts of interest related to grant support and lecture fees from pharmaceutical companies. The data supporting the study's findings are available upon request from the corresponding author. [Extracted from the article]

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]

Simple Summary: Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide. Despite significant progress in the comprehensive management of HCC, continued efforts are still necessary to identify prognostic assessment approaches for patient-specific survival so that more appropriate treatment and management regimens can be proposed for different HCC subpopulations. Here, we comprehensively exploited the expression characteristics of 12 SRSF family members across multiple datasets. We further identified an SRSF score consisting of 18 SRSF-related genes which were associated with overall survival and drug sensitivity in HCC. Moreover, the predictive power of the SRSF score was validated in independent HCC cohorts and different HCC subgroups. We further explored the effect of SRSF11 expression on HCC cell proliferation and drug sensitivity. Overall, our study provides a novel predictive model to assess the prognosis and drug sensitivity of HCC. The serine/arginine-rich splicing factors (SRSF)-mediated alternative splicing plays an essential role in the occurrence and progression of hepatocellular carcinoma (HCC). However, the SRSF-based signature that can predict the prognosis and therapy efficiency is yet to be investigated in HCC. Here, we comprehensively assessed the landscape and prognostic significance of the SRSF family genes in HCC. Then, we screened the SRSF family-related genes for signature construction and explored their biological characteristics. We further established an SRSF score consisting of 18 SRSF-associated genes and evaluated its correlation with prognosis and drug sensitivity in HCC. The predictive power of the SRSF score was validated in independent HCC cohorts and different HCC subgroups. Moreover, we further investigated that knockdown of SRSF11, a pivotal gene in the SRSF score, inhibited CDK1-dependent proliferation and enhanced the drug sensitivity of HCC cells. Overall, our study identified a novel SRSF family-based predictive model, and we demonstrated that SRSF11 is a promising therapeutic target for HCC, which enhances our understanding of the SRSF family genes and provides valuable insights into the clinical treatment and molecular mechanisms of HCC. [ABSTRACT FROM AUTHOR]

Introduction: Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + .Methods: This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival.Results: The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P < 0.05). Compared with that in other indices, in logistic and ANN multivariate analysis, CD4 + -to-FIB-4 ratio (CD4+/FIB-4) had the highest importance with 0.716 C-statistic and 145.93 cut-off value. In terms of overall survival rate, HIV infection was not a risk factor (P = 0.589); however, CD4+/FIB-4 ≤ 145.93 significantly affected patient prognosis (P = 0.002).Conclusion: HIV infection does not affect the prognosis of BCLC-B HCC, but CD4+ have a significant predictive value. CD4+ played a vital role in HCC and this deserves the attention from physicians. Further, the CD4+/FIB-4 is a clinically valuable effective prognostic indicator for these patients. [ABSTRACT FROM AUTHOR]

Objective: The predicting values of programmed cell death protein 1 (PD-1) and programmed death-ligand 1(PD-L1) were unclear in Hepatocellular carcinoma (HCC) patients who receive sorafenib treatment after curative hepatic resection. Methods: We retrospectively enrolled HCC patients who received adjuvant sorafenib treatment after curative resection (N = 154), and patients had resection alone (N = 312). Immunohistochemistry was used to assess expression of PD-1 on tumor infiltration immune cells and PD-L1 on HCC cells. Cox proportional hazard models were used to explore association between clinicopathological factors and risk of tumor recurrence. Results: No significant difference was detected in RFS (p = 0.542), or OS (p = 0.542) between the resection and sorafenib group and resection alone group. In the 154 patients who received adjuvant sorafenib, expression of PD-1 or PD-L1 was not significantly associated with long-term outcomes. However, in the 122 patients at high risk of postoperative recurrence who had adjuvant sorafenib treatment, characterized by maxim tumor size ≥5 cm, or the presence of macro- or micro-vascular invasion, patients with PD-L1 overexpression (≥3.0) had significantly worse RFS (p = 0.021), and overexpression of PD-L1 (HR: 1.88, 95%CI: 1.18–2.99, p = 0.008) was identified as an independent risk factor associated with unfavorable RFS. Conclusion: Overexpression of PD-L1 serves as an independent predictor of recurrence in HCC patients at high risk of relapse who received adjuvant sorafenib treatment after curative resection. [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]

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: Microvascluar invasion and satellite lesion (MS), important unfavourable pathological factors, significantly contribute to tumour recurrence and impair the prognosis in hepatocellular carcinoma. We aimed to construct a model for the prediction of MS in order to plan treatment better. Methods: A total of 1135 consecutive patients with hepatocellular carcinoma who received radical hepatectomy at West China Hospital were randomly assigned to a training set and a validation set. Multivariate analysis was preformed to identify independent risk factors of MS in the training set, and a nomogram was then constructed based on the risk factors. The concordance index (C‐index) and a calibration curve were used to assess the predictive performance of the model. Results: The occurrence rate of MS was about 36.5%. Based on the multivariate analysis, the following six variables were incorporated into the nomogram: age (hazard ratio (HR): 0.531), alpha fetoprotein (HR: 1.327), neutrophil‐to‐lymphocyte ratio (>2.8, HR: 1.732), international normalized ratio (>1.07, HR: 1.702), tumour size (HR: 1.116) and tumour number (HR: 1.842). The model showed satisfactory discrimination abilities, with a C‐index of 0.721 for the training set and 0.704 for the validation set. The receiver operating characteristic curve confirmed the predictive power. Meanwhile, the calibration curve presented a goodness of fit between prediction of the model and actual observations. Conclusions: The user‐friendly model may be useful for prediction of the occurrence of MS and to plan treatment more rationally preoperatively. [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]

Background: Hepatocellular carcinoma (HCC) in adolescent and younger adult (AYA) patients is usually diagnosed at an advanced stage such that curative treatments are often not possible. The aimed of this study was to compare the outcome of attempted curative treatment, liver resection (LR) versus transarterial chemoembolization (TACE), in AYA patients presenting with intermediate or advanced HCC defined by the Barcelona Clinic Liver Cancer (BCLC) stage B and C.Methods: All AYA patients diagnosed with BCLC stage B or C HCC undertaking LR (n = 276) and TACE (n = 136) were included in our study. The prognostic factors of the patients were analyzed and the propensity score-matched patients (120 pairs) were analyzed to adjust for any baseline differences.Results: The overall survival rate of the patients undertaking LR was higher than TACE for the both entire and the propensity matched population (p < 0.001). In the multivariate analysis, propensity scoring analyses suggested that HBsAg positivity, macrovascular invasion, tumor size and TACE treatment were the independent prognostic factors associated with a worse survival outcome.Conclusion: The effect of LR was superior to that of TACE for patients with intermediate and advanced stage HCC. The survival outcome was associated with the tumor size, macrovascular invasion, and hepatitis history in AYA HCC patients. [ABSTRACT FROM AUTHOR]

Background: The treatment of intrahepatic recurrent hepatocellular carcinoma (HCC) has been poorly investigated, and the optimal treatment strategy remains unclear.Aims: The aim of this study was to compare outcomes between salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) for intrahepatic recurrent HCC according to recurrence pattern.Methods: Based on postoperative histopathological examination, 122 patients with intrahepatic recurrent HCC were divided into an intrahepatic metastasis (IM, n = 75) group and a multicentric occurrence (MO, n = 47) group. The demographic, clinical, and primary and recurrent tumor characteristics of the IM group and the MO group were collected and compared. Overall survival (OS) and disease-free survival (DFS) were analyzed, and subgroup analysis according to retreatment type (SLT vs. RR/RFA) was conducted. Twenty-nine clinicopathological variables potentially related to prognostic factors affecting survival were analyzed using a Cox proportional hazard model.Results: The patients that received SLT treatment exhibited favorable DFS compared to patients that received RR/RFA (P = 0.002). OS (P < 0.001) and DFS (P = 0.008) rates were significantly increased in the MO group compared with in the IM group. Subgroup analysis revealed that DFS was significantly improved for patients in the MO group treated with SLT compared to patients treated with RR/RFA (P = 0.017). Recurrence pattern was an independent prognostic factor for both OS [hazard ratio (HR) = 0.093, 95% confidence interval (CI): 0.026-0.337, P < 0.001] and DFS (HR = 0.318, 95% CI: 0.125-0.810, P = 0.016; HR = 3.334, 95% CI: 1.546-7.18, P = 0.002).Conclusions: For patients with intrahepatic recurrent HCC, an MO recurrence pattern is associated with better long-term outcomes than the IM pattern. SLT is the preferred option for intrahepatic recurrent HCC, especially for MO cases. [ABSTRACT FROM AUTHOR]

Background: The surgical decision of performing anatomic resection (AR) or nonanatomic resection (NAR) in patients with hepatocellular carcinoma remains controversial. The aim of the current study is to conduct a meta-analysis on published results to compare surgical outcomes after AR and NAR. Methods: A comprehensive search of the Pubmed, Ovid-Medline, Embase, Cochrane library, and Science Citation indexes was performed. Overall and disease free survival (DFS), perioperative mortality and morbidity were the main outcomes. The meta-analysis was performed using Revman 5.3 statistical software, and the results are expressed as the relative risk (RR) or weighted mean differences with 95% of confidence intervals. Results: After application of the exclusion and inclusion criteria, 25 studies published between 1996~2015 that compared outcomes after AR and NAR in patients with HCC were identified. A total of 10216 patients were included in the meta-analysis, 4576 in the AR group and 5640 in the NAR group. Liver cirrhosis was found in 54.8% (range from 18.8% to 100%) of patients in the AR group and 67.8% (range from 34.3% to 100%) of patients in the NAR group, resulting in a RR of 0.45 (I2 = 18%, fixed model, 95% CI 0.39–0.52; Z = 10.31; P = <0.00001). The meta-analysis revealed a statistically significant 5-year survival (RR of 1.10, 95% CI 1.03–1.17; Z = 2.92, P = 0.004) and DFS (RR: 1.33, 95% CI 1.18–1.51; Z = 4.46, P <0.00001) advantage for patients undergoing AR resection compared to NAR. In regards to safety, no statistical significance was found in mortality and morbidity between the two groups. Eight studies including 1812 patients with small (<5 cm) solitary HCC indicated a better 5-year DFS in the AR group (41.4%) than in the NAR group (28.6%), with a RR of 1.32 (I2 = 42, fixed model, 95%CI: 1.15–1.52, Z = 3.86, P = 0.0001). Conclusion: The current study demonstrates better surgical outcomes after AR than NAR in patients with HCC. Therefore, AR is recommended in resectable HCC, especially with small (<5 cm) solitary tumours. [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]

Background Radiofrequency ablation (RFA) has been recommended as a curative treatment for patients with single early-stage unifocal hepatocellular carcinomas (HCCs) for years; however, the effect of this treatment on multifocal tumours has remained uncertain. Aims We conducted a retrospective study to evaluate the overall survival (OS) and recurrence-free survival (RFS) rates of early HCC patients with multiple tumours subjected to different RFA modalities. Methods One hundred fifty-four HCC patients with multifocal tumours who met the Milan criteria and underwent RFA were enrolled in this study. We divided the patients into 3 groups according to the surgical approach utilised (percutaneous, laparoscopic and open RFA; selection was based on the locations of the tumours for whether they were adhered to the subhepatic inferior vena cava or the gastrointestinal tract) and into 2 subgroups according to the tumour numbers and locations. Results No deaths occurred in the 30-day post-operation period, and there were no significant differences in the complication, OS or RFS rates between the 3 groups. The 1-, 3- and 5-year OS rates were 88.9%, 75.5% and 50.9% in the subgroup with 2 tumours, respectively, versus 91.3%, 56.3% and 17.5% in the subgroup with 3 tumours, respectively ( P = 0.001). The corresponding values were 93.2%, 77.4% and 50.8% in the subgroup with tumours in the same segment and 82.4%, 54.8% and 23.0% in the subgroup with tumours in different segments ( P = 0.001). Conclusion RFA was proven to be an effective and safe method for the treatment of multifocal HCCs. Among the patients with 2 tumours within the same segment, RFA achieved better long-term outcomes in terms of both overall and recurrence-free survival. [ABSTRACT FROM AUTHOR]

The optimum primary treatment strategy for early hepatocellular carcinoma ( HCC) patients with multiple nodules remains unclear. We aimed to compare the outcomes of living donor liver transplantation ( LDLT) with that of liver resection ( LR) for early Child-Pugh A HCC patients with multiple nodules meeting the Milan criteria. From January 2007 to July 2012, 67 of 375 patients with early HCC in our centre fulfilled the inclusion criteria (group LDLT, n = 34 versus group LR, n = 33). Patient and tumour characteristics, operative data, postoperative course and outcomes were analysed retrospectively. The postoperative mortality and rate of major complications were similar in both groups. The 5-year overall survival ( OS; 76.5% vs. 51.2%, P = 0.046) and recurrence-free survival ( RFS; 72.0% vs. 19.8%, P = 0.000) were better in group LDLT than that in group LR. The 5-year OS and RFS were similar between patients with tumours located in the same lobe ( TSL) and those in the different lobes ( TDL) after LDLT, whereas the 5-year RFS was better in patients with tumours in TSL (30.6% vs. 0%, P = 0.012) after LR. In conclusion, primary LDLT might be the optimum treatment for early HCC patients with multiple nodules meeting the Milan criteria. [ABSTRACT FROM AUTHOR]

Objective and Background: Although many studies on evaluating the safety of liver resection in obese patients have been conducted, the results remain contradictory. The aim of our study was to investigate the safety of overweight and obese patients undergoing liver resection for hepatitis B-related hepatocellular carcinoma in a large sample. Methods: In a retrospective cohort with 1543 hepatitis B-related hepatocellular carcinoma patients, the subjects were stratified into four groups according to their body mass index(BMI): obesity(BMI≥28), overweight(BMI:24.0–27.9), normal weight(BMI:18.5–23.9) and underweight(BMI<18.5). The Dindo–Clavien classification system was used for grading complications. Clinical characteristics and operative outcomes were compared among the four groups. Risk factors for postoperative complications were evaluated by multivariate analysis. Results: According to the category criteria of the Working Group on Obesity in China (WGOC) criteria, 73(4.7%) obese, 412(26.7%) overweight, 982(63.6%) normal weight and 76(4.9%) underweight patients were included in our cohort. Overweight and obese patients had more preoperative comorbidities such as hypertension(P<0.001). Mortality, total complications and complications classified by Clavien system were similar among the four groups except that the underweight patients had fewer total complications. However, postoperative wound complication was more common in overweight and obese patients(6.3% vs 2.5%,P<0.001,11.0% vs 2.5%,P = 0.001). Multivariate analysis revealed that BMI was not an independently significant factor for postoperative complications. Conclusions: Liver resection for obese and overweight patients is safe and BMI itself is not a risk factor for mortality and morbidity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The role of laparoscopically anatomical resection (LAR) for hepatocellular carcinoma (HCC) remains unclear due to the more demanding technique required in laparoscopy. This study is to analyze the clinical impact of LAR compared to laparoscopically non-anatomical resection (LNAR) for HCC. All patients received laparoscopic hepatectomy for HCC (diameter 5–10 cm) from January 2015 to December 2018 were retrospectively enrolled in this study. Patients were divided into LAR and LNAR groups. The perioperative and oncological outcomes were evaluated based on propensity score matching (PSM) method. After PSM, 51 patients in each group were enrolled. The operative time in LAR group was longer (240 vs 195.0 min, p = 0.012) and blood loss was more (200.0 vs 150.0 mL, p = 0.030) than those of LNAR group, respectively. The total complication rates were comparable between them (21.6% vs 17.6%, p = 0.500). The 3-year overall survival rates were 59.4% in LAR group and 38.7% in LNAR group, respectively (p = 0.045). The 3-year disease-free survival rates were 52.3% in LAR group and 27.0% in LNAR group, respectively (p = 0.042). LAR could be feasibly performed with comparable perioperative outcomes and contributed to improve long-term survival in patients with HCC (diameter 5–10 cm) when compared to LNAR. [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]

Tumor metastasis is a major cause of cancer mortality. However, little is known regarding the regulation of abnormal cholesterol metabolism in hepatocellular carcinoma (HCC) metastasis. Here, we show that the expression of high-density lipoprotein binding protein (HDLBP), a lipid transporter, is clinically correlated with tumor metastasis in HCC patients. Moreover, HDLBP was required for cholesterol-induced HCC metastasis. We revealed that knockdown and overexpression of HDLBP significantly inhibited and enhanced, respectively, the metastasis, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. Mechanistically, coimmunoprecipitation and mass spectrometry screening uncovered BRAF as a protein target of HDLBP. HDLBP was found to promote EMT signaling in a BRAF-dependent manner. Furthermore, HDLBP interacts with BRAF and inhibits its ubiquitinated degradation by abrogating BRAF-ITCH interactions. Notably, further studies suggest that dabrafenib exhibited a greater metastasis-suppressive effect in HDLBP knockout HCC than isolated treatment. Overall, our findings imply that cholesterol-induced HDLBP contributes to the metastasis and invasion of HCC through BRAF-dependent EMT signaling and that HDLBP may be applied as a biomarker and therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Background Radiofrequency ablation (RFA) is a radical treatment for both primary and recurrent small hepatocellular carcinoma (HCC) with an optimistic outcome which is comparable with surgery. For localized recurrence of HCC after liver transplantation (LTx), surgical resection is considered the most favorable treatment. When surgical resection is contraindicated or technically infeasible, whether RFA is as efficient after transplantation as in nontransplant settings remains unclear. Materials and methods A cohort study was undertaken in a population of patients that had a recurrence of HCC after LTx to evaluate the outcomes of different modalities (surgery, RFA, and conservative therapy) on long-term survival. Results Seventy-eight of the 486 HCC patients who received LTx had a recurrence (16%). Fifteen patients underwent surgical resection, and 11 patients were treated with RFA. The remaining 52 patients received conservative therapy (17 patients with sirolimus plus sorafenib regimen; the others were treated with conventional supportive therapy). The 1-, 3-, and 5-y overall survival rates were 92%, 51%, and 35% for the patients treated with surgery and 87%, 51%, and 28% for the patients that received RFA. The corresponding 1-, 3-, and 5-y rerecurrence-free survival rates were 83%, 16%, and 16% for the patients treated with surgery and 76%, 22%, and 0% for the patients that received RFA, respectively. There was no significant difference in overall survival or rerecurrence-free survival between the surgical resection group and the RFA group ( P = 0.879, P = 0.745). Conclusions For HCC recurrence after LTx, RFA is preferable when surgical resection is contraindicated or technically infeasible and provides comparable long-term survival compared with surgery. [ABSTRACT FROM AUTHOR]

Background: Although hepatic resection (HR) has been recommended as the first-line treatment option for patients with a solitary tumor, the first-line treatment for patients with multifocal tumors meeting the Barcelona-Clinic Liver Cancer (BCLC) stage A still remains unclear. This study compared outcomes for patients with multifocal tumors meeting the BCLC stage A treated by HR and radiofrequency ablation (RFA).Study Design: A total of 384 consecutive patients with multifocal tumors meeting the BCLC stage A, who underwent HR (n = 224) or RFA (n = 160), were included. Moreover, propensity score-matched patients were analyzed to adjust for baseline differences.Results: The 1-, 3-, and 5-year overall survival (OS) rates after HR and RFA were 96%, 71.7%, and 36.3%, and 90.0%, 72.7%, and 37.8%, respectively (p = 0.609); HR provided significantly better recurrence-free survival (RFS) rates than RFA at 1, 3, and 5 years (87.5%, 53.1%, and 20.1% vs 83.1%, 34.0%, and 9.7%, respectively, p = 0.001). Patients selected in the propensity-matching model showed similar results. Subgroup analysis also showed that HR was associated with better RFS than RFA for patients with 2 tumors, multifocal tumors located in the same lobe (Couinaud's segmentation) and segment (Takasaki's segmentation). Multivariate analysis revealed that 3 tumors, portal hypertension, and tumors located in different segments (Takasaki's segmentation) are independent predictors of poor prognosis in patients with multifocal tumors meeting the BCLC stage A.Conclusions: For patients with multifocal tumors meeting the BCLC stage A, HR may offer significantly better RFS than RFA, and HR may be considered as the first-line treatment option for those patients. [ABSTRACT FROM AUTHOR]