Guo-Bin Wu

Microvascular invasion (MVI) serves as a well-established prognostic factor for tumor recurrence and reduced survival following curative hepatectomy in hepatocellular carcinoma (HCC). This investigation aims to assess the therapeutic value of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in HCC patients with MVI and delineate the optimal patient subpopulations for this intervention. This retrospective cohort study analyzed patients with MVI in HCC patients who received curative resection from September 2013 to June 2019. After balancing baseline differences between the PA-TACE group and the non-TACE control group using propensity score matching (PSM), the differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups were compared. A multivariate Cox proportional hazards regression model was used to identify independent prognostic factors. Among 440 evaluable patients, PA-TACE demonstrated statistically significant improvements in both RFS and OS compared to non-TACE management, with consistent results observed in both the entire and propensity score-matched cohorts. Multivariate analysis established PA-TACE as an independent protective predictor for both RFS and OS. Subgroup analyses revealed pronounced clinical benefits in patients exceeding Milan criteria and those presenting with high-risk features including serum AFP ≥400 ng/mL, tumor size ≥5 cm, Edmondson-Steiner grade III/IV differentiation, M2-type MVI, or major hepatectomy. Notably, no survival advantage was observed in patients within Milan criteria or BCLC-A/B stages. PA-TACE provides substantial survival enhancement in HCC patients with MVI exceeding Milan criteria or with high-risk features, but offers limited benefit for Milan-eligible cases. Patient selection based on tumor biology is critical for optimizing adjuvant therapy.

Background: Postoperative early recurrence (ER) poses a major threat to long-term survival in hepatocellular carcinoma (HCC), especially in patients with microvascular invasion (MVI). Although conventional staging systems provide prognostic guidance, they are often inadequate for capturing recurrence risk in this high-risk subgroup. To develop and validate a CART-based prognostic model tailored to ER risk stratification and assessment of long-term outcomes following curative hepatectomy in MVI-positive HCC. Methods: A retrospective cohort of 440 patients with histologically confirmed HCC and MVI who underwent curative resection was analyzed. ER-associated predictors were identified via multivariable Cox regression and used to construct a classification and regression tree (CART) algorithm. Model discrimination, calibration, and clinical utility were evaluated using time-dependent ROC curves and decision curve analysis. Predictive performance for recurrence-free survival (RFS) and overall survival (OS) was compared against established staging systems. Results: Eight independent factors predictive of ER were identified: HBV-DNA load, tumor size, Edmondson-Steiner grade, tumor capsule integrity, MVI classification, satellite nodules, Ki-67 index, and CK19 expression. The CART model demonstrated robust discriminative ability (C-statistic: 0.773 in training; 0.764 in validation), and consistently outperformed conventional staging systems. Furthermore, CART-defined risk strata were significantly associated with both RFS and OS ( P < 0.001). Conclusions: This CART-based framework provides a transparent and clinically implementable tool for ER risk stratification in MVI-positive HCC. By outperforming existing staging algorithms, it offers a basis for individualized surveillance and postoperative management.

Background: This study aimed to evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in cytokeratin 19-positive (CK19+) hepatocellular carcinoma (HCC) patients and to identify cases that may benefit from PA-TACE. Methods: We conducted a retrospective analysis of 453 CK19+ HCC patients who underwent hepatectomy between November 2013 and June 2019 at our institution. We compared the recurrence-free survival (RFS) and overall survival (OS) between patients who received PA-TACE and those who did not, utilizing propensity score matching (PSM) to balance the groups. Results: Before and after PSM, both RFS and OS were significantly greater in PA-TACE group compared to the non-TACE group. Multivariable analysis identified PA-TACE as a significantly favorable factor of RFS and OS. In subgroups analyses, PA-TACE significantly improved RFS and OS in patients with CK19+ HCC under the following conditions: alpha-fetoprotein ≥ 400 ng/mL, cirrhosis, tumor size ≥ 5 cm, multiple tumors, major resection, Edmondson-Steiner stage III–IV, macrovascular invasion and microvascular invasion. Similar results were obtained in patients with higher tumor stages. Further recurrence model analyses revealed that PA-TACE significantly reduced early recurrence in patients with high-risk of postoperative recurrence, but had little effect on late recurrence. Conclusion: Among CK19+ HCC patients with higher recurrence of postoperative risk, PA-TACE could greatly improve RFS and OS.

Background: Systemic inflammatory response is a hallmark of cancer and plays a significant role in the development and progression of various malignant tumors. This research aimed to estimate the prognostic function of the C-reactive protein-albumin ratio (CAR) in patients undergoing hepatectomy for hepatocellular carcinoma (HCC) and compare it with other inflammation-based prognostic scores, including the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, systemic immune inflammation index, prognostic index, Glasgow prognostic score, and modified Glasgow prognostic score. Methods: Retrospective analysis was conducted on data from 1039 HCC cases who underwent curative liver resection. The prognostic performance of CAR was compared with other scores using the area under the time-dependent receiver operating characteristic (t-ROC) curve. Multivariable Cox regression analyses were performed to confirm independent predictors for disease-free survival (DFS) and overall survival (OS). Results: The area under the t-ROC curve for CAR in the evaluation of DFS and OS was significantly greater than that of other scores and alpha-fetoprotein (AFP). Patients were stratified based on the optimal cut-off value of CAR, and the data revealed that both DFS and OS were remarkably worse in the high-CAR set compared to the low-CAR set. Multivariable Cox analysis demonstrated that CAR was an independent prognostic parameters for assessing DFS and OS. Regardless of AFP levels, all patients were subsequently divided into significantly different subgroups of DFS and OS based on CAR risk stratification. Similar results were observed when applying CAR risk stratification to other scoring systems. CAR also showed good clinical applicability in patients with different clinical features. Conclusion: CAR is a more effective inflammation-based prognostic marker than other scores and AFP in predicting DFS as well as OS among patients with HCC after curative hepatectomy.

Bioinformatics tools were used to identify prognosis-related molecular subtypes and biomarkers of hepatocellular carcinoma (HCC). Differential expression analysis of four datasets identified 3330 overlapping differentially expressed genes (DEGs) in the same direction in all four datasets. Those genes were involved in the cell cycle, FOXO signaling pathway, as well as complement and coagulation cascades. Based on non-negative matrix decomposition, two molecular subtypes of HCC with different prognoses were identified, with subtype C2 showing better overall survival than subtype C1. Cox regression and Kaplan-Meier analysis showed that 217 of the overlapping DEGs were closely associated with HCC prognosis. The subset of those genes showing an area under the curve >0.80 was used to construct random survival forest and least absolute shrinkage and selection operator models, which identified seven feature genes (SORBS2, DHRS1, SLC16A2, RCL1, IGFALS, GNA14, and FANCI) that may be involved in HCC occurrence and prognosis. Based on the feature genes, risk score and recurrence models were constructed, while a univariate Cox model identified FANCI as a key gene involved mainly in the cell cycle, DNA replication, and mismatch repair. Further analysis showed that FANCI had two mutation sites and that its gene may undergo methylation. Single-sample gene set enrichment analysis showed that Th2 and T helper cells are significantly upregulated in HCC patients compared to controls. Our results identify FANCI as a potential prognostic biomarker for HCC.

Background: Accurate preoperative estimation of liver function reserve is the key to the safety of hepatectomy. Recently, indocyanine green retention test at 15 minutes (ICG-R15) has been widely used to estimate hepatic function reserve in different liver diseases. The purpose of this research was to investigate the clinical value of ICG-R15 in predicting postoperative major complications and severe posthepatectomy liver failure (PHLF) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) subjected to hepatectomy. Methods: A total of 354 HBV-associated HCC patients who underwent hepatectomy were enrolled. The Child–Pugh, model for end-stage liver disease (MELD), albumin–bilirubin (ALBI) and ICG-R15 for assessing postoperative complications risk were compared using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: Postoperative major complications developed in 32 patients (9.1%) and severe PHLF developed in 57 (16.1%) patients. Multivariate analyses revealed that ICG-R15 were independent factors for predicting postoperative major complications and severe PHLF. ROC curve analyses and DCA plots showed that the predictive abilities of ICG-R15 for postoperative major complications and severe PHLF risk was significantly greater than Child–Pugh, MELD, and ALBI scores. Similar results were obtained by stratifying different background subgroups. Then, patients were divided into three different risk cohorts, emphasizing the significantly discrepancy between the incidence of postoperative major complications and severe PHLF. Conclusion: Compared with Child–Pugh, MELD and ALBI scores, ICG‐R15 revealed significantly advantages in predicting postoperative major complications and severe PHLF in HBV-related HCC patients subjected to liver resection.

Background: Systemic inflammatory response (SIR) plays a crucial role in every step of tumorigenesis and development. More recently, the fibrinogen-to-albumin ratio (FAR), an inflammation-based model, was suggested as a prognostic maker for various cancer patients. This research aimed to estimate the prognostic abilities of FAR, neutrophil–lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet– lymphocyte ratio (PLR), and systemic immune–inflammation index (SII) in patients with hepatocellular carcinoma (HCC) subjected to curative hepatectomy. Methods: A total of 1,502 cases who underwent hepatectomy for HCC were included. The predictive performances of FAR, NLR, MLR, PLR and SII were assessed with regards to overall survival (OS) and disease-free survival (DFS). The area under the time-dependent receiver operating characteristic curve was used to compare prognostic performances. Results: Data revealed that FAR had higher predictive accuracy than other inflammation-based models and alpha-fetoprotein (AFP) in assessing OS and DFS. Indeed, the OS and DFS of patients with high FAR (> 8.9), differentiated by the optimal cut-off value of FAR, were remarkably reduced (p < 0.05 for OS and DFS). Multivariate Cox regression analyses identified that AFP, FAR, clinically significant portal hypertension, tumor size, Barcelona Clinical Liver Cancer staging system, major resection and blood loss were independent indicators for predicting OS and DFS. Furthermore, these patients could be classified according to their FAR into significantly different subgroups, regardless of AFP levels (p < 0.05 for DFS and OS). Similar results were obtained in other inflammation-based prognostic models. Conclusions: Compared with NLR, MLR, PLR, SII and AFP, FAR showed significant advantages in predicting survival of HCC patients subjected to liver resection.

Purpose The purpose of the present study was to use malignant cell-related and tumor microenvironment (TME)-related molecules to develop a novel molecular subtype of hepatocellular carcinoma (HCC). Methods The tumor purity (TP)-related and TME-related genes were identified and separately used to construct the TP-related and TME-related polygenic risk score (PRS). According to the two PRSs, we developed the TP-TME risk classification which was validated in two external data sets from The Cancer Genome Atlas Program and International Cancer Genome Consortium database. We also performed functional enrichment and drug repositioning analysis to reveal the potential biological heterogeneity among different subtypes. Results The three TP-TME risk subtypes of HCC had significantly different prognosis and biological characteristics. The TP-TME low risk subtype had the best prognosis and was characterized by well-differentiated, the TP-TME high risk subtype had the worst prognosis and was characterized by aberrant activation of TGFβ and WNT pathways, and the TP-TME high risk subtype had the moderate prognosis and was characterized by exhibited activated MYC targets and proliferation-related gene sets. These three TP-TME risk subtypes may respond differently to immunotherapy (e.g., immune checkpoint inhibitors and chimeric antigen receptor-modified T cells) or other drug therapies. Conclusion By combining the TP-related PRS and TME-related PRS, we proposed and validated the TP-TME risk subtyping system to divide patients with HCC into three subtypes with distinct biological characteristics and prognoses. These findings highlight the significant clinical implications of the TP-TME risk subtyping system and provide potential personalized immunotherapy strategies for HCC.

Hepatic encephalopathy (HE) is a neurological disorder that occurs in patients with liver insufficiency. However, its pathogenesis has not been fully elucidated. Pharmacotherapy is the main therapeutic option for HE. It targets the pathogenesis of HE by reducing ammonia levels, improving neurotransmitter signal transduction, and modulating intestinal microbiota. Compared to healthy individuals, the intestinal microbiota of patients with liver disease is significantly different and is associated with the occurrence of HE. Moreover, intestinal microbiota is closely associated with multiple links in the pathogenesis of HE, including the theory of ammonia intoxication, bile acid circulation, GABA-ergic tone hypothesis, and neuroinflammation, which contribute to cognitive and motor disorders in patients. Restoring the homeostasis of intestinal bacteria or providing specific probiotics has significant effects on neurological disorders in HE. Therefore, this review aims at elucidating the potential microbial mechanisms and metabolic effects in the progression of HE through the gut–brain axis and its potential role as a therapeutic target in HE.