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OBJECTIVE: Vascular invasion (VI) profoundly impacts the prognosis of hepatocellular carcinoma (HCC), yet the underlying biomarkers and mechanisms remain elusive. This study aimed to identify prognostic biomarkers for HCC patients with VI. METHODS: Transcriptome data from primary HCC tissues and HCC tissues with VI were obtained through the Genome Expression Omnibus database. Differentially expressed genes (DEGs) in the two types of tissues were analyzed using functional enrichment analysis to evaluate their biological functions. We examined the correlation between DEGs and prognosis by combining HCC transcriptome data and clinical information from The Cancer Genome Atlas database. Univariate and multivariate Cox regression analyses, along with the least absolute shrinkage and selection operator (LASSO) method were utilized to develop a prognostic model. The effectiveness of the model was assessed through time-dependent receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. RESULTS: In the GSE20017 and GSE5093 datasets, a total of 83 DEGs were identified. Gene Ontology analysis indicated that these DEGs were predominantly associated with xenobiotic stimulus, collagen-containing extracellular matrix, and oxygen binding. Additionally, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the DEGs were primarily involved in immune defense and cellular signal transduction. Cox and LASSO regression further identified 7 genes (HSPA8, ABCF2, EAF1, MARCO, EPS8L3, PLA3G1B, C6), which were used to construct a predictive model in the training cohort. We used X-tile software to calculate the optimal cut-off value to stratify HCC patients into low-risk and high-risk groups. Notably, the high-risk group exhibited poorer prognosis than the low-risk group (P < 0.001). The model demonstrated area under the ROC curve (AUC) values of 0.815, 0.730, and 0.710 at 1-year, 3-year, and 5-year intervals in the training cohort, respectively. In the validation cohort, the corresponding AUC values were 0.701, 0.571, and 0.575, respectively. The C-index of the calibration curve for the training and validation cohorts were 0.716 and 0.665. Decision curve analysis revealed the model's efficacy in guiding clinical decision-making. CONCLUSIONS: The study indicates that 7 genes may be potential prognostic biomarkers and treatment targets for HCC patients with VI.
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Background and Aims: The objective of this study was to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) on the survival of cirrhotic patients with esophagogastric variceal bleeding (EGVB) treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: A total of 293 patients treated with TIPS were included. The receiver operator characteristic curve (ROC) was used to calculate the optimal cut-off values of parameters such as NLR. The Kaplan-Meier curve and Cox proportional risk model were used to evaluate the effects of NLR and other variables on 2-year all-cause mortality. Results: The area under the ROC for NLR was 0.634, with an optimal cutoff value of 4.9. Two-year mortality rates for patients with high (≥4.9) and low (<4.9) NLR were 22.1% and 9.3%, respectively (Log rank test: P = 0.002). After correcting for confounders, multivariate analysis demonstrated that NLR ≥ 4.9 (HR = 2.741, 95% CI 1.467-5.121, P = 0.002), age ≥ 63 (HR = 3.403, 95% CI 1.835-6.310, P < 0.001), and gender (male) (HR = 2.842, 95% CI 1.366-5.912, P = 0.001) were independent risk factors for the mortality outcome. Considering the stratification of early and selective TIPS treatment, high NLR still significantly increased the risk of mortality for patients (Log rank test: P = 0.007, HR = 2.317, 95% CI 1.232-4.356). Conclusion: NLR can help to predict survival in EGVB patients after TIPS, and the type of TIPS should also be considered in practical applications.
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Objective: To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE). Methods: We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs). Results: A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0-27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373-6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492-20.078, P < 0.001) were associated with the median OS. Conclusion: Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.
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Background: This study aimed to evaluate whether a large paraumbilical vein (L-PUV) was independently associated with the occurrence of overt hepatic encephalopathy (OHE) after the implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Methods: This bi-center retrospective study included patients with cirrhotic variceal bleeding treated with a TIPS between December 2015 and June 2021. An L-PUV was defined in line with the following criteria: cross-sectional areas > 83 square millimeters, diameter ≥ 8 mm, or greater than half of the diameter of the main portal vein. The primary outcome was the 2-year OHE rate, and secondary outcomes included the 2-year mortality, all-cause rebleeding rate, and shunt dysfunction rate. Results: After 1:2 propensity score matching, a total of 27 patients with an L-PUV and 54 patients without any SPSS (control group) were included. Patients with an L-PUV had significantly higher 2-year OHE rates compared with the control group (51.9% vs. 25.9%, HR = 2.301, 95%CI 1.094−4.839, p = 0.028) and similar rates of 2-year mortality (14.8% vs. 11.1%, HR = 1.497, 95%CI 0.422−5.314, p = 0.532), as well as variceal rebleeding (11.1% vs. 13.0%, HR = 0.860, 95%CI 0.222−3.327, p = 0.827). Liver function parameters were similar in both groups during the follow-up, with a tendency toward higher shunt patency in the L-PUV group (p = 0.067). Multivariate analysis indicated that having an L-PUV (HR = 2.127, 95%CI 1.050−4.682, p = 0.037) was the only independent risk factor for the incidence of 2-year OHE. Conclusions: Having an L-PUV was associated with an increased risk of OHE after a TIPS. Prophylaxis management should be considered during clinical management.
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PURPOSE: The aim of this study was to validate and compare the prognostic performance of the albumin-bilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, Child-Pugh (CP) grade, and Model for End-Stage Liver Disease (MELD) score in predicting the 1-year variceal rebleeding probability using artificial intelligence for patients with cirrhosis and variceal bleeding undergoing early transjugular intrahepatic portosystemic shunt (TIPS) procedures. MATERIALS AND METHODS: This dual-center retrospective study included two cohorts, with patients enrolled between January 2016 and September 2018 in the training cohort and January 2017 and September 2018 in the validation cohort. In the training cohort, independent risk factors associated with the 1-year variceal rebleeding probability were identified using univariate and multivariate logistic analyses. ALBI-, PALBI-, Child-Pugh-, and MELD-based nomograms and an artificial neural network (ANN) model were established and validated internally in the training cohort and externally in the validation cohort, which included patients with variceal bleeding who were treated with preventive TIPS. RESULTS: A total of 259 patients were included. The median follow-up periods were 24.1 and 18.9 months, and the 1-year variceal rebleeding rates were 12.3% (14/114) and 10.3% (15/145) in the training and validation cohorts, respectively. In the training cohort, all four variables were identified as independent risk factors. Four nomograms were then established and showed comparable prognostic performances after internal (C-index: 0.879, 0.829, 0.874, and 0.798) and external (C-index: 0.720, 0.719, 0.718, and 0.703) validation. The ANN demonstrated that these four variables had comparable importance in predicting the 1-year variceal rebleeding probability. CONCLUSION: None of the four variables are optimal in predicting the 1-year variceal rebleeding probability for patients with cirrhosis and variceal bleeding undergoing early TIPS.
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Enfermedad Hepática en Estado Terminal , Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Albúminas , Inteligencia Artificial , Bilirrubina , Enfermedad Hepática en Estado Terminal/complicaciones , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/etiología , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Six pigs underwent implantation of a portal vein infusion port by transjugular access. The technical success rate was 100% (n = 6), with no surgical complications or deaths. At 1 month after implantation, the catheter tip had moved from the splenic vein to the main portal vein, while the catheter protruded into the right ventricle through the right atrium in all cases. Hence, the infusion port system has not been used in clinical practice due to its obvious displacement after implantation. However, this study provides a new idea for future exploration of portal vein infusion pathways.