Feasibility Study of Computed Tomographic Radiomics Model for the Prediction of Early and Intermediate Stage Hepatocellular Carcinoma Using BCLC Staging.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious health concern because of its high morbidity and mortality. The prognosis of HCC largely depends on the disease stage at diagnosis. Computed tomography (CT) image textural analysis is an image analysis technique that has emerged in recent years. OBJECTIVE: To probe the feasibility of a CT radiomic model for predicting early (stages 0, A) and intermediate (stage B) HCC using Barcelona Clinic Liver Cancer (BCLC) staging. METHODS: A total of 190 patients with stages 0, A, or B HCC according to CT-enhanced arterial and portal vein phase images were retrospectively assessed. The lesions were delineated manually to construct a region of interest (ROI) consisting of the entire tumor mass. Consequently, the textural profiles of the ROIs were extracted by specific software. Least absolute shrinkage and selection operator dimensionality reduction was used to screen the textural profiles and obtain the area under the receiver operating characteristic curve values. RESULTS: Within the test cohort, the area under the curve (AUC) values associated with arterial-phase images and BCLC stages 0, A, and B disease were 0.99, 0.98, and 0.99, respectively. The overall accuracy rate was 92.7%. The AUC values associated with portal vein phase images and BCLC stages 0, A, and B disease were 0.98, 0.95, and 0.99, respectively, with an overall accuracy of 90.9%. CONCLUSION: The CT radiomic model can be used to predict the BCLC stage of early-stage and intermediate-stage HCC.

Comparison of post-resection survival between hepatocellular carcinoma patients in BCLC stage A or B who experience tumor rupture and patients in BCLC stage C who do not.

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication, and patients who experience it are formally assigned to stage T4 in the TNM system, while many clinicians informally assign them to stage C in the more widely used Barcelona Clinic Liver Cancer (BCLC) system. The present study explored whether these re-staging practices are appropriate for HCC patients who suffer tumor rupture. Methods: We retrospectively reviewed the records of 1952 HCC patients who underwent hepatic resection at our hospital between January 2017 and June 2021. We compared recurrence-free and overall survival between 143 patients who had BCLC stage A or B disease at the time of spontaneous rupture and 449 patients who had BCLC stage C disease without rupture. Results: Overall survival rate was significantly higher among the 143 patients (1, 3, 5-year survival rate was 80.3%, 60.4%, 51.4%) with rupture than among the 449 (1, 3, 5-year survival rate was 69.5%, 41.5%, 32.4%) with BCLC stage C disease (hazard ratio 1.65, 95% confidence interval 1.29 to 2.12). The two groups had similar recurrence-free survival (hazard ratio 1.19, 95% confidence interval 0.92 to 1.53), but most patients with rupture were able to receive interventional and potentially curative treatments after recurrence, whereas most patients in BCLC stage C received interventional or supportive care. Similar results were obtained after propensity score matching. Conclusion: HCC patients who experience spontaneous rupture tumor while in BCLC stage A or B have better prognosis than patients in BCLC stage C without rupture. Our results suggest that HCC patients who suffer rupture in BCLC stage A or B should not be assigned to BCLC stage C.

The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma.

PURPOSE: The GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC. METHODS: A total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria. RESULTS: The GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001). In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP. CONCLUSION: The GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

Prognostic Factors for Mortality in Hepatocellular Carcinoma at Diagnosis: Development of a Predictive Model Using Artificial Intelligence.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for 75% of primary liver tumors. Controlling risk factors associated with its development and implementing screenings in risk populations does not seem sufficient to improve the prognosis of these patients at diagnosis. The development of a predictive prognostic model for mortality at the diagnosis of HCC is proposed. METHODS: In this retrospective multicenter study, the analysis of data from 191 HCC patients was conducted using machine learning (ML) techniques to analyze the prognostic factors of mortality that are significant at the time of diagnosis. Clinical and analytical data of interest in patients with HCC were gathered. RESULTS: Meeting Milan criteria, Barcelona Clinic Liver Cancer (BCLC) classification and albumin levels were the variables with the greatest impact on the prognosis of HCC patients. The ML algorithm that achieved the best results was random forest (RF). CONCLUSIONS: The development of a predictive prognostic model at the diagnosis is a valuable tool for patients with HCC and for application in clinical practice. RF is useful and reliable in the analysis of prognostic factors in the diagnosis of HCC. The search for new prognostic factors is still necessary in patients with HCC.

Optimizing hepatocellular carcinoma disease staging systems by incorporating tumor micronecrosis: A multi-institutional retrospective study.

Tumor micronecrosis is a pathological feature that reflects malignant biological behavior in hepatocellular carcinoma (HCC). However, whether micronecrosis can optimize HCC staging systems remains unilluminated. A total of 1632 HCC patients who underwent curative hepatectomy in four institutions from January 2014 to December 2021 were enrolled in this study. Independent prognostic factors were identified, and optimized staging models were established using a training cohort (n = 934). The performance of optimized staging models was validated using an external cohort consisting of cases from three other institutions (n = 232). In addition, patients from our prospectively collected database (n = 379) tested the application effectiveness of the models. Harrel's c-statistics and the corrected Akaike information criterion (AICc) were used to assess the performance of staging models. In most of Barcelona Clinic Liver Cancer (BCLC) and tumor (T) stages, HCC patients with tumor micronecrosis showed poorer prognosis than those without. Tumor micronecrosis, microvascular invasion, multiple tumors and tumor size >2 cm were independent prognostic-related factors. The BCLC and T staging models incorporating tumor micronecrosis showed better performance than the original systems (c-statistic, 0.712 and 0.711 vs. 0.664 and 0.679; AICc, 2314.8 and 2322.3 vs. 2338.2 and 2338.1; respectively). Furthermore, the external validation cohort confirmed that the optimized staging models had improved efficiency compared with the original ones. Moreover, the prospective cohort demonstrated the applicability of the optimized staging systems. Tumor micronecrosis plays a stage-ascending role in HCC patients. The BCLC and T staging systems incorporating tumor micronecrosis can improve the prognosis stratification efficiency of patients.

Comparative Analysis of Subclassification Systems in Patients with Intermediate-Stage Hepatocellular Carcinoma (Barcelona Clinic Liver Classification B) Receiving Systemic Therapy.

BACKGROUND: Intermediate-stage hepatocellular carcinoma (BCLC B HCC) occurs in a heterogeneous group of patients and can be addressed with a wide spectrum of treatments. Consequently, survival significantly varies among patients. In recent years, several subclassification systems have been proposed to stratify patients' prognosis. We analyzed and compared these systems (Bolondi, Yamakado, Kinki, Wang, Lee, and Kim criteria) in patients undergoing systemic therapy. METHODS: We considered 171 patients with BCLC B HCC treated with sorafenib as first-line systemic therapy in six Italian centers from 2010 to 2021 and retrospectively applied the criteria of six different subclassification systems. RESULTS: Except for the Yamakado criteria, all the subclassification systems showed a statistically significant correlation to overall survival (OS). In the postestimation analysis, the Bolondi criteria (OS of subgroups 22.5, 11.9, and 6.6 mo, respectively; C-index 0.586; AIC 1338; BIC 1344) and the Wang criteria (OS of subgroups 20.6, 11.9, and 7.0, respectively; C-index 0.607; AIC 1337; BIC 1344) presented the best accuracy. Further analyses of these two subclassification systems implemented with the prognostic factor of alpha-fetoprotein (AFP) > 400 ng/mL have shown an increase in accuracy for both systems (C-index 0.599 and 0.624, respectively). CONCLUSIONS: Intermediate-stage subclassification systems maintain their predictive value also in the setting of systemic therapy. The Bolondi and Wang criteria showed the highest accuracy. AFP > 400 ng/mL enhances the performance of these systems.

Improving prognostication in patients with hepatocellular carcinoma undergoing loco-regional therapy using pre- and post-locoregional therapy scores.

BACKGROUND: Many scoring systems have been proposed for predicting survival in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT). We aimed to study the role of the NIACE score, hepatoma arterial embolization prognostic score (HAP), and ABCR score in predicting transplant-free survival (TFS) in these patients. METHODS: In this retrospective multicenter study of a United States Veteran cohort who underwent LRT, NIACE, HAP, and ABCR scores were calculated, and their predictive accuracy for TFS within different modified BCLC (mod-BCLC) stages was analyzed. RESULTS: 180 subjects underwent LRT between January-2012 and March-2019 were followed till January-2022, mean age 65.6 ± 6.3 years, model for end-stage liver disease -sodium (MELD-Na) score (at first LRT) 14.1 ± 6.7. A total of 43.9%, 35%, and 21.1% of patients had mod-BCLC A, B, and C stage disease, respectively. A total of 76.7% underwent transarterial embolization (TAE), 6.1% underwent ablation, and 17.2% underwent transarterial radioembolization (TARE) as the first intervention and were followed for a median of 576.5 patient-years. The NIACE score, HAP score, and ABCR scores differentiated patients within mod-BCLC stages A and B into groups with significant differences in TFS. In the stratified analysis of those undergoing only TAE, all three scores identified subgroups with significantly different TFS. CONCLUSION: In patients with HCC undergoing LRT, the mod-BCLC stages have subgroups with variable overall TFS. The NIACE score, HAP score, and ABCR score identified differential prognoses is within mod-BCLC stages and characterized subgroups with different TFS following LRT (TAE). Integration of these scoring systems into treatment decisions would help to improve prognostication within respective mod-BCLC groups, which may help with more customized treatment allocation.

The Complexity of the Tumor Microenvironment in Hepatocellular Carcinoma and Emerging Therapeutic Developments.

This review explores various aspects of the HCC TME, including both cellular and non-cellular components, to elucidate their roles in tumor development and progression. Specifically, it highlights the significance of cancer-associated fibroblasts (CAFs) and their contributions to tumor progression, angiogenesis, immune suppression, and therapeutic resistance. Moreover, this review emphasizes the role of immune cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T-cells (Tregs), in shaping the immunosuppressive microenvironment that promotes tumor growth and immune evasion. Furthermore, we also focused only on the non-cellular components of the HCC TME, including the extracellular matrix (ECM) and the role of hypoxia-induced angiogenesis. Alterations in the composition of ECM and stiffness have been implicated in tumor invasion and metastasis, while hypoxia-driven angiogenesis promotes tumor growth and metastatic spread. The molecular mechanisms underlying these processes, including the activation of hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF) signaling, are also discussed. In addition to elucidating the complex TME of HCC, this review focuses on emerging therapeutic strategies that target the TME. It highlights the potential of second-line treatments, such as regorafenib, cabozantinib, and ramucirumab, in improving overall survival for advanced HCC patients who have progressed on or were intolerant to first-line therapy. Furthermore, this review explores the implications of the Barcelona Clinic Liver Cancer (BCLC) staging and classification system in guiding HCC management decisions. The BCLC system, which incorporates tumor stage, liver function, and performance status, provides a framework for treatment stratification and prognosis prediction in HCC patients. The insights gained from this review contribute to the development of novel therapeutic interventions and personalized treatment approaches for HCC patients, ultimately improving clinical outcomes in this challenging disease.

Association of Serum ɣ-Glutamyl Transpeptidase Levels With Overall Survival in Intermediate and Advanced Hepatocellular Carcinoma Treated With Transarterial Chemoembolization.

Introduction: This article aims to evaluate the prognostic significance of pretreatment serum É£-glutamyl transpeptidase (GGT) levels in patients with intermediate (BCLC B) and advanced stage (BCLC C) hepatocellular carcinoma receiving transarterial chemoembolization (TACE) as first-line treatment. Methods: In this single-center retrospective study, a total of 608 patients with BCLC B and BCLC C class were included who received TACE as first-line treatment modality. Patients were divided into low and high GGT groups based on a cutoff value of pretreatment serum GGT levels calculated by receiver operating curve. Overall survival was evaluated with Kaplan-Meier method, and intergroup significance was calculated by log-rank test for overall patients, each BCLC B and BCLC C group. Univariate and multivariate analysis were used for significance for prognostic factors. Results: Median follow-up time was 20, 22, and 9 months for overall patients, BCLC B, and BCLC C group, respectively. Optimal cut value for GGT was calculated at 90.5 U/L. One-year and 3-year survival rates were 84.2% and 27.9% in low GGT, 49.4% and 8.6% in high-GGT group for overall patients. Multivariate analysis in overall patients showed Child-Pugh B (HR,1.801; 95%CI, 1.373-2.362, P < .001), ascites (1.393, 1.070-1.812; P = .014), multiple tumors (1.397, 1.137-1.716; P = .001), AST >40 (1.407, 1.095-1.808; P = .008), albumin <3.2 (.735, .612-.884; P = .001), AFP > 400 (1.648, 1.351-2.011; P < .001), high GGT (2.009, 1.631-2.475; P < .001), or receipt of chemo/ablation (.463, .377-.569; P < .001) as independent risk factors for overall survival. Serum GGT levels and AFP showed significant correlation in between with significance coefficient of .155 (P < .001). Conclusion: Elevated pretreatment serum GGT level was feasible and promising independent prognostic marker for overall survival in intermediate and advanced stage hepatocellular carcinoma patients treated with TACE.

Pre-transarterial Radioembolization of Tumoral Arteriovenous Fistula Associated With Recanalized Umbilical Vein Shunt in a Case of Hepatocellular Carcinoma With Hepatic Vein and Inferior Vena Cava Invasion.

Hepatocellular carcinoma (HCC) is the most common liver cancer and has a propensity to develop arteriovenous fistulas with the surrounding vasculature, making targeted intravascular treatment more difficult. HCC can oftentimes be accompanied by portal hypertension and liver cirrhosis, which can, in turn, cause recanalization of the umbilical vein. In rare circumstances, arteriovenous fistula formation and shunting into the recanalized and enlarged umbilical vein can occur. In the following presented case of HCC, an arteriovenous shunt between the anterior division of the right hepatic artery and a recanalized umbilical vein is demonstrated. Subsequent successful endovascular coil embolization of the fistula was performed to avoid shunting and non-target embolization of the radiation particles in the umbilical vein territory. Post-embolization angiogram with DynaCT and lack of Tc-99m macroaggregated albumin deposition in the umbilical vein distribution confirmed the resolution of the shunt. The patient then received targeted Y-90 transarterial radioembolization locoregional therapy in combination with systemic therapy.

Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization.

Background and Aims: To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Methods: This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals. Based on overall survival (OS), the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination [C statistic and Akaike information criterion (AIC)], monotonicity of the gradient (linear trend chi-square test), homogeneity (likelihood ratio chi-square test), and calibration (calibration plots). A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes. Results: Median OS was 19.1 (18.2-20.0) months, with significant differences in OS between stages defined by the CNLC and BCLC observed (p<0.001). The CNLC performed better than the BCLC regarding model discrimination (C-index: 0.661 vs. 0.644; AIC: 10,583.28 vs. 10,583.72), model monotonicity of the gradient (linear trend chi-square test: 66.107 vs. 57.418; p<0.001), model homogeneity (159.2 vs. 158.7; p<0.001). Both staging systems had good model calibration. Similar results were observed in the prospective cohort. Conclusions: Combining model discrimination, gradient monotonicity, homogeneity, and calibration, the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

Adding nutritional status to the original BCLC stage improves mortality prediction for hepatocellular carcinoma patients in HBV-endemic regions.

Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.

Survival Prediction After Transarterial Chemoembolization for Hepatocellular Carcinoma: a Deep Multitask Survival Analysis Approach.

The accurate prediction of postoperative survival time of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is important for postoperative health care. Survival analysis is a common method used to predict the occurrence time of events of interest in the medical field. At present, the mainstream survival analysis models, such as the Cox proportional risk model, should make strict assumptions about the potential random process to solve the censored data, thus potentially limiting their application in clinical practice. In this paper, we propose a novel deep multitask survival model (DMSM) to analyze HCC survival data. Specifically, DMSM transforms the traditional survival time prediction problem of patients with HCC into a survival probability prediction problem at multiple time points and applies entropy regularization and ranking loss to optimize a multitask neural network. Compared with the traditional methods of deleting censored data and strong hypothesis, DMSM makes full use of all the information in the censored data but does not need to make any assumption. In addition, we identify the risk factors affecting the prognosis of patients with HCC and visualize the importance of ranking these factors. On the basis of the analysis of a real dataset of patients with BCLC stage B HCC, experimental results on three different validation datasets show that the DMSM achieves competitive performance with concordance index of 0.779, 0.727, and 0.780 and integrated Brier score (IBS) of 0.172, 0.138, and 0.135, respectively. Our DMSM has a comparatively small standard deviation (0.002, 0.002, and 0.003) for IBS of bootstrapping 100 times. The DMSM we proposed can be utilized as an effective survival analysis model and provide an important means for the accurate prediction of postoperative survival time of patients with BCLC stage B HCC.

Multidisciplinary consensus recommendations for management of hepatocellular carcinoma in Middle East and North Africa region.

Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre-meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population-based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region.

Prevalencia y patrón de consumo de alcohol en pacientes con carcinoma hepatocelular / Prevalence and pattern of alcohol consumption in patients with hepatocellular carcinoma

Objetivo Estudio transversal prospectivo realizado para conocer la prevalencia y el patrón de consumo de alcohol (CA) de los pacientes con carcinoma hepatocelular (CHC) y evaluar la utilidad del AUDIT en estos. Métodos Se incluyeron 102 pacientes consecutivos atendidos en consulta entre febrero y marzo de 2022; se excluyeron aquellos con encefalopatía hepática en el momento de la entrevista, pacientes en lista de espera para trasplante por esta indicación y aquellos en seguimiento postrasplante. Resultados La prevalencia del CA en pacientes con diagnóstico de CHC es del 35%, si bien menos del 10% consume más de 100g de etanol a la semana. El CA fue más frecuente en varones, ambiente urbano, con diagnóstico de CHC hace más de un año y en pacientes en estadio inicial/muy inicial del BCLC. La puntuación AUDIT mayor o igual a 3 (AUROC 0,849) predice cualquier CA con una sensibilidad del 75% (IC 95%: 59,47-90,53%) y con una especificidad del 84% (IC 95%: 74,70-94,05%). Conclusiones A pesar del diagnóstico de CHC, más de un tercio de los pacientes consume alcohol. La puntuación AUDIT igual o mayor de 3 discrimina cualquier CA con una sensibilidad del 75% y una especificidad del 84% en esta población (AU)

Aim Prospective cross-sectional study conducted to determine the prevalence and pattern of alcohol consumption (AC) in patients with hepatocellular carcinoma (HCC) and to assess the utility of the AUDIT in HCC patients. Methods One hundred and two consecutive patients form our HCC monographic outpatient clinic visited between February and March 2022 were included. Patients with hepatic encephalopathy at the time of the interview, on the waiting list for liver transplantation and those undergoing post-transplant follow-up were excluded. Results The prevalence of AC in patients diagnosed with HCC is 35%, although less than 10% consume more than 100g per week. AC was more frequent in males, in an urban environment, with a diagnosis of HCC more than a year ago, and in patients in early/very early stages of BCLC. AUDIT score greater than or equal to 3 (AUROC 0.849) predicts any AC with a sensitivity of 75% (95% CI: 59.47-90.53%) and a specificity of 84% (95% CI: 74.70-94.05%). Conclusions Despite the diagnosis of HCC, more than a third of the patients consume alcohol. An AUDIT score equal to or greater than 3 discriminates any AC with a sensitivity of 75% and a specificity of 84% in this population (AU)

Transarterial chemoembolization for advanced hepatocellular carcinoma without macrovascular invasion or extrahepatic metastasis: analysis of factors prognostic of clinical outcomes.

Objectives: To evaluate the safety and efficacy of TACE and factors predicting survival in patients with advanced hepatocellular carcinoma (HCC) without macrovascular invasion (MVI) or extrahepatic spread (EHS). Methods: This single-center retrospective study included 236 treatment-naïve patients who underwent TACE as first-line treatment for advanced HCC without MVI or EHS between January 2007 and December 2021. Results: Following TACE, the median overall survival (OS) was 24 months. Multivariate Cox regression analyses revealed that tumor number ≥4 (risk point: 3), maximal tumor size >10 cm (risk point: 2), Child-Pugh class B (risk point: 2), alpha-fetoprotein (AFP) concentration ≥400 ng/mL (risk point: 2), and presence of HCC rupture (risk point: 2) were risk factors significantly associated with OS. The expected median OS among patients with <2, 2-4, and 5-9 risk points were 72, 29, and 12 months respectively. The major complication rates were significantly lower in patients with maximal tumor size ≤10 cm than in those with maximal tumor size >10 cm (4% [5/138] vs 21% [21/98], p = 0.001). Conclusion: TACE may be safe and effective in selected patients with advanced HCC without MVI or EHS, with a median OS of 24 months. Patients with limited tumor burden, compensated liver function, absence of HCC rupture, and favorable biologic markers may benefit the most from TACE. TACE is not recommended for patients with huge HCCs (>10 cm) because of its high rate of major complications (21%).

The aMAP Score is an Independent Risk Factor for Intermediate-stage Hepatocellular Carcinoma: A Large Retrospective Cohort Study.

Background: A less effective nomogram for patients with intermediate-stage hepatocellular carcinoma (HCC) to predict overall survival (OS) is available. This study aimed to investigate the role of age-male-albumin-bilirubin-platelet (aMAP) scores in the prognosis of patients with intermediate-stage HCC and develop an aMAP score-based nomogram to predict OS. Methods: Data on newly diagnosed intermediate-stage patients with HCC at Sun Yat-sen University Cancer Center between January 2007 and May 2012 were retrospectively collected. Independent risk factors affecting prognosis were selected by multivariate analyses. The optimal cut-off value for the aMAP score was determined using X-tile. The survival prognostic models were presented by the nomogram. Results: For the 875 patients with intermediate-stage HCC included, the median OS was 22.2 months (95% CI 19.6-25.1). Patients were classified into three groups by X-tile plots (aMAP score < 49.42; 49.42 ≤ aMAP score < 56; aMAP score ≥ 56). Alpha-fetoprotein, lactate dehydrogenase, aMAP score, diameter of main tumor, number of intrahepatic lesions, and treatment regimen were independent risk factors for prognosis. A predicted model was constructed with a C-index of 0.70 (95% CI: 0.68-0.72) in the training goup, and its 1-, 3-, and 5-year area under the receiver operating curve were: 0.75, 0.73, and 0.72. The validation group of the C-index is 0.82. Calibration graphs showed good consistency between the actual and predicted survival rates. The decision curve analysis suggested the clinical utility of the model, which may help clinicians guide clinical decision-making. Conclusion: The aMAP score was an independent risk factor for intermediate-stage HCC. The aMAP score-based nomogram has good discrimination, calibration, and clinical utility.

Subclassification of advanced-stage hepatocellular carcinoma with macrovascular invasion: combined transarterial chemoembolization and radiotherapy as an alternative first-line treatment.

Background/Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods: A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results: The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0-4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Conclusions: Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation.

Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.