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Oxaliplatin is currently used for chemotherapy in patients with hepatocellular carcinoma, but its increasing tolerance to tumours over time limits its clinical application. Studies have shown that high PD-L1 expression promotes the polarization of M2 macrophages. The increased infiltration of M2 macrophages, including those in HCC, is positively correlated with poor prognosis in various solid tumours. We found that oxaliplatin promoted the expression of PD-L1 in liver cancer cells, which might be attributed partly to the tolerance of tumours to oxaliplatin. Therefore, in this study, we explored the antitumour effect of attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin via Western blotting, immunohistochemistry, immunofluorescence, and flow cytometry. The results revealed that attenuated Salmonella carrying siRNA-PD-L1 combined with oxaliplatin more significantly inhibited tumour growth in tumour-bearing mice, suppressed the expression of PD-L1 in tumour tissue, increased the apoptosis of tumour cells and the expression of the tumour-related protein cleaved-caspase3, and increased the infiltration of M1 macrophages and T lymphocytes in tumour tissues. Moreover, the combination therapy increased the activation of T cells and the number of T lymphocytes and NK cells in the spleens of the mice and improved the overall antitumour immune response in the mice. Our results confirmed that attenuated Salmonella harbouring siRNA-PD-L1 combined with oxaliplatin had a significant antitumour effect and did not increase the incidence of toxic side effects, providing a theoretical reference for addressing oxaliplatin tolerance in the treatment of hepatocellular carcinoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To investigate associations between tissue diffusion, stiffness, and different tumor microenvironment features in resected hepatocellular carcinoma (HCC)., Methods: Seventy-two patients were prospectively included for preoperative magnetic resonance (MR) diffusion-weighted imaging and MR elastography examination. The mean apparent diffusion coefficient (ADC) and stiffness value were measured on the central three slices of the tumor and peri-tumor area. Cell density, tumor-stroma ratio (TSR), lymphocyte-rich HCC (LR-HCC), and CD8 + T cell infiltration were estimated in resected tumors. The interobserver agreement of MRI measurements and subjective pathological evaluation was assessed. Variables influencing ADC and stiffness were screened with univariate analyses, and then identified with multivariable linear regression. The potential relationship between explored imaging biomarkers and histopathological features was assessed with linear regression after adjustment for other influencing factors., Results: Seventy-two patients (male/female: 59/13, mean age: 56 ± 10.2 years) were included for analysis. Inter-reader agreement was good or excellent regarding MRI measurements and histopathological evaluation. No correlation between tumor ADC and tumor stiffness was found. Multivariable linear regression confirmed that cell density was the only factor associated with tumor ADC (Estimate = -0.03, p = 0.006), and tumor-stroma ratio was the only factor associated with tumor stiffness (Estimate = -0.18, p = 0.03). After adjustment for fibrosis stage (Estimate = 0.43, p < 0.001) and age (Estimate = 0.04, p < 0.001) in the multivariate linear regression, intra-tumoral CD8 + T cell infiltration remained a significant factor associated with peri-tumor stiffness (Estimate = 0.63, p = 0.02)., Conclusions: Tumor ADC surpasses tumor stiffness as a biomarker of cellularity. Tumor stiffness is associated with tumor-stroma ratio and peri-tumor stiffness might be an imaging biomarker of intra-tumoral immune microenvironment., Clinical Relevance Statement: Tissue stiffness could potentially serve as an imaging biomarker of the intra-tumoral immune microenvironment of hepatocellular carcinoma and aid in patient selection for immunotherapy., Key Points: Apparent diffusion coefficient reflects cellularity of hepatocellular carcinoma. Tumor stiffness reflects tumor-stroma ratio of hepatocellular carcinoma and is associated with tumor-infiltrating lymphocytes. Tumor and peri-tumor stiffness might serve as imaging biomarkers of intra-tumoral immune microenvironment., (© 2024. The Author(s).)

Introduction: Despite superior outcomes with liver transplantation, cirrhotic patients with HCC may turn to other forms of definitive treatment. To understand perioperative outcomes, we examined perioperative mortality and major morbidity after hepatectomy for HCC among cirrhotic and non-cirrhotic patients., Method: ology: The American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database was queried for liver resection for HCC. Multivariable logistic regression was performed to determine the association between liver texture and risk of major non-infectious morbidity, post-hepatectomy liver failure (PHLF) and 30-day mortality., Results: From 2014 to 2018, 2203 patients underwent hepatectomy: 58.6 % cirrhotic, 12.8 % fatty and 28.6 % normal texture. Overall 30 day-mortality was 2.1 % (n = 46), although higher among fatty liver (2.8 %) and cirrhotic (2.6 %; p = 0.025) patients. The incidence of PHLF was 6.9 %, with hepatectomy type, cirrhosis, and platelet count as major risk factors. Age, resection type, and platelet count were associated with major complications. Trisegmentectomy and right hepatectomy (OR = 3.60, OR = 3.46, respectively) conferred a greater risk of major noninfectious morbidity compared to partial hepatectomy. Among cirrhotics alone, hepatectomy type, platelet count, preoperative sepsis and ASA class were associated with major morbidity., Discussion: Hepatic parenchymal disease/texture and function, presence of portal hypertension, and the extent of the liver resection are critical determinants of perioperative risk among HCC patients., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background & Aims: Optimizing transarterial chemoembolization (TACE) can enhance treatment efficacy for hepatocellular carcinoma (HCC). This study compares modified TACE (M-TACE), which combines a lipiodol-based emulsion and drug-eluting beads, with drug-eluting bead TACE (DEB-TACE) as initial therapies for solitary HCC., Methods: In this retrospective study, 185 patients undergoing M-TACE or DEB-TACE were evaluated. Propensity score matching was used to create 69 balanced pairs. Initial tumor response, repeated treatments within six months, local tumor progression (LTP), overall survival (OS), and adverse events (AEs) were assessed., Results: M-TACE exhibited significantly higher initial complete response (CR) rates (39.1% vs. 23.2%, p  = 0.043) and fewer repeated treatments within six months (1.7 ± 0.9 vs. 2.1 ± 0.7; p  = 0.033) compared to DEB-TACE. LTP rates were notably lower with M-TACE at 12 months (39.1% vs. 65.2%, p  = 0.002), and median time to LTP was prolonged with M-TACE (13.3 vs. 8.2 months, p  = 0.038). Stratified analysis revealed a significantly longer OS in individuals achieving a CR after the initial M-TACE (50.5 vs. 33.4 months, p  = 0.043). However, the overall study population did not exhibit a significant difference in OS between the two groups. Comparable AEs (all p  > 0.05) were observed., Conclusions: M-TACE showed higher initial CR rates, lower LTP rates, and extended time to LTP compared to DEB-TACE, indicating its potential to enhance TACE effectiveness for solitary HCC.

Purpose: Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria., Patients and Methods: Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs)., Results: There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p  = 0.007; PFS: 15.4 months vs. 4.8 months, p  < 0.001). The objective response rate (ORR) in the TACE-MTAs-ICIs group was higher than that in the TACE group (65.1% vs. 37.2%, p  = 0.010). Reversible AEs (grade 3 or 4) occurred differently in TACE-MTAs-ICIs and TACE groups (83.7% vs. 51.2%, p  = 0.001). Univariate and multivariate analyses revealed that TACE-MTAs-ICIs treatment was an independent favourable prognostic factor for both PFS and OS ( p  < 0.001)., Conclusion: For uHCC patients beyond the up-to-seven criteria, TACE-MTAs-ICIs provided superior ORR and OS. Early combined TACE and systemic treatment should shift for patients who are beyond these criteria.

Background: Highly aggressive hepatocellular carcinoma (HCC) is characterized by high tumor recurrence and poor outcomes, but its definition and imaging characteristics have not been clearly described., Purpose: To develop and validate a fusion model on gadobenate dimeglumine-enhanced MRI for identifying highly aggressive HCC., Study Type: Retrospective., Population: 341 patients (M/F = 294/47) with surgically resected HCC, divided into a training cohort (n = 177), temporal validation cohort (n = 77), and multiscanner validation cohort (n = 87)., Field Strength/sequence: 3T, dynamic contrast-enhanced MRI with T1-weighted volumetric interpolated breath-hold examination gradient-echo sequences, especially arterial phase (AP) and hepatobiliary phase (HBP, 80-100 min)., Assessment: Clinical factors and diagnosis assessment based on radiologic morphology characteristics associated with highly aggressive HCCs were evaluated. The radiomics signatures were extracted from AP and HBP. Multivariable logistic regression was performed to construct clinical-radiologic morphology (CR) model and clinical-radiologic morphology-radiomics (CRR) model. A nomogram based on the optimal model was established. Early recurrence-free survival (RFS) was evaluated in actual groups and risk groups calculated by the nomogram., Statistical Tests: The performance was evaluated by receiver operating characteristic curve (ROC) analysis, calibration curves analysis, and decision curves. Early RFS was evaluated by using Kaplan-Meier analysis. A P value <0.05 was considered statistically significant., Results: The CRR model incorporating corona enhancement, cloud-like hyperintensity on HBP, and radiomics signatures showed the highest diagnostic performance. The area under the curves (AUCs) of CRR were significantly higher than those of the CR model (AUC = 0.883 vs. 0.815, respectively, for the training cohort), 0.874 vs. 0.769 for temporal validation, and 0.892 vs. 0.792 for multiscanner validation. In both actual and risk groups, highly and low aggressive HCCs showed statistically significant differences in early recurrence., Data Conclusion: The clinical-radiologic morphology-radiomics model on gadobenate dimeglumine-enhanced MRI has potential to identify highly aggressive HCCs and non-invasively obtain prognostic information., Level of Evidence: 4 TECHNICAL EFFICACY: Stage 2., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP)., Methods: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups., Results: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups., Conclusions: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery., (© 2024. The Author(s).)

Background and Aims: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC., Methods: Participants underwent full HLA class I/KIR typing and long-term HCV follow-up., Results: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow-up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA-treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell-mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK-cell-mediated immunity did not predict HCC., Conclusion: Cirrhosis is the main risk state predisposing to HCC, but weak NK-cell-mediated immunity may predispose to post-2G DAA HCC more than intermediate or strong NK-cell-mediated immunity., (© ([0‐9]+) Wiley‐VCH GmbH.)

Purpose: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT)., Materials and Methods: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups., Results: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437)., Conclusion: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose: Magnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence., Methods: We retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival., Results: During a median follow-up period of 32 months (range, 4-52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5-23.1) and MVI (HR, 3.4; 95% CI, 1.0-11.3) were independent predictors of intrahepatic recurrence., Conclusions: Patients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pediatric hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) are primary liver malignant neoplasms with 5-year event-free survival of >80% and <30%, respectively. In these patients, α-fetoprotein levels can guide surgical intervention and monitor disease progression. Although histology and immunohistochemical stains support diagnosis, genetic testing can elucidate mechanisms that drive pathogenesis. Pediatric HBL and HCC harbor well-characterized molecular signatures such as alterations in CTNNB1, TERT, and AXIN1 that alter the Wnt/β-catenin pathway. Approximately 8% of individuals with HCC harbor RPS6KA3 variants that appear with other gene mutations. Herein, we report a novel solitary pathogenic RPS6KA3 variant finding in a 6-year-old boy whose final diagnosis was hepatocellular malignant neoplasm, not otherwise specified., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

RATIONALE AND OBJECTIVES: As an effective locoregional therapy, transarterial chemoembolization (TACE) can induce vascular endothelial growth factor and PD-1/PDL-1 upregulation, accompanied by a reduction in tumor burden. The present study aimed to compare the efficacy of TACE combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICIs) versus TKIs plus ICIs (TKI-ICIs) in patients with unresectable hepatocellular carcinoma (HCC)., Materials and Methods: The clinical data of 198 patients diagnosed with unresectable HCC who received a TKI (lenvatinib or sorafenib) plus an ICI (sintilimab or camrelizumab) with or without TACE were retrospectively reviewed between October 2019 and April 2022. Baseline characteristics of the TACE-TKI-ICI group and the TKI-ICI group were matched by propensity score matching in a 1:1 ratio. The tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated and compared between the two groups., Results: After matching, 54 patients were enrolled in each group. The objective response rate (ORR) and disease control rate (DCR) were higher in the TACE-TKI-ICI group (ORR: 63.0% vs. 29.6%, P < 0.001; DCR: 85.2% vs. 53.7%, P < 0.001). The median PFS was significantly longer in the TACE-TKI-ICI group (9.9 vs. 5.8 months; P = 0.026). The median OS between the two groups also reached a significant difference (not reached vs. 18.5 months; P = 0.003)., Conclusion: In this retrospective study, the results indicated that the addition of TACE to TKI-ICI therapy could contribute to better tumor control, PFS, and OS benefits in patients with unresectable HCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: The predictive value of Lipiodol was evaluated for response evaluation of hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE) by analysis of the enhancement pattern during angiography and in postinterventional computed tomography (CT). Materials and Methods: This retrospective study included 30 patients (mean age 63 years, range: 36 to 82 years, 22 males) with HCC. Patients received three Lipiodol-based cTACE sessions, each followed by an unenhanced CT within 24-h. Contrast-enhanced magnetic resonance imaging (MRI) was acquired before and after the treatment to determine tumor response. Lipiodol enhancement pattern, tumor vascularization, and density were evaluated by angiography and CT. Initial tumor size and response to cTACE were analyzed by MRI according to modified response evaluation criteria in solid tumors (mRECIST) in a 4-week follow-up. Results: Analysis of HCC lesions (68 lesions in 30 patients) during cTACE revealed clear visibility and hypervascularization in angiography as a potential independent parameter able to predict tumor response. A significant correlation was found for response measurements by volume ( p  = 0.012), diameter ( p  = 0.006), and according to mRECIST ( p  = 0.039). The amount of Lipiodol and enhancement pattern in postinterventional CT did not correlate with therapy response. Measurements of Hounsfield unit values after cTACE do not allow sufficient prediction of the tumor response. Conclusion: Hypervascularized HCC lesions with clear visibility after Lipiodol administration in the angiography respond significantly better to cTACE compared to hypo- or nonvascularized lesions.

Background/purpose: Hepatocellular carcinoma (HCC) can be noninvasively diagnosed through dynamic computed tomography (CT) and magnetic resonance imaging (MRI). We compared the diagnostic performance of CT and gadoxetic acid-enhanced MRI (EOB-MRI) in categorizing tumors by using the 2018 version of the Liver Imaging Reporting And Data System (LI-RADS v2018) and assessing liver tumors before resection., Methods: Data from a prospective cohort from October 2011 to March 2019 on 106 hepatic tumors in 96 patients with suspected malignancy were included in this study. We performed preoperative CT and EOB-MRI, and reviewed these images retrospectively. Ninety-seven tumors from 87 patients were pathologically diagnosed as HCC, and nine tumors were non-HCC. The clinical data, imaging characteristics, diagnostic performance, and outcomes of CT and EOB-MRI were analyzed and compared., Results: EOB-MRI had more favorable diagnostic performance (area under curve: 0.920 vs. 0.868) and significantly higher sensitivity (86.87% vs. 69.70%, p = 0.005) than did CT. However, the specificity of EOB-MRI did not differ from that of CT (88.89% vs. 88.89%, p > 0.999). Fourteen (14.5%) patients with pathologically verified HCC had lesions categorized as LI-RADS 4 through CT and as LI-RADS 5 through EOB-MRI. Patients with EOB-MRI-categorized but not CT-categorized LI-RADS 5 lesions had significantly longer overall survival than did those with LI-RADS 4 lesions (p < 0.001)., Conclusion: EOB-MRI had higher sensitivity than did CT in diagnosing HCC. Patients with EOB-MRI-categorized LI-RADS 5 lesions had more favorable outcomes than did those with LI-RADS 4 lesions after liver resection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Introduction and Objectives: Liver transplantation is the optimal treatment for patients with early hepatocellular carcinoma and cirrhosis. However, hepatocellular carcinoma recurs in approximately 15 % of individuals. This study aimed to assess the efficacy of predictive models for hepatocellular carcinoma recurrence after liver transplantation., Patients and Methods: This retrospective study included 381 patients with HCC and evaluated the performance of the following models: R3-AFP score, alpha-fetoprotein (AFP) model, University of California, Los Angeles (UCLA) nomogram, Pre-Model of Recurrence after Liver Transplantation (MORAL), Post-MORAL, and Combo MORAL models, Risk Estimation of Tumor Recurrence (RETREAT) model and Platelet to Lymphocyte Ratio (PLR) model., Results: The R3-AFP score, UCLA nomogram, AFP model, RETREAT, Combo MORAL, and Post-MORAL models exhibited comparable AUROCs, ranging from 0.785 to 0.733. The AUROCs for the R3-AFP model and AFP model were superior to those of the Pre-MORAL and PLR models. The UCLA nomogram, RETREAT score, Combo MORAL model, and Post-MORAL model performed similarly to the first two models, but were only superior to the PLR model., Conclusions: The R3-AFP model, UCLA nomogram, AFP model, RETREAT, Combo MORAL, and Post-MORAL models demonstrated a moderate predictive capacity for hepatocellular carcinoma recurrence following transplantation. No significant differences were observed among these models in their ability to predict recurrence., Competing Interests: Declaration of interests None., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI., Methods: This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics., Results: Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p < 0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p = 0.031) with comparable accuracy (95.2% vs. 94.7%; p > 0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p = 0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ = 0.64)., Conclusion: Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea., Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study., Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib; 2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400-600 mg (9.6 months)., Conclusions: Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.

Background/aims: With the wide application of direct-acting antivirals (DAAs) for hepatitis C virus infection, the number of patients achieving a sustained virologic response (SVR) will continue to increase. However, no consensus has been achieved on exempting SVR-achieving patients from hepatocellular carcinoma (HCC) surveillance., Methods: Between 2013 and 2021, 873 Korean patients who achieved SVR following DAA treatment were analyzed. We evaluated the predictive performance of seven noninvasive scores (PAGE-B, modified PAGE-B, Toronto HCC risk index, fibrosis-4, aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin, and age male albumin-bilirubin platelet [aMAP]) at baseline and after SVR., Results: The mean age of the 873 patients (39.3% males) was 59.1 years, and 224 patients (25.7%) had cirrhosis. During 3,542 person-years of follow-up, 44 patients developed HCC, with an annual incidence of 1.24/100 person-years. Male sex (adjusted hazard ratio [AHR], 2.21), cirrhosis (AHR, 7.93), and older age (AHR, 1.05) were associated with a significantly higher HCC risk in multivariate analysis. The performance of all scores at the time of SVR were numerically better than those at baseline as determined by the integrated area under the curve. Time-dependent area under the curves for predicting the 3-, 5-, and 7-year risk of HCC after SVR were higher in mPAGE-B (0.778, 0.746, and 0.812, respectively) and aMAP (0.776, 0.747, and 0.790, respectively) systems than others. No patients predicted as low-risk by the aMAP or mPAGE-B systems developed HCC., Conclusions: aMAP and mPAGE-B scores demonstrated the highest predictive performance for de novo HCC in DAA-treated, SVR-achieving patients. Hence, these two systems may be used to identify low-risk patients that can be exempted from HCC surveillance.

The rapidly increasing incidence of nonalcoholic fatty liver disease (NAFLD) is a growing health crisis worldwide. If not detected early, NAFLD progression can lead to irreversible pathological states, including liver fibrosis and cirrhosis. Using in vitro models to understand the molecular pathogenesis has been extremely beneficial; however, most studies have utilized only short-term exposures, highlighting a limitation in current research to model extended fat-induced liver injury. We treated Hep3B cells continuously with a low dose of oleic and palmitic free fatty acids (FFAs) for 7 or 28 days. Transcriptomic analysis identified dysregulated molecular pathways and differential expression of 984 and 917 genes after FFA treatment for 7 and 28 days respectively. DNA methylation analysis of altered DNA methylated regions (DMRs) found 7 DMRs in common. Pathway analysis of differentially expressed genes (DEGs) revealed transcriptomic changes primarily involved in lipid metabolism, small molecule biochemistry, and molecular transport. Western blot analysis revealed changes in PDK4 and CPT1A protein levels, indicative of mitochondrial stress. In line with this, there was mitochondrial morphological change demonstrating breakdown of the mitochondrial network. This in vitro model of human NAFL mimics results observed in human patients and may be used as a pre-clinical model for drug intervention.

Purpose: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC)., Method: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups., Results: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922)., Conclusions: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A 30-year-old female intact Malayan wreathed hornbill ( Rhyticeros undulatus ) was presented for presumed nesting behavior, progressive anorexia, dropping food, and coelomic distension. A complete blood count and plasma biochemistry analysis revealed marked inflammation, severe electrolyte abnormalities, elevated liver enzyme activities and bile acids, and normal plasma iron concentrations. Radiographic images of the patient were consistent with hepatomegaly and loss of serosal detail in the coelomic cavity. A computed tomography study revealed multiple poorly contrast-enhancing hepatic nodules, hepatoperitoneal and intestinal peritoneal fluid and gas, and a contrast-enhancing mass in the ventral coelom. Cytologic samples of the liver were consistent with necrosis, and the coelomic effusion was characterized as an aseptic suppurative exudate. An exploratory coeliotomy was performed and biopsy samples of the liver and a mesenteric mass were histologically interpreted as a tubular carcinoma with metastasis to the liver and secondary portal hepatitis. Euthanasia was elected and multiple liver masses and a peripancreatic mass were identified on necropsy. Histopathological samples collected during the postmortem gross examination showed multiple well-demarcated hepatic masses consisting of neoplastic hepatocytes encapsulated by fibrous tissue and proliferation of dysplastic biliary ductules, as well as a peripancreatic heterophilic granuloma with adjacent pancreatic atrophy and ductular proliferation. Ultimately, the patient was diagnosed with multifocal hepatocellular carcinoma and chronic granulomatous and heterophilic pancreatitis, steatitis, and coelomitis with intralesional bacteria. Malignant hepatobiliary neoplasia has been poorly documented in hornbills despite high anecdotal incidence in this and other avian species predisposed to iron storage disease. This report illustrates clinical and pathological information, including advanced imaging, which could aid in the diagnosis of this condition in hornbills and other avian species.

Objective: Our meta-analysis was performed to explore the prognostic factors for overall survival among post-hepatectomy patients with spontaneous ruptured hepatocellular carcinoma (SRHCC)., Methods: PubMed, EMBASE, the Cochrane Library, and Web of Science were all searched up for relevant studies regarding prognostic factors with SRHCC. RevMan5.3 software and Stata 14.0 software were used for statistical analysis., Results: A total of nineteen studies with 1876 resected SRHCC patients were finally identified. Pooled results indicated that preoperative AFP (high vs low) (P = 0.003), concurrent liver cirrhosis (yes vs no) (P = 0.02), preoperative liver function (child A vs non-child A) (P = 0.0007), tumor size (large vs small) (P < 0.00001), tumor number (solitary vs multiple) (P = 0.002), satellite foci (yes vs no) (P = 0.0006), micro-vascular invasion (yes vs no) (P < 0.00001), type of hepatectomy (major or minor) (P = 0.04), surgical margin (R + vs R -) (P < 0.00001), and type of hepatectomy (emergency hepatectomy vs staged hepatectomy) (P = 0.005) were prognostic factors for overall survival among post-hepatectomy SRHCC patients., Conclusion: Apart from some conventional prognostic factors identified in resected patients with SRHCC, numerous prognostic factors have also been unmasked, which might provide clinical reference to stratify patients with different therapeutic regimes., (© 2023. The Society for Surgery of the Alimentary Tract.)

Oxaliplatin is a chemotherapy drug currently utilized in the treatment of advanced cancer patients. However, its tolerability poses a limitation to its clinical application. Studies have demonstrated that the presence of tumor-associated macrophages is positively correlated with poor prognosis in various solid tumors, including hepatocellular carcinoma (HCC), and is a significant factor contributing to oxaliplatin resistance. Therefore, targeting tumor-associated macrophages may be an effective strategy to improve the efficacy of oxaliplatin in the treatment of HCC patients. CD24 is a novel target for tumor therapy that can interact with the inhibitory receptor Siglec-10 on tumor-associated macrophages, transmitting immune inhibitory signals and inhibiting macrophage phagocytosis function. In this study, we utilized RNAi technology to inhibit the expression of CD24 in tumor cells and combined it with oxaliplatin, resulting in reduced tumor invasion, migration, and proliferation, as well as increased cell apoptosis. Furthermore, immunofluorescence and flow cytometry results indicated that both the single treatment group and combination treatment group enhanced the infiltration of immune cells. This study presents a novel approach to identifying combination therapy and targets for the clinical treatment of HCC with oxaliplatin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: The World Health Assembly recommends integration of palliative care into treatment of patients with any life-limiting condition, yet patients with non-malignant disease are less likely to receive specialist palliative care (SPC). This study compares SPC offered to patients with hepatocellular carcinoma (HCC) versus patients with chronic liver disease without HCC (CLD without HCC)., Methods: Patients who died from CLD or HCC over 5 years (2013-2017) in England were identified using a dataset linking national data on all hospital admissions (Hospital Episode Statistics - HES) with national mortality data from the Office for National Statistics (HES - ONS). The primary outcome was the proportion of patients who received inpatient SPC in their last year of life (LYOL). Secondary outcomes were (1) early inpatient SPC input and (2) the proportion dying in a hospice. The outcomes were compared between patients with HCC and CLD without HCC., Results: 29 669 patients were identified, 8143 of whom had HCC. Patients with HCC were significantly more likely to receive inpatient SPC input-adjusted OR 3.74 (95% CI 3.52-3.97) and early inpatient SPC input-adjusted OR 7.26 (95% CI 6.38-8.25) and die in a hospice OR 8.23 (95% CI 7.33-9.24) than patients with CLD without HCC., Conclusions: These data highlight the stark inequity in access to SPC services between patients with HCC and patients with CLD without HCC in England. Addressing these inequities will improve end-of-life care for patients with CLD., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objective: The aim of the work described here was to evaluate the diagnostic performance of perfluorobutane (PFB)-enhanced ultrasound in differentiating hepatocellular carcinoma (HCC) from non-HCC malignancies and other benign lesions using different acquisition methods., Methods: This prospective study included 69 patients with solid liver lesions larger than 1 cm who were scheduled for biopsy or radiofrequency ablation between September 2020 and March 2021. Lesion diagnosis was designated by three blinded radiologists after reviewing three different sets of acquired images selected according to the following presumed acquisition methods: (i) method A, acquisition up to 5 min after contrast injection; (ii) method B, acquisition up to 1 min after contrast injection with additional Kupffer phase; and (iii) method C, acquisition up to 5 min after contrast injection with additional Kupffer phase., Results: After excluding 7 technical failures, 62 patients with liver lesions (mean size: 24.2 ± 14.8 mm), which consisted of 7 benign lesions, 37 non-HCC malignancies and 18 HCCs. For the HCC diagnosis, method C had the highest sensitivity (75.9%), followed by method B (72.2%) and method A (68.5%), but failed to exhibit statistical significance (p = 0.12). There was no significant difference with respect to the pooled specificity between the three methods (p = 0.28). Diagnostic accuracy was the highest with method C (87.1%) but failed to exhibit statistical significance (p = 0.24)., Conclusion: Image acquisition up to 5 min after contrast injection with additional Kupffer phase could potentially result in high accuracy and sensitivity without loss of specificity in diagnosing HCC with PFB-enhanced ultrasound., Competing Interests: Conflict of interest J.M.L. reports grants from Philips Healthcare, GE Healthcare, Central Medical Service, Guerbet, Samsung Medison and Bracco and personal fees from Bayer Healthcare, Siemens Healthineers, Samsung Medison and Guerbet, outside the submitted work. J.H.Y. reports an honorarium from Bayer Healthcare and a personal fee from Philips Healthcare, outside the submitted work., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: As a result of the lack of screening programs and the difficulty in making a proper diagnosis, the majority of hepatocellular carcinoma (HHC) patients present late in low-resource countries. The study therefore assesses the clinical features, stage and prognostic variables of patients with HCC in The Gambia., Methods: From December 2015 to January 2019, patients with a confirmed diagnosis of HCC were enrolled. All patients' medical history, ultrasound scan, FibroScan and laboratory details were collected., Results: Two hundred and sixty (260) patients were enrolled. The mean age of HCC patients was 40 years, and 210 (80.7%) of them were male. The most common gastrointestinal symptoms were early satiety 229 (88.1%) and abdominal pain 288 (87.7%), while the most common constitutional symptoms were weight loss 237 (91.2%) and easy fatiguability 237 (91.2%). Hepatomegaly 205 (78.8%) was the most common sign. On ultrasound scan, lesions were mostly multifocal 175 (67.3%), and the median FibroScan score was 75 kPa. The median fibrosis 4 and aspartate transferase platelet ratio index were 4.6 and 2.2, respectively. Hepatitis B surface antigen (HBsAg) was positive in 170 (65.4%) patients, and the median AFP level was 3263 ng/ml. HCC patients with positive HBsAg were more likely to be male 145 (85.3%) vs 62 (72.1%) (p = 0.011), much younger 39.9 vs 51.4 yrs (p =  < 0.0001), more likely to have abdominal pain 156 (91.8%) vs 68 (79.1%) (p = 0.002), jaundice 78 (45.9%) vs 29 (33.7%) (p = 0.042), dark urine 117 (68.8%) vs 46 (53.5%) (p = 0.018), raised transaminases (Aspartate transaminases 224.5 (32-7886) vs 153 (18-610), p =  < 0.01, Alanine transferases 71 (5-937) vs 47 (8-271), p =  < 0.001) and decreased platelet count 207 (33-941) vs 252 (52- 641) (p = 0.021) compared to patients with HCC who were HBsAg-negative., Conclusions: The prognosis of patients with HCC is poor in developing countries such as The Gambia, where screening programs and treatment modalities are scarce. Young males are disproportionately affected, and HBV is a major cause of HCC in The Gambia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Liver tumors account for approximately 1%-2% of all pediatric malignancies, with the two most common tumors being hepatoblastoma (HB) and hepatocellular carcinoma (HCC). Previous Children's Oncology Group studies have meaningfully contributed to the current understanding of disease pathophysiology and treatment, laying groundwork for the ongoing prospective international study of both HB and HCC. Future work is focused on elucidating the biologic underpinnings of disease to support an evolution in risk categorization, advancements in the multidimensional care required to treat these patients, and the discovery of novel therapies., (© 2023 Wiley Periodicals LLC.)

Indolent T-lymphoblastic proliferation (iT-LBP) is a rare, non-clonal, extrathymic lymphoid proliferation with an immature T cell phenotype, indolent clinical course, and excellent prognosis. Although their pathogenesis is unclear, they are reported to be associated with Castleman disease, follicular dendritic cell tumors/sarcomas, angioimmunoblastic T cell lymphoma, hepatocellular carcinoma (HCC), myasthenia gravis, and acinic cell carcinoma. There are around 51 reported cases of iT-LBP in the literature. Recognition and accurate diagnosis of this entity is critical as it shares morphologic and immunophenotypic features with an aggressive malignancy-acute T cell leukemia/lymphoma (T-ALL). IT-LBP in HCC post-liver transplant and in metastatic sites has not been reported in the literature. Two case reports of patients presenting with recurrent and metastatic HCC in post-liver transplant settings are described. A 50-year-old man with an end-stage liver disease with HCC underwent liver transplant. A year later, he developed pulmonary metastasis with associated iT-LBP. A 69-year-old man underwent liver transplant for end-stage liver disease and HCC. Eighteen months later, he developed recurrent HCC in the transplanted liver and omental metastasis; both sites showed HCC with iT-LBP. iT-LBP in both patients expressed TdT, CD3, and CD4 and lacked CD34 and clonal T cell receptor gene rearrangements. On retrospective review, the pre-transplant HCC specimens lacked iT-LBP. We present two cases of iT-LBP associated with HCC in novel settings-in post-liver transplant patients and in recurrent/metastatic sites of HCC. In addition, a comprehensive literature review of clinical, histological, and immunophenotypic characteristics of reported cases of iT-LBP is presented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: Liver cancer constitutes one of the leading cancers globally. During pregnancy, however, liver cancer is an absolute rarity, with very few cases reported in the international literature. The aim of the present review was to provide a useful update and summarize all case studies of liver cancer in pregnancy published between 2012-2023., Materials and Methods: A literature review was conducted using the MEDLINE, LIVIVO, and Google Scholar databases. Solely case reports and case studies written in the English language that explicitly reported on the presence of histologically confirmed HCC or intrahepatic cholangiocarcinoma during pregnancy were included in the data analysis., Results: After detailed evaluation, a total of 35 reported cases of liver cancer during pregnancy were identified, hence bringing the total number of reported cases globally to 83. Oncological challenges during pregnancy call for an interdisciplinary approach. Although the desire to preserve the pregnancy should be taken into consideration, specialists need to evaluate maternal and fetal well-being and choose the optimal oncological treatment with the least dangers for both the maternal and fetal safety., Conclusion: The present review proves that, despite its scarcity, liver cancer may always occur during pregnancy and clinicians should, therefore, remain vigilant and endeavor to detect and evaluate any hepatic mass or symptoms of liver cancer promptly and exhaustively., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Needle core biopsies of liver lesions can be challenging, particularly in cases with limited material. The differential diagnosis for well-differentiated hepatocellular lesions includes focal nodular hyperplasia, hepatocellular adenoma, and well-differentiated hepatocellular carcinoma (HCC) in noncirrhotic liver, while dysplastic nodules and well-differentiated HCC are the primary considerations in cirrhotic liver. The first part of this review focuses on histochemical and immunohistochemical stains as well as molecular assays that are useful in the differential diagnosis. The second portion describes the features of hepatocellular adenoma subtypes and focuses on the differential diagnoses in commonly encountered clinicopathologic scenarios., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aim: The host dietary fibre is fermented into short-chain fatty acids (SCFA) by intestinal microbiota as bacterial metabolites like propionate, acetate and butyrate. Among these metabolites, the role of butyrate is well documented to provide energy to intestinal epithelial cells. Also, butyrate has anti-inflammatory and anti-tumour properties and decrease in its level by unbalanced diet can develops cancer. Lately, some research has suggested that sodium butyrate as an inhibitor of histone deacetylase (HDAC) may have anticancer potential for hepatocellular carcinoma (HCC), the most common type of liver cancer. Since, HCC is asymptomatic it is usually diagnosed at its advanced stage. Sorafenib with antiproliferative and antiangiogenic effects is the first line of treatment in advanced HCC. However, prolonged drug treatment to HCC patients develops adaptive resistance towards the sorafenib. Sorafenib resistance can also be enhanced by differentially expressed microRNAs. However, the significance of butyrate in HCC sorafenib resistance and its association with sorafenib-targeted microRNAs is yet to be unfurled. Here, an attempt has been made to explore the role of bacterial metabolite butyrate on sorafenib resistant HCC as well as on sorafenib-targeted microRNAs (miR-7641 and miR-199) to curtail sorafenib resistance in HCC., Methods: Initially, in-silico analysis was performed using Human Metabolome Database (HMDB) so to identify specific butyrate producing faecal bacteria. Then, their specific 16s rRNA expression was compared between HCC patients and healthy individuals using qRT-PCR. Additionally, the cell viability (MTT) and apoptosis assays were performed in both parental and sorafenib resistant HepG2 cells to evaluate the role of sodium butyrate in sorafenib resistant HCC. Moreover, the association of sodium butyrate with sorafenib-targeted miR-7641 and miR-199 was also assessed using real time PCR, cell viability, cell apoptosis and transfection assays., Results: In silico analysis demonstrated Roseburia cecical, Roseburia intestinalis, Eubacterium rectal, Faecalibacterium prausnitzii as specific butyrate producing faecal bacteria and their 16s rRNA expression was downregulated in HCC patients. In vitro study revealed the presence of sodium butyrate also decreased the cell viability as well as enhanced cell apoptosis of both parental and resistant HepG2 cells. Interestingly, sodium butyrate also decreased the expression of both sorafenib-targeted miR-7641 and miR-199. Further, combination of both sodium butyrate and antimiR-7641 or antimiR-199 also increased apoptosis and decreased viability of resistant cells., Conclusion: This is first study to unravel the association of butyrate producing bacteria with HCC patients and the significance of bacterial metabolite butyrate as anti-tumour in sorafenib resistant hepatocellular carcinoma. The study also demonstrated the plausible new aspects of bacterial metabolite butyrate association with sorafenib-targeted miRNAs (miR-7641 and miR-199). Hence, the study highlighted the therapeutic potential of bacterial metabolite butyrate that might improve the clinical management of hepatocellular carcinoma., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To explore whether intravoxel incoherent motion (IVIM) parameters could evaluate liver regeneration preoperatively., Methods: A total of 175 HCC patients were initially recruited. The apparent diffusion coefficient, true diffusion coefficient (D), pseudodiffusion coefficient (D * ), pseudodiffusion fraction (f), diffusion distribution coefficient, and diffusion heterogeneity index (Alpha) were measured by two independent radiologists. Spearman's correlation test was used to assess correlations between IVIM parameters and the regeneration index (RI), calculated as 100% × (the volume of the postoperative remnant liver - the volume of the preoperative remnant liver) / the volume of the preoperative remnant liver. Multivariate linear regression analyses were used to identify the factors for RI., Results: Finally, 54 HCC patients (45 men and 9 women, mean age 51.26 ± 10.41 years) were retrospectively analyzed. The intraclass correlation coefficient ranged from 0.842 to 0.918. In all patients, fibrosis stage was reclassified as F0-1 (n = 10), F2-3 (n = 26), and F4 (n = 18) using the METAVIR system. Spearman correlation test showed D * (r = 0.303, p = 0.026) was associated with RI; however, multivariate analysis showed that only D value was a significant predictor (p < 0.05) of RI. D and D * showed moderate correlations with fibrosis stage (r = -0.361, p = 0.007; r = -0.457, p = 0.001). Fibrosis stage showed a negative correlation with RI (r = -0.263, p = 0.015). In the 29 patients who underwent minor hepatectomy, only the D value showed a positive association (p < 0.05) with RI, and a negative correlation with fibrosis stage (r = -0.360, p = 0.018). However, in the 25 patients who underwent major hepatectomy, no IVIM parameters were associated with RI (p > 0.05)., Conclusions: The D and D * values, especially the D value, may be reliable preoperative predictors of liver regeneration., Key Points: • The D and D * values, especially the D value, derived from IVIM diffusion-weighted imaging may be useful markers for the preoperative prediction of liver regeneration in patients with HCC. • The D and D * values derived from IVIM diffusion-weighted imaging show significant negative correlations with fibrosis, an important predictor of liver regeneration. • No IVIM parameters were associated with liver regeneration in patients who underwent major hepatectomy, but the D value was a significant predictor of liver regeneration in patients who underwent minor hepatectomy., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: This study aimed to explore the expression of the C-type lectin domain family 4 member G (CLEC4G) gene in the liver sinusoidal endothelial cells (LSECs) during liver pathogenesis, and to evaluate its correlation with CD34 and clinical significance in hepatocellular carcinoma patients., Methods: We conducted bioinformatics analysis of the differential expression of CLEC4G in various human organs, carcinomatous and adjacent tissues. Then, mRNA and protein expression levels of CD34 in hepatocellular carcinoma (HCC) samples were detected via real-time quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical (IHC), respectively. ELISA was applied to detect serum levels of CLEC4G in healthy controls, liver fibrosis and HCC patients., Results: The expressions of mRNA and protein levels of CLEC4G were higher in normal liver tissues, moderately expressed in cirrhotic and para-cancerous tissues ( P <0.001), and lowest in HCC tissues ( P <0.001). We also found high CD34 expression in tumors, which was negatively correlated with CLEC4G at both mRNA and protein levels. Compared to the healthy controls, the CLEC4G levels in liver fibrosis patients and HCC patients gradually became lower ( P <0.001)., Conclusions: The low expression of CLEC4G is potentially correlated with LSEC capillarization and the appearance of micro-vessels. Such a phenomenon may serve as a reliable diagnostic marker for hepatocellular carcinoma., (© 2023 by the Association of Clinical Scientists, Inc.)

There is scant literature on primary nonhematopoietic malignant liver tumours (PMLT) in cats. In this retrospective study, medical data of 40 cats diagnosed with PMLT were reviewed over a period of 22 years (2000-2021). The most frequent epithelial tumours were hepatocellular (42.5%) and bile duct carcinomas (32.5%), only six (15%) cats had mesenchymal tumours. The median age was 13 years and clinical signs commonly included ano-/hyporexia (62.5%), apathy/lethargy (52.5%), weight loss (42.5%) and vomiting (35%). At initial diagnosis, metastases were confirmed in 1 (2.5%) and suspected in three (7.5%) cats. Massive was the most frequent morphology (75%). Most intrahepatic tumours were left-sided (54.2%) with the left medial lobe being primarily affected (25%). Extrahepatic tumours were rare (5%). In 34 (85%) cats, liver lobectomy was performed (surgery group), four (10%) were treated palliatively (non-surgery group), and two (5%) received no treatment. Intraoperative complications occurred in 11.8% with four (15.4%) postoperative deaths. Recurrence was detected in 28.6% at a median of 151 days (range, 79-684 days), while postoperative metastases were suspected in 21.4% at a median of 186 days (range, 79-479 days). The median survival time (MST) was significantly longer in cats of the surgery group (375 days) than in the non-surgery group (16 days) (p = .002). MST was 868 days for hepatocellular compared to 270 days for bile duct carcinomas (p = .06). In summary, liver lobectomy is associated with prolonged survival times and good prognosis in cats with hepatocellular, and an acceptable prognosis in cats with bile duct carcinoma., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Purpose: To summarize the magnetic resonance imaging manifestations of hepatocellular carcinoma (HCC) with and without progression after stereotactic body radiation therapy (SBRT) and evaluate the treatment effect using the modified Liver Reporting and Data System (LI-RADS)., Methods: Between January 2015 and December 2020, 102 patients with SBRT-treated HCC were included. Tumor size, signal intensity, and enhancement patterns at each follow-up period were analyzed. Three different patterns of enhancement: APHE and wash-out, non-enhancement, and delayed enhancement. For modified LI-RADS, delayed enhancement with no size increase were considered to be a "treatment-specific expected enhancement pattern" for LR-TR non-viable., Results: Patients were divided into two groups: without (n = 96) and with local progression (n = 6). Among patients without local progression, APHE and wash-out pattern demonstrated conversion to the delayed enhancement (71.9%) and non-enhancement (20.8%) patterns, with decreased signal intensity on T1WI(92.9%) and DWI(99%), increased signal intensity on T1WI (99%), and decreased size. The signal intensity and enhancement patterns stabilized after 6-9 months. Six cases with progression exhibited tumor growth, APHE and wash-out, and increased signal intensity on T2WI/DWI. Based on the modified LI-RADS criteria, 74% and 95% showed LR-TR-nonviable in 3 and 12 months post-SBRT, respectively., Conclusions: After SBRT, the signal intensity and enhancement patterns of HCCs showed a temporal evolution. Tumor growth, APHE and wash-out, and increased signal intensity on T2WI/DWI indicates tumor progression. Modified LI-RADS criteria showed good performance in evaluating nonviable lesions after SBRT., (© 2023. The Author(s).)

Background: Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment for hepatocellular carcinoma (HCC). Currently, there are no consensus guidelines to advise optimal patient selection and radiotherapy planning parameters to minimise the risk of surgical and medical complications after liver transplant (LT) in patients who have had prior SBRT for HCC, whilst optimising treatment benefit., Methods: We performed a retrospective analysis of all adult patients who received liver SBRT as a bridge to LT at a tertiary institution between 2017 and 2019., Results: Nine patients received SBRT as bridging therapy to LT. HCC location varied from peripheral to central/hilar regions and HCC diameter was 13-54 mm. Median time between SBRT and LT was 141 days (range 27-461 days). Median operating time was 360 min (range 270-480 min). Four patients (44%) had visible SBRT reaction or fibrosis at the time of LT. SBRT reaction resulted in clinical impact in one patient (11%) only, where vascular clamping of the IVC was required for 10 min., Conclusion: SBRT is a safe and effective treatment for HCC enabling patients to remain within LT criteria, even for lesions not amenable to other more conventional bridging therapies. We describe a preliminary decision pathway to guide the optimal use of SBRT as a bridge to LT developed in our institution., (© 2023 Royal Australian and New Zealand College of Radiologists.)

Background: There is little evidence on the efficacy of external beam radiation (EBR) compared to liver resection (LR) for patients with solitary small (≤5 cm) hepatocellular carcinoma (HCC)., Objective: We aimed to investigate this clinical question based on the Surveillance, Epidemiology, and End Results (SEER) database., Method: SEER database was used to identify 416 patients with solitary small HCC who underwent LR or EBR. Survival analysis and Cox proportional hazards model were performed to evaluate overall survival (OS) and identify prognostic factors for OS. Propensity score matching (PSM) method was used to adjust the baseline characteristics of the two groups., Result: Before PSM, the 1- and 2-year OS rates were 92.0% and 85.2% in the LR cohort and 76.0% and 60.3% in the EBR cohort, respectively (P < 0.001). After PSM, LR (n = 62) demonstrated improved OS compared to EBR (n = 62) (1-year OS rate: 96.5% vs. 76.0%; 2-year OS rate: 89.3% vs. 60.3%, P < 0.001), despite stratification on tumor size. Multivariate Cox regression analysis indicated that treatment type was the only factor associated with OS (hazard ratio: 5.297; 95% confidence interval: 1.952-14.371, P = 0.001)., Conclusion: For patients with solitary small HCC, LR may offer better survival outcomes than EBR.

Since hepatocellular carcinoma (HCC) represents an important cause of mortality and morbidity all over the world. Currently, it is fundamental not only to achieve a curative treatment but also to manage in the best way any possible recurrence. Even if the latest update of the Barcelona Clinic Liver Cancer guidelines for HCC treatment has introduced new locoregional techniques and confirmed others as well-established clinical practices, there is still no consensus about the treatment of recurrent HCC (RHCC). Locoregional treatments and medical therapy represent two of the most widely accepted approaches for disease control, especially in the advanced stage of liver disease. Different medical treatments are now approved, and others are under investigation. On this basis, radiology plays a central role in the diagnosis of RHCC and the assessment of response to locoregional treatments and medical therapy for RHCC. This review summarized the actual clinical practice by underlining the importance of the radiological approach both in the diagnosis and treatment of RHCC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: We aimed to prospectively compare the diagnostic performance of gadoxetic acid-enhanced MRI (EOB-MRI) and contrast-enhanced Computed Tomography (CECT) for hepatocellular carcinoma (HCC) detection and liver transplant (LT) eligibility assessment in cirrhotic patients with explant histopathology correlation., Methods: In this prospective, single-institution ethics-approved study, 101 cirrhotic patients were enrolled consecutively from the pre-LT clinic with written informed consent. Patients underwent CECT and EOB-MRI alternately every 3 months until LT or study exclusion. Two blinded radiologists independently scored hepatic lesions on CECT and EOB-MRI utilizing the liver imaging reporting and data system (LI-RADS) version 2018. Liver explant histopathology was the reference standard. Pre-LT eligibility accuracies with EOB-MRI and CECT as per Milan criteria (MC) were assessed in reference to post-LT explant histopathology. Lesion-level and patient-level statistical analyses were performed., Results: Sixty patients (49 men; age 33-72 years) underwent LT successfully. One hundred four non-treated HCC and 42 viable HCC in previously treated HCC were identified at explant histopathology. For LR-4/5 category lesions, EOB-MRI had a higher pooled sensitivity (86.7% versus 75.3%, p <  0.001) but lower specificity (84.6% versus 100%, p <  0.001) compared to CECT. EOB-MRI had a sensitivity twice that of CECT (65.9% versus 32.2%, p <  0.001) when all HCC identified at explant histopathology were included in the analysis instead of imaging visible lesions only. Disregarding the hepatobiliary phase resulted in a significant drop in EOB-MRI performance (86.7 to 72.8%, p <  0.001). EOB-MRI had significantly lower pooled sensitivity and specificity versus CECT in the LR5 category with lesion size < 2 cm (50% versus 79%, p = 0.002 and 88.9% versus 100%, p = 0.002). EOB-MRI had higher sensitivity (84.8% versus 75%, p <  0.037) compared to CECT for detecting < 2 cm viable HCC in treated lesions. Accuracies of LT eligibility assessment were comparable between EOB-MRI (90-91.7%, p = 0.156) and CECT (90-95%, p = 0.158)., Conclusion: EOB-MRI had superior sensitivity for HCC detection; however, with lower specificity compared to CECT in LR4/5 category lesions while it was inferior to CECT in the LR5 category under 2 cm. The accuracy for LT eligibility assessment based on MC was not significantly different between EOB-MRI and CECT., Trial Registration: ClinicalTrials.gov Identifier: NCT03342677 , Registered: November 17, 2017., (© 2023. The Author(s).)

Purpose: Raltitrexed shows therapeutic effects and safety in many types of malignant tumors. However, reports of the clinical outcomes of raltitrexed-based transarterial chemoembolization (TACE) or drug-eluting beads TACE (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC) are rare. We aim to report the preliminary outcomes of DEB-TACE loaded with raltitrexed in patients with unresectable or recurrent HCC., Methods: From June 2018 to March 2020, 29 patients with unresectable or recurrent HCC were recruited from our department and treated by DEB-TACE loaded with raltitrexed. Overall survival and progression-free survival were the primary end points. Tumor response was investigated by using the modified response evaluation criteria in solid tumors (mRECIST) criteria., Results: A total of 49 sessions of DEB-TACE were performed, with a technique success rate of 100%. The overall response rate and disease control rate at 1, 3, and 6 months after DEB-TACE were 72.0% and 96.0%, 57.1% and 85.7%, 47.6% and 66.7% respectively. The median progression-free survival and overall survival was 25.7 and 33.9 months, respectively. The 6-, 24- and 36-month overall survival rates were 88.4%, 66.3% and 46.3%, respectively. Minor complications were observed in 17 patients (58.6%), with no treatment-related mortality or severe adverse events. The most common treatment-related complications were abdominal pain (41.4%) and elevated ALT/AST (27.6%)., Conclusion: DEB-TACE loaded with raltitrexed is suggested as a safe, feasible, efficacious palliative regimen in unresectable or recurrent HCC patients., (© 2023. The Author(s).)

Primary hepatic neuroendocrine tumors and primary hepatic neuroendocrine carcinomas are rare and pose challenges for both diagnosis and for determining whether the tumor is primary to the liver versus metastatic disease. The lack of a uniform definition for primary hepatic neuroendocrine neoplasms is also a limitation to understanding and treating these rare tumors. Recently, there have been significant histological advances in the diagnosis and classification of neuroendocrine tumors in general, as well as significant advances in imaging for neuroendocrine neoplasms, all of which are important for their treatment. This article presents a multiple disciplinary definition and proposed guidelines for diagnosing a neuroendocrine tumor/neuroendocrine carcinomas as being primary to the liver., (Copyright © 2022. Published by Elsevier Inc.)

Unresectable hepatocellular carcinoma (HCC) is an advanced primary liver malignancy with a poor prognosis. The Food and Drug Administration (FDA) has, to date, approved nivolumab, pembrolizumab, ramucirumab, nivolumab/ipilimumab, atezolizumab/bevacizumab, as well as tremelimumab/durvalumab, as first- or second-line monoclonal antibodies (mAbs) for unresectable HCC. The present review examines the current state of knowledge, and provides a useful update on the safety and efficacy of these therapeutic agents, thus attempting to define the suitability of each mAb for different patient subgroups.

Aims: To investigate the efficacy and safety of lenvatinib and idarubicin-loaded drug-eluting beads transarterial chemoembolization (IDADEB-TACE) in primary advanced hepatocellular carcinoma (HCC)., Methods: This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB-TACE as first-line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score-matching was used to reduce the influence of confounding factors on the outcomes., Results: The study reviewed 118 patients who received lenvatinib plus IDADEB-TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score-matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post-treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6- and 12-month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression-free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α-fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group., Conclusions: Lenvatinib plus IDADEB-TACE is well-tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To develop a radiomics-based hepatocellular carcinoma (HCC) grade classifier model based on data from gadoxetic acid-enhanced MRI., Methods: This retrospective study included 137 patients who underwent hepatectomy for a single HCC and gadoxetic acid-enhanced MRI within 60 days before surgery. HCC grade was categorized as low or high (modified Edmondson-Steiner grade I-II vs. III-IV). We used the hepatobiliary phase (HBP), portal venous phase, T2-weighted image(T2WI), and T1-weighted image(T1WI). From the volume of interest in HCC, 833 radiomic features were extracted. Radiomic and clinical features were selected using a random forest regressor, and the classification model was trained and validated using a random forest classifier and tenfold stratified cross-validation. Eight models were developed using the radiomic features alone or by combining the radiomic and clinical features. Models were validated with internal enrolled data (internal validation) and a dataset (28 patients) at a separate institution (external validation). The area under the curve (AUC) of the validation results was compared using the DeLong test., Results: In internal and external validation, the HBP radiomics-only model showed the highest AUC (internal 0.80 ± 0.09, external 0.70 ± 0.09). In external validation, all models showed lower AUC than those for internal validation, while the T2WI and T1WI models failed to predict the HCC grade (AUC 0.30-0.58) in contrast to the internal validation results (AUC 0.67-0.78)., Conclusion: The radiomics-based machine learning model from gadoxetic acid-enhanced liver MRI could distinguish between low- and high-grade HCCs. The radiomics-only HBP model showed the best AUC among the eight models, good performance in internal validation, and fair performance in external validation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Skeletal muscle index (SMI) is a promising predictor of clinical outcomes in patients with malignant diseases. As a simpler surrogate of sarcopenia-psoas muscle index (PMI), its predict value for overall survival (OS) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been reported. To determine if changes in the PMI predicted OS in individuals with HCC treated with TACE., Patients and Methods: A retrospective analysis was performed in HCC patients treated with TACE between January 2018 and March 2019. The survival curve according to PMI was estimated by the Kaplan-Meier method and then compared by the log-rank test. Cox proportional hazards models were conducted to identify the prognostic factors for OS. Furthermore, the predictive abilities of PMI and SMI were compared by using Harrell's concordance index (C-index)., Results: Two hundred and twenty-eight patients (175 men, mean age 59 ± 11 years) were analysed. The OS was less in patients with low PMI than those with high PMI (median OS: 16.9 vs. 38.5 months, p  < .001). Multivariate analysis found that either PMI (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.45-0.91; p  < .001) or SMI (HR = 0.51; 95% CI, 0.36-0.72; p  < .001) was significantly associated with OS. In the multivariate analysis, the C-index for PMI was 0.78 and 0.79 for SMI ( p  = .985)., Conclusion: PMI is a simple tool to predict OS in HCC patients treated with TACE. The predictive ability of PMI is comparable to that of SMI. Key messagesLow psoas-muscle index is associated with decreased overall survival in hepatocellular carcinoma treated with transarterial chemoembolization (TACE).Psoas-muscle index has advantages of being faster and easier to acquire, which thus makes it more likely to achieve widespread clinical application.

Objectives: To evaluate the diagnostic accuracy of perfluorobutane contrast-enhanced ultrasonography (CEUS) for hepatocellular carcinoma (HCC) and to explore how accuracy can be improved compared to conventional diagnostic criteria in at-risk patients., Methods: A total of 123 hepatic nodules (≥ 1 cm) from 123 at-risk patients who underwent perfluorobutane CEUS between 2013 and 2020 at three institutions were retrospectively analyzed. Ninety-three percent of subjects had pathological results, except benign lesions stable in follow-up images. We evaluated presence of arterial phase hyperenhancement (APHE), washout time and degree, and Kupffer phase (KP) defects. KP defects are defined as hypoenhancing lesions relative to the liver in KP. HCC was diagnosed in two ways: (1) Liver Imaging Reporting and Data System (LI-RADS) criteria defined as APHE and late (≥ 60 s)/mild washout, and (2) APHE and Kupffer (AK) criteria defined as APHE and KP defect. We explored grayscale features that cause misdiagnosis of HCC and reflected in the adjustment. Diagnostic performance was compared using McNemar's test., Results: There were 77 HCCs, 15 non-HCC malignancies, and 31 benign lesions. An ill-defined margin without hypoechoic halo on grayscale applied as a finding that did not suggest HCC. Regarding diagnosis of HCC, sensitivity of AK criteria (83.1%; 95% confidence interval [CI]: 72.9-90.7%) was higher than that of LI-RADS criteria (75.3%; 95% CI: 64.2-84.4%; p = 0.041). Specificity was 91.3% (95% CI: 79.2-97.6%) in both groups., Conclusion: On perfluorobutane CEUS, diagnostic criteria for HCC using KP defect with adjustment by grayscale findings had higher diagnostic performance than conventional criteria without losing specificity., Key Points: • Applying Kupffer phase defect instead of late/mild washout and adjusting with grayscale findings can improve the diagnostic performance of perfluorobutane-enhanced US for HCC. • Adjustment with ill-defined margins without a hypoechoic halo for features unlikely to be HCC decreases false positives for HCC diagnosis using the perfluorobutane-enhanced US. • After adjustment with grayscale findings, the sensitivity and accuracy of the APHE and Kupffer criteria were higher than those of the LI-RADS criteria; specificity was 91.3% for both., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.

Background/aims: We studied the impact of socioeconomic status (SES) on mortality in hepatocellular carcinoma patients and analyzed the effect of SES on initial treatment allocation., Methods: A cohort study was conducted using data from the National Health Insurance Service- National Sample Cohort of Korea. A total of 3,032 hepatocellular carcinoma patients who were newly diagnosed between January 2003 and December 2013 were included. Income level was categorized as Medical Aid and ≤30th, 31st-70th, or >70th percentile as an SES indicator., Results: The proportion of Medical Aid was 4.3%. The highest risks of all-cause mortality associated with Medical Aid were evident in the transcatheter arterial chemoembolization group (fully adjusted hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.25 to 4.58), the other treatments group (fully adjusted HR, 2.86; 95% CI, 1.85 to 4.41), and the no treatment group (fully adjusted HR, 2.69; 95% CI, 1.79 to 4.04) but not in the curative treatment group. An association between the lower-income percentile and higher liver cancer-specific mortality was also observed, except in the curative treatment group. The association between income percentile and all-cause mortality was nonlinear, with a stronger association in the lower-income percentiles than in the higher income percentiles (p-value for nonlinear spline terms <0.05)., Conclusions: Patients in the lower SES group, especially patients not eligible for curative treatment, had an increased risk of mortality. In addition, the association between SES and the risk for mortality was stronger in the lower-income percentile than in the moderate to higher income percentiles.