Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Intermediate-stage HCC is often treated with either transcatheter arterial chemoembolisation (TACE) or transcatheter arterial embolisation (TAE). Integrating machine learning (ML) offers the possibility of improving treatment outcomes through enhanced patient selection. This systematic review evaluates the effectiveness of ML models in improving the precision and efficacy of both TACE and TAE for intermediate-stage HCC. A comprehensive search of PubMed, EMBASE, Web of Science, and Cochrane Library databases was conducted for studies applying ML models to TACE and TAE in patients with intermediate-stage HCC. Seven studies involving 4,017 patients were included. All included studies were from China. Various ML models, including deep learning and radiomics, were used to predict treatment response, yielding a high predictive accuracy (AUC 0.90). However, study heterogeneity limited comparisons. While ML shows potential in predicting treatment outcomes, further research with standardised protocols and larger, multi-centre trials is needed for clinical integration.

tRNA-derived fragments (tRFs), a novel class of small non-coding RNAs cleaved from transfer RNAs, have been implicated in tumor regulation. In this study, the role of a specific tRF, HCETSR is investigated, which is significantly downregulated in hepatocellular carcinoma (HCC) and correlates with advanced tumor burden and higher HCC mortality. Functional analyses revealed that HCETSR inhibits HCC malignancy and serves as an independent predictor of poor prognosis. Mechanistically, a novel SPTBN1/catenin complex axis regulated by HCETSR is identified. HCETSR binds to a critical domain of SPTBN1, disrupting its interaction with the catenin complex (comprising β-catenin, α-catenin, and P120-catenin), and facilitates the transfer of the catenin complex from the cell membrane to the nucleus. Specifically, HCETSR decreases the proteasomal degradation of β-catenin and inhibits the synthesis of nascent β-catenin. Furthermore, HCETSR suppresses the transcriptional activity of LEF1 through P120-catenin rather than α-catenin, thereby reducing β-catenin's influence on LEF1 activity. It is demonstrated that HCETSR is spliced from tRNA-Glu/TTC. The biogenesis of HCETSR and tRNA-Glu/TTC is regulated by the spliceosome and Dicer1. In conclusion, These findings suggest that HCETSR, derived from tRNA-Glu/TTC, inhibits HCC malignancy via modulation of the SPTBN1/catenin axis and may represent a promising prognostic marker and therapeutic strategy for HCC.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Radiofrequency ablation (RFA) can be utilized in elderly patients and those with cirrhosis with reduced functional liver reserve as it is less invasive. The arfa RFA system is the first system to offer a linear mode. However, the differences in performance between the linear and existing (nonlinear) modes remain unknown.

This retrospective observational study compared the performance of the linear (linear group) and nonlinear RFA modes (nonlinear group) in HCC.

Data of 425 patients with one to three HCC tumors measuring ≤ 3 cm who underwent RFA were analyzed. Recurrence (local and distant), survival, and complication rates between the linear and nonlinear groups were determined.

The intrahepatic distant recurrence rate was lower in the linear group than in the nonlinear group (p < 0.05). Multivariate analysis showed that the high platelet count, low AFP-L3 levels, initial case, and linear mode were independent factors associated with a low intrahepatic distant recurrence rate following RFA. Liver disease-related survival, HCC survival, overall survival of the initial HCC, local recurrence, and complication rates were comparable between the linear and nonlinear groups.

The linear mode of the RFA protocol results in a lower intrahepatic distant recurrence rate compared with the nonlinear protocol.

The treatment of early stage hepatocellular carcinoma (HCC) has become increasingly complex. This study evaluates the effectiveness of radiofrequency ablation (RFA) versus laparoscopic liver resection (LLR) for treating solitary hepatocellular carcinoma (HCC) ≤ 3 cm, with a focus on tumor location and depth.

We conducted a retrospective analysis of patients treated for solitary HCC ≤ 3 cm in the right liver lobe from 2004 to 2022. Tumor depth was categorized into three zones based on proximity to portal vein branches: Zone I (near first-order branches), Zone II (adjacent to second-order branches), and Zone III (near third-order branches). Outcomes were measured using overall survival (OS) and recurrence-free survival (RFS) rates.

Of the 662 patients, for Zone I, II, and III, 240 (65 LLR, 175 RFA); 174 (100 LLR, 74 RFA); and, 248 patients were treated (244 LLR, 4 RFA), respectively. Statistically significant differences in the treatment outcomes based on the tumor depth were observed. For Zone I, LLR demonstrated superior OS (p = 0.043) and RFS rates (p = 0.030) than did RFA. For Zone II, both treatments had comparable survival outcomes, with no statistically significant differences in the OS (p = 0.460) and RFS (p = 0.358). For Zone III, LLR was principally favored, due to easier surgical access and cleaner margins.

This study highlighted the importance of including tumor location and depth, in addition to the tumor size and liver function, in the management of early stage HCC. A multidisciplinary approach is essential for treatment planning and optimizing survival outcomes.

Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options. Systemic therapies provide modest survival benefits, underscoring the need for alternative treatments. Locoregional approaches, such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and the requirement to interrupt systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent related to disease control and symptom management, or as bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. This review outlines institutional protocols for histotripsy, covering pre- and post-procedural management, along with ethical considerations of current treatment paradigms. As a patient-centered approach, histotripsy offers a novel treatment option with a favorable safety profile and compatibility with systemic therapies.

Background and Objectives: Primary liver cancer is a major cause of mortality, ranking third among the most fatal cancers. In Egypt, liver cancer constitutes 11.75% of gastrointestinal malignancies, with HCC representing 70.5% of cases. The landscape of HCC management was revolutionized by locoregional modalities, which offer a comparable alternative to conventional techniques, with low complications and minimal invasiveness. RFA is a technique that is suitable for early-stage lesions in the liver, with a high overall survival and low complication rates. However, the associated complications cause potential mortality and morbidity. The proper selection of patients may avoid such complications. This study presents a five-year experience of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in Egypt, analyzing the predictors of complications and the computed tomography (CT) features associated with complications post-ablation. Materials and Methods: The study included 1000 cases (84% males with a mean age of 60), with 90% having HCC. Exclusion criteria included prior chemoembolization and non-HCC primary hepatic tumors. Patients underwent RFA at Cairo University Hospital and two private centers from January 2014 to January 2019. The workup involved clinical assessments, lab tests, and CT scans. Complications were classified as major or minor. Statistical analysis was conducted via SPSS software Version 22.0, with associations evaluated using a chi-square test. A decision tree was employed to determine the predictive values for different variables associated with the complications. Results: Overall, the rate of complications was 4%, and mortality stood low at 0.1%. Subcapsular lesions were associated with complications, as well as the lesion size, site, Child-Pugh classification, and the number of RFA sessions. Decision tree analysis determined the size of a lesion to be the most predictive factor of major complications, whereas the site of the lesion predicted the occurrence of minor complications. Conclusions: RFA offers low complication rates; however, precise patient selection is critical. The approach and imaging modality choice influence the outcomes. Clinician experience enhances early complication detection, thereby allowing for effective treatments.

Many guidelines for hepatocellular carcinoma (HCC) have been published and are regularly updated worldwide. HCC management involves a broad range of treatment options and requires multidisciplinary care, resulting in significant heterogeneity in management practices across international communities. To support standardized care for HCC, we systematically appraised 13 globally recognized guidelines and expert consensus statements, including five from Asia, four from Europe, and four from the United States. These guidelines share similarities but reveal notable discrepancies in surveillance strategies, treatment allocation, and other recommendations. Geographic differences in tumor biology (e.g., prevalence of viral hepatitis, alcohol-related liver disease, or metabolic dysfunction-associated steatotic liver disease) and disparities in available medical resources (e.g., organ availability, healthcare infrastructure, and treatment accessibility) complicate the creation of universally applicable guidelines. Previously, significant gaps existed between Asian and Western guidelines, particularly regarding treatment strategies. However, these differences have diminished over the years. Presently, variations are often more attributable to publication dates than to regional differences. Nonetheless, Asia-Pacific experts continue to diverge from the Barcelona Clinic Liver Cancer system, particularly with respect to surgical resection and locoregional therapies, which are viewed as overly conservative in Western guidelines. Advancements in systemic therapies have prompted ongoing updates to these guidelines. Given that each set of guidelines reflects distinct regional characteristics, strengths, and limitations, fostering collaboration and mutual complementarity is essential for addressing discrepancies and advancing global HCC care.

To predict outcomes for patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) by assessing the ablative margin.

We retrospectively analyzed 163 HCC patients with complete RFA treatment at National Taiwan University Hospital (NTUH) from 2015 to 2020. Local tumor progression (LTP) is defined as the reappearance of HCC around the ablative zone. Various ablative margins (AM) are measured on post-RFA computed tomography (CT), including the minimal and maximal AM covering or not covering the liver surfaces (AMCLSmin, AMCLSmax, AMULSmin, AMULSmax). Average ablative margins (AMCLSavg, AMULSavg) are calculated from the minimal and maximal AM. Tumors at high-risk locations, including subdiaphragmatic, subcapsular, and perivascular regions, were further analyzed. The Kaplan-Meier method was utilized to analyze the recurrence-free survival (RFS) of different groups of patients. Patients were grouped by their ablative margin width with a cutting-off value of 3 mm or 5 mm.

Of the 163 HCC patients enrolled, 29 had LTP within two years, and 20 had LTP after two years. AMULSmin and AMULSavg were shown to be significant factors contributing to local tumor recurrences. Patients with AMULSmin≧3 mm had significantly better RFS than those with AMULSmin<3 mm (p = 0.0236). In high-risk locations, AMULSavg ≧5 mm had better RFS in subdiaphragmatic and subcapsular regions, and AMULSavg ≧3 mm had better RFS in perivascular region.

Measuring the ablative margin without covering the liver surface (especially AMULSmin, AMULSavg) in the post-RFA CT may be helpful prognosis indicators of LTP and RFS in HCC patients.

Promoting the early detection and diagnosis of hepatocellular carcinoma (HCC) is a critical strategy to improve patient outcomes as this can lead to greater access to curative treatments. This review highlights the diagnostic tests for HCC, including the use of the Liver Imaging Reporting and Data System systems and histopathology. Staging is essential for informing prognosis and guiding treatment decisions; this review also covers a widely used and well-validated staging system called the Barcelona-Clinic Liver Cancer (BCLC) algorithm. The BCLC incorporates tumor status, liver function, and patient performance to stage patients with newly diagnosed HCC.

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. Multiphasic computed tomography or MRI is the standard for HCC diagnosis, but histological confirmation should be considered, especially when inconclusive findings are seen on cross-sectional imaging. Staging and treatment decisions are complex and should be made in multidisciplinary settings, incorporating multiple factors including tumor burden, degree of liver dysfunction, patient performance status, available expertise, and patient preferences. Early-stage HCC is best treated with curative options such as resection, ablation, or transplantation. For intermediate-stage disease, locoregional therapies are primarily recommended although systemic therapies may be preferred for patients with large intrahepatic tumor burden. In advanced-stage disease, immune checkpoint inhibitor-based therapy is the preferred treatment regimen. In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

To determine the diagnostic value of ultrasound, multi-phase enhanced computed tomography, and magnetic resonance imaging of small hepatocellular carcinoma.

Experimental studies on diagnosing small hepatocellular carcinoma in four databases: PubMed, Cochrane Library, Web of Science, and Embase, were comprehensively searched from October 2007 to October 2024. Relevant diagnostic accuracy data were extracted and a Bayesian model that combined direct and indirect evidence was used for analysis.

16 original studies were included and data from 2,447 patients were collated to assess the diagnostic value of 10 different methods. The methodological quality of the included studies was good and there was no obvious publication bias. The pooled DOR of all diagnostic methods was 19.61, which was statistically significant (I2 = 76.0%, P < 0.01, 95% CI:13.30 - 28.92). Normal US + CEUS + ultrasonic elastic imaging had the highest specificity (92.9), accuracy (93.6), and positive predictive value (94.4). Unenhanced MRI + Contrast-enhanced MRI had the highest sensitivity (96.6) and negative predictive value (96.6), but specificity (12.5) and positive predictive value (34.4) were extremely poor. Contrast-enhanced MRI had the highest diagnostic value in individual imaging methods (sensitivity: 66, specificity: 55.5, accuracy: 67.9, positive predictive value: 64.4, negative predictive value: 66.5). There was significant inconsistency and high heterogeneity in this study.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024507883.

Percutaneous tumor ablation has become a widely accepted and used treatment option for both soft and hard tissue malignancies. The current standard-of-care techniques for performing these minimally invasive procedures require providers to navigate a needle to their intended target using two-dimensional (2D) US or CT to obtain complete local response. These traditional image-guidance systems require operators to mentally transpose what is visualized on a 2D screen into the inherent three-dimensional (3D) context of human anatomy. Advanced navigation systems designed specifically for percutaneous needle-based procedures often fuse multiple imaging modalities to provide greater awareness and planned needle trajectories for the avoidance of critical structures. However, even many of these advanced systems still require mental transposition of anatomy from a 2D screen to human anatomy. Augmented reality (AR)-based systems have the potential to provide a 3D view of the patient's anatomy, eliminating the need for mental transposition by the operator. The purpose of this article is to review commercially available advanced percutaneous surgical navigation platforms and discuss the current state of AR-based navigation systems, including their potential benefits, challenges for adoption, and future developments. Keywords: Computer Applications-Virtual Imaging, Technology Assessment, Augmented Reality, Surgical Navigation, Percutaneous Ablation, Interventional Radiology ©RSNA, 2025.

Background/Objectives: Radiofrequency ablation (RFA) is an important local treatment for hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristics of tumor recurrence after RFA and analyze predictors of tumor recurrence and survival in patients with HCC. Methods: We retrospectively reviewed data from treatment-naïve patients with HCC who underwent RFA for HCC treatment between 2008 and 2017 at four tertiary hospitals in South Korea. Results: A total of 636 patients with HCC treated with RFA were enrolled in the study. The mean age was 66.3 ± 10.4 years, with 75.0% of patients being male. Most patients (96.7%) had underlying liver cirrhosis, and viral hepatitis (types B and C) accounted for most cases. The average maximum tumor size was 2.2 ± 0.9 cm, with 84.3% of tumors being single lesions. During the follow-up period, 331 patients experienced recurrence, with 95.5% of cases being intrahepatic and one-fifth occurring at the RFA site. Most patients underwent RFA or transarterial chemoembolization as subsequent therapy for recurrence. Multivariate analysis revealed that age, the albumin-bilirubin (ALBI) grade, and Child-Pugh class B status were independent factors associated with tumor recurrence. Only the ALBI grade was significantly associated with mortality. Additionally, the ALBI grade differentiated between recurrence-free survival and overall survival in the Kaplan-Meier survival curve. Conclusions: The ALBI grade was independently associated with tumor recurrence and prognosis in patients with HCC following RFA. This grading system can help clinicians identify high-risk patients, optimize treatment strategies, and enhance patient care.

Hepatocellular carcinoma (HCC) is one of the most common forms of primary liver cancer worldwide. Herein, we present a review article that provides a broad overview of the current landscape of HCC, including the etiology, potential risk factors, and molecular pathways that can serve as potential therapeutic targets. The risk factors tend to vary depending on the geographic distribution; hepatitis B-induced cirrhosis and HCC occur more frequently in Asia and Sub-Saharan Africa, whereas metabolic disorders are the culprits in Western Europe and the Americas. The exact molecular alterations that drive hepatocarcinogenesis have yet to be elucidated; however, a complex interplay exists between oxidative stress and chronic inflammation. Diagnostic modalities such as tri-phasic MRI or CT also have distinct patterns for HCC, which aid significantly in diagnosis. Furthermore, the review aims to highlight treatment strategies, including transplantation, locoregional radiation therapies, and interventional radiological techniques such as chemotherapy or radioembolization. Finally, systemic therapies will be discussed, taking advantage of molecular pathways that influence cellular proliferation and survival as well as immunotherapy.

The management of early stage hepatocellular carcinoma (HCC) presents significant challenges. While radiofrequency ablation (RFA) has shown safety and effectiveness in treating HCC, with lower mortality rates and shorter hospital stays, its high recurrence rate remains a significant impediment. Consequently, achieving improved survival solely through RFA is challenging, particularly in retrospective studies with inherent biases. Ultrasound is commonly used for guiding percutaneous RFA, but its low contrast can lead to missed tumors and the risk of HCC recurrence. To enhance the efficiency of ultrasound-guided percutaneous RFA, various techniques such as artificial ascites and contrast-enhanced ultrasound have been developed to facilitate complete tumor ablation. Minimally invasive surgery (MIS) offers advantages over open surgery and has gained traction in various surgical fields. Recent studies suggest that laparoscopic intraoperative RFA (IORFA) may be more effective than percutaneous RFA in terms of survival for HCC patients unsuitable for surgery, highlighting its significance. Therefore, combining MIS-IORFA with these enhanced percutaneous RFA techniques may hold greater significance for HCC treatment using the MIS-IORFA approach. This article reviews liver resection and RFA in HCC treatment, comparing their merits and proposing a trajectory involving their combination in future therapy.

Liver in the body plays vital role including digestion, detoxification, metabolism and even production of hormones. Hepatocellular carcinoma is recognized as one of leading cause of death worldwide. Infection with hepatitis B and C virus, nonalcoholic fatty liver disease and excessive consumption of alcohol are among the most common risk factors associated with the development of hepatocellular carcinoma.

The present research study involves formulation of liposomal delivery of methanolic extract of Annona muricata as an alternative for the treatment of hepatocellular carcinoma.

The methanolic extract of Annona muricata was subjected for both nonvolatile and volatile content analysis by performing phytochemical screening and GCMS. The methanolic extract was entrapped within the liposomes for its effective delivery. The prepared liposomes were characterized in-vitro, and the optimized formulation was further evaluated against hepatocellular carcinoma induced in the animal model.

The methanolic extract showed the presence of alkaloid, carbohydrate, flavonoid, tannin, proteins and acetogenins, whereas the GMCS analysis depicts presence of 12 different compounds. The optimized in-vitro analysis of prepared liposomes showed a particle size of 107.2 ± 1.7 nm, zeta potential of -30.6 mV and entrapment efficiency of 62.15%. TEM micrograph of the optimized liposome formulation has showed spherical geometry with homogenous distribution and negligible agglomeration. In-vivo anticancer study reveals the potent efficacy of the formulation for the treatment of hepatocellular carcinoma.

The research findings have established the efficacy of the methanolic extract of Annona muricata in the treatment of hepatocellular carcinoma.

Liver resection and percutaneous thermal ablation (PTA) are considered curative option for hepatocellular carcinoma (HCC). This study aims to compare short- and long-term outcomes between open liver resection (OLR), laparoscopic liver resection (LLR), and PTA in elderly patients with single HCC and to define a liver map for therapeutic strategy according to HCC location and size.

A multicenter retrospective study was conducted in 10 European Hospital Center, including 239 consecutive liver resection (OLR and LLR) and PTA in elderly patients ≥ 70 years old with single HCC ≤ 30 mm. Perioperative data and long-term oncological outcomes were collected and compared between groups before and after propensity score matching.

A total of 239 patients were enrolled, distributed as follows: 61 in the ORL group, 88 in the LLR group, and 90 in the PTA group. The hospital stay was longer in OLR and LLR groups compared to the PTA group (6, 5 and 3 days, respectively, p < 0.05). Morbidity was lower in the PTA group compared to the OLR group (11 vs. 26%, respectively, p < 0.05). Overall survival (OS) at 5 years was significantly higher in the OLR and LLR groups compared to the PTA group (82, 81, and 34%, respectively, p < 0.001). Disease-free survival (DFS) at 5 years was also significantly higher in the ORL and LLR groups compared to the PTA group (66, 50 and 20%, respectively, p < 0.001). These results were also confirmed after a propensity score matching analysis between surgery group (OLR and LLR) and the PTA group. PTA was the most used treatment for subcapsular and deep HCC not in contact with vascular structures compared to OLR and LLR.

PTA in elderly patients ensures a shorter hospital stay and lower morbidity but worst survival compared to liver resection.

Local ablation for hepatocellular carcinoma, a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage hepatocellular carcinoma. The lack of organized evidence and expert opinions regarding patient selection, preprocedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-Guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation.

A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.

A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1-14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5-11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1-95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7-64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups.

Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.

To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A).

The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS).

The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group.

RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function.

This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas.

• The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups.

Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the first-line treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and post-treatment management of patients.

Local ablation for hepatocellular carcinoma (HCC), a non-surgical option that directly targets and destroys tumor cells, has advanced significantly since the 1990s. Therapies with different energy sources, such as radiofrequency ablation, microwave ablation, and cryoablation, employ different mechanisms to induce tumor necrosis. The precision, safety, and effectiveness of these therapies have increased with advances in guiding technologies and device improvements. Consequently, local ablation has become the firstline treatment for early-stage HCC. The lack of organized evidence and expert opinions regarding patient selection, pre-procedure preparation, procedural methods, swift post-treatment evaluation, and follow-up has resulted in clinicians following varied practices. Therefore, an expert consensus-based practical recommendation for local ablation was developed by a group of experts in radiology and hepatology from the Research Committee of the Korean Liver Cancer Association in collaboration with the Korean Society of Image-guided Tumor Ablation to provide useful information and guidance for performing local ablation and for the pre- and posttreatment management of patients.

Background Histotripsy is a nonthermal, nonionizing, noninvasive, focused US technique that relies on cavitation for mechanical tissue breakdown at the focal point. Preclinical data have shown its safety and technical success in the ablation of liver tumors. Purpose To evaluate the safety and technical success of histotripsy in destroying primary or metastatic liver tumors. Materials and Methods The parallel United States and European Union and England #HOPE4LIVER trials were prospective, multicenter, single-arm studies. Eligible patients were recruited at 14 sites in Europe and the United States from January 2021 to July 2022. Up to three tumors smaller than 3 cm in size could be treated. CT or MRI and clinic visits were performed at 1 week or less preprocedure, at index-procedure, 36 hours or less postprocedure, and 30 days postprocedure. There were co-primary end points of technical success of tumor treatment and absence of procedure-related major complications within 30 days, with performance goals of greater than 70% and less than 25%, respectively. A two-sided 95% Wilson score CI was derived for each end point. Results Forty-four participants (21 from the United States, 23 from the European Union or England; 22 female participants, 22 male participants; mean age, 64 years ± 12 [SD]) with 49 tumors were enrolled and treated. Eighteen participants (41%) had hepatocellular carcinoma and 26 (59%) had non-hepatocellular carcinoma liver metastases. The maximum pretreatment tumor diameter was 1.5 cm ± 0.6 and the maximum post-histotripsy treatment zone diameter was 3.6 cm ± 1.4. Technical success was observed in 42 of 44 treated tumors (95%; 95% CI: 84, 100) and procedure-related major complications were reported in three of 44 participants (7%; 95% CI: 2, 18), both meeting the performance goal. Conclusion The #HOPE4LIVER trials met the co-primary end-point performance goals for technical success and the absence of procedure-related major complications, supporting early clinical adoption. Clinical trial registration nos. NCT04572633, NCT04573881 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Nezami and Georgiades in this issue.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, often arising in the context of chronic liver disease and cirrhosis. This case report describes the clinical presentation, diagnostic evaluation, and therapeutic intervention of a 72-year-old male with a long-standing history of alcohol use who presented with right hypochondrial pain. A 72-year-old male with a 20-year history of alcohol consumption presented with a one-month history of dull, aching pain in the right hypochondrium. Diagnostic imaging, including abdominal ultrasound and contrast-enhanced computed tomography (CECT), revealed significant hepatomegaly with nodular and irregular liver margins, free fluid in the abdomen and pelvis, and multiple hypodense nodules in both liver lobes. One nodule in the right lobe exhibited characteristic imaging features of hepatocellular carcinoma, including peripheral enhancement on the arterial phase and washout on the delayed phase. Histopathological analysis of a biopsy from the suspicious nodule confirmed the diagnosis of hepatocellular carcinoma. The patient was diagnosed with hepatocellular carcinoma based on clinical, radiological, and histopathological findings. He was subsequently scheduled for radiofrequency tumor ablation. This case underscores the importance of comprehensive diagnostic imaging and histopathological evaluation in patients with liver cirrhosis and suspected HCC, particularly in those with a history of chronic alcohol use.

Liver resection and ablation remain the most common therapeutic options for Barcelona Clinic Liver Cancer (BCLC) stage 0-A hepatocellular carcinoma (HCC), but there is a lack of evidence to show which is the most suitable therapy. This study aimed to make concurrent multi-arm comparisons of the short-term and long-term outcomes of percutaneous ablation (PA), open (OLR) or laparoscopic liver resection (LLR) for these patients.

This was a retrospective observational cohort study. A series of generalized propensity score methods for multiple treatment groups were performed to concurrently compare the clinical outcomes of these three treatment options to balance potential confounders. Regression standardization was used to account for hazard of all-cause mortality and recurrence of intergroup differences.

Of the 1778 patients included, 1237, 307 and 234 underwent OLR, LLR and PA, respectively. After overlap weighting, which was the optimal adjustment strategy, patients in the minimally invasive group (LLR and PA groups) had few postoperative complications and short postoperative hospital stays (both P < 0.001). The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate were significantly higher in the LLR group when compared with the OLR and PA groups (RFS: 55.6% vs 48.0% vs 30.2%, P < 0.001; OS: 89.1% vs 79.7% vs 84.0%, P = 0.020). Multivariable Cox analysis and regression standardization showed that LLR was an independent factor for better RFS when compared with OLR and PA. In subgroup analysis, the long-term outcomes of patients with BCLC stage A HCC were consistent with the whole population.

In the observational study using various covariate adjustment analysis with excellent balance, LLR is not only minimally invasive, but also provides better RFS and equivalent OS for patients with BCLC stage 0-A HCC when compared with OLR and PA.

We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure.

We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models.

Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%.

Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.

(1) Background: HBV-DNA is an essential clinical indicator of primary hepatocellular carcinoma (HCC) prognosis. Our study aimed to investigate the prognostic implication of a low load of HBV-DNA in HCC patients who underwent local treatment. Additionally, we developed and validated a nomogram to predict the recurrence of patients with low (20-100 IU/mL) viral loads (L-VL). (2) Methods: A total of 475 HBV-HCC patients were enrolled, including 403 L-VL patients and 72 patients with very low (<20 IU/mL) viral loads (VL-VL). L-VL HCC patients were randomly divided into a training set (N = 282) and a validation set (N = 121) at a ratio of 7:3. Utilizing the Lasso-Cox regression analysis, we identified independent risk factors for constructing a nomogram. (3) Results: L-VL patients had significantly shorter RFS than VL-VL patients (38.2 m vs. 23.4 m, p = 0.024). The content of the nomogram included gender, BCLC stage, Glob, and MLR. The C-index (0.682 vs. 0.609); 1-, 3-, and 5-year AUCs (0.729, 0.784, and 0.783, vs. 0.631, 0.634, the 0.665); calibration curves; and decision curve analysis (DCA) curves of the training and validation cohorts proved the excellent predictive performance of the nomogram. There was a statistically significant difference in RFS between the low-, immediate-, and high-risk groups both in the training and validation cohorts (p < 0.001); (4) Conclusions: Patients with L-VL had a worse prognosis. The nomogram developed and validated in this study has the advantage of predicting patients with L-VL.

Hepatocellular Carcinoma (HCC) still is one of the most detrimental malignant diseases in the world. As two curative surgical therapies exist, the discussion whether to opt for liver resection (LR) or transplantation (LT) is ongoing, especially as novel techniques to improve outcome have emerged for both. The aim of the study was to investigate how the utilization and outcome of the respective modalities changed through time.

We searched Medline and PubMed for relevant publications comparing LT and LR in HCC patients during the time period from 1990 to 2022, prior to March 31, 2023. A total of 63 studies involving 19,804 patients - of whom 8178 patients received a liver graft and 11,626 underwent partial hepatectomy - were included in this meta-analysis.

LT is associated with significantly better 5-year overall survival (OS) (64.83%) and recurrence-free survival (RFS) (70.20%) than LR (OS: 50.83%, OR: 1.79, p < 0.001; RFS: 34.46%, OR: 5.32, p < 0.001). However, these differences are not as evident in short-term intervals. Older cohorts showed comparable disparities between the outcome of the respective modalities, as did newer cohorts after 2005. This might be due to the similar improvement in survival rates that were observed for both, LT (15-23%) and LR (12-20%) during the last 30 years.

LT still outperforms LR in the therapy of HCC in terms of long-term survival rates. Yet, LR outcome has remarkably improved which is of major importance in reference to the well-known limitations that occur in LT.

Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument.

The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated.

Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively).

Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.

With the increasing prevalence of hepatocellular carcinoma (HCC), ablative therapy is a critical treatment option to achieve a cancer-free state. The anatomic location of the tumor can be a challenge, and select hepatic locations of a tumor require laparoscopic-assisted strategies to safely reach and treat the lesion.

To assess the association of real-time ultrasonography-augmented navigation for HCC ablation with patient survival, operative time, and rate of incomplete ablations.

This retrospective case-control study was conducted among a prospectively collected database of more than 750 patients with HCC who were treated with ablation therapy with and without the use of navigation at a single quaternary medical center from June 2011 to January 2021. Data were analyzed from October 2022 through June 2023.

Real-time ultrasonography-augmented navigation.

The primary outcome was rate of incomplete ablations in patients undergoing HCC ablation with vs without navigation. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and operative time.

The analytic cohort included 467 patients (mean [SD] age, 62.4 [7.8] years; 355 male [76.0%]; 21 Hispanic [4.5%], 67 non-Hispanic Black [14.5%], and 347 Non-Hispanic White [75.0%] among 463 patients with race and ethnicity data). The most common etiology of liver disease was hepatitis C infection (187 patients with etiology data [40.0%]), and 348 of 458 patients with TMN staging data (76.0%) had TNM stage 1 disease. There were 187 individuals treated with navigation and 280 individuals treated without navigation. Patients who underwent navigation-assisted ablation were more likely to have stage 2 disease based on TNM staging (62 of 183 patients [33.9%] vs 47 of 275 patients [17.1%] with TMN data; P < .002) and had a higher mean (SD) number of lesions (1.3 [0.5] vs 1.2 [0.5] lesions; P = .002) and a longer mean (SD) operation time (113.2 [29.4] vs 109.6 [32.3] minutes; P = .04). Patients who underwent navigation were also more likely to have tumors in segment 8 (59 patients [32.1%] vs 53 of 275 patients with segment data [19.3%] with segment data; P = .005) and less likely to have tumors in segment 4 (20 patients [10.9%] vs 54 patients with segment data [19.6%]; P = .005). Overall mean (SD) time to recurrence after treatment was 10.0 (12.5) months, with similar rates for patients with navigation vs no navigation. There were no differences in incomplete ablation rate (10 patients [9.2%] vs 10 patients [10.5%]; P = .32), OS, or PFS between patients undergoing ablation with and without navigation.

In this study, use of navigation was associated with comparable outcomes to undergoing ablation without navigation, although patients with navigation had more locally advanced disease. These findings suggest that use of real-time navigation in laparoscopic-assisted ablation of liver cancer should be considered as a useful tool for treating challenging tumors.

The outcomes of cirrhotic patients with hepatocellular carcinoma (HCC) after thermal ablation (TA) versus liver resection (LR) are debated. We aimed to compare the overall survival (OS), disease-free survival (DFS), and operative outcomes after TA and LR for HCC in patients with cirrhosis. Until November 15, 2022, we searched PubMed, Embase, and Cochrane databases by using Medical Subject Heading terms and other terms, and used the Newcastle-Ottawa literature evaluation scale to assess the quality of selected studies. OS, DFS, and operative outcomes were extracted and analyzed. The meta-analysis showed that 5 propensity-score matched (PSM) studies including 933 patients (463 TA vs. 470 LR) were included. After analysis, TA and LR had similar results at 1-year OS (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.01-2.78; P = 0.05) and 3-year OS (OR 0.76; 95% CI 0.56-1.04; P = 0.08), whereas LR increased 5-years OS (OR 0.37; 95% CI 0.18-0.74; P = 0.005). In addition to the DFS, the 1-year DFS was significantly higher in patients with LR. However, there were no obvious differences in 3-year and 5-year DFS when comparing TA and LR. The length of operative time and hospital stay were longer in the LR group. Besides, the LR group had significantly higher rate of perioperative blood transfusions and major complications. Our research proved that LR took advantage of OS and DFS for HCC patients with cirrhosis. Additional well-designed randomized controlled trials are needed.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.

Percutaneous thermal ablation (PTA) is a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). However, intrahepatic distant recurrence (IDR) occurs in the majority of patients after PTA. The aim of this study was to evaluate the immune signature associated with very early IDR.

Thirty-one patients (26 men, 5 women; mean age:72.4 ± 8.6; age range:57-86 years) who underwent PTA for HCC were included in this study. After PTA for HCC, patients were followed and later divided into two groups: a "very early recurrence" group in case of IDR within 12 months after PTA, and a "prolonged recurrence-free" group in case of no recurrence before 12 months of follow-up. Freshly harvested intratumoral and nontumoral liver tissues and peripheral blood were obtained before PTA and explored by multiparametric flow cytometry.

The frequency of PD1+CD4+ T cells was higher in the early recurrence group than in the prolonged recurrence-free group in the peripheral blood (24.3%, IQR: 22.3-36.5 vs 14.0%, IQR: 11.5-16.4, p<0.0001), in the nontumoral liver (37.9%, IQR: 36.0-50.0 vs 22.5%, IQR: 18.0-29.9, p=0.0004), and in the tumor (37.6%, IQR: 32.3-39.3 vs 24.0%, IQR: 20.0-30.3, p=0.0137). Similarly, the frequency of TIM+CD8+ T cells was higher in the very early recurrence group in the peripheral blood (p=0.0021), non-tumoral liver (p=0.0012), and tumor (p=0.0239).

The expression of immune checkpoint molecules, such as PD1 and TIM3 on T cells identified HCC patients at risk of very early IDR after PTA who would likely benefit from adjuvant immunotherapy. Thus, our study contributes to a better understanding of the potential association of PTA with adjuvant immunotherapies.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the eighth most common cancer in women worldwide. It is also the second leading cause of cancer death worldwide, with 780,000 deaths in 2018. Seventy-two percent of HCC cases occur in Asia, 10% in Europe, 8% in Africa, 5% in North America, and 5% in Latin America (Singal et al. in J Hepatol 72(2):250-261, 2020 [1]).

Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis.

We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective.

In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY.

The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.