• Carcinoma, Hepatocellular/therapy
• Carcinoma, Hepatocellular/diagnosis
• Liver Neoplasms/therapy
• Liver Neoplasms/diagnosis
• Humans
• Liver Transplantation/methods
• Liver Transplantation/standards
• Disease Management

• IMbrave150 trial
• hepatocellular carcinoma
• immune-checkpoint inhibitors
• immunotherapy
• neoadjuvant therapy

• Child-Pugh B
• cirrhosis
• hepatocellular carcinoma
• immuno-oncology
• multi-kinase inhibitors

• Humans
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/drug therapy
• Liver Neoplasms/complications
• Liver Neoplasms/drug therapy
• Randomized Controlled Trials as Topic

• P30 CA008748 NCI NIH HHS

• bioengineering technolog
• hepatocellular carcinoma
• personalized therapy
• precision medicine
• target therapy

• hyperoxia
• hypoxia‐inducible factor (HIF)
• immunotherapy
• targeted theraphy
• tumor hypoxia

• National Natural Science Foundation of China

• FDA
• HCC
• bevacizumab
• drug therapies
• molecular targets
• preclinical

• Humans
• Carcinoma, Hepatocellular/drug therapy
• Liver Neoplasms/drug therapy
• Pharmaceutical Preparations
• Protein Kinase Inhibitors/pharmacology

• HCC
• chemotherapy
• hepatocellular carcinoma
• immunotherapy
• neoadjuvant therapy
• systemic therapy

• National Natural Science Foundation of China
• Guangdong Provincial Science and Technology Program
• Natural Science Foundation of Guangdong Province of China
• Guangdong Province Regional Joint Fund-Key Projects
• Guangdong Basic and Applied Basic Research Foundation, Sanming Project of Medicine in Shenzhen
• Shenzhen Key Laboratory Foundation
• Shenzhen International Cooperative Research Project

• HDACis-resistant cells
• calreticulin
• chemosensitivity
• hepatocellular carcinoma

• Apoptosis/physiology
• Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics
• Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
• Calreticulin/genetics
• Calreticulin/metabolism
• Carcinoma, Hepatocellular/drug therapy
• Cell Nucleus/metabolism
• Endoplasmic Reticulum Stress
• Histone Deacetylase Inhibitors/pharmacology
• Histone Deacetylase Inhibitors/therapeutic use
• Humans
• Liver Neoplasms/drug therapy
• Signal Transduction

Ramucirumab has been shown to be effective as a second-line agent after sorafenib in hepatocellular carcinoma (HCC) patients whose α-fetoprotein was ≥400 ng/mL. We performed a retrospective cohort study to investigate ramucirumab efficacy in a real-world setting. Progression-free survival (PFS) was consistent through treatment lines, modified albumin–bilirubin (mALBI) grade, Barcelona Clinic for Liver Cancer (BCLC) stage, and α-fetoprotein (AFP) level. By contrast, ascites was more frequently seen in mALBI 2b/3 patients and, therefore, should be carefully monitored.

Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin–bilirubin (mALBI) 2b/3 patients than in mALBI 1/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC.

• hepatocellular carcinoma
• molecularly targeted agents
• ramucirumab

• BCLC stage
• ECOG performance status
• hepatocellular carcinoma
• immuno-oncology agent
• similarity assessment
• systemic treatment

• AstraZeneca

Hepatocellular carcinoma remains one of the leading causes of death from cancer worldwide as most cases are diagnosed at an advanced disease stage. Ramucirumab, a human anti-VEGFR-2 monoclonal antibody, is approved as a monotherapy for the treatment of patients with hepatocellular carcinoma and α-fetoprotein levels ≥400 ng/mL previously treated with sorafenib. As most patients present with an advanced disease, patients with α-fetoprotein levels ≥400 ng/mL have an aggressive disease and a poor prognosis, making ramucirumab an important treatment option for this subgroup of patients. This article provides a comprehensive review of the clinical efficacy of ramucirumab as highlighted in the two major trials that lead to its approval. We also briefly review the agent pharmacologic properties, as well as its safety and toxicity profile, before discussing certain limitations and challenges associated with ramucirumab use. Finally, we review completed and ongoing clinical trials and focus on those involving ramucirumab-based combinations, namely with immune therapy.

• hepatocellular carcinoma
• ramucirumab
• targeted therapy

• HCC
• TACE
• ablation
• hepatocellular carcinoma
• immunotherapy
• interventional radiology
• locoregional therapy
• microwave ablation
• radiofrequency
• tumor immunology

Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer in the world. Recently, the effectiveness of new antiviral therapies and the HBV vaccine have reduced HCC’s incidence, while non-alcoholic steato-hepatitis is an emerging risk factor. This review focuses on antiangiogenic molecules and immune checkpoint inhibitors approved for HCC treatment and possible future approaches. Sorafenib was the first drug approved for the treatment of advanced HCC (aHCC) and it has been shown to increase survival by a few months. Lenvatinib, a multikinase inhibitor, has shown non-inferiority in survival compared with sorafenib and an improvement in progression-free survival (PFS). The combination of atezolizumab (an anti-PDL1 antibody) and bevacizumab (an anti-VEGF antibody) was the first drug combination approved for HCC, demonstrating improved survival compared with sorafenib (19.2 vs. 13.4 months). As a second line of therapy, three regimens (regorafenib, cabozantinib, and ramucirumab) have been approved for the treatment of aHCC after progression on sorafenib according to guidelines. Furthermore, nivolumab, pembrolizumab, and nivolumab plus ipilimumab have been approved by the FDA (2017, 2018, and 2020, respectively). Finally, immune target therapy, cancer vaccines, and epigenetic drugs represent three new possible weapons for the treatment of HCC.

• HCC
• drugs
• liver
• trials

The population of patients with hepatocellular carcinoma (HCC) overlaps to a high degree with those for chronic kidney disease (CKD) and end-stage renal disease (ESRD). The degrees of renal dysfunction vary, from the various stages of CKD to dialysis-dependent ESRD, which often affects the prognosis and treatment choice of patients with HCC. In addition, renal dysfunction makes treatment more difficult and may negatively affect treatment outcomes. This study summarized the possible causes of the high comorbidity of HCC and renal dysfunction. The possible mechanisms of CKD causing HCC involve uremia itself, long-term dialysis status, immunosuppressive agents for postrenal transplant status, and miscellaneous factors such as hormone alterations and dysbiosis. The possible mechanisms of HCC affecting renal function include direct tumor invasion and hepatorenal syndrome. Finally, we categorized the risk factors that could lead to both HCC and CKD into four categories: Environmental toxins, viral hepatitis, metabolic syndrome, and vasoactive factors. Both CKD and ESRD have been reported to negatively affect HCC prognosis, but more research is warranted to confirm this. Furthermore, ESRD status itself ought not to prevent patients receiving aggressive treatments. This study then adopted the well-known Barcelona Clinic Liver Cancer guidelines as a framework to discuss the indicators for each stage of HCC treatment, treatment-related adverse renal effects, and concerns that are specific to patients with pre-existing renal dysfunction when undergoing aggressive treatments against CKD and ESRD. Such aggressive treatments include liver resection, simultaneous liver kidney transplantation, radiofrequency ablation, and transarterial chemoembolization. Finally, focusing on patients unable to receive active treatment, this study compiled information on the latest systemic pharmacological therapies, including targeted and immunotherapeutic drugs. Based on available clinical studies and Food and Drug Administration labels, this study details the drug indications, side effects, and dose adjustments for patients with renal dysfunction. It also provides a comprehensive review of information on HCC patients with renal dysfunction from disease onset to treatment.

• Hepatocellular carcinoma
• Chronic kidney disease
• End-stage renal disease
• Hemodialysis
• Cancer prognosis
• Cancer therapeutics

• Carcinoma, Hepatocellular/complications
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic
• Humans
• Kidney Failure, Chronic
• Liver Neoplasms/complications
• Liver Neoplasms/therapy
• Prognosis

• Cabozantinib
• Hepatocellular carcinoma

• cisplatin
• hepatocellular carcinoma
• transcatheter arterial chemoembolization
• transcatheter arterial infusion chemotherapy

• Biomarkers
• Cirrhosis
• Liver Cancer

• Adult
• Biomarkers, Tumor/analysis
• Carcinoma, Hepatocellular/diagnosis
• Case-Control Studies
• Early Detection of Cancer/methods
• Female
• Humans
• Liver Neoplasms/diagnosis
• Male
• Middle Aged
• Neoplasm Grading
• Predictive Value of Tests
• Research Design
• Retrospective Studies
• Risk Assessment/methods
• Societies, Medical

• U01 CA226052 NCI NIH HHS
• R01 CA212008 NCI NIH HHS
• R01 CA230503 NCI NIH HHS
• 26813 Cancer Research UK
• U24 CA230144 NCI NIH HHS
• R01 CA222900 NCI NIH HHS
• 671231 European Research Council
• U24 CA086368 NCI NIH HHS
• U01 CA230694 NCI NIH HHS
• U01 CA230669 NCI NIH HHS
• C9380/A26813 Cancer Research UK
• Wellcome Trust
• R01 CA233794 NCI NIH HHS
• P30 CA196521 NCI NIH HHS

• Autoimmune diseases
• Child-Pugh B
• Diabetes
• Elderly
• Fibrolamellar
• HIV
• Haemodialysis
• Hepatocellular carcinoma
• Metabolic syndrome
• Mixed HCC/CCC
• Transplant
• Vascular invasion

• hepatocellular carcinoma
• lenvatinib
• ramucirumab
• sorafenib

• HCC
• immune checkpoint
• small molecule drugs
• sorafenib
• targeted therapy

• AE
• RAM
• hepatoma
• malnutrition
• severe ascites

• Hepatocellular carcinoma
• immune checkpoint inhibitors
• monoclonal antibody
• tyrosine-kinase inhibitor
• unresectable

• Therapeutic monoclonal antibodies
• antibody modeling softwares
• antibody developmental technologies
• antibody engineering
• diseases
• pharmacological therapies

• Child–Pugh B
• hepatocellular carcinoma
• namodenoson
• overall survival
• randomized clinical trial

• NA Can-Fite BioPharma

Sorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma (HCC). However, sorafenib resistance significantly limits its therapeutic efficacy, and the mechanisms underlying resistance have not been fully clarified. Here we report that a circular RNA, circRNA-SORE (a circular RNA upregulated in sorafenib-resistant HCC cells), plays a significant role in sorafenib resistance in HCC. We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib. Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm, which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation. Moreover, our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells. Using different HCC mouse models, we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance. Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.

• Albumin-bilirubin grade
• Hepatocellular carcinoma
• Modified albumin-bilirubin grade
• Ramucirumab
• α-Fetoprotein

• Aged
• Antibodies, Monoclonal, Humanized/adverse effects
• Antineoplastic Agents/adverse effects
• Bilirubin/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/pathology
• Female
• Humans
• Japan/epidemiology
• Liver Function Tests
• Liver Neoplasms/blood
• Liver Neoplasms/drug therapy
• Liver Neoplasms/epidemiology
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Progression-Free Survival
• Retrospective Studies
• Serum Albumin, Human/analysis
• alpha-Fetoproteins/analysis
• Ramucirumab

• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Cell Line, Tumor
• Cell Survival/drug effects
• Cell Survival/genetics
• Drug Evaluation, Preclinical
• Drug Synergism
• Fluorouracil/administration & dosage
• Fluorouracil/pharmacokinetics
• Gene Expression Regulation, Neoplastic
• Genetic Engineering
• Humans
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• MicroRNAs/administration & dosage
• MicroRNAs/genetics
• MicroRNAs/pharmacokinetics
• Multidrug Resistance-Associated Proteins/antagonists & inhibitors
• Multidrug Resistance-Associated Proteins/genetics
• Multidrug Resistance-Associated Proteins/metabolism

• P30 CA093373 NCI NIH HHS
• R01 CA225958 NCI NIH HHS
• R01 GM113888 NIGMS NIH HHS
• T32 GM099608 NIGMS NIH HHS

The albumin–bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC.

Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2 weeks. Data were analysed by trial and as a meta-analysis of individual patient-level data (pooled population) from REACH (alpha-fetoprotein ≥400 ng/ml) and REACH-2. Patients from REACH with Child-Pugh class B were analysed as a separate cohort. The ALBI grades and scores were calculated at baseline and before each treatment cycle.

Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13–1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445–0.824]) and ALBI grade 2 (HR 0.814 [0.630–1.051]).

Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade.

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. Prognosis is affected by many clinical factors including liver function both before and during anticancer treatment. Here we have used a validated approach to assess liver function using 2 laboratory parameters, serum albumin and bilirubin (ALBI), both before and during treatment with ramucirumab in 2 phase III placebo-controlled studies. We confirm the practicality of using this more simplistic approach in assessing liver function prior to and during anticancer therapy, and demonstrate ramucirumab did not impair liver function when compared with placebo.

•

In patients with HCC, the severity of coexisting liver dysfunction is usually categorised using the Child-Pugh system.

• AE, adverse event
• AESI, adverse event of special interest
• AFP, alpha-fetoprotein
• ALBI
• ALBI, albumin–bilirubin
• ALT, alanine aminotransferase
• AST, aspartate aminotransferase
• BCLC, Barcelona Clinic Liver Cancer
• BOR, best overall response
• BSC, best supportive care
• CP, Child-Pugh
• CR, complete response
• ECOG PS, Eastern Cooperative Oncology Group performance status
• EoT, end of treatment
• GGT, gamma-glutamyltransferase
• HCC, hepatocellular carcinoma
• HR, hazard ratio
• IQR, inter-quartile range
• ITT, intent-to-treat
• Liver function
• MVI, macrovascular invasion
• OS, overall survival
• PD, progressive disease
• PR, partial response
• Prognosis
• Ram, ramucirumab
• SD, stable disease
• Safety
• Survival
• TACE, transarterial chemoembolisation
• Tumour response
• VEGF, vascular endothelial growth factor
• VEGFRs, vascular endothelial growth factor receptors

Increasing evidence has demonstrated the involvement of microRNAs in the pathogenesis of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). The aims of this study were to analyze whether miR-487b can be used as a diagnostic and prognostic biomarker for HBV-related HCC and to explore its effect on the biological function of HCC.

The expression levels of miR-487b in the serum of all subjects were measured by real-time quantitative fluorescence polymerase chain reaction. The diagnostic value of miR-487b in serum was assessed using the receiver operating characteristic (ROC) curve. The relationship between miR-487b and the clinical data of patients was analyzed using the chi-square test. The prognostic value of miR-487b in HCC was assessed by Cox regression analysis and Kaplan-Meier survival. Moreover, CCK-8 and Transwell assays were performed to investigate the effect of miR-487b on HBV-related HCC function.

Our data indicated that miR-487b in HCC patients was significantly higher than in chronic hepatitis B (CHB) patients and healthy controls. Meanwhile, the ROC curve showed that miR-487b had high specificity and sensitivity in the diagnosis of HBV-related HCC. MiR-487b can significantly distinguish between HCC patients and healthy controls and can differentiate HCC patients from CHB patients. Cox regression analysis showed that miR-487b was an independent risk factor. Overexpression of miR-487b was associated with Tumor Node Metastasis stage stage and Barcelona Clinic Liver Cancer stage in HCC patients. Cell function experiments demonstrated that upregulated miR-487b promoted cell proliferation, migration, and invasion.

Combined the results of the current study demonstrate that the upregulation of serum miR-487b may serve as a promising noninvasive diagnostic biomarker for HBV-related HCC.

• diagnosis
• hepatitis B virus
• hepatocellular carcinoma
• miR-487b
• prognosis

Background: The anti-programmed cell death protein-1 (PD-1) inhibitor is one of the second-line therapies for advanced hepatocellular carcinoma (HCC) after sorafenib failure. The goal of this study is to evaluate the feasibility and safety of ablation on the tumor in patients with advanced HCC who had stable disease or atypical response during single anti-PD-1 therapy after sorafenib failure. Atypical response defined as mixed responses in different lesions of the same individual (e.g., active or stable lesions mixed with progressive lesions).

Patients and Methods: This proof-of-concept clinical trial enrolled 50 patients treated with an anti-PD-1 inhibitor of nivolumab or pembrolizumab monotherapy between July 2015 and Nov 2017. Thirty-three cases with stable disease or atypical response to anti-PD-1 inhibitor received subtotal thermal ablation. The safety and the response of ablation during anti-PD-1 therapy were evaluated. The survival was estimated by the Kaplan-Meier curve.

Results: Of all 50 patients treated with anti-PD-1 therapy, the rate of response, stable disease, atypical and typical progression were 10% (n = 5), 42% (n = 21) 32% (n = 16), and 12% (n = 6), respectively. Additional ablation improved efficacy with tolerable toxicity, and the response rate was increased from 10 to 24% (12/50). The median time to progression, progression-free survival, and overall survival was 6.1 months (95%CI, 2.6–11.2), 5 months (95%CI, 2.9–7.1), and 16.9 months (95%CI, 7.7–26.1), respectively.

Conclusions: This proof-of-concept trial suggested that additional ablation may increase the objective response rate with tolerated toxicity and achieved a relatively better median survival, in advanced HCC patients who had stable or atypical progressive diseases during anti-PD-1 therapy, which may provide a potentially promising strategy to treat advanced HCC.

Trial registration number:ClinicalTrials.gov identifier: NCT03939975.

• anti-PD-1 mAbs
• hepatocellular carcinoma
• nivolumab
• pembrolizumab
• thermal ablation

• programmed death receptor 1 (pd-1)
• vegf receptor (vegfr)-2
• advanced hepatocellular carcinoma (hcc)
• immunotherapy
• vascular normalization

• Angiogenesis Inhibitors/therapeutic use
• Animals
• Antibodies/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoma, Hepatocellular/blood supply
• Carcinoma, Hepatocellular/drug therapy
• Cell Line, Tumor
• Liver Neoplasms/blood supply
• Liver Neoplasms/drug therapy
• Lymphocytes, Tumor-Infiltrating
• Mice
• Neoplasms, Experimental
• Neovascularization, Pathologic/drug therapy
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Programmed Cell Death 1 Receptor/immunology
• Spheroids, Cellular
• T-Lymphocytes, Cytotoxic
• Tumor-Associated Macrophages
• Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
• Vascular Endothelial Growth Factor Receptor-2/immunology

• R35-CA197743 NIH HHS
• U01 CA224348 NCI NIH HHS
• U01-CA224173 NIH HHS
• R01 CA208205 NCI NIH HHS
• R01-CA208205 NCI NIH HHS
• R41-CA213678 NCI NIH HHS
• R41 CA213678 NCI NIH HHS
• R35 CA197743 NCI NIH HHS
• P01 CA080124 NCI NIH HHS
• P01-CA080124 NCI NIH HHS

This study aimed to compare the safety and efficacy of transradial access (TRA) with transfemoral access (TFA) chemoembolization in treatment of hepatocellular carcinoma (HCC).

HCC patients who were late for curative treatment on initial diagnosis or HCC patients who had undergone one or several rounds of transarterial chemoembolization (TACE) were enrolled. The clinical and angiographic characteristics, the procedure related details, and the follow-up data from patients who underwent TRA and TFA were analyzed and compared.

In total, 112 patients undergoing 160 TRA-TACE and 107 patients undergoing 163 TFA-TACE were included. The technical success rate of TRA was 95.0% and that of TFA was 98.8% (P=0.102). In the TFA-TACE group, 5.5% of cases suffered access site-related complications, including 6 with minor bleeding and 3 with severe bleeding or pseudoaneurysm. In the TRA-TACE group, 1.9% of cases underwent crossover to femoral access for selective cannulation failure. The rate of radial artery occlusion (RAO) was 2.7% (3 of 112 patients), and none of the RAO patients suffered paresthesia, pain at the site of occlusion, hand function loss or distal ischemia. Comparing patients with/without access site-related complications in the TFA-TACE group, there was a statistical difference in patient age and in the percentage of patient with a PT time >15 s (72.6% vs. 57.1%, P<0.001; 44.4% vs. 11.7%, P=0.022).

TRA is a safe and effective method for patients undergoing TACE. Compared with TFA, TRA may reduce the occurrence of access site-related bleeding and vascular complications. TRA-TACE may especially benefit older patients or those with a longer prothrombin time (PT).

• Transarterial chemoembolization (TACE)
• access site-related complication
• transfemoral access (TFA)
• transradial access (TRA)

• cabozantinib
• lenvatinib
• nivolumab
• pembrolizumab
• ramucirumab
• regorafenib
• sorafenib