Hepatocellular carcinoma (HCC) is the most common primary cancer of liver tissue and is often caused by chronic liver diseases. The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly used to determine the stage and prognosis of HCC. Transarterial chemoembolization (TACE) is the recommended first-line therapy for intermediate-stage HCC (patients who have asymptomatic, multi-nodular hepatocellular carcinoma). Over the past 10 years, the combination of TACE with immune checkpoint inhibitors, such as Camrelizumab, has shown promising results in treating HCC. We conducted a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, MEDLINE, Elsevier, Scopus, ATC abstracts, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed to identify relevant studies on the effectiveness of TACE combined with Camrelizumab in the treatment of HCC. Study selection, data extraction, and quality assurance were conducted by independent investigators. From 1023 identified citations, six studies were included in the final analysis. The combined results of these studies showed a complete response rate of 7.35%, a partial response rate of 37.10%, stable disease in 28.76% of patients, an objective response rate of 46.13%, a disease control rate of 77.19%, and progression-free survival of 6.2 months. The combination of TACE and Camrelizumab appears to be a safe and effective treatment option for patients with advanced, recurrent, and unresectable HCC. However, the included studies had limitations such as retrospective design and small sample sizes. Further research is needed to validate and expand on these findings.

UNASSIGNED: The prognosis of hepatocellular carcinoma combined with portal vein tumor thrombus is poor, with a median survival of only 3-6 months. PD-1 combined with targeted therapy may provide an opportunity for patients with BCLC C stage hepatocellular carcinoma combined with portal vein tumor thrombus to undergo radical surgery, significantly prolonging their survival time.
UNASSIGNED: A middle-aged 51-year-old male who was diagnosed with hepatocellular carcinoma combined with portal vein main stem tumor thrombus at our center in May 2020, with a BCLC stage of C, liver cirrhosis, HBV infection, and preoperative evaluation as unresectable. The liver function was Child-Pugh A. The initial treatment was lenvatinib combined with PD-1 therapy, followed by one cycle of TACE treatment. The tumor and thrombus volume significantly reduced, followed by continuous TACE combined with immunotherapy and targeted therapy, leading to the appearance of portal vein main stem emboli. After multidisciplinary discussion, surgical resection was performed, and the embolus was removed, achieving a cure. The patient has been tumor-free for over 34 months.
UNASSIGNED: PD-1 combined with lenvatinib and local TACE create conditions for radical surgery, and it is hoped that more real-world research data can provide better evidence for the transformational treatment of hepatocellular carcinoma combined with portal vein tumor thrombus.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is recommended as the first-line therapy for unresected primary liver cancer (PLC), but only partial patients could benefit from TACE due to the serious adverse reactions. Clearing heat and resolving toxin (CHRT), one of most critical traditional Chinese medicine (TCM) therapeutic principles, has been widely used in the treatment of PLC patients especially after TACE. However, there is no enough clinical evidence to confirm the efficacy and safety of the combined therapy.
OBJECTIVE: To comprehensively evaluate the efficacy and safety of the combined CHRT-CHF with TACE in the treatment of PLC.
METHODS: 7 databases were searched from their inception until February 1, 2023. The primary outcomes included survival rate (1-, 2-year), objective response rate (ORR) and disease control rate (DCR), liver function indicators (AST, ALT), adverse reactions including fever, upper digestive tract side and myelosuppression, AFP were selected as the secondary outcomes. RevMan5.4 software was used to evaluate the quality of included studies; meta-analysis, subgroup analysis, meta-regression analysis, publication bias and trial sequential analyses (TSA) was conducted by Stata software 12.0.
RESULTS: There were 40 RCTs involving 3649 patients. Patients treated with TACE plus CHRT-CHF showed significantly better 1-, 2-year survival (respectively: OR, 2.23 [1.67-2.97]; OR, 2.13 [1.56-2.92]), ORR (OR, 2.14 [1.82-2.52]), DCR (OR, 2.13 [1.73-2.62]) compared with TACE alone. There was a decreased incidence of aspartate transaminase (AST), alanine transaminase (ALT), alpha-fetoprotein (AFP) and postembolization syndrome (PES) in patients receiving the combined TACE with CHRT-CHF compared with TACE alone. Subgroup analysis found that lower proportion (20-30%) of CHRT-CHF significantly enhanced survival rate and DCR, higher proportion (≥40%) of CHRT-CHF reduced PES after TACE treatment.
CONCLUSIONS: The efficacy and safety of the combined CHRT-CHF with TACE were validated in this meta-analysis, the optimal proportion of CHRT-CHF in enhancing the efficacy may be 20-30%; Additionally, higher proportion (≥40%) of CHRT-CHF appears to reduce PES after TACE treatment. The potential role of combined relative proportion of CHRT-CHF with TACE should be emphasized in clinic.

A 43-year-old female patient was found to have an abnormal liver function, abnormally elevated alpha-fetoprotein and space-occupying lesions in the liver on routine screening. The patient came to our hospital for further diagnosis and treatment.
Investigations: Laboratory investigations, digital subtraction angiography (DSA) of the hepatic artery, abdominal ultrasound examination, and magnetic resonance imaging (MRI) scan were conducted using pathological staining and immunohistochemistry.
Clinical diagnosis: cT3NxM0. Barcelona clinic liver cancer (BCLC) staging: BCLC stage C. China liver cancer (CNLC) staging: CNLC IIIa.
The patient was hospitalized for the first time for transcatheter arterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Then, the second and third hospital admissions were given HAIC based on FOLFOX. Camrelizumab and oncolytic virus were also injected into the liver cancer through the microcatheter in the first three treatments. On the fourth admission, the patient\'s indicators were improved, and the tumor shrank. Furthermore, as the patient suffered adverse reactions the first few times, we suspended the treatment of FOLFOX and the oncolytic virus. Before surgical treatment, lenvatinib was used throughout the treatment. On the fifth admission, the patient underwent liver cancer resection.
It proves the value of multiple combination therapy, which can provide guidance for patients with advanced hepatocellular carcinoma that cannot be surgically removed.

OBJECTIVE: Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC.
METHODS: We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio\'s random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs).
RESULTS: The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42).
CONCLUSIONS: Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings.
BACKGROUND: PROSPERO registration number: CRD42022298003.

UNASSIGNED: Lenvatinib combined with programmed cell death protein-1 inhibitor has achieved good survival results in the treatment of hepatocellular carcinoma with portal vein tumor thrombus. Transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) has attracted attention because of its high response rate and favorable survival rate in patients with liver cancer and portal vein tumor thrombus. This study aimed to compare the efficacy and safety of Lenvatinib combined with programmed cell death protein-1 inhibitor plus transarterial chemoembolization or hepatic arterial infusion chemotherapy in patients with hepatocellular carcinoma with portal vein tumor thrombus.
UNASSIGNED: We searched PubMed, Embase and the Cochrane Library for studies. These included randomized controlled trials or clinical trials of Lenvatinib plus programmed cell death protein-1 inhibitor plus transarterial chemoembolization or hepatic arterial infusion chemotherapy (intervention group) versus Lenvatinib plus programmed cell death protein-1 inhibitor or Lenvatinib plus transarterial chemoembolization/hepatic arterial infusion chemotherapy or Lenvatinib alone (control group) in liver cancer with portal vein tumor thrombus The primary outcomes were overall survival and progression-free time, and the secondary outcomes were response rate and the rate of adverse events. According to the heterogeneity among different studies, Revman5.4 was used to conduct fixed effect or random effect model analysis.
UNASSIGNED: Five clinical trials were included, including 311 cases in the intervention group and 309 cases in the control group. In terms of efficacy, compared with the control group, the overall survival (HR=1.88, 95%CI: 1.57-2.25, P < 0.00001) and progression-free survival (HR=1.62, 95%CI: 1.41-1.86, P < 0.00001), better efficacy, and better disease response than the control group. In terms of safety, the risk of treatment-related adverse events in the intervention group was higher than that in the control group, and White Blood cell count decreased (RR=0.72, 95%CI: 0.38-1.37, P=0.32), Platelet count decreased (RR=0.99, 95%CI: 0.65-1.51, P=0.96) and Total bilirubin increased (RR=0.86, 95%CI: Increased) 0.88-1.28, P=0.46) were lower than those in the control group, and the rest were higher than those in the control group, and the differences in some results were statistically significant.
UNASSIGNED: Transarterial chemoembolization or hepatic arterial infusion chemotherapy combined with Lenvatinib plus programmed cell death protein-1 inhibitor can effectively delay the progression, prolong the survival period and improve the quality of life of liver cancer patients with portal vein tumor thrombus.

Large primary hepatocellular carcinoma (HCC) has a high mortality rate and a variety of treatments. Surgery and transcatheter arterial chemoembolization (TACE) are important treatments. Which could be better remain debatable. The objective of the study is to compare the long-term overall survival of surgical resection (SR) and the use of TACE in patients with large hepatocellular carcinoma.
We assessed clinical trials through PubMed, Medline, Embase, and the Cochrane Library up to March 2022. Two researchers independently screened articles, extracted data, and assessed the study quality according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses)guidelines. The primary outcome was overall survival (OS). The secondary outcomes were OS after propensity scores matching (PSM) and progression-free survival (PFS).
A total of 14 studies, including 3609 patients, were enrolled in the meta-analysis. The meta-analysis indicated a significant improvement in the 1-year OS, 3-year OS, and 5-year OS favoring SR over TACE (OR = 2.19, 95% CI 1,60-3.00; OR = 3.47, 95% CI 2.47-4.88; OR = 2.72, 95% CI 2.03-3.64, p < 0.001, random model). The results were consistent across subgroups of tumor size and tumor numbers (p > 0.05). The pooled outcome indicated that 1-year OS, 3-year OS, and 5-year OS after PSM were higher in the SR group than in the TACE group (p < 0.001).
This meta-analysis indicates that among patients with large primary hepatocellular carcinoma, the overall survival rate of patients undergoing surgical resection was higher than that of patients undergoing TACE.

Background: Locoregional therapies (LRTs) are commonly used to increase the number of potential candidates for liver transplantation (LT). The aim of this paper is to assess the outcomes of LRTs prior to LT in patients with hepatocellular carcinoma (HCC) beyond the listing criteria. Methods: In accordance with the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before May 2021. We included papers assessing adult patients with HCC considered for LT and reporting intention-to-treat (ITT) survival outcomes. Two reviewers independently identified and extracted the data and evaluated the papers. Outcomes analysed were drop-out rate; time on the waiting list; and 1, 3 and 5 year survival after LT and based on an ITT analysis. Results: The literature search yielded 3,106 records, of which 11 papers (1874 patients) met the inclusion criteria. Patients with HCC beyond the listing criteria and successfully downstaged presented a higher drop-out rate (OR 2.05, 95% CI 1.45−2.88, p < 0.001) and a longer time from the initial assessment to LT than those with HCC within the listing criteria (MD 1.93, 95% CI 0.91−2.94, p < 0.001). The 1, 3 and 5 year survival post-LT and based on an ITT analysis did not show significant differences between the two groups. Patients with HCC beyond the listing criteria, successfully downstaged and then transplanted, presented longer 3 year (OR 3.77, 95% CI 1.26−11.32, p = 0.02) and 5 year overall survival (OS) (OR 3.08, 95% CI 1.15−8.23, p = 0.02) in comparison with those that were not submitted to LT. Conclusions: Patients with HCC beyond the listing criteria undergoing downstaging presented a higher drop-out rate in comparison with those with HCC within the listing criteria. However, the two groups did not present significant differences in 1, 3 and 5 year survival rates based on an ITT analysis. Patients with HCC beyond the listing, when successfully downstaged and transplanted, presented longer 3 and 5-year OS in comparison with those who were not transplanted.

OBJECTIVE: Hepatic function is a key prognostic marker in patients with hepatocellular cancer (HCC) and central to patient selection for transarterial chemoembolization (TACE). We investigated the clinical utility of the Albumin-Bilirubin (ALBI) grade, an emerging prognostic model, in this heterogenous cohort via a meta-analysis of published studies.
METHODS: Publications including full text articles and abstracts regarding ALBI grade were sourced by two independent researchers from databases including PubMed, Embase, Medline and Cochrane Library. Studies analysing patients with HCC undergoing TACE treatment were systematically screened utilising the PRISMA tool for data extraction and synthesis, after exclusion of duplicates, irrelevant studies and overlapping cohorts. The primary outcome was overall survival (OS), as determined by ALBI grade and assessed by hazard ratio (HRs) with 95% confidence intervals (CIs), with analysis of collated data using comprehensive meta-analysis, version 3.0 software.
RESULTS: Eight studies were included, with a pooled population of 6538 patients with HCC that underwent TACE treatment. Higher pre-treatment grade was associated with poor OS, with median OS of 12.0 months (P < 0.001) in ALBI grade 3, compared to 33.5 months in ALBI grade 1 (P < 0.001). Significant heterogeneity within each ALBI grade was associated with age and tumour size (P < 0.001) in ALBI grades 1 and 2. In contrast, age and alcohol-related liver disease were significant in the ALBI grade 3 group (P < 0.001).
CONCLUSIONS: High pre-treatment ALBI grade is associated with poorer prognosis in patients with HCC undergoing TACE therapy. The ALBI grade demonstrates clinical utility for clinical prognostication and patient selection for TACE.

This systematic review and meta-analysis compares the efficacy of three combination therapies, including transarterial chemoembolization (TACE) with radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CRA) for the treatment of patients with hepatocellular carcinoma (HCC).
Online databases, including Scopus, Web of Science, PubMed, Embase, CNKI, Google Scholar, and Cochrane Library were searched.
Forty-two studies with 5468 pooled patients (TACE + RFA: 21 studies with 3398 patients, TACE + MWA:14 studies with 1477 patients, and TACE + CRA: 7 studies with 593 patients) reported combination therapy versus TACE alone. The TACE + MWA subcohort had the best odds of long-term overall survival (OR 4.81, 95% CI 1.44, 16.08, P = 0.011) and objective response rate (OR 3.93, 95% CI 2.34, 6.61, P < 0.001) compared with the other two combination subcohorts. The TACE + RFA and TACE + MWA subcohorts had approximately similar odds of 1-year recurrence-free survival (OR 5.21, 95% CI 2.13, 12.75, P < 0.001 and OR 4.61, 95% CI 1.70, 12.51, P = 0.003, respectively). The disease control rate was similar between the TACE + MWA and TACE + CRA subcohorts (OR 4.01, 95% CI 2.66, 6.04, P < 0.001 and OR 4.05, 95% CI 1.68, 9.74, P = 0.002) but greater than the TACE + RFA subcohort (OR 3.23, 95% CI 2.14, 4.86, P < 0.001).
Overall, the TACE + MWA subcohort had the best efficacy and outcomes, especially for younger patients (less than 60-year-old) with tumor size of ≤ 3 cm, compared with the TACE + RFA or TACE + CRA subcohorts.