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Journal of Clinical Medicine Research Jul 2023Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma...
BACKGROUND
Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC.
METHODS
A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker.
RESULTS
Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70 - 0.72) and 0.64 (0.63 - 0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89 - 0.90) and 0.87 (0.87 - 0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88 - 0.90) and 0.78 (0.77 - 0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100).
CONCLUSION
This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.
PubMed: 37575350
DOI: 10.14740/jocmr4951 -
Heliyon Aug 2023Traditional Chinese medicine and radiofrequency ablation are becoming increasingly important in the treatment of primary liver cancer. However, the clinical outcome of...
BACKGROUND & AIMS
Traditional Chinese medicine and radiofrequency ablation are becoming increasingly important in the treatment of primary liver cancer. However, the clinical outcome of traditional Chinese medicine plus radiofrequency ablation is contentious. This study aimed to conduct a meta-analysis of randomized controlled clinical trials to address this gap.
METHODS
Short-term efficacy, alpha-fetoprotein level, immune function, liver function, and quality of life outcomes in patients with primary liver cancer treated with Chinese herbal medicine adjuvant radiofrequency ablation were systematically reviewed.
RESULTS
Eighteen randomized controlled clinical trials with 1488 patients with primary liver cancer were included. The combination treatment significantly increased the objective remission rate and quality of patient survival compared to the control group. Combination treatment significantly improved immunity and liver function factors, including CD3, CD4, CD4/CD8, alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin levels. However, there were no statistical differences in CD8 levels across treatments. Trial sequential analysis showed that the cumulative Z-curve of the Objective response rate crossed the conventional and test sequence monitoring boundaries; however, it did not cross the required information size line.
CONCLUSIONS
Traditional Chinese medicine combined with radiofrequency ablation for primary liver cancer can effectively reduce alpha-fetoprotein and improve clinical efficacy, immune function, liver function, as well as the quality of life.
PubMed: 37554780
DOI: 10.1016/j.heliyon.2023.e18591 -
Acta Obstetricia Et Gynecologica... Apr 2024Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis... (Review)
Review
INTRODUCTION
Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor and typically develops in the context of chronic liver disease, such as liver cirrhosis or chronic hepatitis B virus infection. Ultrasound evaluation, CT scan, and MRI are used to detect HCC. α-fetoprotein (AFP) is a common marker used to detect HCC in the non-pregnant population, which notoriously increases in pregnant women in relation to gestational age. Treatment is driven by the extent of the disease and the severity of underlying liver disease. Pregnancy may represent an obstacle to diagnosis and appropriate treatment of HCC. The aim of this descriptive systematic review was to describe the clinical features and maternal and neonatal outcomes of HCC in pregnancy.
MATERIAL AND METHODS
We performed a systematic review of the literature about HCC diagnosed in pregnancy and the postpartum period, with signs or symptoms arising in pregnancy. We included case reports and case series describing the clinical features of women diagnosed with HCC, fibrolamellar variant of HCC, and mixed HCC and cholangiocarcinoma during pregnancy or the postpartum period (with onset of symptoms during pregnancy), from inception to March 2023. The study protocol was registered with the PROSPERO database (Registration number: ID CRD42021275584).
RESULTS
We identified 180 records. The articles included in this systematic review were 47 case reports and 5 case series, for a total of 63 pregnancies. The two most frequent predisposing conditions were hepatitis B virus infection (30/63; 47%) and liver cirrhosis (14/63; 22%). Ultrasound evaluation was the most used technique to detect HCC. AFP was higher than normal in 28/46 patients tested (61%). Surgical treatment was the most used therapy, both during pregnancy and after delivery. Twenty-six patients (26/63; 42%) died within 6 months of diagnosis. Survival >24 months was 9% (4/46) in symptomatic and 29% (5/17) in asymptomatic women. No patient with cirrhotic liver survived more than 12 months. Thirty-eight newborns were alive at 28 days of age (38/63; 61%).
CONCLUSIONS
Hepatocellular carcinoma in pregnancy is associated with a high risk of maternal and neonatal mortality. Diagnosis in asymptomatic high-risk women or following abnormal maternal serum AFP screening is associated with better maternal outcomes.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Carcinoma, Hepatocellular; alpha-Fetoproteins; Liver Neoplasms; Hepatitis B, Chronic; Liver Cirrhosis
PubMed: 37533304
DOI: 10.1111/aogs.14640 -
Frontiers in Immunology 2023To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis.... (Meta-Analysis)
Meta-Analysis
Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts.
OBJECTIVE
To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.
METHODS
We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.
RESULTS
A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.
CONCLUSION
Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model's selected indicators are easily obtainable, making them suitable for further application in clinical practice.
Topics: Humans; Carcinoma, Hepatocellular; Prognosis; Immune Checkpoint Inhibitors; Liver Neoplasms; alpha-Fetoproteins
PubMed: 37520554
DOI: 10.3389/fimmu.2023.1215745 -
EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
Cancers Apr 2023Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The... (Review)
Review
BACKGROUND
Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The currently used biomarkers such as AFP (alpha-fetoprotein) and CA19.9 lack sensitivity and specificity. Hence, there is an unmet need for an alternative biomarker.
AIM
To evaluate the diagnostic accuracy of volatile organic compounds (VOCs) for the detection of hepatobiliary and pancreatic cancers.
METHODS
A systematic review of VOCs' use in the detection of hepatobiliary and pancreatic cancers was performed. A meta-analysis was performed using the software R. Heterogeneity was explored through meta-regression analysis.
RESULTS
A total of 18 studies looking at 2296 patients were evaluated. Pooled sensitivity and specificity of VOCs for the detection of hepatobiliary and pancreatic cancer were 0.79 (95% CI, 0.72-0.85) and 0.81 (97.5% CI, 0.76-0.85), respectively. The area under the curve was 0.86. Meta-regression analysis showed that the sample media used contributed to heterogeneity. Bile-based VOCs showed the highest precision values, although urine and breath are preferred for their feasibility.
CONCLUSIONS
Volatile organic compounds have the potential to be used as an adjunct tool to aid in the early diagnosis of hepatobiliary cancers.
PubMed: 37190235
DOI: 10.3390/cancers15082308 -
International Journal of Molecular... Mar 2023This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular... (Meta-Analysis)
Meta-Analysis Review
Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment.
This systematic review aimed to assess the prognostic significance of programmed cell death-ligand 1 (PDL-1) and programmed cell death protein 1 (PD-1) in hepatocellular carcinoma (HCC). Medline, EMBASE, and Cochrane Library database searches were conducted, revealing nine relevant cohort studies (seven PDL-1 and three PD-1). Our meta-analysis showed that PD-1/PDL-1 was a marker of poor survival, regardless of the assessment method (PD-1 overall survival (OS): hazard ratio (HR) 2.40; 95% confidence interval (CI), 1.30-4.42; disease-free survival (DFS): HR 2.12; 95% CI, 1.45-3.10; PDL-1: OS: HR 3.61; 95% CI, 2.75-4.75; and DFS: HR 2.74; 95% CI, 2.09-3.59). Additionally, high level of PD-1/PDL-1 expression was associated with aging, multiple tumors, high alpha-fetoprotein levels, and advanced Barcelona Clinic Liver Cancer stage. This high level significantly predicted a poor prognosis for HCC, suggesting that anti-PD-1 therapy is plausible for patients with HCC. Furthermore, HIF-1 induces PD-1 expression, and PD1SOCS3 is associated with a better prognosis. Taken together, combination therapy may be the key to effective immunotherapy. Thus, exploring other markers, such as HIF-1 and SOCS3, along with PD-1/PDL-1 immunotherapy, may lead to improved outcomes.
Topics: Humans; B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Hepatocellular; Immunotherapy; Ligands; Liver Neoplasms; Tumor Microenvironment; Programmed Cell Death 1 Receptor
PubMed: 37047482
DOI: 10.3390/ijms24076495 -
BMC Gastroenterology Mar 2023The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis.
METHODS
36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software.
RESULTS
The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74-0.83),0.85(95%CI 0.80-0.89),5.4(95%CI 3.8-7.5), 0.25(95%CI 0.20-0.31), 22(95%CI 13-35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64-0.81),0.70(95%CI 0.49-0.85),2.40(95%CI 1.3-4.7),0.38(95%CI 0.23-0.61),6(95%CI 2-19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis.
CONCLUSION
The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Membrane Proteins; Liver Cirrhosis; Fibrosis; Biomarkers, Tumor
PubMed: 36964524
DOI: 10.1186/s12876-023-02685-8 -
Diagnostics (Basel, Switzerland) Feb 2023the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography,...
BACKGROUND AND OBJECTIVES
the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP.
MATERIALS AND METHODS
systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022.
RESULTS
a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.
PubMed: 36899960
DOI: 10.3390/diagnostics13050816 -
Liver Cancer Feb 2023Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab....
INTRODUCTION
Sorafenib was historically the standard of care for advanced hepatocellular carcinoma (aHCC) until it was superseded by the combination of atezolizumab and bevacizumab. Thereafter, several novel first-line combination therapies have demonstrated favorable outcomes. The efficacies of these treatments in relation to current and previous standards of care are unknown, necessitating an overarching evaluation.
METHODS
A systematic literature search was conducted on PubMed, EMBASE, Scopus, and the Cochrane Controlled Register of Trials for phase III randomized controlled trials investigating first-line systemic therapies for aHCC. Kaplan-Meier curves for overall survival (OS) and progression-free survival (PFS) were graphically reconstructed to retrieve individual patient-level data. Derived hazard ratios (HRs) for each study were pooled in a random-effects network meta-analysis (NMA). NMAs were also conducted using study-level HRs for various subgroups, according to viral etiology, Barcelona Clinic Liver Cancer (BCLC) staging, alpha-fetoprotein (AFP) levels, macrovascular invasion, and extrahepatic spread. Treatment strategies were ranked using scores.
RESULTS
Among 4,321 articles identified, 12 trials and 9,589 patients were included for analysis. Only two therapies showed OS benefit over sorafenib: combined anti-programmed-death and anti-VEGF pathway inhibitor monoclonal antibodies (Anti-PD-(L)1/VEGF Ab), including atezolizumab-bevacizumab and sintilimab-bevacizumab biosimilar (HR = 0.63, 95% CI = 0.53-0.76) and tremelimumab-durvalumab (HR = 0.78, 95% CI = 0.66-0.92). Anti-PD-(L)1/VEGF Ab showed OS benefit over all other therapies except tremelimumab-durvalumab. Low heterogeneity ( = 0%) and inconsistency (Cochran's = 0.52, = 0.773) was observed. scores for OS ranked Anti-PD-(L)1/VEGF Ab as the best treatment in all subgroups, except hepatitis B where atezolizumab-cabozantinib ranked highest for both OS and PFS, as well as nonviral HCC and AFP ≥400 μg/L where tremelimumab-durvalumab ranked highest for OS.
CONCLUSION
This NMA supports Anti-PD-(L)1/VEGF Ab as the first-line therapy for aHCC and demonstrates a comparable benefit for tremelimumab-durvalumab which also extends to certain subgroups. Results of the subgroup analysis may guide treatment according to baseline characteristics, while pending further studies.
PubMed: 36872922
DOI: 10.1159/000526639