Developments and current status of cell-free DNA in the early detection and management of hepatocellular carcinoma.

Nowadays, hepatocellular carcinoma (HCC) is still a major threat to human health globally, with a disappointing prognosis. Regular monitoring of patients at high risk, utilizing abdominal ultrasonography combined with alpha-fetoprotein (AFP) serum analysis, enables the early detection of potentially treatable tumors. However, the approach has limitations due to its lack of sensitivity. Meanwhile, the current standard procedure for obtaining a tumor biopsy in cases of HCC is invasive and lacks the ability to assess the dynamic progression of cancer or account for tumor heterogeneity. Hence, there is a pressing need to develop non-invasive, highly sensitive biomarkers for HCC which can improve the accuracy of early diagnosis, assess treatment response and accurately predict the prognosis. In contrast to the conventional method of tissue biopsy, liquid biopsy offers a non-invasive approach that can be readily repeated. As a liquid biopsy approach, the analysis of cell-free DNA (cfDNA) offers real-time insights that can accurately portray the tumor burden and provide a comprehensive depiction of the genetic profile associated with HCC. In this review, we present a comprehensive summary of the recent research findings pertaining to the significance and potential practicality of cfDNA analysis in the early detection and effective management of HCC.

A bibliometric and visualized analysis of preoperative future liver remnant augmentation techniques from 1997 to 2022.

Background: The size and function of the future liver remnant (FLR) is an essential consideration for both eligibility for treatment and postoperative prognosis when planning surgical hepatectomy. Over time, a variety of preoperative FLR augmentation techniques have been investigated, from the earliest portal vein embolization (PVE) to the more recent Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) procedures. Despite numerous publications on this topic, no bibliometric analysis has yet been conducted. Methods: Web of Science Core Collection (WoSCC) database was searched to identify studies related to preoperative FLR augmentation techniques published from 1997 to 2022. The analysis was performed using the CiteSpace [version 6.1.R6 (64-bit)] and VOSviewer [version 1.6.19]. Results: A total of 973 academic studies were published by 4431 authors from 920 institutions in 51 countries/regions. The University of Zurich was the most published institution while Japan was the most productive country. Eduardo de Santibanes had the most published articles, and Masato Nagino was the most frequently co-cited author. The most frequently published journal was HPB, and the most cited journal was Ann Surg, with 8088 citations. The main aspects of preoperative FLR augmentation technique is to enhance surgical technology, expand clinical indications, prevent and treat postoperative complications, ensure long-term survival, and evaluate the growth rate of FLR. Recently, hot keywords in this field include ALPPS, LVD, and Hepatobiliary Scintigraphy. Conclusion: This bibliometric analysis provides a comprehensive overview of preoperative FLR augmentation techniques, offering valuable insights and ideas for scholars in this field.

Comprehensive analysis of anoikis-related lncRNAs for predicting prognosis and response of immunotherapy in hepatocellular carcinoma.

Nowadays, primary liver cancer is still a major threat to human health. Anoikis is a particular form of programed cell death that has an inhibitory effect on neoplasm metastasis. Although several prognostic models based on anoikis-related genes for Hepatocellular carcinoma (HCC) have been established, signatures associated with anoikis-related lncRNAs have not been identified. To fill this blank space, the authors built up a prognostic signature and appraised its value in guiding immunotherapy. Eleven prognostic anoikis-related lncRNAs were identified through Least Absolute Shrinkage and Selection Operator Cox analysis. The accuracy of the risk signature in predicting prognosis was verified by K-M survival analysis and Receiver operating characteristic analysis. We further discovered that the high-risk group was often enriched in signal pathways related to cell growth and death and immune response; in addition, in the low-risk group, cells often undergo metabolic changes through gene set enrichment analysis. Finally, we realised that HCC patients in the high-risk group were upregulated in immune-checkpoint molecules and tend to have a higher tumour mutation burden level which indicated a higher sensitivity to immunotherapy. All in all, the anoikis-related lncRNAs risk signature showed excellent ability in predicting prognosis and may guide the application of immunotherapy in future clinical practice.

Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients. METHODS: To compare the effectiveness of Atez/Bev and lenvatinib in treating advanced HCC, we systematically searched the PubMed, EMBASE, and Web of Science databases. We utilized Review Manager 5.3 to extract and analyze the data. RESULTS: The present systematic review included 8 nonrandomized studies comprising a total of 6628 cases. There was no significant difference in 0.5-, 1-, 1.5-year OS rates and 0.5-, 1-year PFS rates between the 2 groups. However, patients with HCC caused by viral hepatitis would benefit more from the Atez/Bev therapy (hazard ratio = 0.75, 95% confidence interval: 0.63-0.89) but patients with a Child-Pugh class B liver function would benefit more from lenvatinib (hazard ratio = 1.70, 95% confidence interval: 1.07-2.70). At the same time, there are no major differences in safety between the 2 treatment options. CONCLUSION: Our study did not find any significant difference in effectiveness and safety between Atez/Bev and lenvatinib. However, Additional verification is required to determine whether these 2 therapeutic approaches have varying effects on distinct populations.

Serum microRNA expression profiling identifies serum biomarkers for HCV-related hepatocellular carcinoma.

BACKGROUND: The identification of high-sensitivity biomarkers for detection of hepatocellular carcinoma (HCC) from high-risk individuals is essential. OBJECTIVE: The present study was undertaken to identify and validate serum microRNAs (miRNAs) as potential biomarkers for hepatitis C virus (HCV)-related HCC. METHODS: Illumina sequencing was employed to screen the expression profiles of miRNAs in serum samples of HCV-related HCC patients and liver cirrhosis (LC) patients. RT-qPCR was used to confirm the altered miRNAs between the two groups. Moreover, candidate miRNAs were examined in serum samples of 40 HCC patients, 54 LC patients, 55 patients with chronic HCV hepatitis and 45 healthy controls. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the miRNAs for the detection of HCC. RESULTS: Four miRNAs (miR-122-5p, miR-331-3p, miR-494-3p, miR-224-5p) were significantly increased and two miRNAs (miR-185-5p, miR-23b-3p) were significantly decreased in HCC patients compared to LC patients. ROC curve analysis demonstrated that the six miRNAs could be used as potential biomarkers for HCC detection. Combination of the six miRNAs could efficiently detect HCC in LC patients with the area under the ROC curve (AUC) of 0.995 and combination of the six miRNAs also provided high diagnostic accuracy (AUC = 0.961) for detection of HCC in non-HCC subjects. CONCLUSIONS: The six serum miRNAs can be utilized as a surrogate and non-invasive biomarker for HCV-related HCC diagnosis.

Impact of metabolic syndrome on quality of life of liver transplant recipients.

Objective The incidence of metabolic syndrome (MS) increases after liver transplantation. This study was performed to evaluate the impact of MS on patients' quality of life after liver transplantation. Methods We collected the medical records of 152 patients during their post-liver transplantation outpatient follow-up. Quality of life was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey. Data on the patients' general condition as well as MS-related indicators were assessed in all patients. Based on the MS diagnostic criteria proposed by the International Diabetes Federation in 2005, the patients were divided into two groups: those with and without MS. We then analyzed the factors influencing MS and their impact on the patients' quality of life. Results After liver transplantation, age and underlying liver disease were significantly associated with MS and diabetes, and sex and body mass index were associated with central obesity. Central obesity affected the patients' general health (GH) score and health transition (HT) score, and hypertension affected their GH score and physical component score (PCS). Conclusions After liver transplantation, central obesity had a negative impact on patients' GH score and HT score, and hypertension affected their GH score and PCS.

Diagnosis accuracy of serum glypican-3 level in patients with hepatocellular carcinoma: a systematic review with meta-analysis.

BACKGROUND: Previous studies have evaluated the diagnostic value of serum glypican-3 in patients with hepatocellular carcinoma. However, the results remain inconsistent and even controversial. Thus, the aim of the present meta-analysis was to clarify the diagnostic accuracy of serum glypican-3 for hepatocellular carcinoma. METHODS: A meta-analysis including 22 studies was performed with 2325 cases and 2280 controls. Relevant studies were searched in the EMBASE, PubMed, and Web of Science databases, covering relevant papers published until November 1, 2017. The quality of the studies was assessed by revised QUADAS tools. Sensitivity, specificity, and other measures were pooled and determined to evaluate the accuracy of serum glypican-3 in the diagnosis of hepatocellular carcinoma by random-effects models. Summary receiver operating characteristic curve (sROC) analysis was performed to summarize the overall test performance. RESULTS: The results showed that the pooled overall diagnostic sensitivity, specificity, and 95% confidence interval (CI) for serum glypican-3 in the diagnosis of hepatocellular carcinoma were 68% (56-79%) and 92% (82-96.0%), respectively. Besides, the summary diagnostic odds ratio and 95% CI for glypican-3 were 23.53 (8.57-64.63). In addition, the area under sROC and 95% CI was 0.87 (0.84-0.90). The major design deficiencies of included studies were differential verification bias, and a lack of clear exclusion and inclusion criteria. CONCLUSIONS: The results of this meta-analysis suggested that serum glypican-3 was acceptable as a moderate diagnostic marker in the diagnosis of hepatocellular carcinoma compared with healthy individuals, which could elevate the sensitivity and specificity of diagnosis. Furthermore, more well-designed studies with large sample sizes are needed to show the effectiveness of glypican-3 in the differential diagnosis of hepatocellular carcinoma.

Development and application of a fluorescence protein microarray for detecting serum alpha-fetoprotein in patients with hepatocellular carcinoma.

Objective To develop a simple, effective, time-saving and low-cost fluorescence protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC). Method Non-contact piezoelectric print techniques were applied to fluorescence protein microarray to reduce the cost of prey antibody. Serum samples from patients with HCC and healthy control subjects were collected and evaluated for the presence of AFP using a novel fluorescence protein microarray. To validate the fluorescence protein microarray, serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA). Results A total of 110 serum samples from patients with HCC ( n = 65) and healthy control subjects ( n = 45) were analysed. When the AFP cut-off value was set at 20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a specificity of 93.24% for detecting serum AFP. Serum AFP quantified via fluorescence protein microarray had a similar diagnostic performance compared with ELISA in distinguishing patients with HCC from healthy control subjects (area under receiver operating characteristic curve: 0.906 for fluorescence protein microarray; 0.880 for ELISA). Conclusion A fluorescence protein microarray method was developed for detecting serum AFP in patients with HCC.