Productivity loss by cancer stage in patients newly diagnosed with hepatocellular carcinoma: A claims database analysis.

BACKGROUND: New cancer diagnoses are associated with employment decrease, workplace absenteeism, and attributable costs to employers. OBJECTIVE: To estimate the workplace productivity loss in the year following a new diagnosis of early-, intermediate-, or advanced-stage hepatocellular carcinoma (HCC) in commercially insured US adults. METHODS: We conducted a retrospective cohort study using Merative MarketScan commercial claims to identify incident HCC diagnoses from 2010 to 2020. Patients were stratified into early-, intermediate-, or advanced-stage cohorts based on presence of secondary malignancy codes or first treatment received. Mean workdays lost and attributable cost in the year following a new diagnosis were calculated using the Kaplan-Meier sample averages to account for censoring. An exploratory analysis was conducted on subgroups in the early and advanced cohorts to assess productivity loss in patients with and without treatment. RESULTS: Mean workdays lost in the year following a new HCC diagnosis among the early, intermediate, and advanced cohorts was 22.6 days (95% CI = 16.0-29.8), 17.4 days (95% CI = 11.9-23.2), and 19.5 days (95% CI = 15.6-23.6), respectively. Corresponding indirect costs were $6,031(95% CI = $4,270-$7,953), $4,644 (95% CI = $3,176-$6,192), and $5,204 (95% CI = $4,163-$6,298). Early-stage patients without a liver transplant and advanced-stage patients who received systemic therapy had 19.7 (95% CI = 12.7-27.4) and 22.0 (95% CI = 16.6-27.7) mean workdays lost, respectively. CONCLUSIONS: Productivity loss varies by stage and appears to be higher in early-stage patients who receive more intensive treatments in the first year following a new HCC diagnosis.

Anti-BIRC5 autoantibody serves as a valuable biomarker for diagnosing AFP-negative hepatocellular carcinoma.

Background: Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC). Methods: This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level. Results: In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation. Conclusion: The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.

Serum ß-klotho is a potential biomarker for the progression of hepatitis B virus-related liver diseases.

INTRODUCTION: Hepatitis B virus (HBV) infection is a global epidemic that can lead to several liver diseases, seriously affecting people's health. This study aimed to investigate the clinical potential of serum ß-klotho (KLB) as a promising biomarker in HBV-related liver diseases. METHODOLOGY: This study enrolled 30 patients with chronic hepatitis B (CHB), 35 with HBV-related cirrhosis, 66 with HBV-related hepatocellular carcinoma (HCC), and 48 healthy individuals. ELISA measured the levels of serum KLB in the four groups. We then compared the differences in serum KLB levels among the groups and analyzed the relationship between serum KLB and routine clinical parameters. RESULTS: The concentrations of serum KLB levels were increased sequentially among the healthy subjects, the HBV-related CHB group, the HBV-related cirrhosis group, and the HBV-related HCC group (p < 0.05). Expression of KLB was positively correlated with alpha-fetoprotein (AFP), total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl-transferase, alkaline phosphatase, total bile acid, serum markers for liver fibrosis, ascites, cirrhosis, splenomegaly, and model for end-stage liver disease sodium, while negatively correlated with platelet count, albumin, and prothrombin activity (p < 0.05). In addition, serum KLB has better sensitivity in diagnosing HCC than AFP, and serum KLB combined with AFP has higher sensitivity and specificity than AFP alone in diagnosing HCC. CONCLUSIONS: Serum KLB level is associated with the severity of HBV-related liver diseases and has important diagnostic value for HCC. Therefore, it could be a predictive biomarker for monitoring disease progression.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

[New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients].

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

Epidemiological, Diagnostic and Therapeutic Aspects of Hepatocellular Carcinoma in Morocco: A Case Series and Review of Literature.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common primary liver tumor. It is considered a global public health problem given its incidence and high mortality rate. Epidemiological studies on hepatocellular carcinoma in our Moroccan and North African contexts are rare. Hence, our study aims to determine the epidemiological, clinical, paraclinical, etiological and therapeutic aspects of this pathology in our context. MATERIALS AND METHODS: We conducted a descriptive retrospective study on patients with HCC treated by the Hepato-gastroenterology department of the university hospital of Mohammed VI in Marrakech over a period of 7 years spread between 01/01/2015 and 31/12/2021. The epidemiological characteristics, diagnostic methods and therapeutic management of HCC in these patients have been described and analyzed. RESULTS: 100 patients with HCC were identified and included in our study. The average age was 63.3 ± 12.63 years with a male predominance. The predominant etiology was cirrhosis (87% of cases) then viral hepatitis C (35%) and B (27%) and of unknown origin in 29% of cases. HCC revealed cirrhosis in 41% and was diagnosed during cirrhosis surveillance in 36% of cases. The functional signs were dominated by abdominal pain (68%), deterioration of general condition (58%) and abdominal distension (43%). Alfa-fetoprotein was elevated in 73% of cases and was above 400ng/ml in 41% of cases. The diagnosis was mainly radiological in 92% and histological in 8% of cases. The radiological aspects of HCC were dominated by mononodular form (58%), a right lobar location (80%), a diameter greater than 5 cm (58%), a typical vascular aspect (86%) with portal thrombosis in 24% and metastases in 36% of cases, especially in lymph nodes. The majority of cirrhosis in our series was classified as Child-Pugh stage B (46%) at the time of diagnosis and most patients had an advanced stage of HCC with 31% at BCLC C and 28% at BCLC D. 72% of patients received palliative treatment, and only 6% received curative treatment. At the end of the study, 48% of patients had died with an overall survival of 6.5 months. CONCLUSION: Our study achieved its main objective by providing a snapshot of HCC in our context and confirmed that HCC remains with poor prognosis since its diagnosis is often late, limiting the therapeutic choices with a very short median survival. It also noted that the viral etiology remains the main cause of HCC in our population. Therefore, prevention remains the best therapeutic approach against HCC and the need for a national or at least a regional HCC registry in our country is essential in order to develop targeted preventive measures adapted to our context and to improve the diagnostic and therapeutic approaches for our patients.

Biosensing of Alpha-Fetoprotein: A Key Direction toward the Early Detection and Management of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is currently one of the most prevalent cancers worldwide. Associated risk factors include, but are not limited to, cirrhosis and underlying liver diseases, including chronic hepatitis B or C infections, excessive alcohol consumption, nonalcoholic fatty liver disease (NAFLD), and exposure to chemical carcinogens. It is crucial to detect this disease early on before it metastasizes to adjoining parts of the body, worsening the prognosis. Serum biomarkers have proven to be a more accurate diagnostic tool compared to imaging. Among various markers such as nucleic acids, circulating genetic material, proteins, enzymes, and other metabolites, alpha-fetoprotein (AFP) is a protein marker primarily used to diagnose HCC. However, current methods need a large sample and carry a high cost, among other challenges, which can be improved using biosensing technology. Early and accurate detection of AFP can prevent severe progression of the disease and ensure better management of HCC patients. This review sheds light on HCC development in the human body. Afterward, we outline various types of biosensors (optical, electrochemical, and mass-based), as well as the most relevant studies of biosensing modalities for non-invasive monitoring of AFP. The review also explains these sensing platforms, detection substrates, surface modification agents, and fluorescent probes used to develop such biosensors. Finally, the challenges and future trends in routine clinical analysis are discussed to motivate further developments.

Metabolic dysfunction-associated steatotic liver disease: Navigating terminological evolution, diagnostic frontiers and therapeutic horizon-an editorial exploration.

Metabolic dysfunction-associated steatotic liver disease (MASLD), once known as non-alcoholic fatty liver disease (NAFLD), represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes. The redefinition of NAFLD in 2023 marked a significant reposition in terminology, emphasizing a broader understanding of liver steatosis and its associated risks. MASLD is now recognized as a major risk factor for liver cirrhosis, hepatocellular carcinoma, and systemic complications such as cardiovascular diseases or systemic inflammation. Diagnostic challenges arise, particularly in identifying MASLD in lean individuals, necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools. Therapeutically, there is an urgent need for effective treatments targeting MASLD, with emerging pharmacological options focusing on, among others, carbohydrate and lipid metabolism. Additionally, understanding the roles of bile acid metabolism, the microbiome, and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches. There is a strong need to emphasize the importance of collaborative efforts in understanding, diagnosing, and managing MASLD to improve physicians' approaches and patient outcomes.

Expression of Fascin-1 and its diagnostic value in liver cancer.

Although some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC.

Early detection of HCC in patients with cirrhosis using AI; a Systematic Review.

Introduction: Hepatocellular carcinoma constitutes for approximately 75% of primary cancers of liver. Around 80- 90% of patients with HCC have cirrhosis at the time of diagnosis. Use of AI has recently gained significance in the field of hepatology, especially for the detection of HCC, owing to its increasing incidence and specific radiological features which have been established for its diagnostic criteria. Objectives: A systematic review was performed to evaluate the current literature for early diagnosis of hepatocellular carcinoma in cirrhotic patients. METHODS: Systematic review was conducted using PRISMA guidelines and the relevant studies were narrated in detail with assessment of quality for each paper. RESULTS: This systematic review displays the significance of AI in early detection and prognosis of HCC with the pressing need for further exploration in this field. CONCLUSIONS: AI can have a significant role in early diagnosis of HCC in cirrhotic patients.

Development of a machine learning-based model to predict prognosis of alpha-fetoprotein-positive hepatocellular carcinoma.

BACKGROUND: Patients with alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) have aggressive biological behavior and poor prognosis. Therefore, survival time is one of the greatest concerns for patients with AFP-positive HCC. This study aimed to demonstrate the utilization of six machine learning (ML)-based prognostic models to predict overall survival of patients with AFP-positive HCC. METHODS: Data on patients with AFP-positive HCC were extracted from the Surveillance, Epidemiology, and End Results database. Six ML algorithms (extreme gradient boosting [XGBoost], logistic regression [LR], support vector machine [SVM], random forest [RF], K-nearest neighbor [KNN], and decision tree [ID3]) were used to develop the prognostic models of patients with AFP-positive HCC at one year, three years, and five years. Area under the receiver operating characteristic curve (AUC), confusion matrix, calibration curves, and decision curve analysis (DCA) were used to evaluate the model. RESULTS: A total of 2,038 patients with AFP-positive HCC were included for analysis. The 1-, 3-, and 5-year overall survival rates were 60.7%, 28.9%, and 14.3%, respectively. Seventeen features regarding demographics and clinicopathology were included in six ML algorithms to generate a prognostic model. The XGBoost model showed the best performance in predicting survival at 1-year (train set: AUC = 0.771; test set: AUC = 0.782), 3-year (train set: AUC = 0.763; test set: AUC = 0.749) and 5-year (train set: AUC = 0.807; test set: AUC = 0.740). Furthermore, for 1-, 3-, and 5-year survival prediction, the accuracy in the training and test sets was 0.709 and 0.726, 0.721 and 0.726, and 0.778 and 0.784 for the XGBoost model, respectively. Calibration curves and DCA exhibited good predictive performance as well. CONCLUSIONS: The XGBoost model exhibited good predictive performance, which may provide physicians with an effective tool for early medical intervention and improve the survival of patients.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study.

BACKGROUND: The GALAD score has improved early hepatocellular carcinoma (HCC) detection rate. The role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular interest. AIM: To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis, tumor features, and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum biomarkers. METHODS: This prospective, diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira Hospital. Eligible patients had HCC staging allocation using the Barcelona Clinic Liver Cancer (BCLC) categorization. Demographics, HCC etiology, and HCC features were recorded. Biomarkers and the GALAD score were obtained at baseline. The performance of the GALAD score and biomarkers were prospectively assessed. RESULTS: Exactly 115 individuals were diagnosed with HCC. The GALAD score increased with disease severity. Between BCLC-0/A and BCLC-B/C/D, the GALAD score predicted HCC staging with an area under the curve (AUC) of 0.868 (95%CI: 0.80-0.93). For identifying the curative HCC, the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein (AFP) (0.753) and Lens culinaris agglutinin-reactive fraction of AFP-L3 (0.706), and as good as that of Protein induced by vitamin K absence-II (PIVKA-II) (0.897). For detecting aggressive features, the GALAD score gave an AUC of 0.839 (95%CI: 0.75-0.92) and significantly outperformed compared to that of AFP (0.761) and AFP-L3 (0.697), with a trend of superiority to that of PIVKA-II (0.772). The performance to predict 1-year mortality of GALAD score (AUC: 0.711, 95%CI: 0.60-0.82) was better than that of AFP (0.541) and as good as that of PIVKA-II (0.736). The optimal cutoff value of GALAD score was ≥ 6.83, with a specificity of 72.63% for exhibiting substantial reduction in the 1-year mortality. CONCLUSION: The GALAD model can diagnose HCC at the curative stage, including the characteristic of advanced disease, more than that by AFP and AFP-L3, but not PIVKA-II. The GALAD score can be used to predict the 1-year mortality of HCC.

Evaluating the diagnostic accuracy of heat shock proteins and their combination with Alpha-Fetoprotein in the detection of hepatocellular carcinoma: a meta-analysis.

BACKGROUND: A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection. METHODS: Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined. RESULTS: A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69-0.85) compared to 0.73 (95% CI: 0.65-0.80); specificity of 0.89 (95% CI: 0.81-0.95) compared to 0.86 (95% CI: 0.77-0.91); PLR of 7.4 (95% CI: 3.7-14.9) compared to 5.1 (95% CI: 3.3-8.1); NLR of 0.24 (95% CI: 0.16-0.37) compared to 0.31 (95% CI: 0.24-0.41); DOR of 30.19 (95% CI: 10.68-85.37) compared to 16.34 (95% CI: 9.69-27.56); and AUC of 0.90 (95% CI: 0.87-0.92) compared to 0.85 (95% CI: 0.82-0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82-0.95), 0.94 (95% CI: 0.82-0.98), 14.5 (95% CI: 4.6-45.4), 0.11 (95% CI: 0.06-0.20), 133.34 (95% CI: 29.65-599.61), and 0.96 (95% CI: 0.94-0.98) for the combination of HSPs and AFP. CONCLUSION: Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.

Based on Gadolinium Ethoxybenzyl DTPA-Enhanced MRI: Diagnostic Performance of the Category-Modified LR-5 Criteria in Patients At Risk for Hepatocellular Carcinoma.

Introduction: We aimed to modify the LR-5 strategy to improve the diagnostic sensitivity for hepatocellular carcinoma (HCC) in high-risk patients while maintaining specificity. Methods: This study retrospectively analyzed 412 patients with 445 liver observations who underwent preoperative gadolinium ethoxybenzyl DTPA (GD-EOB-DTPA)-enhanced MRI followed by surgical procedures or biopsies. All observations were classified according to LI-RADS v2018, and the classifications were adjusted by modifying major features (MF)(substituting threshold growth with a more HCC-specific ancillary features (AF): presence of blood products within the mass, arterial phase hyperenhancement (APHE) was interpreted with hypointensity on precontrast imaging- isointensity in arterial phase (AP) and extending washout to transitional phase (TP)(2 min)). The specificity, sensitivity, and positive predictive value (PPV) were assessed to compare LR-5 (definitely HCC) diagnostic efficacy between LI-RADS version 2018 and modified LI-RADS. Results: Apart from nonenhancing "capsule", the interreader agreement of MFs and HCC-specific AFs between the two readers reached substantial or excellent ranges (κ values ranging from 0.631 to 0.911). According to LI-5 v2018, the specificity, sensitivity and PPV of HCC were 90.74%, 82.35%, and 98.17%, respectively. Based on a more HCC-specific AF, signal intensity in AP and TP (2 min), the sensitivity of the three modified strategies were 86.19%, 93.09%, 96.67% (P < .05)), while maintaining high specificity and PPV rates at 88.89% and 98.25% (P > .05) Conclusion: Further investigation into the efficacy of threshold growth as a MF is warranted. By utilizing GD-EOB-DTPA-enhanced MRI, enhancing the sensitivity of the modified LR-5 category may be achieved without compromising specificity and PPV in diagnosing HCC among high-risk patients.

Serum interleukin-10 and alpha-fetoprotein: A combined diagnostic approach for hepatocellular carcinoma in Egyptians with HCV.

PURPOSE: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although alpha-fetoprotein (AFP) has been used for 60+ years as an HCC diagnostic serum marker, its accuracy is debated. Notably, the role of interleukin 10 (IL-10) in cancer development and metastasis is elevated in various tumor types, including HCC and chronic HCV infection. Our study aimed to investigate the diagnostic performance of IL-10 and AFP as biomarkers for HCV-induced HCC in an Egyptian population. METHODS: Eighty participants were recruited and categorized into three groups: HCV-related HCC (n=40), HCV-related cirrhosis (n=40), and control (n=20).The collected blood samples were analyzed to evaluate liver function, AFP levels, and IL-10 levels. RESULTS: Our analysis showed that AFP demonstrated low sensitivity (40% false-negative) and low specificity (33% false-positive).IL-10 levels were significantly higher (P < 0.001) in patients with HCC than in the cirrhosis and control groups. The serum AFP and IL-10 combination revealed significantly increased sensitivity (97.5%), diagnostic accuracy (71.1%), AUC (0.798), PPV (73.3%), and NPV ( 69.5%) when compared with either of them alone. CONCLUSION: the reliability of AFP as a major HCC marker was poor. However, IL-10 levels are a novel biomarker for the degree of HCC inflammation, considering IL-10's potential role in HCV-HCC development. We suggest combining AFP with IL-10 to improve the diagnostic and prognostic value of HCC considerably. Future research on these biomarkers should prioritize their clinical validity, prognostic usefulness, and compatibility with other therapeutic approaches as immunotherapy.

Nomogram for predicting post-therapy recurrence in BCLC A/B hepatocellular carcinoma with Child-Pugh B cirrhosis.

Introduction: This study conducts a retrospective analysis on patients with BCLC stage A/B hepatocellular carcinoma (HCC) accompanied by Child-Pugh B cirrhosis, who underwent transarterial chemoembolization (TACE) in combination with local ablation therapy. Our goal was to uncover risk factors contributing to post-treatment recurrence and to develop and validate an innovative 1-, 3-, and 5-year recurrence free survival (RFS) nomogram. Methods: Data from 255 BCLC A/B HCC patients with Child-Pugh B cirrhosis treated at Beijing You'an Hospital (January 2014 - January 2020) were analyzed using random survival forest (RSF), LASSO regression, and multivariate Cox regression to identify independent risk factors for RFS. The prognostic nomogram was then constructed and validated, categorizing patients into low, intermediate, and high-risk groups, with RFS assessed using Kaplan-Meier curves. Results: The nomogram, integrating the albumin/globulin ratio, gender, tumor number, and size, showcased robust predictive performance. Harrell's concordance index (C-index) values for the training and validation cohorts were 0.744 (95% CI: 0.703-0.785) and 0.724 (95% CI: 0.644-0.804), respectively. The area under the curve (AUC) values for 1-, 3-, and 5-year RFS in the two cohorts were also promising. Calibration curves highlighted the nomogram's reliability and decision curve analysis (DCA) confirmed its practical clinical benefits. Through meticulous patient stratification, we also revealed the nomogram's efficacy in distinguishing varying recurrence risks. Conclusion: This study advances recurrence prediction in BCLC A/B HCC patients with Child-Pugh B cirrhosis following TACE combined with ablation. The established nomogram accurately predicts 1-, 3-, and 5-year RFS, facilitating timely identification of high-risk populations.

[Fonction de l'ARNnc exosomal HEIH dans le carcinome hépatocellulaire associé au virus de l'hépatite B]. / Function of exosomal lncRNA-HEIH in hepatocellular carcinoma associated with hepatitis B virus.

Long non-coding RNA-HEIH (lncRNA-HEIH) is a potential biomarker for patients with hepatocellular carcinoma (HCC), but exosomal lncRNA-HEIH in patients with hepatitis B virus-associated HCC (B-HCC) is unclear. This study aimed to investigate the expression of exosomal lncRNA-HEIH in B-HCC patients and explore its clinical significance. We collected blood samples from 60 B-HCC patients, 60 non-hepatitis virus-associated HCC (N-HCC) patients, and 50 healthy volunteers. Exosomal lncRNA-HEIH levels were measured by real-time PCR and analyzed for their correlation with patient prognosis using Kaplan-Meier analysis. Multivariate COX regression analysis was conducted to identify factors affecting patient outcomes. The effects of lncRNA-HEIH on carcinogenesis were also investigated by constructing a Huh7 cell line stably expressing the hepatitis B virus. In the B-HCC group, there was a positive correlation between hepatitis B virus and exosomal lncRNA-HEIH. The 5-year survival rate of the exosomal lncRNA-HEIH high-expression group was significantly lower than that of the low-expression group in the B-HCC group, but not in the N-HCC group. Exosomal lncRNA-HEIH level was related to the TNM stage, lymph node metastasis and AFP. Exosomal lncRNA-HEIH level was independent risk factors for poor prognosis in B-HCC patients. In Huh7-HBV cells, lncRNA-HEIH level was significantly higher than in control, and the migration capacity of Huh7-HBV cells decreased significantly after down-regulating lncRNA-HEIH. Our findings suggest that exosomal lncRNA-HEIH is abnormally expressed and closely related to poor prognosis in B-HCC patients, indicating its potential as a diagnostic and therapeutic target for HBV-associated HCC.

Clinical usefulness of newly developed prognostic predictive score for atezolizumab plus bevacizumab for hepatocellular carcinoma.

AIMS: The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment. METHODS: A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results. RESULTS: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS. CONCLUSION: The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy.