Hepatocellular Carcinoma Cases Research Articles

Hepatocellular carcinoma presenting as an extrahepatic mass: A case report and review of literature

BACKGROUND Hepatocellular carcinoma (HCC) is a primary liver tumor generally diagnosed based on radiographic findings. Metastatic disease is typically associated with increased tumor diameter, multifocality, and vascular invasion. We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography (CT). We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC. CASE SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval, mixed cystic-solid mass. Serial CT evaluations demonstrated steatosis, but no cirrhosis or liver lesions. Endoscopic ultrasound demonstrated a normal-appearing pancreas, biliary tree, and liver. Fine needle aspiration yielded atypical cells. The differential diagnosis included duodenal or pancreatic cyst, lymphoproliferative cyst, stromal or mesenchymal lesions, nodal involvement from gastrointestinal or hematologic malignancy, or duodenal gastro-intestinal stromal tumor. After review by a multidisciplinary tumor board, the patient underwent open surgical resection of a 5.2 cm × 5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC. Magnetic resonance imaging (MRI) subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement, fatty sparing, and intrinsic T1 hyperintensity. Alpha fetoprotein was 23.3 ng/mL. The patient was diagnosed with HCC with portocaval nodal involvement. Review: We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC. We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions, and 30 cases of extrahepatic HCC found to be primary, ectopic HCC. CONCLUSION Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary. In patients with risk factors for HCC and lesions suspicious for metastatic disease, MRI may be integral to identifying small hepatic lesions and differentiating from ectopic HCC. Tumor markers may also have utility in establishing the diagnosis.

Identification of vitamin D-related signature for predicting the clinical outcome and immunotherapy response in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers globally, seriously endangering people health. Vitamin D was significantly associated with tumor progression and patients' prognosis. Integrative 10 machine learning algorithms were used to develop a Vitamin D-related signature (VRS) with one training cohort and 3 testing cohorts. The performance of VRS in predicting the immunology response was verified using several predicting approaches. The optimal VRS was constructed by stepCox + superPC algorithm. VRS acted as a risk factor for HCC patients. HCC patients with high-risk score had a poor clinical outcome and the AUCs of 1-, 3-, and 5-year ROC were 0.786, 0.755, and 0.786, respectively. A higher level of CD8 + cytotoxic T cells and B cells was obtained in HCC patients with low-risk score. There is higher PD1&CTLA4 immunophenoscore and TMB score in low-risk score in HCC patients. Lower TIDE score and tumor escape score was found in HCC cases with low-risk score. The IC50 value of camptothecin, docetaxel, crizotinib, dasatinib, and erlotinib was lower in HCC cases with high-risk score. HCC patients with high-risk score had a higher score of cancer-related hallmarks, including angiogenesis, glycolysis, and NOTCH signaling. Our study proposed a novel VRS for HCC, which served as an indicator for predicting clinical outcome and immunotherapy responses in HCC.

Progression of chronic liver disease to hepatocellular carcinoma: implications for surveillance and management

BackgroundCurrent opinion holds that hepatocellular carcinoma (HCC) arises as a stepwise progression from chronic liver disease (CLD) to cirrhosis and then to HCC. However, some HCCs may develop in a non-cirrhotic liver, raising uncertainty about their origin.MethodsWe analysed a prospectively accrued cohort of 2592 CLD patients (median follow-up = 13 years) with no prior evidence of liver cirrhosis. To track the progression of liver fibrosis prior to HCC diagnosis, we examined serial measurements of Fib-4 (an index of liver fibrosis). We also evaluated fibrosis progression in response to antiviral treatment in patients with hepatitis C (HCV) and hepatitis B (HBV). Recognising the limitations of serologic fibrosis assessment, we correlated Fib-4 and fibrosis histology within this cohort.ResultsAmong HCC patients, 28% had no indication of cirrhosis prior to HCC diagnosis. Only 31% of HBV-related HCC cases followed the cirrhotic pathway. HCV patients who achieved sustained virological response (SVR) developed cirrhosis approximately 7 years before HCC diagnosis.ConclusionsOur analysis challenges the notion of cirrhosis as an obligatory stage of HCC development in CLD patients. We affirm HBV’s direct oncogenic potential and find that achieving SVR does not universally prevent HCC development. Our findings have major implications for HCC surveillance.

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.

Hepatocellular Carcinoma With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in the Absence of Cirrhosis

ABSTRACT This report describes a rare case of hepatocellular carcinoma (HCC) concurrent with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without traditional risk factors, such as hepatic fibrosis or chronic hepatitis. Initially presenting with hematuria, incidental imaging revealed a liver lesion, later diagnosed as moderately differentiated HCC. Notably, the patient had no history of well-established risk factors of HCC including viral hepatitis or liver cirrhosis. CLL/SLL was unexpectedly discovered in the surgical specimen during the hepatectomy. This case challenges traditional perceptions of HCC etiology, suggesting a potential link between HCC and CLL/SLL even without established risk factors.

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

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. 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). 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). 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.

Pre-diagnostic plasma proteomics profile for hepatocellular carcinoma.

Proteomics may discover pathophysiological changes related to hepatocellular carcinoma (HCC), an aggressive and lethal type of cancer with low sensitivity for early-stage diagnosis. We measured 1,305 pre-diagnostic (median 12.7 years) SOMAscan proteins from 54 pairs of healthy individuals who subsequently developed HCC and matched non-HCC controls from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Candidate proteins were validated in the independent, prospective UK Biobank Pharma Proteomics Project (UKB-PPP). In NHS/HPFS, we identified 56 elevated proteins in HCC with absolute fold-change >1.2 and Wald test P < .05 in conditional logistic regression analysis. Ingenuity Pathway Analysis identified enrichment of pathways associated with cell viability, adhesion, proteolysis, apoptosis, and inflammatory response. Four proteins, chitinase-3-like protein 1, growth/differentiation factor 15, interleukin-1 receptor antagonist protein, and E-selectin, showed strong positive associations with HCC and were thus validated by ELISA (odds ratio ranged 2.48-14.7, all P < .05) in the NHS/HPFS and by Olink platform (hazard ratio ranged 1.90-3.93, all P < .05) in the UKB-PPP. Adding these four proteins to a logistic regression model of traditional HCC risk factors increased the area under the curve (AUC) from 0.67 to 0.87 in the NHS/HPFS. Consistently, model AUC was 0.88 for HCC risk prediction in the UKB-PPP. However, the limited number of HCC cases in the cohorts necessitates caution in interpreting our findings, emphasizing the need for further validation in high-risk populations.

Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.

Hepatocellular carcinoma (HCC) is a common type of cancer that ranks first in cancer-associated death worldwide. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) are the key components of the pyrimidine pathway, which promotes cancer development. However, the function of CAD in HCC needs to be clarified. In this study, the clinical and transcriptome data of 424 TCGA-derived HCC cases were analyzed. The results demonstrated that high CAD expression was associated with poor prognosis in HCC patients. The effect of CAD on HCC was then investigated comprehensively using GO annotation analysis, KEGG enrichment analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT algorithm. The results showed that CAD expression was correlated with immune checkpoint inhibitors and immune cell infiltration. In addition, low CAD levels in HCC patients predicted increased sensitivity to anti-CTLA4 and PD1, while HCC patients with high CAD expression exhibited high sensitivity to chemotherapeutic and molecular-targeted agents, including gemcitabine, paclitaxel, and sorafenib. Finally, the results from clinical sample suggested that CAD expression increased remarkably in HCC compared with non-cancerous tissues. Loss of function experiments demonstrated that CAD knockdown could significantly inhibit HCC cell growth and migration both in vitro and in vivo. Collectively, the results indicated that CAD is a potential oncogene during HCC metastasis and progression. Therefore, CAD is recommended as a candidate marker and target for HCC prediction and treatment.

Right anatomical hepatectomy using extrahepatic glissonean pedicle approach combined liver hanging for hepatocellular carcinoma: Surgical approach in a developing country

Backgrounds/Aims: To evaluate the outcomes of hepatocellular carcinoma (HCC) patients who underwent right anatomical hepatectomy using the combination of the extrahepatic Glissonean pedicle approach (Takasaki’s technique) and liver hanging maneuver (LHM) (Belghiti’s technique). Patients and Methods: A retrospective analysis of 30 cases of HCC treated with right hepatectomy using extrahepatic Glissonean pedicle approach and liver hanging maneuver by only one surgeon at our department from March 2020 to August 2023. Clinical characteristics, pathological results, postoperative outcomes, and survival rate were analyzed. Results: Among the 30 HCC patients analyzed, males accounted for 96.7% of patients. The mean age was 54.9 ± 11 years. 96.7% had normal preoperative liver function (Child-Pugh A). LHM with an extrahepatic Glissonean approach was feasible in 100% of cases with minor blood loss, no blood transfusion, intraoperative complications, or perioperative mortality. The mean operative time was 123.8 ± 29.0 minutes. The mean hospital stay was 9.37 ± 4.02 days. Postoperative liver failure accounted for 6.7%. Pathological results: 63.3% moderately differentiated HCC; 36.7% poorly differentiated HCC. 1-, 2- and 3-year survival rates were 86.1%, 73.8% and 59.0%, respectively. Recurrence was witnessed in 13 (43.3%) cases, with 6 (20%) cases in remnant liver. 1-, 2-, and 3-year disease-free survival were 69.3%, 42.0%, and 28.0% respectively. Conclusion: Right anatomical hepatectomy using extrahepatic Glissonean pedicle approach combined LHM for hepatocellular carcinoma was feasible and safe at our high-volume oncology center in a developing country.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV)

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

Prognostic analysis of hepatocellular carcinoma based on cuproptosis -associated lncRNAs

ObjectivesCuproptosis represents an innovative type of cell death, distinct from apoptosis, driven by copper dependency, yet the involvement of copper apoptosis-associated long non-coding RNAs (CRLncRNAs) in hepatocellular carcinoma (HCC) remains unclear. This study is dedicated to unveiling the role and significance of these copper apoptosis-related lncRNAs within the context of HCC, focusing on their impact on both the development of the disease and its prognosis.MethodsWe conducted an analysis of gene transcriptomic and clinical data for HCC cases by sourcing information from The Cancer Genome Atlas database. By incorporating cuproptosis-related genes, we established prognostic features associated with cuproptosis-related lncRNAs. Furthermore, we elucidated the mechanism of cuproptosis-related lncRNAs in the prognosis and treatment of HCC through comprehensive approaches, including Lasso and Cox regression analyses, survival analyses of samples, as well as examinations of tumor mutation burden and immune function.ResultsWe developed a prognostic model featuring six cuproptosis-related lncRNAs: AC026412.3, AC125437.1, AL353572.4, MKLN1-AS, TMCC1-AS1, and SLC6A1-AS1. This model demonstrated exceptional prognostic accuracy in both training and validation cohorts for patients with tumors, showing significantly longer survival times for those categorized in the low-risk group compared to the high-risk group. Additionally, our analyses, including tumor mutation burden, immune function, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and drug sensitivity, further elucidated the potential mechanisms through which cuproptosis-associated lncRNAs may influence disease outcome.ConclusionsThe model developed using cuproptosis-related long non-coding RNAs (lncRNAs) demonstrates promising predictive capabilities for both the prognosis and immunotherapy outcomes of tumor patients. This could play a crucial role in patient management and the optimization of immunotherapeutic strategies, offering valuable insights for future research.

Des-gamma-carboxy prothrombin and alpha-fetoprotein levels as biomarkers for hepatocellular carcinoma and their correlation with radiological characteristics.

Alpha-fetoprotein (AFP), a commonly used biomarker for hepatocellular carcinoma (HCC), is normal in up to one-third of patients. To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin (DCP) alone and in combination with AFP. In this study, 202 patients with radiologically proven HCC were enrolled, and their DCP and AFP levels were evaluated for their diagnostic performance. The mean age of the enrolled patients was 58.5 years; 72.0% were male. DCP was elevated in 86.6% (n = 175) of all patients, 100.0% (n = 74) of patients with portal vein thrombus, and 87.4% (n = 111) of patients with multicentric HCC. AFP was elevated in 64.3% (n = 130) of all the patients, 74% (n = 55) of the patients with portal vein thrombus, and 71.6% (n = 91) of the patients with multicentric HCC (P = 0.030, 0.001, and 0.015, respectively). In tumors less than 2 cm in size (n = 46), DCP was increased in 32 (69.5%) patients, and AFP was increased in 25 (54.3%) patients (P = 0.801). There was good pairing between DCP and AFP for HCCs of 2 cm size or larger (P < 0.001); however, the pairing among tumors < 2 cm size was not significant (P = 0.210). In 69 of the patients (34.1%), only one of the tumor markers was positive; DCP was elevated alone in 57/202 (28.2%) of all patients, and AFP alone was elevated in 12/202 (5.9%) of the patients. The areas under receiver operating characteristic curves (AUROC) for tumors > 2 cm was 0.74 for DCP and 0.59 for AFP; combining both markers resulted in an AUROC of 0.73. For tumors < 2 cm, the AUROC was 0.25 for DCP and 0.40 for AFP. DCP, as an individual marker, had a better diagnostic performance in many cases of HCC. Hence, DCP may replace AFP as the primary HCC biomarker.

Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Photodynamic effect of indocyanine green and its application to hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC) stands as the primary cause of liver cancers, with limited treatment options outside of surgical resection or transplant. Photodynamic therapy (PDT) using indocyanine green (ICG) as a photosensitizer offers a promising therapeutic option for HCC. ICG PDT has demonstrated efficacy in vitro and in vivo , providing a safe treatment option for patients ineligible for resection or transplant. Challenges in PDT optimization include limited light delivery, poor photosensitizer optimization, and low oxygen generation. Innovative solutions, such as ICG incorporation into nanostructures and direct administration for HCC cases, show promise. Combining ICG PDT with Lentinula edodes mycelia (LEM) and hydrogen gas inhalation may address oxygen production limitations. Utilizing a combination of therapeutic approaches and therapies may increase the efficacy of ICG PDT, making it the safer and more effective treatment option for patients. ICG’s proven clinical safety may expedite potential approval for its use in PDT. Advancements in photosensitizer technology, such as aggregation-induced emission photosensitizers (AIE-PSs), and combination therapies will enhance PDT efficacy shortly, as developments show promise for improved outcomes. For HCC patients, ICG PDT presents a valuable therapeutic option. This work is novel because it explores new combination therapy approaches, leveraging the benefits of PDT with ICG and the developments in photosensitizer technology, nanotechnology, and the combination of other treatments such as LEM and hydrogen gas, which could potentially revolutionize the treatment of HCC and offer a better prognosis for patients.

The Diagnostic Value of Alpha-fetoprotein and Lens Culinaris Agglutinin-reactive Alpha-fetoprotein in Liver Cirrhosis and Hepatocellular Carcinoma patients in Pakistan

Background: Hepatocellular carcinoma (HCC) is the most commonly encountered liver cancer and it accounts for 7% of all cancers and is accountable for a million deaths yearly.&#x0D; Because of latent HCV infections in our general population, there is projected rise in new HCC cases in Pakistan; with the onset of HCC several decades after initial infection has occurred. The poor predicted outcome of HCC is because of the fact that in the disease course of HCC, it is diagnosed at a very late stage. This results in effective medical intervention difficult.&#x0D; The purpose of this study is to establish a serum marker and/or panels of serum markers, that can detect the at risk patients with chronic liver disease, not only before but also after early development of HCC.&#x0D; Methodology: This study was conducted for ten months in Lahore General Hospital, Lahore, Punjab, Pakistan after taking the approval from the ethical board. A total of eighty patients (40 patients of HCC and 40 patients of LC) were included using non-probability, consecutive sampling. AFP and AFP-L3 levels of these patients were measured. The data was analyzed using SPSS Ver. 25. A p-value of ≤0.05 was considered as statistically significant.&#x0D; Results: In group 1, the mean age of patients was 60.02 ± 11.5 years and in group 2, it was 60.80 ± 7.42 years. In group 1, the mean of AFP was 64.93 ± 171.76 (ng/mL) and AFP-L3 was 0.56 ± 0.51(ng/mL). On the other hand, in group 2, the mean of AFP was 329.88 ± 231.55 (ng/mL) and AFP-L3 was 177.59 ± 104.10 (ng/mL). Significant association was found between AFP and AFP-L3 in both groups. Receiver operating characteristic (ROC) curve for AFP and AFP-L3 in relation to both groups obtained. The sensitivity of AFP was 85% and specificity was 80%. The sensitivity and specificity of AFP-L3 was 90 and 100%, respectively.&#x0D;  Conclusion: AFP-L3 has a better diagnostic value for hepatocellular carcinoma than AFP.

E2F-mediated POLA2 upregulation is correlated with macrophage infiltration and poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the major histological type of primary liver cancer with a relatively poor prognosis, because most HCC cases are usually diagnosed at an advanced stage. Thus, it is essential to explore novel candidate biomarkers for early diagnosis and prognosis predication of HCC. HCC transcription sequencing data were downloaded and analyzed. POLA2 expression pattern was characterized in tumor development process. POLA2 expression was evaluated by western blotting. Kaplan-Meier plot was utilized to evaluate POLA2's ability for prognosis predication. Correlation analysis and enrichment analysis were performed to explore the functional role of POLA2 in HCC development. Knockdown of E2F1 or E2F4 was used to evaluate their ability in regulating POLA2 expression. CYBERSORT (https://cibersortx.stanford.edu/) was used to estimate the infiltration levels of immune cells. POLA2 was overexpressed in HCC. Moreover, western blotting results showed that POLA2 was upregulated by transcription factors E2F1 rather than E2F4 in HCC. POLA2 facilitated cell cycle progression, DNA replication and DNA repair. High POLA2 expression was correlated with poor overall survival in HCC patients. POLA2 induced macrophage infiltration in the tumor microenvironment by upregulating the expression CSF1 and VEGFA expression. POLA2 is a novel diagnostic and prognostic biomarker of HCC with potential clinical value.

Macrophage-coated tumor cluster aggravates hepatoma invasion and immunotherapy resistance via generating local immune deprivation.

Immune checkpoint inhibitors (ICIs) represent a promising treatment for hepatocellular carcinoma (HCC) due to their capacity for abundant lymphocyte infiltration. However, some patients with HCC respond poorly toICI therapy due to the presence of various immunosuppressive factors in the tumor microenvironment. Our research reveals that a macrophage-coated tumor cluster (MCTC) signifies a unique spatial structural organization in HCC correlating with diminished recurrence-free survival and overall survival in a total of 572 HCC cases from 3 internal cohorts and 2 independent external validation cohorts. Mechanistically, tumor-derived macrophage-associated lectin Mac-2 binding protein (M2BP) induces MCTC formation andtraps immunocompetent cells at the edge of MCTCs to induce intratumoral cytotoxic Tcell exclusion and local immune deprivation. Blocking M2BP with a Mac-2 antagonist might provide an effective approach to prevent MCTC formation, enhance Tcell infiltration, and thereby improve the efficacy of ICI therapy in HCC.

Monitoring for liver cancer post-gene therapy-How much and how often?

Hepatocellular carcinoma (HCC) has long been recognized as a complication in people with chronic liver disease, particularly those with cirrhosis. Two gene therapies for haemophilia A and B recently approved in Europe and the US utilize adeno-associated virus (AAV) vectors designed to target hepatocytes. A number of other AAV gene therapies are undergoing clinical investigation for both liver and extrahepatic diseases, many of which likely transduce hepatocytes as well. Although AAV vectors predominantly persist in episomal forms, concerns about insertional mutagenesis have arisen due to findings in pre-clinical models and in a small subset of human HCC cases featuring wild-type AAV integrations in proximity to potential oncogenes. Despite the absence of any causative link between AAV vector therapy and HCC in approved extrahepatic gene therapies or haemophilia gene therapy trials, the package inserts for the recently approved haemophilia gene therapies advise HCC screening in subsets of individuals with additional risk factors. In this review, we discuss HCC risk factors, compare various screening modalities, discuss optimal screening intervals, and consider when to initiate and possibly discontinue screening. At this early point in the evolution of gene therapy, we lack sufficient data to make evidence-based recommendations on HCC screening. While AAV vectors may eventually be shown to be unassociated with risk of HCC, we presently favour a cautious approach that entails regular surveillance until such time as it is hopefully proven to be unnecessary.

Serum microRNA-16 as a potential biomarker for HCV-induced hepato-cellular carcinoma in Egyptian patients

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Two risk factors that cause 80–90% of HCC cases globally are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The diagnostic value of circulating microRNAs (miRNAs) in numerous tumors has been described. Our research assessed microRNA-16 (miR-16) as a novel biomarker in patients with HCV-induced HCC. The study included three groups. Group 1 included 55 individuals with cirrhosis caused by liver HCV infection in addition to HCC. Group 2 included 55 individuals with cirrhosis brought on by HCV infection. Group 3 included 55 normal control individuals. Expression of miR-16 in blood was assessed by real-time polymerase chain reaction (RT-PCR). The mean level of miR-16 was significantly different in the three groups, with group 1 having the greatest value (1.098 ± 0.647), followed by group 2 (1.1035 ± 0.8567) and group 3 (control subjects) having the lowest value (0.3842 ± 0.21485). The receiver operating characteristic (ROC) curve analysis showed that miR-16 had a higher diagnostic value at area under the curve (AUC) of 0.935 than alpha-feto protein (AUC of 0.859) to differentiate between HCC and control subjects. MiR-16 has a sensitivity of 81.82 % and a specificity of 69.09%, to distinguish between patients with liver cirrhosis and HCC patients. Our findings illustrated that circulating miR-16 can be proposed as a marker for detection of patients with HCV-induced HCC.

Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants

BackgroundPre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of “hot” or “immune-sensitive” tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs.MethodsElectronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations.ResultsA total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57–0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14–1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56–1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection.ConclusionsThis study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.