Hepatocellular Carcinoma In Cirrhotic Patients Research Articles

The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

Red Blood Cell Distribution Width as a Diagnostic Marker of Hepatocellular Carcinoma in Cirrhotic Patients

Background and Aim Although α-fetoprotein (AFP) is the main marker used for the diagnosis of hepatocellular carcinoma(HCC), its sensitivity and specificity as a screening tool have been questionable. Red blood cell distribution width (RDW) has been involved as a prognostic tool for many diseases and cancers including liver diseases. Still, its role in the diagnosis of HCC needs to be identified. This study aimed to evaluate the clinical importance of RDW as a novel marker in the diagnosis of HCC in Egyptian cirrhotic patients. Patients and Methods This cross-sectional study was carried out on 162 cirrhotic patients who attended Tropical medicine department clinics and inpatient wards at the Faculty of Medicine, Tanta University. Then they were divided into 2 groups of 81 patients each depending on their diagnosis with or without HCC (group I and group II respectively). Complete blood picture (CBC) that included red cell distribution width- coefficient of variation (RDW-CV) and AFP were obtained from all patients. Results There was a statistically significant elevation in RDW-CV in the HCC group as its mean± SD was 15.2.± 1.86 in HCC group versus 13.8 ± 1.99 in non HCC group (P<0.001). In addition, AFP was significantly elevated in group I than in group II (P<0.001). RDW-CV at a cut–off >14% had a 66.76%sensitivity and 61.73%specificity while AFP at a cut-off value>20 ng/ml had a 60.49%sensitivity and 79.01%specificity in the diagnosis of HCC. The combination of RDW-CV and AFP increased the sensitivity and specificity for the diagnosis of HCC(72.84% and 87.65% respectively) than each marker alone. Conclusions RDW may be considered a novel and cheap biomarker for the diagnosis of HCC either alone or in combination with AFP as it is readily available in CBC and does not need sophisticated techniques.

The relationship between hepatocellular carcinoma and Resolvin D1

Aims: Liver cancer is the second most common cause of cancer death, and hepatocellular carcinoma (HCC) is the most common hepatic primary tumor. Hepatocellular carcinoma develops based on inflammation in the cirrhotic liver. The aim of our study was to determine the relationship between the decrease in Resolvin D1, the lipid mediator involved in the resolution, and hepatocarcinogenesis. Methods: Thirty patients with HCC, thirty patients with cirrhosis, and thirty healthy subjects followed in our clinic between March 2018 and June 2019 were included in the study. Routine laboratory test results of the patients were recorded from the institutional database. Resolvin D1 and other parameters of the study groups were compared. Results: The Resolvin D1 levels were found to be significantly different from each other group, with the ranking as follows: the HCC group (1.71 ± 1.46 ng/ml)< the cirrhotic group (3.63 ± 2.92 ng/ml)< the healthy control group (6.24 ± 3.18 ng/ml). Moreover, Resolvin D1 levels were negatively correlated with ?-fetoprotein (AFP) level and tumor stage. Conclusion: Reduced lipid mediators that aid in the resolution process cause an increase in pro-inflammatory cytokines involved in the development of hepatocellular carcinoma. A decrease in Resolvin D1 may serve as a biomarker contributing to the diagnosis of progression to HCC in cirrhotic patients by triggering chronic inflammation and hepatocarcinogenesis.

Hepatic venous pressure gradient in hepatic resection for hepatocellular carcinoma

Liver transplantation is considered the gold standard for curative treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis, but limited organ availability and high costs necessitate alternative options. Hepatic resection (HR) is preferred for select patients, providing tumor removal and prognostic information. However, HR has been associated with life-threatening complications, especially in the presence of clinically significant portal hypertension (CSPH). Current guidelines recommend HR only for patients with well-preserved liver function, normal bilirubin levels, good performance status, and no CSPH. However, advancements in surgical techniques and portal hypertension management are challenging these guidelines, potentially allowing the consideration of hepatic resection for HCC in cirrhotic patients with CSPH. Indeed, minimally invasive approaches improve safety and outcomes for selected CSPH patients and accurate assessment of CSPH allows risk stratification according to liver function, tumor location, and extent of resection. Thus, despite the negative impact of CSPH on HR outcomes, careful patient selection and minimally invasive techniques expand the potential for HR in CSPH patients. This comprehensive review examines the evidence on HR in HCC treatment for cirrhotic patients with CSPH, highlighting challenges in surgical decision-making, the importance of direct measurement of hepatic venous pressure gradient, and exploring the benefits and risks associated with HR. Moreover, it underscores the need for refined prediction models and algorithms to optimize patient selection and enhance surgical outcomes.

The impact of liver fibrosis on the progression of hepatocellular carcinoma via a hypoxia-immune-integrated prognostic model

The impact of liver fibrosis on the deterioration of hepatocellular carcinoma (HCC) remains controversial. We hope to explore this issue through establishing a fibrosis-hypoxia-glycolysis-immune related prognostic model. Liver fibrosis-related genes from Molecular Signatures Database were used to evaluate the degree of fibrosis in HCC patients from the TCGA database. The patients were divided into two groups using the fibrosis-related expression matrix based on the algorithm uniform manifold approximation and projection (UMAP) and evaluated for fibrosis by UMAP cluster and gene enrichment analysis. Prognostic model was constructed by differential analysis, LASSO, and multivariate regression analysis. Immune-infiltration analysis was performed by CIBERSORT. Quantitative PCR and immunohistochemistry were performed to measure the gene expression levels in HCC patients from our hospital. In 365 HCC patients from the TCGA database, 111 HCC patients with high fibrosis score have a worse prognosis than those with low fibrosis based on 129 genes related to liver fibrosis, which may be caused by the interaction between fibrosis, angiogenesis, hypoxia, glycolysis, inflammatory response, and high immune infiltration. We constructed a Fibrosis-Hypoxia-Glycolysis-Immune Prognostic Model (FHGISig), which could significantly predict disease progression in HCC patients. Furthermore, we revealed a close correlation between FHGISig and immune cell infiltration level as well as immune checkpoints. Finally, PCR results found TFF3 mRNA was significantly lower in cirrhotic HCC patients compared with non-cirrhotic ones. Liver fibrosis is a poor-prognostic factor for HCC, and our FHGISig could significantly predict disease progression, which could also be a potential predictive marker for immunotherapy in HCC patients.

Hepatobiliary phase imaging in cirrhotic patients using compressed sensing and controlled aliasing in parallel imaging results in higher acceleration.

We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15s and 1.3 × 1.3 × 3 mm3 and 16s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.

Fuzheng Huayu capsules reducing development of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B based on the ratio of neutrophils/lymphocytes

Objective: To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC). Methods: 916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ(2) test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results: There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ(2) = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ(2) = 4.519, P = 0.029; 13.2% vs. 26.2%, χ(2) = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group (P = 0.38). Conclusion: Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.

Study for the Significance of Osteopontin vs Alpha Feto Protein as a Diagnostic Marker for Hepatocellular Carcinoma in Cirrhotic Patients with HCV

Abstract Background Outcome of hepatocellular carcinoma (HCC) depends mainly on its early diagnosis. The performance of traditional biomarkers is not satisfactory. Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. Several studies have reported that osteopontin (OPN) is a promising marker for the diagnosis of hepatocellular carcinoma (HCC); however, some studies emerged with conflicting results, Aim of the Work To evaluate the clinical significance of the plasma osteopontin (OPN) versus alpha-fetoprotein (AFP) in the diagnosis of HCC in cirrhotic patients Patients and Methods This study was Case-Control study, was conducted at internal Medicine and Gastroenterology outpatient clinics and ward in Ain Shams University Hospitals on Patients divided into 3 groups: (Group 1): 50 patients with previously diagnosed HCC on top of chronic HCV induced cirrhosis, (Group II): 15 chronic HCV patients with cirrhosis, (Group III):15 healthy controls during a period of Six months Results There was high statistically significant difference between the studied groups as regard OPN and AFP, Conclusion Plasma OPN level was elevated in the HCV-related HCC patients by comparison to the chronic HCV patients with cirrhosis and healthy controls. OPN is a promising tumor marker that could be added to the current standard tests for the diagnosis of HCC in patients with liver cirrhosis, due to Chronic HCV infection, in order to detect the disease at an early stage and, hence, improve the prognosis and survival rates of these patients

Evaluation of washout using subtraction MRI for the diagnosis of hepatocellular carcinoma in cirrhotic patients with spontaneously T1-hyperintense nodules

PurposeThe purpose of this study was to assess the value of subtraction imaging on post-arterial phase images (i.e., portal venous, delayed/transitional and hepatobiliary phases) for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in spontaneously hyperintense nodules on T1-weighted imaging in patients with cirrhosis. Materials and methodsForty-five patients with a total 55 hepatic nodules that were spontaneously hyperintense on T1-weighted images were initially retrieved. All patients underwent MRI examination of the liver using extracellular agent. Each nodule was assessed for sensitivity and specificity using LI-RADS (Liver Imaging Reporting and Data System) during two reading sessions performed first without then with subtraction images on post-arterial phase images. The final standard of reference was defined by a step-by-step algorithm previously published combining histology, typical imaging, alfa fetoprotein and follow-up. ResultsForty-six nodules (26 HCC) in 39 patients with cirrhosis were analyzed. Using LI-RADS, the sensitivity and specificity for the diagnosis of HCC were 64% (95% CI: 41–83) and 67% (95% CI: 41–87) without subtraction; and 73% (95% CI: 50–89) (P > 0.999) and 33% (95% CI: 13–59) (P = 0.553) on subtraction imaging using extracellular contrast agent. Fifty-five percent (22/40) of nodules displayed a washout without subtraction and 70% (28/40) did so on subtraction imaging obtained with extracellular contrast agent. Twenty nodules out of 40 (50%) were classified LI-RADS 5 without subtraction, and 28 out of 40 nodules (70%) with subtraction. ConclusionThe results of this study suggest that the use of subtraction imaging on post-arterial phase images (i.e., PVP, DP/TP and HBP) is not relevant for the non-invasive diagnosis of HCC for spontaneously hyperintense nodules on T1-weighted images in patients with liver cirrhosis.

Interleukin-6: A New Marker of Advanced-Sarcopenic HCC Cirrhotic Patients.

Hepatocellular carcinoma (HCC) is the major cause of liver-related death worldwide. Interleukin 6 (IL-6) promotes the growth of the HCC microenvironment. The correlation between Child-Pugh (CP) and HCC stage and between HCC stage and sarcopenia is still not clear. Our aim was to investigate whether IL-6 is correlated with HCC stage and could represent a diagnostic marker for sarcopenia. Ninety-three HCC cirrhotic patients in different stages, according to BCLC-2022 (stages A, B, and C), were enrolled. Anthropometric and biochemical parameters, comprehensive of IL-6, were collected. The skeletal muscle index (SMI) was measured using dedicated software on computer tomography (CT) images. IL-6 level was higher in advanced (BCLC C) compared to the early-intermediate (BCLC A-B) stages (21.4 vs. 7.7 pg/mL, p < 0.005). On multivariate analysis, IL-6 levels were statistically dependent on the degree of liver disease severity (CP score) and HCC stages (p = 0.001 and p = 0.044, respectively). Sarcopenic patients presented lower BMI (24.7 ± 5.3 vs. 28.5 ± 7.0), higher PMN/lymphocyte ratio (2.9 ± 2.4 vs. 2.3 ± 1.2) and increased values of log (IL-6) (1.3 ± 0.6 vs. 1.1 ± 0.3). Univariate logistic regression between sarcopenia and log (IL-6) showed a significant odds ratio (OR 14.88, p = 0.044) with an AUC of 0.72. IL-6 appears to be an effective biomarker for the diagnosis of advanced cirrhotic HCC. In addition, IL-6 could be considered a marker of cirrhotic HCC-related sarcopenia, suggesting further investigation with BIA- or CT-dedicated software.

Abstract 3336: A novel clinical and biomarker model accurately predicts hepatocellular carcinoma (HCC) across racial groups

Abstract Purpose: HCC incidence, which is highest in Asians and Pacific Islanders (API), followed by Black/African Americans (AA), Hispanics (H), and non-Hispanic Whites (W), is rising at an alarming rate in the United States. Most HCC is diagnosed at an advanced incurable stage, emphasizing the need for accurate biomarkers for early diagnosis. The predictive accuracy in available biomarkers such as alpha-fetoprotein (AFP) is sub-optimal, and these have not been systematically assessed across ethnic and racial subgroups. Here, we report on the performance characteristics of a model derived from an ethnically diverse population including API, distinct from the mainland USA. This model includes biologically relevant proteins, as well as clinical characteristics and seeks to capture the molecular changes underlying hepatocarcinogenesis. Experimental Procedures: We combined human genomic studies using The Cancer Genome Atlas (TCGA) and mechanistic insight from animal models to identify biologically relevant proteins. A proteomic analysis of 7,000 proteins (SomaScan) utilizing serum samples (55 uL/each) from 520 individuals with cirrhosis, 158 of whom had HCC by imaging criteria. Patients were recruited from three participating centers with significant cohorts of ethnic minorities (27% AA, 3% H, 2.3% API, 63%W patients, 3.8% other). We combined serum biomarkers with clinical and demographic risk factors to develop a risk prediction model. Results: Using multivariate logistic regression analysis, we developed a model that incorporated race and ethnicity in predicting the likelihood of HCC in cirrhotic patients. This functional model included 4 clinical variables (age, serum AFP and Bilirubin levels, HBV infection or not) and 3 serum protein biomarkers (AKR1B10, COL15A1, and INHBB), resulting in an area under the receiver operating characteristics curve (AUC) of 0.86 and sensitivity of 57% at 91% specificity. Focusing on the TGF-β superfamily signaling, clustering analysis identified several proteomic signatures that performed well in distinguishing HCC patients from cirrhosis. Our model outperformed both AFP alone and the Doylestown model by clinically relevant margins: at 90% specificity, the sensitivity of our model was 20% higher than AFP alone and 33% higher than the Doylestown model in the derivation samples. Conclusions and Next Steps: This study successfully demonstrates the performance of our biologically functional model combining 4 serum biomarkers with 3 clinical parameters to predict HCC across cirrhotic patients from a racially and ethnically diverse population, which outperformed the Doylestown model or AFP alone. The next steps will be large-scale validations of this biomarker panel in cirrhotic patients across all racial and ethnic subgroups in Phase II/III studies. Citation Format: Xiyan Xiang, Anil K. Vegesna, Richard L. Amdur, Kirti Shetty, Herbert Yu, Linda L. Wong, Sharon S. Fox, Michael G. Ryan, Nyasha Chambwe, Sanjaya K. Satapathy, James M. Crawford, Gregory M. Grimaldi, Vikas Kundra, Lopa Mishra. A novel clinical and biomarker model accurately predicts hepatocellular carcinoma (HCC) across racial groups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3336.

Single-cell RNA-seq Revealed that Altered Tumor Infiltrating Lymphocytes in Cirrhotic Liver Indicate Development of Hepatocellular Carcinoma.

Cirrhosis is the precursor lesion for most hepatocellular carcinoma (HCC) cases. However, no biomarker effectively predicted HCC initiation before diagnosis by imaging. We aimed to investigate the hallmarks of immune microenvironments in healthy, cirrhotic livers and HCC tumor tissues and to identify immune biomarkers of cirrhosis-HCC transition. Expression matrices of single-cell RNA sequencing studies were downloaded and integrated with Seurat package vignettes. Clustering was performed to analyze the immune cell compositions of different sample types. The cirrhotic liver and HCC tumors had distinct immune microenvironments, but the immune landscape of cirrhotic livers was not markedly modified compared with healthy livers. Two subsets of B cells and three subsets of T cells were identified in the samples. Among the T cells, naïve T cells were more prominent in the cirrhotic and healthy liver samples than in the HCC samples. In contrast, the neutrophil count was lower in cirrhotic livers. Two macrophage clusters were identified, one that actively interacted with T cells and B cells and was enriched in cirrhotic blood compared with HCC blood samples. Decreased naïve T cell infiltration and increased neutrophil infiltration in the liver may indicate the development of HCC in cirrhotic patients. Alterations in blood-resident immune cells may also be a sign of HCC development in cirrhotic patients. The dynamics of the immune cell subsets may serve as novel biomarkers to predict the transition from cirrhosis to HCC.

Direct Acting Anti-Viral Therapy, and Potential Increase in the Incidence of Hepato-Cellular Carcinoma in Cirrhotic Patients With Hepatitis C Virus

Direct Acting Anti-Viral Therapy, and Potential Increase in the Incidence of Hepato-Cellular Carcinoma in Cirrhotic Patients With Hepatitis C Virus

The Value of Thioredoxin Level and its Gene Polymorphism in the Diagnosis of Post- HCV Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Indeed, we need a novel tumor marker other than AFP for early detection and to improve the outcome. Serum thioredoxin is a promising protein involved in the pathogenesis of many malignancies. The study aims to evaluate serum thioredoxin and its gene polymorphism in HCC in cirrhotic patients due to HCV infection. Patients and Methods: 350 patients with HCC, 350 patients with chronic liver diseases, and 300 healthy controls were enrolled in our study. Serum thioredoxin level was measured by ELISA, and molecular study of thioredoxin domain-containing 5 (TXNDC5) gene polymorphism (rs1225943) polymorphism using real-time polymerase chain reaction by Taqman allele discrimination was done for all subjects. Results: Our study revealed a significant increase in serum thioredoxin levels in patients with HCC compared to chronic liver diseases and healthy controls. Using the Receiver operating characteristic (ROC) curve at the area under the curve (AUC) 0.917 and a cut-off value of &gt; 14.6 U/ml, our overall sensitivity and specificity for the HCC group over the other groups were 86 % and 92.15%, respectively with 92.2% positive predictive value and 54.9% negative predictive value. The molecular study of TXNDC5 gene polymorphism (rs1225943) polymorphism revealed no significant difference between the studied groups. Conclusion: Serum thioredoxin may be used as a promising tumor marker for HCC. Future research is needed to assess its use as a single or combined with other markers in the diagnosis and follow-up of the patients after interventions.

HCC: RNA-Sequencing in Cirrhosis.

Hepatocellular carcinoma (HCC) ranks the most common types of cancer worldwide. As the fourth leading cause of cancer-related deaths, its prognosis remains poor. Most patients developed HCC on the basis of chronic liver disease. Cirrhosis is an important precancerous lesion for HCC. However, the molecular mechanisms in HCC development are still unclear. To explore the changes at the level of transcriptome in this process, we performed RNA-sequencing on cirrhosis, HCC and paracancerous tissues. Continuously changing mRNA was identified using Mfuzz cluster analysis, then their functions were explored by enrichment analyses. Data of cirrhotic HCC patients were obtained from TCGA, and a fatty acid metabolism (FAM)-related prognostic signature was then established. The performance and immunity relevance of the signature were verified in internal and external datasets. Finally, we validated the expression and function of ADH1C by experiments. As a result, 2012 differently expressed mRNA were identified by RNA-sequencing and bioinformatics analyses. Fatty acid metabolism was identified as a critical pathway by enrichment analyses of the DEGs. A FAM-related prognostic model and nomogram based on it were efficient in predicting the prognosis of cirrhotic HCC patients, as patients with higher risk scores had shorter survival time. Risk scores calculated by the signature were then proved to be associated with a tumor immune environment. ADH1C were downregulated in HCC, while silence of ADH1C could significantly promote proliferation and motility of the HCC cell line.

EVALUATION OF DIAGNOSTIC VALIDITY OF PIVKA-II FOR DIAGNOSIS OF HEPATOCELLULAR CARCINOMA IN PATIENTS OF CIRRHOSIS WITH LIVER NODULES PRESENTED IN A TERTIARY CARE HOSPITAL OF LAHORE

Objectives: To evaluate the diagnostic validity of PIVKA-II for Hepatocellular carcinoma in cirrhotic patients with uncertain liver nodules on Ultrasound.&#x0D; Methods: This was a cross-sectional study conducted in 01-11-2020 and 31-12-2021 at Hepatitis clinic at Jinnah Hospital Lahore. Patients who fulfilled the selection criteria(n=100) were enlisted for this study. Blood samples were obtained to test for PVKA-11 and AFP in cirrhotic patients who had liver nodules that had been previously verified by ultrasound imaging. Data were entered and analyzed in SPSS ver: 21.0. Sensitivity, specificity and predictive values were calculated using CT imaging and biopsy as gold standard. ROC curve evaluating AFP, PIVKA-II, and a combination as indicators for Hepatocellular carcinoma at 95% Confidence Interval was calculated with a p &lt; .05 value was taken as statistical significant.&#x0D; Results: HCC was confirmed in 45 of the 100 instances, and it was invariably at an early or very early stage. At a threshold of 62.5 mAU/mL, PIVKA-II and HCC were significantly correlated (P =.015 and P =.036, respectively) in univariate and multivariate analyses. For AFP, 7.5 ng/mL was the ideal cut-off. For PIVKA- II, sensitivity was 62% and specificity was 91% , while for AFP, they are 66% and 69% respectively. The positive and negative predictive values for PIVKA-II were 81% and 74%, respectively, while for AFP sensitivity was 63% and specificity was 72%. The combination of both biomarkers improved the precision of diagnosing HCC (sensitivity = 74%, specificity = 95.5%, NPV = 81%, PPV = 92%, and AUC = 0.781).&#x0D; Conclusion: PIVKA-II is a valid indicator for defining the characteristics of liver nodules in cirrhosis and when combined with AFP, it signifies superior accuracy for HCC diagnosis.

Bone morphogenic protein-7 (BMP-7) polymorphism: Susceptibility to cirrhosis and hepatocellular carcinoma after viral hepatitis in Egyptian patients.

Bone morphogenic proteins (BMPs) have both inhibitory and stimulatory effects on growth of a tumor that depend on the type of cells, the dosage and the tumor microenvironment. We aimed to investigate the impact of the bone morphogenic protein-7 (BMP-7) single nucleotide polymorphism (SNP) rs230205 [A/G] on susceptibility to hepatocellular carcinoma (HCC) progression from liver cirrhosis after viral hepatitis infection in Egyptian patients. The amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) method was used to genotype the rs230205 [A/G] SNP in 150 subjects (50 patients with post-hepatitis C or B cirrhosis, 50 HCC patients, and 50 controls). Expression level of BMP-7 protein was assessed using enzyme-linked immunosorbent assay (ELISA). The results revealed insignificant changes in distribution of all genotypes/alleles of the BMP-7 rs230205 [A/G] SNP between cirrhotic patients, HCC patients and controls. The AA genotype and A allele could be considered risk factors for cirrhosis (OR = 1.75, 1.50) and HCC (OR = 2.19, 1.74), respectively. The AA genotype (95% CI: 0.45-6.79) and A allele (OR = 1.50, 95% CI: 0.77-2.93) may be viewed as cirrhosis risk factors based on group segregation. Additionally, the A allele, AG and AA genotypes and their combined ORs of 2.19 (95% CI: 0.58-8.23), 1.74 (95% CI: 0.90-3.37), and 1.70 (95% CI: 0.68-4.29) could all be risk factors for HCC. No genotype or allele could be regarded as a risk factor for progression of cirrhosis to HCC, according to OR values. The results showed no correlation between BMP-7 rs230205 [A/G] SNP and progression of cirrhosis to HCC. To confirm our findings, additional prospective large-scale research is required.

Advanced Hepatocellular Carcinoma in Adults Without Cirrhosis: A Single-Institution Retrospective Review.

Although up to one in five cases of hepatocellular carcinoma (HCC) occurs in patients without cirrhosis, there is scarce literature characterizing non-cirrhotic HCC (NCHCC). Existing NCHCC research is primarily limited to surgical case series and there is a lack of data on unresectable NCHCC. The purpose of this retrospective review was to compare the characteristics of unresectable NCHCC and cirrhotic hepatocellular carcinoma (CHCC). A retrospective chart review of adult patients with unresectable HCC treated from 2007 to 2017 was performed at the University of Florida Shands Hospital. The data set was stratified into two cohorts: NCHCC and CHCC. Continuous variables were compared using Wilcoxon-Mann-Whitney tests and Kruskal-Wallis rank-sum tests. Categorical variables were compared using Pearson's Chi-squared tests and Fisher's exact tests. Overall survival was explored utilizing the Kaplan-Meier and log-rank method. There were 1494 adult patients included in the final analysis, including 264 patients (17.7%) with NCHCC and 1230 patients (82.3%) with CHCC. Median age was 61.0 years old and median follow-up time was 30.2 months. NCHCC patients were older than CHCC patients (66.3 years vs 61.9 years; p < 0.0001). NHCC tumors were larger than CHCC tumors (7.92 ± 4.85 vs 4.38 ± 3.12 cm; p < 0.0001) and more likely to be associated with distant metastases (23.35% vs 15.91%; p = 0.0055). There was no difference in overall survival, with a median of 23.5 months in NCHCC and 22.4 months in CHCC (p = 0.9196). Our findings suggest that unresectable NCHCC and CHCC have unique characteristics but similar overall survival. To the best of our knowledge, this is the largest comparison of CHCC and NCHCC.

Profile of Hepatocellular Carcinoma: An Experience from a Tertiary Care Hospital

Background and Aim: Hepatocellular carcinoma (HCC) is the primary liver cancer around the world, and it has now become the third leading cause of cancer-related mortality. With an increasing global incidence, HCC is becoming a major health burden. The incidence of HCC varies from 0.3% to 1.6% in Asian countries. The present study aimed to assess the clinical and etiological profile of hepatocellular carcinoma in a tertiary care hospital. Methodology: This retrospective study was conducted on 124 hepatocellular carcinoma patients in the Department of Gastroenterology, Jinnah Hospital, Lahore from June 2019 to May 2022. All the patients of age 10 years to 75 years fulfilling the diagnostic criteria were enrolled in this study. Patient’s cytohistological, clinical, radiological, and etiological data were recorded and analyzed. Individual relevant features were noted in pre-designed proforma. SPSS version 25 was used for data analysis. Results: Of the total 124 HCC patients, there were 78 (62.9%) male and 46 (37.1%) females. The overall mean age was 48.63±6.78 years. Liver cirrhosis was present in 91 (73.4%) patients out of which 14 (15.4%) were asymptomatic. The prevalent signs of hepatic decompensation were ascites 67 (54%) and Jaundice 23 (18.5%). Based on etiological data, the prevalence of the cryptogenic, Hepatitis B, and C were 58 (46.8%), 20 (16.1%), and 6 (4.8%) respectively. Tumor thrombosis was found in 18 (14.5%). Based on biopsy specimens, HCC with steatosis were seen in 19 (15.3%) patients. During surveillance, about 32 (25.8%) cirrhotic HCC patients were diagnosed. Conclusion: The present study found that the most prevalent etiology was hepatocellular carcinoma. Most patients were asymptomatic and had major complaints of abdominal pain with certain specific comorbidities. Hypertension, diabetes, and ischemic heart disease were the specific co-morbidities in hepatocellular carcinoma patients. In our population, the prevalent cause of HCC was Hepatitis B. Keywords: Clinical profile, Etiology, Hepatocellular Carcinoma

A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy.

Simple SummaryMac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 cirrhotic patients receiving entecavir or tenofovir monotherapy to construct an HCC risk score. The ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi at 12 months of treatment, was developed. The ASPAM-B scores accurately classified patients into low (0–3.5), medium (4–7) and high (>7) risk (p < 0.001). The values of AUROC for predicting 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively. All AUROCs between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3–9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received antiviral treatment.Mac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 patients with chronic hepatitis B and cirrhosis receiving entecavir or tenofovir therapy for more than12 months to construct an HCC risk score. In the development cohort, Cox regression analysis identified male gender, age, platelet count, AFP and M2BPGi levels at 12 months of treatment as independent risk factors of HCC. We developed the HCC risk prediction model, the ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi levels at 12 months of treatment, with the total scores ranging from 0 to 11.5. This risk model accurately classified patients into low (0–3.5), medium (4–7), and high (>7) risk in the development and validation groups (p < 0.001). The areas under the receiver operating characteristic curve (AUROC) of 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively, in the development cohort. All AUROC between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3–9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received long-term antiviral treatment.