HCV-related Hepatocellular Carcinoma Research Articles

Biomarkers of gut barrier dysfunction and risk of hepatocellular carcinoma in the REVEAL-HBV and REVEAL-HCV cohort studies.

Gut barrier dysfunction can result in the liver being exposed to an elevated level of gut-derived bacterial products via portal circulation. Growing evidence suggests that systemic exposure to these bacterial products promotes liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, prospective studies have not examined the association between biomarkers of gut barrier dysfunction and HCC risk in a population of hepatitis B or C viral (HBV/HCV) carriers. We investigated whether prediagnostic, circulating biomarkers of gut barrier dysfunction were associated with HCC risk, using the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer (REVEAL)-HBV and REVEAL-HCV cohorts from Taiwan. REVEAL-HBV included 185 cases and 161 matched controls, and REVEAL-HCV 96 cases and 96 matched controls. The biomarkers quantitated were immunoglobulin A (IgA), IgG, and IgM against lipopolysaccharide (LPS) and flagellin, soluble CD14 (an LPS coreceptor), and LPS-binding protein (LBP). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarker levels and HCC were calculated using multivariable-adjusted logistic regression. A doubling of the circulating levels of antiflagellin IgA or LBP was associated with a 76% to 93% increased risk of HBV-related HCC (OR per one unit change in log2 antiflagellin IgA=1.76, 95% CI: 1.06-2.93; OR for LBP=1.93, 95% CI: 1.10-3.38). None of the other markers were associated with an increased risk of HBV-related or HCV-related HCC. Results were similar when cases diagnosed in the first 5 years of follow-up were excluded. Our findings contribute to understanding the interplay of gut barrier dysfunction and primary liver cancer etiology.

Efficacy and Safety of Tyrosine Kinase Inhibitors Alone or Combination with Programmed Death-1 Inhibitors in Treating of Hepatitis C-Related Hepatocellular Carcinoma.

Tyrosine kinase inhibitors (TKI) combined with programmed cell death-1 (PD-1) inhibitor is a potential treatment modality for patients with HCV-related unresectable hepatocellular carcinoma (uHCC). The participants of the present work included the patients having HCV-related uHCC who were treated with TKI monotherapy (TKI group) or TKI combined with PD-1 inhibitors therapy (combination group) in our center between June 2018 and June 2021. In addition, the patients were classified into RNA-positive and RNA-negative groups based on whether or not the baseline HCV RNA was detectable. The overall survival (OS) was used as the primary efficacy endpoint, while progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were used as secondary endpoints. The adverse events were recorded and evaluated. Among the 67 patients contained this work, 43 patients were classified into the TKI group, while 24 patients formed the combination group. In relative to the TKI group, the combination group presented notably better median OS (21 months vs 13 months, p = 0.043) and median PFS (8 months vs 5 months, p = 0.005). No evident differences were observed between the two groups in terms of the DCR (58.1% vs 79.2%, p = 0.080), ORR (13.9% vs 25.0%, p = 0.425) and the incidence of grade 3-4 adverse events (34.8% vs 33.3%, p = 1.000). In addition, there existed no obvious difference between the RNA-positive group and RNA-negative group in terms of median OS (14 months vs 19 months, p = 0.578) and median PFS (4 months vs 6 months, p = 0.238). The patients having HCV-related uHCC after being treated with the TKI and PD-1 inhibitor combination therapy exhibited a better prognosis and manageable toxicity compared to the patients who underwent TKI monotherapy.

Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency. The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated. A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04-1.67, P = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96-2.10, P = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09-1.87, P = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01-2.57, P = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09-1.79, P = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models. Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.

Clinical study of lenvatinib in the treatment of hepatitis virus-related hepatocellular carcinoma and antiviral therapy.

Background: Lenvatinib is recommended as a first-line tyrosine kinase inhibitor for advanced hepatocellular carcinoma (HCC) since 2017. The aim of this study was to compare the clinical action of lenvatinib in hepatitis B virus (HBV)-related HCC and hepatitis C virus (HCV)-related HCC. Methods: A continuous cohort of advanced HCC was retrospectively enrolled. And the patients were divided into HBV-related HCC and HCV-related HCC based on previous history of hepatitis virus infection. Then propensity score matching (PSM) was conducted to compare objective response rate (ORR),disease control rate (DCR),progression-free survival (PFS),overall survival (OS) and safety between the two groups. Results: A total of 203 eligible patients were included, with 72 HBV-related HCC and 36 HCV-related HCC after PSM. Both ORR (20.8% vs. 5.6%, P = .0759) and DCR (76.4% vs. 52.8%, P = .0232) were significantly higher in the HBV-related HCC than in the HCV-related HCC. Although no statistical differences in PFS (6.1months vs. 3.3months, P = .17) and OS (14.9months vs. 17.7months, P = .96) were observed between the two groups, there was a trend of difference in the PFS survival curve. On multivariate regression analysis of PFS, both HBV infection (HR, .54; 95% CI, .31-.95; P = .0332) and antiviral time >5years (HR, .49; 95% CI, .26-.9; P = .0219) were identified as independent favorable factors, and AFP >200ng/mL (HR, 1.88; 95% CI, 1.1-3.22; P = .0216) were found to be an independent adverse factor. In addition, compared with HCC who received the first dose of antiviral drugs less than 5years, the patients who were administered those drugs over 5years had a significantly favorable PFS (11.27months vs. 3.87 months, P = .0011). Lenvatinib was well tolerated in all patients and the adverse events (AEs) were similar between the two groups. Conclusion: It seemed that lenvatinib benefited more in HBV-related advanced HCC in delaying disease progression, compared to those with HCV-related advanced HCC.

Impact of miR-23b and miR-331 Gene Expressions on HCV-Related Hepatocellular Carcinoma in Egyptian Patients

Impact of miR-23b and miR-331 Gene Expressions on HCV-Related Hepatocellular Carcinoma in Egyptian Patients

The Impact of interferon lambda 3 Polymorphism on Hepato-Cellular Carcinoma Progression in Hepatitis C Virus Patients: Treatment-Naïve and Experienced.

In this study, we investigated the association between the IFN-λ3 rs12979860 single nucleotide polymorphism (SNP) and the transition from late fibrosis to HCC in Egyptian HCV-chronically infected patients. The rs12979860 SNP was genotyped using real-time PCR in DNA from the whole blood of healthy subjects (n=60) and HCV patient s (n=342). We stratified the patients into (1) treatment-naïve patients (n=218) with advanced fibrosis (F2-F4, n=123) and HCC (n=95 Treatment-experienced patients (n=124) who received SOF-based therapy for 12 weeks and achieved SVR (SVR12). DAA-treated patients were divided into 2 groups: group I (n=63) included patients with advanced hepatic fibrosis (F2-F4) who did not develop HCC within a year after treatment, and group II (n=61) included patients who were free of focal hepatic lesions before starting DAA therapy but developed HCC within a year. Our results demonstrated that treatment-naïve patients with the CT/TT genotypes and the T allele were more likely to have HCC (odds ratio 3.1, 95% CI 1.44-6.71, P = 0.003 and odds ratio 1.89, 95% CI 1.28-2.76, P = 0.001, respectively). Binary regression analysis defined 3 independent predictors associated with HCC development: age (odds ratio 1.039, 95% CI 1.004-1.076, P = 0.028), alanine aminotransferase (odds ratio 1.008, 95% CI 1.002-1.015, P = 0.010), and rs12979860 (odds ratio 3.65, 95% CI 1.484-8.969, P = 0.005). However, the rs12979860 SNP did not show any correlation with the progression of HCC post-treatment. Despite the debate on the contribution of IFN-λ3 rs12979860 to susceptibility to HCV-related HCC, our data confirm the role of this SNP in this context.

Evaluating the Serum Markers for Early Diagnosis of HCV Induced Hepatocellular Carcinoma

Hepatocellular carcinoma is a global public health problem which is intensified at developing countries due to lack of early diagnosis. Since Hepatitis C virus related morbidity accounts five million people in Pakistan, rate of morbidity and mortality of HCV related Hepatocellular carcinoma infections is high in Pakistan, and it is attributed to its diagnosis after its development. The public has the lack of awareness about the importance and benefits of liver biopsy testing; therefore, improved, and non-invasive methods of HCC diagnosis are urgently needed. The aim of the present study was to evaluate the importance of serum markers in early diagnosis of HCV induced Hepatocellular carcinoma and to develop a robust set of serological markers for their early detection and diagnosis. A total of 60 HCV positive patients including Chronic Liver disease (n=20), Cirrhosis (n=20), HCC patients (n=20) and 20 healthy volunteers (n=20) were enrolled in this study after an extensive screening process. Blood samples were collected from all the subjects and processed for serum separation followed by immunological, molecular, and biochemical analysis using Enzyme Linked Immunosorbant Assay, Real-Time PCR, complete blood picture, and a range of biochemical tests. Results showed gender wise variability among the subjects from each of the study groups where in the male subjects remained dominant with male and female ratio as 61.75:38.75. The average age of male subjects was observed between 42y, 43y, 49y and 37 years in comparison of female subjects who were 46y, 53y, 50y and 47y in CLD, cirrhosis, Hepatocellular carcinoma, and control groups, respectively. The data has also demonstrated that Hepatocellular carcinoma patients having Alpha Fetoprotein level >1000 showed the increased level of ALP and GGT with decreased HB and HCT. However, the Hepatocellular carcinoma patients having AFP level in the range of 100-500 had total bilirubin level > 3.0, while those having AFP level <100 has all serological markers in normal range. In addition, the patients of HCC showed increased PT with decreased albumin level. The increases level of albumin level (>3-<4.0) was observed from the serum samples of cirrhosis and Chronic liver disease patients. The increase in albumin up to 4.0 accompanied with the increased level of ALP and PT while decreased HB. In conclusion, different biochemical parameters may be used to distinguish the patients having Hepatocellular carcinoma from those suffering from cirrhosis and chronic liver disease induced by HCV infection. The findings of present study may help to enhance the outcome for patients with HCC by enabling the diagnosis to be made at an earlier stage of the disease.

Plasma Long Non-Coding RNA ZFAS1 as a Potential Diagnostic Biomarker for HCV-Related Hepatocellular Carcinoma

Plasma Long Non-Coding RNA ZFAS1 as a Potential Diagnostic Biomarker for HCV-Related Hepatocellular Carcinoma

REVIEW ARTICLE: HCV IMPACTON THE PATTERN OF CIRC-RNAEXPRESSION IN HCV RELATED HCC

Circular RNAs (circRNAs) are a class of non-coding RNAs with a circular, covalent structure, which are highly conserved, stable unique molecules found in eukaryotic cells. The most notable character of circRNAs is their high stability in biological systems which is a key factor in their potential for use in a variety of RNA-focused medical applications. Despite the fact that circRNAs have a wide range of biological roles and regulatory functions, their circular structure and sequence overlap with their linear mRNA counterparts make it difficult to research them in depth. Furthermore, little is known about their function in viral infections and in immune responses.Since circRNAs have been found to be involved in a number of viral infections (including hepatitis B virus infection and human papilloma virus infection), their significance in viral infections is being more recognized in the last years.In this review, we aimed to provide a broad basis and overview on the biogenesis, significance and regulatory roles of circRNAs in the context of viral hepatitis C virus (HCV) infection, and HCV related hepatocellular carcinoma. Owing to the fact that the chronic HCV infection is the leading cause of HCC in the western countries especially Egypt. HCV can act directly on cell signaling pathways to promote HCC by inhibiting tumor suppressor genes or by causing activation of signaling pathways that up-regulate growth and division. Because viruses frequently manipulate cellular pathways to control viral gene expression, cellular and viral circRNA landscapes in virus-infected cells are altered. Studying the contribution of circRNAs in these pathways may give valuable information in the pathogenesis of HCC caused by HCV or in finding more reliable therapeutic approaches.

Down-regulation of hepatic expression of GHR/STAT5/IGF-1 signaling pathway fosters development and aggressiveness of HCV-related hepatocellular carcinoma: Crosstalk with Snail-1 and type 2 transforming growth factor-beta receptor.

So far, few clinical trials are available concerning the role of growth hormone receptor (GHR)/signal transducer and activator of transcription 5 (STAT5)/insulin like growth factor-1 (IGF-1) axis in hepatocarcinogenesis. The aim of this study was to evaluate the hepatic expression of GHR/STAT5/IGF-1 signaling pathway in hepatocellular carcinoma (HCC) patients and to correlate the results with the clinico-pathological features and disease outcome. The interaction between this signaling pathway and some inducers of epithelial-mesenchymal transition (EMT), namely Snail-1 and type 2 transforming growth factor-beta receptor (TGFBR2) was studied too. A total of 40 patients with HCV-associated HCC were included in this study. They were compared to 40 patients with HCV-related cirrhosis without HCC, and 20 healthy controls. The hepatic expression of GHR, STAT5, IGF-1, Snail-1 and TGFBR2 proteins were assessed by immunohistochemistry. Compared with cirrhotic patients without HCC and healthy controls, cirrhotic patients with HCC had significantly lower hepatic expression of GHR, STAT5, and IGF-1proteins. They also displayed significantly lower hepatic expression of TGFBR2, but higher expression of Snail-1 versus the non-HCC cirrhotic patients and controls. Serum levels of alpha-fetoprotein (AFP) showed significant negative correlations with hepatic expression of GHR (r = -0.31; p = 0.029) and STAT5 (r = -0.29; p = 0.04). Hepatic expression of Snail-1 also showed negative correlations with GHR, STAT5, and IGF-1 expression (r = -0.55, p = 0.02; r = -0.472, p = 0.035, and r = -0.51, p = 0.009, respectively), whereas, hepatic expression of TGFBR2 was correlated positively with the expression of all these proteins (r = 0.47, p = 0.034; 0.49, p = 0.023, and r = 0.57, p<0.001, respectively). Moreover, we reported that decreased expression of GHR was significantly associated with serum AFP level>100 ng/ml (p = 0.048), increased tumor size (p = 0.02), vascular invasion (p = 0.002), and advanced pathological stage (p = 0.01). Similar significant associations were found between down-regulation of STAT5 expression and AFP level > 100 ng/ml (p = 0.006), vascular invasion (p = 0.009), and advanced tumor stage (p = 0.007). Also, attenuated expression of IGF-1 showed a significant association with vascular invasion (p < 0.001). Intriguingly, we detected that lower expression of GHR, STAT5 and IGF-1 were considered independent predictors for worse outcome in HCC. Decreased expression of GHR/STAT5/IGF-1 signaling pathway may have a role in development, aggressiveness, and worse outcome of HCV-associated HCC irrespective of the liver functional status. Snail-1 and TGFBR2 as inducers of EMT may be key players. However, large prospective multicenter studies are needed to validate these results.

Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR.

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR.

Cytotoxic T Cell Expression of Leukocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1) in Viral Hepatitis C-Mediated Hepatocellular Carcinoma.

Virus-related hepatocellular carcinoma (HCC) pathogenesis involves liver inflammation, therefore, despite successful treatment, hepatitis C virus (HCV) may progress to HCC from initiated liver cirrhosis. Cytotoxic T cells (Tcs) are known to be involved in HCV-related cirrhotic complications and HCC pathogenesis. The inhibitory checkpoint leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is expressed on Tcs. Therefore, we aimed to determine whether the Tc expression level of LAIR-1 is associated with HCC progression and to evaluate LAIR-1 expression as a noninvasive biomarker for HCC progression in the context of liver cirrhosis related to HCV genotype 4 (G4) in Egyptian patients’ peripheral venous blood liquid biopsy. A total of 64 patients with HCC and 37 patients with liver cirrhosis were enrolled in this case-controlled study, and their LAIR-1 expression on Tc related to the progression of liver cirrhosis was examined and compared to that of the apparently healthy control group (n = 20). LAIR-1 expression was analyzed using flow cytometry. Results: The HCC group had significantly higher LAIR-1 expression on Tc and percentage of Tc positive for LAIR-1 (LAIR-1+Tc%) than the HCV G4-related liver cirrhosis group. LAIR-1+Tc% was correlated with the HCC surrogate tumor marker AFP (r = 0.367, p = 0.001) and insulin resistance and inflammation prognostic ratios/indices. A receiver operating characteristic (ROC) curve revealed that adding LAIR-1+Tc% to AFP can distinguish HCC transformation in the Egyptian patients’ cohort. Upregulated LAIR-1 expression on Tc could be a potential screening noninvasive molecular marker for chronic inflammatory HCV G4 related liver cirrhosis. Moreover, LAIR-1 expression on Tc may be one of the players involved in the progression of liver cirrhosis to HCC.

Prognostic Factors for Overall Survival in Patients with HCV-Related HCC Undergoing Molecular Targeted Therapies: Beyond a Sustained Virological Response.

Simple SummaryThe eradication of the hepatitis C virus (HCV) has had a significant impact on the management of patients with HCV-related hepatocellular carcinoma (HCC). However, its eradication has not completely resolved survival issues in patients with HCV-related HCC. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC undergoing molecular targeted therapies. In total, 359 HCC patients treated with first-line chemotherapy were enrolled. The median follow-up duration was 16.0 months (range, 1.0–115.7) and the median duration of first-line systemic therapy was 3.7 months (range, 0.7–86.9). The achievement of a sustained virological response (SVR) (p < 0.001), albumin-bilirubin (ALBI) grade II/III (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p = 0.005), extrahepatic spread (p < 0.001), baseline AFP level ≥ 90 (p = 0.038), baseline DCP level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p = 0.003) were identified as independent prognostic factors for overall survival.Background: The treatment of the hepatitis C virus (HCV) has reduced the risk of hepatocellular carcinoma (HCC)-related mortality. Many patients with advanced HCC have achieved longer survival through systemic chemotherapy. However, survivors of HCC may develop liver cancer during and after treatment. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC in the new era of molecular targeted therapy. Methods: A total of 359 patients with HCV-related HCC treated with first-line chemotherapy were reviewed. A Cox proportional hazards model and Kaplan–Meier curve were used to identify prognostic factors associated with survival outcomes. Results: The median follow-up duration was 16.0 months (range, 1.0–115.7) and the median duration of first-line systemic therapy was 3.73 months (range, 0.7–86.9). The achievement of a sustained virological response (SVR) (p < 0.001), albumin–bilirubin (ALBI) grade II/III (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p = 0.005), extrahepatic spread (p < 0.001), baseline AFP (alpha-fetoprotein) level ≥ 90 (p = 0.038), baseline DCP (des-γ-carboxy prothrombin) level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p = 0.003) were identified as prognostic factors for overall survival. Conclusions: The achievement of SVR was most strongly associated with overall survival. Other factors, such as the BCLC stage, extrahepatic spread, baseline tumor marker (AFP/DCP) levels, ALBI grade, and FIB-4 index need to be considered in the management of patients with HCV-related HCC.

Construction of novel lncRNA-miRNA-mRNA ceRNA networks associated with prognosis of hepatitis C virus related hepatocellular carcinoma

BackgroundHepatitis C virus (HCV) infection contribute to liver fibrosis and cirrhosis, which significantly increases the risk of hepatocellular carcinoma (HCC) development. Previous studies have demonstrated the pivotal role of competitive endogenous RNA (ceRNA) networks in tumorigenesis and cancer progression. Consequently, we herein seek to identify and evaluate the prognostic relevance of a novel ceRNA network associated with HCV-related HCC. MethodsDifferentially expressed genes (DEGs) in GSE140846 dataset from GEO were identified using Network Analyst, and GO, KEGG and Reactome analyses were performed. Furthermore, a protein-protein interaction network was generated, and hub genes were detected. Hub gene expression levels, as well as those of their upstream lncRNAs and miRNAs and associated survival analyses were conducted using appropriate bioinformatics databases. Predicted target relationships were used to establish putative ceRNA networks for HCV-related HCC. ResultsA total of 372 and 360 up- and down-regulated DE-mRNA were identified, which were associated with nuclear division, cell cycle, and ATPase activity. A PPI network containing 704 DE-mRNAs was constructed, and the 6 hub gene with the highest degree of connectivity were selected for subsequent analysis. We discovered that 22 miRNAs and 4 lncRNAs upstream of 11 hub gene were significantly associated with poor prognosis of HCV-related HCC, and used them to constructe a prognostic ceRNA network. Further experiments confirmed the ceRNA-regulatory relationship of BUB1-hsa-miR-193a-3p-MALAT1. ConclusionThis study provides novel insights into the lncRNA-miRNA-mRNA ceRNA network, and reveals potential lncRNA biomarkers in HCV related HCC.

MACHINE LEARNING-BASED CLASSIFICATION OF HBV AND HCV-RELATED HEPATOCELLULAR CARCINOMA USING GENOMIC BIOMARKERS

Objective: It is crucial to know the underlying causes of hepatocellular carcinoma (HCC) for optimal management. This study aims to classify open access gene expression data of HCC patients who have an HBV or HCV infection using the XGboost method. Material and Methods: This case-control study considered the open-access gene expression data of patients with HBV-related HCC and HCV-related HCC. For this purpose, data from 17 patients with HBV+HCC and 17 patients with HCV+HCC were included. XGboost was constructed for the classification via tenfold cross-validation. Accuracy, balanced accuracy, sensitivity, specificity, the positive predictive value, the negative predictive value, and F1 score performance metrics were evaluated for a model performance. Results: With the feature selection approach, 17 genes were chosen, and modeling was done using these input variables. Accuracy, balanced accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and the F1 score obtained from the XGboost model were 97.1%, 97.1%, 94.1%, 100%, 100%, 94.4%, and 97%, respectively. Based on the variable importance findings from the XGboost, the ALDOC, GLUD2, TRAPPC10, FLJ12998, RPL39, KDELR2, and KIAA0446 genes can be employed as potential biomarkers for HBV-related HCC. Conclusion: As a result of the study, two different etiological factors (HBV and HCV) causing HCC were classified using a machine learning-based prediction approach, and genes that could be biomarkers for HBV-related HCC were identified. After the&nbsp;resulting genes have been clinically validated in subsequent research, therapeutic procedures based on these genes can be established and their utility in clinical practice documented.

Percutaneous thermal ablation combined with transcatheter arterial chemoembolization for hepatitis C virus-related hepatocellular carcinoma: Efficacy and survival.

ObjectiveThe aim of this study was to investigate the efficacy and survival of Hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) undergoing percutaneous thermal ablation combined with transcatheter arterial chemoembolization (TACE).MethodsA total of 83 HCV-related HCC patients who were treated with percutaneous thermal ablation combined with TACE were retrospectively analyzed. The demographic and clinical data were collected. The overall survival (OS) and recurrence free survival (RFS) rates were assessed by the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to assess independent risk factors of OS and RFS.Results92.8% patients (77/83) and 96.6% (170/176) tumor lesions achieved complete response (CR) 1 month after all treatment, and 10.8% (9/83) patients had minor complications. The median OS was 60 months (95% confidence interval (CI)= 48.0-72.0), and the 1-, 2-, 3-, 5- and 10-year cumulative OS rates were 94%, 78.3%, 72.3%, 43.4% and 27.5%, respectively. The cumulative RFS rates at 1-, 2-, 3- and 5-year were 74.7%, 49.3%, 30.7% and 25.3%, respectively. Sex (HR =0.529, P=0.048), ablation result (HR=5.824, P=0.000) and Albumin-bilirubin (ALBI) score (HR=2.725, P=0.011) were independent prognostic factors for OS. Alpha-fetoprotein (AFP) (HR =2.360, P = 0.005) and tumor number(HR=2.786, P=0.000) were independent prognostic factors for RFS.ConclusionsPercutaneous thermal ablation combined with TACE is a safe and effective treatment for HCV-related HCC. Sex, ablation result and ALBI are significant prognostic factors for OS. AFP and tumor number are significant prognostic factors for RFS.

Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study

BackgroundNew direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.MethodsWe conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.ResultsA decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.ConclusionsElderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.

Liver resection of hepatocellular carcinoma in HIV-HCV co-infected patients: a retrospective case series

IntroductionDespite the effectiveness of new therapies and awareness campaigns, the number of seropositive patients is increasing every year. Recently, other causes of death, not directly related to HIV, have emerged, such as chronic liver disease. The risk of hepatocellular carcinoma (HCC) is seven times greater in HIV patients than in noninfected patients, and it is especially attributable to HCV infection. The aim of our study was to evaluate clinical outcomes of HCC in HIV-HCV co-infected patients after liver resection (LR).Materials and methodsThe current study was conducted on a prospective database and reviewed retrospectively. All consecutive patients with HCC treated by LR from January 2013 to March 2019 at the Luigi Sacco University Hospital in Milan were enrolled. We included patients older than 18 years of age with HCV-related HCC, and in this set of patients, we identified two groups based on the presence of HIV infection.ResultsWe identified 16 patients with HCV infection and precisely five with HIV-HCV co-infection and eleven with HCV infection alone. All HIV patients were male against 72.7% in the non-HIV group (p = 0.509). All patients had optimal HIV virologic control and a normal CD4 T-cell count. The mean diagnosis-to-treatment interval was statistically different between the two groups (HIV versus non-HIV: 1.2 ± 0.55 months versus 2.39 ± 1.09 months, p = 0.039).No other significant differences were found between HIV-HCV co-infected patients and HCV-infected patients. Long-term outcomes in terms of OS and RFS were similar between the two groups.ConclusionsWith a multidisciplinary approach and intensive support, LR can be a safe and efficacious procedure in HIV-HCV patients. For these reasons, we should not exclude potential patients merely on the basis of their HIV seropositivity.

Temporal trends of waitlistings for liver transplantation in Italy: The ECALITA (Evolution of IndiCAtion in LIver transplantation in ITAly) registry study

BackgroundOver the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities. AimTo investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy. MethodsWe recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004–2011),2(2012–2014) and 3(2015–2020). ResultsWaitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%. ConclusionsA sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis.

Hepatocellular carcinoma (HCC) is changing its face: analysis of the temporal trends in aetiology and clinical patterns of HCC in South Australia.

The epidemiology of chronic liver disease is changing with the introduction of potent antiviral therapies for chronic hepatitis C virus (HCV) and the increasing prevalence of non-alcoholic steatohepatitis (NASH). To establish the impact of this change on the rates and clinical patterns of hepatocellular carcinoma (HCC) in South Australia (SA). Newly diagnosed HCC patients from January 2014 until December 2019 from four tertiary centres in SA were included. The overall age-standardised incidence rates (ASIR) of HCC were calculated using 2016 SA population as the standard. To assess the trends, Join-Point regression models were used to calculate the average annual percentage change (AAPC). Forecasting of overall and aetiology-specific HCC from 2020 to 2024 was performed using linear regression. There were 626 new cases of HCC in SA (males 80%; median age 64 years) during the study period. There was a significant increase in NASH-related HCC (AAPC: +7.0%; P < 0.05) from 2014 to 2019. However, there were no significant differences in the ASIR for overall HCC (AAPC: -4.1%), HCV-related HCC (AAPC: -8.0%) and stage of HCC diagnosis (AAPC: +3.0%; P > 0.05). Forecasting analysis projected the decline and increase in the incidence of HCV and NASH-related HCC, respectively, over the next few years. Overall ASIR of HCC has plateaued in SA. However, NASH-related HCC has increased significantly and is expected to continue to increase in the near future. Further research and intervention is required to reduce NASH-related HCC, a major contributor to the current and future burden of HCC.