Virus-related Hepatocellular Carcinoma Research Articles

Correlation between CTNNB1 mutation status and tumour phenotype in hepatitis B virus-related hepatocellular carcinoma.

The frequency of CTNNB1 mutation, one of the most frequent genetic events in hepatocellular carcinoma (HCC), is lower in Asian countries and in hepatitis B virus (HBV)-related HCCs. In this study, we evaluated the prevalence and types of CTNNB1-mutation in HBV-related HCC and correlated the molecular status with the histomorphological and immunohistochemical features. A total of 108 consecutive cases of treatment-naïve, surgically resected HBV-related HCCs were selected. Targeted sequencing for CTNNB1 exons 3, 7 and 8 was performed, and the results were correlated with the expression pattern of glutamine synthetase (GS), nuclear β-catenin expression status and the histomorphological characteristics of the tumour. CTNNB1 mutations were identified in 13% of HBV-related HCCs; of these cases, mutations were found in D32-S37 (7%), T41 (4%) and S45 (2%) of exon 3. None of the HCCs demonstrated alterations in exons 7 and 8. CTNNB1 mutation was strongly associated with diffuse strong GS expression (P < 0.001), nuclear β-catenin expression (P < 0.001) and the classic CTNNB1 morphology (P = 0.038). Diffuse strong GS expression was observed in 78.6% of the CTNNB1-mutated HCCs, and nuclear β-catenin expression was identified in 64.3% of these cases. The classic CTNNB1 morphology was observed in 57% of all CTNNB1-mutated HCCs. Furthermore, programmed death-ligand 1 (PD-L1) was less frequently expressed in HCCs with classic CTNNB1 morphology. CTNNB1 mutation was observed in 13% of HBV-related HCCs in this Korean cohort, and was associated with diffuse strong GS expression, nuclear β-catenin expression and classic CTNNB1 morphology.

Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy.

The present study aimed to clarify the long-term outcomes after curative resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with and without sustained virologic response (SVR) to antiviral therapy. This single-center retrospective cohort study included 216 patients with HCV-related HCC who underwent primary curative resection. Patients were divided into preoperatively achieved SVR, postoperatively achieved SVR through direct-acting antiviral (DAA) therapy and no SVR groups. Associations of SVR and other clinicopathological and surgical variables with overall survival (OS) and recurrence-free survival (RFS) were analyzed. Propensity score (PS) matching was used to reduce selection bias. Patients with pre-SVR (108) and post-SVR (28) had better liver function and less liver fibrosis than those without SVR (80). In multivariate analysis, pre- or post-SVR [hazard ratio (HR), 0.13; 95% confidence interval (CI), 0.03-0.38; P < 0.001] was the only independent predictor of OS. For RFS, pre- or post-SVR (HR, 0.36; 95% CI, 0.18-0.64; P = 0.001) was one of several independent predictors. The study population was divided into the SVR (136 patients) and non-SVR groups. After PS matching, OS and RFS were significantly better in the SVR group (n = 53) than in the non-SVR group (n = 53) (P <0.001 and P = 0.012, respectively). Additionally, OS rates of SVR achieved with DAA were significantly higher than those achieved with interferon (P = 0.019). Achieving SVR by DAA before or after curative resection suppressed recurrence and prevented death in patients with HCV-related HCC.

Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma

Background and aimMicroRNAs (miRs) are now a well-known subject in various tumor genesis and are studied as early diagnostic biomarker. Many arrays of miRs were incorporated in the pathogenesis of HCV-related hepatocellular carcinomas (HCV-HCC). In this respect, we aimed to evaluate the diagnostic role of circulating miR-21, miR-122, and miR-222 in Egyptian patients with HCV-HCC.Patient and methodsBetween June 2018 and April 2019, a cross-sectional comparative study was designed to evaluate the circulating miR-21, miR-122, and miR-222 by quantitative Real-Time PCR. For analytical purposes, patients were categorized into three groups: chronic HCV group (CHC-group, n = 22), HCV-related liver cirrhosis (LC-group, n = 22), and HCV-related hepatocellular carcinoma (HCV-HCC-group, n = 54).ResultsSerum levels of miR-21 and miR-222 increased with the progressive course from CHC to LC and HCC; p < .001. Serum levels of miR-122 in HCC patients were significantly lower than non-HCC patients (CHC and LC patients, n = 44); p < .001. However, the differences in levels of serum miR-122 between CHC and LC were not statistically significant; P = 0.8.ROC curve analysis showed that the sensitivity and specificity of miR-21 were 61.1% and 95.5%, miR-222 were 71.7% and 93.2%, and miR-122 were 98.2% and 100%. The positive predictive value for miRNA-21, miRNA-122, and miRNA-222 were 13.4%, 93.3%, and 10.5% respectively. The Negative predictive value for miRNA-21, miRNA-122, and miRNA-222 were 94.3%, 97.8%, and 92.7% respectively.ConclusionMiR-21 and miR-222 could be potential markers for advanced liver damage, while miR-122 had the best diagnostic accuracy and could be a promising marker for detection of HCC.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.

LncRNA POLR2J4 Plays a Biomarker Role in Hepatitis B Virus-Related Hepatocellular Carcinoma Through Regulating miR-214-3p.

Identifying novel therapeutic targets for hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) has become a key goal in liver cancer research. Even though long non-coding RNAs (lncRNAs) do not code proteins, they could regulate the expression of functional genes and thus mediate disease development. The aim of this study was to estimate the role of lncRNA POLR2J4 (POLR2J4) in the progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) to pinpoint a potential biomarker. This study included 109 patients diagnosed with HBV-positive HCC, from whom tissue samples were collected. The expression level of POLR2J4 was evaluated by qPCR. The significance of POLR2J4 in HBV-HCC development and prognosis was estimated by Chi-square, Kaplan-Meier, and Cox analysis. In vitro, POLR2J4 was regulated in HBV-HCC cells, and its effect on cell growth and metastasis was assessed by CCK8 and Transwell assay. The interaction between POLR2J4 and miR-214-3p was evaluated through the luciferase reporter and RNA immunoprecipitation assays. In tumor tissues of HBV-HCC patients, there was an observed increase in the expression of POLR2J4. The increase was closely related with patients' presence of cirrhosis and vascular invasion, higher AFP, and advanced Edmondson grade and TNM stage. An upregulation of POLR2J4 predicted a poor prognosis for HBV-HCC patients and served as an independent indicator. In HBV-related HCC cells, silencing POLR2J4 suppressed cell proliferation, migration, and invasion. Furthermore, POLR2J4 negatively regulated miR-214-3p reversing the inhibition of cellular processes. POLR2J4 acted as a prognostic biomarker and a tumor promoter of HBV-HCC by modulating miR-214-3p.

The Clinical Significance of Long Non-Coding RNA (Taurine Up-Regulated Gene1) in Hepatitis C Virus-Related Hepatocellular Carcinoma Patients.

The Clinical Significance of Long Non-Coding RNA (Taurine Up-Regulated Gene1) in Hepatitis C Virus-Related Hepatocellular Carcinoma Patients.

Partial hepatectomy versus interventional treatment in patients with hepatitis B virus-related hepatocellular carcinoma and clinically significant portal hypertension: a randomized comparative clinical trial.

The widely accepted view that portal hypertension (PHT) is a contraindication to hepatectomy for patients with hepatocellular carcinoma (HCC) is being increasingly challenged. The long-term survival outcomes and safety of partial hepatectomy versus interventional treatment using ablation with or without pre-ablation transarterial chemoembolization (TACE) in patients with HBV-related HCC within the Milan criteria and with clinically significant PHT were compared in this study. This open-label randomized clinical trial was conducted on consecutive patients with clinically PHT and hepatitis B virus (HBV)-related HCC with tumors which were within the Milan criteria. These patients were randomized 1:1 to receive either partial hepatectomy or interventional treatment between December 2012 and June 2018. The primary endpoint was overall survival (OS); secondary endpoints included recurrence-free survival (RFS) and therapeutic safety. Each of the 2 groups had 80 patients. The 1-, 3- and 5-year OS rates in the partial hepatectomy group and the interventional treatment group were 95.0%, 86.2%, 69.5% versus 93.8%, 77.5%, 64.9%, respectively (P = 0.325). The corresponding RFS rates were 78.8%, 55.0%, 46.2% versus 71.3%, 52.5%, 45.0%, respectively (P = 0.783). The partial hepatectomy group had a higher complication rate compared to the interventional group (67.5% vs. 20%, P < 0.001). However, the differences were mainly in Clavien-Dindo Grade I complications (P < 0.001), while not significant in Grade II/III/IV/V (All P > 0.05). This study shows that partial hepatectomy treatment did not meet prespecified significance for improved OS and RFS compared to interventional treatment for patients with HBV-related HCC within the Milan criteria and with clinically significant PHT. However, partial hepatectomy is still a safe procedure and should be considered as a treatment option rather than a contraindication.

Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy.

Globally, hepatocellular carcinoma (HCC) is among the most prevalent and deadly cancers. Hepatitis B virus (HBV) infection is an important etiology and disease progression factor for HCC. Hepatectomy is a widely accepted curative treatment for HCC, but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection. Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy. However, many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently, necessitating the start of remedial antiviral therapy in the perioperative phase. Therefore, it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.

Nucleos(T)ide Analogue Treatment Has a More Pronounced Impact on Immune Repertoires of CHB Patients Compared to HCC Patients.

Nucleos(t)ide analogues (NAs) as the first-line treatment for chronic hepatitis B (CHB) have been shown to partially restore the antiviral immunity of the patients. However, hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients have a relatively longer duration of HBV infection and lower level of HBV DNA. Whether NAs treatments have a different effect on their immune repertoires between CHB and HCC patients remains to be determined. In this study, 126 CHB patients and 85 HBV-related HCC patients who received or did not receive NAs treatment, as well as 361 healthy individuals were enrolled to analyze the effect of NAs treatment on T cell receptor β chain (TCRβ) and B cell receptor heavy chain (BCRh) repertoires in peripheral blood of the patients. We found that after NAs therapy, the richness and evenness of TCRβ and BCRh repertoires in CHB patients were significantly lower than those in untreated patients and healthy controls, while the diversity of TCRβ and BCRh repertoires was stable in HCC patients. The alanine aminotransferase and HBV DNA levels were not correlated with the TCR or BCR diversity in CHB and HCC patients. The results suggest that NAs therapy could influence the overall T cell and B cell repertoires diversity in CHB patients but has minimal impact on HCC patients, indicating a significant difference in the potential to restore antiviral immunity between CHB and HCC patients by NAs treatment.

AC099850.3 promotes HBV-HCC cell proliferation and invasion through regulating CD276: a novel strategy for sorafenib and immune checkpoint combination therapy

BackgroundThis study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC).MethodsA dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan–Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied.ResultsA prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC.ConclusionsAC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC.

Changes in systemic immune-inflammation index (SII) predict the prognosis of patients with hepatitis B-related hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors.

This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. Multivariate analysis revealed that an alpha-fetoprotein (AFP) level 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) 65.43 (HR 0.50; 95% CI 0.30-0.84; P and SII 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.

Novel genetic variants in the NLRP3 inflammasome-related PANX1 and APP genes predict survival of patients with hepatitis B virus-related hepatocellular carcinoma.

The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes involved in the pathogenesis of several cancers, including hepatocellular carcinoma (HCC). However, the effects of genetic variants in the NLRP3 inflammasome-related genes on survival of hepatitis B virus (HBV)-related HCC patients are unclear. We performed multivariable Cox proportional hazards regression analysis to evaluate associations between 299 single-nucleotide polymorphisms (SNPs) in 16 NLRP3 inflammasome-related genes and overall survival (OS) of 866 patients with HBV-related HCC. We further performed expression quantitative trait loci (eQTL) analysis using the data from the GTEx project and 1000 Genomes projects, and performed differential expression analysis using the TCGA dataset to explore possible molecular mechanisms underlying the observed associations. We found that two functional SNPs (PANX1 rs3020013 A > G and APP rs9976425 C > T) were significantly associated with HBV-related HCC OS with the adjusted hazard ratio (HR) of 0.83 [95% confidence interval (CI) = 0.73-0.95, P = 0.008], and 1.26 (95% CI = 1.02-1.55, P = 0.033), respectively. Moreover, the eQTL analysis revealed that the rs3020013 G allele was correlated with decreased mRNA expression levels of PANX1 in both normal liver tissues (P = 0.044) and whole blood (P < 0.001) in the GTEx dataset, and PANX1 mRNA expression levels were significantly higher in HCC samples and associated with a poorer survival of HCC patients. However, we did not observe such correlations for APP rs9976425. These results indicated that SNPs in the NLRP3 inflammasome-related genes may serve as potential biomarkers for HBV-related HCC survival, once replicated by additional larger studies.

Effect of nucleos(t)ide analogue discontinuation on the prognosis of HBeAg-negative hepatitis B virus-related hepatocellular carcinoma after hepatectomy: A propensity score matching analysis.

Although nucleos(t)ide analogues (NAs) are thought to reduce the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), the effect of NA discontinuation on the prognosis of HBV-related HCC after hepatectomy is rarely reported. We aimed to investigate the potential for hepatitis B virus e antigen (HBeAg)-negative HBV-related HCC patients to discontinue NAs based on preoperative hepatitis B virus surface antigen (HBsAg) status. This historical cohort study involved 1232 NA-treated HBeAg-negative patients who underwent curative hepatectomy for HBV-related HCC from 2014 to 2019. The recurrence-free survival (RFS) and overall survival (OS) of patients discontinuing NAs before surgery were compared with those continuing NAs. Propensity score matching (PSM) was used to balance baseline characteristics. Of all enrolled patients, 839 (68.1%) patients continued NAs, and 393 (31.9%) patients discontinued NAs. Continuation of NAs was identified as an independent risk factor for RFS (HR 2.047, 95% CI 1.348-3.109, p < 0.001 before PSM and HR 2.756, 95% CI 1.537-4.942, p < 0.001 after PSM) in HBsAg-negative patients. Similarly, subgroup survival analyses showed that NA discontinuation was associated with better RFS (p = 0.029 before PSM and p < 0.001 after PSM) and comparable OS (p = 0.935 before PSM and p = 0.115 after PSM) than NA continuation in HBsAg-negative patients. The interaction between HBsAg status and continuation or discontinuation of NAs was significant (p for interaction <0.001). These findings demonstrate the potential for HBeAg-negative HBV-related HCC patients who have achieved HBsAg seroclearance to discontinue NAs under strict monitoring.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma.

Post-hepatectomy liver failure (PHLF) is a common consequence of radical partial hepatectomy in hepatocellular carcinoma (HCC). To investigate the relationship between preoperative antiviral therapy and PHLF, as well as assess the potential efficacy of hepatitis B virus (HBV) DNA level in predicting PHLF. A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy. Receiver operating characteristic (ROC) analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses. Logistic regression analyses were performed to assess the independent risk factors of PHLF. The increase in the area under the ROC curve, categorical net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to quantify the efficacy of HBV DNA level for predicting PHLF. The P < 0.05 was considered statistically significant. Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF (P < 0.05). HBV DNA level with an optimal cutoff value of 269 IU/mL (P < 0.001) was an independent risk factor of PHLF. All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve, categorical NRI, and IDI, particularly for the fibrosis-4 model, with values of 0.729 (95%CI: 0.705-0.754), 1.382 (95%CI: 1.341-1.423), and 0.112 (95%CI: 0.110-0.114), respectively. All the above findings were statistically significant. In summary, preoperative antiviral treatment can reduce the incidence of PHLF, whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

An Extensive Pharmacological Evaluation of New Anti-carcinoma CDK1 and SERPINE1 Targeted Compound Homoorientin from T.officinale's with In-depth Molecular Docking and Simulation Studies.

Hepatitis B Virus-Related Hepatocellular Carcinoma (HBV- HCC) constitutes a formidable global health challenge, demanding an in-depth understanding of its intricate pathogenesis. The research conducted a comprehensive analysis of the multifaceted relationship between HBV-HCC. It further examined the potential of Taraxacum officinale, which could serve as an effective adjunct therapy in treating HBV- associated HCC. Our approach integrates network pharmacology, pathway analysis, molecular docking, and dynamics simulations, offering an intricate unraveling of the molecular mechanisms that underlie T. officinale's potential impact on HBV-HCC. Additionally, we delve into microarray analysis to unearth differentially expressed genes (DEGs) associated with HBV-HCC, molecular docking to validate compound interactions with key proteins, and molecular dynamics simulations to elucidate the stability of these interactions. These multifaceted approaches enhance our understanding of T. officinale's therapeutic potential. This work represents a significant advancement toward the development of more effective strategies for the management of this challenging disease, offering a comprehensive exploration of T. officinale's therapeutic prowess. Within this multidimensional framework, we identify CDK1, SERPINE1, and PTGS2 as promising therapeutic targets, shedding light on the molecular intricacies of disease progression. Further, Homoorientin from T. officinale's demonstrates a strong binding affinity with proteins CDK1, SERPINE1, and PTGS2, suggesting a potential synergistic effect in therapeutic applications. Moreover, our enrichment analysis uncovers a rich tapestry of pathways enriched in HBV-HCC, providing insights into the multifaceted landscape of disease complexity. These findings not only pave the way for potential targeted therapies but also deepen our comprehension of the intricate molecular underpinnings of HBV-HCC. This work represents a significant advancement toward the development of more effective strategies for the management of this challenging disease, offering a multifaceted exploration of T. officinale's therapeutic potential.

Evaluation of Serum Kallistatin in Patients with Hepatocellular Carcinoma

Abstract Background Liver cirrhosis is the most frequent long-term consequence of all chronic liver diseases. Cirrhosis is often asymptomatic and unsuspected until complications. The annual incidence rates of liver cirrhosis and hepatocellular carcinoma is related with chronic hepatitis B or C all over the world. The majority of patients with liver cirrhosis or hepatocellular carcinoma die from complications, which happened relatively early in the course of the disease. Thus, the early diagnosis of liver diseases is the only solution for this great problem. Aim of the Work In the current study we aimed to evaluate serum kallistatin in Egyptian patients with hepatitis C virus related liver cirrhosis and hepatocellular carcinoma. Patients and Methods This case control study enrolled 90 Egyptian subjects aged ≥ 18 years old at Ain shams university hospitals, participants were classified into 3 groups as follow: Group 1: 30 patients with hepatocellular carcinoma (patients have been diagnosed with triphasic CT). Group 2: 30 patients with hepatitis C virus related liver cirrhosis (patients diagnosed according to clinical, laboratory and radiological findings. Group 3: 30 healthy subjects serving as a control group. Results This study found that patients with liver cirrhosis and HCC have lower levels of serum Kallistatin compared to a control group. In the HCC group, patients with more severe liver disease (Child class C) had lower Kallistatin levels than those with less severe disease (Child class A and B). Kallistatin was negatively correlated with certain markers of liver disease and inflammation in both groups, and positively correlated with hemoglobin and albumin. The study also tested the diagnostic accuracy of Kallistatin for detecting liver cirrhosis and HCC, and found that it had 66.5% accuracy for cirrhosis and 98% accuracy for HCC at specific cutoff points. Conclusion Serum Kallistatin has a potential rule as a new biomarker for the diagnosis and evaluation of liver cirrhosis and HCC. The present study was limited by the small sample size. Also, all participants were from the Egyptian population with liver disease induced by HCV- infection with no information if our findings would be valid for other population with different etiologies. Thus, further investigation should be carried out in order to validate these findings

WED-438-YI Real-world based cost effectiveness analysis of entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy

WED-438-YI Real-world based cost effectiveness analysis of entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy

Discovering urinary protein biomarkers for hepatocellular carcinoma in the population of patients with chronic hepatitis B: A single-center case-control study.

e16230 Background: Chronic hepatitis B (CHB) can result in hepatocellular carcinoma (HCC) imposing a substantial health and economic burden worldwide. Early detection of hepatitis B virus-related HCC (HBV-HCC) in CHB with potential biomarkers has emerged as an urgent and challenging task. Recent progression of urinary proteomics provides a promising method for HBV-HCC biomarker discovery. Methods: This single-center case-control study, conducted at Peking Union Medical College Hospital, enrolled 33 patients with HBV-HCC, 26 patients with CHB, 30 healthy controls, and 33 controls with other types of cancer. Urine proteomes were analyzed using liquid chromatography with tandem mass spectrometry by data-dependent acquisition or parallel reaction monitoring, respectively. Differential analysis was carried out with limma package in R software, and the origin of selected proteins was confirmed with immunohistochemistry of surgical specimens. The diagnostic performance of the biomarker panel was evaluated with area under receiver operator curves (AUROC). Results: 21 urinary proteins were significantly upregulated in HBV-HCC compared with CHB samples, playing key roles in vesicular transportation, cytoskeleton-extracellular matrix interaction, and tumor development according to enrichment analysis. Immunohistochemistry validated the differential expression of 4 urinary proteins (4UP: HNRNPM, ADGRG1, APOC1, and RALA) across cancerous and adjacent normal liver tissues. These proteins were specifically found in HBV-HCC but not in CHB, healthy control, or other cancer controls. The AUROCs of 4UP individually (0.642 for APOC1, 0.780 for HNRNPM, 0.755 for ADGRG1, 0.729 for RALA) were no worse than that of serum α-fetoprotein (AUROC = 0.751), and the 4UP panel unified via logistic regression showed an AUROC of 0.828. Conclusions: Urinary proteomics revealed HNRNPM, ADGRG1, APOC1, and RALA as biomarkers to distinguish HBV-HCC from CHB. The 4UP could be traced back to HBV-HCC tumor cells, shedding light on pathogenesis of HBV-HCC. [Table: see text]

Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma

Background and aimsHepatocellular carcinoma (HCC), which is prevalent worldwide and has a high mortality rate, needs to be effectively diagnosed. We aimed to evaluate the significance of plasma microRNA-15a/16-1 (miR-15a/16) as a biomarker of hepatitis B virus-related HCC (HBV-HCC) using the machine learning model. This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. MethodsUsing quantitative polymerase chain reaction, we measured the plasma miR-15a/16 levels in a total of 766 participants, including 74 healthy controls, 335 with chronic hepatitis B (CHB), 47 with compensated liver cirrhosis, and 310 with HBV-HCC. The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein (AFP). Lastly, to validate the diagnostic efficiency of miR-15a/16, we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. ResultsPlasma miR-15a/16 was significantly decreased in HCC than in all control groups (P < 0.05 for all). In the training cohort, the area under the receiver operating characteristic curve (AUC), sensitivity, and average precision (AP) for the detection of HCC were higher for miR-15a (AUC = 0.80, 67.3%, AP = 0.80) and miR-16 (AUC = 0.83, 79.0%, AP = 0.83) than for AFP (AUC = 0.74, 61.7%, AP = 0.72). Combining miR-15a/16 with AFP increased the AUC to 0.86 (sensitivity 85.9%) and the AP to 0.85 and was significantly superior to the other markers in this study (P < 0.05 for all), as further demonstrated by the detection error tradeoff curves. Moreover, miR-15a/16 impressively showed potent diagnostic power in early-stage, small-tumor, and AFP-negative HCC. A validation cohort confirmed these results. Lastly, the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16. ConclusionsWe developed and validated a plasma miR-15a/16-based machine learning model, which exhibited better diagnostic performance for the early diagnosis of HCC compared to that of AFP.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome.

Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.