scholarly journals Mutations in TP53 and CTNNB1 in Relation to Hepatitis B and C Infections in Hepatocellular Carcinomas from Thailand

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Olivier Galy ◽  
Isabelle Chemin ◽  
Emilie Le Roux ◽  
Stéphanie Villar ◽  
Florence Le Calvez-Kelm ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Hcv Infection ◽  
Hbv Infection ◽  
The Other ◽  
Hepatocellular Carcinomas ◽  
Induced Mutagenesis

Hepatocellular carcinoma (HCC) may develop according to two major pathways, one involving HBV infection and TP53 mutation and the other characterized by HCV infection and CTNNB1 mutation. We have investigated HBV/HCV infections and TP53/CTNNB1 mutations in 26 HCC patients from Thailand. HBV DNA (genotype B or C) was detected in 19 (73%) of the cases, including 5 occult infections and 3 coinfections with HCV. TP53 and CTNNB1 mutations were not mutually exclusive, and most of TP53 mutations were R249S, suggesting a significant impact of aflatoxin-induced mutagenesis in HCC development.

scholarly journals Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh

2013 ◽  
Vol 38 (3) ◽  
pp. 104-107 ◽  
Author(s):  
MA Mahtab ◽  
SMF Akbar ◽  
S Rahman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Healthy Subjects ◽  
Hepatitis B Surface Antigen ◽  
Hbv Dna ◽  
Hbv Infection ◽  
B Virus ◽  
Control And Management

Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B virus (HBV) infection in Bangladesh and most other developing countries. However, some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may cause HBV infection in recipients. HBV DNA was checked in 20 patients with cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without any known etiology, and 10 apparently healthy subjects with elevated levels of serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma, and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them were negative for HBsAg in the sera. This study indicates that some additional mechanisms should be developed for detection of HBsAg-negative HBV-infected subjects for efficient control and management of HBV infection in Bangladesh. DOI: http://dx.doi.org/10.3329/bmrcb.v38i3.14337 Bangladesh Med Res Counc Bull 2012; 38(3): 104-107 (December)

scholarly journals Hepatitis B virus (HBV) DNA integration in patients with occult HBV infection and hepatocellular carcinoma

2015 ◽  
Vol 35 (10) ◽  
pp. 2311-2317 ◽  
Author(s):  
Carlo Saitta ◽  
Gianluca Tripodi ◽  
Adalberto Barbera ◽  
Antonio Bertuccio ◽  
Antonina Smedile ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Occult Hbv Infection ◽  
Dna Integration ◽  
Occult Hbv ◽  
B Virus ◽  
Hbv Dna Integration

scholarly journals MicroRNA miR-212-3p targets NFIA to suppress HBV replication and tumor progression in hepatocellular carcinoma via repressing Enhancer I activity

2021 ◽  
Author(s):  
Hui Tian ◽  
Zhenkun He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Cell Viability ◽  
Hbv Dna ◽  
Hbv Infection ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Hbv Replication ◽  
Dual Luciferase Reporter Assay

IntroductionEmerging evidence identifies that microRNAs (miRNAs) are associated with hepatitis B virus (HBV) infection. In the current study, we mainly focus on the functions and underlying mechanisms of miR-212-3p in HBV replication in hepatocellular carcinoma (HCC).Material and methodsThe levels of miR-212-3p, nuclear factor I A (NFIA) and HBV DNA copies were measured by qRT-PCR. The level of core particle-associated HBV DNA, the productions of hepatitis B surface antigen (HBsAg) and hepatitis B e-antigen (HBeAg), and the expression of NFIA were detected via southern blot assay, ELISA and western blot assay, respectively. The putative target of miR-212-3p was predicted by TargetScan and Pictar, followed by the dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay to validate the interaction. The interaction between miR-212-3p and Enhancer I/X promoter (EnI/Xp) reporter was also verified by dual luciferase reporter assay. In addition, the cell viability and apoptotic rate were detected by MTT and flow cytometry, respectively.ResultsmiR-212-3p mimics or NFIA knockdown inhibited HBV expression and replication in HepG2.2.15 cells, while miR-212-3p inhibitor or NFIA overexpression showed the opposite trend. NFIA was confirmed as a direct target of miR-212-3p. Furthermore, miR-212-3p impeded HBV expression and replication by suppressing NFIA. Besides, miR-212-3p lowered EnI/Xp activity by regulating NFIA. In addition, miR-212-3p retarded cell viability and induced apoptosis through targeting NFIA.ConclusionsmiR-212-3p targets NFIA to down-regulate its expression, thereby inhibiting HBV replication and tumorigenesis in HCC. Our finding might provide a promising therapeutic target for HBV infection.

scholarly journals Interleukin-34 is associated with hepatocellular carcinoma in chronic hepatitis B patients

2020 ◽  
Author(s):  
Kehui Liu ◽  
Yezhou Ding ◽  
Yun Wang ◽  
Qingqing Zhao ◽  
Lei Yan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Tumor Size ◽  
Hbv Dna ◽  
The Other ◽  
Tumor Differentiation ◽  
Tumor Number ◽  
Control Serum ◽  
B Virus ◽  
Healthy Control

Abstract Backgrounds: IL‑34 is involved in a number of auto-immunities and cancers. We explored the relationship between serum/hepatic IL‑34 and hepatitis B virus (HBV) related hepatocellular carcinoma (HBV‑HCC) patients.Methods: Serum was obtained from the HBV patients or healthy control with written consents. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV‑HCC patients. Serum IL‑34 and MCSF were measured, using ELISA. HepaticIL‑34, MCSF and CD68 were determined, using immunohistochemistry.Results: Serum IL‑34 was 1.7, 1.6 or 1.7 fold higher in HBV‑HCC than that of the other three groups (CHB, HBV related cirrhosis, and healthy control). Serum IL‑34 was significantly reduced after trans‑hepatic arterial chemoembolization (TACE) in HBV‑HCC patients. There was significant correlation between the incidence of HBV‑HCC and IL‑34 (rs=0.160, p<0.05) as well as AFP (rs=0.442, p<0.01). Furthermore, intra-hepatic IL‑34 was higher in HBV‑HCC than that of the other three groups. Intra-hepatic IL‑34 was associated with high HBV‑DNA, HBeAg-, low tumor differentiation and small tumor size of HBV‑HCC patients. Intra-hepaticCD68+ TAMs were increased 1.6 or 1.3 fold in HBV‑HCC compared to that from CHB or HBV-cirrhosis. Intra-hepatic CD68+ TAMs were associated with high HBV‑DNA, high tumor differentiation, big tumor size, abnormal AFP and more tumor number.Conclusions: IL‑34, correlated with HBV‑HCC and IL‑34, may be used as a therapeutic target in precise medicine for management of HBV‑HCC.

Assessment of miR-212 and Other Biomarkers in the Diagnosis and Treatment of HBV-infection-related Liver Diseases

2019 ◽  
Vol 20 (10) ◽  
pp. 785-798 ◽  
Author(s):  
Yigan Zhang ◽  
Huaze Xi ◽  
Xin Nie ◽  
Peng Zhang ◽  
Ning Lan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Diseases ◽  
Meld Score ◽  
Hbv Infection ◽  
Expression Level ◽  
Control Group

Objective: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.

scholarly journals Clinical value evaluation of microRNA-324-3p and other available biomarkers in patients with HBV-infection-related hepatocellular carcinoma

2021 ◽  
Author(s):  
Li Zhao ◽  
Qian Yang ◽  
Jianbo Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Hepatitis B ◽  
Diagnostic Performance ◽  
Cox Regression ◽  
Hbv Infection ◽  
Healthy Controls ◽  
Survival Prognosis ◽  
Diagnosis And Prognosis ◽  
Hcc Cells

Abstract Background Patients with hepatitis B virus (HBV) infection are at high risk of hepatocellular carcinoma (HCC). This study aimed to evaluate the expression of microRNA-324-3p (miR-324-3p) in HBV-related HCC, and explore the clinical significance of serum miR-324-3p and other available biomarkers in the diagnosis and prognosis of HBV-related HCC. Methods Expression of miR-324-3p in HBV-infection-related cells and patients was estimated using quantitative real-time PCR. The receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of serum miR-324-3p, AFP and PIVKA-II in the differentiation of HBV-related HCC from healthy controls and chronic hepatitis B (CHB). The relationship between serum miR-324-3p and patients’ clinical features was assessed using Chi-square test, and the value of miR-324-3p to predict overall survival prognosis was evaluated using Kaplan-Meier methods and Cox regression assay in patients with HBV-related HCC. Results HBV-related HCC cells had significantly increased miR-324-3p compared with normal and HBV-unrelated HCC cells, and serum miR-324-3p in HCC patients with HBV infection was also higher than that in healthy controls and CHB. Serum miR-324-3p had relatively high diagnostic accuracy for the screening of HCC case with HBV infection, and the combination of miR-324-3p, AFP and PIVKA-II showed the improved diagnostic performance. Additionally, high serum miR-324-2p in HBV-related HCC patients was associated with cirrhosis, tumor size, clinical stage and poor overall survival prognosis. Conclusion Serum increased miR-324-3p may be involved in the progression of HBV-related hepatitis to HCC, and may serve as a candidate biomarker for the diagnosis and prognosis of HBV-related HCC.

272 Use of LioCyx-M, autologous hepatitis B virus (HBV)-Specific T cell receptor (TCR) T-cells, in advanced HBV-related hepatocellular carcinoma (HCC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A297-A297
Author(s):  
Fu-Sheng Wang ◽  
Fanping Meng ◽  
Jiehua Jin ◽  
Yuanyuan Li ◽  
Regina Wanju Wong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Receptor ◽  
Dose Level ◽  
Cell Receptor ◽  
Hbv Dna ◽  
B Virus

BackgroundWe have demonstrated the ability of Hepatitis-B-virus (HBV)-specific T cell receptor (TCR) bioengineered T cells to recognize and lyse Hepatocellular carcinoma (HCC) cells expressing HBV antigens derived from HBV-DNA integration in patients with liver transplant.1 LioCyx-M is an immunotherapeutic product composing of autologous T cells transiently modified with in-vitro transcribed mRNA encoding HBV-specific TCR. The transient TCR expression makes LioCyx -M amenable to a dose escalating posology.MethodsThe primary endpoint of this phase 1 trial is to assess the safety and tolerability of LioCyx-M in patients with advanced HBV-HCC without curative treatment options. Eligible patients were diagnosed with Barcelona clinic liver cancer stage B or C HCC (Child-Pugh < 7 points), receiving >1 year antiviral treatment prior to enrollment. These patients had matching HLA class I genotypes which present HBV encoded antigen. Peripheral blood was collected from each patient prior to each dose for LioCyx-M manufacturing. Patients received 4 escalating doses of 1×104 cells/kg, 1×105 cells/kg, 1×106 cells/kg, 5×106 cells/kg bodyweight (BW) in the first treatment cycle, each intravenously administered weekly. Patients underwent 1-month safety assessment post the 4th infusion, according to Common Terminology NCI CTCAE Version 4.0.3. If there were no dose associated toxicities, patients were eligible to continue administration of LioCyx-M at dose of 5 × 106 cells/kg BW weekly. Tumor response per RECIST 1.1 criteria and survival time were assessed.ResultsAt data cutoff (30 April 2020), eight patients were enrolled, with a median age of 53 (range: 49 - 67). These patients received a median number of 6 (range: 4 - 12) infusions of LioCyx-M. 1 patient developed Grade 3 elevations in alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and bilirubin after receiving LioCyx-M at dose level of 1×105 cells/kg BW. Another patient had Grade 1 transient fever after receiving LioCyx-M at dose level 5×106 cells/kg BW in the 4th, 5th and 6th infusions. No treatment-related adverse events (trAEs) such as cytokine release syndrome or neurotoxicity were observed. No fatal trAEs were observed. The median time to progression was 1.9 months (range: 0.2 - 9.5 months). The median overall survival was 34 months (range: 3 - 38.2 months).ConclusionsThe encouraging clinical outcome and tolerable safety highlight the good benefit-risk profile of LioCyx-M. Therefore, further exploration of efficacy of LioCyx-M treatment for advanced HBV-HCC is warranted in a Phase 2 proof-of-concept clinical study.AcknowledgementsFunding: Lion TCR.Trial RegistrationNCT03899415Ethics ApprovalThe study was approved by Fifth Medical Center of Chinese PLA General Hospital’s Ethics Board, approval number R2016185DI010.ReferenceTan AT, Yang N, Lee Krishnamoorthy T, et al. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology 2019;156(6):1862–1876.e9.

High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection

2013 ◽  
Vol 62 (8) ◽  
pp. 1235-1238 ◽  
Author(s):  
Inmaculada Castillo ◽  
Javier Bartolomé ◽  
Juan Antonio Quiroga ◽  
Vicente Carreño
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Virus Infection ◽  
Hepatitis B ◽  
Hcv Infection ◽  
Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

scholarly journals Creation of a Six-fingered Artificial Transcription Factor That Represses the Hepatitis B Virus HBx Gene Integrated into a Human Hepatocellular Carcinoma Cell Line

2012 ◽  
Vol 18 (4) ◽  
pp. 378-387 ◽  
Author(s):  
Xinghui Zhao ◽  
Zhanzhong Zhao ◽  
Junwei Guo ◽  
Peitang Huang ◽  
Xudong Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Hbv Infection ◽  
Luciferase Reporter ◽  
Artificial Transcription Factor ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.

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