scholarly journals In situ analysis of hepatitis B virus (HBV) antigen and DNA in HBV-induced hepatocellular carcinoma

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Ye Zheng ◽  
Mingzhu Xu ◽  
Dong Zeng ◽  
Haitao Tong ◽  
Yuhan Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nuclear Localization ◽  
Tumor Tissue ◽  
Staining Pattern ◽  
Hbv Dna ◽  
Surrounding Tissue ◽  
Adjacent Tissue ◽  
B Virus ◽  
Positive Rate

Abstract Aims Hepatitis B Virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in East Asia. Here we aimed to further investigate the abundance of viral antigen and DNA within HBV-related HCC and surrounding tissues at histological level. Method In addition to routine histopathology, in situ hybridization (ISH) of HBV DNA and immunohistochemistry (IHC) of HBsAg were performed in tissues from 131 HBsAg-positive HCC patients undergoing liver resection. Serum α-fetoprotein together with basic biochemical and immunological parameter was also measured. Results Overall, the ISH of HBV DNA and IHC of HBsAg showed 31.3% and 92.9% positive rate respectively (p < 0.0001). The level of correlation between these two markers was much more significant in tumor (p < 0.0001) than in tumor-surrounding tissue (p = 0.01). HBsAg exhibited a much higher positive rate in tumor-adjacent tissue than in tumor tissue (86.6% versus 29.9%, p < 0.0001) with significantly different staining pattern. By contrast, the positive rate of HBV DNA ISH was comparable in tumor and surrounding tissue (17.6% versus 22.9%, p = 0.36). Yet the HBV DNA signal in tumor tissue showed predominant nuclear localization (87.0%) whereas staining pattern in adjacent tissue was mixed (43.3% nuclear localization, p = 0.0015). Finally, no significant association between intra-tumor HBV DNA/HBsAg positivity and major histological markers (microvascular invasion, tumor differentiation, etc.) or recurrence after surgery was observed. Conclusions These data confirmed the largely integrated state of HBV DNA, weaker expression and altered localization of surface antigen in tumor compared with surrounding tissue. The strikingly different prevalence and localization of HBsAg and HBV DNA reflected the complex and heterogeneous mechanisms leading to HBV-induced tumorigenesis.

Real-time quantitation of hepatitis B virus (HBV) DNA in tumorous and surrounding tissue from patients with hepatocellular carcinoma

2002 ◽  
Vol 68 (4) ◽  
pp. 494-499 ◽  
Author(s):  
Isabella Zanella ◽  
Angelo Rossini ◽  
Daniela Domenighini ◽  
Alberto Albertini ◽  
Elisabetta Cariani
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Real Time ◽  
Hbv Dna ◽  
Surrounding Tissue ◽  
B Virus

Detection of HBV-DNA and HBV-related antigens in hepatocellular carcinoma by an in situ hydridization and PAP method.

Kanzo ◽  
1989 ◽  
Vol 30 (8) ◽  
pp. 926-927
Author(s):  
Susumu IMOTO ◽  
Hiroyuki KOKURYU ◽  
Yoshihiro FUKUDA ◽  
Hidetoshi MATSUMOTO ◽  
Mikako OYA ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hbv Dna ◽  
Pap Method

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.

scholarly journals Intermediate-stage hepatocellular carcinoma patients with a high HBV-DNA load may benefit from postoperative anti-hepatitis B virus therapy

Medicine ◽  
2017 ◽  
Vol 96 (30) ◽  
pp. e7608 ◽  
Author(s):  
Shaozhen Rui ◽  
Jun Yan ◽  
Hui Zhang ◽  
Zhengfeng Wang ◽  
Wence Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Intermediate Stage ◽  
Hbv Dna ◽  
B Virus

Comparision of adefovir and lamivudine for patients with hepatitis B virus-related hepatocellular carcinoma after hepatic resection.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 257-257
Author(s):  
Xiao Xiang ◽  
Jian-Hong Zhong ◽  
Yang Ke ◽  
Xue-Mei You ◽  
Ning-Fu Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Antiviral Treatment ◽  
Radical Resection ◽  
Hbv Dna ◽  
Antiviral Resistance ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Medication Costs ◽  
B Virus

257 Background: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few studies have directly compared their therapeutic efficacy and treatment cost. This study aims to compare LAM with ADV head-to-head in these patients. Methods: We retrospectively analyzed 201 patients with HBV-related HCC who underwent radical resection and subsequently received LAM (n = 155) or ADV (n = 46). The two groups were compared in terms of HBV-DNA levels, liver function, antiviral resistance, recurrence-free and overall survival, as well as antiviral medication costs. Results: Despite significant improvement in HBV-DNA and ALT level in the LAM group after 1 year of antiviral therapy, these parameters did not differ significantly between the two groups over the following 2 years. Incidence of antiviral resistance after 1, 2 and 3 years of antiviral treatment was significantly higher in the LAM group (19.5%, 45.7%, 56.4%) than in the ADV group (0%, 3.3%, 14.5%; P < 0.001). Overall survival at 1, 2, 3 years after resection was similar for the LAM group (84.5%, 69.3%, 64.6%) and the ADV group (84.1%, 77.8%, 63.4%; P = 0.905). Recurrence-free survival at the three follow-up points was also similar for the LAM group (71.7%, 58.3%, 43.9%) and the ADV group (81.1%, 66.1%, 53.0%; P = 0.452). Cox regression analysis confirmed that both nucleos(t)ide analogues were associated with similar overall and recurrence-free survival. However, the average medication costs after 1, 2, 3 years of antiviral treatment were significantly higher in the LAM group (€3.0, €4.8, €5.6 per person per day) than in the ADV group (€2.2, €2.4, €3.1 per person per day; all P < 0.05). Conclusions: ADV and LAM are associated with similar survival benefit in patients with HBV-related HCC after radical resection, but ADV is more cost-effective.

scholarly journals Association of Virological Response to Antiviral Therapy With Survival in Intermediate-Stage Hepatitis B Virus-Related Hepatocellular Carcinoma After Chemoembolization

2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Jin ◽  
Yong Chen ◽  
Shuifang Hu ◽  
Meiyan Zhu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Therapy ◽  
Virological Response ◽  
Cox Regression ◽  
Intermediate Stage ◽  
Hbv Dna ◽  
Rank Test ◽  
B Virus

IntroductionRole of response to antiviral therapies on survival of patients with intermediate-stage hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) undergoing transarterial chemoembolization (TACE) remains unknown. We aimed to determine whether virological response (VR) or prolonged maintained virological response (MVR) to nucelos(t)ide analogues (NA) therapy could result in improved survival in HBV-HCC patients receiving TACE.MethodsBetween January 2012 and October 2018, data of patients with intermediate HBV-HCC who underwent TACE and started NA therapy within one week prior to TACE treatment at our institution were reviewed. Overall survival (OS) was compared using the Kaplan-Meier method with log-rank test between different VR status groups. Univariable and multivariable Cox regression analyses were used to determine the association between achievement of VR or MVR and OS. VR was defined as an undetectable HBV DNA level (&lt;100 IU/ml) on two consecutive measurements during NA treatment. MVR was defined as a persistently undetectable HBV DNA level after achieving a VR.ResultsA total of 1265 patients undergoing TACE with a median follow-up time of 18 months (range, 2-78 months) were included in the analysis. Of 1265 NA-treated patients [1123 (88.8%) male, median (range) age, 56 (18-75) years], 744 patients (58.8%) achieved VR and the remaining patients (41.2%) did not. Patients with achievement of VR showed a significantly longer OS than those without VR (median OS: 21 vs 16 months; HR, 0.707; 95% CI, 0.622-0.804; P&lt;0.001). Among patients with VR, MVR was present in 542 patients (72.8%), while the other 202 patients (27.2%) in the non-MVR group. The OS for the MVR group was significantly higher than the non-MVR group (median OS: 23.2 vs 18 months; HR, 0.736; 95% CI, 0.612-0.885; P=0.001). Additionally, patients with MVR status more than two years showed a better OS than those with just one-year (HR, 0.719; 95% CI, 0.650-0.797; P&lt;0.001) or one-to-two-year MVR (HR, 0.612; 95% CI, 0.471-0.795; P=0.024). On multivariable analyses, splenomegaly and up-to-seven criteria were independent prognostic factors of OS in both VR and MVR cohorts.ConclusionsIn patients with intermediate-stage HBV-HCC, both VR to antiviral therapy and prolonged response are associated with prolonged OS after TACE, especially for those within up-to-seven criteria.

scholarly journals Hepatocellular carcinoma and multiple myeloma with elevated globulin: a case report and literature review

2020 ◽  
Vol 48 (5) ◽  
pp. 030006052092039
Author(s):  
Ling Xu ◽  
Wei Yang ◽  
Ye-Fei Shu ◽  
Xiao-Feng Xu
Keyword(s):  
Magnetic Resonance Imaging ◽  
Hepatocellular Carcinoma ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Examination ◽  
Hbv Dna ◽  
Resonance Imaging ◽  
Serum Globulin ◽  
B Virus ◽  
Immunofixation Electrophoresis

A 60-year-old male patient presented with a serum α-fetoprotein (AFP) level of 2940.5 ng/mL accompanied by a significant increase in serum globulin. Hepatitis B virus (HBV) DNA was 2.85 × 103 (normal value <1.0 × 103). B-mode ultrasound and magnetic resonance imaging showed characteristic manifestations and he was clinically diagnosed with hepatocellular carcinoma in January 2015. He received radiofrequency ablation and tenofovir disoproxil anti-HBV therapy and his serum AFP and globulin levels were significantly reduced. In March 2018, he presented at our Hematology Department with fatigue and a pale complexion. At that time, his serum AFP level was normal, with hemoglobin 61 g/L and globulin 64.7 g/L. He was diagnosed with multiple myeloma (MM) by bone marrow examination, and immunofixation electrophoresis. The patient received PCD chemotherapy (bortezomib 2.0 g/dL on days 1, 4, 8, and 11 plus cyclophosphamide 0.3 g/dL on days 1–4 plus dexamethasone 20 mg/dL on days 1–2, 4–5, 8–9, and 11–12). The patient finally died of MM complicated by disseminated intravascular coagulation.

Role of hepatitis B virus genotypes and quantitative HBV DNA in metastasis and recurrence of hepatocellular carcinoma

2008 ◽  
Vol 80 (4) ◽  
pp. 591-597 ◽  
Author(s):  
Yuehua Huang ◽  
Zhanhui Wang ◽  
Shengli An ◽  
Bin Zhou ◽  
Yuanping Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hbv Dna ◽  
B Virus ◽  
Virus Genotypes
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