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Wang J, Hou H, Mao L, Wang F, Yu J, Luo Y, Lin Q, Sun Z. TIGIT Signaling Pathway Regulates Natural Killer Cell Function in Chronic Hepatitis B Virus Infection. Front Med (Lausanne) 2022; 8:816474. [PMID: 35265633 PMCID: PMC8898961 DOI: 10.3389/fmed.2021.816474] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/29/2021] [Indexed: 12/24/2022] Open
Abstract
Background and Objective Persistent infection of hepatitis B virus (HBV) and liver damage in immune active chronic hepatitis B (CHB) could be partly due to the overreaction of natural killer (NK) cells, including pro-inflammatory cytokine secretion and cytotoxicity. An immunosuppressive receptor, T-cell immunoglobulin and immunoreceptor tyrosine–based inhibitory motif (ITIM) domain (TIGIT) is specifically expressed in NK cells. This study aims to investigate the role of the TIGIT signaling pathway in regulating NK cell functions in patients with CHB. Method We comparatively assessed the expression of TIGIT in NK cells of patients with immune active CHB (CHB-IA), carriers of immune control chronic HBV (CHB-IC), and healthy controls (HCs), and then explored mechanisms of the TIGIT signaling pathway in regulating NK cell-mediated liver injury by different molecular assessments. Result The expression of TIGIT in NK cells was enhanced in CHB-IC but was reduced in CHB-IA compared with the HC group. In patients with CHB-IA, the expression of TIGIT was inversely correlated with intensity of the liver damage. Moreover, TIGIT-NK cells show higher IFN-γ secretion capability, degranulation activity, and cytotoxicity but lower apoptosis than TIGIT+ NK cells. Blockade of the TIGIT pathway with anti-TIGIT antibody increased NK cell function, while activation of the TIGIT pathway with TIGIT Fc and CD155 Fc chimera protein down-regulated NK cell function. Conclusion Our data showed that the TIGIT signaling pathway participates in NK cell impairment, which could be used as a new therapeutic target to protect patients with chronic HBV infection from severe liver injury.
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Affiliation(s)
- Juan Wang
- Department of Blood Transfusion, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Hongyan Hou
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Lie Mao
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Feng Wang
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Yu
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Luo
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Qun Lin
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Ziyong Sun
- Department of Laboratory Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
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Khoo T, Lam D, Olynyk JK. Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease. World J Gastroenterol 2021; 27:4831-4845. [PMID: 34447229 PMCID: PMC8371504 DOI: 10.3748/wjg.v27.i29.4831] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/14/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts. Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients. The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments. Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence, the number of new infections. Antiviral treatments have decreased the rates of liver decompensation and as a result, lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection. The quality of life of chronically infected patients has also been improved significantly by modern treatment. Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis. Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation. This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.
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Affiliation(s)
- Tiffany Khoo
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia
| | - Danielle Lam
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia
| | - John K Olynyk
- Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch 6150, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia
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Chang CH, Liu CY, Chen SJ, Tsai HC. Hepatitis C virus and hepatitis B virus in patients with schizophrenia. Medicine (Baltimore) 2021; 100:e26218. [PMID: 34087899 PMCID: PMC8183751 DOI: 10.1097/md.0000000000026218] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 05/17/2021] [Indexed: 01/04/2023] Open
Abstract
This study evaluated the severe hepatic outcome (SHO) in patients with schizophrenia and viral hepatitis who received antipsychotics.Using the nationwide Taiwan National Health Insurance Research Database, patients first diagnosed with schizophrenia between 2002 and 2013 were identified. Patients diagnosed with schizophrenia who had viral hepatitis, including hepatitis B virus (HBV) or hepatitis C virus (HCV), were designated as the viral hepatitis group. A control group without viral hepatitis was matched for age, sex, and index year in a 2:1 ratio. Patients with severe hepatic outcomes before enrollment were excluded. The 2 cohorts were observed until December 31, 2013. The primary endpoint was occurrence of a SHO, including liver cancer, liver failure, liver decompensation, or transplantation.Among the 16,365 patients newly diagnosed with schizophrenia between January 2002 and December 2013, we identified 614 patients with viral hepatitis and 1228 matched patients without viral hepatitis. Of these 1842 patients, 41 (2.22%) developed SHOs, including 26 (4.23%) in the viral hepatitis group and 15 (1.22%) in the control group, during the mean follow-up period of 3.71 ± 2.49 years. Cox proportional hazard analysis indicated that the SHO risk increased by 3.58 (95% confidence interval [CI]: 1.859-6.754; P < .001) in patients with schizophrenia and viral hepatitis. Moreover, patients with schizophrenia having HCV had a higher SHO risk than those without viral hepatitis (hazard ratio: 5.07, 95% CI: 1.612-15.956; P < .0001). Patients having both schizophrenia and viral hepatitis, especially HCV, had a higher risk of SHOs.
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Affiliation(s)
- Chun-Hung Chang
- Institute of Clinical Medical Science, China Medical University
- Department of Psychiatry & Brain Disease Research Center, China Medical University Hospital, Taichung
- An Nan Hospital, China Medical University, Tainan
| | - Chieh-Yu Liu
- Biostatistical Consulting Lab, Department of Speech Language Pathology and Audiology, National Taipei University of Nursing and Health Sciences, Taipei
| | - Shaw-Ji Chen
- Department of Psychiatry, Taitung MacKay Memorial Hospital, Taitung
- Department of Medicine, Mackay Medical College, New Taipei
| | - Hsin-Chi Tsai
- Department of Psychiatry, Tzu-Chi General Hospital, Hualien City
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, R.O.C
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Jiang L, Li Y, Xu Z, Li X, Li Y, Liu Q, Wang P, Dong Y. Simultaneous electrochemical determination of two hepatitis B antigens using graphene-SnO 2 hybridized with sea urchin-like bimetallic nanoparticles. Mikrochim Acta 2021; 188:109. [PMID: 33660023 DOI: 10.1007/s00604-021-04763-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 02/16/2021] [Indexed: 10/22/2022]
Abstract
The hepatitis B virus (HBV) can cause chronic hepatitis and hepatocellular carcinoma. Hepatitis B surface antigen (HBs-Ag) and Hepatitis B e-antigen (HBe-Ag) are key markers for the diagnosis of HBV. In this study, electrodeposited gold was used as a sensing platform. Three-dimensional (3D) SnO2-loaded graphene sheets functionalized by Thionine (Thi) and ferrocene (Fc) and hybridized by sea urchin-like bimetallic nanoparticles (GS-SnO2-BMNPs) were used as redox probes for labeling antibodies to fabricate sandwich-type immunosensors for the simultaneous determination of HBs-Ag and HBe-Ag. The bimetallic nanoparticles, gold hybrid platinum nanoparticles (Au@Pt) and L-cysteine-connected gold-silver nanoparticles (Ag-cys-Au), have large electroactive surface areas. They were prepared by an efficient and economical method. Additionally, the sea urchin morphology accelerates spatial utilization, thus increasing the number of combination sites. Therefore, the immune probe can load a mass of signal source molecules (Thi and Fc). Furthermore, GS-SnO2-BMNPs (GS-SnO2-Au@Pt and GS-SnO2-Ag-cys-Au) with excellent electrical conductivity and bimetallic synergy can enhance the square wave voltammetry (SWV) signal. SWV was used to record the electrochemical signal by scanning the potential from - 0.6 to 0.6 V (vs. SCE). The signal peaks resulted from the reduction reaction of Thi and Fc, and two signal peaks were completely separate. The peak position and current intensity reflect the identity and level of the corresponding antigens. Therefore, the simultaneous detection of two viral biomarkers was achieved by the proposed immunosensor. The fabricated immunosensor showed a linear concentration range for HBs-Ag (0.01-100 ng·mL-1) and HBe-Ag (0.01-100 ng·mL-1), with detection limits for HBs-Ag and HBe-Ag of 4.67 pg·mL-1 and 4.68 pg·mL-1, respectively. The RSD of HBs-Ag ranged between 2.0 and 4.4%and the recovery was in the range 98.7 to 99.4%. For HBe-Ag the RSD was between 2.6 and 3.3% andrecoveries in the range 99.2 to 100.5% were obtained.
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Affiliation(s)
- Liping Jiang
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China.,College of Engineering, Yantai Nanshan University, Yantai, Shandong, 265700, People's Republic of China
| | - Yueyuan Li
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China
| | - Zhen Xu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China
| | - Xinjin Li
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China
| | - Yueyun Li
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China.
| | - Qing Liu
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China
| | - Ping Wang
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China
| | - Yunhui Dong
- School of Chemical Engineering, Shandong University of Technology, Zibo, 255049, People's Republic of China
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Zhang Z, Zhou Y, Yang J, Hu K, Huang Y. The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis. BMC Cancer 2019; 19:511. [PMID: 31142283 PMCID: PMC6542001 DOI: 10.1186/s12885-019-5735-9] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 05/21/2019] [Indexed: 02/07/2023] Open
Abstract
Background It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir monotherapy among chronic hepatitis B (CHB) patients by analyzing their long-term clinical outcomes. Methods Databases including PubMed, Embase, Cochrane Central Register of Controlled Trial, and ISI Web of Science were fully investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the included articles, two of the authors independently extracted and confirmed relevant data. Review Manager software (RevMan 5.3) was using for meta analysis. Results Seven articles with 3698 patients were finally included in this research, 1574 in tenofovir group and 2124 in entecavir group. For meta analysis, the incidence of HCC was significantly lower among the tenofovir group than entecavir group [rate ratio (95% CI) of 0.66 (0.49, 0.89), P = 0.008], while there was no statistical significance in incidence of death or transplantation [rate ratio (95% CI) of 0.78 (0.55, 1.13), P = 0.19], encephalopathy [risk ratio (95% CI) of 0.72 (0.45, 1.13), P = 0.15] or variceal bleeding [risk ratio (95% CI) of 0.71 (0.34, 1.50), P = 0.37] between the two groups. Conclusion There is a better effect of tenofovir in reducing HCC incidence than entecavir, which indicates tenofovir should be used more widely while treating chronic hepatitis B patients. However before applying, randomized controlled trial and large prospective cohort study should be performed in the future. Electronic supplementary material The online version of this article (10.1186/s12885-019-5735-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Zeyu Zhang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yufan Zhou
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jiajin Yang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Kuan Hu
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yun Huang
- Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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Jia J, Li H, Wang H, Chen S, Wang M, Feng H, Gao Y, Wang Y, Fang M, Gao C. Hepatitis B virus core antigen mutations predict post-operative prognosis of patients with primary hepatocellular carcinoma. J Gen Virol 2017; 98:1399-1409. [PMID: 28640739 PMCID: PMC5656792 DOI: 10.1099/jgv.0.000790] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 03/26/2017] [Indexed: 12/11/2022] Open
Abstract
The aim of this study was to explore the relationship between hepatitis B virus (HBV) core antigen (HBc) mutations and the post-operative prognosis of HBV-related hepatocellular carcinoma (HCC). In total, 98 patients suffering from HBV-related HCC and treated with surgery were enrolled, with a 48 month follow-up. The preCore/Core region of the HBV genome from tumour tissue (TT) and paired adjacent non-tumour tissue (ANTT) of these patients was sequenced, and a phylogenetic tree was reconstructed. The correlations between the viral features and evolutionary divergence of preCore/Core amino acid sequences from 67 paired TTs and ANTTs were analysed. Cox proportional hazard model analysis was applied for post-operative hazard risk evaluation. Phylogenetic analysis revealed that all of the sequences were ascribed to genotype C. The evolutionary divergence of amino acid sequences from matched TTs and ANTTs was significantly negatively correlated with serum and intrahepatic HBV DNA levels. Multivariate analysis showed that the HBc E77 mutation was associated with shorter overall survival, and HBc S87 and P156 mutations were independent risk factors for relapse. Furthermore, in contrast to with patients without the S87 mutation, no correlation was observed between serum HBV DNA and intrahepatic HBV DNA in HCC patients with the S87 mutation. Analysis of the intrahepatic sequence may advance our understanding of viral status; thus, it is useful for prognosis prediction for HBV-related HCC.
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Affiliation(s)
- Jian’an Jia
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
- Department of Laboratory Medicine, 105th Hospital of PLA, Hefei 230031, PR China
| | - Huiming Li
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Hui Wang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
- Department of Clinical Laboratory, First Affiliated Hospital of Chinese PLA’s General Hospital, Beijing 100048, PR China
| | - Shipeng Chen
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Mengmeng Wang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Huijuan Feng
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Yuzhen Gao
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Yunjiu Wang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Meng Fang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
| | - Chunfang Gao
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China
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Shi BM, Lu W, Ji K, Wang YF, Xiao S, Wang XY. Study on the value of serum miR-106b for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol 2017; 23:3713-3720. [PMID: 28611524 PMCID: PMC5449428 DOI: 10.3748/wjg.v23.i20.3713] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 03/07/2017] [Accepted: 03/21/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze the incidence of hepatocellular carcinoma (HCC) in a population that underwent health checkups and had high serum miR-106b levels. METHODS A total of 335 subjects who underwent checkups in the Digestive and Liver Disease Department of our hospital were randomly selected. RT-PCR was used to detect the level of miR-106b in serum samples. Laboratory and imaging examinations were carried out to confirm the HCC diagnosis in patients who had a > 2-fold change in miR-106b levels. Ultrasound-guided biopsy was also used for HCC diagnosis when necessary. On this basis, the clinical data of these subjects, including history of hepatitis virus infection, obesity, long-term history of alcohol use and stage of HCC, were collected. Then, the impact of these factors on the level of miR-106b in serum was analyzed. Furthermore, receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic efficacy of miR-106b for HCC. RESULTS A total of 35 subjects had abnormal serum miR-106b levels, of which 20 subjects were diagnosed with HCC. t-test revealed that the difference in serum miR-106b level in terms of sex, age, history of hepatitis virus infection, obesity and long-term history of alcohol use was not statistically significant. However, serum miR-106b levels in patients with advanced HCC (stage III/IV) was higher than in patients with early HCC (stage I/II), and the difference was statistically significant (P = 0.000). Moreover, the ROC curve revealed that the area under the curve value for miR-106b was 0.885, which shows that serum miR-106b level has a certain clinical value for HCC diagnosis. CONCLUSION The random sampling survey shows that serum miR-106b level is a valuable diagnostic marker for HCC. However, the diagnostic threshold value needs to be further researched.
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