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Manea M, Mărunțelu I, Constantinescu I. Extended analysis on peripheral blood cytokines correlated with hepatitis B virus viral load in chronically infected patients - a systematic review and meta-analysis. Front Med (Lausanne) 2024; 11:1429926. [PMID: 39149606 PMCID: PMC11325457 DOI: 10.3389/fmed.2024.1429926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 07/08/2024] [Indexed: 08/17/2024] Open
Abstract
Background Hepatitis B Virus (HBV) can affect life quality. Monitoring and understanding the fluctuations of the HBV level of viremia related to the intricate immune activity of the host helps in the development of new treatment strategies and evaluation patterns. This meta-analysis presents the correlations between cytokines and the level of viremia in chronic HBV patients for a better comprehension of the immune mechanisms behind this infection. Methods We used PRISMA guidelines for this meta-analysis. The databases assessed were PUBMED, WEB OF SCIENCE, SCOPUS, and Cochrane Library. ZOTERO and PlotDigitizer helped the systematic research process. We extracted information related to the correlations between cytokines and the HBV-DNA level. Effect measures included comparisons between standardized mean differences and correlation coefficients. We evaluated retrieved articles with the Newcastle-Ottawa Quality Assessment Scale (NOS). The R 4.2.2 software displayed the statistical calculation and graphical representations. Results From 58,169 records, we extracted 16 articles with 32 different cytokine determinations. The main interleukins included in detection panels were IL-10 and IL-21. The meta-correlation analysis comprised 1,199 chronic HBV patients. The standardized mean difference between cytokine levels in HBV patients and healthy controls was 0.82 (95% CI = [-0.19, 1.84], p = 0.11). We observed a significant, fair, pooled correlation coefficient between IL-10, IL-9, and the viral load (r = 0.52, 95% CI = [0.19, 0.85]). Conclusion This meta-analysis brings novelty because it gives a first rigorous systematic look at multiple studies with many cytokines. Our research approaches a debatable issue and gives a possible solution for settling controversies. Future studies can arise towards understanding the immune disruption in HBV and the development of new, improved assays for prognosis.
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Affiliation(s)
- Marina Manea
- Immunology and Transplant Immunology, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
| | - Ion Mărunțelu
- Immunology and Transplant Immunology, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
- Center of Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania
| | - Ileana Constantinescu
- Immunology and Transplant Immunology, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
- Center of Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania
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Asghari A, Jafari F, Jameshorani M, Chiti H, Naseri M, Ghafourirankouhi A, Kooshkaki O, Abdshah A, Parsamanesh N. Vitamin D role in hepatitis B: focus on immune system and genetics mechanism. Heliyon 2022; 8:e11569. [PMID: 36411916 PMCID: PMC9674901 DOI: 10.1016/j.heliyon.2022.e11569] [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: 05/02/2022] [Revised: 08/01/2022] [Accepted: 11/07/2022] [Indexed: 11/16/2022] Open
Abstract
According to the World Health Organization (WHO) report, viral hepatitis has been a problem in human society. Vitamins play a significant role in preventing the hepatocarcinoma and liver cirrhosis. In this report, we will first focus on the vitamin D function in the immune system reactions, and then investigate its role in the viral infections and the signaling pathway of hepatitis B virus. The existence of the cytochrome P450 (CYP) 27B1 enzyme, which is involved in vitamin D synthesis in immune system cells, has drawn researchers ' attention to the field of immune system. Toll like receptor (TLR) play a significant role in the immune system, and are one of the primary receptors of the innate immune system. In addition, the synthesis of inflammatory cytokines, such as Interferon γ (IFNγ) and Interleukin-2 (IL-2) is one of the key roles of T helper type 1 (Th1) cells; these cells can suppress two cited cytokines via vitamin D. In the chronic phase of hepatitis B, Cytotoxic T lymphocytes (CTLs) cells have weaker performance than the acute phase of the disease. The association between vitamin D physiologies with viral infections is also confirmed by genetic studies, carried out on genetic variations of vitamin D receptor (VDR) R-encoding disease susceptibility gene. Vitamin D affects different phases of the disease. Therefore, further experiments in this area are proposed.
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Affiliation(s)
- Arghavan Asghari
- Infectious Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
- Birjand University of Medical Sciences, Birjand, Iran
| | - Fatemeh Jafari
- Radiation Oncology Research Center, Iran Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Radiation Oncology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Jameshorani
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
- Department of Internal Medicine, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
| | - Hossein Chiti
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
| | - Mohsen Naseri
- Department of Immunology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | | | | | - Alireza Abdshah
- School of Medicine, Tehran University of Medical Science, Tehran, Iran
| | - Negin Parsamanesh
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Science, Zanjan, Iran
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Effects of Tenofovir Combined with Recombinant Human Interferon α-2b on Negative Conversion Rate, Liver Function, Immune Status, and Drug Safety in Patients with Chronic Hepatitis B: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:1889628. [PMID: 35815265 PMCID: PMC9262527 DOI: 10.1155/2022/1889628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 05/25/2022] [Accepted: 05/29/2022] [Indexed: 11/18/2022]
Abstract
Objective To systematically evaluate the clinical value of tenofovir combined with recombinant human interferon α-2b in the treatment of chronic hepatitis B and to provide evidence-based medicine for its popularization and use. Methods The randomized controlled trials (RCTs) of tenofovir combined with recombinant human interferon α-2b in the online database of PubMed, EMBASE, ScienceDirect, Cochrane Library, China knowledge Network (CNKI), China VIP database, Wanfang database, and China Biomedical Literature Database (CBM) were searched. The data included in this study were extracted by two independent researchers. After extracting the data of the study, the Cochrane manual 5.1.0 standard was used to evaluate the bias risk of all the literature included in this study. RevMan5.4 statistical software was used to analyze the collected data by meta. Results Entecavir combined with recombinant human interferon α-2b can inhibit the activity of HBV polymerase and improve the inflammatory response of the liver. Recombinant human interferon α-2b can regulate immune function by inducing T cell differentiation and maturation and enhancing the production of cytokines. The systematic evaluation showed that entecavir combined with recombinant human interferon α-2b had higher serum HBeAg negative conversion rate, higher drug safety compared with entecavir alone, and improved liver function and immune status. Conclusion Tenofovir combined with recombinant human interferon alpha-2b has a high serum HBeAg negative rate and safety profile for the treatment of chronic hepatitis B. The combination treatment can improve liver function and immune status in patients, but more studies with higher methodological quality and longer duration of intervention are needed for further validation.
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Zhao Y, Kong LX, Feng FS, Yang J, Wei G. A simple CD4+ T cells to FIB-4 ratio for evaluating prognosis of BCLC-B hepatocellular carcinoma: a retrospective cohort study. BMC Cancer 2022; 22:311. [PMID: 35321670 PMCID: PMC8941753 DOI: 10.1186/s12885-022-09433-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 03/21/2022] [Indexed: 02/08/2023] Open
Abstract
Introduction Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + . Methods This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival. Results The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P < 0.05). Compared with that in other indices, in logistic and ANN multivariate analysis, CD4 + -to-FIB-4 ratio (CD4+/FIB-4) had the highest importance with 0.716 C-statistic and 145.93 cut-off value. In terms of overall survival rate, HIV infection was not a risk factor (P = 0.589); however, CD4+/FIB-4 ≤ 145.93 significantly affected patient prognosis (P = 0.002). Conclusion HIV infection does not affect the prognosis of BCLC-B HCC, but CD4+ have a significant predictive value. CD4+ played a vital role in HCC and this deserves the attention from physicians. Further, the CD4+/FIB-4 is a clinically valuable effective prognostic indicator for these patients.
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Affiliation(s)
- Yong Zhao
- Department of General Surgery, Chengdu Public Health Clinical Medical Center, Sichuan Province, Chengdu, China
| | - Ling Xiang Kong
- Department of Liver Surgery and Liver transplantation Laboratory, West China Hospital of Sichuan University, Sichuan Province, Chengdu, China
| | - Feng Shi Feng
- Department of General Surgery, Chengdu Public Health Clinical Medical Center, Sichuan Province, Chengdu, China
| | - Jiayin Yang
- Department of Liver Surgery and Liver transplantation Laboratory, West China Hospital of Sichuan University, Sichuan Province, Chengdu, China.
| | - Guo Wei
- Department of General Surgery, Chengdu Public Health Clinical Medical Center, Sichuan Province, Chengdu, China.
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Abstract
Chronic hepatitis B (CHB) remains a global healthcare burden. Although the recent developments in the field have led to a reduction in incidence, the morbidity and mortality including liver cirrhosis and hepatocellular carcinoma (HCC) remain a formidable challenge. Advances in understanding the immunopathogenesis of CHB have led to a recent change in clinical categorization. EASL introduced the term hepatitis B 'e' antigen (HBeAg)-negative chronic infection, to replace the historical term 'inactive carrier' disease phase, the commonest CHB phase. Although this disease phase is associated with a favorable prognosis, it is not a truly 'inactive' disease phase with no ostensible liver disease, as inferred by the previous anachronistic terminology, and the risk of spontaneous reactivation and the potential risk of disease progression and HCC development are not negligible. Likewise, the APASL also uses the term "Incidentally Detected Asymptomatic Hepatitis B surface antigen (HBsAg)-positive Subject (IDAHS)", comprising all HBsAg-positive subjects who are incidentally detected during routine tests, without any previous or present symptoms of liver disease. This entity includes HBV infection with varied stages of liver disease. Antiviral treatment is generally reserved for patients with active inflammation and/or at risk of disease progression and HCC development. HBsAg loss is considered an optimal treatment endpoint, and may also be achievable in HBeAg-negative chronic infection and IDAHS. In light of this, and the emerging novel HBV therapies, lowering the treatment threshold and a 'Treat All' approach should now be considered. In this review, we summarize the literature and guidance on HBeAg-negative chronic infection, and we make a concerted effort to present the reasons why the one-dimensional term 'inactive carrier' should be abandoned.
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Shokoohifar N, Ahmady-Asbchin S, Besharat S, Roudbari F, Mohammadi S, Amiriani T, Khodabakhshi B, Norouzi A, Shahabinasab I. The Impaired Balance of CD4+/CD8+ Ratio in Patients with Chronic Hepatitis B. HEPATITIS MONTHLY 2020; 20. [DOI: 10.5812/hepatmon.96799] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Programmed Cell Death 1 (PD-1) and Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) in Viral Hepatitis. Int J Mol Sci 2017; 18:ijms18071517. [PMID: 28703774 PMCID: PMC5536007 DOI: 10.3390/ijms18071517] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/03/2017] [Accepted: 07/04/2017] [Indexed: 12/21/2022] Open
Abstract
Virus-specific cluster of differentiation 8 (CD8+) cytotoxic T cells (CTL) recognize viral antigens presented on major histocompatibility complex (MHC) class I chains on infected hepatocytes, with help from CD4+ T cells. However, this CTL response is frequently weak or undetectable in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are receptors in the CD28 family of costimulatory molecules, providing inhibitory signals to T cells. The overexpressions of PD-1 and CTLA-4 in patients with viral infection have been shown to associate with functional impairment of virus-specific T cells. In acute viral hepatitis, PD-1 and CTLA-4 are up-regulated during the symptomatic phase, and then down-regulated after recovery. These findings suggest that PD-1 and CTLA-4 have protective effects as inhibitory molecules to suppress cytotoxic T cells which induce harmful destruction of viral infected hepatocytes in self-limited viral hepatitis. In chronic viral hepatitis, the extended upregulations of PD-1 and CTLA-4 are associated with T cell exhaustion and persistent viral infection, suggesting positive correlations between expression of immune inhibitory factors and the chronicity of viral disease. In this review, we summarize recent literature relating to PD-1, CTLA-4, and other inhibitory receptors in antigen-specific T cell exhaustion in viral hepatitis, including hepatitis A, B, C, and others.
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Wang H, Wu D, Wang X, Chen G, Zhang Y, Yan W, Luo X, Han M, Ning Q. Hepatitis B virus surface protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways. Biol Chem 2016; 397:1173-1185. [DOI: 10.1515/hsz-2015-0290] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Accepted: 06/06/2016] [Indexed: 12/30/2022]
Abstract
Abstract
The protein inhibitor of activated STAT1 (PIAS1) plays important roles in regulating virus-induced chronic hepatitis, but the interaction between hepatitis B virus (HBV) and hPIAS1 is not clear. Our aim was to verify if HBV encoding proteins enhance the transcription of hPIAS1 and which cis-elements and transcription factors were involved in the mechanism. In order to do, so a series of molecular biological methods, along with functional and histological studies, were performed. We found that the HBV surface protein (HBs) enhanced hPIAS1 transcription through the activities of TAL1, E47, myogenin (MYOG), and NFI, dependent on the activation of p38MAPK and ERK signaling pathways in vitro, which might contribute to the ineffectiveness of treatment in CHB patients. Furthermore, liver samples from patients with high HBsAg levels and HBV DNA displayed increased hPIAS1 expression and high levels of TAL1, E47, MYOG, and NFI, compared to those patients with low HBsAg levels and HBV DNA, and healthy controls. These findings suggest that the HBs protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways. It provides new potential targets for antiviral therapeutic strategies for controlling HBV-associated diseases.
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Quan M, Li L, Yuan X, Jiang Z, Wang X, Wu H, Li X. Influence of multiple factors on the incidence of occupational blood and body fluid exposures in health care workers in Guizhou, China: A structural equation modeling approach. Am J Infect Control 2015; 43:e73-8. [PMID: 26521935 DOI: 10.1016/j.ajic.2015.07.014] [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: 01/27/2015] [Revised: 07/07/2015] [Accepted: 07/08/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND We investigated the influence of multiple factors on the incidence of occupational blood and body fluid exposures (BBFEs) in health care workers (HCWs) in Guizhou, China, using structural equation modeling (SEM). METHODS SEM tested in general hospitals was evaluated using survey data from a sample of 1,774 HCWs from 25 hospitals in Guizhou, China, between January and April 2014. RESULTS The incidence of occupational BBFEs in HCWs was affected by HCWs' knowledge of safe work practices, HCWs' belief in their ability to use safe work practices, HCWs' use of safe work practices, the workplace safety environment, sufficiency of the controls implemented at health care facilities, and workloads. Knowledge of safe work practices had the most influence on the incidence of occupational BBFE in doctors and laboratory technicians. Ability to use safe work practices had the most influence on the incidence of occupational BBFEs in nurses. CONCLUSION The workplace safety environment, sufficiency of controls implemented at health care facilities, HCWs' knowledge of safe work practices, HCWs' belief in their ability to use safe work practices, HCWs' use of safe work practices, and workload influence the incidence of occupational BBFEs in HCWs.
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Balmasova IP, Yushchuk ND, Mynbaev OA, Alla NR, Malova ES, Shi Z, Gao CL. Immunopathogenesis of chronic hepatitis B. World J Gastroenterol 2014; 20:14156-14171. [PMID: 25339804 PMCID: PMC4202346 DOI: 10.3748/wjg.v20.i39.14156] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Accepted: 04/23/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that “avoid” control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.
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Zgair AK, Ghafil JA, Al-Sayidi RHE. Direct role of antibody-secreting B cells in the severity of chronic hepatitis B. J Med Virol 2014; 87:407-16. [PMID: 25163843 DOI: 10.1002/jmv.24067] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/01/2014] [Indexed: 01/15/2023]
Abstract
Chronic hepatitis B involves different immune cells. The direct role of antibody-secreting B cells in the severity of chronic hepatitis B unclear. In this study, the number of plaque forming cells [PFC-(IgG, IgM, anti-HBc IgG, and anti-HBc IgM)], liver function tests (LFT) [alkaline phosphatase (ALP), alanine aminotransferase (ALT), and total serum bilirubin (TSB)], the levels of IL-10 in sera and in lymphocyte cultures, the number of CD4(+) and CD8(+) cells were measured in the peripheral blood of patients and in the controls. In addition, the hepatocytotoxic effect of anti-HBc and anti-HBe in vitro was studied. The largest number of PFCs was observed in the peripheral blood of patients with chronic hepatitis B. This was concomitant with a decrease in CD4(+) /CD8(+) ratio versus this ratio in asymptomatic HBV carriers and in healthy volunteers (P < 0.05). An increase in immunoglobulin (IgG and IgM) levels, anti-HBc IgG, and anti-HBc IgM levels and LFTs in peripheral blood of patients with chronic hepatitis B was seen. Anti-HBc induced hepatocytotoxicity in vitro. The expression of mRNA and protein for IL-10 production was observed at a significant level in culture of lymphocytes isolated from patients with chronic hepatitis B. In addition, a high level of IL-10 was found only in the sera of patients with chronic hepatitis B. It is concluded that the antibody-secreting B cells and the antibodies, which are produced, play an important role in the severity of chronic hepatitis B, which was related negatively with CD4(+) /CD8(+) ratio and positively with IL-10 expression.
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Affiliation(s)
- Ayaid Khadem Zgair
- Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq; Central Public Health Laboratory, Baghdad, Iraq
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Shi Y, Lan Y, Cao F, Teng Y, Li L, Wang F, Li J, Zhou J, Li Y. Infected hematopoietic stem cells and with integrated HBV DNA generate defective T cells in chronic HBV infection patients. J Viral Hepat 2014; 21:e39-47. [PMID: 24620791 PMCID: PMC4237112 DOI: 10.1111/jvh.12236] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Accepted: 12/12/2013] [Indexed: 12/22/2022]
Abstract
A weak T-cell response plays a key role in the persistence of hepatitis B virus (HBV) infection. We aimed to confirm that T-cell defects in patients with chronic HBV infection are associated with HBV DNA infection of bone marrow (BM) hematopoietic stem cells (HSCs). Using reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH), we observed the transcription of HBsAg coding genes and confirmed the integration of HBV DNA in CD34(+) BM HSCs from chronic HBV infection patients. T cells were generated by coculturing the HSCs with delta-like ligand 1-expressing OP9 (OP9-DL1) cells. The phenotypes of the T cells were then evaluated by flow cytometric (FACS) analysis on days 14 and 25. The results demonstrated that fewer CD3(+) TCRaβ(+) CD3(+) CD4(+) and CD4(+) CD8(+) T cells were generated from the HSCs of the patients than from the healthy controls, (P < 0.01) but the frequency of CD3(+) D8(+) T cells was not significantly different between the two group (P > 0.05). In contrast, CD4(+) CD25(+) T cells were more in the patient group than in healthy controls (P < 0.01) on both days 14 and 25. There were fewer CD3(+) CD4(+) /CD3(+) CD8(+) cells in the patient group than in the healthy control group on day 25 (P < 0.05). Less proliferation and lower levels of IL-2 and IFN- γ were also observed in the patient group compared with the control group (P < 0.05).These data suggest that HBV DNA infected and integrated into the BM HSCs from patients with chronic HBV infection and that these BM HSCs generated defective T cells.
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Affiliation(s)
- Y Shi
- Department of Infectious Disease, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - Y Lan
- Department of Infectious Disease, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - F Cao
- Stem Cell Laboratory, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - Y Teng
- Stem Cell Laboratory, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - L Li
- Hematology Department, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - F Wang
- Department of Infectious Disease, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - J Li
- Hematology Department, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - J Zhou
- Hematology Department, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
| | - Y Li
- Department of Infectious Disease, the First Affiliated Hospital of Harbin Medical UniversityHarbin, China
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13
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Boglione L, Cusato J, Cariti G, Di Perri G, D'Avolio A. The E genotype of hepatitis B: clinical and virological characteristics, and response to interferon. J Infect 2014; 69:81-7. [PMID: 24631900 DOI: 10.1016/j.jinf.2014.02.018] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Revised: 01/24/2014] [Accepted: 02/24/2014] [Indexed: 02/06/2023]
Abstract
OBJECTIVES 10 hepatitis B virus (HBV) genotypes are known with different geographic distribution and response to interferon (IFN) therapy. The E genotype is the more prevalent genotype in West and Central Africa, but few data about response to IFN are available. We describe the epidemiological and clinical characteristics in a cohort of patients immigrants from Africa in our country with HBV E genotype chronic hepatitis infection (CHB). METHODS 63 patients with CHB and E genotype were included; 41 with CHB and low viral load were treated with PEG-IFN monotherapy; 10 with CHB and high viral load with sequential approach (entecavir and PEG-IFN). 12 patients with inactive CHB were followed with blood sample and abdomen ultrasonography every six months. RESULTS The virological response in the monotherapy group was 17.9%. Hepatitis B surface antigen (HBsAg) loss was observed in 1 patient (2.5%); 56 patients (88%) showed at the time of diagnosis of CHB another infectious diseases that required specific treatment before PEG-IFN; this treatment was also affected by an higher incidence of side-effects (>50%). All patients with high viremia showed a primary non-response to PEG-IFN. CONCLUSIONS The HBV E genotype evidences the worse response to PEG-IFN and maybe requires novel treatment options.
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Affiliation(s)
- Lucio Boglione
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy.
| | - Jessica Cusato
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy
| | - Giuseppe Cariti
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy
| | - Antonio D'Avolio
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy.
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Liu H, Li M, Jin M, Jing F, Wang H, Chen K. Public awareness of three major infectious diseases in rural Zhejiang province, China: a cross-sectional study. BMC Infect Dis 2013; 13:192. [PMID: 23627258 PMCID: PMC3644285 DOI: 10.1186/1471-2334-13-192] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Accepted: 04/19/2013] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND This study aimed to investigate the level of awareness of and factors associated with major infectious diseases in rural China and to provide the most recent baseline data for the prevention and control of these diseases. METHODS This cross-sectional study was carried out in Zhejiang province between December 2010 and April 2011. Participants were recruited from 36 villages and interviewed by doctors from the community health service using a structured questionnaire. RESULTS The study sample consisted of 36,377 subjects aged 15 to 80 years old. Study results showed that knowledge of HIV was adequate in 44.21% of rural residents; knowledge of TB was adequate in 52.66% of respondents; and knowledge of HBV was adequate in 60.18% of respondents. People in older age groups and with lower education levels were more likely to have low levels of awareness of these three infectious diseases. Participants in the farming industry had poorer awareness of HIV and HBV, while students and factory workers knew little of TB. The proportions of people reporting being fully satisfied with the control policies for HIV, TB and HBV were 37.70%, 34.25% and 36.12%, respectively. CONCLUSIONS The level of awareness of HIV, TB and HBV is still low among rural residents. Further national disease control plans for major infectious diseases should emphasise effective and comprehensive health education campaigns to increase public awareness of these diseases in rural areas of China.
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Affiliation(s)
- He Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
| | - Mei Li
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
| | - Mingjuan Jin
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
| | - Fangyuan Jing
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
| | - Hui Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
| | - Kun Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
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15
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Parikh N, Nonnemacher MR, Pirrone V, Block T, Mehta A, Wigdahl B. Substance abuse, HIV-1 and hepatitis. Curr HIV Res 2013; 10:557-71. [PMID: 22973853 DOI: 10.2174/157016212803306023] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Revised: 07/16/2012] [Accepted: 09/05/2012] [Indexed: 02/06/2023]
Abstract
During the course of human immunodeficiency virus type 1 (HIV-1) disease, the virus has been shown to effectively escape the immune response with the subsequent establishment of latent viral reservoirs in specific cell populations within the peripheral blood (PB) and associated lymphoid tissues, bone marrow (BM), brain, and potentially other end organs. HIV-1, along with hepatitis B and C viruses (HBV and HCV), are known to share similar routes of transmission, including intravenous drug use, blood transfusions, sexual intercourse, and perinatal exposure. Substance abuse, including the use of opioids and cocaine, is a significant risk factor for exposure to HIV-1 and the development of acquired immune deficiency syndrome, as well as HBV and HCV exposure, infection, and disease. Thus, coinfection with HIV-1 and HBV or HCV is common and may be impacted by chronic substance abuse during the course of disease. HIV- 1 impacts the natural course of HBV and HCV infection by accelerating the progression of HBV/HCV-associated liver disease toward end-stage cirrhosis and quantitative depletion of the CD4+ T-cell compartment. HBV or HCV coinfection with HIV-1 is also associated with increased mortality when compared to either infection alone. This review focuses on the impact of substance abuse and coinfection with HBV and HCV in the PB, BM, and brain on the HIV-1 pathogenic process as it relates to viral pathogenesis, disease progression, and the associated immune response during the course of this complex interplay. The impact of HIV-1 and substance abuse on hepatitis virus-induced disease is also a focal point.
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Affiliation(s)
- Nirzari Parikh
- Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
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16
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Boglione L, D'Avolio A, Cariti G, Milia MG, Simiele M, De Nicolò A, Ghisetti V, Di Perri G. Sequential therapy with entecavir and PEG-INF in patients affected by chronic hepatitis B and high levels of HBV-DNA with non-D genotypes. J Viral Hepat 2013; 20:e11-9. [PMID: 23490378 DOI: 10.1111/jvh.12018] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Accepted: 08/01/2012] [Indexed: 12/14/2022]
Abstract
Complete eradication of hepatitis B virus (HBV) is rarely achieved. Treatment options include currently available nucleos(t)ide analogues and pegylated interferon. The aim of our exploratory study was to assess the effectiveness of sequential therapy for chronic hepatitis B (CHB) vs the current standard of care. We evaluated an association with entecavir and pegylated interferon alfa-2a (PEG-IFN) in 20 patients with hepatitis B, high HBV viremia and genotypes A, B, C and E. Patients received entecavir alone for 12 weeks, then entecavir and PEG-IFN for 12 weeks, lastly PEG-IFN alone for 36 weeks. The results were compared with 20 patients (control group) treated in the past with 48 weeks of PEG-IFN monotherapy. Our results show that complete sustained virological response (SVR) and partial SVR were, respectively, 60% and 80% in the study group and 10% and 30% in the control group; anti-HBe seroconversion rate were 76.9% vs 15%, and anti-HBs seroconversion were 20% vs 0%, respectively. We found a correlation among different genotypes and virological and serological outcomes - genotype C has a better virological response, while genotype A had a better serological response, and E genotype had a poor response. These results show that a sequential approach is a promising strategy of treatment in patients with CHB and high viremia in comparison with PEG-IFN monotherapy. The E genotype seems to have the worse rate of response and requires other treatment strategies.
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Affiliation(s)
- L Boglione
- Department of Infectious Diseases, Amedeo di Savoia Hospital, University of Turin, Turin, Italy
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Engell CA, Pham VP, Holzman RS, Aberg JA. Virologic Outcome of Using Tenofovir/Emtricitabine to Treat Hepatitis B in HIV-Coinfected Patients. ISRN GASTROENTEROLOGY 2011; 2011:405390. [PMID: 21991507 PMCID: PMC3168392 DOI: 10.5402/2011/405390] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2011] [Accepted: 05/18/2011] [Indexed: 12/15/2022]
Abstract
Goal. To study the effect of combination antiviral therapy with tenofovir and emtricitabine or lamivudine with and without prior monotherapy with lamivudine. Study. We reviewed charts of 31 HIV-/HBV-coinfected patients. Twelve 3TC-naïve patients initially received tenofovir plus emtricitabine. Nineteen epivir experienced patients who had previously failed epivir were given tenofovir plus emtricitabine. Results. Baseline median HBV DNA was similar in the epivir-naïve (5.8×107 copies/mL) and experienced group (7.3×107 copies/mL, P = .65). The median time to complete suppression of HBV was 466 days in the naïve group and 877 days in the experienced (P = .001). After 12 months, 6/10 (60%) naïve patients and 3/14 (21%) experienced patients had HBV DNA below the detectionlimit (P = .067). After 24 months, 5/5 (100%) naïve patients and 4/13 (31%) experienced patients had an undetectable HBV DNA level (P = .015). Conclusions. The median time to suppression of HBV DNA was significantly shorter among treatment naïve patients. There was a significantly greater proportion of naïve patients with suppressed HBV DNA at 24 months. Our results support using initial dual therapy in those with HIV/HBV coinfection.
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Affiliation(s)
- Christian A Engell
- Department of Medicine, Division of Infectious Diseases and Immunology, New York University School of Medicine at Bellevue Hospital Center, New York, NY 10016, USA
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18
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Pandey RS, Dixit VK. Evaluation of ISCOM vaccines for mucosal immunization against hepatitis B. J Drug Target 2010; 18:282-91. [PMID: 19958131 DOI: 10.3109/10611860903450015] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Immune stimulating complexes (ISCOMs) incorporating recombinant hepatitis B surface antigen (HBsAg) was prepared for induction of humoral, cellular and mucosal immunity by intranasal administration. Prepared ISCOMs were characterized for its size, shape, incorporation efficiency, zeta potential, and antigen integrity. Designed ISCOMs possessed negative zeta potential (-21.7 mV) and an average size of 44.1 nm with antigen incorporation efficiency approximately 39 %. Serum anti-HBsAg IgG titer after three high nasal doses of ISCOMs was comparable with titer recorded after alum-HBsAg administered subcutaneously. Similarly, modest but higher cellular response (cytokines level in spleen homogenates) and significantly higher secretory sIgA response in mucosal secretions was observed (P < 0.001) in case of HBsAg ISCOM vaccines. Whereas, alum-HBsAg vaccine did not elicit considerable cellular or mucosal response. Thus, ISCOMs produced humoral, mucosal, and cellular immune responses upon nasal administration although high and multidose administrations were required to elicit potent immune responses. These data demonstrate potential of ISCOMs in their use as a carrier adjuvant for nasal subunit vaccines against hepatitis B.
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Affiliation(s)
- R S Pandey
- Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar - 470 003, Madhya Pradesh, India
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He YF, Jin J, Wei W, Chang Y, Hu B, Ji CS, Jia WD, Wang XQ, Chen K, Chen J. Overexpression of cyclooxygenase-2 in noncancerous liver tissue increases the postoperative recurrence of hepatocellular carcinoma in patients with hepatitis B virus-related cirrhosis. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2010; 24:435-440. [PMID: 20652159 PMCID: PMC2918484 DOI: 10.1155/2010/872570] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2008] [Accepted: 01/19/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND Many previous studies have evaluated the histopathological features of tumours as risk factors for postoperative recurrence in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). However, there have been few large studies investigating the relationship between cyclooxygenase-2 (COX-2) expression in noncancerous regions of the liver and postoperative recurrence in the remnant liver, especially in HBV-related HCC. OBJECTIVE To evaluate the significance of COX-2 expression levels in noncancerous liver regions as a prognostic indicator of HCC in patients with HBV-related cirrhosis. METHODS A total of 124 patients who underwent curative resection for HCC were reviewed retrospectively. Immunohistochemistry was used to evaluate the expression of COX-2 in noncancerous liver tissue. Clinicopathological variables were compared between patients with high COX-2 expression (n=58 [COX-2-positive group]) and patients with low COX-2 expression (n=66; [COX-2-negative group]). Univariate and multivariate analyses were performed to identify factors that affected disease recurrence. RESULTS There was a significant correlation between COX-2 expression and alanine aminotransferase levels and vascular invasion. The recurrence-free survival rates in the COX-2-positive group were significantly lower than the rates in the COX-2-negative group. On multivariate analysis, the overexpression of COX-2 in noncancerous liver regions was found to be an unfavourable prognostic indicator for the recurrence of HCC. CONCLUSIONS The results of the current study suggest that overexpression of COX-2 in noncancerous liver regions is an independent and significant indicator predictive of early recurrence of HCC in patients with HBV-related cirrhosis.
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Affiliation(s)
- Yi-Fu He
- Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Pharmacology of the Education Ministry of China
- Department of Medical Oncology
| | - Juan Jin
- Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Pharmacology of the Education Ministry of China
| | - Wei Wei
- Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Pharmacology of the Education Ministry of China
| | - Yan Chang
- Institute of Clinical Pharmacology, Anhui Medical University; Key Laboratory of Anti-inflammatory and Immune Pharmacology of the Education Ministry of China
| | - Bing Hu
- Department of Medical Oncology
| | | | | | - Xiao-Qiu Wang
- Department of Pathology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, People’s Republic of China
| | - Ke Chen
- Department of Pathology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, People’s Republic of China
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Sukriti S, Pati NT, Bose S, Hissar SS, Sarin SK. Impaired antigen processing and presentation machinery is associated with immunotolerant state in chronic hepatitis B virus infection. J Clin Immunol 2010; 30:419-25. [PMID: 20300807 DOI: 10.1007/s10875-010-9379-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2009] [Accepted: 02/05/2010] [Indexed: 01/19/2023]
Abstract
BACKGROUND AND AIMS The mechanism of hepatitis B virus (HBV)-specific T cell hyporesponsiveness in hepatitis Be antigen (HBeAg)-positive subjects is not well understood. Inefficient antigen processing and transport to major histocompatibility complex class I molecules, namely due to low molecular weight protein (LMP) 2 and 7 and transporter associated with antigen processing (TAP) 1 and 2 genes could be playing a role. PATIENTS AND METHODS Forty patients with chronic hepatitis B (CHB) infection, hepatitis B surface antigen, and HBeAg positive; 26 with raised (Gr. I) and 14 with persistently normal ALT levels (Gr. II) and 11 healthy controls (Gr. III) were studied. Total RNA was isolated from peripheral blood mononuclear cells and mRNA expression of TAP1, TAP2, LMP2, and LMP7 genes was analyzed by semi-quantitative reverse transcriptase-polymerase chain reaction method. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels were quantified by enzyme-linked immunosorbent assay (ELISA) using log-log and linear graphs, respectively. RESULTS Group II CHB patients had significantly lower mRNA expression for TAP1 (p = 0.003) and LMP2 (p = 0.002) genes as compared to Gr. I patients. The mRNA expression of TAP2 and LMP7 genes was comparable between the groups. However, expression of TAP1 (p = 0.02), TAP2 (p = 0.035), and LMP2 (p = 0.041) was found to be significantly higher in Gr. III subjects compared to Gr. I and Gr. II patients. In Gr. I and II, the IFN-gamma {s54.2{9.4-165} pg/ml), (59.5{28.5-110} pg/ml)}, and TNF-alpha {12.0 (8.0-23.2)},{10.8(6.2-20.8)} pg/ml levels were comparable but were significantly (p = 0.00,0.004, respectively) higher than Gr. III subjects. CONCLUSIONS Low expression of TAP1 and LMP2 suggests an important role of these genes in defective viral antigen processing in immune tolerant state of CHB patients. Higher IFN-gamma and TNF-alpha production in CHB are probably enough to potentiate liver injury but not enough to clear the chronic HBV infection. These novel observations could pave way for new therapeutic strategies for immune restoration in CHB infected patients.
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Affiliation(s)
- Sukriti Sukriti
- Department of Gastroenterology, G.B. Pant Hospital, University of Delhi, 201, Academic Block, New Delhi, India
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Zhao YX, Feng LY. Current status and advance of CD8+CTL in occurrence of hepatitis B. Shijie Huaren Xiaohua Zazhi 2009; 17:384-388. [DOI: 10.11569/wcjd.v17.i4.384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The cellular immune response is thought to play a critical role in viral clearance and disease pathogenesis during HBV infection. Cytotoxic T-lymphocytes (CTLs) response to HBV plays a key role in the viral clearance and liver cell injuries. As a main subpopulation of CTL, CD8+CTL can eliminate viral through cytotoxic mechanism and non-cytotoxic mechanism. In acute hepatitis B, the CTL response is polyclonal and multispecific, which can eliminate the virus in time; but the CTL response is monoclonal and monospecific in chronic HBV infection, which causes persistent HBV infection. This may be concerned with the dysfunction and insufficiency of the CD8+CTL.
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