Hepatitis G Viral RNA Co-infection in Plasma and Peripheral Blood Mononuclear Cells in Patients with Hepatitis C

The incidence of the co-infection of hepatitis G virus (HGV) and hepatitis C virus (HCV) and its clinical implication was investigated and the difference in the positive rate of HGV RNA and HCV RNA between plasma and peripheral blood mononuclear cells (PBMCs) observed. By using reverse transcriptase polymerase chain reaction (RT-PCR) assay, HCV-RNA and HGV-RNA in plasma and PBMCs of 72 patients with hepatitis C was detected. It was showed that HGV RNA was positive in plasma of 11 patients, in PBMCs of 15 patients, and simultaneously in both of plasma and PBMCs of 10 patients with the co-infection rate being 22.2 %. Nine patients were both HGV RNA and HCV RNA positive in plasma, 11 patients were both HGV RNA and HCV RNA positive in PBMC, and 6 patients were both HGV RNA and HCV RNA positive in both plasma and PBMC with the positive rate being 12.4 %,15.3 % and 8.3 % respectively. The positive rate of both HGV RNA and HCV RNA in PBMCs was higher than in plasma. It was concluded that the HGV co-infection rate in the patients with hepatitis C was 22.2 %. Simultaneous examination of plasma and PBMC can improve clinically detectable rate.

Risk Factors, Clinical Features, Baseline Alanine Aminotransferase and CD4+ Count of Children with HIV Co-Infection with Hepatitis B and C at a Tertiary Hospital in Southwest Nigeria

Background: Human immunodeficiency virus and hepatitis B and C viruses are endemic in sub- Saharan African countries including Nigeria. Researchers have studied the burden of co-infection of HIV with hepatitis B and hepatitis C but the risk factors and clinical presentation have not been much addressed especially in children. Methodology: This was a prospective cross sectional study that determined the prevalence, risk factors, clinical features, baseline CD4+ count, CD4+ percentage, and alanine aminotransferase (ALT) of newly diagnosed, HAART na?ve HIV co-infection among children who were managed at a Tertiary Hospital in Ilorin, Nigeria. Result: Of the 60 HIV- infected children recruited, 11.7% had HIV co-infection with HBV or HCV. Children with co-infec- tions (mean age 8.43 ± 2.37 years) were significantly older than their HIV mono-infected counterparts (mean age 5.25 ± 3.96 years) (p = 0.011). There was no significant difference between HIV monoinfection and HIV co-infection with respect to gender (p = 0.758), ethnicity (p = 0.707), religion of parents (p = 0.436), family type (p = 0.184), social class (p = 0.535), previous transfusion (p = 0.053), scarification (p = 0.612), female genital mutilation (p = 0.778), and sharing of clippers (p = 0.806). The mean BMI, immunological staging (p = 0.535), baseline ALT (p = 0.940), and mean baseline CD4+ count (p = 0.928) were comparable. However, the body mass index of HIV co-infec- ted children decreased with age up till age 10 years. Conclusion: There were no risk factors, nor clinical features predictive of co-infection identified in this study. Co-infection did not negatively impact baseline, CD4+ count and ALT.

Unexpected Association of HIV, Hepatitis C Virus Infection, Lymph Node Tuberculosis, and Sickle Cell Disease: A Case Report in a 35-Year-Old Woman from Cameroon

Introduction: HIV infection is a public health issue. Developing countries are facing the challenge of patient populations that remain undiagnosed and under-served in combined antiretroviral treatment (cART) leading to opportunistic infections. Lymph node tuberculosis is one of the most common. His firm diagnosis is not always easy in resources limited country. Case Presentation: We report a case of a 35-year-old woman known HIV for the past 10 years but not on treatment. She presented with a four-month history of fatigue, weight loss and pain in the right flank. The diagnosis of lymph node tuberculosis, hepatitis c virus infection and sickle cell disease was done. After 6 months of treatment, there was a favourable clinical evolution. Conclusion: This case report highlights the necessity to screen for opportunistic and non-opportunistic co-infection in HIV infected patient.

Analysis of causes for liver function deteriora-tion in patients with HIV/HCV co-infection

BACKGROUND:Co-infection of hepatitis C virus (HCV) and human immunodeficiency virus type 1 ( HIV-1 ) is common in hemophiliacs and drug abusers. To assess the interaction between HIV and HCV disease progression, we examined 82 HIV/HCV co-infection patients and 62 HCV infection patients. METHODS: Liver function, pathological changes, infec- tion duration, immune function and qualitative HCV-RNA and HCV antibody were compared retrospectively between the two groups of patients. RESULTS: Fourty-eight patients (58.5%) in the HIV/ HCV co-infection group and 53 patients (85.5%) in the HCV infection group showed abnormal liver function. No significant difference was observed in inflammation and fi- brosis in the two groups P =0.187, 0.954). However, liver abnormality in the patients with HIV/HCV co-infection appeared 8 years earlier than in those with HCV infection alone (P<0.001). As to immune function, the counts of CD4+T and CD8+ T in the HIV/HCV group were (226.35 ± 173.49)×106/L and (914. 40 ±448. 28)×106/L, whereas in the HCV group they were (752.31±251.69)×l06/L and (529.011170.67)×106/L respectively. The difference in the two groups was highly significant (P<0.001; P<0.001). The ratio of the number of people with both HCV-RNA and HCV antibody positive to the number of HCV-RNA positive and HCV antibody negative in the HIV/HCV group was 52:9, whereas in the HCV group it was 44:1 (P = 0.043). CONCLUSION: HIV/HCV co-infection can accelerate de- terioration of hepatitis C, which may be due to the effect of HIV on cellular immunity and humoral immunity of the body.

Dendritic cells: The warriors upfront-turned defunct in chronic hepatitis C infection

Hepatitis C virus(HCV) infection causes tremendousmorbidity and mortality with over 170 million people infected worldwide. HCV gives rise to a sustained, chronic disease in the majority of infected individuals owing to a failure of the host immune system to clear the virus. In general, an adequate immune response is elicited by an efficient antigen presentation by dendritic cells(DCs), the cells that connect innate and adaptive immune system to generate a specific immune response against a pathogen. However, HCV seems to dysregulate the activity of DCs, making them less proficient antigen presenting cells for the optimal stimulation of virusspecific T cells, hence interfering with an optimal antiviral immune response. There are discordant reports on the functional status of DCs in chronic HCV infection(CHC), from no phenotypic or functional defects to abnormal functions of DCs. Furthermore, the molecular mechanisms behind the impairment of DC function are even so not completely elucidated during CHC. Understanding the mechanisms of immune dysfunction would help in devising strategies for better management of the disease at the immunological level and help to predict the prognosis of the disease in the patients receiving antiviral therapy. In this review, we have discussed the outcomes of the interaction of DCs with HCV and the mechanisms of DC impairment during HCV infection with its adverse effects on the immune response in the infected host.

Induction of hepatitis C virus-specific cytotoxic T and B cell responses by dendritic cells expressing a modified antigen targeting receptor

AIM: To find a novel antigen (Ag) presentation strategy to improve the immune responses induced by dendritic cell (DC)vaccine expressing hepatitis C virus (HCV) core antigen (pcDNA3HCV C-Fc) in Balb/c mice (H-2d).METHODS: pcDNA3HCV C-Fc plasmid and eukaryotic expression vector pcDNA3 were injected into mice sc. Immune responses to pcDNA3HCV C-Fc were studied. Meanwhile the effect of pcDNA3HCV C-Fc on anti-translated subcutaneous tumor of SP2/0 cells stably expressing HCV C Ag (SP2/0-HCV C-FC) was also studied. Anti-HCV C in serum was detected by enzyme-linked immunoadsordent assay (ELISA) and HCV specific cytotoxic T lymphocyte (CTL) activity was measured by LDH release assay. After 3 wk of DNA immunization,the cells of SP2/0-HCV C-FC were inoculated into mice subcutaneously and tumor growth was measured every 5 d.The survival rate and living time of mice were also calculated.RESULTS: After 4 wk of DC immunization, the A450 nm values of sera in mice immunized with pcDNA3HCV C-Fc-DC and pcDNA3-DC were 0.56±0.17 and 0.12±0.03 respectively. The antibody titres in mice codeliveried with pcDNA3HCV C-Fc with DC were significantly higher than those of mice injected with pcDNA3-DC. The HCV specific CTL activities in mice coinjected with DC and pcDNA3HCV C-Fc or empty expression vectors were(73.2±3.1) % and (24.4±8.8) %, which were significantly higher than those of mice injected with water.The DC vaccine could evidently inhibit tumor growth, prolong the survival time of mice and improve the survival rate of mice and these effects could be improved by HCV C-Fc (pcDNA3HCV C-Fc) gene codelivered.CONCLUSION: DC vaccine has a strong antigenicity in humoral and cellular immunities, which can be promoted by transduced pcDNA3HCV C-Fc expressing HCV C or Fc.Thus, pcDNA3HCV C-Fc-transduced DCs may be a promising candidate for a CTL-based vaccine against HCV.

Vaccination with dendritic cells pulsed with hepatitis C pseudo particles induces specific immune responses in mice

AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole "viral surface" induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cellsdirected against HCV. Furthermore, T-cell responses confi rmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further.

Analysis of peripheral blood dendritic cells as a non-invasivetool in the follow-up of patients with chronic hepatitis C

Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.

The global and regional prevalence of hepatitis C and B co-infections among prisoners living with HIV:a systematic review and meta-analysis

Background Hepatitis B virus(HBV)and hepatitis C virus(HCV)infections are common among individuals with human immune deficiency virus(HIV)infection worldwide.In this study,we did a systematic review and meta-analysis of the published literature to estimate the global and regional prevalence of HCV,HBV and HIV coinfections among HIV-positive prisoners.Methods We searched PubMed via MEDLINE,Embase,the Cochrane Library,SCOPUS,and Web of science(ISI)to identify studies that reported the prevalence of HBV and HCV among prisoners living with HIV.We used an eight-item checklist for critically appraisal studies of prevalence/incidence of a health problem to assess the quality of publications in the included 48 cross-sectional and 4 cohort studies.We used random-effect models and meta-regression for the meta-analysis of the results of the included studies.Results The number of the included studies were 50 for HCV-HIV,and 23 for HBV-HIV co-infections.The pooled prevalence rates of the coinfections were 12%[95%confidence interval(CI)9.0–16.0]for HBV-HIV and 62%(95%CI 53.0–71.0)for HCV-HIV.Among HIV-positive prisoners who reported drug injection,the prevalence of HBV increased to 15%(95%CI 5.0–23.0),and the HCV prevalence increased to 78%(95%CI 51.0–100).The prevalence of HBV-HIV coinfection among prisoners ranged from 3%in the East Mediterranean region to 27%in the American region.Also,the prevalence of HCV-HIV coinfections among prisoners ranged from 6%in Europe to 98%in the East Mediterranean regions.Conclusions Our findings suggested that the high prevalence of HBV and HCV co-infection among HIV-positive prisoners,particularly among those with a history of drug injection,varies significantly across the globe.The results of Meta-regression analysis showed a sliding increase in the prevalence of the studied co-infections among prisoners over the past decades,rising a call for better screening and treatment programs targeting this high-risk population.To prevent the above coinfections among prisoners,aimed public health services(e.g.harm reduction via access to clean needles),human rights,equity,and ethics are to be seriously delivered or practiced in prisons.

Dominating expression of negative regulatory factors downmodulates major histocompatibility complex Class-Ⅱexpression on dendritic cells in chronic hepatitis C infection

AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.RESULTS: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral proteins.CONCLUSION: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.

Dendritic cells in hepatitis C virus infection:Key players in the IFNL3-genotype response

Recently,single nucleotide polymorphisms,in the vicinity of the interferon lambda 3(IFNL3)gene have been identified as the strongest predictor of spontaneous and treatment induced clearance of hepatitis C virus(HCV)infection.Since then,increasing evidence has implicated the innate immune response in mediating the IFNL3 genotype effect.Dendritic cells(DCs)are key to the host immune response in HCV infection and their vital role in the IFNL3 genotype effect is emerging.Reports have identified subclasses of DCs,particularly myeloid DC2s and potentially plasmacytoid DCs as the major producers of IFNL3 in the setting of HCV infection.Given the complexities of dendritic cell biology and the conflicting current available data,this review aims to summarize what is currently known regarding the role of dendritic cells in HCV infection and to placeit into context of what is know about lambda interferons and dendritic cells in general.

Genetic vaccination with Flt3-L and GM-CSF as adjuvants: Enhancement of cellular and humoral mmune responses that results in protective immunity in a murine model of hepatitis C virus infection

AIM: To investigate whether transfection of plasmid DNA encoding these cytokines enhances both humoral and cellular immune responses to hepatitis C virus (HCV) in a murine model. METHODS: We established a tumor model of HCV infection using syngenic mouse myeloma cells stably transfected with NS5. Co-vaccination of DNA encoding granulocyte macrophage colony-stimulating factor (GM- CSF) and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein was carried out. Mice were sacrificed 14 d after the last immunization event with collection of spleen cells and serum to determine humoral and cellular immune responses. RESULTS: Co-vaccination of DNA encoding GM-CSF and Flt-3 ligand together with a plasmid encoding for the HCV NS5 protein induced increased antibody responses and CD4+ T cell proliferation to this protein. Vaccination with DNA encoding GM-CSF and Flt-3L promoted protection against tumor formation and/or reduction in mice co- immunized with cytokine-encoding DNA constructs. This suggests this strategy is capable of generating cytotoxic T lymphocyte activity in vivo. Following inoculation withplasmid DNA encoding Flt-3L, no increase in spleen size or in dendritic cell (DC) and natural killer cell numbers was observed. This was in contrast to a dramatic increase of both cell types after administration of recombinant Flt3-L in vivo. This suggests that vaccination with plasmid DNA encoding cytokines that regulate DC generation and mobilization may not promote unwanted side effects, such as autoimmunity, splenic fibrosis or hematopoietic malignancies that may occur with administration of recombinant forms of these proteins. CONCLUSION: Our data support the view that plasmid DNA vaccination is a promising approach for HCV immunization, and may provide a general adjuvant vaccination strategy against malignancies and other pathogens.

Hepatitis B and C Immunological and Molecular Parameter Analysis in HIV-Positive Patients Undergoing Antiretroviral Therapy at Saint Camille Hospital in Ouagadougou (HOSCO), Burkina Faso

Knowledge of the clinical and biological profile of patients infected with HIV and hepatitis B and/or C is essential in order to identify and implement effective management strategies. Methods: This was a retrospective descriptive study from January 01, 2016 to June 01, 2021. Adult patients aged at least 18 years infected with HIV type 1 and/or 2, na?ve to ARV treatment. Univariate analyses were assessed using Pearson’s Chi2 test. The Student Newman test was used for comparison between groups using R software version 4.0.2. Objective: To draw up the epidemiological, clinical, paraclinical and evolutionary profiles of HIV-treated-patients in relation to HIV/HBV and HIV/HCV co-infections in order to allow the identification and the implementation of effective management strategies. Results: Of the 379 patients included 280 (73.88%) were women. At treatment initiation, the mean age was 40.14 ± 11.84 years. The majority of patients consulted at WHO stage III (51.45%). Clinical suspicion was the most frequent screening circumstance (51.71%). The pathologies frequently reported at the first consultation were diarrhea (28%) and shingles (16%). Body mass index was normal in 50.5% of patients. HIV1 infection was the majority (91.03%). A total of 270 had a CD4 count at treatment initiation. The mean CD4 cell count was 304.17 ± 242.06 cells/μL, and 116 (42.59%) of them had a CD4 ≤ 200 cells/μL. Viral load at treatment initiation was documented in 62 patients (16.35%) and 70.97% of them had a detectable viral load (greater than 1000 copies/mL). The clinical and biological evolution was relatively good in patients after therapeutic initiation. HIV-HBV co-infection was 24.11% and HIV-HCV co-infection was 2.26%. The mortality rate was 3.69%. Conclusion: These results reflect a significant delay in HIV infection diagnosis. Furthermore, hepatitis B and/or C is co-infections that increasingly affect people living with HIV. It also appears that COVID 19 disease has had a strong impact on patient management. Thus, new screening strategies must be implemented to encourage early diagnosis of HIV, hepatitis B and C. Effective strategies are also necessary to fight HIV in the context of epidemics and/or pandemics.

Role of macrophages and monocytes in hepatitis C virus infections

A number of studies conducted over many years have shown that hepatitis C virus(HCV)can infect a variety of cell types.In vivo infection of monocytes,macrophages,and dendritic cells by HCV has been frequently shown by a number of researchers.These studies have demonstrated replication of HCV by detecting the presence of both negative genomic strands and a variety of non-structural HCV proteins in infected cells.In addition,analyses of genome sequences have also shown that different cell types can harbor different HCV variants.Investigators have also done preliminary studies of which cellular genes are affected by HCV infection,but there have not yet been a sufficient number of these studies to understand the effects of infection on these cells.Analyses of in vitro HCV replication have shown that monocytes,macrophages and dendritic cells can be infected by HCV from patient sera or plasma.These studies suggest that entry and cellular locations may vary between different cell types.Some studies suggest that macrophages may preferentially allow HCV genotype 1 to replicate,but macrophages do not appear to select particular hypervariable regions.Overall,these studies agree with a model where monocytes and macrophages act as an amplification system,in which these cells are infected and show few cytopathic effects,but continuously produce HCV.This allows them to produce virus over an extended time and allows its spread to other cell types.

Mononuclear phagocyte system in hepatitis C virus infection

The mononuclear phagocyte system(MPS), which con-sists of monocytes, dendritic cells(DCs), and macro-phages, plays a vital role in the innate immune defense against pathogens. Hepatitis C virus(HCV) is efficient in evading the host immunity, thereby facilitating its devel-opment into chronic infection. Chronic HCV infection is the leading cause of end-stage liver diseases, liver cirrhosis, and hepatocellular carcinoma. Acquired im-mune response was regarded as the key factor to era-dicate HCV. However, innate immunity can regulate the acquired immune response. Innate immunity-derived cytokines shape the adaptive immunity by regulating T-cell differentiation, which determines the outcome of acute HCV infection. Inhibition of HCV-specific T-cell responses is one of the most important strategies for im-mune system evasion. It is meaningful to illustrate the role of innate immune response in HCV infection. With the MPS being the important factor in innate immunity, therefore, understanding the role of the MPS in HCV infection will shed light on the pathophysiology of chronic HCV infection. In this review, we outline the impact of HCV infection on the MPS and cytokine production. We discuss how HCV is detected by the MPS and describe the function and impairment of MPS components in HCV infection.

Studies on the allostimulatory function of dendritic cells from HCV-HIV-1 co-infected patients

There is increasing recognition of the potential morbidity and mortality associated with HIV-1 and hepatitis C (HCV)co-infection. HIV appears to adversely affect HCV disease while the reciprocal effect of HCV on HIV remains controversial.We therefore studied the effect of co-infection on dendritic cell function versus HIV infection alone, as previous work has shown that HCV impairs dendritic cell (DC) function. HIV-1 positive individuals with HCV were matched for CD4count, HIV- 1 RNA viral load and therapy, to HIV- 1 positive patients without HCV. Monocyte-derived DC were generated and mixed leukocyte reactions were performed. We assessed allostimulatory capacity with and without administration of exogenous Thl cytokines, using thymidine uptake and cell division analyses with the vital dye CFSE. We found that monocyte-derived DC from co-infected individuals showed no significant differences in allostimulatory capacity to ex vivo generated DC from HIV-1 infected individuals without HCV. Unlike the situation with HCV infection alone, this impairment was not reversed by increasing concentrations of either interleukin-2 or -12. Monocyte-derived DC from HIV-1 and HCV co-infected individuals have a similar allostimulatory capacity to DC from matched patients with HIV-1alone. These findings are compatible with results of prior clinical studies that found no evidence that HCV co-infection altered HIV disease progression and has implications for immunotherapeutic approaches in co-infected individuals.

Mathematical analysis of Hepatitis C Virus infection model in the framework of non-local and non-singular kernel fractionalderivative

In this paper,we study a mathematical model of Hepatitis C Virus(HCV)infection.We present a compartmental mathematical model involving healthy hepatocytes,infected hepatocytes,non-activated dendritic cells,activated dendritic cells and cytotoxic T lymphocytes.The derivative used is of non-local fractional order and with non-singular kernel.The existence and uniqueness of the system is proven and its stability is analyzed.Then,by applying the Laplace Adomian decomposition method for the fractional derivative,we present the semi-analytical solution of the model.Finally,some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions.

Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: An Egyptian study

AIM:To assess co-stimulatory and co-inhibitory markers of dendritic cells(DCs)in hepatitis C virus(HCV)infected subjects with and without uremia.METHODS:Three subject groups were included in the study:group 1 involved 50 control subjects,group2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis.CD83,CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by realtime polymerase chain reaction.Interleukin-10(IL-10)and hyaluronic acid(HA)levels were also assessed.All findings were correlated with disease activity,viral load and fibrogenesis.RESULTS:There was a significant decrease in costimulatory markers;CD83,CD86 and CD40 in groups2 and 3 vs the control group.Co-stimulatory markers were significantly higher in group 3 vs group 2.There was a significant elevation in PD-L1 in both HCV groups vs the control group.PD-L1 was significantly lower in group 3 vs group 2.There was a significant elevation in IL-10 and HA levels in groups 2 and 3,where IL-10was higher in group 3 and HA was lower in group 3 vs group 2.HA level was significantly correlated with disease activity and fibrosis grade in group 2.IL-10 was significantly correlated with fibrosis grade in group 2.There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and3,except CD83 in dialysis patients.There was a significant positive correlation between PD-L1 and viral load in both HCV groups.CONCLUSION:A significant decrease in DC co-stimulatory markers and a significant increase in a DC coinhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients.

Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P < 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P < 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P < 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P < 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P < 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P <0.01,P < 0.001 and P < 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P < 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P < 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P < 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.

HIV/HCV重叠感染患者肝脏功能进展原因分析

探讨HIV/HCV重叠感染患者肝脏功能进展的原因。回顾性比较HIV/HCV重叠感染患者和单独HCV感染患者两组的肝脏功能、病理情况、感染时间、免疫功能及综合分析HCVRNA定性检测与HCV抗体检测在两组中的异同。HIV/HCV重叠感染患者中肝功异常者占 5 8 5 % ,HCV感染组为 85 5 % ,肝功损伤程度亦较后者轻微 (P<0 0 5 ) ;两组患者在肝脏病理炎症活动和纤维化程度方面差异无显著性 (P =0 187,0 95 4 ) ;而重叠感染患者进展到肝功能异常的时间较单独HCV感染者提前 8年 (P <0 0 0 1) ;免疫功能方面 (CD+ 4 T、CD+ 8T)重叠感染者组与单独HCV感染者组比较 ,差异非常显著 (P <0 0 0 1;P <0 0 0 1) ;HCVRNA(+)同时HCV抗体 (+)的人数与HCVRNA(+)同时HCV抗体 (- )的人数比较在重叠感染组为 5 2∶9例 ,在HCV感染组 4 4∶1例 ,两组间差异显著P =0 0 4 3。HIV/HCV重叠感染可加速丙型病毒性肝炎的进展 ,可能与HIV对机体的细胞免疫。