Ribavirin contributes to eradicate hepatitis C virus through polarization of T helper 1/2 cell balance into T helper 1 dominance

The mechanism of action of ribavirin(RBV) as an immunomodulatory and antiviral agent and its clinical significance in the future treatment of patients with hepatitis C virus(HCV) infection are reviewed.RBV up-regulates type 1 and/or 2 cytokines to modulate the T helper(Th) 1/2 cell balance to Th1 dominance.Examination of co-stimulatory signaling indicated that RBV down-modulates inducible co-stimulator on Th cells,which contributes to differentiating na?ve Th cells into Th2 cells while reducing their interleukin-10 production.The effects on T-regulatory(Treg) cells were also investigated,and RBV inhibited the differentiation of na?ve Th cells into adaptive Treg cells by downmodulating forkhead box-P3.These findings indicate that RBV mainly down-regulates the activity of Th2 cells,resulting in the maintenance of Th1 activity that contributes to abrogating HCV-infected hepatocytes.Although an interferon-free treatment regimen exhibits almost the same efficacy without serious complications,regimens with RBV will be still be used because of their ability to facilitate the cellular immune response,which may contribute to reducing the development of hepatocellular carcinogenesis in patients infected with HCV.

Immune and non-immune responses to hepatitis C virus infection

The host innate and adaptive immune systems are involved in nearly every step of hepatitis C virus(HCV) infection. In patients,the outcome is determined by a series of complex host-virus interactions,whether it is a natural infection or results from clinical intervention. Strong and persistent CD8+ and CD4+ T-cell responses are critical in HCV clearance,as well as cytokineinduced factors that can directly inhibit virus replication. Newly available direct-acting antivirals(DAAs) are very effective in viral clearance in patients. DAA treatment may further result in the down-regulation of programmed death-1,leading to rapid restoration of HCV-specific CD8+ T cell functions. In this review,we focus on recent studies that address the host responses critical for viral clearance and disease resolution. Additional discussion is devoted to the prophylactic vaccine development as well as to current efforts aimed at understanding the host innate responses against HCV infection. Current theories on how the ubiquitin system and interferon-stimulated genes may affect HCV replication are also discussed.

CD4+ T cell responses in hepatitis C virus infection

Hepatitis C virus (HCV) infection is a major cause of liver damage, with virus-induced end-stage disease such as liver cirrhosis and hepatocellular carcinoma resulting in a high rate of morbidity and mortality worldwide. Evidence that CD4+ T cell responses to HCV play an important role in the outcome of acute infection has been shown in several studies. However, the mechanisms behind viral persistence and the failure of CD4+ T cell responses to contain virus are poorly understood. During chronic HCV infection, HCV-specific CD4+ T cell responses are rela- tively weak or absent whereas in resolved infection these responses are vigorous and multispecific. Persons with a T-helper type I profile, which promotes cellular effec- tor mechanisms are thought to be more likely to experi- ence viral clearance, but the overall role of these cells in the immunopathogenesis of chronic liver disease is not known. To define this, much more data is required on the function and specificity of virus-specific CD4+ T cells, especially in the early phases of acute disease and in the liver during chronic infection. The role and possible mechanisms of action of CD4+ T cell responses in deter- mining the outcome of acute and chronic HCV infection will be discussed in this review.

Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier

AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice. METHODS: We constructed the plasmid pTrc-coreNheI using gene engineering technique, constructed the pcDNA3.1-coreNheI-GFP plasmid with GFP as the reporter gene, and transfected them into Hela cells. The expression of GFP was observed under confocal microscopy and the feasibility of using HBcAg as an immuno-carrier vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of HCV (35-44aa) was fused and expressed in the plasmid pTrc- core-HCV (T). For the fusion of the HBcAg-T protein, sucrose, density gradient centrifugation was used, and its molecular weight and purity were analyzed by SDS- PAGE. Then balb/c mice were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as control. The tumor regression potential was investigated in mice and evaluated at appropriate time. After three times of immunization, the peripheral blood and spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and nonspecific T lymphocyte proliferation and response of splenocytes were respectively examined by MTT assay. T cell subset of blood and spleen were detected by FACS. RESULTS: GFP was successfully expressed. Tumor regression trial showed that no tumor formation was found in the group receiving immunization, while tumor xenograft progression was not changed in the control group. Strong nonspecific lymphocyte proliferation response was induced. FACS also showed that the ratio of CD8+ T cells in the experimental group was higher than the controls, but the serum HBcAb in experimental group was similar to the control. CONCLUSION: HBcAg can be used as an immuno-carrier of vaccine, the fusion of HBcAg-T protein could induce stronger cellular immune responses and it might be a candidate for therapeutic vaccines specific for HCV.

CD4+ T cells and natural killer cells: Biomarkers for hepatic fibrosis in human immunodeficiency virus/hepatitis C virus-coinfected patients

AIM To characterize peripheral blood natural killer(NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients.METHODS Peripheral mononuclear cells from 24 HIV/HCV(HBVnegative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4. NK surface cell staining was performed with: AntiCD3(APC/Cy7), anti-CD56(PE/Cy5), anti-CD57(APC), anti-CD25(PE), anti-CD69(FITC), anti-NKp30(PE), antiNKp46(PE/Cy7), anti-NKG2D(APC), anti-DNAM(FITC); anti-CD62L(PE/Cy7), anti-CCR7(PE), anti-TRAIL(PE), anti-Fas L(PE), anti CD94(FITC). Flow cytometry data acquisition was performed on BD FACSCanto, analyzed using Flow Jo software. Frequency of fluorescence was analyzed for all single markers. Clinical records were reviewed, and epidemiological and clinical data were obtained.RESULTS Samples from 11 patients were included in G1 and from 13 in G2. All patients were on ARV, with undetectable HIV viral load. Liver fibrosis was evaluated by transient elastography in 90% of the patients and with biopsy in 10% of the patients. Mean HCV viral load was(6.18 ± 0.7 log10). Even though, no major significant differences were observed between G1 and G2 regarding NK surface markers, it was found that patients with higher liver fibrosis presented statistically lower percentage of NK cells than individual with low to mild fibrosis and healthy controls(G2: 5.4% ± 2.3%, G1: 12.6% ± 8.2%, P = 0.002 and healthy controls 12.2% ± 2.7%, P = 0.008). It was also found that individuals with higher liver fibrosis presented lower CD4 LT count than those from G1(G2: 521 ± 312 cells/μL, G1: 770 ± 205 cells/μL; P = 0.035).CONCLUSION Higher levels of liver fibrosis were associated with lower percentage of NK cells and LTCD4+ count; and they may serve as noninvasive biomarkers of liver damage.

Challenges in managing hepatitis C virus infection in cancer patients

Cancer patients have unique problems associated with hepatitis C virus(HCV)infection and treatment not seen in the general population.HCV infection poses additional challenges and considerations for the management of cancer,and vice versa.HCV infection also can lead to the development of cancer,particularly hepatocellular carcinoma and non-Hodgkin lymphoma.In severely immunocompromised cancer patients,diagnosis of HCV infection requires increased reliance on RNA detection techniques.HCV infection can affect chemotherapy,and delay of HCV infection treatment until completion of chemotherapy and achievement of cancer remission may be required to decrease the potential for drug-drug interactions between antineoplastic agents and HCV therapeutics and potentiation of side effects of these agents.In addition,hematopoietic stem cell transplant(HSCT)recipients have an increased risk of early development of cirrhosis and fibrosis.Whether this increased risk applies to all patients regardless of cancer treatment is unknown.Furthermore,patients with cancer may have poorer sustained virological responses to HCV infection treatment than do those without cancer.Unfortunately,not all cancer patients are candidates for HCV infection therapy.In this article,we review the challenges in managing HCV infection in cancer patients and HSCT recipients.

Direct effects of hepatitis C virus on the lymphoid cells

It has been reported that the direct binding of hepatitis C virus(HCV)and/or the replication of HCV in the extrahepatic organs and,especially,lymphoid cells,might affect the pathogenesis of extrahepatic diseases with HCV infection.More than one decade ago,several reports described the existence of HCV-RNA in peripheral blood mononuclear cells.Moreover,many reports describing the existence of HCV in B lymphocytes and B cell lymphoma have been published.In addition to B lymphocytes,it was reported that HCV replication could be detected in T lymphocytes and T cell lines.Among the extrahepatic diseases with HCV infection,mixed cryoglobulinemia-related diseases and autoimmunerelated diseases are important for understanding the immunopathogensis of HCV persistent infection.Moreover,HCV persistent infection can cause malignant lymphoma.The biological significance of lymphotropic HCV has not yet become clear.However,several candidates have been considered for a long time.One is that lymphotropic HCV is an HCV reservoir that might contribute to the recurrence of HCV infection and difficultto-treat disease status.The other important issue is the carcinogenesis of the lymphoid cells and disturbances of the immune responses.Therefore,the extrahepatic diseases might be induced by direct interaction between HCV and lymphoid cells.In this article,we summarize various studies showing the direct effect of HCV on lymphoid cells and discuss the biological significance of lymphotropic HCV.

All-oral interferon-free treatments:The end of hepatitis C virus story,the dream and the reality

The year 2014 marked the beginning of the end of the interferon era and the triumph of the all-oral interferon-free regimens for treatment of hepatitis C virus(HCV) infection. These innovative therapies are safe and yield a cure rate of over 90%. The scientifichepatology community is euphoric about the possibility of elimination and even eradication of HCV infection. However,the current high cost of the new all-oral regimens allows access to treatment only for a restricted number of HCV-infected patients. In addition,many other conditions such as modality of access and delivery of care,inadequate knowledge of HCV epidemiology and political commitments to be undertaken,hamper the fulfillment of the dream to eliminate the virus. Since,such conditions are not impossible to overcome,a global urgent effort must be made to allow a widespread access to the new treatments which will permit in the next years to avoid million of HCV-related deaths.

Associations of IFN-γ rs2430561 T/A,IL28B rs12979860 C/T and ERα rs2077647 T/C polymorphisms with outcomes of hepatitis B virus infection:a meta-analysis

Several studies investigated associations of IFN-γ rs2430561 T/A,IL28 B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus（HBV） infection,but the results were controversial.Therefore,we performed a meta-analysis of all published observational studies to address this inconsistency.Literature was searched in online database and a systematic review was conducted based on the search results.A total of 24 studies were included and dichotomous data were presented as odds ratio（OR） with a 95%confidence interval（CI）.The rs2430561 T allele was associated with reduced persistent HBV infection risk（T vs.A：OR,0.690;95%CI,[0.490,0.971]）,while the rs2077647 T allele significantly increased the risk of persistent HBV infection（T vs.C：OR.1.678;95%CI,[1.212,2.3231）.Rs 2077647 CC might play a role in protecting individuals against HBV persistence（TT vs.CC：OR,4.109;95%CI,[2.609,6.473]）.Furthermore,carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype（TT vs.AA：OR,0.555;95%CI,[0.359,0.856]）.For rs12979860 C/T polymorphism,no significant correlation with HBV infection outcomes was found.In subgroup analyses,the results were similar to those of overall analysis.However,for rs2077647 TT vs.TC＋CC,significantly increased risks were observed in the Asian and hospital-based population,but not in the overall analysis.IFN-γrs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection,but no association was found between IL28 B rs12979860 C/T and HBV infection.

Adaptive immune response during hepatitis C virus infection

Hepatitis C virus(HCV)infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma.HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control.Liver damage and disease progression during HCV infection are driven by both viral and host factors.Specifically,adaptive immune response carries out an essential task in controllingnon-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery.HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion.To impair HCV-specific T cell reactivity,HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro-and antiapoptotic proteins.In this review,the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.

Hepatitis C virus/human T lymphotropic virus 1/2 coinfection:Regional burden and virological outcomes in people who inject drugs

This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.

Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity

AIMTo investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODSA prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTSChronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSIONElevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.

Host and viral factors contributing to CD8+ T cell failure in hepatitis C virus infection

Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV) infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified, including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host’s human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCV- specific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.

Immune mechanisms of vaccine induced protection against chronic hepatitis C virus infection in chimpanzees

Hepatitis C virus(HCV) infection is characterized by a high propensity for development of life-long viral persistence. An estimated 170 million people suffer from chronic hepatitis caused by HCV. Currently,there is no approved prophylactic HCV vaccine available.With the near disappearance of the most relevant animal model for HCV,the chimpanzee,we review the progression that has been made regarding prophylactic vaccine development against HCV. We describe the results of the individual vaccine evaluation experiments in chimpanzees,in relation to what has been observed in humans. The results of the different studies indicate that partial protection against infection can be achieved,but a clear correlate of protection has thus far not yet been defined.

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma(HCC) in patients chronically infected with hepatitis B virus(HBV) or hepatitis C virus(HCV). The approved medication for the treatment of chronic HBV infection is interferon-α(IFNα) and nucleos(t)ide analogues(NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181 T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-totreat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients(both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

Role of T cell death in maintaining immune tolerance during persistent viral hepatitis

Virus-specific T cells play an important role in the resolution of hepatic infection. However, during chronic hepatitis infection these cells lack their effector functions and fail to control the virus. Hepatitis B virus and hepatitis C virus have developed several mechanisms to generate immune tolerance. One of these strategies is the depletion of virus-specific T cells by apoptosis. The immunotolerogenic liver has unique property to retain and activate na ve T cell to avoid the over reactivation of immune response against antigens which is exploited by hepatotropic viruses to persist. The deletion of the virus-specific T cells occurs by intrinsic (passive) apoptotic mechanism. The pro-apoptotic molecule Bcl-2 interacting mediator (Bim) has attracted increasing attention as a pivotal involvement in apoptosis, as a regulator of tissue homeostasis and an enhancer for the viral persistence. Here, we reviewed our current knowledge on the evidence showing critical role of Bim in viral-specific T cell death by apoptotic pathways and helps in the immune tolerance.

Current progress in the treatment of chronic hepatitis C

Over the last decade, the standard of care for the treat- ment of chronic hepatitis C has been the combination of pegylated-interferon-alfa （PEG-IFN） and ribavirin （RBV） which results in sustained virological response （SVR） rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Cur- rently, there are rapid and continuous developments of numerous new agents against hepatitis C virus （HCV）, which are the focus of this review. Boceprevir and tela- previr, two first-generation NS3/4A HCV protease inhibi- tors, have been recently licensed in several countries around the world to be used in combination with PEG- IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, com- pared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naTve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-na＇ive patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events （anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir）, new drug interactions and increasing dif- ficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG- IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well toler- ated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.

Hepatocellular Carcinoma: Known and Emerging Risk Factors

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.

HIV合并HBV/HCV感染患者外周血T细胞亚群的变迁

目的了解HIV合并HBV、HCV感染患者外周血T细胞亚群的变化特征,探讨HIV合并HBV和HCV感染后患者的免疫功能。方法采用三色流式细胞学检测技术,对26例HIV合并HBV和HCV感染患者(合并感染组)、35例单纯HIV感染患者(单纯感染组)和194例健康人群(健康对照组)外周血总T细胞、T4细胞、T8细胞含量进行测定并计算T4/T8比值。结果单纯感染组患者外周血总T细胞、T4细胞、T8细胞的百分含量和T4/T8比值分别为66.42±4.11、27.74±2.34、47.72±3.86和0.74±0.19,合并感染组分别为54.76±3.42、22.31±1.87、58.23±4.62和0.33±0.12,健康对照组值分别为69.98±5.79、35.25±5.16、25.08±4.34和1.45±0.28单纯感染组患者T4细胞和T4/T8比值明显低于健康对照组(P<0.05,P<0.01),T8细胞较对照组明显升高(P<0.05);合并感染组总T细胞、T4细胞和T4/T8比值明显低于健康对照组和单纯感染组(P<0.05,P<0.01),T8细胞较健康对照组和单纯感染组明显升高(P<0.05,P<0.01)。结论 HIV感染患者合并HBV和HCV感染将进一步加重体内免疫功能的紊乱;检测外周血T细胞亚群有利于HIV、HBV和HCV多重感染患者的鉴别诊断、病情监测以及预后判断,是一项十分有效的客观依据。

肝癌组织、癌旁组织中HBsAg、HCV抗原表达与T细胞亚群及NK活性的相关性研究

研究肝癌组织、癌旁组织中HBsAg、HCV抗原表达与T细胞亚群及NK活性的相关性。采用免疫组织化学方法(SP法)对肝癌组织及癌旁组织中的HBsAg、HCV抗原表达进行了标记和分析,同时对外周血T细胞亚群及 NK活性进行检测。肝癌患者中,CD4+细胞减少,CD8+细胞升高,CD4+／CD8+比值及NK细胞的活性均比正常对照组明显降低,且HBsAg阳性、HCV抗原阳性者比阴性者下降更显著。肝癌组织、癌旁组织中HBsAg、HCV抗原表达与外周血T细胞亚群及NK活性Spearman相关性分析,与NK细胞、CD4+细胞、CD8+细胞、CD4+／CD8+相关系数分别为-0．67,-0．28,0．35,-0．50(P<0．001)。肝癌患者出现免疫紊乱与乙肝、丙肝病毒感染有关,且混合感染者免疫功能紊乱较显著,提示抗病毒治疗可能改善肝癌患者的免疫功能。