Potential role of hepatic progenitor cells expression in cases of chronic hepatitis C and their relation to response to therapy: a clinicopathologic study.

BACKGROUND: This study investigates the correlation of hepatic progenitor cells (HPC) expression with treatment response in patients with chronic hepatitis C. DESIGN: The study comprised 77 liver biopsies with chronic hepatitis C (HCV). All patients were PCR-HCV (+) and received antiviral therapy with interferon or pegylated interferon alpha-2b and ribavirin. Twenty-nine patients were assigned as responders (group A), 29 as nonresponders (group B) and 19 as relapsers (group C). Ten normal liver biopsies were used as controls. Liver paraffin sections were subjected (a) to immunohistochemistry using antibodies for cytokeratins 19 (CK19) and 7 (CK7), alpha-fetoprotein (AFP), leukocyte common antigen (LCA) and CD34 antigen (b) to in situ hybridization for AFP mRNA and (c) to immunohistochemistry+in situ hybridization. Results were expressed as % of positive cells following morphometric analysis. RESULTS: HPC expression was present in all 87 specimens. In the control biopsies, rare HPC were detected. In the CH cases and according to AFP mRNA expression, the grade for % HPC expression was: group B: 53.2+/-2.6> group C: 48.37+/-1.8> group A: 31.4+/-1.6 (group A vs B P<0.01, group A vs C P<0.01, group B vs C P>0.05. Double stain revealed that HPC coexpressed CK19/AFP mRNA, CK7/AFP mRNa and AFP protein/AFP mRNA. HPC-percentages were directly correlated with total HAI score (P<0.01), fibrosis stage (P<0.01), and transaminase values (P<0.05). CONCLUSIONS: This study demonstrates that in cases of chronic hepatitis C, the significant association of HPC expression with the severity of disease and more specifically with the response to treatment implies that HPC development and proliferation may provide additional prognostic information and predict prognosis in such cases.     

DC-SIGN在慢性乙型肝炎病毒感染时树突状细胞成熟活化中的作用

目的研究慢性HBV感染时,DC-SIGN在树突状细胞（DC）成熟和活化中介导的作用。方法将α-甘露糖苷酶抑制剂-基夫碱作用于HepG2.2.15细胞,收获上清中的高甘露糖型HBV颗粒,并于第5 d加入到外周血单核细胞衍生的DC培养基中,培养至第7 d,采用流式细胞仪检测DC表面CDla、CD83、CD80、CD86、HLA-DR分子的表达,MTT法检测DC刺激淋巴细胞增殖的能力,ELISA法检测DC分泌IL-12的水平。结果高甘露糖型HBV组,与天然的HBV组相比,DC表面CDla、CD83、CD80、CD86、HLA-DR分子的表达增加,分泌IL-12的水平升高,刺激同种异体淋巴细胞增殖的能力亦明显增强,且上述效应均可被DC-SIGN特异性抗体所阻断。结论 DC-SIGN识别高甘露糖型HBV后可以促进DC的成熟和活化,天然的HBV可能利用α-甘露糖苷酶参与的去甘露聚糖修饰来逃避DC-SIGN的识别,从而诱导DC功能的缺陷。     

慢性重型肝炎患者肝组织内胆管增生的免疫组织化学研究

在慢性重型肝炎患者的肝组织切片中,除肝细胞大面积坏死、纤维组织增生、炎症细胞浸润及不同程度的肝细胞再生等病理特征外,还常有明显的胆管增生现象,但这种胆管增生的本质及意义尚不清楚。新近提出肝组织内胆管增生与肝干细胞     

Elevated serum CK18 levels in chronic hepatitis C patients are associated with advanced fibrosis but not steatosis

Summary. Cytokeratin‐18 (CK‐18) is a major intermediate filament protein in liver cells. The M30 fragment of CK‐18 has been identified as a useful marker of apoptosis associated with fibrosis and steatosis in nonalcoholic steatohepatitis (NASH). We sought to assess the relationship of this marker and steatosis in a cohort of adult patients with chronic hepatitis C. The study cohort included sera from 267 treatment‐naïve chronic hepatitis C (CHC) patients and 100 healthy controls with normal alanine aminotransferase (ALT). Biopsies from CHC patients were assessed for METAVIR fibrosis stage, Histology Activity Index (HAI) inflammation score and steatosis grade by expert histopathologists. The M30 fragment of CK‐18 was quantified by ELISA. Wilcoxon Rank Sum, Spearman Correlation and Linear Regression tests were performed for statistical analysis. Median CK‐18 levels were higher in CHC patients compared to controls (411 vs 196 U/L, P < 0.0001). Fibrosis stage was associated with increasing serum CK‐18 levels (P = 0.015) and CK‐18 levels were higher for F2–F4 vs F0–F1 (500 vs 344 U/L; P = 0.001). There was no association between CK‐18 and increasing steatosis grade 1, 2 or 3 (460.7 vs 416.8 vs 508.3 U/L; P = 0.35) and presence or absence of steatosis (445.3 vs 365.8 U/L; P = 0.075). Fibrosis stage was independently associated with serum M30 in a multivariable linear regression model (P = 0.03). CK‐18 levels were higher in CHC compared to healthy controls and associated with hepatic fibrosis. There was no difference in CK‐18 M30 levels between CHC patients with and without steatosis. Although apoptosis may still contribute to hepatitis C virus (HCV)‐mediated steatosis, our results suggest that serum CK‐18 will not be a clinically useful test for identifying significant steatosis in CHC.     

Viral suppression correlates with dendritic cell restoration in chronic hepatitis B patients with autologous cytokine‐induced killer cell transfusion

Background: Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are functionally impaired in patients with chronic hepatitis B (CHB). Adoptive immunotherapy can suppress hepatitis B virus (HBV) replication in CHB patients, but whether it can restore the functionality of mDCs and pDCs remains unknown. Methods: Autologous cytokine‐induced killer (CIK) cells obtained from 14 CHB patients were transfused back to patients, case by case, to observe the effect of CIK‐cell treatment on the frequency and functionality of mDCs and pDCs in CHB patients during a 24‐week follow‐up investigation. Results: Seven virological responders exhibited a sustained decrease in HBV load after CIK‐cell transfusion; another seven non‐virological responders showed only sustained high levels of HBV load during the 24‐week period following CIK‐cell transfusion. The rate of hepatitis B e antigen loss or seroconversion was also higher in virological responders than in non‐virological responders. Importantly, we found that the frequency and cytokine‐producing capacity of mDCs and pDCs increased significantly in virological responders, but not in non‐virological responders. In addition, these patients exhibited a close correlation between restoration DC subsets and a decrease in HBV DNA load, rather than a change in the alanine aminotransferase level. Conclusion: Cytokine‐induced killer‐cell treatment reduced HBV DNA load in some CHB patients; the efficiency at least partially correlates with the restoration of frequency and functionality of mDCs and pDCs.     

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.     

Comparing the safety,tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha‐2a

Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha‐2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)‐positive (n=271) and HBeAg‐negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg peginterferon alpha‐2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health‐related quality of life (HRQL) was assessed using the Short‐Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24‐week treatment‐free follow‐up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression‐related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha‐2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon‐related AEs and a significantly lower incidence of depression.     

HBsAg阴性的慢性乙型和丙型重叠感染肝炎患者临床研究

为探讨HBsAg阴性的慢性乙型重叠丙型肝炎患者HBV -DNA水平及临床特征 ,采用PCR -微板核酸杂交 -ELISA法对 2 0 3例HBVM一项 /一项以上阳性的慢性丙型肝炎患者进行HBV -DNA定量及HCV -RNA基因分型检测 ,并分析患者性别、年龄以及肝功能等临床特征。HBsAg阴性及HBsAg阳性慢性丙型肝炎患者在性别、年龄分布上无差异 ;但血清ALT及总胆红素水平在HBsAg阳性者较高。Ⅱ / 1b型HCV感染在HBsAg阴性者中的比例高于HBsAg阳性者 (P <0 0 5 )。HBsAg阴性慢性丙肝患者HBV -DNA阳性率及HBV水平均低于HBsAg阳性患者。HBsAg阴性的慢性丙肝患者中 ,抗HBc单独阳性者HBV -DNA阳性率最高 ,但HBV -DNA水平无显著性差异。Ⅱ /1b型HCV感染在HBV -DNA阴性患者中的出现频率较高 ,与HBV -DNA阳性患者相比差异有显著性。因此 ,临床上对于那些肝功能损害严重 ,同时有抗HBc阳性或Ⅱ / 1b型HCV感染 ,尤其是HCV -RNA阴性而肝功能仍有持续损害的患者要及时行HBV -DNA检测 ,以除外HBV活动的可能     

细胞因子诱导的自体杀伤细胞回输治疗慢性乙型肝炎患者树突状细胞功能的研究

目的了解细胞因子诱导的自体杀伤（CIK）细胞回输治疗是否能恢复慢性乙型肝炎（CHB）患者树突状细胞（DC）的功能。方法12例CHB患者应用CIK细胞回输治疗,入组前6个月至CIK细胞治疗随访期间,患者未接受任何抗病毒及免疫调节治疗。观察24周后患者髓样树突状细胞（mDC）、浆细胞样树突状细胞（pDC）比例和功能变化,并对其变化结果进行分析。结果应用CIK细胞回输治疗24周后,病毒载量下降≥2个log或转阴的患者外周血mDC、pDC功能明显提高。病毒学应答患者（n=6）病毒载量下降水平与外周血DC功能的恢复密切相关。结论CHB患者接受CIK细胞回输治疗可以提高外周血mDC和pDC功能。     

Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan.

BACKGROUND/AIMS: The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. We therefore studied the prevalence of HFE mutations and their impact on the progression of chronic viral hepatitis in Taiwan. PATIENTS & METHODS: H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism in 152 chronic hepatitis B patients with various stages of liver disease, 87 chronic hepatitis C patients with various stages of liver disease, and 49 healthy controls. The distribution of each allele frequency was then compared among different groups of patients and in various stages of liver disease. RESULTS: All three groups of patients were C282Y wild type and the majority of H63D mutations were heterozygotes. Although statistically not significant, allele frequencies of H63D mutation in hepatitis B-related liver cirrhosis (6%) and hepatitis C-related liver cirrhosis (9.1%) were higher than those in healthy control (2%). After adjustment for age and sex, hepatitis B patients with H63D heterozygosity had a higher likelihood of cirrhosis than those with H63D wild type (odds ratios (OR): 3.2, confidence interval (CI): 0.49-20.5, P = 0.22). Similarly, hepatitis C patients with H63D homozygosity had a higher likelihood of cirrhosis compared with those with H63D wild type (OR: 2.35, CI : 0.19-28.5, P = 0.52). CONCLUSIONS: Almost all Taiwanese are C282Y wild type. H63D heterozygote and homozygote, occurring in less than 5% of the subjects, tended to be associated with the development of liver cirrhosis, irrespective of viral etiology. Screening for H63D mutation might be considered in patients with chronic viral hepatitis in Taiwan.     

Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus‐induced activation

Chronic hepatitis C virus (HCV) infection is characterized by persistent B‐cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B‐cell subset distribution, we examined ex vivo frequencies and B‐cell inhibitory receptor expression in 37 chronic HCV‐infected patients and 25 healthy donors (HD). In addition, we determined whether short‐term exposure to culture‐derived HCV (HCVcc) resulted in B‐cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue‐like memory (TLM) B cells in HCV‐infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor‐like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B‐cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell‐free HCVcc in vitro did not result in B‐cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV‐infected patients but not in HD, in whom cell‐associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B‐cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B‐cell subsets does not impair virus‐induced B‐cell activation.     

Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment

Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases (CLD) is crucial, as liver fibrosis is important in determining the prognosis of liver diseases. Currently, liver biopsy (LB) is considered the gold standard for staging liver fibrosis or cirrhosis. However, utilization of LB in clinical practice is often limited because of its invasive nature, sampling error and interobserver variability. Recently, transient elastography (TE) was introduced as a noninvasive, highly reproducible technique for assessing the degree of liver fibrosis. After extensive studies, TE is now regarded as a reliable surrogate marker for grading the severity of liver fibrosis in patients with CLD. In the past few years, the role of TE in monitoring liver stiffness and determining prognosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who are undergoing antiviral treatment has been investigated. In patients with CHB, liver stiffness values decrease with antiviral treatment. TE can also be used to predict the incidence of liver‐related events during antiviral treatment. In patients with CHC, TE can be used to monitor potential regression of liver fibrosis after antiviral treatment and may predict the treatment outcome of CHC. In addition, TE is an adjunct tool for distinguishing inactive hepatitis B virus carriers from patients with chronic active hepatitis. This review article discusses the important findings from recent studies focusing on the clinical application of TE in patients with chronic viral hepatitis who are undergoing antiviral treatments.     

Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN-alpha therapy.

AIMS: The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. METHODS: Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. RESULTS: The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. CONCLUSIONS: IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.     

Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection

Summary. A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte‐derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti‐HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti‐HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte‐derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA‐II), B7 expression and interleukin‐12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor‐α improved HLA‐II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC‐T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.     

Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2)

BACKGROUND AND AIM: To investigate the frequencies, numbers and function of circulating dendritic cell (DC) subsets in patients with hepatitis B virus (HBV) infection, we assayed the circulating precursor DC subsets (including pDC1 and pDC2) and their ability in patients at various stages of HBV infection in vitro. METHODS: Circulating pDC1 and pDC2 frequencies in peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometric analysis. Costimulatory molecule expression and allostimulatory mixed lymphocyte reaction (AMLR) of DC1, cultured from PBMC in vitro, were detected in patients with chronic hepatitis B (CHB). On behalf of pDC2, interferon (IFN)-alpha production of PBMC was determined by the ELISA method in HBV-infected patients. RESULTS: The number of circulating pDC1 decreased only in patients with liver cirrhosis (LC) compared with that in normal controls. However, pDC2 numbers decreased in both CHB and LC patients. DC1 from CHB patients showed lower expression of costimulatory molecules CD80, CD86 and impaired allostimulatory mixed lymphocyte reaction (AMLR) compared with those in normal controls. The ability of PBMC to secrete IFN-alpha also decreased significantly in patients with chronic HBV infection. CONCLUSIONS: Our results suggest that patients with chronic HBV infection have a significantly lower expression of costimulatory molecules and impaired AMLR of pDC1, as well as decreased number and impaired function of circulating pDC2, which may be partially related to HBV disease progression in these patients.     

不同类型慢性乙肝病毒感染者外周血树突状前体细胞亚群的变化特点

目的观察不同类型慢性乙肝病毒感染者外周血树突状前体细胞（pDC）亚群的变化,探讨pDC亚群在慢性乙肝病毒感染自然史中的意义。方法采集健康对照组15例,免疫耐受组19例,慢性乙型肝炎组26例,非活动性组33例的外周血,用流式细胞技术检测髓样树突状前体细胞（pDC1）和浆细胞样树突状前体细胞（pDC2）。结果与健康对照组比较,慢性乙型肝炎组pDC2显著下降（P〈0.05）,慢性乙型肝炎组pDC1显著高于免疫耐受组（P〈0.05）,非活动性组pDC2显著高于免疫耐受组和慢性乙型肝炎组（P〈0.05）。相关性分析表明,HBVDNA水平与pDC2之间存在正相关（r=0.303,P=0.043）。结论慢性乙肝病毒感染自然史不同阶段的外周血树突状前体细胞（pDC）亚群的频率和数量的变化,可能与HBV持续感染的机制和肝炎的发病机制有关。     

Characteristics of regulatory T‐cell function in patients with chronic hepatitis B and C coinfection

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy‐four untreated HBV/HCV co‐infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV‐active/HCV‐active (BACA), HBV‐inactive/HCV‐active (BICA), HBV‐active/HCV‐inactive (BACI) and HBV‐inactive/HCV‐inactive (BICI). Treg frequency was calculated as the fraction of CD4⁺Foxp3⁺T cells among CD4⁺T cells. Treg‐mediated inhibition was measured as percent of inhibition of T‐cell proliferation. The expression of interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and interleukin (IL)‐10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4⁺Foxp3⁺T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis‐4 (FIB‐4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN‐γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co‐infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.     

负载HBcAg对慢性HBV感染患者树突状细胞的活化作用及功能影响

目的:探讨免疫耐受期慢性乙型肝炎(CHB)患者外周血树突状细胞(DC)负载HBcAg后细胞表型及免疫功能的改变。方法:从CHB免疫耐受期患者外周血分离培养DC,在DC成熟前,加入重组HBcAg表位肽,诱导HBV特异性DC分化成熟,流式细胞仪检测DC表面共刺激分子CD1a、CD80、CD83的表达水平,应用淋巴细胞增殖试验评估DC功能。结果:负载不同剂量的HBcAg后,DC细胞活化增强,DC细胞共刺激分子标志物CD1a、CD80以及CD83表达率均明显上升,且随着抗原负载剂量的增加,表达率进一步增加,各组之间差异具有统计学意义(均P<0.001);未负载HBcAg的DC细胞激活的淋巴细胞反应较弱,负载HBcAg的DC细胞刺激同种异体健康成人T淋巴细胞增殖能力增强,且随着负载抗原剂量的加大,T淋巴细胞的增殖能力进一步提高,与未负载抗原的对照组相比,差异具有统计学意义(F=428.14,P=0.000)。结论:体外负载HBcAg刺激CHB患者DC细胞可增强其有效抗原提呈能力,促进T淋巴细胞增殖。