Fcγ receptor expression on hepatic macrophages and histological activity of chronic hepatitis

Abstract: Aims/Background: Activated liver macrophages in chronic hepatitis express a high affinity receptor for IgG named FcγRI. This study was performed to find the difference in FcγRI expression between chronic hepatitis B (CHB) and C (CHC) with reference to histological activity. Methods: Consecutive patients with CHB (20 cases) and CHC (25 cases) were enrolled in the study. Inflammatory activity was evaluated using the modified histological activity index (HAI). FcγRI-positive macrophages were quantitatively measured by computer assisted morphometry. Results: Total HAI score was significantly higher in CHB than in CHC. Confluent necrosis was observed in significantly higher frequency in CHB at Stages 3–5 than in CHC. The percentage area of FcγRI-positive macrophages was significantly higher in CHB than in CHC. In CHB, the percentage area of FcγRI-positive macrophages correlated with total HAI (< 0.01) as well as the degree of confluent necrosis (< 0.01), interface hepatitis (< 0.05) and portal inflammation (< 0.05). FcγRI-positive macrophages accumulated mainly at the site of confluent necrosis. In CHC, no correlation was observed between activated macrophages and any histological categories. Conclusion: These results suggest that FcγRI-positive macrophages are associated with confluent necrosis in CHB, which is more common in CHB patients than in CHC.     

The impact of antiviral therapy for HCV on kidney disease: a systematic review and meta-analysis

BackgroundControversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease.Study Aims and DesignA systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out.ResultsFifteen studies were eligible (n = 356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n = 7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p = 0.0016) and between-study heterogeneity was found (p-value by Q test = 0.004). Aggregation of studies comparing treated vs untreated cohorts (n = 8, n = 333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p = 0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p = 0.02) and HBV infection (p = 0.0001) increase among HCV-infected individuals.ConclusionsAntiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing.     

Factors associated with progression of the disease before transplantation in patients with autoimmune hepatitis

Abstract: Aims/Background: Studies on transplanted patients may provide clinically useful data on factors influencing progression of autoimmune hepatitis (AIH) since transplantation rather than death may now be considered as the most likely end-point of the disease. The aim of this work was to analyze risk factors related to progression of AIH before transplantation and provide guidelines for further prognostication with regards to the timing of transplantation. Methods: 80 liver transplants in 68 patients with AIH were performed in our unit. The diagnosis was established on conventional clinical criteria. Parameters such as sex, age at diagnosis and transplantation or duration of the disease were evaluated in relation to: patient HLA DR status, disease presentation (aggressive or non-aggressive), presence of anti-LKM antibodies and concurrent immune disease. Results: AIH with concurrent immune disease occurred more commonly in females (90 vs. 61%; p= 0.0075) and was linked with markedly slower progression of the disease (125 vs. 66 mo; p=0.002) as compared to subjects without such association. AIH without concurrent autoimmune disease occurred significantly more commonly in patients with DR3 phenotype (p= 0.01). Patients with positive anti-LKM autoantibodies were younger at transplantation (25.6 vs 43.5 yr; p= 0.006) and had more rapid progression of their disease (14.3 vs. 103 mo; p= 0.001). Unlike previously reported series of non-transplanted patients, all anti-LKM positive subjects had no concurrent autoimmune disease. Conclusions: Coincidence with another autoimmune disease is associated with a significantly longer disease history prior to transplantation and may possibly reflect greater responsiveness to immunosuppressive therapy before grafting. AIH without concurrent autoimmune disease, particularly if associated with DR4 negative phenotype, male sex and anti-LKM antibodies may characterize patients with rapid progression of the disease. None of these factors had a significant influence on 5 year survival after surgery.     

改良PCR法检测外周血单个核细胞中的HBV DNA与HBVcccDNA

目的检测慢性HBV感染者外周血单个核细胞(PBMCs)中HBV DNA的存在状况。方法采用改良PCR法检测慢性HBV感染者PBMCs中HBV DNA、共价闭合环状DNA(cccDNA)。结果120例慢性HBV感染者PBMCs中HBV DNA、cccDNA阳性检出率分别为62.50%、45.83%,HBV DNA阳性检出率高于cccDNA(P<0.01);其中HBeAg阳性组PBMCs中HBV DNA(80.00%)和cccDNA阳性检出率(45.00%)分别明显高于HBeAg阴性组(61.67%)(30.00%)(P均<0.01);PBMCs中HBVDNA检测阳性者血清HBVDNA水平明显高于HBVDNA检测阴性者(P<0.01)。结论改良PCR法检测表明HBV DNA不仅可感染PBMCs,且部分参与复制;PBMCs中HBVDNA存在和复制能力与HBeAg阳性相关;PBMCs中HBV DNA阳性检出率与血清HBV DNA水平有一致性。     

慢性乙型肝炎患者应用泌胆剂的益处

目的：探讨泌胆剂对慢性乙型肝炎的辅助治疗作用。方法：158例慢性乙型肝炎患者随机分为泌胆剂组和对照组。对照组给予一般护肝治疗，泌胆剂组在一般护肝治疗基础上同时给予泌胆剂（加诺，3次／d，1～2片／次）治疗3月。两组病例如具备抗病毒治疗指针，则给予干扰素抗病毒治疗6个月。比较各组患者治疗中和治疗结束时的生化和／或病毒学指标。结果：和对照组相比，泌胆剂组患者血清ALT、AST和TBil治疗后下降幅度均较大。其中，在非抗病毒患者，泌胆剂组治疗1月和3月时的AST及TBil水平、治疗3月时ALT水平显著低于对照组；在抗病毒治疗患者，泌胆剂组治疗1、3、6月时的TBil水平及治疗1、6月时AsT水平与对照组比较差异有显著意义。在抗病毒治疗的患者，泌胆剂组病毒应答指标（包括治疗3和6月时的HBV DNA阴转率、e系统血清学转换率）以及ALT复常率较高，但未达统计学意义水平。结论：泌胆剂作为慢性乙型肝炎患者的辅助治疗，能改善患者肝功能生化指标。是否增强陧性乙型肝炎干扰素抗病毒疗效有待进一步研究。     

苦参素对慢性病毒性肝炎及肝硬化患者血清胆碱酯酶影响的初步观察

观察苦参素对慢性病毒性肝炎及肝炎后肝硬化患者血清胆碱酯酶的影响。 4 8例患者分成慢性肝炎组(36例 )和肝硬化组 (12例 ) ,检测苦参素治疗前、后患者血清中胆碱酯酶及肝功能生化指标。苦参素治疗后患者血清胆碱酯酶明显下降 ,但疗程大于 3个月后 ,胆碱酯酶可稳定于一个较低的水平 ;患者均未出现明显的副反应 ;停药后胆碱酯酶能较快地恢复原水平。苦参素能明显降低患者血清中胆碱酯酶水平 ,而且这种作用为可逆性 ,可能不会引起明显的不良反应。     

乙型肝炎病毒基因型与干扰素α1b疗效关系的研究

目的　探讨乙型肝炎病毒 (HBV)基因型与干扰素α1b治疗慢性乙型肝炎疗效的关系。方法　采用PCR、核酸杂交和酶联显色技术对慢性乙型肝炎患者进行HBV基因分型 ,随机观察 10 5例 (B型 5 3例和C型 5 2例 )慢性乙型肝炎患者干扰素α1b治疗 6个月和随访半年后肝功能和病毒学指标的变化。结果　干扰素α1b治疗 6个月和随访半年后 ,B基因型患者的HBeAg阴转率、HBVDNA阴转率和HBeAg/抗 HBe的血清转换率均显著高于C基因型 (P <0 . 0 1) ,B基因型患者的有效应答率为 5 2 . 83 %,显著高于C基因型的 2 5 . 0 0 %(P <0 . 0 1)。B基因型的持续应答率高于C型 ,复发率低于C型 ,但两组差异无显著性 (P >0 . 0 5 )。结论　B基因型对干扰素α1b的抗病毒疗效显著高于C型 ,HBV基因型是影响干扰素α1b疗效的重要因素之一。     

乙肝病毒特异性转移因子治疗慢性乙型肝炎的临床研究

目的　评价乙肝病毒特异性转移因子治疗慢性乙型肝炎的临床疗效。方法　选择慢性乙型肝炎 86例 ,随机分为两组。对照组 40例 ,应用常规保肝降酶疗法 ;研究组 46例 ,在保肝降酶疗法的基础上加用乙肝病毒特异性转移因子。结果　研究组HBeAg及HBVDNA的阴转率显著高于对照组 (P <0 0 5 ) ,抗 HBe阳转率亦显著高于对照组 (P <0 0 1)。结论　乙肝病毒特异性转移因子用于治疗慢性乙型肝炎 ,可以改善患者的乙肝病毒病原学指标。     

插入CpG序列的乙肝病毒核心抗原基因真核表达质粒的构建及在树突状细胞中的表达

目的：构建pEGFP—N1／CpG-HBcAg（ISS）真核表达载体，探讨乙肝病毒核心抗原（HBcAg）在树突状细胞（DC）中的表达，为研制乙肝治疗性疫苗奠定基础。方法：根据HBcAg基因序列，设计合成两对引物，在引物中引入针对人敏感的CpG基序和不合CpG的片段，用PCR方法从慢性乙型肝炎患者血清HBVDNA中扩增出HBcAg基因片段，将扩增产物与pEGFP—N1连接，构建重组体pEGFP—N1／CpG-HBcAg，进行酶切、PCR及测序鉴定；分离人外周血单个核细胞（PBMC），体外诱导分化为DC，通过脂质体将重组质粒pEGFP—N1／CpG-HBcAg和空载体分别转染DC，Western blot检测HBcAg在DC的表达。结果：HBcAg基因体外扩增产物大小为530bp。所构建的pEGFP-N1／CpG—HBcAg经双酶切及PCR鉴定，与预期片段的大小相符。测序结果与GenBank中收录的HBcAg全长序列一致，表明pEGFP—NI／CpG-HBcAg真核表达体构建正确；PBMC体外成功刺激分化为DC，HBcAg可在DC中表达。结论：成功构建了真核重组表达载体pEGFP—N1／CpG—HBcAg，且可在DC中表达，为CpG的功能研究和乙型肝炎治疗性疫苗的研制奠定基础。     

Interleukin-10 promoter polymorphisms are associated with the mode and sequel of HBeAg seroconversion in patients with chronic hepatitis B virus infection.

BACKGROUND: The influence of interleukin-10 (IL-10) gene promoter polymorphisms on the mode and sequel of HBeAg seroconversion (a favorable event usually) in patients with chronic Hepatitis B virus (HBV) infection has not been clarified. PATIENTS AND METHODS: IL-10 genotyping and haplotype analyses of 340 HBsAg carriers and 100 volunteers with self-limiting HBV infection from southern China, a high prevalent area of HBV were performed according to the single nucleotide polymorphisms in its promoter (-1,082, -819 and -592) using a competitively differentiated PCR. RESULTS: High-producer genotype (GG at -1,082) or haplotype (GCC) was rarely found in patients from southern China (<1%). Intermediate-producer haplotype (ACC) was closely associated with chronic liver disease (P=0.004); compared with this, low-producer genotype (AA at -592) and haplotype (ATA) were closely associated with asymptomatic carriers (P=0.035 and 0.035). Intermediate-producer genotype (AC at -592) and haplotype (ACC) were closely associated with covert seroconversion of HBeAg (P=0.0086 and 0.0013) and progressive sequel after HBeAg seroconversion (P=0.013 and 0.0008), while, low-producer genotype (AA at -592) and haplotype (ATA) were closely associated with overt seroconversion of HBeAg (P=0.0023 and 0.0061) and silent sequel after HBeAg seroconversion (P=0.0009 and 0.001). CONCLUSIONS: IL-10 gene promoter polymorphisms significantly influence the mode and sequel of HBeAg seroconversion in patients with chronic HBV infection.