Alcohol-Induced Expression of the CD14 Endotoxin Receptor Protein in Rat Kupffer Cells

Gut-derived endotoxins (lipopolysaccharide, LPS) are believed to contribute to alcohol-induced liver disease (ALD) by stimulating Kupffer cells, the resident liver macrophages, to release proinflammatory cytokines. This activation is largely mediated by CD14, a high-affinity membrane-anchored receptor for LPS. We observed, by chemiluminescence-enhanced detection, an increase in immunoreactive CD14 protein in Kupffer cells isolated from rats treated with ethanol for 2 weeks. Immunocytofluorescence experiments confirmed that this increase was confined to the membranes of Kupffer cells from the alcohol-treated rats. The increase was regulated pretranslationally: a 3-fold elevation ( p < 0.01) in the hepatic level of CD14 mRNA was observed. The marked increase in CD14 expression suggests a new mechanism by which alcohol increases the LPS-mediated cytokine signaling by the liver macrophages, thus promoting the interaction between alcohol and endotoxins in the development of liver damage.     

Association of promoter polymorphism of the CD14 C （-159） T endotoxin receptor gene with chronic hepatitis B

INTRODUCTION An estimated 350 million persons worldwide are infected with hepatitis B virus (HBV). Hepatitis B carriers are at risk for development of cirrhosis and hepatocellular carcinoma. Persons with chronic hepatitis B infection need life-long monito…     

CD36 genetic variation,fat intake and liver fibrosis in chronic hepatitis C virus infection

AIM To analyze the association of the CD36 polymorphism(rs1761667) with dietary intake and liver fibrosis(LF) in chronic hepatitis C(CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 genotype(G A) was determined by a TaqM an real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography(Fibroscan~)and APRI score was classified as mild LF(F1-F2) and advanced LF(F3-F4).RESULTS Overall, the CD36 genotypic frequencies were AA(30.1%), AG(54.8%), and GG(15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase(AST) serum values were higher in AA genotype carriers compared to non-AA carriers(91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST(β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG(OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes(OR = 3.52, 95%CI: 1.18-10.45, P = 0.02).CONCLUSION This study suggests that the CD36(rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients.     

丙型肝炎患者IL28B基因型和HCV基因型对抗病毒治疗的影响

目的:研究丙型肝炎患者IL28B基因相关的rs12979860基因型和HCV基因型对聚乙二醇干扰素α和利巴韦林联合抗病毒治疗疗效的影响.方法:对干扰素α联合利巴韦林治疗后获得持续病毒学应答(SVR)和无应答(NR)的各30例丙型肝炎患者的血液样品样进行检测,采用PCR反向斑点杂交法进行HCV基因分型,采用聚合酶链-连接...     

Relevance of endotoxin receptor CD14 and TLR4 gene variants in chronic liver disease

Objective. The lipopolysaccharide (LPS)-triggered release of inflammatory cytokines from Kupffer cells is mediated via the CD14/TLR4 receptor complex. This inflammatory pathway can be influenced by alterations in genes encoding for LPS receptor components. Thus, a -260 C>T transition in the CD14 promoter is thought to result in enhanced CD14 expression thereby increasing the LPS responsiveness in chronic liver diseases, whereas a D299G exchange in the TLR4 gene has the opposite effect. Our objective was to analyze these two variations. Material and methods. The study comprised 1712 patients with chronic liver diseases of different etiologies and 385 healthy controls. Genotyping was carried out by melting curve analysis with fluorescence resonance energy transfer (FRET) probes in the LightCycler. Results. Genotype frequencies of CD14 -260C>T and TLR4 D299G did not significantly differ between patients and controls (CD14 TT 21.6% versus 21.8%; TLR4 DG or GG 9.7% versus 10.4%). We found no significant correlation of these alterations with disease course either in the groups of patients with alcoholic liver disease or hepatitis C virus (HCV) infection or among patients requiring liver transplantation. A significantly higher frequency of the CD14 -260TT genotype was observed (36.6% versus 21.8% in healthy controls, p=0.036) only in a small subgroup of patients (n=41) with mild cryptogenic chronic liver disease. Conclusions. Variants within these LPS receptor genes were equally distributed among patients with chronic liver diseases of different etiologies and obviously do not confer an increased risk for the severity of these chronic liver processes.     

CD14的基因型及血清水平与急性心肌梗死的关系

目的 研究CD14基因启动子-159C/T、-260C/T多态性各等位基因及基因型在急性心肌梗死(AMI)患者中的分布频率,初步分析其基因型及血清水平与AMI的相关性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测120例AMI患者及130例正常对照组CD14的基因多态性,同时采用酶联免疫吸附试验(ELISA)检测血清CD14水平.结果 AMI组血清CD14水平显著高于对照组(P<0.01),CD14基因-159C/T多态性在AMI组和正常人群中的分布差异无显著性(P>0.05),而CD14基因-260C/T多态性在两组人群中的分布差异存在显著性(P<0.05),等位基因频率的相对风险分析发现,T等位基因携带者患AMI的风险是C等位基因的1.654倍(OR=1.654,95%CI:1.161～2.356),携带T等位基因的AMI患者血清CD14水平显著高于不携带者(P<0.05).结论 CD14基因启动子-260C/T多态性与AMI的发病具有相关性,其中T等位基因可能是AMI发病的遗传易感基因;携带T等位基因的个体可能通过促进CD14的高度表达进而增加了AMI的发病风险.     

实验性酒精性肝病时脂多糖结合蛋白和脂多糖受体CD14的表达

目的观察大鼠酒精性肝病时脂多糖结合蛋白(lipopolysaccharide binding protein,LBP)和脂多糖受体CD14的表达及其在酒精性肝损害中的作用.方法随机将Wistar大鼠分为乙醇喂养组和葡萄糖喂养对照组,分剐在饮水中加入乙醇(剂量5-12 g@kg-1@d-1)和相同量的葡萄糖.两组大鼠分别于4周和8周测定其血浆中内毒揪素(LPS)浓度及血清中ALT变化,同时用RT-PCR测定肝组织中LBP和CD14 mRNA的表达,并在光镜和电镜下观察肝脏的形态学改变.结果乙醇喂养组4周和8周时大鼠血浆LPS浓度分别为(129±21)pg/ml和(187±35)Pg/m1,明显高于对照组的(48±9)pg/ml和(53±11)pg/ml(f值分别为11.2和11.6,P＜0.05);乙醇组大鼠血清ALT浓度为(112±15)U/L和(147±22)U/L,也明显高于对照组的(31±12)U/L和(33±9)U/L(t值分别为5.9和20.6,P＜0.05).乙醇组大鼠肝组织中LBP和CD14 mRNA的表达水平明显高于对照组(P＜0.05),其肝组织发生显著的病理变化,主要表现为脂肪变性、炎性细胞浸润及细胞坏死.对照组肝组织中LBP和CD14mRNA无明显表达,其病理变化也不明显.结论乙醇能诱导大鼠血中LPS浓度升高和肝缝织中LBP与CD14 mRNA的表达显著增强,增高的LBP和CD14 mRNA能增加肝脏对LPS的敏感性,可能造成肝脏损害.     

CD14和Toll样受体4的表达在内毒素致肝炎重型化中的意义

目的 探讨CD14和Toll样受体4(TLR4)在内毒素(LPS)诱导机体炎性因子分泌过程中的作用,阐明乙型肝炎重型化的机制. 方法 采用流式细胞学方法和逆转录聚合酶链反应等技术,检测30例慢性重型乙型肝炎患者,30例慢性乙型肝炎患者和20名健康者(对照组)的外周血单核细胞的mCD14水平及CD14 mRNA,TLR4 mRNA表达水平,同时应用动态浊度法测定患者血浆LPS水平,应用酶联免疫吸附法检测患者血清肿瘤坏死因子(TNF)α、白细胞介素(IL)-1 β,IL-6的含量.数据的统计分析采用SPSS11.5统计软件完成,分别采用单因素方差分析、非参数检验、Nemenyi法和直线相关分析.结果 外周血单个核细胞mCD14表达水平:慢性重型乙型肝炎组为74.2%±12.3%,慢性乙型肝炎组为63.6%±11.8%,对照组为60.3%±7.20/;CD14mRNA和TLR4 mRNA的相对表达:慢性重型乙型肝炎组分别为2.92±0.67和1.86±0.45,慢性乙型肝炎组分别为1.34±0.51和0.93±0.18,对照组分别为0.92±0.58和0.73±0.16,慢性重型乙型肝炎组均明显高于慢性乙型肝炎组和对照组,F值分别为11.473、85.037和102.328,P值均<0.01,差异有统计学意义.血浆LPS、IL-l,IL-6水平:慢性重型乙型肝炎组分别为(1.87±1.61)Eu/ml,(0.96±0.16)pg/ml和(68.34±48.30)pg/ml,慢性乙型肝炎组分别为(0.11±0.11)Eu/ml、(0.19±0.02)pg/ml,(19.28±4.65)pg/ml,对照组分别为(0.03±0.03)Eu/ml、(0.15±0.01)pg/ml、(12.01±3.88)pg/ml,慢性重型乙型肝炎组均明显高于慢性乙型肝炎组和对照组,χ2值分别为32.065、83.472、36.236,P值均<0.01.外周血TNFα表达水平:慢性重型乙型肝炎组为(19.78±9.25)pg/ml、慢性乙型肝炎组分别为(7.26±6.52)pg/ml、对照组分别为(4.15±4.06)pg/ml、F=35.092,P<0.01.相关分析显示,在慢性重型乙型肝炎组LPS水平与mCD14、CD14:mRNA,TLR4 mRNA表达水平呈明显的相关性,n=0.865、r2=0.415、r3=0.524,P值均<0.05.结论 LPS可能通过以CD14和TLR4为主的LPS受体激活及其信号传导,刺激炎性因子分泌的途径,在肝炎重型化过程中发挥重要作用.     

Role of simple biomarkers in predicting fibrosis progression in HCV infection

AIM: To examine the accuracy of the aspartate aminotransferase (AST)/Platelet Ratio Index (APRI) and FIB-4, in predicting longitudinal changes in liver histology in hepatitis C virus (HCV) patients.METHODS: Patients that underwent repeat liver biopsies at least 1 year apart from 1999 to 2007 were identified. Liver fibrosis was staged on needle core biopsies evaluated by a single expert liver pathologist. Only laboratory values within 3 mo of the liver biopsies were used.RESULTS: Thirty-six patients met the inclusion criteria with 50% stage 1 on initial biopsy, 25% stage 2, and 22% stage 3. Nineteen of 36 (53%) had progression of fibrosis on repeat biopsies, while 16 (44%) showed no change in stage, and one (3%) showed improvement. Patients that showed progression of fibrosis had significantly higher alanine aminotransferase and aspartate aminotransferase levels than the group that did not show progression. A significant correlation was seen between change in stage of fibrosis and change in APRI (r2 = 0.39, P = 0.00001) and a change in FIB-4 (r2 = 0.31, P = 0.00004). A change in APRI (ΔAPRI) of 0.18 had 80% positive predictive value (PPV) and 67% nega- tive predictive value (NPV) for progression of fibrosis. A change in FIB-4 (ΔFIB-4) of 0.39 had 75% PPV and 75% NPV for predicting progression of fibrosis. CONCLUSION: ΔAPRI and ΔFIB-4 parallel changes in fibrosis progression, and could be useful tools for clinicians in following patients with active chronic HCV infection.     

Distinct toil-like receptor expression in monocytes and T cells in chronic HCV infection

AIM: Hepatitis C virus often establishes chronic infections. Recent studies suggest that viral and bacterial infections are more common in HCV-infected patients compared to controls. Pathogens are recognized by Toil-like receptors (TLRs) to shape adaptive and innate immune responses.METHODS: In this study, to assess the ability of HCV-infected host to recognize invading pathogens, we investigated Toil-like receptor expression in innate (monocytes) and adaptive (T cells) immune cells by real-time PCR.RESULTS: We determined that RNA levels for TLRs 2, 6. 7, 8, 9 and 10 mRNA levels were upregulated in both monocytes and T cells in HCV-infected patients compared to controls. TLR4 was only upregulated in T lymphocytes, while TLR5 was selectively increased in monocytes of HCV-infected patients. MD-2, a TLR4 coreceptor, was increased in patients' monocytes and T cells while CD14 and MyD88 were increased only in monocytes.CONCLUSION: Our data reveal novel details on TLR expression that likely relates to innate recognition of pathogens and immune defense in HCV-infected individuals.     

Distinct Toll-like receptor expression in monocytes and T cells in chronic HCV infection

AIM: Hepatitis C virus often establishes chronic infections. Recent studies suggest that viral and bacterial infections are more common in HCV-infected patients compared to controls. Pathogens are recognized by Toll-like receptors (TLRs) to shape adaptive and innate immune responses. METHODS: In this study, to assess the ability of HCV-infected host to recognize invading pathogens, we investigated Toll-like receptor expression in innate (monocytes) and adaptive (T cells) immune cells by real-time PCR. RESULTS: We determined that RNA levels for TLRs 2, 6. 7, 8, 9 and 10 mRNA levels were upregulated in both monocytes and T cells in HCV-infected patients compared to controls. TLR4 was only upregulated in T lymphocytes, while TLR5 was selectively increased in monocytes of HCV-infected patients. MD-2, a TLR4 co-receptor, was increased in patients' monocytes and T cells while CD14 and MyD88 were increased only in monocytes. CONCLUSION: Our data reveal novel details on TLR expression that likely relates to innate recognition of pathogens and immune defense in HCV-infected individuals.     

Keratoconjunctivitis sicca and chronic HCV infection

Background: The aim of this study was to determine the prevalence of keratoconjunctivitis sicca (KCS) in Greek patients with chronic hepatitis C virus (HCV) infection and its association with HCV genotypes and liver histology. Patients and Methods: 93 HCVAb (+) patients underwent lacrimal function testing (Schirmer-1 test, break-up time test and Rose-Bengal staining test) and estimation of serum cryoglobulins and autoantibodies. 80 healthy volunteers were included in the study as controls. Results: 34 out of 93 HCV patients (36.6%) and eight out of 80 healthy subjects (10%) had at least two abnormal lacrimal function tests suggestive of KCS (p < 0.001). Cryoglobulinemia was evident in 20 patients (21.5%), rheumatoid factor (RF) in 43 (46.2%), antinuclear antibodies (ANA) in 19 (20.4%), antinuclear antigens (anti-SS-A and anti-SS-B) in one (1.1%) and two (2.2%) patients, respectively. Reduced prevalence of KCS was found in patients with genotype 3a compared to those with other genotypes (5/30, 16.7% vs 20/42, 47.6%, p = 0.007), probably because of their younger age. In patients with KCS a higher staging score was noted in liver biopsy compared to those without KCS (4.50 ± 1.65 vs 3.06 ± 1.88, p = 0.005). Conclusion: Greek patients with chronic HCV infection have a high prevalence of KCS (36.6%). The tow frequency of antiSS-A and anti-SS-B antibodies in these patients denotes different pathogenetic associations from primary Sjogren's syndrome. Received: May 5, 2001 · Revision accepted: April 4, 2002     

丙型肝炎病毒感染与脂肪性肝病

HCV除引起肝脏损害外,还与肝细胞癌(HCC)以及某些肝外组织的损害表现密切相关.大量研究报道,HCV慢性感染与2型糖尿病、脂肪肝等代谢性疾病的发生,发展密切相关[1].     

慢性丙型肝炎患者HCV准种的变化及其意义

目的　探讨HCV准种与丙型肝炎慢性化的关系。方法　以 3 0例HCVRNA(HVR1区PCR )阳性的丙型肝炎患者为研究对象 ,采用单链构象多态性分析 (SSCP)进行HCV准种检测。结果　 8例急性丙型肝炎、15例慢性丙型肝炎和 7例肝硬化患者的SSCP条带数分别为 ( 3 .13± 1.0 7)、( 5 .0 7± 1.48)和 ( 5 .5 7± 2 .15 ) ,慢性肝炎组、肝硬化组与急性肝炎组SSCP条带数比较有显著差异 (P <0 .0 5 )。通过输血或使用血制品感染HCV者共 17例 ,SSCP条带数为 ( 5 .3± 1.8) ,散发感染组 11例 ,SSCP条带数为 ( 3 .9± 1.6) ,两组比较有显著差异 (P <0 .0 5 )。 2 2例慢性丙型肝炎和肝硬化患者的SSCP条带数与病程相关系数分别为 0 .5 72 (Pearson’s相关 )和 0 .5 5 6(Spearman’s相关 ) ,与性别、年龄、ALT水平无相关性。结论　HCV准种数量与丙型肝炎慢性化密切相关 ;HCV准种数量与丙型肝炎感染途径相关 ,输血或血制品感染者HCV准种数量增多 ;HCV准种数量与病程呈正相关 ,感染时间长 ,HCV准种数量多。     

Polymorphisms in programmed death-1 gene are not associated with chronic HBV infection in Chinese patients

AIM:To investigate the association between the programmed death-1(PD-1) polymorphisms and genetic susceptibility of chronic hepatitis B virus(HBV) infection in Chinese patients.METHODS:Two single nucleotide polymorphisms(SNPs),PD-1.1 G > A and PD-1.2 G > A,were genotyped in 539 patients with chronic HBV infection and 353 other family members(HbsAg-) from 256 nuclear families using polymerase chain reactiorestriction fragment length polymorphisms assay.The associations between PD-1 polymorphisms and genetic susceptibilityof chronic HBV infection were analyzed usng the familybased association analysis method.RESULTS:No association or linkage was detected among 539 patients.Univariate(single-marker) familybased association tests demonstrated that PD-1 genotypes,alleles and transmitted haplotypes are not associated with chronic HBV infection(all with P value more than 0.05).Transmission/disequilibrium test and sibship disequilibrium test analysis showed no excess of the alleles from heterozygous parents to affected offspring(P = 0.688880,P = 1.000000 respectively).CONCLUSION:The data demonstrated that PD-1.1 and PD-1.2 polymorphisms are not associated with chronic HBV infection in Chinese patients.     

CD14和Toll样受体4的表达在内毒素致肝炎重型化中的意义

Objective To explore the roles of CD14 and TLR4 in severe hepatitis B induced by endotoxin. Methods The levels of mCD14 on PBMCs from 30 cases of severe hepatitis B, 20 cases of chronic hepatitis B and 20 cases of healthy controls were detected by flow cytometry. The expressions of CD14 mRNA and TLR4 mRNA in PBMCs from these patients were also detected by RT-PCR. Meanwhile, the concentration of plasma endotoxin was detected by limulus amebocyte lysate test and the levels of TNFα, IL-1, IL-6 in serum were detected by ELISA. Results The levels of mCD14 on PBMCs in severe hepatitis B, chronic hepatitis B and control were 74.2 ± 12.3,63.6 ± 11.8 and 60.3 ± 7.2 respectively. There was a significant difference among severe hepatitis B,chronic hepatitis B and healthy controls (both of P < 0.01). The expressions of CD14 mRNA and TLR4 mRNA (2.92 ± 0.67 and 1.86 ± 0.45) were also upregulated, compared with that in chronic hepatitis B patients (1.34 ± 0.51, 0.93 ±0.18) and healthy group (0.92 ± 0.58,0.73 ± 0.16) (P < 0.01). Similarly, the concentration of plasma endotoxin was much higher in severe hepatitis B (1.87 ± 1.61) than that in chronic hepatitis B patients (0.11 ±0.11) and that in healthy group (0.03 ± 0.03) (P < 0.01). As a result, the inflammation cytokines, shuch as TNF α, IL-1 and IL-6 (19.78 ± 9. 21,0.96 ± 0.16,68.34 ± 48.30) also increased significantly in severe hepatitis B, which were remarkably higher than those in chronic hepatitis B patients (7.26 ± 6.52,0.19 ± 0.02 and 19.28 ± 4.65) and healthy group (4.15 ± 4.06,0.15 ± 0.01 and 12.01 ± 3.88) (P< 0.01). Furthermore, correlation analysis showed there was positive correlation among the level of mCD14, the expression of CD14 mRNA/TLR4 mRNA, the concentration of endotoxin and the levels of inflammation cytokines in severe hepatitis B (r1 = 0.865, r2 = 0.415, r3 = 0.524, all of P < 0.05). Conclusion Endotoxin is an important factor in the aggravation of hepatitis B. Meanwhile, mCD14, CD14 mRNA and TLR4 mRNA are remarkably upregulated during the endotoxin stimulation. The inflammation cytokines (TNF α, IL-1 and IL-6) are also elevated, which may finally result in the aggravation of the hepatitis B. Therefore, CD14, TLR4 and inflammation cytokines play important roles in pathogenesis of severe hepatitis B induced by endotoxin.     

CD14和Toll样受体4的表达在内毒素致肝炎重型化中的意义

Objective To explore the roles of CD14 and TLR4 in severe hepatitis B induced by endotoxin. Methods The levels of mCD14 on PBMCs from 30 cases of severe hepatitis B, 20 cases of chronic hepatitis B and 20 cases of healthy controls were detected by flow cytometry. The expressions of CD14 mRNA and TLR4 mRNA in PBMCs from these patients were also detected by RT-PCR. Meanwhile, the concentration of plasma endotoxin was detected by limulus amebocyte lysate test and the levels of TNFα, IL-1, IL-6 in serum were detected by ELISA. Results The levels of mCD14 on PBMCs in severe hepatitis B, chronic hepatitis B and control were 74.2 ± 12.3,63.6 ± 11.8 and 60.3 ± 7.2 respectively. There was a significant difference among severe hepatitis B,chronic hepatitis B and healthy controls (both of P < 0.01). The expressions of CD14 mRNA and TLR4 mRNA (2.92 ± 0.67 and 1.86 ± 0.45) were also upregulated, compared with that in chronic hepatitis B patients (1.34 ± 0.51, 0.93 ±0.18) and healthy group (0.92 ± 0.58,0.73 ± 0.16) (P < 0.01). Similarly, the concentration of plasma endotoxin was much higher in severe hepatitis B (1.87 ± 1.61) than that in chronic hepatitis B patients (0.11 ±0.11) and that in healthy group (0.03 ± 0.03) (P < 0.01). As a result, the inflammation cytokines, shuch as TNF α, IL-1 and IL-6 (19.78 ± 9. 21,0.96 ± 0.16,68.34 ± 48.30) also increased significantly in severe hepatitis B, which were remarkably higher than those in chronic hepatitis B patients (7.26 ± 6.52,0.19 ± 0.02 and 19.28 ± 4.65) and healthy group (4.15 ± 4.06,0.15 ± 0.01 and 12.01 ± 3.88) (P< 0.01). Furthermore, correlation analysis showed there was positive correlation among the level of mCD14, the expression of CD14 mRNA/TLR4 mRNA, the concentration of endotoxin and the levels of inflammation cytokines in severe hepatitis B (r1 = 0.865, r2 = 0.415, r3 = 0.524, all of P < 0.05). Conclusion Endotoxin is an important factor in the aggravation of hepatitis B. Meanwhile, mCD14, CD14 mRNA and TLR4 mRNA are remarkably upregulated during the endotoxin stimulation. The inflammation cytokines (TNF α, IL-1 and IL-6) are also elevated, which may finally result in the aggravation of the hepatitis B. Therefore, CD14, TLR4 and inflammation cytokines play important roles in pathogenesis of severe hepatitis B induced by endotoxin.     

丙型、乙型肝炎混合感染者病毒基因型与临床特征分析

探讨丙型、乙型肝炎病毒混合感染的基因型特点及临床特征。采用ELISA法进行病毒血清标志物检测 ,采用PCR -微板核酸杂交 -ELISA法进行HBV -DNA定量及HCV -RNA基因分型检测。丙型、乙型肝炎病毒混合感染者HCV -RNA及HBV -DNA阳性率 (72 5 1%和 30 4 1% )分别低于丙型、乙型肝炎病毒单独感染者 (85 4 2 %和 6 0 72 % ) ,Ⅰ / 1a型和Ⅲ / 2a型HCV与HBV混合感染较同类基因型HCV单独感染明显增加 ,Ⅱ / 1b型丙型肝炎病毒合并乙型肝炎病毒感染者血清转氨酶及总胆红素水平最高 ,白蛋白和胆碱酯酶水平最低 ,尽管HCV、HBV混合感染的临床症状可能更为严重 ,但在病毒学上两者的确存在着相互抑制作用