丙型肝炎病毒感染者的自身抗体分析

对161名丙型肝炎病毒(HCV)感染者进行了8种自身抗体(抗核抗体、类风湿因子、抗甲状腺球蛋白抗体、抗甲状腺微粒体抗体、抗双链DNA抗体、抗RNP抗体、抗Sm抗体、抗精子抗体)的检测。有52名检出69项次自身抗体,自身抗体检出率为32.3％,显著高于健康人对照组(P<0.005)(未计抗精子抗体)。认为HCV感染可能是诱发自身免疫反应的一个重要因素。     

非病毒性肝炎患者血清的自身抗体检测

我们通过对6 0例非病毒性肝炎患者血清进行自身免疫抗体的测定,观察此类肝病与自身免疫性抗体之间的关系。1　材料和方法1.1　材料　1999～2 0 0 1年北京佑安医院收治的非病毒性肝炎患者6 0例标本,这些标本检测甲、乙、丙、丁、戊型肝炎的病毒学指标均为阴性。试剂采用德国EURO     

检测丙型肝炎患者NS5区抗体的临床意义探讨

目的检测慢性丙型肝炎患者和１４例ＨＣＶ原发感染后ＮＳ５抗体长达一年半的动态变化，探讨ＮＳ５抗体的临床意义。方法应用重组ＮＳ５抗原，建立ＥＩＡ方法进行检测。结果慢性丙型肝炎患者抗－ＮＳ５抗体阳性率为６０．４８％，ＨＣＶ感染后一月抗－ＮＳ５抗体阳性率为１６．３５％，三月为７５％。结论抗－ＮＳ５抗体无早期诊断价值。抗－ＮＳ５抗体持续阳性者，血清ＡＬＴ多明显升高，抗－ＮＳ５抗体与肝脏疾病活动性相关。丙型肝炎患者中存在抗－Ｃ、抗－ＮＳ３、抗－ＮＳ４抗体阴性，而抗－ＮＳ５抗体单独阳性，表明检测抗－ＮＳ５抗体具有独特的诊断价值     

慢性丙型肝炎患者血清ANA、anti-LKM1的检测及其产生机制探讨

目的 观察慢性丙型肝炎(CHC)患者中抗核抗体(ANA)、抗肝肾微粒体抗体(anti-LKM1)的检出情况,并深入探讨其产生机制.方法 通过多因素分析探讨自身抗体产生与年龄、性别、HCV RNA含量、HCV基因型、生化指标及临床特征等指标的关系.结果 360例CHC患者中,ANA阳性率为12.5%(451360),anti-LKMi的阳性率为2.5%(91360).CHC患者的自身抗体检出率高于慢性乙型肝炎(CHB)患者(15%vs2.9%,P=0.006)而低于自身免疫性肝炎(AIH)患者(15%vs47.9%,P<0.001);女性患者的自身抗体检出率高于男性(P<0.05);自身抗体阳性组HCV RNA含量低于自身抗体阴性组(1.23×107 vs 7.2× 107拷贝/L,P<0.05).自身抗体阳性组和阴性组患者的年龄、HCV基因型、生化指标、肝硬化发生率的差异均无统计学意义.接受干扰素治疗组和未接受干扰紊治疗组患者的自身抗体检出率差异无统计学意义(P>0.05).结论 CHC患者血清中可检测出AIH相关自身抗体;自身抗体可能并非由干扰素治疗所诱发;很可能是HCV引发自身免疫,导致自身抗体的出现.     

丙型肝炎病毒感染者血清细胞因子的检测

目的 探讨丙型肝炎病毒（ＨＣＶ）感染慢性化的宿主免疫机制。方法 用酶联免疫吸附实验测定了１８例慢性ＨＣＶ感染者、１１例正常对照和１０例慢性ＨＢＶ感染者的Ｔ辅助淋巴细胞（Ｔｈ０细胞因子ＩＦＮ－γ,ＩＬ－２,ＩＬ－４和ＩＬ－１０的血清浓度。结果 ＨＣＶ感染者的ＩＬ－２（Ｔｈ１细胞因子）、ＩＬ－４的ＩＬ－１０（Ｔｈ２细胞因子）较正常对照均明显增高（Ｐ〈０．０５,Ｐ〈０．０２５,Ｐ〈０．００１）,但以Ｔｈ     

自身免疫性肝炎与自身抗体的临床探讨

自身免疫肝炎(AIH)是1992年在英国召开的消化系统国际会议上由自身免疫肝炎组的专家们提出,用以代替自身免疫活动性肝炎的一个自身免疫病[1]。以前,AIH未曾被注意被诊断为慢性活动性肝炎,乙型肝炎病毒的出现使人们认识到慢性活动性肝炎的多因性和异质性。病毒、药物、免疫异常都是AIH的病因。随着自身抗体和淋巴细胞介导对肝细胞的细胞毒反应在病毒标记阴性的慢性活动性肝炎的出现。可以说明以往的慢性活动性肝炎中有一部分是AIH。     

丙型肝炎患者血清抗丙型肝炎病毒抗体IgM及HCVRNA检测结果的比较

用酶联免疫吸附试验（ＥＬＩＳＡ）对住院病人抗丙型肝炎病毒抗体（抗－ＨＣＶ）阳性血清标本进行抗－ＨＣＶＩｇＭ的检测，并与ＨＣＶＲＮＡ检测结果比较。结果表明，ＨＣＶＲＮＡ阳性、抗－ＨＣＶ阳性，ＨＣＶＲＮＡ阳性、抗－ＨＣＶ阴性及ＨＣＶＲＮＡ阴性、抗－ＨＣＶ阳性三种类型中均有抗－ＨＣＶＩｇＭ阳性者。结果还表明ＨＣＶＲＮＡ阳性病例的抗－ＨＣＶＩｇＭ阳性率明显高于ＨＣＶＲＮＡ阴性的病例（Ｐ＜０．０５），在临床诊断上ＨＣＶＲＮＡ阳性与阴性病例的肝病大多数为急性肝炎（ＡＨ）和慢性活动性肝炎（ＣＡＨ），ＨＣＶＲＮＡ阳性与阴性比较，各类肝病的病例数无明显差别。     

慢性丙型肝炎患者自身抗体的检测分析

采用荧光抗体间接法（ＩＦＡ）对３９例慢性丙型肝炎患者血清进行了自身抗体检测。结果显示慢活肝（ＣＡＨ）抗核抗体（ＡＮＡ）和抗平滑肌抗体（ＳＭＡ）检出率均高于健康人（Ｐ＜０．０５，Ｐ＜０．０１）。自身抗体阳性的慢性丙型肝炎患者血清转氨酶显著高于自身抗体阴性患者。因此认为自身免疫可能是丙型肝炎病毒（ＨＣＶ）慢性感染后肝组织损伤的重要因素。     

慢性丙型肝炎相关的自身抗体

近年的研究发现慢性丙型肝炎（CHC）血清常有自身抗体出现，因而CHC相关的自身抗体对病情的影响以及与自身免疫性肝炎（AIH）相关的自身抗体的鉴别成为当前研究热点。本文就这方面的研究进展作一综述。1自身抗体的种类及阳性率＊＊C相关的自身抗体已被广泛研究，多数学者报道：大约有1／3的CHC患者有自身抗体，主要是抗核抗体（ANA），抗平滑肌抗体（SMA）和肝肾微粒抗体（抗一LKMI）。明确的亚型有同种ANA（ANA－H）和SMA特异性抗肌纤蛋白抗体（SMA－AA），AIH血清可见到这两种亚型。最近Cassani一项纳人290例CHC患者的…     

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.     

Serum cytokine profile in hepatitis C virus carriers presenting cryoglobulinaemia and non-organ-specific autoantibodies

This work investigated the serum cytokine profile (IL-2, IL-4, IL-5, IL-10, IFN-γ and BAFF) of hepatitis C virus (HCV) carriers with autoimmunity. Forty-seven HCV carriers and 28 healthy controls were evaluated. Cytokine levels were measured by ELISA. Patients and controls presented similar levels of IL-2, IL-4, IL-5, IL-10, IFN-γ and BAFF (p > 0.05). Cryoglobulinaemic HCV carriers had increased IL-2 (p = 0.013), IL-5 (p = 0.018) and BAFF (p = 0.050). IFN-γ level was decreased in HCV carriers with rheumatoid factor in comparison with those that were RF-seronegative (p = 0.035). Patients with β2GPI IgA antibodies when were compared with those without this autoantibody, had more serum IL-2 (p = 0.009), IL-5 (p = 0.018) and BAFF (p = 0.039). Interleukin-2 was increased in HCV carriers with positive ANA when they were compared with ANA-seronegative carriers (p = 0.044). Interleukins IL-4 and IL-10 were not associated with autoimmunity (P > 0.05). In HCV carriers, IL-2 was correlated with IL-5 (p < 0.0001) and IFN-γ (p = 0.015), and IL-5 with IFN-γ (p = 0.015). We concluded that the serum profile of cytokines in HCV carriers presenting autoimmune markers may be mainly represented by increased IL-2, IL-5 and BAFF.     

Management of patients with chronic hepatitis C infection

Abstract Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality throughout the world. Although reliable figures regarding the global prevalence of HCV infection are wanting, it is likely that HCV prevalence will continue to increase. Injection drug use is the most important source of HCV transmission in the developed world, while unsafe therapeutic injection is an important source of transmission in developing nations. The majority of exposed individuals become chronically infected, of whom 50% develop chronic liver injury. Cirrhosis and hepatocellular carcinoma can arise in those chronically infected over a mean of 20–30 years. Despite this high prevalence and morbidity, recommendations regarding who to screen by antibody testing remain disparate. Quantitative measurement of HCV RNA and HCV genotyping is useful in predicting response to antiviral therapy. Noninvasive methods of detecting liver injury, such as serologic batteries, have not been as informative or predictable as liver biopsy. The current pharmacologic standard of care for chronic HCV infection is the combination of subcutaneous peginterferon and oral ribavirin, which yields sustained virologic response in 54%–56%. Higher rates of SVR are seen in those patients who are infected with HCV genotypes 2 and 3. As intravenous drug use remains the most important source of HCV transmission in the US and Europe, education within this group is an important preventive tool.     

Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients

Background/Aims

We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease.

Methods

Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR.

Results

Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity.

Conclusions

Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.     

重组干扰素对慢性丙型肝炎抗病毒疗效5年随访观察

目的观察重组干扰素α－２ａ，α－２ｂ抗丙型肝炎病毒（ＨＣＶ）的近、远期疗效。方法重组干扰素α－２ａ治疗组７０例，重组干扰素α－２ｂ４６例对照组２８例，治疗后随访５年。结果治疗结束时，ＨＣＶＲＮＡ阴转率和血清ＡＬＴ复常率α－２ａ组分别为６７１４％和７０００％，α－２ｂ组分别为６９５６％和７１７３％，随访５年后，α－２ａ组ＨＣＶＲＮＡ阴转率和血清ＡＬＴ复常率分别为３５７１％和４７１４％，α－２ｂ组分别为３９１３％和５２１７％，均显著高于对照组（Ｐ＜００１和Ｐ＜００５）。基因分型以ＨＣＶⅠ组感染为主（７５８６％），干扰素对ＨＣＶⅡ组感染的疗效优于ＨＣＶⅠ组。结论重组干扰素α－２ａ与α－２ｂ均为有效的抗丙型肝炎病毒药物，慢性丙型肝炎患者干扰素治疗的早期疗效较好。ＨＣＶ基因型有预测干扰素疗效的意义     

Clinical features and treatment efficacy of peginterferon alfa plus ribavirin in chronic hepatitis C patients coinfected with hepatitis B virus

Background/Aims

Cross-sectional studies have documented that 2-10% of patients who are chronically infected with hepatitis C virus (HCV) are also positive for hepatitis B virus (HBV) surface antigen (HBsAg). Data related to HCV-HBV coinfection are lacking in Korea. This study evaluated the clinical characteristics, the treatment efficacy of peginterferon alfa plus ribavirin, and the changes induced by such treatment in HBV status in chronic hepatitis C (CHC) patients coinfected with HBV.

Methods

Eighteen (2.37%) HBsAg-positive CHC patients were selected from among the 758 subjects from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin in chronic hepatitis C Treatment (KIPECT) study, which evaluated the treatment efficacy and safety of peginterferon alfa plus ribavirin in CHC patients. Data on changes in the status of HBV infections were obtained.

Results

HCV genotype 1b was the most common (44%). The overall sustained virologic response rate was 72% in all patients, and 60% and 87.5% in genotypes 1 and 2, respectively. Two of the 18 patients were positive for HBeAg, and 15 had baseline HBV DNA level of less than 2,000 IU/mL. Two of the three whose levels exceeded this threshold showed no detectable DNA after treatment. After the completion of treatment, serum HBV DNA levels were increased in the two patients whose baseline HBV DNA levels were less than 2,000 IU/mL.

Conclusions

The prevalence of HBV coinfection in CHC patients was 2.37% and most of the patients were inactive carriers. The treatment efficacy was similar to that of HCV mono-infection. Reactivation of HBV replication was observed in some patients after CHC treatment.     

慢性丙型肝炎患者氧化损伤的研究

目的 探讨慢性丙型肝炎(CHC)患者体内氧化损伤的情况.方法 52例CHC患者,按丙氨酸转氨酶(ALT)水平分为A组(ALT上升组)和B组(ALT正常组).正常对照组为20例健康志愿者.利用酶联免疫吸附法(ELISA)测定研究对象血清黄嘌呤氧化酶(XOD),丙二醛(MDA),氧化型谷胱甘肽(GSSG),谷胱甘肽(GSH),谷胱甘肽过氧化物酶(GSH-Px),谷胱甘肽巯基转移酶(GST),谷胱甘肽还原酶(GR)及维生素C(Vc)水平,并作出统计分析.结果 CHC患者血清XOD,MDA,GST和GR水平较正常对照组显著升高,而GSH,GSH-Px和Vc水平则明显降低.同时,A组患者血清XOD,MDA,GSSG,GST及GR水平较B组患者显著上调,而GSH,GSH-Px和Vc水平则显著下调.在CHC患者中,血清XOD,MDA,GSSG,GST水平与ALT水平呈正相关,血清GSH,GSH-Px,Vc与ALT水平呈负相关;血清XOD,MDA,GSSG,GR,GST水平与AST水平呈正相关,血清GSH-Px水平与AST水平呈负相关;血清GR水平与GGT水平呈正相关,血清GSH水平与GGT水平呈负相关;血清MDA,GR水平与AKP水平呈正相关.在CHC组中,仅血清XOD水平与血清HCV RNA水平间存在正相关关系.结论 CHC患者体内存在一定程度的氧化损伤,随血清ALT水平的升高,机体氧化损伤程度进一步加重.     

1年以上血透患者HCV感染状况的调查

目的 研究1年以上的长期血液透析患者丙型肝炎（HCV）感染状况。方法 用ELISA法和RT－PCR法检测137例长期血透患者血清中的抗－HCV和HCVRNA,并且同时检测谷丙转氨酶（ALT）和谷草转氨酶（AST）,计算其变动率。结果 透析时间超过1年以上的137例患者中仅抗－HCV阳性8例,仅HCV－RNA阳性13例,抗－HCV与HCVRNA同时阳性者24例,感染率34．3％。且透析时间小于2年的,HCV感染率为15％,透析时间大于2年以上的其感染率增至37．6％。结论 血透患者中HCV的感染应引起重视,透析的年限越长,被HCV感染的机率就越大。酶学指证的变动率不能作为长期透析患者HCV感染的敏感指标。