自体与异体LAK细胞治疗慢性肝炎130例

目的对ＬＡＫ细胞治疗慢性肝炎作客观估价．方法治疗与对照组均口服维生素，肌注肝炎灵．治疗Ａ组加回输自体ＬＡＫ细胞，每周２次，６周为１个疗程；Ｂ组每周输注异体ＬＡＫ细胞悬液１次，５次为１疗程．结果ＬＡＫ细胞治疗慢性肝炎能使部分患者ＨＢｅＡｇ及ＨＢＶＤＮＡ阴转．治疗结束时ＨＢｅＡｇ阴转率Ａ组为４７５％，Ｂ组为５８０％；而对照组Ｃ为１５０％（Ｐ＜００５）．ＨＢＶＤＮＡ阴转率Ａ组为４５０％，Ｂ组为６６０％，而对照组Ｃ为１１８％，（Ｐ＜００５％）．结论ＬＡＫ细胞治疗对ＨＢＶ复制有明显抑制作用．异体ＬＡＫ组的ＨＢｅＡｇ及ＨＢＶＤＮＡ阴转率高于自体ＬＡＫ组．     

HBV特异性T细胞治疗慢性乙型肝炎的研究

为寻求一种治疗慢性乙型肝炎的新方法,应用ＨＢＶ特异性Ｔ细胞输注治疗慢性乙型肝炎９例,结果显示,在疗程结束后,患者的ＨＢｓＡｇ,ＨＢｅＡｇＨＢＶＤＮＡ的含量均有所下降,其中ＨＢｅＡｇ下降较明显,Ｐ〈０．０１,２例ＨＢｃＡｇ阳性患者,ＨＢｃＡｇ阴转,ＣＤ＾＋３,ＣＤ＾＋４,ＣＤ＾＋４／ＣＤ＾＋８ＮＫ活性上升,ＣＤ＾＋８,ｓＩＬ－２Ｒ较治疗前后所回复,表明特异性Ｔ细胞治疗慢性乙型肝炎有一定疗效,远期疗效     

慢性重型肝炎患者外周血单个核细胞内干扰素和白细胞介素的表达及意义

目的探讨慢性重型肝炎（ＣＳＨ）病人外用血单个核细胞（ＰＢＭＣ）内干扰素－γ（ＩＦＮ－γ）及白细胞介素－４（ＩＬ－４）的表达及其临床意义。方法常规分离ＰＢＭＣ,在ＰＭＡ、Ｉｏｎｏｍｙｃｉｎ、Ｍｏｎｅｎｓｉｎ的刺激下,采用流式细胞术（ＦＡＣＳ）,对１７例ＣＳＨ患者及１９例正常健康者ＣＤ４＋Ｔ细胞内ＩＦＮ－γ和ＩＬ－４的表达进行分析,并应用荧光定量聚合酶链反应检测ＨＢＶ ＤＮＡ含量。结果 ＣＤ４＋Ｔｈ１、 Ｔｈ２细胞在ＣＳＨ组分别为７．２％—２６．３％（平均１５％）和０、ｌ％—１０．９％（平均２．０％）,正常对照组则分别为２．２％—１１．９％（平均５．９％）和０．４％—３．９％（平均２．２％）;ＣＤ４＋Ｔｈ１细胞百分数两组间差异有显著意义（Ｐ＜０．０１）。荧光定量ＰＣＲ结果表明ＣＳＨ组中１３例ＨＢＶ　ＤＮＡ阳性,其ＨＢＶ ＤＮＡ的含量与ＩＦＮ－γ表达细胞百分数呈负相关。结论 Ｔｈ１细胞与肝脏的炎症活动明显相关,ＩＦＮ－γ的表达对ＨＢＶ复制可能具有一定的影响。     

抗HBe(+)慢性乙型肝炎的重组干扰素治疗应答及其影响因素

目的探讨抗ＨＢｅ／ＨＢＶＤＮＡ（＋）慢性乙型肝炎（ＣＨＢ）的干扰素治疗效果及其影响因素。方法对１５例ＨＢｅ（＋）和２５例ＨＢｅＡｇ（＋）ＣＨＢ患者用重组干扰素α－１ｂ治疗，治疗前、后和随访半年后检测ＨＢＶ及前Ｃ区Ａ１８９６终止变异。结果抗ＨＢｅ（＋）慢性乙型肝炎干扰素治疗近期应答率为７３％（１１／１５），与ＨＢｅＡｇ（＋）组比较差异无显著性（Ｐ＞００５）；治疗前抗ＨＢｅ（＋）组ＨＢＶＤＮＡ含量明显低于ＨＢｅＡｇ（＋）组（Ｐ＜０００５）；但前Ｃ区Ａ１８９６变异检出率４７％（７／１５）显著高于ＨＢｅＡｇ（＋）组的１６％（４／２５），Ｐ＜００５；４例复发者都是Ａ１８９６变异感染。结论血清ＨＢＶＤＮＡ水平可能是影响其应答的重要因素，前Ｃ区Ａ１８９６变异并不影响干扰素的近期应答率，但可能是其复发的一个重要因素。     

40例慢性乙型肝炎后肝硬化的LAK细胞回输治疗

４０例慢性乙型肝炎后肝硬化的ＬＡＫ细胞回输治疗申淑兰，李玉彬，陈乃玲我们选用小剂量基因工程ＩＬ－２（北京希波公司提供），与患者静脉血ＰＢＭＣ在体外短时孵育后的自体ＬＡＫ细胞回输，配合对症治疗慢性乙型肝炎后肝硬化４０例，使部分患者ＨＢｅＡｇ和ＨＢＶ－Ｄ...     

基因工程干扰素 α-2b 加CD_3AK治疗慢性乙型肝炎

４５例慢性活动性乙型病毒性肝炎随机分为三组。Ａ组用干扰素α－２ｂ（ＩｎｔｒｏｎＡ，干扰能）加经ＣＤ３单克隆抗体激活的杀伤细胞（ＣＤ３ＡＫ）；Ｂ组单用α－２ｂ；Ｃ组为对照组。结果：Ａ组ＨＢｅＡｇ和ＨＢＶＤＮＡ近期阴转率为７３．３％，远期疗效为５３．３％；Ｂ组分别为４６．７％和３３．３％。两组均明显优于对照组。表明α－２ｂ可有效抑制ＨＢＶ复制，加用ＣＤ３ＡＫ可增强对乙肝病毒的抑制作用。     

HBV感染与肝癌患者血清可溶性IL—2受体及T淋巴细胞亚群的变化及意义

用ＥＬＩＳＡ及ＡＰＡＡＰ法分别检测了３９例乙型肝炎病毒（ＨＢＶ）感染者、１５例者ＨＢＶ感染的肝癌患者及２０例正常人的血清可溶性白细胞介素－２受体（ＳＩＬ－２Ｒ）和外周血Ｔ淋巴细胞亚群结果显示,肝癌及ＨＢＶ感染者（Ｐ〈０．０１）。吕患者及ＨＢＶ感染者ＣＤ３、ＣＤ４、ＣＤ８、ＣＤ４／ＣＤ８与对照相比均有显著差异（Ｐ〈０．０５）,而肝癌与ＨＢＶ感染者相比无显著差异（Ｐ〉０．０５）。提示ＨＢＶ感染者及肝癌     

间质性肺疾病支气管肺泡灌洗液的酶活性研究

目的探讨支气管肺泡灌洗液（ＢＡＬＦ）多项酶活性与间质性肺疾病（ＩＬＤ）的关系。方法检测３０例ＩＬＤｓ：包括特发性肺纤维化（ＩＰＦ）１８例和结节病（Ｓａｒｃ）１２例与９例正常对照者的ＢＡＬＦ中超氧化歧化酶（ＳＯＤ）、谷胱甘肽过氧化物酶（ＧＳＨ－ＰＸ）、血管紧张素转换酶（ＡＣＥ）和乳酸脱氢酶（ＬＤＨ）活性，并分类计数ＢＡＬＦ细胞成份。结果（１）ＩＰＦ组ＢＡＬＦ中各项酶活性均与对照组间差异有显著性（ＳＯＤ和ＧＳＨ－ＰＸ降低，ＡＣＥ和ＬＤＨ升高）（Ｐ＜０．０５）；而Ｓａｒｃ组仅见ＡＣＥ明显增高（Ｐ＜０．０５）。（２）ＢＡＬＦ－ＡＣＥ与Ｓａｒｃ组淋巴细胞百分比及ＣＤ＋４／ＣＤ＋８比值均有显著线性相关（Ｐ＜０．０５）。结论ＢＡＬＦ中ＳＯＤ、ＧＳＨ－ＰＸ、ＡＣＥ和ＬＤＨ活性测定，有助于进一步探讨ＩＬＤ发病机理和提供辅助诊断依据，ＢＡＬＦ－ＡＣＥ对判断Ｓａｒｃ活动性有重要临床意义。     

拉米夫定治疗HBeAg阴性的慢性HBV感染近期临床观察

观察和评价拉米夫定治疗ＨＢｅＡｇ阴性慢性ＨＢＶ感染的近期疗效。ＨＢｅＡｇ阴性／ＨＢＶ ＤＮＡ阳性的慢性ＨＢｖ感染者２６例（包括１１例乙肝肝硬化），ＨＢｅＡｇ阳性／ＨＢＶ　ＤＮＡ阳性的慢性ＨＢＶ感染者３０例（包括１０例乙肝肝硬化），均以拉米夫定治疗６个月后进行疗效评价，并继续观察５－１６个月。两组的ＡＬＴ／ＡＳＴ复常率分别为８４．７％／８８．５％和８６．７％／８６．７％（Ｐ＞０．０５），肝硬化患者Ｃｈｉｌｄ－Ｐｕｇｈ积分均明显下降，ＨＢＶ　ＤＮＡ全部阴转。ＨＢｅＡｇ阳性组３例发生ＹＭＤＤ变异，ＨＢｅＡｇ阴性组无１例变异。拉米夫定对于ＨＢｅＡｇ阴性／ＨＢＶ　ＤＮＡ阳性者，同样是十分安全有效的抗病毒治疗药物。ＨＢｅＡｇ阴性者的耐药发生率可能低于ＨＢｅＡｇ阳性者。     

拉米夫定、治肝灵冲剂联合治疗慢性乙型肝炎近期疗效研究

研究单用拉米夫定（３－ＴＣ）及联合应用中药治肝灵冲剂对慢性乙型肝炎（ＣＨＢ）的治疗作用，探讨两者联合治疗的近期疗效和安全性。５０例ＣＨＢ患者随机分为Ａ，Ｂ两组，Ａ组采用３－ＴＣ和治肝灵冲剂联合治疗；Ｂ组单用３—ＴＣ，疗程均为６个月，治疗前、治疗２周、４周、８周、１２周、１６周，２０周、２６周分别检测ＨＢＶ标志、肝功能，血清学指标，肾功能，并记录治疗期间临床和实验室检查发生的一切不良事件。治疗２６周后Ａ组血清ＨＢｅＡｇ转阴率６４．０％（１６／２５）．明显高于Ｂ组１６．０％（４／２５）Ｐ＜０．０１． Ａ组与Ｂ组分别有４例（１６．０％），２例（８．０％）实现ＨＢｅＡｇ血清转换。Ｐ＞０．０５。转阴患者未发现ＨＢＶ前Ｃ区变异株。Ａ组和Ｂ组ＨＢＶＤＮＡ转阴例数分别为２４（９６．０％）和２３（９２．０％）Ｐ＞０．０５。治疗结束时Ａ组和Ｂ组ＡＬＴ的复常率分别为８８．０％（２２／２５）、６４．０％（１６／２５），Ｐ＜０．０５。采用３－ＴＣ与治肝灵冲剂联合治疗ＣＨＢ，短期疗效明显优于单一用药组，且副作用少，是安全、有效的治疗ＣＨＢ的方案。     

Long-term follow-up of chronic hepatitis non-A,non-B – with special reference to hepatitis C

ABSTRACT— One hundred and twenty-seven patients with histologically verified chronic non-A, non-B hepatitis were followed for up to 23 years (mean 6.3 years). Thirty-nine were infected by blood transfusion, 58 were drug-addicts and 30 had no obvious source of infection. Chronic persistent hepatitis (CPH) was diagnosed in 84 (66%), while 43 patients (34%) had chronic active hepatitis (CAH) with or without cirrhosis. Patients with CPH were significantly younger (29.7 years vs 46.8 years; p<0.01), irrespective of the type of virus exposure. Antibodies to hepatitis C virus (anti-HCV) were detectable in 91 patients (72%) and 36 (28%) were anti-HCV negative. Fifteen patients with acute onset, and negative for anti-HCV at the start, became positive during follow-up; 12 of them within 4.5 months. We found no differences among anti-HCV positive and anti-HCV negative patients in liver function tests, resolving rate, morphological progression in serial biopsies or mortality rate. Five previously anti-HCV positive patients became negative during follow-up and in two of them this was accompanied by decreasing hepatic inflammation.     

CD127在慢性重型乙型肝炎患者外周血T细胞中的表达及意义

目的:研究慢性重型乙型肝炎患者外周血T细胞表面CD127表达水平的变化及与慢性重型乙型肝炎发病的关系。方法:流式细胞术检测30例慢性重型乙型肝炎、20例慢性乙型肝炎(CHB)患者和20例健康志愿者外周血T细胞中CD127的表达,用ELISA方法检测血清中细胞因子IL-7(白细胞介素-7)的表达。结果:慢性重型乙型肝炎组和CHB组CD8+T比例均较健康对照组高(P均<0.01),慢性重型乙型肝炎组CD4+T比例较健康对照组高(P<0.01)。慢性重型乙型肝炎与CHB组CD127+细胞的比例均较健康对照组低(P均<0.05)。慢性重型乙型肝炎组CD4+CD127+双阳性细胞的比例低于CHB组,CHB组又低于健康对照组(P均<0.01);慢性重型乙型肝炎组CD8+CD127+双阳性细胞比例较CHB组和健康对照组低(P均<0.01)。CD8+CD127+细胞的表达与HBV DNA载量呈负相关。慢性重型乙型肝炎组和CHB组血清IL-7含量均较健康对照组高(P均<0.01)。结论:慢性重型乙型肝炎患者外周血中CD4+CD127+、CD8+CD127+细胞表达降低;以CD8+CD127+降低更明显,并与HBV DNA载量呈负相关;血清中IL-7表达增高,可能与慢性重型乙型肝炎的发病有关。     

Detection of hepatitis C virus antibody in patients with autoimmune hepatitis and other chronic liver diseases

To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20% ), and in 5 out of 9 with multiple myeloma (56% ). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibodypositive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV -related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma. This study was supported by the Ministry of Health, Science and Welfare of Japan.     

Estimation of IgG subclasses of anti-HCV (C100-3) in non-A,non-B fulminant,acute and chronic hepatitis and it’s significance

To determine whether identification of subclasses of anti-HCV IgG would help distinguish between acute and fulminant hepatitis, we assayed serum IgG subclasses of anti-HCV (C100-3) in non-A, non-B hepatitis. Anti-HCV IgG was restricted to two subclasses in different diagnostic conditions; anti-HCV IgGl and anti-HCV IgG3. Anti-HCV IgGl was the main subclass in acute hepatitis (AH), and was positive in all the cases and only one case was positive for anti-HCV IgG3. Anti-HCV IgG3 was the dominant subclass in fulminant hepatitis (FH). Out of the total 12 cases of FH, who were positive for either anti-HCV IgG or for any of it’s subclasses, in 10 cases (83%), anti-HCV IgG3 had higher optical density (OD) values than anti-HCV IgGl and in 6 cases (50%) was the only subclass of anti-HCV IgG being positive. In 5 cases with FH, anti-HCV IgG3 became positive even when anti-HCV IgG was negative. These findings form the basis of a new observation and are likely to be helpful in the diagnosis of non-A, non-B fulminant hepatitis. This study was supported by a Grant-in-Aid for Scientific Research from viral Hepatitis and Research Foundation of Japan, 1991.     

Relationship between serum HCV markers and response to interferon therapy in chronic hepatitis C

Hepatitis C virus is the most frequent cause of chronic non-A, non-B hepatitis, and the antibodies to structural and nonstructural proteins encoded by viral genome have been suggested to be markers of ongoing HCV infection. We studied the behavior of these antibodies during interferon therapy in 18 patients with chronic hepatitis C and also during a follow-up period of at least four years. A significant decrease of anti-HCV titer was found only in patients who had shown positive response to therapy and all of them were anti-HCV negative at the end of follow-up. Analysis by recombinant immunoblotting assay showed that only anti-c100 were affected by interferon therapy, whereas anti-c22 and anti-c33 were not modified. Using polymerase chain reaction to detect small amounts of HCV genome in serum, we could confirm that the behavior of HCV-RNA during and after interferon therapy is similar to that of anti-HCV and the loss of anti-c100 seems to be closely related to HCV-RNA disappearance from serum. Our patients with chronic hepatitis C were found to be of type 1b and 2, according to the recent score of Simmonds, and the clearance of serum HCV-RNA during treatment and its sustained negative status are closely related to genotype 2 and to long-term positive response to interferon.     

Abrupt onset of type 1 diabetes mellitus during recombinant interferon-alpha 2b therapy in a patient with chronic hepatitis B

We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus （DM） after a 13-mo period of treatment with recombinant human interferon-alpha （IFN-α） 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody （ICAb）. IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.     

Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis

One hundred and thirty-five patients who developed non-A, non-B post-transfusion hepatitis mostly after cardiac surgery, were followed for a mean (±S.D.) of 90±41 months (range: 13–180) to evaluate clinical and histological outcome.Thirty-one cases resolved within 12 months, while 104 (77%) progressed to chronicity. Twenty-one of 65 (32%) biopsied patients developed cirrhosis at the end of the follow-up, and one further progressed to hepatocellular carcinoma. One patient had a complete histological remission (1%). The remaining cases had chronic active (37%), chronic persistent (27%) or chronic lobular hepatitis (3%). About half of the cases with cirrhosis developed portal hypertension, and three of these died due to esophageal varices hemorrhage, one due to liver failure, and one due to hepatocellular carcinoma. Out of 26 patients with the initial histologic diagnosis of chronic hepatitis that were rebiopsied during follow-up, 13 (50%) progressed to cirrhosis. These patients were significantly older than patients who did not develop cirrhosis (mean age 57 and 45 years respectively; p<0.01).During acute hepatitis anti-HCV was positive in all but one of the 114 patients tested. Percentages were similar for patients who recovered (95%) and those who developed chronic hepatitis (100%). However, during follow-up, 71% of the 1st generation and 21% of the 2nd generation ELISA test patients with acute resolved hepatitis became anti-HCV negative, while the same figures in chronic cases were only 8.5% (p<0.0001) and 1.4% (p=0.012). This suggests a correlation between anti-HCV antibody activity, hepatitis C virus replication, and the development of chronic liver disease.     

Anti-HCV immunoglobulin M antibody in patients with hepatitis C

Anti-hepatitis C virus (HCV) immunoglobulin M antibody titres were measured by an enzyme-linked immunosorbent assay method in 16 patients with non-A, non-B acute hepatitis (NANB AH), 13 with non-A, non-B fulminant hepatitis (NANB FH) and nine with type C chronic hepatitis. Anti-HCV IgM was positive in one of the 16 patients with NANB AH, six of the 13 with NANB FH, and five of the nine with type C chronic hepatitis. Anti-HCV IgG was positive in eight of the 16 patients with NANB AH and eight of the 13 with NANB FH. Either anti-HCV IgM or anti-HCV IgG were positive in 10 of the 13 patients with NANB FH. All of the five anti-HCV IgM positive patients with type C chronic hepatitis were undergoing an exacerbation of the diseases, while all of the anti-HCV IgM negative patients were in a remission stage which had lasted for more than 6 months. The findings of this study suggest that anti-HCV IgM is useful for the early diagnosis of type C FH and may be a useful marker of diseases activity in type C chronic hepatitis.