某部新兵病毒性肝炎爆发流行与临床初步研究

目的:查明新兵中以单项血清转氨酶增高为主要特征的肝损害患者的病因、传播途径和临床特点。方法:对207名2001年入伍新兵进行流行病学调查,血清和粪便进行肝炎病毒标志物检测,肝组织活检以及临床特点分析。结果:根据流行病学调查和临床检测结果,这些病人可排除各种中毒因素,已知肝炎病毒的血清标志物均阴性,均无症状体征,肝组织活检肝细胞普遍肿胀变性,点状坏死,汇管区炎症细胞浸润,1个月内转氨酶升高的新兵占新兵总人数的36.23％,从病人血清和粪便中可以检出TTV DNA。结论:本次肝炎流行可能是由TTV引起的,属非甲～庚型病毒性肝炎,传播方式可能是TTV污染碗筷引起的消化道传播。     

一种新型肠传性病毒肝炎的临床流行病学及病毒学的初步研究

目的 阐明长期单项血清转氨酶增高为主要特征的肝损害病人的病因、传播和病变。方法：对３８１例病人行流行病学调查、临床观察、肝活组织检查以及血清和粪便的聚合酶链反应检测。结果 根据临床和检测结果可排除中毒引起，已知肝炎病毒的血清标志物均阴性。症状轻微，病程移呈急性，少数可超过６个月。肝组织呈汇管区炎。散在发病后进行３次人群普查，３个月累计发病率占流行人群的６０．７％。由病人的急性期血清和潜伏期粪便提取     

武汉某单位经血传播病毒流行期间患者 肝组织学特点及预后观察

武汉某职业学校1996年曾发生不明病原肝炎流行,骆抗先等[1]证实为经血传播病毒（TTV）感染。我们对其中18例住院患者进行了肝穿刺活检及TTV DNA原位检测,并临床跟踪观察3年。1. 资料与方法：(1)18例均为男性,年龄21～23岁,排除已知肝炎病毒感染,血清TTV巢式聚合酶链反应（nPCR）检测阳性[1]。(2)组织学观察及原位杂交：首次发病入院2周内行肝穿刺活检,组织连续石蜡切片,常规作HE染色。原位杂交探针采用PCR法标记,引物由南方医院传染病实验室惠赠：P1（nt.1714）5'-CAGTTACCAATAAAAGCAGC; P2（nt.2302）5'-TGTCT…     

非肝炎口腔科患者血清及唾液中HGV 和TTV感染率的调查

目的 检测杭州地区非肝炎口腔科患者血清和唾液标本中庚型肝炎病毒（HGV）和输血传播病毒（TTV）感染率，进一步了解HGV和TTV传播途径和感染的高危人群。方法 分别从上述患者血液和唾液标本中提取RNA和DNA，采用逆转录-套式聚合酶链反应（RT-Nested PCR）和半套式聚合酶链反应（Hemi-nested PCR)分别检测HGV5′-NCR RNA和TTV N22区DNA，部分DNA，部分HGV和TTV扩增产物克隆后进行核苷酸序列测定。结果 226例血清标本中，仅HGV阳性27例（11.9%）、仅TTV阳性21例（9.3%）、HGV和TTV均阳性7例（3.1%）；226例唾液标本中，仅HGV阳性10例（4.4%）、仅TTV阳性9例（3.9%）、HGV和TTV均阳性2例（0.9%）；未见血清标本HGV和/或TTV检测结果阴性而唾液标本阳性者。2例患者血清标本及唾液标本HGV和TTV均阳性的扩增产物分别与报道的HGV和TTV核苷酸序列比较，同源性为88.65%～91.49%和65.32%～66.67%，但各自的血清标本与唾液标本HGV和TTV扩增产物同源性分别高达98.58%～99.29%和98.65%～98.20%。结论 杭州地区非肝炎口腔科患者HGV或TTV感染率均较高，其中部分携带病毒的患者唾液中均可检出HGV或TTV，提示HGV或TTV可能存在唾液传播途径，口腔科医师则是HGV或TTV感染的高危人群。     

原位杂交检测肝组织中TTV DNA研究

目的:研究输血传播病毒(transfusion transmitted virus,TTV)DNA在肝炎患者肝组织中的存在,证实TTV是一种新型嗜肝病毒。方法:用地高辛标记TTV DNA(Dig-TTV DNA)探针,以原位杂交技术进行血清PCR检测,发现单一TTV感染13例,TTV、HBV混合感染4例,非甲～非庚和非TTV感染的肝炎患者6例。与此同时对肝组织进行检测,进行肝组织学、免疫组化、肝功能和临床特点等分析。结果:23例肝组织中TTV DNA阳性15例(65.22％),其中单一TTV感染11例(84.62％),TTV DNA混合感染者3例(75.00％),非甲～非庚和非TTV感染1例,临床分型急性肝炎5例(55.56％),慢性肝炎10例(71.43％)。TTV DNA阳性细胞在急性肝炎患者系弥漫分布于肝小叶内,在慢性肝炎于汇管区附近较为密集。TTV DNA主要存在于肝细胞核,少数位于肝细胞浆内,以核型为主。23例肝组织都有不同程度病理改变,大多数较轻,12例肝组织免疫组化检测HBsAg、HBcAg、HCVNS_3、HGVNS_5均阴性,肝功能均有轻～中度损害,大多数病人有乏力、纳差、尿黄症状,部分病人有肝脾肿大、皮肤或巩膜黄染体征。结论:TTV可能是一种新型嗜肝病毒。     

上海肝炎患者输血传播病毒 (TTV)感染的研究

为了解上海地区肝炎病人中TTV的感染状 况,以期发现TTV感染与肝脏损害的因果关系,进一步探讨其传播途径,我们选择了上海地区肝炎病人162例进行TTV感染的流行病学调查研究,并以健康献血员(ALT正常)作为对照,对分离出的6株TTV部分基因进行测序分析,现报告如下.     

血清谷草转氨酶而不是谷丙转氨酶对成人慢性丙型肝炎病毒感染的组织学特点有预示作用

本研究旨在评估年龄、性别、传播途径、脂肪变性程度、酒精摄入以及血清转氨酶水平对慢性丙型肝炎病毒 (ＨＣＶ)感染病人的组织学特点的预示价值。材料与方法　研究对象为加拿大 79例经血清学检测证实有ＨＣＶ感染的成年病人 ,其中排除既往或现患有其它肝病 (如ＨＢＶ、ＨＩＶ感染 ,药物性肝病、血色病和混杂性肝病 )患者。所有 79例病人的病史均与ＨＣＶ感染相符 ,抗 ＨＣＶ也呈阳性 (ＥＬＩＳＡ法测定阳性后并经免疫印迹试验证实 )。所有病人肝活检标本均由一位对病人临床和实验室结果不知情的专家评定 ,组织学评分按Ｋｎｏｄｅｌｌ记分系…     

隐匿性乙型肝炎病毒感染者临床特点和肝组织病理学检查

目的了解血清肝炎病毒标志物阴性、肝功能反复异常患者中HBV隐匿性感染的比例及其临床和病理学特点。方法对27例血清肝炎病毒标志物阴性、肝功能反复异常患者采用免疫组化法检测肝组织HBsAg、HBcAg和HCVAg，并进行常规的病理学检查。结果肝组织HBsAg和（或）HBcAg阳性9例（33．3％）；HBsAg和（或）HBcAg及HCVAg阳性10例（37．0％）；全阴性8例（29．6％）。在HBV隐匿性感染的19例患者中，慢性肝炎8例，肝硬化11例。结论HBV和HCV感染为血清肝炎病毒标志物阴性患者肝功能反复异常的主要原因之一，尤其是HBV感染。这种HBV隐匿性感染与慢性肝炎、肝硬化的发生关系密切，应引起重视。     

双探针原位杂交法检测慢性肝病和肝细胞癌患者肝组织TTV DNA的感染状况

目的 探讨慢性肝病和肝细胞癌患者肝组织TIV DNA的感染状况。方法采用PCR扩增法分别合成G1a、G2b两种亚型的双链TTV DNA探针。应用两型探针对45例肝组织标本进行TTV DNA原位杂交检测，巢氏PCR法检测血清TTV DNA。结果31例血清TTTV DNA阳性患者的肝组织TTV DNA均为阳性(100％)。14例血清TTV DNA阴性的患者肝组织中TTV DNA阳性者7例(50%)。慢性肝病患者的肝组织中TTV DNA散在分布在汇管区周围的肝细胞核内，肝癌患者TTV DNA则集中分布在肝癌细胞核内及癌组织周围的肝细胞核内。结论慢性肝病与肝癌患者肝组织中TTV DNA的感染状态存在一定差异。     

丙型肝炎病毒与B细胞淋巴瘤

丙型肝炎病毒(HCV)引起肝硬化、肝癌已为人们熟悉，HCV还与淋巴瘤、再生障碍性贫血、多发性骨髓瘤以及原发性血小板减少性紫癜等血液病有关。我国早期局部的流行病学调查表明，普通人群抗HCV抗体阳性率为3．2％。虽然还缺乏大范围的流行病学调查资料，但从HCV传播的途径     

An outbreak of enterically transmitted non-A, non-E viral hepatitis

Patients with isolated serum transaminase elevations of unknown cause are common in China. An outbreak of such disease took place in a technicians' school during 1996. To define the epidemic and determine the etiology, a study was carried out, which included investigation of epidemiological, clinical and histological features. The symptoms of this disease were mild. The major clinical feature was transaminase elevation, and all serum markers of known hepatitis viruses were negative. Although the course of disease in most patients was self-limiting, in a few it was prolonged and relapsed. Histological findings were mild portal hepatitis or non-specific reactive hepatitis. The disease first appeared in 1994, and this outbreak occurred after October 1996. A total of 381 people were affected and the prevalence was as high as 60.7%. Casual contact and small-scale food transmission were considered to be risk factors for infection and the epidemic was under control 2 months later following the introduction of preventive measures for gastroenteric infection. Viral genomic fragments from the so-called transfusion-transmitted virus (TTV) were detected in acute-phase sera and stool samples collected 2 weeks before onset. Therefore, this disease outbreak might be another form of enterically transmitted viral hepatitis, not related to hepatitis A and E.     

TT virus infection in chronic liver disease.

BACKGROUND/AIMS: The exact role of the novel hepatotropic TT virus regarding the etiology of viral hepatitis, as well as the progression towards chronic liver disease has as yet not been defined. Moreover, the contribution of TTV infection to the course of chronic hepatitis B or C virus infections also still awaits clarification. Hence, the aim of our study was to investigate the impact of TTV infection on clinical severity and histology of chronic liver disease originating from HBV and/or HCV infections in Thai patients concomitant with the determination of TTV's association with non-B, non-C chronic liver disease and compared to its prevalence among voluntary blood donors. METHODOLOGY: DNA was extracted from the sera collected from 115 hepatitis B patients, 41 hepatitis C, and 48 negative for either viral marker, who had all been diagnosed with chronic liver disease ranging from chronic hepatitis over cirrhosis to hepatocellular carcinoma. The sera obtained from 200 voluntary blood donors served as controls. TTV DNA was amplified by seminested polymerase chain reaction (PCR) employing primers derived from the genome's most conserved region. The PCR products were analyzed by gel electrophoresis. Liver function tests were performed by means of a chemical analyzer. RESULTS: TTV DNA was detected in 20% of the HBV-positive and 19.5% of the HCV-positive chronic liver disease patients. Within the group of patients seronegative for both viral markers, TTV was detected in 8.3%. Furthermore, its DNA was identified in 6.8% of the HCC patients and finally, in 7% of the blood donors. Yet, no significant differences between TTV infected and non-infected patients were found as to demographic data, assumed source of infection, biochemical abnormalities, or severity of liver histology. CONCLUSIONS: TTV appears to be highly prevalent on a worldwide scale but regarding etiology of and progression towards serious liver disease, its contribution seems to be minor if not altogether non-existent. Hence, regarding clarification of its clinical significance, further studies are certainly required.     

Transfusion transmissible virus TTV and its putative role in the etiology of liver disease

TTV, the transfusion transmissible hepatitis virus infects mainly patients at risk for parenteral exposure and hence, prone to develop chronic liver disease, as well as healthy populations worldwide. Most TTV infections appear to occur parenterally, with viremia detected frequently in blood donors and blood products. The substantial proportion of asymptomatic individuals never exposed to blood-borne agents, and its high prevalence among healthy subjects implicates the fecal-oral route as another potential for transmission. According to the TTV DNA levels detected in liver tissue, it apparently replicates in hepatocytes, and TTV DNA is present in sera of patients with posttransfusion hepatitis of unknown etiology closely correlated with ALT levels. However, TTV initiating the development of chronic liver disease or causing posttransfusion hepatitis could not be confirmed, as most patients positive for TTV DNA remain asymptomatic and those progressing towards chronic liver disease are invariably coinfected with either the hepatitis B or C virus. Also, TTV coinfection does not aggravate the symptoms associated with hepatitis B or C. Similarly, it does not cause posthepatitis aplastic anemia, and high-risk patients can immunologically clear the viral DNA. In conclusion, being widely distributed and apparently nonpathogenic, TTV might represent an opportunistic but innocent virus reminiscent of hepatitis G virus, with a negligible role in the etiology of chronic liver disease.     

TTV与其它肝炎病混合感染及其基因型的研究

研究TTV与其它肝炎病混合感染对肝脏病变的影响及本地区TTVDNA的基因型。选TTV ORF1的保守序列作内外引物,采用微板核酸杂交－ELISA方法检测患者血清TTVDNA并对检测结果和临床资料进行统计学分析。选取异源性大于50％的序列作显色探针Ⅰ和显色探针Ⅱ,进行分型研究。学生、非甲－非戊型肝炎、慢性乙型肝炎和肝硬化患者血清TTV阳性率分别为3．3％、14．3％、12％、16％。TTV阳性和TTV阴性的慢性乙型肝炎及肝硬化患者,在年龄、性别、ALT和TBil之间无显著差异（P＞0．05）。本地区流行的TTV可分为两个主要的基因型,即I型（66．75）、Ⅱ型（25％）,部分存在混合感染（8．3％）。TTV可能与HBV、HCV有类似的传播途径,故常重叠感染。TTV与乙型肝炎及肝硬化混合感染后不影响两者的肝脏病变。TTV不是本地区非甲－非戊型肝炎的主要病因。     

The role of TT virus infection in acute viral hepatitis.

Recently, transfusion-transmitted virus (TTV) was discovered to be a potential causative agent for non-A-E hepatitis. Little is known about the relation between TTV and the clinical courses of various types of acute viral hepatitis. One hundred twenty-five patients with acute viral hepatitis who were admitted to the Chiba University Hospital between 1984 and 1998 and 100 persons with normal liver function tests were tested for the presence of TTV in their sera. Serum samples were tested for TTV DNA and genotype by polymerase chain reaction (PCR). TTV DNA was detected in 15 of 35 patients (43%) with non-A-E hepatitis, 14 of 33 patients (42%) with hepatitis C, 8 of 28 patients (29%) with hepatitis A, 7 of 29 patients (24%) with hepatitis B, and 37 of 100 subjects with normal liver function tests (37%). The detection rate did not differ statistically between non-A-E hepatitis and hepatitis A, B, C, or controls. The distribution of TTV genotypes was similar in non-A-E, A, B, C types, and controls. The clinical characteristics of the acute illnesses were similar for patients with or without TTV in hepatitis non-A-E, A, B, or C. Although TTV was detected frequently in non-A-E acute hepatitis, no etiologic role for TTV could be established.     

Persistently normal alanine transaminase levels in chronic C hepatitis: what does it tell us?

BACKGROUND/AIMS: We evaluated the demographic, clinical, histological and serological characteristics of chronic hepatitis C infection with persistently normal serum alanine transaminase levels and compared the results with those obtained in a group of chronic hepatitis C infection with serum alanine transaminase levels above normal. METHODOLOGY: Twenty-one patients who had chronic hepatitis C infection with normal alanine transaminase during the follow-up period and 34 patients who had chronic C infection with serum alanine transaminase levels above normal were included in this study. Demographic, clinical, histological and serological parameters of these two groups were evaluated. RESULTS: There were no significant differences in age, gender, known route of infection, viral load and genotype distribution between the two groups (P > 0.05). The gamma-glutamyltransferase and gamma-globulin levels were significantly higher in the serum alanine transaminase levels above normal group (P < 0.01 and P < 0.05). Among the patients with normal alanine transaminase, liver biopsy findings were normal in eight patients (38%). None of the patients with serum alanine transaminase levels above normal had normal liver biopsy findings. Histologic activity index was significantly higher in serum alanine transaminase levels above normal group (9.7 +/- 2.2 vs. 6.4 +/- 1.9; P < 0.001). Histologic activity index and alanine transaminase levels correlate with the stage of the disease (P < 0.05). CONCLUSIONS: For a definite diagnosis in patients with HCV-RNA+ and normal alanine transaminase liver biopsy is necessary and significant liver disease may be present in such patients irrespective of viral load, genotype and alanine transaminase levels.     

TTV阳性肝病患者的临床与病理学特征初步观察

目的 观察ＴＴＶ阳性肝病患者的临床和病理特征。方法 用巢式ＰＣＲ法检测ＴＴＶ－ＤＮＡ,同时观察血清生化指标,肝组织活检观察其病理变化。结果 ＴＴＶ感染者的血清学模式以重叠ＨＢＶ、ＨＣＶ、ＨＡＶ、ＨＥＶ、ＨＧＶ二重感染为主占５７．９％（２２／３８）,以乏力、纳差、腹胀为临床特征,ＴＢｉＬ、ＡＬＴ变化不明显,ＴＴＶ单独感染者为４２．１％（１６／３８）,急性发病者临床特征多与“急性黄疸性肝炎”相似,病理改变与各型病毒性肝炎的病理变化基本相似,但主要以肝门脉区炎症,小叶间胆管损伤,灶状坏死为多见。结论 ＴＴＶ可与各型已知肝炎病毒重叠感染也可单独感染。     

Transfusion-transmitted virus in association with hepatitis A-E viral infections in various forms of liver diseases in India

AIM: To describe the prevalence of transfusion-transmitted virus (TTV) infection in association with hepatitis A-E viral infections in different forms of liver diseases in North India. METHODS: Sera from a total number of 137 patients, including 37 patients with acute viral hepatitis (AVH), 37 patients with chronic viral hepatitis (CVH), 31 patients with cirrhosis of liver and 32 patients with fulminant hepatic failure (FHF), were analyzed both for TTV-DNA and hepatitis A-E viral markers. Presence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis E virus (HEV) infections was detected in different proportions in different groups. Moreover, TTV-DNA was simultaneously tested in 100 healthy blood donors also. RESULTS: None of the patients had hepatitis A virus (HAV) and hepatitis D virus (HDV) infections. Overall prevalence of TTV-DNA was detected in 27.1% cases with AVH, 18.9% cases with CVH, 48.4% cases with cirrhosis and 9.4% cases with FHF. TTV-DNA simultaneously tested in 100 healthy blood donors showed 27% positivity. On establishing a relation between TTV infection with other hepatitis viral infections, TTV demonstrated co-infection with HBV, HCV and HEV in these disease groups. Correlation of TTV with ALT level in sera did not demonstrate high ALT level in TTV-infected patients, suggesting that TTV does not cause severe liver damage. CONCLUSION: TTV infection is prevalent both in patients and healthy individuals in India. However, it does not have any significant correlation with other hepatitis viral infections, nor does it produce an evidence of severe liver damage in patients with liver diseases.