Komatsu Haruki, Inui Ayno, Sogo Tsuyoshi, Kuroda Koichi, Tanaka Toshio, Fujisawa Tomoo
Department of Pediatrics, National Defense Medical College, Saitama, Japan.
J Med Virol. 2004 Nov;74(3):499-506. doi: 10.1002/jmv.20204.
The TT virus (TTV) was isolated recently from the serum of a patient with post-transfusion hepatitis. TTV infection is widespread in the general population, and its prevalence increases continuously with age. The pathogenic role of TTV in liver disease remains controversial, and the source of transmission is still unclear. We investigated the pathogenicity and epidemiology of TTV infection in infants born to TTV DNA-positive mothers. Enrolled in this study were 22 mother-child pairs testing negative for antibodies to hepatitis B, hepatitis C, and the human immunodeficiency viruses (HIVs). The children were followed for 30 months after birth. Serum TTV DNA was detected by N22-PCR, and the PCR products were cloned and sequenced. The prevalence of TTV infection in children increased with age. Of the 22 children, 13 (59%) became positive for TTV DNA during the follow-up period. Of these 13 children, 6 (46%) had elevated levels of serum alanine aminotransferase (ALT), although the elevations were transient and mild. TTV viremia was not associated significantly with the abnormal ALT levels. Children with TTV viremia developed neither severe liver disease nor fulminant hepatitis. Phylogenetic analysis showed that, in 11 (85%) of the 13 pairs, the mother and child had the same genotype at the first PCR-positive time point. Among those 11 mother-child pairs, 6 (55%) had identical TTV nucleotide sequences. However, the genotype of predominant clones changed in 5 (50%) of 10 children who were positive for TTV DNA at two or more time points during the follow-up period. In conclusion, this study did not provide evidence that TTV infection is related to liver disease in children. Although the main source of TTV infection in children is presumed to be their mothers, transmitted via non-parenteral routes in the course of daily contact, intrafamilial carriers may also be sources of TTV infection.
TT病毒(TTV)最近从一名输血后肝炎患者的血清中分离出来。TTV感染在普通人群中广泛存在,并且其流行率随年龄不断增加。TTV在肝脏疾病中的致病作用仍存在争议,传播来源也尚不清楚。我们调查了TTV DNA阳性母亲所生婴儿中TTV感染的致病性和流行病学情况。本研究纳入了22对母婴,这些母婴的乙肝、丙肝和人类免疫缺陷病毒(HIV)抗体检测均为阴性。对这些儿童在出生后进行了30个月的随访。通过N22-PCR检测血清TTV DNA,并对PCR产物进行克隆和测序。儿童中TTV感染的流行率随年龄增加。在这22名儿童中,13名(59%)在随访期间TTV DNA转为阳性。在这13名儿童中,6名(46%)血清丙氨酸氨基转移酶(ALT)水平升高,不过这些升高是短暂且轻微的。TTV病毒血症与ALT水平异常无显著关联。患有TTV病毒血症的儿童既未发生严重肝脏疾病也未发生暴发性肝炎。系统发育分析表明,在13对中的11对(85%)中,母婴在首次PCR阳性时间点具有相同的基因型。在这11对母婴中,6对(55%)具有相同的TTV核苷酸序列。然而,在随访期间两个或更多时间点TTV DNA呈阳性的10名儿童中,5名(50%)的优势克隆基因型发生了变化。总之,本研究未提供证据表明TTV感染与儿童肝脏疾病有关。虽然儿童TTV感染的主要来源推测是其母亲,通过日常接触中的非肠道外途径传播,但家庭内携带者也可能是TTV感染的来源。