Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By Metagenomic Next-Generation Sequencing.

Viral Surveillance in Serum Samples From Patients With Acute Liver Failure By Metagenomic Next-Generation Sequencing.
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DOI:
10.1093/cid/cix596
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发表时间:
2017-10-16
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Chiu CY
Chiu CY
中科院分区:
其他
文献类型:
--
作者:
Somasekar S;Lee D;Rule J;Naccache SN;Stone M;Busch MP;Sanders C;Lee WM;Chiu CY

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1998-2010年间对187例不明原因急性肝功能衰竭(ALF)患者进行的病毒总基因组监测表明,尽管未发现与ALF相关的新病毒,但应对这些患者进行罕见病毒及其合并感染的筛查。所有急性肝功能衰竭(ALF)病例中有12%的原因不明,通常被称为不明原因。一种以前未知的嗜肝病毒被怀疑为潜在的病原体。我们比较了元基因组下一代测序(MNGS)和确认性核酸测试(NAT)以及常规临床诊断测试在检测与ALF相关的已知或新病毒方面的性能。对1998年至2010年收集的204名成年ALF患者的血清样本进行了分析,这是全国登记的一部分。187名患者(92%)被归类为不明原因,其余17名患者(8%)作为对照组,既有甲型肝炎病毒感染,也有乙肝病毒感染,或有ALF的非感染性原因。MNGS检出8例未知病原体感染,其中单纯疱疹病毒1型4例,其中单纯疱疹病毒与乙肝病毒混合感染1例,乙肝病毒、细小病毒B19、巨细胞病毒、人类疱疹病毒7型各1例。还发现了几个遗漏的双重或三重感染,组装的病毒基因组提供了关于基因分型和耐药突变的更多信息。重要的是,没有检测到与新病毒相对应的序列。这些结果表明,ALF患者应该进行罕见病毒和混合感染的筛查,而美国大多数不明原因的ALF病例似乎不是由新的病毒病原体引起的。在未来,mNGS检测可能有助于ALF相关病毒的综合诊断,或用于排除感染性病因。
Viral metagenomic surveillance of 187 patients with indeterminate acute liver failure (ALF) from 1998 to 2010 suggests that these patients should be screened for the presence of uncommon viruses and coinfections, although novel viruses associated with ALF were not identified. Twelve percent of all acute liver failure (ALF) cases are of unknown origin, often termed indeterminate. A previously unrecognized hepatotropic virus has been suspected as a potential etiologic agent. We compared the performance of metagenomic next-generation sequencing (mNGS) with confirmatory nucleic acid testing (NAT) to routine clinical diagnostic testing in detection of known or novel viruses associated with ALF. Serum samples from 204 adult ALF patients collected from 1998 to 2010 as part of a nationwide registry were analyzed. One hundred eighty-seven patients (92%) were classified as indeterminate, while the remaining 17 patients (8%) served as controls, with infections by either hepatitis A virus or hepatitis B virus (HBV), or a noninfectious cause for their ALF. Eight cases of infection from previously unrecognized viral pathogens were detected by mNGS (4 cases of herpes simplex virus type 1, including 1 case of coinfection with HBV, and 1 case each of HBV, parvovirus B19, cytomegalovirus, and human herpesvirus 7). Several missed dual or triple infections were also identified, and assembled viral genomes provided additional information on genotyping and drug resistance mutations. Importantly, no sequences corresponding to novel viruses were detected. These results suggest that ALF patients should be screened for the presence of uncommon viruses and coinfections, and that most cases of indeterminate ALF in the United States do not appear to be caused by novel viral pathogens. In the future, mNGS testing may be useful for comprehensive diagnosis of viruses associated with ALF, or to exclude infectious etiologies.
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