戊型肝炎病毒(Hepatitis E virus,HEV)是造成急性肝炎最常见的原因之一。HEV基因组由5′非编码区、3个开放阅读框(ORF1、ORF2、ORF3)和3′非编码区组成,仅在HEV-1中发现了ORF4,并与ORF1重叠。各种编码蛋白在HEV的复制和感染中发挥着不...戊型肝炎病毒(Hepatitis E virus,HEV)是造成急性肝炎最常见的原因之一。HEV基因组由5′非编码区、3个开放阅读框(ORF1、ORF2、ORF3)和3′非编码区组成,仅在HEV-1中发现了ORF4,并与ORF1重叠。各种编码蛋白在HEV的复制和感染中发挥着不同的作用,而HEV的复制是由ORF1编码的RNA依赖性RNA聚合酶(RNA-dependent RNA polymerase,RdRp)所介导的。HEV RdRp是由多个蛋白亚基组成的复合酶,具有7个保守基序,这些保守基序在RNA合成过程中发挥核苷酸识别、合成、延伸、修饰和稳定等作用,保证了RdRp的功能,在HEV的复制和转录中起到关键作用。因此,以RdRp作为抗HEV药物作用靶点的治疗方案具有很好的应用前景,是目前药物开发的一种主流思路。目前,已发现利巴韦林、索非布韦、2′-C-甲基胞苷(2CMC)等核苷类RdRp抑制剂和锌、GPC-N114等非核苷类RdRp抑制剂对HEV有较强的抑制作用,可作为潜在的抗HEV药物进行深入研究。笔者对HEV编码蛋白和HEV RdRp的结构与功能进行阐述,总结目前发现的对HEV有抑制作用的RdRp抑制剂,以期为HEV的药物开发提供一种新的思路。展开更多
BACKGROUND: The duration of viremia during hepatitis E virus (HEV) infection has rarely been reported. This study was undertaken to detect HEV RNA in sera of patients with hepatitis E and to understand the process of ...BACKGROUND: The duration of viremia during hepatitis E virus (HEV) infection has rarely been reported. This study was undertaken to detect HEV RNA in sera of patients with hepatitis E and to understand the process of HEV infection more thoroughly. METHODS: HEV RNA was detected in the serum samples of hospitalized patients with acute hepatitis E by reverse transcriptase-nested polymerase chain reaction (RT-nPCR) using two pairs of primers from open reading frame (ORF) I of the HEV genome. RESULTS: The serum samples from 44 (70%) of 62 patients were positive for HEV RNA. Thirty-two of these patients, with 288 serial serum specimens, were followed up for the whole process, and 24 patients (75%) were positive for HEV RNA. The positive rates declined with the course of the disease, serum HEV RNA persisting for 20.6 days on average after onset of illness. Serum HEV RNA remained positive in 36 (81.8%) of the 44 patients at the time their alanine aminotransferase (ALT) began to decrease. There was no difference in HEV RNA positivity between serum with high levels of HEV antibody (peak P/N ratio >= 4.0) and that with low levels (peak P/N ratio 4.0), with 25 out of 35 and 19 out of 27 (71.4% vs. 70.4%, P>0.05), respectively. CONCLUSIONS: There is a relatively long period of HEV viremia in patients with hepatitis E. The proportion of HEV viremia and its duration are not directly related to serum ALT values or HEV antibody levels.展开更多
Although hepatitis E virus(HEV)is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries,locally acquired HEV infections are increasing in nonendemic countries.As such,HEV is...Although hepatitis E virus(HEV)is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries,locally acquired HEV infections are increasing in nonendemic countries.As such,HEV is emerging as an underdiagnosed cause of infection.This report describes three clinically variable cases of HEV infection with unusual clinical presentations.These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis(acute or chronic)with or without extrahepatic manifestations.HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions.Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection.展开更多
文摘BACKGROUND: The duration of viremia during hepatitis E virus (HEV) infection has rarely been reported. This study was undertaken to detect HEV RNA in sera of patients with hepatitis E and to understand the process of HEV infection more thoroughly. METHODS: HEV RNA was detected in the serum samples of hospitalized patients with acute hepatitis E by reverse transcriptase-nested polymerase chain reaction (RT-nPCR) using two pairs of primers from open reading frame (ORF) I of the HEV genome. RESULTS: The serum samples from 44 (70%) of 62 patients were positive for HEV RNA. Thirty-two of these patients, with 288 serial serum specimens, were followed up for the whole process, and 24 patients (75%) were positive for HEV RNA. The positive rates declined with the course of the disease, serum HEV RNA persisting for 20.6 days on average after onset of illness. Serum HEV RNA remained positive in 36 (81.8%) of the 44 patients at the time their alanine aminotransferase (ALT) began to decrease. There was no difference in HEV RNA positivity between serum with high levels of HEV antibody (peak P/N ratio >= 4.0) and that with low levels (peak P/N ratio 4.0), with 25 out of 35 and 19 out of 27 (71.4% vs. 70.4%, P>0.05), respectively. CONCLUSIONS: There is a relatively long period of HEV viremia in patients with hepatitis E. The proportion of HEV viremia and its duration are not directly related to serum ALT values or HEV antibody levels.
文摘Although hepatitis E virus(HEV)is the primary cause of enterically transmitted acute hepatitis and jaundice in developing countries,locally acquired HEV infections are increasing in nonendemic countries.As such,HEV is emerging as an underdiagnosed cause of infection.This report describes three clinically variable cases of HEV infection with unusual clinical presentations.These cases highlight the fact that HEV should be considered in the differential diagnosis of patients with unexplained hepatitis(acute or chronic)with or without extrahepatic manifestations.HEV should also be considered in patients with persistently elevated liver enzymes who have not travelled to known HEV-endemic regions.Lack of knowledge among physicians and an absence of standardized diagnostic tests may result in increased morbidity and mortality from HEV infection.
