丙型肝炎病毒IgG抗体阳性者确诊丙型肝炎的高危因素分析及列线图预测模型构建

目的分析丙型肝炎(丙肝)病毒(HCV)免疫球蛋白G(IgG)抗体阳性者中确诊HCV的高危因素,同时建立列线图(nomogram)预测模型,为基层医疗机构丙肝的临床诊断和转诊决策提供依据。方法回顾性收集2022年1月—2023年10月住院筛查患者中同时进行HCV\|RNA、HCV-IgG抗体、肝功能和血常规检测HCV-IgG抗体阳性者的人口学特征及丙肝相关各项指标。采用logistic回归分析HCV-IgG抗体阳性者确诊丙肝的高危因素,并构建nomogram模型,分别采用一致性系数和校准曲线评估模型的预测性能和符合度。结果394例HCV-IgG抗体阳性者中,HCV-RNA阳性率为30.2%。多因素logistic分析显示,在HCV-IgG抗体阳性的人群中,HCV-IgG≥5.0 S/CO、天冬氨酸氨基转移酶(AST)>35 U/L和有肝炎相关临床症状为HCV-RNA阳性的独立危险因素,其OR值分别为233.926(95%CI:31.814~1720.046)、4.079(95%CI:2.105~7.904)和5.295(95%CI:1.505~18.634)。用于预测HCV-RNA阳性的nomogram模型准确度为0.923,灵敏度为99.2%,特异度为74.5%。结论基于HCV-IgG抗体、AST和肝炎相关临床症状的nomogram模型具有高准确度,可用于指导临床医生判断HCV-IgG抗体阳性者确诊HCV感染的风险。

A high frequency of GBV-C/HGV coinfection in hepatitis C patients in Germany

AIM To detect infection rate of GBV-C/HGV inhepatitis C patients,to determine the methodsof higher sensitivity and the primers of higherefficiency for GBV-C/HGV RNA detection and tostudy the dominant subtype and mutation ofGBV-C/HGV.METHODS Quantitative RT-PCR for detectionpf HCV RNA concentration in serum samples,RT-nested PCR with two sets of primers fordetection of GBV-C RNA,RT-PCR ELISA with twosets of primers for detection of HGV RNA,nucleotide sequence and putative amino acidsequence analysis.RESULTS The positive rates of GBV-C RNA atthe 5’-NCR and NS3 region in 211 serums amplesfrom the patients with HCV infection were 31.8%and 22.8% respectively.The positive rates ofHGV RNA at the 5’-NCR and NS5 region in thesame samples were 47.9% and 31.8%respectively.The total positive rate of GBV-C/HGV RNA was as high as 55.5%.HCV copynumbers in the patients without GBV-C/ HGVcoinfection were statistically higher than that inthe patients with GBV-C/ HGV coinfection(P【0.01).Frequent mutation of nucleotideresidue was present in the amplificationproducts.Frameshift mutation was found in twosamples with GBV-C NS3 region nucleotidesequences.All nucleotide sequences fromamplification products showed higher homologyto HGV genome than to GBV-C genome even though part of the sequences were amplifiedwith GBV-C primers.CONCLUSION A high frequency of GBV-C/ HGV coinfection existed in the hepatitis C patients. RT-PCR ELISA was more sensitive than RT-nested PCR for detection of GBV-C/ HGV RNA. The primers derived from the 5 -NCR was more efficient than those derived from the NS3 and NS5 regions. A reverse relationship was found to exist between HCV RNA concentration and GBV-C/ HGV infection frequency. HGV was the dominant subtype of the virus in the local area. The major mutations of GBV-C/ HGV genomes were random mutation of nucleotide residue.

Serological prevalence and risk factor analysis of hepatitis G virus infection in Hubei Province of China

Hepatitis G virus (HGV),also known as GB virus C, is a recently cloned virus which may be associated with human non A-E hepatitis[1，2] It is parenterally transmitted and usually coinfected or superinfected with hepatitis B or hepatitis C virus[3-5]. Some investigations have been reported on the seroprevalence and molecular prevalence of HGV infection in different areas and different population[6-15]. Current infection of HGV is diagnosed by detection of HGV RNA, and past infection with HGV is detectable by testing anti-HGV envelope protein (E2)[16-17]. To investigate the prevalence of HGV in Hubei Province, a central area of the People's Republic of China, ELISA and RT-PCR were employed to detect serum anti-HGV and HGV RNA in 1516 patients who were divided into 16 groups.

Hepatitis viruses and non-Hodgkin's lymphoma: A review

Non-Hodgkin's lymphoma(NHL) is among the haematological malignancies with high prevalence worldwide, causing estimated 355 900 new cases and 191 400 deaths in 2008. High prevalence of NHL is documented in economically more developed areas while low prevalence is observed in less developed areas of the globe. A wide array of environmental factors have been reported to be either directly involved or in modifying the risk of NHL development. In addition to these factors, a number of infectious agents, chiefly viruses have also been implicated in the development of NHL. This article reviews the available literature to discuss the role of hepatitis viruses in NHL development, possible mechanisms of lymphomagenesis and also identify the areas in which further research is required to better understand this disease. A brief discussion on the clinical aspects such as classification, staging, treatment approaches have also been included in this article.

Hepatitis G virus

A number of new hepatitis viruses (G, TT, SEN) were discovered late in the past century. We review the data available in the literature and our own findings suggesting that the new hepatitis G virus (HGV), disclosed in the late 1990s, has been rather well studied. Analysis of many studies dealing with HGV mainly suggests the lymphotropicity of this virus. HGV or GBV-C has been ascertained to influence course and prognosis in the HIV-infected patient. Until now, the frequent presence of GBV-C in coinfections, hematological diseases, and biliary pathology gives no grounds to determine it as an "accidental tourist" that is of no significance. The similarity in properties of GBV-C and hepatitis C virus (HCV) offers the possibility of using HGV, and its induced experimental infection, as a model to study hepatitis C and to develop a hepatitis C vaccine.

A study on pathogenicity of hepatitis G virus

AIM To study the pathogenicity of hepatitis G virus (HGV) and observe the genesis and pathological process of hepatitis G.METHODS HGV-RNA in serum was detected by RT-PCR assay. The immunohistochemical assays of liver tissue were performed with HGV monocoloned antibody (McAb)expressed from the region of HGV NS5 nucleic acid sequence. The clinical and pathological data of 52 patients with hepatitis G were discussed. In animal experiment,the Chinese Rhesus monkeys were infected with the serum of a patient with HGV infection. And the dynamic changes in serology and liver histology of animals were observed.RESULTS One hundred and fifty-four patients with HGVRNA positive were selected from 1552 patients with various kinds of hepatitis. Of 154 patients with HGV infection, 52 were infected with HGV only, which accounted for 33.8% (52/154) and 102 with positive HGVRNA were super-infected with other hepatitis viruses,which accounted for 66.2% (102/154). The clinical and pathological observation showed that the acute and chronic hepatitis could be induced by HGV. The slight abnormality of transaminases ALT and AST in serum of monkeys lasted nearly 12 months and histological results showed a series of pathological changes.CONCLUSION HGV is a hepatotropic virus and has pathogenicty.

Inhibition of hepatitis B virus replication by APOBEC3G in vitro and in vivo

AIM： To investigate the effect of APOBEC3G mediated antiviral activity against hepatitis B virus （HBV） in cell cultures and replication competent HBV vector-based mouse model. METHODS： The mammalian hepatoma cells Huh7 and HepG2 were cotransfected with various amounts of CMV-driven expression vector encoding APOBEC3G and replication competent 1.3 fold over-length HBV. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA. The expression of HBcAg in transfected cells was detected by western blot. HBV DNA and RNA from intracellular core particles were examined by Northern and Southern blot analyses. To assess activity of the APOBEC3G in vivo, an HBV vector-based model was used in which APOBEC3G and the HBV vector were co-delivered via high-volume tail vein injection. Levels of HBsAg and HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by ELISA and quantitative PCR analysis respectively. RESULTS： There was a dose dependent decrease in the levels of intracellular core-associated HBV DNA and extracellular production of HBsAg and HBeAg. The levels of intracellular core-associated viral RNA also decreased, but the expression of HBcAg in transfected cells showed almost no change. Consistent with in vitro results, levels of HBsAg in the sera of mice were dramatically decreased. More than 1.5 log10 decrease in levels of serum HBV DNA and liver HBV RNA were observed in the APOBEC3G-treated groups compared with the control groups.CONCLUSION： These findings indicate that APOBEC3G could suppress HBV replication and antigen expression both in vivo and in vitro, promising an advance in treatment of HBV infection.

Hepatitis B virus subgenotype F3 reactivation with vaccine escape mutations:A case report and review of the literature

Hepatitis B represents a global health threat because its chronic course and sequelae contribute to a high morbidity and mortality. Hepatitis B virus(HBV) infection can be controlled by vaccines, antiviral treatment, and by interrupting transmission. Rare vaccine escape mutants are serious because they eliminate vaccine protection. Here, we present a 74-year-old vaccinated patient with HBV reactivation 11 years after kidney transplantation. The patient was HBV-positive but HBs Ag-negative prior to vaccination 6 years before transplantation. The reactivated virus was HBV genotype F3 with vaccine escape mutations G145 R, P120 Q, and Q129 P. The patient was successfully treated with entecavir. The epidemiological reasons for this subgenotype, which is extremely rare in Western Europe, were unclear. This case illustrates that second-generation vaccines are not always effective in a specific group of patients.

N-terminal and C-terminal cytosine deaminase domain of APOBEC3G inhibit hepatitis B virus replication

AIM: To investigate the effect of human apolipoprotein B mRNA-editing enzyme catalytic-polypeptide 3G (APOBEC3G) and its N-terminal or C-terminal cytosine deaminase domain-mediated antiviral activity against hepatitis B virus (HBV) in vitro and in vivo. METHODS: The mammalian hepatoma cells HepG2 and HuH7 were cotransfected with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vector and 1.3-fold-overlength HBV DNA as well as the linear monomeric HBV of genotype B and C. For in vivo study, an HBV vector-based mouse model was used in which APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vectors were co-delivered with 1.3-fold-overlength HBV DNA via high-volume tail vein injection. Levels of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) in the media of the transfected cells and in the sera of mice were determined by ELISA.The expression of hepatitis B virus core antigen (HBcAg) in the transfected cells was determined by Western blot analysis. Core-associated HBV DNA was examined by Southern blot analysis. Levels of HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by quantitative PCR and quantitative RT-PCR analysis, respectively. RESULTS: Human APOBEC3G exerted an anti-HBV activity in a dose-dependent manner in HepG2 cells, and comparable suppressive effects were observed on genotype B and C as that of genotype A. Interestingly, the N-terminal or C-terminal cytosine deaminase domain alone could also inhibit HBV replication in HepG2 cells as well as Huh7 cells. Consistent with in vitro results, the levels of HBsAg in the sera of mice were dramatically decreased, with more than 50 times decrease in the levels of serum HBV DNA and core-associated RNA in the liver of mice treated with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain as compared to the controls. CONCLUSION: Our findings provide probably the first evidence showing that APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain could suppress HBV replication in vitro and in vivo.

Detection of hepatitis G virus RNA in hepatitis C patients and hepatitis C virus infected hemodialysis patients

Two sets of PCR primers in the 5’ non-coding region were designed according to published hepatitis G virus (HGV) sequence. Using these primers, a nested reverse transcription PCR was carried out in 47 hepatitis C patients and 10 HCV RNA (+ ) hemodialysis patients. Ten of the hepatitis C patients and one of the hemodialysis patients (11/57, 19. 3% ) were found to be positive for HGV RNA. The PCR products from two HGV RNA positive patients were cloned and sequenced. The cDNA homologies were 83% -90% as compared with the published sequences. The results show that HGV infection is rather common in hepatitis C-infected patients, suggesting that it is necessary to investigate the effect of HGV on the course of HCV infection.

Hepatitis G virus genomic RNA is pathogenic to Macaca mulatta

AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum.METHODS: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological,histological assays.RESULTS: Serum HGV RNA was detectable in all the 3Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohistochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes.RT-PCR and quantitative PCR results showed that HGV could replicate in liver.CONCLUSION: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.

SEQUENCE ANALYSIS OF THE NS5 REGION OF GBVC/HGV AND DETECTION OF THE VIRUS BY REVERSE TRANSCRIPTASE PCR

GBV C/HGV is a newly identified virus associated with human hepatitis In this study, the nucleotide sequences of the partial NS5 gene of GBV C/HGV derived from sera of 8 Chinese patients were determined The nucleotide homology among the 8 isolates were 92% on average On the basis of sequence analysis, two sets of oligonucleotide primers derived from highly conserved region of GBV C/HGV NS5 gene were designed to establish both sensitive and specific nested PCR for detection of GBV C/HGV RNA 253 Chinese patients were examined for the virus RNA GBV C/HGV RNA positive rates in patients infected with HBV, HCV and patients with chronic non B,non C hepatitis were 18 4%, 19 8% and 8 9% respectively This result suggested that HBV,HCV and GBV C/HGV shared the same transmission risk factors 8 patients with GBV C/HGV and HCV coinfection were retrospectively observed for the response to interferon Coinfection with GBV/HGV did not negatively influence the responsiveness of HCV, and GBV C/HGV was sensitive to interferon to a certain degree

中国庚型肝炎病毒(HGV)全基因结构特点及其感染地理分布

分析和讨论了中国人庚型肝炎病毒（HGV）的基因结构特点及我国HGV感染的地理分布状况。中国庚型肝炎病毒株（HGVC964）基因全长9128个核苷酸，编码一个长度为2870个氨基酸残基的多聚前体蛋白。5’端有一个367bp的非翻译区，3’端非编码区为147个核苷酸。基因组中G＋C占59．9％。该株病毒与国外报道的三株HGV序列比较，核苷酸同源性为82．0％～86．2％，氨基酸同源性均大于90％。对我国部分地区的某些人群进行的分子流行病学研究表明，在我国北方、南方及广西少数民族地区也存在HGV感染。HCV自然感染者中，HGVRNA阳性率为6．7％；HC病人中，HGVRNA阳性率为9．6％；非甲一非戊型肝炎病人中，HGVRNA阳性率为5．0％。这表明，在我国HGV感染分布广泛，不同地理区带均有可能存在该型病毒感染。

HGV/GBV-C与HCV混合感染者肝组织中相关病毒抗原表达

庚型肝炎病毒(HGV/GBV-C)的致病性是目前研究焦点之一,多数研究表明大多数HGV/GBV-C感染者体内常有两种或两种以上的肝炎病毒混合感染,并认为HGV/GBV-C感染对原有乙型肝炎病毒(HBV)或丙型肝炎病毒(HCV)感染的基础病变似无明显影响,但仅从血清学、临床表现及常规病理角度试图说明HGV/GBV-C对机体有无损害的研究工作是很困难,我们应用免疫组织化学技术对HGV/GBV-C与HCV混合感染者肝组织中HGV/GBV-C。HCV相关抗原表达进行研究,试图从免疫病理学角度探讨HGV/GBV-C对机体肝脏的致病性。 1

山东地区输血后丙肝患者HGV感染状况及HGV部分核酸序列测定

应用 RT- PCR法检测庚肝病毒 ( HGV) RNA,并对阳性扩增的产物采用 PCR技术片段直接克隆法测定。结果从 86例输血后丙型肝炎 ( PTH- C)患者血清中检出 HGVRNA阳性者 31例 ( 36.0 % ) ,其中 1例 HGVNS5区部分核苷酸序列与美国原始株 ( u4 4 40 2 )和另 1例日本株 ( d872 55)核苷酸同源性比较分别为 86.0 %和 84 .0 %。证实山东地区 PTH- C患者存在着 HGV感染和 HGV/ HCV混合感染 ,但是否存在不同亚型或 HGVRNA阳性携带者 。

庚型肝炎病毒(HGV)NS5区部分基因的克隆和cDNA序列测定

用RT－PCR技术从一例献血员血清标本中扩增出HGV非结构区的部分基因片段，克隆后测定。cDNA序列。该序列与国外三株HGV的核苷酸同源性在90％以上；与GBV—A和GBV—B的同源性分别为44．7％和33．17％；与已发表的23个HCV全序列的相应序列比较，同源性均小于40％。结果表明，克隆的病毒株为HGV中国株。同时，用RT—PCR检测了河北固安和南京地区的115份HCV感染者标本．HGVRNA阳性率为3．47％。表明我国某些特殊人群中HGV感染率较高，是一个不容忽视的问题。

HIV和HCV感染者重叠感染HGV对病毒复制的影响

目的 :了解人免疫缺陷病毒 (HIV)感染者和丙型肝炎病毒 (HCV)感染者重叠感染庚型肝炎病毒 (HGV)的情况 ,探讨重叠感染病毒在体内的相互作用机理。方法 :用定量 PCR测定 HIV和 HCV感染者血浆中病毒载量 ,同时用 RT- PCR检测这些患者 HGV的感染情况 ,并对部分 HGV阳性者进行序列测定。结果 :317例 HIV患者中检出 HGV阳性 12 3例 ,阳性率为 38.8% ;91例 HCV患者中 HGV阳性 19例 ,阳性率为 2 0 .9% ,统计学分析有显著差异。进一步研究显示 ,HIV和 HGV重叠感染中 HIV病毒载量明显低于单独 HIV感染者 [(1.8± 0 .6 )× 10copies/ ml vs(1.9± 1.1)× 10 2 copies/ ml];而 HCV和 HGV重叠感染者中 HCV的病毒载量与单独 HCV感染者比较没有显著差异 [(1.5± 0 .6 )× 10 4copies/ ml vs(5 .4± 1.8)× 10 4copies/ ml]。序例分析表明 ,与 HIV或 HCV重叠感染的 HGV来源于同一病毒株。结论 :HIV感染者有很高的 HGV重叠感染率 ,而且 HGV感染能明显抑制 HIV在体内的病毒复制。

二重RT-PCR同时检测HGV与HCVRNA

庚型肝炎病毒（ＨＧＶ）与丙型肝炎病毒（ＨＣＶ）具有相近的传播途径与类似的检测方法，本文建立了二重ＲＴ－ＰＣＲ法，用于同时检测ＨＧＶ与ＨＣＶ病毒核酸，其扩增产物分别为６０９ｂｐ与２５７ｂｐ，在琼脂糖或聚丙烯酰胺凝胶上均能完全分离。ＨＧＶ产物经测序显示与报道的核酸序列同源性为８９．２％～９２．６％，该法具较好的批间重复性。二重ＰＣＲ法减轻了实验人员的操作强度，可降低测定费用近５０％。

深圳市一般人群HGV和TTV感染的研究

为探讨深圳市一般人群中HGV和TTV感染状况及其影响因素。方法采用随机抽样法选取研究对象 ,对HGV感染的检测先用ELISA法检测样本中的抗 -HGV ,对其中阳性样本再用反转录PCR(RT -PCR)进行检测 ;TTVDNA则采用巢式PCR方法检测。结果表明 ,深圳市一般人群中HGVRNA和TTVDNA阳性率分别为 2 33%和 14 77% ,男女阳性率HGVRNA为 2 4 5%和2 2 0 % ,TTVDNA阳性率为 17 86%和 12 0 %。年龄组间HGVRNA及TTVDNA阳性率差异均无显著性 ;单因素和Logistic回归分析未显示肝炎病史、近期手术史、注射史、拔牙史及乙型肝炎疫苗接种史等因素与HGV及TTV感染有关 ;HBsAg、抗 -HBS和抗 -HBc与HGV及TTV感染无统计学意义。不同职业人群中HGVRNA阳性率以中学生和教师较高 ;TTVDNA阳性率则以税务干部和教师高于其他人群 ,因此证明 ,深圳市一般人群中HGV和TTV感染率较高 。

单纯HGV感染急性肝炎患者的临床与病理研究

目的 通过对一组急性HGV感染患者的肝组织病理和临床资料分析 ,探讨庚型肝炎病毒感染的致病性。方法 采用免疫组织化学技术对 5 9例不明原因急性肝炎患者的肝组织 ,进行乙、丙和庚型肝炎病毒抗原检测 ,部分病例经原位杂交证实。结果 HGVNS5抗原的检出率为 ( 5 7 6% ,3 4 /5 9) ,其中 2 0例肝组织中HBsAg和 /或HCVNS3Ag同时阳性 (HGV合并感染组 ) ,HGV阳性信号主要位于肝细胞浆内。HGV单纯感染病例与HGV重叠感染组相比 ,无论在病理改变或生化指标方面均无显著性差别。结论 HGV是一种嗜肝病毒 。