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急性/近期丙型肝炎病毒感染。临床病程、病毒复制动力学及疾病转归。

Acute/recent HCV infection. Clinical course, viral replication kunetic and disease outcome.

作者信息

Tsertsvadze T, Sharvadze L, Dzigua L, Dolmazashvili E, Nelson Kenrad E

机构信息

Iv. Javakhishvili Tbilisi State University, Faculty of Medicine, Georgia.

出版信息

Georgian Med News. 2008 Dec(165):43-9.

Abstract

The aim of the study was to reveal and investigate acute/recent HCV infection at the very early stage in seronegative blood donors and seronegative Injecting Drug Users (IDUs) and to assess clinical laboratory variants of infection, viral replication kinetic, disease outcome, host and viral characteristics. Two groups of patients were included in this study. The first group consisted of ELISA negative 7000 blood donors; the second group included 3000 Injecting Drug Users (IDUs). All patients were investigated on HCV RNA by qualitative PCR using mini pool method. A pool of 6 was applied for blood donors' and a pool of 5 for IDUs. PCR negative pools were excluded from the study, while PCR positives were examined on individual samples. Anti-HCV was detected by ELISA and RIBA. Detection HCV RNA was performed by Real time PCR technique using COBAS TaqMan Test. HCV genotyping--by INNO-Lipa. HLA typing--by Sequence Specific Primer Amplification (SSP). 16 patients with acute/recent HCV were revealed: 7 from blood donors, 9 from IDUs. Among them: 4 were symptomatics and 12 asymptomatics. Out of 4 symptomatics 3 were with jaundice. Among 12 asymptomatics: 8 had elevated ALT; 2 neither elevated ALT nor symptoms but developed anti-HCV; 2 were with normal ALT and without further anti-HCV seroconversion. Among 16 subjects: 9 had genotype -1b, 1--genotype 1a, 3--genotype 2a/2c and 3--genotype 3a. Out of 16 cases 4 cleared the virus; 12 developed chronic infection. Spontaneous clearance (recovery from the disease) was observed in 2 out of 4 symptomatic patients and only in 2 patients out of 12 asymptomatics. In all patients viremia increased rapidly and reached a peak by week 4. Viral titer was remarkably stable for the next three weeks, followed by two or three fold decrease by week 9. After week 10 the viremia rapidly decreased: 4 or 5 logs by week 12 and it became either undetectable by weeks 16-18 (viral clearance), or virus was not eliminated and viral titer persisted in all follow up period (chronic infection). HLA DRB1 1101, DQB1 0301 and DRB1 1301/DQA1 0103 alleles were associated with clearance of HCV whereas DRB1 0301 was associated with chronic infection. Prevalence of HCV among seronegative blood donors was 0.1% and among IDUs 0.3%. Among acute/recent HCV infected patients rate of chronicity was 75% (50% in symptomatics and 83% in asymptomatics). Rate of recovery was 50% in symptomatic patients and about 16% in asymptomatics. Acute/recent HCV infection might have following clinical laboratory forms: symptomatic disease with or without jaundice, asymptomatic with or without elevated ALT, but with further anti-HCV seroconversion. It remains unclear whether enigmatic form of disease--acute/recent HCV infection without further seroconversion exists or not.

摘要

本研究的目的是在血清学阴性的献血者和血清学阴性的注射吸毒者(IDU)中揭示和调查极早期的急性/近期丙型肝炎病毒(HCV)感染,并评估感染的临床实验室变异、病毒复制动力学、疾病转归、宿主和病毒特征。本研究纳入了两组患者。第一组由7000名ELISA阴性的献血者组成;第二组包括3000名注射吸毒者(IDU)。所有患者均采用微量混合法通过定性PCR检测HCV RNA。献血者采用6人混合样本,注射吸毒者采用5人混合样本。PCR阴性的混合样本被排除在研究之外,而PCR阳性的则对个体样本进行检测。采用ELISA和RIBA检测抗-HCV。使用COBAS TaqMan检测通过实时PCR技术检测HCV RNA。通过INNO-Lipa进行HCV基因分型。通过序列特异性引物扩增(SSP)进行HLA分型。共发现16例急性/近期HCV感染患者:7例来自献血者,9例来自注射吸毒者。其中:4例有症状,12例无症状。在4例有症状的患者中,3例有黄疸。在12例无症状的患者中:8例ALT升高;2例ALT既未升高也无症状,但出现了抗-HCV;2例ALT正常且未进一步发生抗-HCV血清转化。在16名受试者中:9例为基因1b型,1例为基因1a型,3例为基因2a/2c型,3例为基因3a型。16例病例中4例病毒清除;12例发展为慢性感染。4例有症状的患者中有2例出现自发清除(疾病康复),12例无症状的患者中仅2例出现自发清除。所有患者的病毒血症迅速上升,并在第4周达到峰值。病毒滴度在接下来的三周内显著稳定,随后在第9周下降两到三倍。第10周后病毒血症迅速下降:到第12周下降4或5个对数,在第16 - 18周时要么病毒检测不到(病毒清除),要么病毒未被清除且病毒滴度在所有随访期间持续存在(慢性感染)。HLA DRB1 1101、DQB1 0301以及DRB1 1301/DQA1 0103等位基因与HCV清除相关,而DRB1 0301与慢性感染相关。血清学阴性的献血者中HCV患病率为0.1%,注射吸毒者中为0.3%。在急性/近期HCV感染患者中,慢性化率为75%(有症状者为50%,无症状者为83%)。有症状患者的康复率为50%,无症状患者约为16%。急性/近期HCV感染可能有以下临床实验室表现形式:有或无黄疸的有症状疾病、有或无ALT升高的无症状疾病,但会进一步发生抗-HCV血清转化。尚不清楚是否存在一种神秘的疾病形式——急性/近期HCV感染且无进一步血清转化。

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