Quantification of hepatitis C virus by competitive reverse transcription—polymerase chain reaction: Increase of the virus in advanced liver disease

Kato, Naoya; Yokosuka, Osamu; Hosoda, Kei; Ito, Yoshimi; Ohto, Masao; Omata, Masao

doi:10.1002/hep.1840180104

Cited by 180 publications

(101 citation statements)

References 17 publications

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“…Some investigators have shown that viral load increased in proportion to the length of HCV infection, suggesting that this fact might be a cause of progression of HCV-induced chronic liver disease. 28 However, liver histology data of our post-transfusional patients showed a more severe liver damage in adults than in children, both with a similar duration of HCV infection,…”

Section: Discussionmentioning

confidence: 56%

Chronic Hepatitis C in Children: A Clinical and Immunohistochemical Comparative Study With Adult Patients

et al. 1998

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Limited information is available regarding the characteristics of the hepatitis C virus (HCV) infection in children.We compared the epidemiological background along with the virological and histological features as well as the intrahepatic immunologic phenotype of both children and adults with chronic hepatitis C (CHC). Serum samples of 24 pediatric and 32 adult patients were drawn for alanine transaminase (ALT) levels, HCV-typing, and viral load. The histological diagnosis and a semiquantitative immunohistochemical assessment were performed in all patients. The majority of children (62%) had been transfused and the mean duration of viral infection in these cases was 11 ؎ 4 years, being similar in adults (11 ؎ 9 years, not significant). Although genotype distribution was similar, viral load was lower in children than in adults. The mildest histological forms of chronic hepatitis along with a weak intrahepatic immunological phenotype were significantly more frequent among children than adult patients. In conclusion, in children with CHC, perinatal blood transfusion was the most frequent source of viral infection and the liver disease was characterized by both low ALT level and viral load, as well as the mildest histological and immunohistochemical forms of chronic hepatitis. (HEPATOLOGY 1998;28:1696-1701.)Hepatitis C virus (HCV) is a recognized causative agent of blood-borne non-A, non-B hepatitis 1 and chronic liver disease in both adults and children. 2-4 Currently, six major HCV types have been recognized 5 and these have a significant effect on the course of HCV-induced liver disease. 6,7 In adult patients, the natural history of chronic HCV infection is becoming better understood. It is estimated that 65% of those infected will develop some degree of chronic liver disease. 8,9 In addition, a number of immunohistochemical studies performed in adult patients with chronic hepatitis C (CHC) strongly support the assumption that T-cell-mediated immune reactions play an important role in the pathogenesis of liver damage, showing a high number of liver-infiltrating activated T cells along with an intrahepatic up-regulated expression of antigen recognition and intercellular and vascular adhesion molecules, which are essential for the cytolytic immune response. [10][11][12][13] By contrast, little is known concerning the clinical features and the histological outcome of CHC when the HCV infection is acquired early in life. Therefore, the aims of the present study were, first, to compare the epidemiological, clinical, virological, and histological features of both children and adult patients with CHC and, second, to characterize by immunohistochemistry the intrahepatic immunological phenotype of these patients. PATIENTS AND METHODS PatientsTwenty four Spanish children, who were referred to the Pediatric Hepatology Unit of the Hospital La Paz in Madrid, Spain because of persistently elevated serum alanine transaminase (ALT) levels, were included in this study. The diagnosis of CHC was further based on the presence of bo...

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Section: Discussionmentioning

confidence: 56%

Chronic Hepatitis C in Children: A Clinical and Immunohistochemical Comparative Study With Adult Patients

et al. 1998

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“…Many previous studies have examined the significance of both parameters independently. The wide range of clinicopathological correlations between serum and intrahepatic RNA levels (20,23,24,31,32,35,38,42,47,50,51), together with discrepancies in the literature among authors who find correlation between quasispecies complexity and liver damage (25,28,33,61) and those who do not (22,36,48,56), suggests that the relation between viral load and liver injury is more complex than expected.Recently, we have proven that, within an infected patient, the composition of the circulating viral population does not necessarily reflect the composition of the hepatic population (5), although the causes for this difference remain obscure. Heterogeneous quasispecies in peripheral blood mononuclear cells (PBMC) of humans and in chimpanzees have been described (34, 37, 49, 54, 57), and it has been proposed that replication in this tissue might contribute to HCV serum quasispecies complexity.…”

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confidence: 99%

Nucleotide and Amino Acid Complexity of Hepatitis C Virus Quasispecies in Serum and Liver

Cabot

Martell

Esteban

et al. 2000

J Virol

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The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maintaining and modulating viral replication. Several studies have tried to unravel, through the parameters that characterize HCV circulating quasispecies, prognostic markers of the disease. In a previous work we demonstrated that the parameters of circulating viral quasispecies do not always reflect those of the intrahepatic virus. Here, we have analyzed paired serum and liver quasispecies from 39 genotype 1b-infected patients with different degrees of liver damage, ranging from minimal changes to cirrhosis. Viral level was quantified by real-time reverse transcription-PCR, and viral heterogeneity was characterized through the cloning and sequencing of 540 HCV variants of a genomic fragment encompassing the E2-NS2 junction. Although in 95% of patients, serum and liver consensus HCV amino acid sequences were identical, quasispecies complexity varied considerably between the viruses isolated from each compartment. Patients with HCV quasispecies in serum more complex (26%) than, less complex (28%) than, or similarly complex (41%) to those in liver were found. Among the last, a significant correlation between fibrosis and all the parameters that measure the viral amino acid complexity was found. Correlation between fibrosis and serum viral load was found as well (R ‫؍‬ 0.7). With regard to the origin of the differences in quasispecies complexity between serum and liver populations, sequence analysis argued against extrahepatic replication as a quantitatively important contributing factor and supported the idea of a differential effect or different selective forces on the virus depending on whether it is circulating in serum or replicating in the liver. Flaviviridae (7,29,45). Its genome consists of a single-stranded RNA, with plus polarity, of 9,600 nucleotides, which does not integrate in the host genome, yet persistence is the rule. The damage caused during infection ranges from minimal changes to cirrhosis of the liver and hepatocarcinoma, but little is known about the mechanism of hepatocyte injury due to chronic infection. It seems very likely that the pathogenesis of HCV infection is directly related to a strong interplay between the host defense mechanisms and the virus's ability to evade them efficiently. Moreover, in order to persist, HCV must regulate its lytic potential and avoid elimination by the host immune system. Due to the quasispecies structure of the HCV viral population infecting single patients (39), the virus may use a variety of strategies to fulfill both requirements (11,17). Hepatitis C virus (HCV) is an enveloped virus classified in the familyThe dynamic component of the quasispecies structure is responsible for the rapid virus evolution (12). It works through a complex mixture of genomic sequences (quasispecies) which behaves as a single unit when facing changes in the environment. The genetic interaction within the viral population allows the system to distinguish the best possibility at any given...

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“…To quantify a very small copy number of the viral RNA, it was essential to develop a quantitative and competitive polymerase chain reaction (QCPCR) assay as used for titration of human immunodeficiency virus (Kato et al, 1993;Piatak et al, 1993). The strategy of the QCPCR for titration of HCV RNA is described in Fig.…”

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confidence: 99%

Association of hepatitis C virus particles with immunoglobulin: a mechanism for persistent infection

Choo

Cho

et al. 1995

Journal of General Virology

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The physical properties of hepatitis C virus (HCV) particles were determined by ultracentrifugation on 20-60 % isopycnic sucrose density gradients. We report that (i) two populations of HCV particles were found in the sera of patients with chronic HCV infection [at high density (1.186-1.213 g/ml) and at low density (1.099-1.127 g/ml)], (ii) virus particles with high density values were associated with immunoglobulin, and (iii) virus particles with low density values accumulated base changes within a hypervariable region (HVR) of the E2 envelope domain of the RNA genome. The results indicate that base changes within the HVR of E2 lead to the accumulation ofimmunoglobulin-free virus particles. Therefore, these findings imply that persistent HCV infection is established as a consequence of sequence variation in the E2 envelope domain.

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Quantification of hepatitis C virus by competitive reverse transcription—polymerase chain reaction: Increase of the virus in advanced liver disease

Cited by 180 publications

References 17 publications

Chronic Hepatitis C in Children: A Clinical and Immunohistochemical Comparative Study With Adult Patients

Chronic Hepatitis C in Children: A Clinical and Immunohistochemical Comparative Study With Adult Patients

Nucleotide and Amino Acid Complexity of Hepatitis C Virus Quasispecies in Serum and Liver

Association of hepatitis C virus particles with immunoglobulin: a mechanism for persistent infection

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