Viral load and clinicopathological features of chronic hepatitis C (1b) in a homogeneous patient population

Fanning, Liam J.; Kenny, Elizabeth; Sheehan, Margaret; Cannon, Bradley; Whelton, M. J.; O’Connell, Joe; Collins, John; Shanahan, Fergus

doi:10.1002/hep.510290310

Cited by 88 publications

(63 citation statements)

References 41 publications

(45 reference statements)

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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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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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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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“…[29][30][31] The contaminating HCV 1b was derived from a single infected donor. [30][31][32][33] The homogeneity of this group allows one to examine variation in host response to HCV infection without the potentially confounding influence of factors such as gender, specific HCV genotype, age range, and general health status.…”

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confidence: 99%

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Fanning¹,

Levis²,

Kenny-Walsh³

et al. 2000

Hepatology

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Hepatitis C virus (HCV) infection is the main cause of non-A, non-B hepatitis. 1-5 HCV consists of a heterogeneous mix of isolates defined by genotype, each of which is further classified into subtypes. 6,7 A number of factors have been considered in terms of their potential to predict the outcome of the disease. These include age of infection, viral typesubtype, quasispecies, viral load, and mode of infection. [8][9][10][11][12][13] Clinical heterogeneity in disease progression may reflect viral heterogeneity and variations in host response. 14-17 The human leukocyte antigen (HLA) has been shown to influence host response to infection. [18][19][20][21][22] Although HLA class II genes have shown associations with viral clearance or persistence of the HCV these findings are not uniform. [23][24][25][26][27][28] In addition, direct comparisons between studies is often difficult because of heterogeneity of ethnic background, viral genotype, phenotype frequencies of individual alleles between populations, gender, and duration of disease. To avoid heterogeneity of risk factors and confounding variables in viral type/subtype we studied a unique cohort of individuals all infected by anti-D contaminated from a single source of HCV 1b. The patients were of similar ethnogeographic background and had an absence of competing risk factors for liver disease.The present study is a follow-up investigation of the well-documented series of Irish women who were inadvertently infected with HCV as a result of receiving contaminated anti-D immunoglobulin (from a single source) in 1977 to 1978. [29][30][31] The contaminating HCV 1b was derived from a single infected donor. [30][31][32][33] The homogeneity of this group allows one to examine variation in host response to HCV infection without the potentially confounding influence of factors such as gender, specific HCV genotype, age range, and general health status. The purpose of the present study was to address whether particular HLA class II alleles are associated with clearance or persistence of HCV type 1b. PATIENTS AND METHODSThe study group consisted of 156 female individuals all of whom were iatrogenically infected between May 1977 and November 1978 with HCV type 1b from a single source. All 156 cases tested positive for antibodies to HCV (by recombinant immunoblot assay; Chiron Corporation, Emeryville, CA) and 46% (n ϭ 72) were positive for HCV RNA by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) using the Roche AMPLICOR test (F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland). The HCV status of the 84 patients who tested negative on initial qualitative HCV RT-PCR screening was confirmed by retesting within an 18-month period. The HCV genotype of the 72 virus-positive individuals was confirmed to be HCV 1b by reverse line probe assay (Inno-Lipa HCV II, INNOGENETICS N.V., Zwijndrecht, Belgium).Investigations were performed with informed consent and complied with a standardized protocol in compliance with standard of care and in accordance hospital eth...

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“…Population-based studies in the United States indicate that approximately 75% of patients remain chronically infected with hepatitis C (1). In contrast, up to 50% of patients have been reported to spontaneously resolve hepatitis C infection when exposure occurred in children undergoing cardiac surgery or cancer chemotherapy, in young women after a common-source outbreak of contaminated anti-D immunoglobulin, or in healthcare workers after needlestick exposures (2)(3)(4).…”

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confidence: 99%

“…Last two platelet counts < 100,000 cells/mm 3 The date of ADV was considered to be the date of the earliest diagnosed event in categories 1-5 above, and the date of the second abnormal laboratory result in categories 6-7…”

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Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

et al. 2006

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Viral load and clinicopathological features of chronic hepatitis C (1b) in a homogeneous patient population

Cited by 88 publications

References 41 publications

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

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

Viral clearance in hepatitis C (1b) infection: Relationship with human leukocyte antigen class II in a homogeneous population

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

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