Serum and liver HCV RNA levels in patients with chronic hepatitis C: correlation with clinical and histological features

Moliner, Lorena De; Pontisso, Patrizia; Salvo, Gian Luca De; Cavalletto, Luisa; Chemello, Liliana; Alberti, Alfredo

doi:10.1136/gut.42.6.856

Cited by 81 publications

(73 citation statements)

References 32 publications

(22 reference statements)

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“…1 The factors that determine the severity of liver disease in chronic HCV infection and their relative importance are not fully defined. Serum HCV RNA levels, as a proxy measurement of viral replication, correlate poorly with disease severity, 3,4 whereas conflicting data exist as to whether measurements of intrahepatic HCV replication correlate better with liver injury. [3][4][5][6][7][8][9] Virus-host interactions are also thought to be a significant cause of liver injury.…”

Section: Hronic Infection With Hepatitis C Virus (Hcv) Ismentioning

confidence: 99%

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C

et al. 2005

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The relationships among host immune and viral factors and the severity of liver disease due to hepatitis C virus (HCV) are poorly understood. Previous studies have focused on individual components of the immune response to HCV, often in relatively small numbers of patients. We measured HCV-specific lymphoproliferation (LP), intrahepatic cytotoxic T lymphocyte (CTL), and neutralizing antibody (NA) responses and HCV quasispecies (QS) diversity and complexity in a large cohort of subjects with advanced liver fibrosis (Ishak stages 3-6) on entry into the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. We correlated LP, CTL, NA, and QS results with clinical characteristics, including serum alanine aminotransferase (ALT), HCV RNA level, HCV genotype, and hepatic histopathology. LP, CTL, and NA responses were detected in 37%, 22%, and 22% of subjects tested, respectively. The only association that was statistically significant was higher mean serum ALT values in patients with detectable HCV-specific CTL responses (P ‫؍‬ .03). In conclusion, immune responses to HCV and viral diversity showed little relationship to clinical or histological features at a single time point in this selected population of patients with advanced chronic hepatitis C for whom prior interferon treatment had failed. (HEPATOLOGY 2005;41:617-625.)

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Section: Hronic Infection With Hepatitis C Virus (Hcv) Ismentioning

confidence: 99%

Associations among clinical, immunological, and viral quasispecies measurements in advanced chronic hepatitis C

et al. 2005

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“…As a whole, these studies have failed to find a consistent relationship between serum titers and the degree of hepatic injury. [2][3][4] The ratios of HCV genome RNA in liver and serum compartments are significantly different among chronically infected patients. 2,[5][6][7][8] These reports suggest that hepatic injury, serum titers, and intrahepatic viral replication do not display a linear relationship during chronic hepatitis C infection.…”

Section: Hepatitis C Virus (Hcv) Replication At the Cellular Level Ismentioning

confidence: 99%

Dynamics of Hepatitis C Virus Replication in Human Liver

Chang

Williams

Mittler

et al. 2003

The American Journal of Pathology

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Hepatitis C virus (HCV) replication at the cellular level is not fully understood. This study describes an optimized system for quantifying replication of HCV in hepatocytes and in liver tissues. A digital image analysis method was developed to quantify signal intensities of HCV genomic and replicative-intermediate1 Symptomatic differences among infected individuals have generated considerable interest in elucidating the pathogenic mechanisms of HCV disease.Previous studies have described the levels of HCV genomes in patient sera in cohorts either on therapeutic drug regimens, untreated, or undergoing liver transplantation. As a whole, these studies have failed to find a consistent relationship between serum titers and the degree of hepatic injury.2-4 The ratios of HCV genome RNA in liver and serum compartments are significantly different among chronically infected patients.2,5-8 These reports suggest that hepatic injury, serum titers, and intrahepatic viral replication do not display a linear relationship during chronic hepatitis C infection.HCV is a positive strand RNA virus that is classified as a Hepacivirus within the Flaviviridae family.9 By analogy with other members of the Flaviviridae, it is assumed that HCV replication requires production of negative strand replicative-intermediate RNA, from which progeny genomic strand RNA is transcribed. The presence of negative strand RNA in cells indicates ongoing HCV replication and synthesis of progeny genomic RNA in these cells. Previously, we and others have used strand-specific in situ hybridization to localize positive strand and negative strand HCV RNAs in infected human liver tissue. 10 The percentage of hepatocytes positive for genomic RNA ranged from 4.8 to 87.6%, 10 -12 whereas those positive for replicative-intermediate RNA ranged from 4 to 25%. 10,13 On visualization, the distribution and abundance of genomic RNA appeared to be different from that of replicative-intermediate RNA, suggesting compartmentalization or regulation of replication may occur.To further characterize HCV replication in liver tissue, we developed an image analysis method to measure quantitative amounts of genomic and replicative-intermediate RNAs in infected liver tissues, and to examine the

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“…[33][34][35][36] One recent, compelling study measured and found a positive correlation between serum and liver levels of HCV RNA, but neither level correlated with either ALT activity or histological abnormality. 27 Similarly, in another recent study that found a strong correlation between HCV RNA and core antigen levels, no association was identified between the levels of these two viral markers and fibrosis, necroinflammation, or steatosis on liver biopsy, viral genotype, ALT concentration, or alcohol consumption. 28 So, what accounts for the findings by the present authors of a strong association between HCV RNA levels and ESLD, given that the weight of evidence seems to contradict this relationship?…”

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confidence: 93%

“…[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Most have been single, cross-sectional studies that have not, however, tracked the long-term significance of the findings, as was done in the study reported in this issue of HEPATOLOGY. The results have been varied: the majority found no relationship whatsoever with liver disease severity [19][20][21][22][23][24][25][26][27][28][29] ; some identified increased hepatic inflammation without an impact on fibrosis [30][31][32] ; and a few identified increasing histological severity with increasing levels of virus. [33][34][35][36] One recent, compelling study measured and found a positive correlation between serum and liver levels of HCV RNA, but neither level correlated with either ALT activity or histological abnormality.…”

mentioning

confidence: 99%