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Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection.

ABSTRACT: AIM:To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C. METHODS:Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specific probes. RESULTS:Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6 +/- 12.5 vs 45.7 +/- 11.5, P = 0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P = 0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P = 0.003) and with bile duct damage (P < 0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism. CONCLUSION:The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C.

SUBMITTER: Askar E

PROVIDER: S-EPMC2731250 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection.

Askar Eva E Ramadori Giuliano G Mihm Sabine S

World journal of gastroenterology 20090801 31

<h4>Aim</h4>To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C.<h4>Methods</h4>Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters ...[more]

PMID: 19701968

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Project description:BackgroundPeginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies.MethodsWe conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately.ResultsA total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively.ConclusionsThe addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.).

Dataset Information

Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection.

Publications

Endotoxin receptor CD14 gene variants and histological features in chronic HCV infection.

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