Dataset Information

Identification of treatment efficacy-related host factors in chronic hepatitis C by ProteinChip serum analysis.

ABSTRACT: Recent development of proteomic array technology, including protein profiling coupling ProteinChip array with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), provides a potentially powerful tool for discovery of new biomarkers by comparison of its profiles according to patient phenotypes. We used this approach to identify the host factors associated with treatment response in patients with chronic hepatitis C (CHC) receiving a 48-wk course of pegylated interferon (PEG-IFN) alpha 2b plus ribavirin (RBV). Protein profiles of pretreatment serum samples from 32 patients with genotype 1b and high viral load were conducted by SELDI-TOF/MS by using the three different ProteinChip arrays (CM10, Q10, IMAC30). Proteins showed significantly different peak intensities between sustained virological responders (SVRs), and non-SVRs were identified by chromatography, SDS-PAGE, TOF/MS and tandem mass spectrometry (MS/MS) assay. Eleven peak intensities were significantly different between SVRs and non-SVRs. The three SVR-increased peaks could be identified as two apolipoprotein (Apo) fragments and albumin and, among the eight non-SVR-increased proteins, four peaks identified as two iron-related and two fibrogenesis-related protein fragments, respectively. Multivariate analysis showed that the serum ferritin and three peak intensity values (Apo A1, hemopexin and transferrin) were independent variables associated with SVRs, and the area under the receiver operating characteristic (ROC) curves for SVR prediction by using the Apo A1/hemopexin and hemopexin/transferrin were 0.964 and 0.936. In conclusion, pretreatment serum protein profiling by SELDI-TOF/MS is variable for identification of response-related host factors, which are useful for treatment efficacy prediction in CHC receiving PEG-IFN plus RBV. Our data also may help us understand the mechanism for treatment resistance and development of more effective antiviral therapy targeted toward the modulation of lipogenesis or iron homeostasis in CHC patients.

SUBMITTER: Fujita N

PROVIDER: S-EPMC3022982 | biostudies-literature | 2011 Jan-Feb

REPOSITORIES: biostudies-literature

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Identification of treatment efficacy-related host factors in chronic hepatitis C by ProteinChip serum analysis.

Fujita Naoki N Nakanishi Mamoru M Mukai Jun J Naito Yuuji Y Ichida Takafumi T Kaito Masahiko M Yoshikawa Toshikazu T Takei Yoshiyuki Y

Molecular medicine (Cambridge, Mass.) 20101005 1-2

Recent development of proteomic array technology, including protein profiling coupling ProteinChip array with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), provides a potentially powerful tool for discovery of new biomarkers by comparison of its profiles according to patient phenotypes. We used this approach to identify the host factors associated with treatment response in patients with chronic hepatitis C (CHC) receiving a 48-wk course of pegylat ...[more]

PMID: 20927485

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Project description:BackgroundNon-invasive evaluation for liver fibrosis is clinically important, especially in patients with undetectable hepatitis B virus (HBV) DNA treated with nucleoside analogs.AimTo clarify the monitoring power of hepatitis B core-related antigen (HBcrAg) for hepatic histologic changes in patients with chronic hepatitis B (CHB) treated with entecavir.MethodsThis prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression, respectively, in 403 CHB patients, including 374 with entecavir for 72 weeks (291 underwent paired liver biopsy) and 29 as controls.ResultsLevel of HBcrAg correlated negatively with liver fibrosis staging (γ = -0.357, P < 0.001) in hepatitis B e antigen (HBeAg)-positive patients, and positively with liver fibrosis staging in HBeAg-negative patients. Higher HBcrAg concentration was associated with younger age, HBeAg positive status, high HBV DNA loads, high level of hepatitis B surface antigen (HBsAg) and higher necroinflammation, but not with HBV genotype. Serum concentration of HBcrAg, basal core promoter/precore (BCP/PC) mutant, quantitation of HBsAg (qHBsAg) and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression. HBV DNA was undetectable in 88.37% of patients treated with entecavir at week 72, while their level of HBcrAg was still detectable. A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement. HBcrAg concentration > 6.33 log IU/mL at baseline and logarithmic reduction > 1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement, respectively.ConclusionHBcrAg level is associated with liver fibrosis progression. HBcrAg is an excellent monitor of hepatic histological changes, especially in CHB patients treated with nucleoside analogs.

Project description:Hepatitis B virus (HBV) RNA in serum is a novel biomarker for intrahepatic HBV replication and treatment response. For its proper use, it is essential to identify factors influencing serum HBV RNA level. Using a rapid amplification of complimentary DNA (cDNA) ends (RACE) PCR technique (lower limit of detection [LLD], 800 copies/mL [c/mL]), serum HBV RNA levels were measured in samples of 488 untreated individuals with chronic HBV infection who were eligible to treatment according to currently used recommendations. We explored the association of serum levels of HBV RNA with patient- and virus-associated factors. HBV genotype distribution was 21/10/20/46/3% for A/B/C/D/other. Mean HBV RNA serum level was 5.9 (1.6) log10 c/mL (hepatitis B e antigen [HBeAg]-positive chronic hepatitis B [CHB], 6.5 [1.2] log c/mL; HBeAg-negative CHB, 4.1 [1.2] log c/mL; P < 0.001). By multivariable linear regression, factors associated with lower HBV RNA level were HBeAg negativity (β = -0.69; P < 0.001), HBV genotypes A (β = -0.13; P = 0.002), B (β = -0.07; P = 0.049), and C (β = -0.61; P < 0.001) in comparison to D, and presence of HBV basal core promoter mutation either alone (β = -0.14; P = 0.001) or in combination with precore mutation (β = -0.22; P < 0.001). Higher serum alanine aminotransferase (ALT) was associated with higher HBV RNA (β = 0.23; P < 0.001). HBV RNA correlated strongly with HBV DNA (HBeAg-pos, r = 0.72; P < 0.001; HBeAg-neg, r = 0.78; P < 0.001) and moderately with quantitative hepatitis B surface antigen (qHBsAg; HBeAg-pos, r = 0.54; P < 0.001; HBeAg-neg, r = 0.19; P = 0.04) and quantitative hepatitis B surface antigen (qHBeAg; r = 0.41; P < 0.001).ConclusionIn this multiethnic cohort of 488 untreated individuals with CHB, factors associated with serum HBV RNA level were HBeAg status, serum ALT, HBV genotype, and presence of basal core promotor mutations. For the future use of serum HBV RNA as a clinical marker, it seems mandatory to take these factors into consideration. (Hepatology 2018).

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Project description:HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014).It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing.76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score.HCV-related cirrhosis is resource demanding and sets high direct medical costs as it is related with increased hospitalizations and complications acquiring additional treatment.

Dataset Information

Identification of treatment efficacy-related host factors in chronic hepatitis C by ProteinChip serum analysis.

Publications

Identification of treatment efficacy-related host factors in chronic hepatitis C by ProteinChip serum analysis.

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