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1.  Serum Lipoprotein Profiles and Response to Pegylated Interferon Plus Ribavirin Combination Therapy in Patients With Chronic HCV Genotype 1b Infection 
Hepatitis Monthly  2013;13(5):e8988.
Background
Abnormal serum lipid profiles have been noted in patients with chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b infection who have an unfavorable response to pegylated interferon (peg-IFN) plus ribavirin (RBV) combination therapy. However, after the discovery of single nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent predictive factors affecting the response to peg-IFN plus RBV, lipid factors are thought to be confounding factors.
Objectives
To re-examine the significance of lipoprotein profiles on virological response to peg-IFN plus RBV combination therapy in patients with chronic HCV G1b infection, we examined cholesterol and triglyceride concentrations in each lipoprotein fraction separated by high performance liquid chromatography.
Patients and Methods
Lipoprotein profiles were examined using fasting sera from 108 patients infected with HCV G1b who had chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles and clinical data, including IL28B genotype and amino acid substitution at aa70 of HCV G1b, were compared between patients with a sustained virological response (SVR) and non-SVR or a non-virological response (NVR) and virological responses other than NVR (non-NVR). In addition, significant predictive factors independently associated with virological response to peg-IFNα-2b plus RBV were determined by logistic regression analysis.
Results
An increased ratio of cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917 (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In contrast, lipid factors were not elucidated as independent predictive factors for NVR.
Conclusions
Examination of the fasting lipid profile has clinical importance in predicting the efficacy of peg-IFN-α-2b plus RBV combination therapy for patients with HCV G1b even after the discovery of the IL28 genotype as a potent predictive factor.
doi:10.5812/hepatmon.8988
PMCID: PMC3743300  PMID: 23967025
Hepatitis C; Ribavirin; Lipoproteins; Lipoproteins VLDL; Chromatography, High Pressure Liquid
2.  Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C 
AIM: To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon α plus ribavirin for chronic hepatitis C.
METHODS: Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction. Factors influencing significant anemia (hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors.
RESULTS: Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline: hemoglobin decline at week 2 [P = 3.29 × 10-17, odds ratio (OR) = 7.54 (g/dL)], estimated glomerular filtration rate [P = 2.16 × 10-4, OR = 0.962 (mL/min/1.73 m2)], rs1127354 (P = 5.75 × 10-4, OR = 10.94) and baseline hemoglobin [P = 7.86 × 10-4, OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia.
CONCLUSION: Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.
doi:10.3748/wjg.v18.i41.5879
PMCID: PMC3491594  PMID: 23139603
Chronic hepatitis C virus infection; Ribavirin; Pegylated interferon α; Prediction model; Hemolytic anemia; Single nucleotide polymorphism

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