Dataset Information

Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive patients.

ABSTRACT: BACKGROUND:Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D3 -1? hydroxylase, might activate 25(OH)D3 to 1,25(OH)2 D3 in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients. METHODS:Eighty-seven HBeAg-positive CHB patients infected with HBV genotype B or C were included in the study. All patients were treated with IFN at least 1 year. According to the response to PEG-IFN therapy, they were divided into three groups: 16 complete responses (CR), 42 partial responses (PR), and 29 nonresponses (NR). Sanger-sequencing was utilized to genotype the CYP27B1 SNPs(rs4646536 and rs10877012). RESULTS:In logistic regression analysis, the frequency of rs4646536 CC genotype was observed to be higher in the NR group. Besides, the GG genotype of rs10877012 differed significantly among the three groups. The GG genotype was prevalent in patients with CR, and patients with TT genotype result in NR at the end of IFN treatment. The most common haplotype TG was independently associated with CR, after adjustment, and haplotype CT appeared to be associated with NR and PR, rather than CR. The data also showed that patients with baseline 1,25(OH)2 D3 > 39.39 pg/mL had higher CR rates at the end of IFN therapy. CONCLUSION:These results suggested CYP28B1 gene polymorphisms may be independently associated with the efficacy of IFN in HBeAg-positive patients.

SUBMITTER: Wu Y

PROVIDER: S-EPMC6817160 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive patients.

Wu Yingying Y Zeng Yongbin Y Wu Wennan W Lin Jinpiao J Ou Qishui Q

Journal of clinical laboratory analysis 20180218 5

<h4>Background</h4>Host single nucleotide polymorphisms were associated with antiviral therapy in CHB patients. The CYP27B1 gene, encoding 25(OH)D<sub>3</sub> -1α hydroxylase, might activate 25(OH)D<sub>3</sub> to 1,25(OH)<sub>2</sub> D<sub>3</sub> in kidney resulted in influencing the efficacy of interferon (IFN). The aim of the study was to investigate the association between CYP27B1 polymorphisms and the response to IFN in HBeAg-positive patients.<h4>Methods</h4>Eighty-seven HBeAg-positive CH ...[more]

PMID: 29457277

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Project description:Many factors are associated with post-treatment relapse in CHB patients, and there are no effective factors to predict relapse. In this study, we investigate the influence factors associated with post-treatment relapse and their predictive value in HBeAg positive CHB (eP-CHB).The factors associated with post-treatment relapse were analyzed firstly by a retrospective study in eP-CHB. Variables included age, sex, regimen, baseline HBeAg and HBV DNA level, total course of treatment as well as duration of consolidation therapy after HBeAg seroconversion. The predictive effects of the influence factors were evaluated in an eP-CHB prospective cohort.89 patients were enrolled in the retrospective study, 42(47.2%) relapsed after discontinuation of treatment. Factors related to post-treatment relapse were total course of treatment, duration of consolidation therapy and baseline HBV DNA level. Relapse rates in patients with total course >36 months, consolidation duration >12 months and baseline HBV DNA level < 1.0E+5IU/ml were lower than those of total course <24 months (P = 0.002), consolidation duration?12 months (P = 0.011) and baseline HBV DNA level > 1.0E+7IU/ml (P = 0.01) respectively. Patients with HBV DNA?1.0E+7IU/ml plus HBeAg<200COI at baseline had the highest relapse rate and cumulative relapse rate than the other three arms (P = 0.048 and 0.008 respectively). Logistic regression analysis demonstrated that baseline HBV DNA level, duration of consolidation therapy and combination of baseline HBV DNA and HBeAg (IgDNA/IgHBeAg) were independent factors to predict post-treatment relapse. The model based on baseline IgDNA/IgHBeAg and consolidation duration worked well in predicting post-treatment relapse in the prospective study and the accuracy, specificity, sensitivity, PPV and NPV for prediction were 80.3%, 81.1%, 79.2%, 73.1% and 85.7% respectively.Virological factors including baseline HBV DNA, HBeAg and treatment course were major influence factors associated with post-treatment relapse in eP-CHB. Patients with higher HBV DNA and lower HBeAg levels at baseline, shorter total course as well as consolidation therapy were more likely to develop relapse after discontinuation of therapy. The antiviral therapy in eP-CHB patients should be individually managed at different levels. It is better to treat those with higher viral load and lower HBeAg levels at baseline for a longer course, especially longer consolidation duration so as to decrease the relapse rate.

Project description:ObjectiveTo explore whether the frequencies and functional molecules expression of Natural Killer cells (NK cells) are related to hepatitis B surface antigen (HBsAg) disappearance in hepatitis B e envelope antigen (HBeAg)-positive patients with chronic hepatitis B (CHB) throughout peginterferon alpha-2a (PEG-IFN α-2a) treatment.MethodsIn this prospective research, HBeAg-positive patients with CHB received PEG-IFN α-2a treatment, completing 4-year follow-up. After PEG-IFN α-2a treatment, undetectable HBV DNA, HBsAg loss, and HBeAg disappearance were defined as functional cure. Proportions of NK, CD56dim, CD56bright, NKp46+, NKp46dim, NKp46high, and interferon alpha receptor 2 (IFNAR2)+ NK cells, and the mean fluorescence intensity (MFI) of NK cell surface receptors IFNAR2 and NKp46 were detected.Results66 patients were enrolled into the study in which 17 patients obtained functional cure. At baseline, hepatitis B virus desoxyribose nucleic acid (HBV DNA) titer in patients with functional cure was remarkably lower than that in Non-functional cure group. Compared with baseline, HBV DNA levels, HBsAg levels, and HBeAg levels significantly declined at week 12 and 24 of therapy in patients with functional cure. At baseline, the negative correlation between CD56bright NK% and HBV DNA and the negative correlation between CD56dim NK% and HBV DNA was showed; CD56bright NK% and IFNAR2 MFI in patients with functional cure were remarkably higher than those in patients without functional cure. After therapy, CD56bright NK% and NKp46high NK% in patients with functional cure were higher than those in patients without functional cure. In Functional cure group, after 24 weeks of treatment NK%, CD56bright NK%, IFNAR2 MFI weakly increased, and NKp46high NK% and NKp46 MFI significantly increased, meanwhile, CD56dim NK% and NKp46dim NK% decreased. Only NKp46 MFI increased after therapy in patients without functional cure.ConclusionThe lower HBV DNA load and the higher CD56bright NK% before therapy, and the higher the post-treatment CD56bright NK%, IFNAR2 MFI, NKp46high NK%, the easier to achieve functional cure.

Dataset Information

Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive patients.

Publications

Polymorphisms of CYP27B1 are associated with IFN efficacy in HBeAg-positive patients.

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