Dataset Information

IL28B polymorphism correlates with active hepatitis in patients with HBeAg-negative chronic hepatitis B.

ABSTRACT:

Background aims

The clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).

Methods

The study enrolled consecutive 115 treatment-naive CHB patients. HBV viral loads, genotypes, precore and basal core promotor mutations, serum hepatitis B surface antigen (HBsAg) and interferon-gamma inducible protein 10 (IP-10) levels as well as four SNPs of IL28B were determined. Serial alanine transaminase (ALT) levels in the previous one year before enrollment at an interval of three months were recorded. Factors associated with active hepatitis, defined as persistent ALT >2× upper limit of normal (ULN) or a peak ALT level >5× ULN, were evaluated.

Results

The prevalence of rs8105790 TT, rs12979860 CC, rs8099917 TT, and rs10853728 CC genotypes were 88.3%, 87.4%, 88.4% and 70.9%, respectively. In HBeAg-positive patients (n?=?48), HBV viral load correlated with active hepatitis, while in HBeAg-negative patients (n?=?67), rs10853728 CC genotype (p?=?0.032) and a trend of higher IP-10 levels (p?=?0.092) were associated with active hepatitis. In multivariate analysis, high viral load (HBV DNA >10(8) IU/mL, p?=?0.042, odds ratio?=?3.946) was significantly associated with HBeAg-positive hepatitis, whereas rs10853728 CC genotype (p?=?0.019, odds ratio?=?3.927) was the only independent factor associated with active hepatitis in HBeAg-negative population.

Conclusions

HBV viral load and IL28B rs10853728 CC genotype correlated with hepatitis activity in HBeAg-positive and HBeAg-negative CHB, respectively. Both viral and host factors play roles in disease activity during different phases of CHB.

SUBMITTER: Lee IC

PROVIDER: S-EPMC3585285 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

IL28B polymorphism correlates with active hepatitis in patients with HBeAg-negative chronic hepatitis B.

Lee I-Cheng IC Lin Chen-Hao CH Huang Yi-Hsiang YH Huo Teh-Ia TI Su Chien-Wei CW Hou Ming-Chih MC Huang Hui-Chun HC Lee Kuei-Chuan KC Chan Che-Chang CC Lin Ming-Wei MW Lin Han-Chieh HC Lee Shou-Dong SD

PloS one 20130228 2

<h4>Background aims</h4>The clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).<h4>Methods</h4>The study enrolled consecutive 115 treatment-naive CHB patients. HBV viral loads, genotypes, precore and basal core promotor mutations, serum hepatitis B surfac ...[more]

PMID: 23469142

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Project description:AimTo evaluate the effect of single nucleotide polymorphisms of interleukin (IL)-28B, rs12979860 on progression and treatment response in chronic hepatitis C.MethodsPatients (n = 64; 37 men, 27 women; mean age, 44 ± 12 years) with chronic hepatitis C, genotype 1, received treatment with peg-interferon plus ribavirin. Genotyping of rs12979860 was performed on peripheral blood DNA. Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment. Serum viral load, aminotransferase activity, and insulin level were measured. Insulin resistance index, body mass index, waist/hip ratio, percentage of body fat and fibrosis progression rate were calculated. Applied dose of interferon and ribavirin, platelet and neutrophil count and hemoglobin level were measured.ResultsA sustained virological response (SVR) was significantly associated with IL28B polymorphism (CC vs TT allele: odds ratio (OR), 25; CC vs CT allele: OR, 5.4), inflammation activity (G < 1 vs G > 1: OR, 3.9), fibrosis (F < 1 vs F > 1: OR, 5.9), platelet count (> 200 × 10(9)/L vs < 200 × 10(9)/L: OR, 4.7; OR in patients with genotype CT: 12.8), fatty liver (absence vs presence of steatosis: OR, 4.8), insulin resistance index (< 2.5 vs > 2.5: OR, 3.9), and baseline HCV viral load (< 10(6) IU/mL vs > 10(6) IU/mL: OR, 3.0). There was no association with age, sex, aminotransferases activity, body mass index, waist/hip ratio, or percentage body fat. There was borderline significance (P = 0.064) of increased fibrosis in patients with the TT allele, and no differences in the insulin resistance index between groups of patients with CC, CT and TT alleles (P = 0.12). Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605, respectively (P < 0.001). Significant differences were found in the insulin resistance index (P = 0.01) between patients with and without steatosis. Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon (P = 0.07).ConclusionIL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy. Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.

Project description:Background & aimsFactors associated with a successful outcome upon nucleos(t)ide analogue (NA) treatment withdrawal in HBeAg-negative chronic hepatitis B (CHB) patients have yet to be clarified. The objective of this study was to analyse the HBV-specific T cell response, in parallel with peripheral and intrahepatic viral parameters, in patients undergoing NA discontinuation.MethodsTwenty-seven patients without cirrhosis with HBeAg-negative CHB with complete viral suppression (>3 years) were studied prospectively. Intrahepatic HBV-DNA (iHBV-DNA), intrahepatic HBV-RNA (iHBV-RNA), and covalently closed circular DNA (cccDNA) were quantified at baseline. Additionally, serum markers (HBV-DNA, HBsAg, HBV core-related antigen [HBcrAg] and HBV-RNA) and HBV-specific T cell responses were analysed at baseline and longitudinally throughout follow-up.ResultsAfter a median follow-up of 34 months, 22/27 patients (82%) remained off-therapy, of whom 8 patients (30% of the total cohort) lost HBsAg. Baseline HBsAg significantly correlated with iHBV-DNA and iHBV-RNA, and these parameters were lower in patients who lost HBsAg. All patients had similar levels of detectable cccDNA regardless of their clinical outcome. Patients achieving functional cure had baseline HBsAg levels ≤1,000 IU/ml. Similarly, an increased frequency of functional HBV-specific CD8+ T cells at baseline was associated with sustained viral control off treatment. These HBV-specific T cell responses persisted, but did not increase, after treatment withdrawal. A similar, but not statistically significant trend, was observed for HBV-specific CD4+ T cell responses.ConclusionsDecreased cccDNA transcription and low HBsAg levels are associated with HBsAg loss upon NA discontinuation in patients with HBeAg-negative CHB. The presence of functional HBV-specific T cells at baseline are associated with a successful outcome after treatment withdrawal.Lay summaryNucleos(t)ide analogue therapy can be discontinued in a high proportion of chronic hepatitis B patients without cirrhosis. The strength of HBV-specific immune T cell responses may contribute to successful viral control after antiviral treatment interruption. Our comprehensive study provides in-depth data on virological and immunological factors than can help guide individualised therapy in patients with chronic hepatitis B.

Dataset Information

IL28B polymorphism correlates with active hepatitis in patients with HBeAg-negative chronic hepatitis B.

Background aims

Methods

Results

Conclusions

Publications

IL28B polymorphism correlates with active hepatitis in patients with HBeAg-negative chronic hepatitis B.

Similar Datasets

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