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

Lee IC, Lin CH, Huang YH, Huo TI, Su CW, Hou MC, Huang HC, Lee KC, Chan CC, Lin MW, Lin HC, Lee SD - PLoS ONE (2013)

Bottom Line: Factors associated with active hepatitis, defined as persistent ALT >2× upper limit of normal (ULN) or a peak ALT level >5× ULN, were evaluated.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.Both viral and host factors play roles in disease activity during different phases of CHB.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

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.

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Related in: MedlinePlus

Pairwise linkage disequilibrium (LD) patterns of the four single nucleotide polymorphisms through IL28B regions.Pairwise r2 was used for analyzing the correlation.
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pone-0058071-g002: Pairwise linkage disequilibrium (LD) patterns of the four single nucleotide polymorphisms through IL28B regions.Pairwise r2 was used for analyzing the correlation.

Mentions: Among the 115 CHB patients, 112 (97.4%) had determined rs8099917 genotype, 111 (96.5%) had determined rs8105790 and rs12979860 genotypes, and 110 (95.7%) had determined rs10853728 genotype. The distributions of the four SNPs of IL28B in overall patients and in patients infected with HBV genotypes A, B and C are shown in Figure 1. The prevalence of the major genotypes rs8105790 TT, rs12979860 CC, rs8099917 TT, and rs10853728 CC were 88.3%, 87.4%, 88.4% and 70.9%, respectively. The distributions of the four SNPs were not significantly different among patients infected with HBV genotypes A, B or C (p = 0.749, 0.787, 0.581 and 0.383 for rs8105790, rs12979860, rs8099917 and rs10853728, respectively). Among the four SNPs, rs8105790 and rs12979860 were highly linked, with only 1 (0.9%) patient classified discordantly (r2 = 0.78, Figure 2). The rs10853728 was not so closely linked with the other 3 SNPs (Figure 2). There were no significant correlations between the HBeAg status and the four SNPs of IL28B (Table 1).


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

Lee IC, Lin CH, Huang YH, Huo TI, Su CW, Hou MC, Huang HC, Lee KC, Chan CC, Lin MW, Lin HC, Lee SD - PLoS ONE (2013)

Pairwise linkage disequilibrium (LD) patterns of the four single nucleotide polymorphisms through IL28B regions.Pairwise r2 was used for analyzing the correlation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585285&req=5

pone-0058071-g002: Pairwise linkage disequilibrium (LD) patterns of the four single nucleotide polymorphisms through IL28B regions.Pairwise r2 was used for analyzing the correlation.
Mentions: Among the 115 CHB patients, 112 (97.4%) had determined rs8099917 genotype, 111 (96.5%) had determined rs8105790 and rs12979860 genotypes, and 110 (95.7%) had determined rs10853728 genotype. The distributions of the four SNPs of IL28B in overall patients and in patients infected with HBV genotypes A, B and C are shown in Figure 1. The prevalence of the major genotypes rs8105790 TT, rs12979860 CC, rs8099917 TT, and rs10853728 CC were 88.3%, 87.4%, 88.4% and 70.9%, respectively. The distributions of the four SNPs were not significantly different among patients infected with HBV genotypes A, B or C (p = 0.749, 0.787, 0.581 and 0.383 for rs8105790, rs12979860, rs8099917 and rs10853728, respectively). Among the four SNPs, rs8105790 and rs12979860 were highly linked, with only 1 (0.9%) patient classified discordantly (r2 = 0.78, Figure 2). The rs10853728 was not so closely linked with the other 3 SNPs (Figure 2). There were no significant correlations between the HBeAg status and the four SNPs of IL28B (Table 1).

Bottom Line: Factors associated with active hepatitis, defined as persistent ALT >2× upper limit of normal (ULN) or a peak ALT level >5× ULN, were evaluated.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.Both viral and host factors play roles in disease activity during different phases of CHB.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

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.

Show MeSH
Related in: MedlinePlus