Article

IL-21R gene polymorphisms and serum IL-21 levels predict virological response to interferon-based therapy in Asian chronic hepatitis C patients

Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch.
Antiviral therapy (Impact Factor: 3.14). 01/2013; 18(4). DOI: 10.3851/IMP2502
Source: PubMed

ABSTRACT BACKGROUND: IL-21R polymorphisms have been identified as potential predictors of virologic outcomes in Western chronic hepatitis C (CHC) patients receiving interferon-based treatment. We aimed to examine the associations of IL-21R genotypes and serum IL-21 levels with virologic responses to interferon-based treatment in Asian CHC patients. METHODS: Genomic and clinical data were collected from 178 consecutive Taiwanese HCV genotype 1 patients who received interferon-based therapy and 72 non-HCV healthy subjects. Among them, serum IL-21 levels, IL-21R and IL28B genotypes were determined in 124 CHC patients and healthy controls. RESULTS: Among patients with IL28B rs8099917 non-TT genotypes, patients with IL-21R rs3093390 CC genotype had a higher SVR rate than those with non-CC genotypes (CC vs. non-CC: 14/24 vs. 0/4, P=0.031). Compared to non-HCV controls, CHC patients had higher serum IL-21 levels [HCV vs. non-HCV: 377.8±780.9 vs. 70.5±33.2(pg/mL), P=0.001]. Patients with SVR had higher pretreatment serum IL-21 levels than those without (Adjusted Odds Ratio, 95%CI: 0.23, 0.07-0.80, P=0.021). CONCLUSIONS: CHC patients have higher serum IL-21 levels than healthy adults. Higher pretreatment serum IL-21 levels and IL-21R polymorphisms may serve as potential factors predictive of treatment outcomes in CHC patients with interferon-based therapy.

Download full-text

Full-text

Available from: Jia-Horng Kao, Feb 14, 2014
1 Follower
 · 
91 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-21 (IL-21) is involved in effective primary hepatic immune response against hepatitis B virus (HBV) and profibrotic function. However, the role of IL-21 in HBV-associated liver cirrhosis is poorly understood. This study aimed to investigate the role of IL-21 in HBV-associated liver cirrhosis and possible mechanisms. The study subjects included ten healthy controls and thirty patients with HBV-associated liver cirrhosis that categorized into three sub-groups based on Child-Pugh score (Child-Pugh A: 13; Child-Pugh B: 10; Child-Pugh C: 7). The frequencies of IL-21+CD4+ T cells were detected by flow cytometry, and the level of IL-21 in plasma was measured by ELISA. The distribution of IL-21+ cells in situ in liver was observed by immunohistochemistry. In addition, the in vitro expression of α-smooth muscleactin (α-SMA), apoptosis and proliferation markers of LX-2 cells were examined by flow cytometry and CCK-8 kit. Finally, the collagen levels in the supernatant were measured by chemiluminescence. Increased peripheral number of IL-21+CD4+ cells, elevated plasma level of IL-21, and IL-21+ cells accumulation in liver were observed in patients with HBV-associated liver cirrhosis. In vitro administration of IL-21 was accompanied with increased expression of α-SMA, inhibited LX-2 cells apoptosis, and up-regulated collagen production by LX-2 cells. IL-21 may contribute to the fibrogenesis of HBV-associated liver cirrhosis by activating the hepatic stellate cells. Therefore, neutralization of IL-21 could be a favorable new therapeutic strategy for liver cirrhosis treatment.
    Hepatology Research 08/2013; 44(10). DOI:10.1111/hepr.12215 · 2.22 Impact Factor