Polymorphism of IL28B gene and response to pegylated interferon α2a in chronic hepatitis B

Abstract

A b s t r a c tIntroduction: Because of its worldwide prevalence, chronic hepatitis B constitutes a significant global health issue. Chronic hepatitis B virus (HBV) infection affects about 350 million people, with 1 million deaths annually due to its sequelae. The unique way of replication makes HBV difficult to eradicate with the available treatment. Interferon is currently the only option offering a "curative treatment strategy". Predictors of a sustained response to interferon are desired. The aim of this study was to assess the efficacy of chronic hepatitis B treatment with pegylated interferon α2a in relation to the polymorphisms of the interleukin 28B gene. Material and methods: Eighty-six patients were included in the study. They were treated with PegIFNα2a in the dose of 180 µg weekly for 48 weeks and were followed up for at least 1 year after the end of therapy (EOT). Treatment efficacy was defined as HBsAg clearance or HBV viral load ≤ 2000 IU/ml at the end of therapy and at the end of 12 consecutive months. Two polymorphisms of IL28B at loci rs12979860 and rs809997 were examined in every patient. Results: No associations between any of the IL28B polymorphisms and HBsAg elimination were found. However, a weak but statistically significant association between persistent HBV-DNA decrease and a TT variant (C/T) of IL28B was found (Spearman's correlation coefficient 0.236, p < 0.001). Patients having this polymorphism also had significantly lower HBV-DNA loads after EOT (Spearman's correlation coefficient 0.27, p = 0.02). The weak associations and small number of patients do not allow us to draw firm conclusions. Conclusions: We discovered no associations between any of the IL28B polymorphisms and HBsAg loss, IL28B polymorphisms do not seem to play an important role as predictors of treatment efficacy in the treatment of chronic B hepatitis with pegylated interferon.

Genetic polymorphism of CYP3A4 is associated with poor response to ifosfamide treatment in children with solid embryonic tumors

“…It is used to treat solid tumors, lymphomas and sarcomas with a high degree of malignancy [2]. Single nucleotide polymorphisms (SNPs) in genes that encode antineoplastic drug-metabolizing enzymes could have effects on drug efficacy, toxicity and life span [3][4][5]. The CYP2B6 gene has more than 29 SNPs, but only CYP2B6*2 and CYP2B6*6 are functionally significant and result in decreased enzyme activity [6,7].…”

The Association between Micro-RNA Gene Polymorphisms and Development of Hepatocellular Carcinoma in Egyptian Patients

“…(T/G), and HLA-DP (rs3077) were analyzed in Chinese-origin patients with HBV infection who tested negative for HBsAg [19].The authors reported significantly more frequent HBsAg loss among HLA-DP1 (rs3077) AA genotype carriers than in rs179860CC and rs8099917GG allele carriers. The above-mentioned allele configurations activate the immunological response of the host, leading to non-cytolytic degradation of cccDNA in the hepatocyte nuclei [19].…”

Exposure to biomass smoke, cigarettes, and alcohol modifies the association between tumour necrosis factor (–308G/A, –238G/A) polymorphisms and tuberculosis in Mexican carriers

“…Recently, tumor necrosis factor α (TNF-α) has been associated with heavy alcohol intake [12]. An increased production of cytokines by blood monocytes and Kupffer cells in alcoholic steatosis patients and in animal models with alcohol-induced liver damage has been shown [13][14][15]. Additionally, excessive TNF-α production depends on the amount of alcohol ingested [16].…”