Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3.
Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3.
复制标题
DOI：
10.1371/journal.pone.0029370
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lagging M
中科院分区：
文献类型：
--
作者：
Rembeck K;Alsiö A;Christensen PB;Färkkilä M;Langeland N;Buhl MR;Pedersen C;Mørch K;Westin J;Lindh M;Hellstrand K;Norkrans G;Lagging M
最近，一些全基因组关联研究表明，IL 28 B附近的单核苷酸多态性（SNPs）预测HCV感染的自发清除以及聚乙二醇干扰素和利巴韦林治疗HCV基因型1感染患者后的结果。本研究旨在评估IL 28 B SNP变异性对肝脏组织学的影响，该试验是针对未经治疗的慢性HCV基因型2或3型感染患者进行的III期治疗试验（NORDynamIC），其中治疗前肝活检是强制性的。339例白人患者的样本可用于IL 28 B基因分型（rs 12979860），其中314例患者接受了治疗前肝活检，使用Ishak方案进行了评价，允许对肝脏组织病理学进行详细分级和分期。 与CT或TT基因型患者相比，HCV基因型3感染患者中的IL 28 B CCrs 12979860基因型与更高的ALT水平（p<0.0001）、更高的AST与血小板比率指数（APRI; p =0.001）和更高的基线病毒载量（p<0.0001）相关。 此外，CCrs 12979860基因型导致更明显的门静脉炎症（p = 0.02）和脂肪变性（p = 0.03）。 在HCV基因型2感染的患者中没有发现这些相关性。这项研究表明，CCrs 12979860 SNP与慢性感染HCV基因型3的患者更明显的肝脏组织病理学相关，这可能是继发于较高的病毒载量。IL 28 B变异性不影响基因型2感染患者的肝脏病理学或病毒载量的发现意味着IL 28 B可能差异调节基因型2和3感染的过程。
Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver histology in the context of a phase III treatment trial (NORDynamIC) for treatment-naïve patients with chronic HCV genotype 2 or 3 infection, where pretreatment liver biopsies were mandatory. Three hundred and thirty-nine Caucasian patients had samples available for IL28B genotyping (rs12979860) of whom 314 had pretreatment liver biopsies that were evaluated using the Ishak protocol, allowing for detailed grading and staging of liver histopathology. IL28B CCrs12979860 genotype in HCV genotype 3 infected patients was associated with higher ALT levels (p<0.0001), higher AST to platelet ratio index (APRI; p = 0.001), and higher baseline viral load (p<0.0001) as compared to patients with the CT or TT genotypes. Additionally the CCrs12979860 genotype entailed more pronounced portal inflammation (p = 0.02) and steatosis (p = 0.03). None of these associations were noted among HCV genotype 2 infected patients. This study shows that the CCrs12979860 SNP is associated with more pronounced liver histopathology in patients chronically infected with HCV genotype 3, which may be secondary to higher viral load. The finding that IL28B variability did not impact on liver pathology or viral load among genotype 2 infected patients implies that IL28B may differentially regulate the course of genotype 2 and 3 infection.
登录
查看更多内容
影响因子：
29.4
作者：
McCarthy JJ;Li JH;Thompson A;Suchindran S;Lao XQ;Patel K;Tillmann HL;Muir AJ;McHutchison JG
通讯作者：
McHutchison JG
影响因子：
6.4
作者：
Lindh, Magnus;Lagging, Martin;Hellstrand, Kristoffer
通讯作者：
Hellstrand, Kristoffer
影响因子：
9.8
作者：
Hofer, H;Bankl, HC;Ferenci, P
通讯作者：
Ferenci, P
影响因子：
13.5
作者：
Antonio Montes-Cano, Marco;Raul Garcia-Lozano, Jose;Francisca Gonzalez-Escribano, Maria
通讯作者：
Francisca Gonzalez-Escribano, Maria
影响因子：
25.7
作者：
Abid, K;Pazienza, V;Negro, F
通讯作者：
Negro, F