McKiernan Susan M, Hagan Richard, Curry Michael, McDonald George S A, Kelly Alan, Nolan Niamh, Walsh Anne, Hegarty John, Lawlor Emer, Kelleher Dermot
Hepatology Center, St. James's Hospital and Trinity College, Dublin, Ireland.
Hepatology. 2004 Jul;40(1):108-14. doi: 10.1002/hep.20261.
The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included chi(2) testing and multiple logistic regression analysis. A03, B27, and Cw01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < or = .005). B08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. 19.8%; P =.002). In combination with previously reported class II allele associations, over 75% that successfully eliminate HCV carry either A03, DRB10101, or 0401, compared with only 37% of those with chronic infection (P <.0001). The haplotypes A03-B07-DRB115-DQB10602 and A02-B27-Cw01-DRB10101-DQB10501 are associated with viral clearance (P =.004 and.01, respectively). By multiple logistic regression analysis, the alleles A03, B27, DRB10101, 0401, and 15 are associated with viral clearance, and B27 has the strongest association (odds ratio [OR] 7.99). The haplotype A01-B08-Cw07-DRB103011-DQB10201 is associated with chronic infection (P =.002), being independent for DQB10201 (OR 0.27). In conclusion, certain class I alleles are associated with outcome in this homogeneous cohort. More significantly, either HLA-A03, -DRB10101, or -*0401 are carried by an overwhelming majority of those subjects who successfully clear HCV.
受人类白细胞抗原（HLA）I类等位基因限制的细胞毒性T淋巴细胞反应，在丙型肝炎病毒（HCV）的成功清除中被认为具有高度重要性。对来自单一来源接种HCV 1b基因型的女性中I类等位基因的频率进行了检测，以寻找其与转归的关联。在227名女性受试者中，使用聚合酶链反应序列特异性引物进行I类分型：141例为慢性感染，86例病毒清除。统计分析包括卡方检验和多因素逻辑回归分析。与慢性感染患者相比，病毒清除者中A03、B27和Cw01出现的频率更高（分别为39.5%、14%和9.3%），而慢性感染患者中分别为19.1%、2.1%和1.4%；P≤0.005）。与病毒清除者相比，慢性感染患者中B08出现的频率更高（39.7%对19.8%；P = 0.002）。与先前报道的II类等位基因关联相结合，成功清除HCV的患者中超过75%携带A03、DRB10101或0401，而慢性感染患者中仅为37%（P<0.0001）。单倍型A03 - B07 - DRB115 - DQB10602和A02 - B27 - Cw01 - DRB10101 - DQB10501与病毒清除相关（分别为P = 0.004和0.01）。通过多因素逻辑回归分析，等位基因A03、B27、DRB10101、0401和15与病毒清除相关，且B27的相关性最强（优势比[OR]7.99）。单倍型A01 - B08 - Cw07 - DRB103011 - DQB10201与慢性感染相关（P = 0.002），对于DQB10201具有独立性（OR 0.27）。总之，在这个同质队列中，某些I类等位基因与转归相关。更重要的是，成功清除HCV的绝大多数受试者携带HLA - A03、- DRB10101或 - *0401。
