Li Yi, Huang Qian, Tang Jiang-Tao, Wei Tian-Tian, Yan Lin, Yang Zhi-Qiang, Bai Yang-Juan, Wang Lan-Lan, Shi Yun-Ying
Department of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University West China School of Medicine, Sichuan University Department of Nephrology, West China Hospital of Sichuan University, Chengdu, China.
Medicine (Baltimore). 2017 Jun;96(25):e7205. doi: 10.1097/MD.0000000000007205.
Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence.No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P < .05). Recipients with HLA-DQ (rs7453920) AG and AA genotype had lower direct bilirubin levels than GG genotype individuals, especially on the 14th day after surgery (17.80 vs. 5.35, P = .038). Patients with A alleles displayed earlier liver function recovery than patients with G alleles (7 vs. 6 months). No significant correlation was shown in HLA-DP rs3077 and rs9277535 with HBV infection or liver function recovery (P < .05).Our study concluded that HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were not significantly associated with HBV recurrence or HBV susceptibility, but HLA-DQ rs7453920 was related to prognosis of liver transplant recipients. HLA-DQ rs7453920 A might be used as an indicator of earlier recovery and better prognosis after transplantation.
先前的研究已确定人类白细胞抗原（HLA）-DP/DQ区域的基因变异与乙型肝炎病毒（HBV）感染密切相关。但其在肝移植后肝功能恢复中的作用仍不明确。本研究旨在调查HLA-DP/DQ基因多态性是否与中国肝移植受者的移植后病因及预后相关。
共纳入144例肝移植受者，根据移植病因分为2组：HBV相关疾病组和非HBV相关疾病组。HBV相关疾病包括3个亚组：肝硬化、肝细胞癌和进行性HBV肝炎。通过高分辨率熔解曲线分析对所有受者研究了3个单核苷酸多态性，即HLA-DP（rs3077和rs9277535）以及HLA-DQ（rs7453920）。常规检测肝功能指标（白蛋白、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、γ-谷氨酰转肽酶、直接胆红素、总胆红素）和凝血指标（凝血酶原时间、血小板、国际标准化比值、纤维蛋白原）。移植后，10例HBsAg阳性或HBV病毒载量升高的受者被视为HBV复发。
未观察到HLA-DP/DQ基因多态性与HBV复发或移植病因之间存在显著关联（P<0.05）。携带HLA-DQ（rs7453920）AG和AA基因型的受者直接胆红素水平低于GG基因型个体，尤其是在术后第14天（17.80对5.35，P = 0.038）。携带A等位基因的患者肝功能恢复早于携带G等位基因的患者（7个月对6个月）。未显示HLA-DP rs3077和rs9277535与HBV感染或肝功能恢复之间存在显著相关性（P<0.05）。
我们的研究得出结论，HLA-DP（rs3077和rs9277535）和HLA-DQ（rs7453920）与HBV复发或HBV易感性无显著关联，但HLA-DQ rs7453920与肝移植受者的预后相关。HLA-DQ rs7453920 A可能作为移植后恢复较早和预后较好的一个指标。
