Unidad de enfermedades infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Fundación para la Investigación Biomédica, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
J Transl Med. 2019 Jul 26;17(1):244. doi: 10.1186/s12967-019-1997-x.
Mitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients.
We carried out a retrospective cohort study in HIV/HCV-coinfected patients who were potential candidates for therapy with interferon and ribavirin (IFN/Rib) between 2000 and 2009. The primary endpoint was the occurrence of LREs (decompensation or hepatocellular carcinoma). mtDNA genotyping was performed using the Sequenom MassARRAY platform. We used Fine and Gray proportional hazards model to test the association between mtDNA haplogroups and LREs, considering death as a competitive risk.
The study population comprised 243 patients, of whom 40 had advanced fibrosis or cirrhosis. After a median follow-up of 7.7 years, 90 patients treated with IFN/Rib achieved sustained viral response (SVR), 18 patients had LREs, and 11 patients died. Patients with haplogroup H had lower cumulative incidence than patients with other haplogroups (p = 0.012). However, patients with haplogroup T had higher cumulative incidence than patients with other haplogroups (p = 0.074). In the multivariate analysis, haplogroup T was associated with an increased hazard of developing LREs [adjusted subhazard ratio (aSHR) = 3.56 (95% CI 1.13;11.30); p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [aSHR = 0.36 (95% CI 0.10;1.25); p = 0.105]. When we excluded patients who achieved SVR during follow-up, we obtained similar SHR values.
European mitochondrial haplogroups may influence the natural history of chronic hepatitis C.
线粒体 DNA（mtDNA）单倍群与人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）合并感染患者的晚期肝纤维化和肝硬化有关。我们的目的是确定 mtDNA 单倍群是否与 HIV/HCV 合并感染患者的肝脏相关事件（LREs）有关。
我们对 2000 年至 2009 年间有接受干扰素和利巴韦林（IFN/Rib）治疗可能的 HIV/HCV 合并感染患者进行了回顾性队列研究。主要终点是 LREs（失代偿或肝细胞癌）的发生。使用 Sequenom MassARRAY 平台进行 mtDNA 基因分型。我们使用 Fine 和 Gray 比例风险模型来测试 mtDNA 单倍群与 LREs 之间的关联，将死亡视为竞争风险。
研究人群包括 243 名患者，其中 40 名患有晚期纤维化或肝硬化。中位随访 7.7 年后，90 名接受 IFN/Rib 治疗的患者达到了持续病毒学应答（SVR），18 名患者发生了 LREs，11 名患者死亡。与其他单倍群相比，具有单倍群 H 的患者累积发病率较低（p=0.012）。然而，具有单倍群 T 的患者累积发病率高于其他单倍群（p=0.074）。在多变量分析中，单倍群 T 与发生 LREs 的风险增加相关[调整后的亚危险比（aSHR）=3.56（95%CI 1.13；11.30）；p=0.030]；而单倍群 H 与 LREs 风险降低无关[aSHR=0.36（95%CI 0.10；1.25）；p=0.105]。当我们排除随访期间获得 SVR 的患者时，我们得到了相似的 SHR 值。
欧洲线粒体单倍群可能影响慢性丙型肝炎的自然史。
