Quinn Jeffrey, Astemborski Jacquie, Mehta Shruti H, Kirk Gregory D, Thomas David L, Balagopal Ashwin
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Pathog Immun. 2017;2(1):50-59. doi: 10.20411/pai.v2i1.183. Epub 2017 Mar 3.
We have previously reported that persons co-infected with HIV and hepatitis C virus (HCV) had liver disease stages similar to HIV-uninfected individuals who were approximately 10 years older. Insulin-like growth factor 1(IGF-1) levels have long been known to decline with advancing age in humans and non-humans alike. We examined whether HIV infection affects the expected decline in IGF-1 in persons with chronic hepatitis C virus (HCV) infection and if that alteration in IGF-1 decline contributes to the link between HIV, aging, and liver disease progression.
A total of 553 individuals with HCV infection were studied from the AIDS Linked to the Intravenous Experience (ALIVE) cohort for whom more than 10 years of follow-up was available. Serum IGF-1 levels were determined by ELISA and evaluated according to baseline characteristics and over time by HIV status and liver disease progression. Linear regression with generalized estimating equations was used to determine whether IGF-1 decline over time was independently associated with liver disease progression.
Baseline IGF-1 levels were strongly associated with age ( < 0.0001) but not with gender or HIV infection. Levels of IGF-1 declined at a rate of -1.75 ng/mL each year in HCV mono-infected individuals and at a rate of -1.23 ng/mL each year in HIV/HCV co-infected individuals ( < 0.05). In a multivariable linear regression model, progression of liver fibrosis was associated with HIV infection and age, as well as with a slower rate of IGF-1 decline ( = 0.001); however, the rate of IGF-1 decline did not alter the strength of the associations between HIV, liver disease, and age.
The normal decline in IGF-1 levels with age was attenuated in HIV/HCV co-infected individuals compared to those with HCV mono-infection, and slower IGF-1 decline was independently associated with liver disease progression.
我们之前报道过，同时感染人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）的患者，其肝病阶段与未感染HIV但年龄大约大10岁的个体相似。长期以来已知，无论人类还是非人类，胰岛素样生长因子1（IGF-1）水平都会随着年龄增长而下降。我们研究了HIV感染是否会影响慢性丙型肝炎病毒（HCV）感染患者中IGF-1的预期下降，以及IGF-1下降的这种改变是否会导致HIV、衰老和肝病进展之间的关联。
从“静脉注射相关艾滋病（ALIVE）”队列中对553例HCV感染患者进行了研究，这些患者有超过10年的随访数据。通过酶联免疫吸附测定（ELISA）法测定血清IGF-1水平，并根据基线特征以及随时间按HIV感染状况和肝病进展情况进行评估。使用广义估计方程的线性回归来确定IGF-1随时间的下降是否与肝病进展独立相关。
基线IGF-1水平与年龄密切相关（<0.0001），但与性别或HIV感染无关。在单纯HCV感染个体中，IGF-1水平以每年-1.75 ng/mL的速度下降，而在HIV/HCV合并感染个体中，以每年-1.23 ng/mL的速度下降（<0.05）。在多变量线性回归模型中，肝纤维化进展与HIV感染、年龄以及IGF-1下降速度较慢有关（=0.001）；然而，IGF-1下降速度并未改变HIV、肝病和年龄之间关联的强度。
与单纯HCV感染个体相比，HIV/HCV合并感染个体中IGF-1水平随年龄的正常下降有所减弱，且IGF-1下降较慢与肝病进展独立相关。
