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肝硬度增加与 HIV/HCV 合并感染患者的死亡率相关:法国全国性 ANRS CO13 HEPAVIH 队列研究。

Increased liver stiffness is associated with mortality in HIV/HCV coinfected subjects: The French nationwide ANRS CO13 HEPAVIH cohort study.

机构信息

Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, CIC-EC 1401, Bordeaux, France.

Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévèque, Service d'Hépatologie, Bordeaux, France.

出版信息

PLoS One. 2019 Jan 25;14(1):e0211286. doi: 10.1371/journal.pone.0211286. eCollection 2019.

Abstract

BACKGROUND

The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study.

METHODS

HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates.

RESULTS

1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders.

CONCLUSION

Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

摘要

背景

肝硬度测量(LSM)与死亡率之间的关系尚未完全描述。特别是,在考虑持续病毒学应答(SVR)的情况下,LSM 对全因死亡率的影响需要进一步研究。

方法

本研究纳入了法国全国前瞻性多中心 ANRS CO13 HEPAVIH 队列中接受 FibroScan(FS)检测且至少有 1 次 LSM 值可检测的 HIV/HCV 患者,当首次 FS 值可检测时 HCV RNA 也可检测。采用延迟进入的 Cox 比例风险模型确定与全因死亡率相关的因素。LSM 和 SVR 被视为时间依赖性协变量。

结果

2005 年至 2015 年期间共纳入 1062 例患者(69.8%为男性,中位年龄 45.7 岁(IQR 42.4-49.1))。基线 LSM>12.5kPa 的患者占 21.7%。中位随访时间为 4.9 年(IQR 3.2-6.1)。727 例(68.5%)患者曾接受 HCV 治疗:其中 189 例(26.0%)获得 SVR。共观察到 76 例死亡(26 例与肝脏相关,10 例与 HIV 相关,29 例与肝脏和 HIV 均不相关,11 例原因不明)。在 50 岁时,LSM≤12.5kPa 的患者死亡率为 4.5%,而 LSM>12.5kPa 的患者死亡率为 10.8%。LSM>12.5kPa(调整后的风险比[aHR] = 3.35 [2.06; 5.45],p<0.0001)、HCV 治疗史(aHR = 0.53 [0.32; 0.90],p = 0.01)和吸烟史(既往(aHR = 5.69 [1.56; 20.78])和当前(aHR = 3.22 [0.93; 11.09])与从不吸烟相比,p = 0.01)与全因死亡率相关,独立于 SVR、年龄、性别、饮酒和代谢紊乱等因素。

结论

任何 LSM>12.5kPa 均与全因死亡率显著相关,独立于 SVR 和其他重要的协变量。我们的研究结果表明,即使在获得 SVR 后,这些患者的密切随访也应仍然是优先事项。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/469e/6347250/16a6b5ed5e58/pone.0211286.g001.jpg

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