人类免疫缺陷病毒（HIV）能加剧丙型肝炎病毒（HCV）所致疾病的进程，然而对肝病分期及抗病毒治疗临床结局风险的影响尚未完全阐明。目的：确定终末期肝病（ESLD）、肝细胞癌（HCC）或根据肝脏纤维化基线水平及成人HIV/HCV共同感染抗病毒治疗所致死亡的发生率。方法：前瞻性队列研究共纳入1993年7月至2011年8月期间在约翰霍普金斯大学HIV诊所638例接受治疗的混合感染成年患者（88%为黑人，60%为男性），这些患者都接受了肝活检及前瞻性临床事件监测（随访中位年限：5.82年；四分位数范围：3.42～8.85年）。依照METAVIR评分系统确定肝活检标本的纤维化分期。主要结果判定指标：监测ESLD、HCC或死亡的混合发生率。结果：患者临床结局的发生危险度基于肝纤维化分期基线水平逐级增加（分期，F0～F4）：F0期，23.63（95% CI：16.80～33.24）；F1期，36.33 (95% CI：28.03～47.10)；F2期，53.40 (95% CI：33.65～84.76)；F3期，56.14(95% CI：31.09～101.38)及F4期的79.43 (95% CI, 55.86～112.95)，单位为每1000人/年（P<0.001）。多变量负二项回归分析显示，在根据人口统计学特征、注射吸毒及CD4细胞计数校正后，抗病毒治疗及纤维化F2～F4期与ESLD、HCC或所有因素病死率独立相关。相较于F0期，F2期的发病率比（RR）为2.31 (95% CI：1.23～4.34； P=0.009)；F3期为3.18(95%CI：1.47～6.88；P=0.003)；F4期为3.75(95% CI，2.06～6.19；P<0.001)。接受HCV治疗的226例患者，其临床事件发生率与治疗无效及未接受治疗患者相比没有显著差异（发病率比为1.27；95%CI：0.86～1.86；P=0.23）。相反的，呈持续病毒学应答反应（n=36）及复发（n=15）的51例患者无临床事件发生，其中包含19例显著肝纤维化患者。结论：在此项HIV/HCV共同感染患者的研究队列中，肝纤维化分期与ESLD、HCC或死亡的混合结果独立相关。

 

Human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV) disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood.Objective To determine the incidence of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death according to baseline hepatic fibrosis and antiviral treatment for HIV/HCV coinfected individuals. Methods Prospective cohort of 638 coinfected adults (80% black, 66% men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median follow-up, 5.82 years; interquartile range, 3.42-8.85 years). Histological specimens were scored for hepatic fibrosis stage according to the METAVIR scoring system.Main Outcome Measure Incidence of composite outcome of ESLD, HCC, or death. Results Patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage (classification range, F0-F4): F0, 23.63 (95% CI, 16.80-33.24); F1, 36.33 (95% CI, 28.03-47.10); F2, 53.40 (95% CI, 33.65-84.76); F3, 56.14 (95% CI, 31.09-101.38); and F4, 79.43 (95% CI, 55.86-112.95)per 1000 person-years (P<0.001). In multivariable negative binomial regression, fi-brosis stages F2 through F4 and antiretroviral therapy were independently associated with composite ESLD, HCC, or all cause mortality after adjustment for demographic characteristics, injection drug use, and CD4 cell count. Compared with F0,the incidence rate ratio (RR) for F2 was 2.31 (95% CI, 1.23-4.34; P=.009); F3, 3.18 (95% CI, 1.47-6.88; P=.003); and F4, 3.57 (95% CI, 2.06-6.19; P.001). Human immunodeficiency virus treatment was associated with fewer clinical events (incidence RR,0.27; 95% CI, 0.19-0.38; P<0.001). For the 226 patients who underwent HCV treatment, the incidence of clinical events did not significantly differ between treatmentnonresponders and untreated patients (incidence RR, 1.27; 95% CI, 0.86-1.86; P=.23).In contrast, no events were observed in the 51 patients with sustained virologic response (n= 36) and relapse (n= 15), including 19 with significant fibrosis. Conclusion In this cohort of patients with HIV/HCV coinfection, hepatic fibrosis stage was independently associated with a composite outcome of ESLD, HCC, or death.

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