Mohsen A H, Easterbrook P J, Taylor C, Portmann B, Kulasegaram R, Murad S, Wiselka M, Norris S
Department of HIV/GU Medicine, The Guy's King's and St Thomas School of Medicine, Weston Education Centre, Denmark Hill Campus, Cutcombe Road, London SE5 9RJ, UK.
Gut. 2003 Jul;52(7):1035-40. doi: 10.1136/gut.52.7.1035.
To compare the rate of hepatic fibrosis progression in hepatitis C virus (HCV) infected and human immunodeficiency virus (HIV)-HCV coinfected patients, and to identify factors that may influence fibrosis progression.
A total of 153 HCV infected and 55 HCV-HIV coinfected patients were identified from two London hospitals. Eligible patients had known dates of HCV acquisition, were HCV-RNA positive, and had undergone a liver biopsy, which was graded using the Ishak score. Univariate and multivariate logistic regression analyses were used to identify factors associated with fibrosis progression rate and the development of advanced fibrosis (stages 3 and 4).
The estimated median fibrosis progression rate was 0.17 units/year (interquartile range (IQR) 0.10-0.25) in HIV-HCV coinfected and 0.13 (IQR 0.07-0.17) in HCV monoinfected patients (p=0.01), equating to an estimated time from HCV infection to cirrhosis of 23 and 32 years, respectively. Older age at infection (p<0.001), HIV positivity (p=0.019), higher alanine aminotransferase (ALT) level (p=0.039), and higher inflammatory activity (p<0.001) on first biopsy were all independently associated with more rapid fibrosis progression. ALT was correlated with histological index (r=0.35, p<0.001). A CD4 cell count < or =250 x 10(6)/l was independently associated with advanced liver fibrosis (odds ratio 5.36 (95% confidence interval 1.26-22.79)) and was also correlated with a higher histological index (r=-0.42, p=0.002).
HIV infection modifies the natural history of HCV by accelerating the rate of fibrosis progression by 1.4 fold, and the development of advanced fibrosis threefold. A low CD4 cell count was independently associated with advanced disease and correlated with higher histological index, which suggests that early antiretroviral therapy may be of benefit in slowing HCV progression in coinfected patients.
比较丙型肝炎病毒(HCV)感染患者与人类免疫缺陷病毒(HIV)-HCV合并感染患者肝纤维化进展速率,并确定可能影响纤维化进展的因素。
从伦敦两家医院共识别出153例HCV感染患者和55例HIV-HCV合并感染患者。符合条件的患者已知HCV感染日期,HCV-RNA呈阳性,且接受过肝活检,采用Ishak评分进行分级。单因素和多因素逻辑回归分析用于确定与纤维化进展速率及进展期纤维化(3期和4期)发生相关的因素。
HIV-HCV合并感染患者的估计中位纤维化进展速率为0.17单位/年(四分位间距(IQR)0.10 - 0.25),HCV单感染患者为0.13(IQR 0.07 - 0.17)(p = 0.01),相当于从HCV感染到肝硬化的估计时间分别为23年和32年。感染时年龄较大(p < 0.001)、HIV阳性(p = 0.019)、首次活检时较高的丙氨酸转氨酶(ALT)水平(p = 0.039)以及较高的炎症活动度(p < 0.001)均与更快速的纤维化进展独立相关。ALT与组织学指标相关(r = 0.35,p < 0.001)。CD4细胞计数≤250×10⁶/l与进展期肝纤维化独立相关(比值比5.36(95%置信区间1.26 - 22.79)),且也与较高的组织学指标相关(r = -0.42,p = 0.002)。
HIV感染通过将纤维化进展速率加快1.4倍以及将进展期纤维化的发生加快3倍来改变HCV的自然病程。低CD4细胞计数与疾病进展独立相关且与较高的组织学指标相关,这表明早期抗逆转录病毒治疗可能有助于减缓合并感染患者的HCV进展。