Larrousse Maria, Laguno Montserrat, Segarra Marta, De Lazzari Elisa, Martinez Esteban, Blanco José Luis, León Agathe, Deulofeu Ramón, Miquel Rosa, Milinkovic Ana, Lonca Montserrat, Miró José María, Biglia Alejandra, Murillas Javier, Gatell José María, Mallolas Josep
Infectious Diseases Unit, Hospital Clínic Universitari de Barcelona-IDIBAPS, University of Barcelona, Spain.
J Acquir Immune Defic Syndr. 2007 Nov 1;46(3):304-11. doi: 10.1097/qai.0b013e3181520502.
Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals.
We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC).
Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy.
One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 microg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%.
TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.
在未感染HIV的慢性丙型肝炎患者中，几种反映细胞外基质状态的血清标志物与肝纤维化相关。在HIV/HCV合并感染的个体中，这些指标的研究较少。
我们旨在评估血清标志物对HIV感染的慢性丙型肝炎病毒（HVC）患者肝纤维化的预测价值。
在对HIV感染的慢性丙型肝炎患者进行肝活检时以及考虑抗丙型肝炎治疗之前，测量其血清金属蛋白酶1和2（MMP-1和-2）、基质金属蛋白酶组织抑制剂（TIMP-1）、III型前胶原N端肽（PIIINP）和透明质酸（HA）的水平。
纳入了119例连续的HIV-HVC合并感染患者。TIMP-1（r = 0.6；P < 0.001）、TIMP-1/MMP-1比值（r = 0.5；P < 0.001）、TIMP-1/MMP-2比值（r = 0.3；P < 0.001）、MMP-2（r = 0.2；P = 0.044）、PIIINP（r = 0.4；P < 0.001）和HA（r = 0.5；P < 0.001）与纤维化阶段呈显著正相关。在多变量分析中，TIMP-1（比值比[OR] = 1.004，95%置信区间[CI]：1.002至1.006，P = 0.001）和HA > 95μg/dL（OR = 6.041，95%CI：1.184至30.816，P = 0.031）与肝纤维化独立相关。在使用TIMP-1和HA变量的接受操作分析中，区分轻度（F0-F1）与显著（F2-F4）纤维化的评分曲线下面积为0.84，敏感性为72.9%，特异性为83.1%。
TIMP-1和HA对预测HIV感染的慢性丙型肝炎患者的肝纤维化程度相当敏感且特异。当需要估计肝纤维化程度时，这些参数可能成为肝活检的非侵入性替代方法。
