Laboratory of Molecular Biology, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina.
PLoS One. 2011;6(8):e23218. doi: 10.1371/journal.pone.0023218. Epub 2011 Aug 17.
BACKGROUND/AIMS: Liver biopsy represents the gold standard for damage evaluation, but noninvasive serum markers that mirror liver fibrosis progression are actual goals both in adults and especially in children. The aim was to determine specific serum markers that correlate with liver fibrosis progression during chronic HCV infection.
Liver biopsies and concomitant serum samples from 22 pediatric and 22 adult HCV patients were analyzed. Histological parameters were evaluated. On serum TGF-ß1, tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1), hyaluronic acid (HA) and aminoterminal peptide of procollagen type III (PIIINP) were tested.
Significant fibrosis (F≥2) and advanced fibrosis (F≥3) represented 64% and 20%, respectively in children; while 54% F≥2 and 23% F≥3 in adults. Hyaluronic acid (p = 0.011) and PIIINP (p = 0.016) were related to worse fibrosis stages only in adults, along with TIMP-1 (p = 0.039) just in children; but TGF-ß1 was associated with mild fibrosis (p = 0.022) in adults. The AUROC of TIMP-1 in children to discriminate advanced fibrosis was 0.800 (95%IC 0.598-0.932). In adults, the best AUROCs were that of HA, PIIINP and TGF-ß1 [0.929 (IC95% 0.736-0.994), 0.894 (IC95% 0.689-0.984) and 0.835 (IC95% 0.617-0.957)], respectively. In children, according to the cut off (165.7 ng/mL) value for TIMP-1, biopsies could have been avoided in 72% (18/25). Considering the cut off for HA (109.7 ng/mL), PIIINP (9.1 µg/L), and TGF-ß1 (10,848.3 pg/mL), biopsies could have been avoided in 87% (19/22) of adult patients by using HA and 73% (16/22) using PIIINP or TGF-ß1.
In adults given the diagnostic accuracy of HA, PIIINP, TGF-ß1, their combination may provide a potential useful tool to assess liver fibrosis. This first pediatric study suggests that TIMP-1 is clinically useful for predicting liver fibrosis in HCV patients.
背景/目的：肝活检是评估损伤的金标准，但在成人中，特别是在儿童中，寻找能反映肝纤维化进展的非侵入性血清标志物才是实际目标。本研究旨在确定在慢性 HCV 感染过程中与肝纤维化进展相关的特定血清标志物。
对 22 名儿科和 22 名成人 HCV 患者的肝活检和同时采集的血清样本进行分析。评估组织学参数。检测血清 TGF-β1、基质金属蛋白酶抑制剂 1（TIMP-1）、透明质酸（HA）和 III 型前胶原氨基末端肽（PIIINP）。
儿童中显著纤维化（F≥2）和晚期纤维化（F≥3）分别占 64%和 20%；而在成人中分别占 54%和 23%。仅在成人中，HA（p=0.011）和 PIIINP（p=0.016）与更差的纤维化阶段相关，而 TIMP-1（p=0.039）仅在儿童中相关；但 TGF-β1 与成人轻度纤维化相关（p=0.022）。TIMP-1 在成人中鉴别晚期纤维化的 AUROC 为 0.800（95%CI 0.598-0.932）。在成人中，HA、PIIINP 和 TGF-β1 的最佳 AUROC 分别为 0.929（95%CI 0.736-0.994）、0.894（95%CI 0.689-0.984）和 0.835（95%CI 0.617-0.957）。在儿童中，根据 TIMP-1 的截断值（165.7ng/mL），可以避免 72%（18/25）的活检。考虑到 HA（109.7ng/mL）、PIIINP（9.1μg/L）和 TGF-β1（10848.3pg/mL）的截断值，HA 可避免 87%（19/22）成人患者的活检，PIIINP 或 TGF-β1 可避免 73%（16/22）成人患者的活检。
在成人中，基于 HA、PIIINP、TGF-β1 的诊断准确性，它们的组合可能为评估肝纤维化提供一种有用的工具。这项儿科研究首次表明，TIMP-1 可用于预测 HCV 患者的肝纤维化。
