Calvaruso Vincenza, Burroughs Andrew Kenneth, Standish Richard, Manousou Pinelopi, Grillo Federica, Leandro Gioacchino, Maimone Sergio, Pleguezuelo Maria, Xirouchakis Ilias, Guerrini Gian Piero, Patch David, Yu Dominic, O'Beirne James, Dhillon Amar Paul
The Royal Free Sheila Sherlock Liver Centre and Department of Surgery, Royal Free Hospital, London, UK.
Hepatology. 2009 Apr;49(4):1236-44. doi: 10.1002/hep.22745.
Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies.
CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.
疾病阶段的组织病理学评分使用描述性类别，而不测量纤维化的程度。胶原蛋白是纤维组织的主要成分，可以通过使用组织切片的计算机辅助数字图像分析（DIA）进行量化。我们确定了DIA、伊沙克分期和反映纤维化严重程度的肝静脉压力梯度（HVPG）之间的关系。115例接受过移植的丙型肝炎病毒（HCV）患者连续进行了250次经颈静脉肝活检并测量HVPG（中位数长度为22毫米；门静脉分支总数中位数为12个），使用伊沙克系统进行评估，并用天狼星红染色用于DIA分析。肝脏胶原蛋白以胶原蛋白比例面积（CPA）表示。CPA中位数为6%（0.2 - 45），与伊沙克分期（6期范围为13% - 45%）以及HVPG相关（r = 0.62；P < 0.001）。当HVPG小于6毫米汞柱时，CPA中位数为4.1%；当HVPG为6毫米汞柱或更高时，CPA中位数为13.8%（P < 0.0001）；当HVPG小于10毫米汞柱时，CPA中位数为6%；当HVPG为10毫米汞柱或更高时，CPA中位数为17.3%（P < 0.0001）。通过逻辑回归分析，只有CPA，而非伊沙克分期/分级，与6毫米汞柱或更高的HVPG独立相关[比值比，1.206；95%置信区间（CI），1.094 - 1.331；P < 0.001]，或与10毫米汞柱或更高的HVPG独立相关（比值比，1.105；95%CI，1.026 - 1.191；P = 0.009）。在38例接受重复活检的患者中，CPA增加了50%（3.6%），而HVPG每增加1毫米汞柱时增加20%。
通过DIA评估的CPA与同时测量的伊沙克分期评分和HVPG相关。与伊沙克分期相比，CPA与HVPG的组织学相关性更好，在HVPG较低时数值变化更大，并且能够进一步量化肝硬化中的纤维化程度。
