Delhaye M, Louis H, Degraef C, Le Moine O, Devière J, Peny M O, Adler M, Galand P
Department of Gastroenterology, Erasme Hospital, Brussels, Belgium.
J Hepatol. 1999 Mar;30(3):461-71. doi: 10.1016/s0168-8278(99)80106-8.
BACKGROUND/AIMS: The objective of this study was to validate, with an independent prospective cohort of patients, our previous data indicating that the proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver functional reserve in human cirrhosis and might have prognostic significance for patient survival. We also examined how this proliferative index is related to the expression of transforming growth factor beta1 (TGFbeta1) as a possible correlate of hepatocyte proliferative activity.
The present group (n=70 patients) was similar in composition to our previous group regarding age, sex and severity of liver cirrhosis. PCNA and TGFbeta1 immunostaining were analyzed on methanol-fixed, paraffin-embedded liver biopsies.
Our data show that PCNA-LI declined significantly with worsening Child class and was negatively correlated with the Pugh score. Twenty-five patients died and 10 underwent liver transplantation during the observation period. Liver function, hepatic venous pressure gradient and hepatocyte PCNA-LI were significantly different in survivors and non-survivors. At a mean follow-up of 356 days, the patients with a PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a significantly higher probability of survival than those with a PCNA-LI < or = 4.4% (0.87 vs 0.48, p=0.0009). TGFbeta1 expression in liver parenchyma correlated negatively with PCNA-LI, suggesting that this cytokine could be involved in the impaired regeneration observed in worsened liver cirrhosis.
This prospective study strengthens our previous observation that, in cirrhosis, hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides information on liver functional reserve as well as on the patient's prognosis.
背景/目的：本研究的目的是通过一个独立的前瞻性患者队列来验证我们之前的数据，该数据表明增殖细胞核抗原标记指数（PCNA-LI）反映了人类肝硬化患者的肝脏功能储备，并且可能对患者生存具有预后意义。我们还研究了这个增殖指数与转化生长因子β1（TGFβ1）的表达之间的关系，TGFβ1可能是肝细胞增殖活性的一个相关因素。
目前的研究组（n = 70例患者）在年龄、性别和肝硬化严重程度方面与我们之前的研究组组成相似。对甲醇固定、石蜡包埋的肝活检组织进行PCNA和TGFβ1免疫染色分析。
我们的数据显示，PCNA-LI随着Child分级的恶化而显著下降，并且与Pugh评分呈负相关。在观察期内，25例患者死亡，10例接受了肝移植。存活者和非存活者的肝功能、肝静脉压力梯度和肝细胞PCNA-LI有显著差异。在平均356天的随访中, PCNA-LI高于4.4%（先前确定的最佳临界值）的患者的生存概率显著高于PCNA-LI≤4.4%的患者（0.87对0.48，p = 0.0009）。肝实质中TGFβ1的表达与PCNA-LI呈负相关，这表明这种细胞因子可能参与了肝硬化恶化时观察到的再生受损过程。
这项前瞻性研究强化了我们之前的观察结果，即在肝硬化中，通过PCNA-LI评估的肝细胞增殖活性可提供有关肝脏功能储备以及患者预后的信息。
