Hézode C, Cazeneuve C, Coué O, Roudot-Thoraval F, Lonjon I, Bastie A, Duvoux C, Pawlotsky J M, Zafrani E S, Amselem S, Dhumeaux D
Department of Hepatology-Gastroenterology, Hôpital Henri Mondor, Université Paris XII, Créteil, France.
J Hepatol. 1999 Dec;31(6):979-84. doi: 10.1016/s0168-8278(99)80308-0.
BACKGROUND/AIMS: Liver iron accumulation has been described in patients with chronic active hepatitis (CAH) C, and could play a role in the course of liver disease and negatively influence the response to interferon. The aim of this study was to determine the prevalence and severity of liver iron accumulation in CAH C, to assess its relationship with the HFE C282Y and H63D mutations, and to study its interactions with hepatic histological lesions.
Two hundred and nine patients (131 men, 78 women, mean age 44.3+/-12.0 years) with CAH C, including 19 patients with cirrhosis (9.1%) were studied. A semiquantitative grading system from 0 to 3 was used for histological assessment of liver iron accumulation on Perls' staining. The HFE C282Y and H63D mutations were screened for by restriction enzyme analysis performed on PCR-amplified products. Histological scores of activity and fibrosis were determined according to a previously validated METAVIR score system.
Liver iron accumulation was found in 88/209 patients (42.1%), and was generally mild. The C282Y and H63D allele frequencies were in 23 (11.0%), and 50 (23.9%), respectively. No association was found between the presence of liver iron accumulation and the detection of the C282Y and H63D mutations. A significant relationship was found between the severity of histological activity and liver iron accumulation of macrophagic or mixed (i.e. both macrophagic and hepatocytic) type (p = 0.04). Although the number of cirrhotic patients was small, cirrhosis was more frequently observed in patients with than without liver iron accumulation (17.2% vs. 3.3%, p = 0.004).
Overall, these data suggest that the liver iron accumulation in patients with CAH C is significantly associated with histological activity and cirrhosis, whereas the two missense hemochromatosis gene mutations are not major determinants.
背景/目的：慢性丙型活动性肝炎（CAH C）患者存在肝脏铁蓄积，其可能在肝脏疾病进程中起作用，并对干扰素治疗反应产生负面影响。本研究旨在确定CAH C患者肝脏铁蓄积的患病率和严重程度，评估其与HFE C282Y和H63D突变的关系，并研究其与肝脏组织学病变的相互作用。
对209例CAH C患者（131例男性，78例女性，平均年龄44.3±12.0岁）进行研究，其中包括19例肝硬化患者（9.1%）。采用0至3的半定量分级系统对经派洛宁染色的肝脏铁蓄积进行组织学评估。通过对聚合酶链反应扩增产物进行限制性酶切分析来筛查HFE C282Y和H63D突变。根据先前验证的METAVIR评分系统确定活动度和纤维化的组织学评分。
209例患者中有88例（42.1%）存在肝脏铁蓄积，且通常较轻。C282Y和H63D等位基因频率分别为23例（11.0%）和50例（23.9%）。未发现肝脏铁蓄积的存在与C282Y和H63D突变检测之间存在关联。发现组织学活动度的严重程度与巨噬细胞型或混合型（即巨噬细胞和肝细胞均有）肝脏铁蓄积之间存在显著关系（p = 0.04）。尽管肝硬化患者数量较少，但有肝脏铁蓄积的患者比无肝脏铁蓄积的患者更常出现肝硬化（17.2%对3.3%，p = 0.004）。
总体而言，这些数据表明CAH C患者的肝脏铁蓄积与组织学活动度和肝硬化显著相关，而两个错义血色素沉着症基因突变并非主要决定因素。
