低血清谷氨酸转肽酶进行性家族性肝内胆汁淤积症23例临床分析

目的总结以低血清谷氨酸转肽酶（GGT）为特征的进行性家族性肝内胆汁淤积症（PFIC）各型的临床特征，提高对该病的认识。方法回顾性分析2004年1月至2007年6月在复旦大学附属儿科医院临床诊断为低血清GGT的PFIC患儿的临床症状、实验室检查、肝脏组织病理学检查和随访等资料，根据ATP881和ABCB11全部基因外显子测序结果分为PFIC-Ⅰ、PFIC—Ⅱ和未分型3组，分析3组间临床特征的差异。结果23例低血清GGT的PFIC患儿进入分析，PFIC-Ⅰ、PFIC—Ⅱ和未分型组分别为9、7和7例。23例PFIC患儿出生体重均正常，以黄疸、瘙痒和肝功能损害起病。中位发病年龄40d（0d至7个月），中位就诊年龄6（2—36）个月。①13例（56．5％）病程中出现过白陶土样大便，有明显腹泻症状3例。6例（26．1％）有营养不良、佝偻病和生长发育落后。2例（8．7％）随访中发现胆结石。②15例肝组织病理活检示：7例（46．7％）肝细胞多核巨细胞样转化，14例（93．3％）肝细胞和毛细胆管胆汁淤积明显，未发现脂肪变性病例。③未分型组ALT水平较PFIC—Ⅰ型和PFIC—Ⅱ型组显著升高（P〈0．05）；PFIC—Ⅱ型组ALT、TBA水平显著高于PFIC—Ⅰ型组（P〈0．05）；PFIC—Ⅱ型和未分型组肝细胞多核巨细胞转化发生率显著高于PFIC—Ⅰ型组（P〈0．05）。结论低血清GGT的PFIC患儿以黄疸、瘙痒和肝功能损害为主要临床表现，PFIC—Ⅰ型肝穿刺病理活检未见肝细胞多核巨细胞转化，PFIC—Ⅱ型血清ALT、TBA水平明显高于PFIC-Ⅰ型，有助于临床分型和治疗方法的选择。

Clinical characteristics of progressive familial intrahepatic cholestasis cases with low γ- glutamyltransferase in 23 children

Objective To analyze the clinical manifestations of various types of progressive familial intrahepatic cholestasis （PFIC） characterized by low γ-glutamyhransferase （GGT）. Methods Children were clinically diagnosed as PFIC with low GGT in 2004-2007. Clinical symptoms, laboratory tests and liver histopathological changes were retrospectively analyzed. According to ATPSB1 and ABCBll gene exon sequencing results, they were classified into three groups, PFIC- Ⅰ , PFIC—Ⅱ and unclassified groups. The differences among them were compared. Results A total of 23 cases were born with normal birth weight and the clinical manifestations of onset were jaundice, pruritus and liver function damage. The median age of onset was 40 days and the median treatment age was 6 months. Thirteen cases （56.5%） appeared white bole stool, 3 cases with significant diarrhea and 6 cases with malnutrition, rickets, growth retardation. Two cases in the follow-up were found to have gallstones. Liver biopsy pathology showed non-inflammation or mild inflammation of liver cells, non-fatty degeneration of liver cells, muhinucleated giant cells transformation and cholestasis of liver cells or obvious cholangiole ducts. Patients in PFIC—Ⅰ , PFIC-Ⅱ and unclassified groups were 9, 7 and 7 cases respectively. Clinical symptoms of the unclassified group were the most severe among three groups.Clinical symptoms of patients in PFIC- Ⅱ group were relatively severe, with significantly elevated levels of serum ALT and total bile acid （TBA） than those in PFIC- Ⅰ group, however with lower GGT levels than those in PFIC- Ⅰ group. There was significant difference among three groups in hepatic multinucleated giant cell transformation pathologically （P 〈 0.01 ）. PFIC- Ⅰ group showed no hepatic muhinucleated giant cell transformation. Conclusions PFIC-Ⅰ group shows no hepatic muhinucleated giant cell transformation. The levels of serum ALT and TBA in PFIC-Ⅱ group elevate significantly and are higher than those in PFIC- Ⅰ patients. These results are helpful to the clinical classification and treatment of the disease.