Division of Pediatric Gastroenterology.
Wayne State University School of Medicine, Detroit, MI.
J Pediatr Gastroenterol Nutr. 2020 May;70(5):635-639. doi: 10.1097/MPG.0000000000002671.
To assess the effect of long-term (104 weeks) treatment with recombinant sebelipase alpha (rhSA) on serum lipid and hepatic transaminase levels, and liver histopathology in 4 siblings diagnosed with lysosomal acid lipase deficiency (LAL-D).
Four male siblings from the same nonconsanguineous parents were diagnosed with the late-onset phenotype of LAL-D in 2015. Liver specimens were obtained by biopsy at baseline and after 104 weeks of enzyme replacement with rhSA (1 mg/kg, IV, every 2 weeks). Hepatic transaminase, lipid and lipoprotein levels were assessed at baseline and sequentially every 16 weeks for 104 weeks. Hepatic steatosis was evaluated from hematoxylin and eosin-stained specimens, and fibrosis was evaluated (Metavir-scoring system) from trichrome-stained specimens obtained at baseline and following 104 weeks of treatment with rhSA.
All 4 siblings had improvement in their serum lipid and hepatic transaminase levels after treatment with rhSA. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from baseline by an average of 47% and 56%, respectively. The fasting triglyceride and low-density lipoprotein cholesterol (LDL-C) levels decreased from baseline by an average of 43% and 60%, respectively. Hepatic steatosis decreased from baseline grade 3 to posttreatment grade 1. Hepatic fibrosis did not advance following 104 weeks of treatment with rhSA and regressed in 1 sibling.
Treatment with rhSA for 104 weeks in 4 siblings with LAL-D demonstrated improvement in their hepatic transaminase and serum lipid levels, accompanied by reduction of hepatic steatosis and no progression of fibrosis.
评估重组sebeliapase alpha（rhSA）长期（104 周）治疗对 4 例确诊为溶酶体酸性脂肪酶缺乏症（LAL-D）的兄弟姐妹的血清脂质和肝转氨酶水平及肝组织病理学的影响。
2015 年，我们从同一非近亲的父母处诊断出 4 名男性兄弟姐妹患有溶酶体酸性脂肪酶缺乏症的晚发型表型。基线时及接受 rhSA（1mg/kg，静脉注射，每 2 周 1 次）治疗 104 周后进行肝活检。在基线和 104 周的 rhSA 治疗过程中，每 16 周连续评估肝转氨酶、脂质和脂蛋白水平。从苏木精和伊红染色标本评估肝脂肪变性，从基线和 rhSA 治疗 104 周后获得的三色染色标本评估纤维化（Metavir 评分系统）。
所有 4 名接受 rhSA 治疗的兄弟姐妹的血清脂质和肝转氨酶水平均有所改善。丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平分别平均下降了 47%和 56%。空腹甘油三酯和低密度脂蛋白胆固醇（LDL-C）水平分别平均下降了 43%和 60%。肝脂肪变性从基线 3 级降至治疗后 1 级。rhSA 治疗 104 周后，肝纤维化没有进展，并在 1 名患者中出现消退。
rhSA 治疗 104 周后，4 例 LAL-D 患者的肝转氨酶和血清脂质水平得到改善，肝脂肪变性减轻，纤维化无进展。
