Department of Infectious Diseases, The First Hospital of Jilin University, Changchun 130021, China.
Department of Hepatic Biliary Pancreatic Medicine, The First Hospital of Jilin University, Changchun 130021, China.
Endocr Metab Immune Disord Drug Targets. 2022;22(6):658-662. doi: 10.2174/1871530321666211119145230.
Gaucher Disease (GD) is a rare autosomal recessive inherited disease caused by the deficiency of glucocerebrosidase and characterized by a broad spectrum of clinical manifestations, including hepatosplenomegaly, bone infiltration, and cytopenia. Moreover, it is even involved in the central nervous system. GD is classified into three phenotypes on the ground of neurologic involvement: type 1 (GD1), the commonly adult-onset, non-neuropathic variant; type 2 (GD2), the acute neuropathic form; and type 3 (GD3), the severe chronic neuro-visceral form. Recently, several studies have shown a promising outcome of ambroxol chaperone therapy for the treatment of GD, but its therapeutic role in GD1-associated liver cirrhosis and portal hypertension was not verified.
A 36-year-old male patient was admitted for esophageal varices lasting for one year with a 34-year history of liver and spleen enlargement. The patient was diagnosed with GD1 with cirrhosis and portal hypertension based on the identification of Gaucher cells and advanced fibrosis in the liver biopsy tissue and two known pathogenic mutations on the glucocerebrosidase (GBA) gene. The patient received 660 mg/d of ambroxol for up to two years. At his six-month follow- up, the patient exhibited a remarkable increase in GBA activity (+35.5%) and decrease in liver stiffness (-19.5%) and portal vein diameter (-41.2%) as examined by ultrasound elastography and computer tomography, respectively. At two-year follow-up, the liver stiffness was further reduced (-55.5%) in comparison with untreated patients.
This case report suggests that long-term treatment with high dose ambroxol may play a role in the reduction of hepatic fibrosis in GD1.
戈谢病（Gaucher Disease，GD）是一种罕见的常染色体隐性遗传疾病，由葡萄糖脑苷脂酶缺乏引起，具有广泛的临床表现，包括肝脾肿大、骨骼浸润和细胞减少症。此外，它甚至涉及中枢神经系统。根据神经受累情况，GD 分为三种表型：1 型（GD1），常见的成人发病、非神经病变型；2 型（GD2），急性神经病变型；3 型（GD3），严重的慢性神经内脏型。最近，几项研究表明，氨溴索伴侣治疗对 GD 的治疗有很好的效果，但它在 GD1 相关肝硬化和门静脉高压症中的治疗作用尚未得到验证。
一名 36 岁男性患者因食管静脉曲张持续一年就诊，其肝脾肿大病史已有 34 年。该患者通过肝活检组织中发现戈谢细胞和晚期纤维化，以及葡萄糖脑苷脂酶（GBA）基因上的两个已知致病突变，被诊断为 GD1 伴肝硬化和门静脉高压症。该患者接受了为期两年的氨溴索 660mg/d 治疗。在他的六个月随访中，患者的 GBA 活性显著增加（+35.5%），超声弹性成像和计算机断层扫描分别显示肝脏硬度（-19.5%）和门静脉直径（-41.2%）降低。在两年的随访中，与未治疗的患者相比，肝脏硬度进一步降低（-55.5%）。
本病例报告提示，长期高剂量氨溴索治疗可能在 GD1 患者肝纤维化的减少中发挥作用。
