Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Liver Int. 2020 Dec;40(12):3051-3060. doi: 10.1111/liv.14598. Epub 2020 Aug 4.
Non-invasive screening for liver fibrosis using transient elastography (TE) could be of value in the management of Gaucher disease (GD). Progranulin (PGRN) is a novel disease modifier in GD and an independent marker of liver fibrosis.
We determined PGRN levels in paediatric patients with GD and assessed its role as a potential marker for disease severity and relation to liver stiffness by TE.
Fifty-one GD patients (20 had type 1 and 31 had type 3) with a median age of 9.5 years were compared to 40 age- and sex-matched healthy controls and were studied focusing on visceral manifestations, neurological disease, haematological profile and PGRN levels as well as abdominal ultrasound and TE. Patients were on enzyme replacement therapy (ERT) for various durations and those with viral hepatitis infection were excluded.
By TE, 14 GD patients (27.5%) had elevated liver stiffness ≥7.0 kPa. Liver stiffness was significantly higher in type 1 GD patients than type 3 (P = .002), in splenectomized patients (P = .012) and those with dysphagia (P < .001). Liver stiffness was positively correlated with age of onset of ERT (P < .001). PGRN levels were significantly lower in GD patients compared with controls (P < .001). PGRN was significantly lower in GD patients with squint (P = .025), dysphagia (P = .036) and elevated liver stiffness (P = .015). PGRN was positively correlated with white blood cell count (r = .455, P = .002) and haemoglobin (r = .546, P < .001), while negatively correlated with severity score index (r = -.529, P < .001), liver volume (r = -.298, P = .034) and liver stiffness (r = -.652, P < .001).
Serum PGRN levels were associated with clinical disease severity and elevated liver stiffness in paediatric GD patients.
使用瞬时弹性成像（TE）进行肝纤维化的无创筛查可能对戈谢病（GD）的管理有价值。颗粒蛋白前体（PGRN）是 GD 中的一种新型疾病修饰因子，也是肝纤维化的独立标志物。
我们测定了 GD 患儿的 PGRN 水平，并评估了其作为潜在疾病严重程度标志物的作用，以及与 TE 检测的肝硬度之间的关系。
将 51 名 GD 患儿（20 名 1 型，31 名 3 型）与 40 名年龄和性别匹配的健康对照者进行比较，重点研究内脏表现、神经病变、血液学特征和 PGRN 水平，以及腹部超声和 TE。患者接受了不同时间的酶替代治疗（ERT），且排除了病毒感染性肝炎患者。
通过 TE，14 名 GD 患儿（27.5%）的肝硬度≥7.0kPa。1 型 GD 患儿的肝硬度显著高于 3 型（P=.002），脾切除患者（P=.012）和吞咽困难患者（P<.001）的肝硬度也显著升高。肝硬度与 ERT 发病年龄呈正相关（P<.001）。与对照组相比，GD 患儿的 PGRN 水平显著降低（P<.001）。斜视（P=.025）、吞咽困难（P=.036）和肝硬度升高（P=.015）的 GD 患儿的 PGRN 水平显著降低。PGRN 与白细胞计数呈正相关（r=0.455，P=.002）和血红蛋白（r=0.546，P<.001），与严重程度评分指数呈负相关（r=-.529，P<.001），与肝体积（r=-.298，P=.034）和肝硬度（r=-.652，P<.001）呈负相关。
血清 PGRN 水平与儿科 GD 患者的临床疾病严重程度和肝硬度升高有关。
