Regional Referral Centre for Lysosomal Storage Diseases, Division of Internal Medicine and Metabolism, Civil Hospital, AOU Modena, University of Modena and Reggio Emilia, Modena, Italy.
Rare Diseases Center, Department of Medicine, "Ca' Granda" Foundation IRCCS, Milan, Italy.
Mol Genet Metab. 2018 Sep;125(1-2):64-72. doi: 10.1016/j.ymgme.2018.08.004. Epub 2018 Aug 11.
BACKGROUND & AIMS: Long-term liver-related complications of Gaucher disease (GD) include cirrhosis, portal hypertension and hepatocellular carcinoma. Although liver fibrosis is the main determinant of adverse liver-related clinical outcomes, it has rarely been evaluated in previously published cohorts of GD patients. We aimed at: assessing the prevalence of significant liver fibrosis in a cohort of patients with type 1 GD; identifying its predictors among GD-related variables, enzyme replacement therapy (ERT) and metabolic features.
37 adult type 1 GD patients from two Italian academic referral centers were prospectively submitted to vibration controlled transient elastography (Fibroscan®); significant fibrosis was defined as liver stiffness ≥7 kPa.
Median liver stiffness was 4.6 [3-15.1] kPa and 7 patients (19%) had significant fibrosis. Significant fibrosis was associated with splenectomy (p = .046) and with scores (DS3: p = .002; SSI: p = .026) and biomarkers (ACE: p = .016; HDL cholesterol: p = .004) of GD severity. Length of ERT was significantly lower in GD patients with significant fibrosis. In the subgroup of 29 patients who were on stable ERT for at least 24 months, further to splenectomy, GD severity and non-N370S GBA1 genotypes, also diastolic blood pressure, BMI and the number of metabolic syndrome (MetS) components emerged as factors significantly associated with significant fibrosis.
Significant fibrosis is present in a remarkable proportion of adult type 1 GD patients. Splenectomy, GD severity and GBA1 genotypes are major GD-related predictors of liver fibrosis. Length of ERT is inversely correlated with liver disease in GD patients, suggesting a beneficial effect of ERT on liver fibrosis. However, GD patients on stable ERT should be monitored for metabolic complications, since MetS features may enhance liver disease progression despite optimal GD control.
戈谢病（GD）的长期肝脏相关并发症包括肝硬化、门静脉高压和肝细胞癌。虽然肝纤维化是导致不良肝脏相关临床结局的主要决定因素，但在以前发表的 GD 患者队列研究中很少对其进行评估。我们旨在：评估 1 型 GD 患者队列中显著肝纤维化的患病率；确定其在 GD 相关变量、酶替代疗法（ERT）和代谢特征中的预测因素。
来自意大利两个学术转诊中心的 37 名成人 1 型 GD 患者前瞻性接受振动控制瞬时弹性成像（Fibroscan®）；将显著纤维化定义为肝硬度≥7kPa。
中位肝硬度为 4.6[3-15.1]kPa，7 名患者（19%）存在显著纤维化。显著纤维化与脾切除术（p=0.046）以及 GD 严重程度评分（DS3：p=0.002；SSI：p=0.026）和生物标志物（ACE：p=0.016；HDL 胆固醇：p=0.004）相关。在存在显著纤维化的 GD 患者中，ERT 时间明显缩短。在至少接受 24 个月稳定 ERT 的 29 名患者亚组中，除脾切除术、GD 严重程度和非 N370S GBA1 基因型外，舒张压、BMI 和代谢综合征（MetS）成分数量也成为与显著纤维化显著相关的因素。
显著纤维化在相当比例的成人 1 型 GD 患者中存在。脾切除术、GD 严重程度和 GBA1 基因型是 GD 相关预测肝纤维化的主要因素。ERT 时间与 GD 患者的肝病呈负相关，提示 ERT 对肝纤维化有益。然而，接受稳定 ERT 的 GD 患者应监测代谢并发症，因为尽管 GD 得到了很好的控制，但 MetS 特征可能会加剧肝病的进展。
