Department of Paediatric Neurology, Emma Children's Hospital, Amsterdam University Medical Centre (Amsterdam UMC), University of Amsterdam, Amsterdam, The Netherlands.
Department of Paediatric Gastroenterology, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
J Inherit Metab Dis. 2019 Sep;42(5):955-965. doi: 10.1002/jimd.12132. Epub 2019 Jul 30.
Patients with a Zellweger spectrum disorder (ZSD) have a defect in the assembly or maintenance of peroxisomes, leading to a multisystem disease with variable outcome. Liver disease is an important feature in patients with severe and milder phenotypes and a frequent cause of death. However, the course and histology of liver disease in ZSD patients are ill-defined. We reviewed the hepatic symptoms and histological findings of 13 patients with a ZSD in which one or several liver biopsies have been performed (patient age 0.2-39 years). All patients had at least some histological liver abnormalities, ranging from minor fibrosis to cirrhosis. Five patients demonstrated significant disease progression with liver failure and early death. In others, liver-related symptoms were absent, although some still silently developed cirrhosis. Patients with peroxisomal mosaicism had a better prognosis. In addition, we show that patients are at risk to develop a hepatocellular carcinoma (HCC), as one patient developed a HCC at the age of 36 years and one patient a precancerous lesion at the age of 18 years. Thus, regular examination to detect fibrosis or cirrhosis should be included in the standard care of ZSD patients. In case of advanced fibrosis/cirrhosis expert consultation and HCC screening should be initiated. This study further delineates the spectrum and significance of liver involvement in ZSDs.
患有 Zellweger 谱系障碍 (ZSD) 的患者在过氧化物酶体的组装或维持方面存在缺陷，导致多系统疾病，预后各不相同。肝脏疾病是严重和轻度表型患者的重要特征，也是常见的死亡原因。然而，ZSD 患者的肝脏疾病的病程和组织学特征尚未明确。我们回顾了 13 名接受过一次或多次肝活检的 ZSD 患者的肝脏症状和组织学发现（患者年龄 0.2-39 岁）。所有患者均存在至少一些组织学肝脏异常，从轻微纤维化到肝硬化不等。五名患者出现明显的疾病进展，导致肝功能衰竭和早期死亡。在其他患者中，虽然有些患者仍在无声无息地发展为肝硬化，但没有出现与肝脏相关的症状。具有过氧化物酶体镶嵌现象的患者预后较好。此外，我们还表明，患者有发生肝细胞癌 (HCC) 的风险，因为一名患者在 36 岁时患上了 HCC，一名患者在 18 岁时患上了癌前病变。因此，应将定期检查以检测纤维化或肝硬化纳入 ZSD 患者的标准护理中。在出现晚期纤维化/肝硬化时，应启动专家咨询和 HCC 筛查。本研究进一步阐明了 ZSD 中肝脏受累的范围和意义。
