TY - JOUR
T1 - Hepatic symptoms and histology in 13 patients with a Zellweger spectrum disorder
AU - Berendse, Kevin
AU - Koot, Bart G. P.
AU - Klouwer, Femke C. C.
AU - Engelen, Marc
AU - Roels, Frank
AU - Lacle, Miangela M.
AU - Nikkels, Peter G. J.
AU - Verheij, Joanne
AU - Poll-The, Bwee Tien
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070269420&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31150129
U2 - https://doi.org/10.1002/jimd.12132
DO - https://doi.org/10.1002/jimd.12132
M3 - Article
C2 - 31150129
SN - 0141-8955
VL - 42
SP - 955
EP - 965
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 5
ER -