Characterization of liver disease in a cohort of individuals with Niemann-Pick Disease, Type C1.

PURPOSE: Niemann-Pick Disease, Type C1 (NPC1) is a neurodegenerative lysosomal disease in which the first manifestation is often cholestatic liver disease at birth. The neurodegenerative symptoms typically manifest later. The aim of this study was to see if the presence and severity of liver disease at birth predicted whether a participant would develop liver disease later and if there was any correlation with the age of onset of neurological symptoms. METHODS: Liver disease was characterized in 93 individuals with NPC1 using FibroScan, abdominal ultrasound, and plasma liver function tests at baseline and longitudinally over up to a four-year period. This information was correlated with the presence or absence of liver disease noted at birth. RESULTS: Higher liver stiffness measurement scores, suggesting increased risk for liver fibrosis, were associated with a history of significant liver disease in infancy (p = 0.001). A history of absent or mild/moderate liver disease at birth had no correlation with differences in liver stiffness measurements The presence of any degree of liver disease at birth corresponded to earlier onset of neurological symptoms compared to having no liver disease at birth (p = 0.002). Those with no history of neonatal liver disease had an average age of 10.3 years at time of neurological symptoms, compared to 5.9 years for those with mild/moderate disease and 3.6 years for those with severe disease (p = 0.002). CONCLUSIONS: The presence of liver disease at birth can provide prognostic information on when individuals with NPC1 may manifest neurologic symptoms. In addition, individuals who had severe liver disease at birth are at higher risk for developing clinically significant liver disease after the neonatal period. Given multiple reports of hepatocellular carcinoma in individuals with NPC1, those with a history of severe liver disease should be closely monitored.