Chronic Liver Involvement in Urea Cycle Disorders

G Ranucci, M Rigoldi, G Cotugno, S Bernabei, A Liguori, S Gasperini, B Goffredo, D Martinelli, L Monti, P Francalanci, M Candusso, R Parini, C Dionisi-Vici

Research output: Contribution to journalArticle

Abstract

The increased survival of urea cycle disorders (UCDs) patients has led the attention to clinical manifestations that characterize the long-term disease course. Acute and chronic liver disease have been anecdotally reported since the very first description of UCDs. However a detailed analysis of long-term liver involvement in large patient cohorts is still needed. Chronic liver damage in UCDs has probably a multifactorial origin, but the specific underlying mechanisms of liver disease have not yet been well elucidated. In this study, we report on chronic liver involvement and on associated metabolic abnormalities in a large cohort of 102 UCD patients, followed by two reference centers in Italy. Chronic liver involvement was observed in over 60% of UCDs patients, and comparison between individual diseases showed a significant higher frequency in ASLD and in HHH syndrome with elevation of transaminases and of gamma-GT in ASLD, and of alpha-fetoprotein in HHH syndrome. Also, consistent with a chronic hepatic dysfunction, ultrasound examination revealed more pronounced abnormalities in ASLD and in HHH syndrome, when compared to other UCDs. Our study highlights in a large UCDs patients' cohort that chronic liver disease is a common finding in UCDs, often with a distinct phenotype between different diseases. Furthers studies are needed to elucidate the specific involvement of different metabolic pathways in the pathogenesis of liver dysfunction in UCDs. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalJournal of Inherited Metabolic Disease
DOIs
Publication statusE-pub ahead of print - Jul 1 2019

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Inborn Urea Cycle Disorder
Liver
Liver Diseases
Chronic Disease
alpha-Fetoproteins
Metabolic Networks and Pathways
Transaminases
Italy

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Chronic Liver Involvement in Urea Cycle Disorders. / Ranucci, G; Rigoldi, M; Cotugno, G; Bernabei, S; Liguori, A; Gasperini, S; Goffredo, B; Martinelli, D; Monti, L; Francalanci, P; Candusso, M; Parini, R; Dionisi-Vici, C.

In: Journal of Inherited Metabolic Disease, 01.07.2019.

Research output: Contribution to journalArticle

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abstract = "The increased survival of urea cycle disorders (UCDs) patients has led the attention to clinical manifestations that characterize the long-term disease course. Acute and chronic liver disease have been anecdotally reported since the very first description of UCDs. However a detailed analysis of long-term liver involvement in large patient cohorts is still needed. Chronic liver damage in UCDs has probably a multifactorial origin, but the specific underlying mechanisms of liver disease have not yet been well elucidated. In this study, we report on chronic liver involvement and on associated metabolic abnormalities in a large cohort of 102 UCD patients, followed by two reference centers in Italy. Chronic liver involvement was observed in over 60{\%} of UCDs patients, and comparison between individual diseases showed a significant higher frequency in ASLD and in HHH syndrome with elevation of transaminases and of gamma-GT in ASLD, and of alpha-fetoprotein in HHH syndrome. Also, consistent with a chronic hepatic dysfunction, ultrasound examination revealed more pronounced abnormalities in ASLD and in HHH syndrome, when compared to other UCDs. Our study highlights in a large UCDs patients' cohort that chronic liver disease is a common finding in UCDs, often with a distinct phenotype between different diseases. Furthers studies are needed to elucidate the specific involvement of different metabolic pathways in the pathogenesis of liver dysfunction in UCDs. This article is protected by copyright. All rights reserved.",
author = "G Ranucci and M Rigoldi and G Cotugno and S Bernabei and A Liguori and S Gasperini and B Goffredo and D Martinelli and L Monti and P Francalanci and M Candusso and R Parini and C Dionisi-Vici",
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AU - Ranucci, G

AU - Rigoldi, M

AU - Cotugno, G

AU - Bernabei, S

AU - Liguori, A

AU - Gasperini, S

AU - Goffredo, B

AU - Martinelli, D

AU - Monti, L

AU - Francalanci, P

AU - Candusso, M

AU - Parini, R

AU - Dionisi-Vici, C

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N2 - The increased survival of urea cycle disorders (UCDs) patients has led the attention to clinical manifestations that characterize the long-term disease course. Acute and chronic liver disease have been anecdotally reported since the very first description of UCDs. However a detailed analysis of long-term liver involvement in large patient cohorts is still needed. Chronic liver damage in UCDs has probably a multifactorial origin, but the specific underlying mechanisms of liver disease have not yet been well elucidated. In this study, we report on chronic liver involvement and on associated metabolic abnormalities in a large cohort of 102 UCD patients, followed by two reference centers in Italy. Chronic liver involvement was observed in over 60% of UCDs patients, and comparison between individual diseases showed a significant higher frequency in ASLD and in HHH syndrome with elevation of transaminases and of gamma-GT in ASLD, and of alpha-fetoprotein in HHH syndrome. Also, consistent with a chronic hepatic dysfunction, ultrasound examination revealed more pronounced abnormalities in ASLD and in HHH syndrome, when compared to other UCDs. Our study highlights in a large UCDs patients' cohort that chronic liver disease is a common finding in UCDs, often with a distinct phenotype between different diseases. Furthers studies are needed to elucidate the specific involvement of different metabolic pathways in the pathogenesis of liver dysfunction in UCDs. This article is protected by copyright. All rights reserved.

AB - The increased survival of urea cycle disorders (UCDs) patients has led the attention to clinical manifestations that characterize the long-term disease course. Acute and chronic liver disease have been anecdotally reported since the very first description of UCDs. However a detailed analysis of long-term liver involvement in large patient cohorts is still needed. Chronic liver damage in UCDs has probably a multifactorial origin, but the specific underlying mechanisms of liver disease have not yet been well elucidated. In this study, we report on chronic liver involvement and on associated metabolic abnormalities in a large cohort of 102 UCD patients, followed by two reference centers in Italy. Chronic liver involvement was observed in over 60% of UCDs patients, and comparison between individual diseases showed a significant higher frequency in ASLD and in HHH syndrome with elevation of transaminases and of gamma-GT in ASLD, and of alpha-fetoprotein in HHH syndrome. Also, consistent with a chronic hepatic dysfunction, ultrasound examination revealed more pronounced abnormalities in ASLD and in HHH syndrome, when compared to other UCDs. Our study highlights in a large UCDs patients' cohort that chronic liver disease is a common finding in UCDs, often with a distinct phenotype between different diseases. Furthers studies are needed to elucidate the specific involvement of different metabolic pathways in the pathogenesis of liver dysfunction in UCDs. This article is protected by copyright. All rights reserved.

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