Alpha-1-Antitrypsin Deficiency Presenting as Neonatal Cholestasis: Predictors of Outcome and Effect of Ursodeoxycholic Acid

Silva, Ermelinda Santos; Silva, Helena Moreira; Melo, Cláudia; Rocha, Henrique

doi:10.4172/2167-0889.1000185

Cited by 3 publications

(2 citation statements)

References 28 publications

(53 reference statements)

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“…Patients with biliary atresia were submitted to Kasai porto-enterostomy (PE), performed by a stable and skilled surgical team after January 2000 ( 24 ). Patients with A1ATD born after 1994 were treated by ursodeoxycholic acid (UDCA), 15–20 mg/kg/day, bid ( 25 ). Metabolic diseases were treated with special diets and specific drugs, according to the state of art, which included OLT in some patients ( 26 , 27 ).…”

Section: Methodsmentioning

confidence: 99%

Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients From a Portuguese Tertiary Center

et al. 2020

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Introduction: In the last two decades there have been advances in the diagnosis and management of neonatal cholestasis, which may have changed its epidemiology, diagnostic accuracy, outcomes, and survival. Our goal was to characterize these changes over time in our setting. Methods: Retrospective cohort study in a tertiary center, enrolling patients born between January 1985 and October 2019. The cohort was divided into two periods, before (A; n = 67) and after (B; n = 87) the year 2000; and in two groups, according to patient's outcome (favorable, unfavorable). Overall survival and survival with and without orthotopic liver transplant (OLT) were evaluated in the two periods (A and B) and in different subgroups of underlying entities. Results: We found that the age of cholestasis recognition decreased significantly from period A to period B [median 43 days and 22 days, respectively, (p < 0.001)]; the changes in epidemiology were relevant, with a significant decrease in alpha-1-antitrypsin deficiency (p < 0.001) and an increase in transient cholestasis (p = 0.004). A next-generation sequencing (NGS) panel available since mid-2017 was applied to 13 patients with contributory results in 7, but, so far, only in 2 patients led to conclusive diagnosis of underlying entities. The number of cases of idiopathic cholestasis did not vary significantly. Over time there was no significant change in the outcome (p = 0.116). Overall survival and survival without OLT had no significant improvement during the period of observation (in periods A and B, 86 vs. 88%, and 85 vs. 87%, respectively). However, in period B, with OLT we achieved the goal of 100% of survival rate. Conclusions: Our data suggest that transient cholestasis became a very important subset of neonatal cholestasis, requiring specific guidance. The NGS panels can provide Santos Silva et al. Neonatal Cholestasis Over Time important inputs on disease diagnosis but, if applied without strict criteria and expertise, they can open a Pandora's box due to misinterpretation. Despite all the advances in accurate diagnosis and timely management-including early recognition of cholestasis-the improvement in patient outcomes and survival were still not significant. Keywords: neonatal cholestasis, transient cholestasis, neonatal cholestasis epidemiology, cholestasis risk factors, neonatal cholestasis survival, next generation sequencing panel NGS panel evolution Mid-2017 (54 genes) Since the end of 2019 (95 genes) Genes ABCB11,

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Section: Methodsmentioning

confidence: 99%

Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients From a Portuguese Tertiary Center

et al. 2020

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“…These findings collectively advocate for a proactive discussion regarding the early initiation of UDCA therapy in every patient diagnosed with AATD. While there is a valid argument for commencing treatment when liver disease progresses, there is also a compelling rationale for considering an early start to enhance the likelihood of a favourable disease course [ 24 ]. Supporting this recommendation, Lykavieris et al [ 25 ] reported significant improvements in clinical status and liver test results among patients undergoing UDCA therapy.…”

Section: Discussionmentioning

confidence: 99%

Alpha-1-Antitrypsin Deficiency in Children—Unmet Needs Concerning the Liver Manifestation

Lemke,

Weigert,

Bagci

et al. 2024

Children

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Objectives: This study aimed to analyse the clinical course of 45 children with severe alpha-1-antitrypsin deficiency (AATD) registered in our clinic to detect possible predictors of poor outcomes. Methods: The clinical and biological data of 45 patients with homozygous or compound heterozygous AATD were analysed. The data were collected retrospectively going back to 2005 and prospectively from May 2020 until October 2021. It was based on questionnaires, laboratory values, sonography, and biopsy findings. Liver disease was classified into four grades depending on the grade of liver disease: mild or no liver disease, moderate disease, severe disease, and liver transplantation. Results: Thirty-nine patients (86.7%) had a Pi*ZZ and five (11.1%) a Pi*SZ genotype. One patient showed a new, not-yet-described compound heterozygous genotype (Pi*Z + Asp95Asn). A total of 66.7% of the cohort showed mild or no liver disease, 20% moderate, and 13.3% severe. AATD was diagnosed in most cases because of liver abnormalities, such as the elevation of transaminases (42.2%). A total of 29.4% of the patients with neonatal icterus prolongatus developed severe liver disease, and 25.7% were born small for their gestational age (SGA). Diseases of the atopic type were reported in 47.4% of the cases. Conclusions: The presence of neonatal icterus prolongatus in the first weeks of life was significantly more likely in severe courses of liver disease (r = 0.371, p = 0.012). A tendency toward atopic comorbidity in AAT-deficient children needs to be further evaluated.

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Update Alpha-1-Antitrypsin-Mangel

Katzer

Briem-Richter

Weigert

et al. 2022

Monatsschr Kinderheilkd

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ZusammenfassungDer Alpha-1-Antitrypsin-Mangel (AATM) ist mit einer Prävalenz bis zu 1:2000 eine der häufigsten monogenetischen Ursachen für eine Lebertransplantation im Kindesalter. Pulmonal manifestiert sich der AATM erst im Erwachsenenalter. Er wird oft zu spät oder überhaupt nicht diagnostiziert. Die initiale Diagnostik ist mit einer Serumspiegelbestimmung einfach und günstig durchführbar. Bei Werten unter 1,1 g/l sollte eine Genotypisierung erfolgen, die im Alpha-1-Antitrypsin-Zentrum Marburg kostenfrei angeboten wird. Aufgrund des sehr heterogenen Verlaufs sollte die weiterführende Betreuung von Patienten mit AATM jedoch Spezialisten mit ausreichender Erfahrung vorbehalten bleiben. Hierfür eignen sich insbesondere die pädiatrischen Alpha-1-Center. Einen hohen Stellenwert haben die Aufklärung sowie die Aufrechterhaltung einer guten Compliance mit regelmäßigen ärztlichen Verlaufskontrollen, um eine Progredienz der Lebererkrankung zu erfassen. Neben Anamnese und körperlicher Untersuchung sind regelmäßige Blutentnahmen und Ultraschalluntersuchungen (inkl. Leberelastographie) notwendig. Therapeutisch stehen neben einer kurativen Lebertransplantation derzeit lediglich supportive Therapien zur Wahl. Sollte eine Lebertransplantation indiziert sein, ist das Langzeit-Outcome erfreulicherweise sehr gut.

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Alpha-1-Antitrypsin Deficiency Presenting as Neonatal Cholestasis: Predictors of Outcome and Effect of Ursodeoxycholic Acid

Cited by 3 publications

References 28 publications

Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients From a Portuguese Tertiary Center

Neonatal Cholestasis Over Time: Changes in Epidemiology and Outcome in a Cohort of 154 Patients From a Portuguese Tertiary Center

Alpha-1-Antitrypsin Deficiency in Children—Unmet Needs Concerning the Liver Manifestation

Update Alpha-1-Antitrypsin-Mangel

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