Liver Involvement in Children with Alpha-1 Antitrypsin Deficiency: A Multicenter Study

Abstract

Alpha-1 antitrypsin deficiency (A1ATD) in one of the most common genetic causes of liver disease in children. We aimed to analyze the clinical characteristics and outcomes of patients with A1ATD. Methods: This study included patients with A1ATD from five pediatric hepatology units. Demographics, clinical findings, genetics, and outcome of the patients were recorded (n=25). Results: Eight patients (32.0%) had homozygous PiZZ genotype while 17 (68.0%) had heterozygous genotype. Patients with PiZZ genotype had lower alpha-1 antitrypsin levels than patients with PiMZ genotype (37.6±7.7 mg/dL vs. 66.5±22.7 mg/dL, p=0.0001). Patients with PiZZ genotype were diagnosed earlier than patients with PiMZ genotype, but this was not significant (13±6.8 months vs. 23.7±30.1 months, p=0.192). Follow-up revealed the death of one patient (12.5%) with a homozygous mutation, and revealed that one patient had child A cirrhosis, five patients (62.5%) had chronic hepatitis, and one patient (12.5%) was asymptomatic. Nine of the 17 patients with a heterozygous mutation had chronic hepatitis (52.9%), two (11.7%) had child A cirrhosis, and six (35.2%) were asymptomatic. Overall, 18 (72%) of the 25 children had liver pathology in the long-term. Conclusion: Although prevalence is rare, patients with liver disorders should be checked for alpha-1 antitrypsin levels. Moreover, long-term follow-up is essential because most patients have a liver pathology.

Disease Status at Diagnosis in Danish Children with α1‐antitrypsin Deficiency

“…Compared with the Danish pediatric reference range of S-AAT (1.0-1.7 g/L) (11), the homozygotes were severely deficient of S-AAT while the heterozygotes were moderately deficient. Similarly, French and Turkish studies have reported mean and median S-AAT concentrations of 0.4 g/L ± 0.1 SD (31), 0.37 g/L ± 0.77 SD (25), and 0.35g/L (IQR: 0.23-0.77) (36) in homozygotes and 0.6 g/L ± 0.1 SD in heterozygotes (31). This suggests that an S-AAT value <0.5 g/L is a good indicator of ZZ-homozygosity, and it underlines the importance of genetic testing of children with S-AAT concentrations <1 g/L.…”

Pediatric and Adult Liver Disease in Alpha-1 Antitrypsin Deficiency

“…In children the heterozygous Pi*MZ genotype does not seem to be sufficient to develop a significant liver disease on its own (Figure 2). Transient neonatal cholestasis, mildly elevated liver tests and hepatomegaly may be seen in children, hence phenotyping and/or genotyping should be considered when the AAT level is below 1.1 g/L [20] [38]. On the other hand, carriage of one Pi*Z allele can probably act as a modifier of a simultaneously present pediatric chronic liver diseases.…”

“…Transient neonatal cholestasis, mildly elevated liver tests, and hepatomegaly may be seen in children; hence, phenotyping and/or genotyping should be considered when the AAT level is below 1.1 g/L. 20 38 On the other hand, carriage of one Pi*Z allele can probably act as a modifier of a simultaneously present pediatric chronic liver diseases. For example, patients with biliary atresia and a non-MM genotype were shown to need a liver transplantation earlier.…”

Colestasis neonatal: revisión narrativa del grupo de trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica

“…Dentro del seguimiento, debe buscarse en forma dirigida el hepatocarcinoma, aunque su frecuencia es baja en la edad pediátrica. 18,19 Colestasis intrahepática familiar progresiva La identificación del gen involucrado (ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, MYO5B) ha permitido realizar un tratamiento y seguimiento individual de estos pacientes. Los pacientes con CIFP1 (ATP8B1) y CIFP2 (ABCB11) pueden presentar colestasis, prurito y retraso pondoestatural con distintos grados de severidad desde las primeras semanas de vida.…”