A critical link exists between neonatal cholestasis in children with Alpha-1-antitrypsin deficiency (AATD) and an increased risk of early-onset severe liver disease, particularly impacting males, a study featured in the latest issue of 'Hepatology Communications’ elucidated.

Patients diagnosed with AATD and neonatal cholestasis face a heightened likelihood of progressing to severe liver disease at an early age, extending into childhood. The research, led by Jeffrey Teckman and team aimed to unravel the natural history and disease modifiers of AATD, a prevalent genetic liver condition causing hepatitis and cirrhosis in children and adults.

Since 2004, the Childhood Liver Disease Research Network (ChiLDReN) has been conducting studies comprising of neonates with AATD. The study examined two participant groups: those with neonatal cholestasis before a specific diagnosis (n=46) and a separate group of participants who progressed to liver transplant (n=119). Examining the clinical courses of two specific participant subgroups, the study found a notable male predominance in neonatal cholestasis cases (65% men). Additionally, an association between elevated neonatal gamma-glutamyl transpeptidase and more severe disease was recognized, along with a higher-than-expected rate (41%) of neonatal cholestasis progressing to portal hypertension at a median age of 5 months.

Participants, both with and without preceding neonatal cholestasis, were identified as being at risk of progression to liver transplant. Remarkably, those progressing to liver transplant after neonatal cholestasis were considerably younger at the time of transplant compared to those without neonatal cholestasis (4.1 versus 7.8 years; overall range 0.3 to 17 years). The study also highlighted the negative effect of neonatal cholestasis on the parameters of growth.

Coagulopathy (also known as bleeding disorder) and varices were common before the transplant, but bleeding in the gastrointestinal tract was not observed. Hence, children with AATD deficiency are at risk of neonatal cholestasis. This condition is associated with a higher likelihood of developing severe liver disease at an earlier age, particularly in males.