N Hadzic et al. J Pediatr 2022; 250: 67-74. High Prevalence of Hemophagocytic Lymphohistiocytosis in Acute Liver Failure of Infancy In this retrospective study of pediatric acute liver failure (PALF, n=78) in children <24 months of age: Thirty of the 78 children had the HLH phenotype and underwent genetic assessment, which demonstrated positive findings in 19 (63.3%), including 9 (30%) with biallelic primary HLH mutations and 10 (33.3%) with heterozygous mutations and/or polymorphisms. The mortality in this group was 33% (n=10). The authors conclude that targeted genetic analysis (ie perforin, SIAP, XIAP, and GRA) or whole exome sequencing should become a standard part of PALF workup.

Related blog posts:

• Bookmark This Article on Pediatric Acute Liver Failure
• The MH Score: Separating primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome
• Algorithm for Neonatal Acute Liver Failure
• Growth in Children at Risk for Celiac Disease & Emapalumab for Hemophagocytic Lymphohistiocytosis
• Don’t forget HLH
• Diagnosing hemophagocytic lymphohistiocytosis (HLH)

BM Kamath et al. J Pediaatr 2023; 252: 68-75. Open Access! Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life. Twenty of the 27 patients (74%), all with moderate-to-severe pruritus at enrollment, achieved an Itch-Reported Outcome (Observer) treatment response at week 48. “The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL.”

Related blog posts:

• NASPGHAN Alagille Syndrome Webinar
• Intracranial Hypertension & Papilledema with Alagille Syndrome
• Explaining Differences in Disease Severity for Alagille Syndrome
• Good Review of Cholestatic Liver Diseases
• IQ and Pediatric Chronic Liver Disease
• Aspen Webinar 2021 Part 8 -Neonatal Cholestasis

D Sharma et al. Hepatology 2022; 76: 1845-1861. Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity This articles reviews inborn errors of immunity (IEI) and their liver manifestations. This includes the following:

• T-cell/B-cell deficiency: SCID, CD40 ligand deficiency, DOCK8 deficiency, IL-21R deficiency, and Activated P13K delta syndrome
• Antibody deficiency: CVID, X-linked aggamoglobulinemia
• Phagocytic disorders: CGD
• Primary Immune Regulatory Disorders: STAT1 GOF, STAT3 GOF, IPEX, APECED
• Others: Wiskott-Aldrich syndrome, Immunodeficiency-centromeric instability-facial anomalies syndrome, Hepatic veno-occlusive disease with immunodeficiency, STAT3-deficient hyper IgE syndrome

In patients with IEIs with liver abnormalities, one needs to consider infectious etiologies (eg. HAV, HBV, HCV, HEV, CMV, EBV, HSV, cryptosporidium, liver abscess), autoimmune disorders (eg. AIH), drug-induced liver disease, and sclerosing cholangitis

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