Long-term parenteral nutrition (PN) has considerably improved the management of intestinal failure (IF) in children and adults, particularly those with short bowel syndrome; however, it carries a significant risk of hepatotoxicity, specifically, intestinal failure-associated liver disease (IFALD), also known as PN-associated liver disease. This review provides an update on the latest understanding of IFALD pathogenesis, emerging therapies, and ongoing challenges in the management of this complication. A number of factors are associated with the development of IFALD. PN lipid emulsions, phytosterol exposure, bacterial dysbiosis, an altered gut–liver axis, and episodes of sepsis disrupt bile acid homeostasis and promote liver inflammation in the active phase of IFALD, favoring the development of PN-associated cholestasis (PNAC) and the more chronic form of steatohepatitis with fibrosis. Based on the identification of pathophysiological pathways, potential therapies are being studied in preclinical and clinical trials, including lipid emulsion modifications; targeted therapies such as Farnesoid X receptor (FXR) and liver receptor homolog 1 (LRH-1) agonists, tumor necrosis factor inhibitors, glucagon-like peptide-2 analogs; microbiome modulation; and supplementation with choline and antioxidants. In conclusion, the pathogenesis of IFALD is complex, and PN dependence and liver injury remain challenging, particularly in patients with IF who cannot advance to enteral nutrition and be weaned off PN.

Background: The advent of highly effective modulator therapies (HEMT), namely elexacaftor, tezacaftor, and ivacaftor (ETI), has resulted in substantial improvements in lung function, growth, and quality of life for people with cystic fibrosis (PwCF). However, the understanding of the impact of ETI on gastrointestinal (GI) disease burden is evolving. This study aims to describe and compare the prevalence of GI manifestations, prescribed GI medications, and GI procedures between 2 time periods, pre-ETI and post-ETI approval, in children with CF (CwCF) and adolescents with CF. Methods: This is a retrospective cohort study utilizing TriNetX, a multicenter database. The study includes patients between 6 to 21 years old with ICD-10 diagnostic codes for CF and a prescription for pancreatic enzyme replacement therapy (PERT) to match disease severity. We included 4 years before, and 4 years after the release of the ETI combination therapy. Results: When comparing CwCF taking PERT, on or off ETI, the prevalence of diagnostic codes for chronic pancreatitis, constipation, unspecified noninfective gastroenteritis, and colitis significantly decreased after ETI use (all P < 0.0001). The prevalence of other luminal disorders, liver disorders, and acute pancreatitis did not differ between the 2 groups. The prevalence of prescribed medications, including mucolytics, vitamins, PPI, and antidiarrheal, was similar for both groups except for a reduction in prescribed laxatives ( P -value = 0.0001). The prevalence of GI procedures was also similar in both groups. Conclusions: The reduction in constipation and noninfective gastroenteritis and colitis is important as GI symptoms are linked to the quality of life of CwCF. There remains a great clinical need to evaluate the effects of ETI on GI disorders, especially as the age of initial use of this therapy decreases and the duration of use increases.

Concurrent pediatric autoimmune pancreatitis (AIP) and autoimmune hepatitis (AIH) are rarely reported, and no established pediatric‐specific guidelines are available to guide the diagnosis and management of these conditions in children. While AIP and AIH share an underlying autoimmune mechanism of injury, marked by chronic inflammatory changes such as fibrosis, sclerosis, and infiltration of mononuclear cells like plasma cells and lymphocytes, their concurrent occurrence is infrequent, as they remain distinct clinical entities. In this case report, we present a case of concurrent AIH and AIP with treatment challenges secondary to underlying sickle cell disease (SCD) in an 11‐year‐old female. Herein, we discuss not only the diagnostic challenges faced when determining the cause of cholestasis in a patient with SCD but also the therapeutic strategies adopted throughout the care of this patient.