Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects, which are rare and severe genetic liver diseases. To date there has been no report of the effects of this therapy in children reaching adulthood. The aim of the study was to evaluate the long-term effectiveness and safety of CA therapy. Fifteen patients with either 3β-hydroxy-Δ5-C27-steroid oxidoreductase (3β-HSD) (n = 13) or Δ4–3-oxosteroid 5β-reductase (Δ4–3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed prospectively. The median age at last follow-up and the median time of follow-up with treatment were 24.3 years (range: 15.3–37.2) and 21.4 years (range: 14.6–24.1), respectively. At last evaluation, physical examination findings and blood laboratory test results were normal in all patients. Liver sonograms were normal in most patients. Mean daily CA dose was 6.9 mg/kg of body weight. Mass spectrometry analysis of urine showed that excretion of the atypical metabolites remained low or traces in amount with CA therapy. Liver fibrosis scored in liver biopsies or assessed by elastography in 14 patients, after 10 to 24 years with CA therapy, showed a marked improvement with disappearance of cirrhosis (median score < F1; range: F0-F2). CA was well tolerated in all patients, including five women having 10 uneventful pregnancies during treatment. Oral CA therapy is a safe and effective long-term treatment of 3β-HSD and Δ4–3-oxo-R deficiencies and allows affected children to reach adulthood in good health condition without the need for a liver transplantation.

Background: Congenital portosystemic shunts (CPSS) are rare vascular anomalies resulting in communications between the portal venous system and the systemic venous circulation, affecting an estimated 30,000 to 50,000 live births. CPSS can present at any age as a multi-system disease of variable severity mimicking both common and rare pediatric conditions. Case presentations: Case A: A vascular malformation was identified in the liver of a 10-year-old girl with tall stature, advanced somatic maturation, insulin resistance with hyperinsulinemia, hyperandrogenemia and transient hematuria. Work-up also suggested elevated pulmonary pressures. Case B: A young girl with trisomy 8 mosaicism with a history of neonatal hypoglycemia, transient neonatal cholestasis and tall stature presented newly increased aminotransferase levels at 6 years of age. Case C: A 3-year-old boy with speech delay, tall stature and abdominal pain underwent abdominal ultrasound (US) showing multiple liver nodules, diagnosed as liver hemangiomas by hepatic magnetic resonance imaging (MRI). Management and outcome: After identification of a venous malformation on liver Doppler US, all three patients were referred to a specialized liver center for further work-up within 12 to 18 months from diagnosis. Angio-computed tomography (CT) scan confirmed the presence of either an intrahepatic or extrahepatic CPSS with multiples liver nodules. All three had a hyperintense signal in the globus pallidus on T1 weighted cerebral MRI. Right heart catheterization confirmed pulmonary hypertension in cases A and C. Shunts were closed either using an endovascular or surgical approach. Liver nodules were either surgically removed if there was a risk of malignant degeneration or closely monitored by serial imaging when benign. Conclusion: These cases illustrate most of the common chief complaints and manifestations of CPSS. Liver Doppler US is the key to diagnosis. Considering portosystemic shunts in the diagnostic work-up of a patient with unexplained endocrine, liver, gastro-intestinal, cardiovascular, hematological, renal or neurocognitive disorder is important as prompt referral to a specialized center may significantly impact patient outcome.