Resolution of Severe Hepatosteatosis in a Cystic Fibrosis Patient with Multifactorial Choline Deficiency: A Case Report.

In cystic fibrosis (CF), 85% to 90% of patients develop exocrine pancreatic insufficiency. Despite enzyme substitution, low pancreatic phospholipase A2 (sPLaseA2-IB) activity causes fecal loss of bile phosphatidylcholine and choline deficiency. We report on a female patient who has CF and progressive hepatosteatosis from 4.5 y onward. At 22.3 y, the liver comprised 27% fat (2385 mL volume) and transaminases were strongly increased. Plasma choline was 1.9 mu mol/L (normal: 8-12 mol/L). Supplementation with 3 x 1g/d choline chloride decreased liver fat and volume (3 mo: 8.2%; 1912 mL) and normalized transaminases. Plasma choline increased to only 5.6 mu mol/L upon supplementation, with high trimethylamine oxide levels (12-35 mu mol/L; normal: 3 +/- 1 mol/L) proving intestinal microbial choline degradation. The patient was homozygous for rs12325817, a frequent single-nucleotide polymorphism in the PEMT gene, associated with severe hepatosteatosis in response to choline deficiency. Resolution of steatosis required 2 y (4.5% fat). Discontinuation/resumption of choline supplementation resulted in rapid relapse resolution of steatosis, increased transaminases, and abdominal pain. (C) 2021 Elsevier Inc. All rights reserved.