Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency.

CASTANO G; SANYAL AJ; PURI P; FARIDODDIN MIRSHAHI; SOOKOIAN S; SCIAN R; PIROLA CJ

LIVER INTERNATIONAL

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2017 vol. 37 p. 611 - 619

1478-3223

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) develops from a complex process, which includes changes in the liver methylome. Betaine plays a pivotal role in the regulation of methylogenesis. We performed a two-stagecase?control study, which included patients with biopsy-proven NAFLD to explore circulating levels of betaine and its association with the histological spectrum. We also explored the association between a missense rs1805074, p.Ser646Pro variant in DMGDH (dimethylglycine dehydrogenase mitochondrial) and NAFLD severity (n=390).Results: In the discovery phase (n=48), betaine levels were associated with the disease severity (P=.0030), including liver inflammation (Spearman R:−0.51, P=.001), ballooning degeneration (R: −0.50, P=.01) and fibrosis (R: −0.54, P=.0008). Betaine levels were significantly decreased in nonalcoholic steatohepatitis (NASH) in comparison with nonalcoholic fatty liver (NAFL). Further replication (n=51) showed that betaine levels were associated with advanced NAFLD (P=.0085), and patients with NASH had a 1.26-folddecrease in betaine levels compared with those with NAFL. The rs1805074was significantly associated with the disease severity (P=.011).Conclusion: NAFLD severity is associated with a state of betaine-insufficiency.