Researchers Track Improvements in Rare Pediatric Liver Disease Through Biomarker

In children, prolonged parenteral nutrition (PN) is associated with intestinal failure—associated liver disease (IFALD). In a recently published study of children with IFALD, researchers sought to examine the role of microRNA (MIR) 122, a biomarker for various liver diseases in adults and children.

Until now, MIR122 has not been explored in children with IFALD, a rare disease where cholestasis and periportal inflammation may be common. In severe cases, IFALD can progress to cirrhosis and irreversible liver damage. Risk factors for IFALD include prematurity, sepsis, and altered intestinal permeability.

Although serum conjugated hyperbilirubinemia indicates cholestasis, it does not provide information about inflammation, steatosis, or fibrosis. The gold standard for staging liver disease is a biopsy, but biopsies are expensive and invasive.

MIR 122 makes up >70% of hepatic miRNAs and predicts cholestasis, steatosis, and fibrosis in animals and humans. When liver cells are injured, they release miR-122 into the circulation. Researchers sought to probe changes in plasma miR-122, correlate miR-122 with serum liver function tests and enzymes, and investigate changes in whole blood transcripts including miR-122 targets in children with IFALD who received pure intravenous fish oil (FO) as a treatment for cholestasis.

The researchers had previously studied FO as a treatment for cholestasis in an earlier study. Their hypothesis in this prospective, observational study was that FO would decrease circulating miR-122, correlate with serum conjugated bilirubin (CB), and alter miR-122 pathways and targets involved in inflammation, oxidation stress, antioxidant protection, and lipid metabolism.

The investigators enrolled 14 children with IFALD who received intravenous FO (1 g/kg/d) and whose cholestasis resolved with FO. Plasma miR-122 was measured using reverse transcription-quantitative real-time PCR, and whole blood miR-122 targets were quantified using RNA sequencing.

The median age was 6 months (interquartile range [IQR]: 3—65 months).

RNA sequence data were available for 4 children. When compared with the start of FO, median miR-122 concentrations at 6 months of FO therapy decreased 1.0 (IQR: 1.0—1.0) compared with 0.04 (IQR: 0.01–0.6), P = .009.

At the start of FO, miR-122 correlated with CB (r = 0.56; P = .038). At about 3 months of FO therapy, miR-122 correlated with CB (r = 0.56; P = 0.045).

The presence of miR-122 in patients with IFALD “suggests that measuring levels of the molecule might someday be used to diagnose and monitor this and other liver diseases without the need for biopsies,” said Kara L. Calkins, MD, a neonatal-perinatal specialist at UCLA, in a statement.

Larger clinical trials will be needed to confirm results, the researchers said.

Reference

Calkins KL, Thamotharan S, Ghosh S, Dai Y, Devaskar SU. MicroRNA 122 reflects liver injury in children with intestinal failure—associated liver disease treated with intravenous fish oil [published online February 18, 2020]. J Nutr. doi: 10.1093/jn/nxaa001.