Hedgehog pathway and pediatric nonalcoholic fatty liver disease

• DOI: 10.1002/hep.26230
• Publication Date: 2013-01-09T05:57:39Z
• Authors: Marzena Swiderska...; Ayako Suzuki; Cynthia D. Guy; Jeffrey B. Schwimmer; Manal F. Abdelmalek; Joel E. Lavine; Anna Mae Diehl
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Adolescent; Biopsy; Keratin-7; Age Factors; Kruppel-Like Transcription Factors; Nuclear Proteins; Actins; 3. Good health; Fatty Liver; Portal System; 03 medical and health sciences; Cross-Sectional Studies; Sex Factors; Liver; Non-alcoholic Fatty Liver Disease; Humans; Vimentin; Female; Hedgehog Proteins; Child; Signal Transduction

It is unclear why the histology of pediatric and adult nonalcoholic fatty liver disease (NAFLD) sometimes differs. In adults, severity portal inflammation fibrosis correlate with Hedgehog pathway activity. (Hh) signaling regulates organogenesis, but silent in livers until injury reinduces Hh ligand production. During adolescence, development completed children's normally lose cells that produce and/or respond to ligands. We postulated interferes this process by increasing production, theorized hepatic responses ligands might differ among children according age, gender, puberty status. Using unstained biopsy slides from 56 NAFLD, we performed immunohistochemistry assess activation correlated results clinical information obtained at biopsy. Fibrosis stage generally activity, as demonstrated numbers Hh-ligand-producing ( P < 0.0001) Hh-responsive (glioma-associated oncogene 2-positive [Gli2]) = 0.0013). The Gli2(+) also grade 0.0012). Two distinct zonal patterns Hh-ligand portal/periportal versus lobular, were observed. Higher production was associated male gender. Male gender prepuberty ductular proliferation 0.05), increased 0.017) fibrosis. Conclusion : (progenitor) compartment prepubescent exhibits high This may explain unique histologic features NAFLD because promotes fibroductular response.