20 Ihc demonstrated that numbers of Hh ligand-producing

c

20 Ihc demonstrated that numbers of Hh ligand-producing

cells, Gli2(+) Hh-responsive cells, myofibroblasts (αSMA-positive cells), and progenitors (Sox9- and AFP-positive cells) all decrease significantly as development progresses (Supporting Figs. 1, 2). These results support the concept that Hh pathway activity is normally silenced as the hepatic progenitor compartment shrinks to its adult size. SHh+ periportal nonballooned hepatocytes, SHh+ ballooned hepatocytes, Selleck Metformin Gli2+ portal tract cells, and K7+ cells are associated with gender and puberty (Table 2). Boys had a higher percentage of portal tracts with SHh+ periportal hepatocytes (P < 0.05), higher intensity of SHh+ periportal hepatocellular staining (P < 0.04), higher grade of K7+ cells (P < 0.005), and lower numbers of SHh+ ballooned hepatocytes (P < 0.04). These results indicate that the progenitor

response to fatty liver injury differs between boys and girls, with boys demonstrating more robust expansion of the portal/periportal progenitor compartment despite seemingly milder parenchymal injury (evidenced by fewer ballooned Selleckchem CH5424802 hepatocytes). Regardless of gender, children in prepuberty showed higher grades of K7+ positivity (P < 0.008), and tended to show higher grades of Gli2 positivity (P = 0.055). These findings are consistent with other evidence that children's livers harbor greater numbers of Hh-responsive progenitors than adult livers,14 and suggest that the “switch” from the childhood liver progenitor compartment to the adulthood liver progenitor compartment occurs during puberty. Prepubertal children also demonstrated lower numbers of SHh+ ballooned hepatocytes (P = 0.056). In fact, there was no case in prepuberty (n = 4)

which showed SHh+ ballooned hepatocytes, while 6 out of 11 cases in puberty or postpuberty showed SHh+ ballooned hepatocytes. 上海皓元 Although independent associations adjusting for gender and pubertal stages could not be assessed in this population due to the small sample size, these findings support the concept that young children efficiently mobilize Hh-responsive liver progenitors during fatty liver injury. In adults with NAFLD, ductular-appearing progenitor cells typically intermingle with fibroinflammatory cells along fibrous septae, and the intensity of this fibroductular reaction correlates with the severity of liver fibrosis.21 Therefore, we assessed associations of the patterns of Ihc with grades/stages of the routine histologic features (Table 3). Due to the limited sample size for this analysis, we combined historic grades/stages to create binary variables and compared the patterns of Ihc.

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