Role of hepatic sonic hedgehog protein expression in the diagnosis of metabolic dysfunction-associated steatohepatitis

Figure 1 Changes in ballooned hepatocyte score and nonalcoholic fatty liver disease activity score after cytokeratin 8/18 and sonic hedgehog staining. MASLD: Metabolic dysfunction-associated steatotic liver disease; SHH: Sonic hedgehog; CK8/18: Cytokeratin 8/18; NAS: Nonalcoholic fatty liver disease activity score.

Figure 2 Hematoxylin and eosin, cytokeratin 8/18 and sonic hedgehog stained sections showing ballooned hepatocytes (arrows) in metabolic dysfunction-associated steatohepatitis (200 × magnification). A: Ballooned hepatocytes were enlarged with rarefied cytoplasm; B: Ballooned hepatocytes showed loss of cytokeratin 8/18 expression. Other nonballooned hepatocytes were diffuse positive for cytokeratin 8/18; C: Sonic hedgehog immunostaining highlighted ballooned hepatocytes. Other nonballooned hepatocytes were negative for sonic hedgehog.

Figure 3 Cytokeratin 8/18 and sonic hedgehog protein expression in normal hepatocytes and ballooned hepatocytes. Cytokeratin 8/18 protein is diffusely expressed in normal hepatocytes but absent in ballooned hepatocytes. Conversely, sonic hedgehog protein is absent in normal hepatocytes but present in ballooned hepatocytes. A: Ballooned hepatocytes showed loss of cytokeratin 8/18 expression; B: Sonic hedgehog immunostaining highlighted ballooned hepatocytes (arrows, 100 × magnification).

Figure 4 Sonic hedgehog expression correlates with the grade of hepatocyte ballooning. A-D: Photomicrographs of sonic hedgehog immunohistochemistry in patients with grade 0 (A), 1 (B), and 2 (C and D) ballooning show increased numbers of positive cells with increased ballooning grade (arrows, 200 × magnification). Sonic hedgehog expression was plotted relative to the grade of hepatocyte ballooning, as scored by the Nonalcoholic Steatohepatitis Clinical Research Network Pathology Committee.

Figure 5 Sonic hedgehog expression correlates with fibrosis stage in metabolic dysfunction-associated steatotic liver disease. A-E: Photomicrographs of sonic hedgehog immunohistochemistry in patients with S0 (A), S1 (B), S2 (C), S3 (D) and S4 (E) fibrosis show increased numbers of positive cells with increased fibrosis stage (arrows, 200 × magnification).

Figure 6 Sonic hedgehog protein expression was increased in metabolic dysfunction-associated steatohepatitis patients, which was correlated with the severity of hepatocellular ballooning, lobular inflammatory responses, and fibrotic progression. A-D: Sonic hedgehog protein showed increased expression in metabolic dysfunction-associated steatohepatitis patients (A), and with severity of hepatocellular ballooning (B), lobular inflammatory responses (C) and fibrotic progression in metabolic dysfunction-associated steatohepatitis patients (D). SHH: Sonic hedgehog; MASL: Metabolic dysfunction-associated steatotic liver; MASH: Metabolic dysfunction-associated steatohepatitis.