Hepatic stellate cells are involved in the pathogenesis of acute-on-chronic liver failure (ACLF).

ACLF is a condition with varied acute and chronic underlying etiologies and high mortality. Hepatic stellate cells (HSCs) are known to play an important role in hepatic fibrogenesis. Experimental data suggest that HSCs also display characteristics of hepatic stem/progenitor cells (HPCs). We investigated the number of activated HSC and their relationship to HPCs in ACLF in comparison to acute and chronic stages of other liver diseases. Immunohistochemical analysis of the number of activated HSCs and HPCs was performed in liver biopsies of 70 cases of ACLF and in the biopsies of patients with cirrhosis (45), acute hepatitis (25), chronic hepatitis (25), and normal live-related liver transplantation (LDLT) donor biopsies (15). The number of α-SMA-positive HSCs was assessed both quantitatively and semi-quantitatively. Keratin-19 (K19)-positive HPCs were estimated semi-quantitatively, and we looked for correlations between numbers of HSCs and HPCs. We found significantly more α-SMA activated HSCs/1,000 hepatocytes in ACLF biopsies (231 ± 91) than in biopsies of patients with acute hepatitis (147 ± 77), cirrhosis (73 ± 35), chronic hepatitis (66 ± 30), and normal LDLT donor biopsies (25 ± 10), respectively (p < 0.0001). A significant correlation between the presence of HPCs and ACLF versus other etiologies of liver disease was found (p < 0.001). There was a significant correlation between the numbers of HPCs and of activated HSCs (p < 0.001). ACLF is associated with more significant HSC activation than in acute hepatitis and other chronic liver diseases. There is a significant relationship between the presence of HSCs and that of HPCs, indicating a possible dynamic role of HSCs in liver regeneration and pathobiology of ACLF.