Cytochrome c is a possible new marker for fulminant hepatitis in humans

Background. Cytochrome c is known as a substance related to apoptosis. We investigated serum cytochrome c levels in patients with fulminant hepatitis (FH) compared with these levels in patients with acute or chronic liver diseases. Methods. Serum cytochrome c was measured by an electrochemiluminescence immunoassay (ECLIA) method. The numbers of patients were as follows: fulminant hepatitis (FH; n = 15), acute hepatitis (AH; n = 12), chronic hepatitis (CH; n = 30), chronic hepatitis with acute aggravation (CHA; n = 6), liver cirrhosis (LC; n = 30), hepatocellular carcinoma (HCC; n = 30), and healthy volunteers (controls; n = 9). Results. The serum cytochrome c level in FH was 10686 +/- 7787 pg/ml, with a significant difference (P < 0.01) compared to levels in the other groups. In the FH patients, the serum cytochrome c level was significantly correlated to serum mitochondria (m)-GOT, hepatocyte growth factor (HGF), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and alkaline phosphatase (ALP), and it was negatively correlated to serum alpha-fetoprotein (AFP), and total bilirubin (T.Bil.) The serum cytochrome c level seemed to parallel the severity of hepatic coma. Immunohistochemical study indicated TdT mediated dUTP nick end labeling (TUNEL)-positive cells in the livers of patients with FH. Conclusions. These results suggest that serum cytochrome c may be a possible new marker for acute liver failure.