Circulating soluble cytochrome c in liver disease as a marker of apoptosis

• Published in: Journal of internal medicine 2003-08, Vol.254 (2), p.168-175
• Main Authors: Ben‐Ari, Z., Schmilovotz‐Weiss, H., Belinki, A., Pappo, O., Sulkes, J., Neuman, M. G., Kaganovsky, E., Kfir, B., Tur‐Kaspa, R., Klein, T.
• Format: Article
• Language: English
• Subjects: Adult; apoptosis; Apoptosis - physiology; Bile - metabolism; Biological and medical sciences; Biomarkers - blood; cytochrome c; Cytochrome c Group - blood; Enzyme-Linked Immunosorbent Assay - methods; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatic Veins - metabolism; Hepatitis B - blood; Hepatitis B - drug therapy; Hepatitis B - physiopathology; Hepatitis C - blood; Hepatitis C - drug therapy; Hepatitis C - physiopathology; Humans; In Situ Nick-End Labeling - methods; liver disease; Liver Diseases - blood; Liver Diseases - drug therapy; Liver Diseases - physiopathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Other diseases. Semiology; Portal Vein - metabolism; Solubility; soluble
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1046/j.1365-2796.2003.01171.x

. Ben‐Ari Z, Schmilovotz‐Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur‐Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168–175. Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. Design. Laboratory research study with comparison group. Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. Subjects. A total of 108 patients with liver disease and 30 healthy controls. Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme‐linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick‐end‐labelling (TUNEL) assay. Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings. Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL−1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL−1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL−1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL−1) than the portal vein (mean 169.2 ± 143.3 ng mL−1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL−1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL−1) than treated patients (77.9 ± 35.8 ng mL−1; P = 0.001). Conclusions. Soluble cytochrome c levels are increas