Onset of heart failure determines the hepatic cell death pattern

Acute and chronic heart failure (HF) may affect the liver, but the underlying mechanisms that lead to progressive liver damage are poorly understood. The hepatic cytokeratin-18 (CK18) epitopes M65 and M30 have been reported to distinguish between overall (necrotic) and apoptotic cell death, respectively. We aimed to evaluate the predominant hepatic cell death pattern in acute vs. chronic heart failure and examined if these assays predict the course of the disease. In a prospective study comprising 21 patients with acute HF (AHF) and 18 patients with chronic HF (CHF) serum levels of M65 and M30 were assessed. Compared with CHF, M65 levels were significantly increased in patients with AHF (CHF: 1,283 ± 591.6U/l vs. AHF: 20,912 ± 15,132U/l, p < 0.001). In addition, M30 levels were significantly increased in AHF (CHF: 642.2 ± 177.4U/l vs. AHF: 3,844 ± 5,293U/l, p < 0.05), but the M30/M65 ratio was significantly higher in CHF (CHF: 0.54 ± 0.15 vs. AHF: 0.20 ± 0.19, p < 0.001), indicating a greater contribution of apoptotic cell death in CHF. AHF patients with higher M30 values had a worse prognosis. The ratio of CK18 M30/M65 is a potential marker to discriminate AHF from CHF induced LF and M30 might be a prognostic marker for survival in AHF induced liver injury.