Alpha-fetoprotein: A biomarker for the recruitment of progenitor cells in the liver in patients with acute liver injury or failure.
OBJECTIVE
The optimal conditions for hepatocyte proliferation should be clarified in an attempt to improve the impaired liver regeneration observed in patients with acute liver failure (ALF). In order to evaluate the significance of the serum α-fetoprotein (AFP). level and prothrombin time international normalized ratio (PT-INR) as possible biomarkers of the proliferation of liver stem/progenitor cells (LPC) and mature hepatocytes (MH), respectively, we focused on donors of living donor liver transplantation (LDLT) and patients with acute liver injury (ALI), including ALF.


METHODS
Seventy-three patients with ALI/ALF and 11 donors for LDLT were evaluated. LPC induction was histologically evaluated using cytokeratin (CK)-7 staining in 45 ALI/ALF patients.


RESULTS
The AFP level was not apparently elevated during the observation period in any of the LDLT donors, whereas the serum AFP levels were substantially increased in the patients with ALI/ALF and significantly correlated with the number of CK-7 positive LPC in the liver, except for very severe damaged liver. All patients exhibiting an early peak in the AFP level prior to PT-INR elevation died.


CONCLUSIONS
The serum AFP level may reflect the induction of LPC in ALI/ALF patients. The substantial and persistent induction of LPC until sufficient regeneration of MH may be needed for a recovery from ALF. We herein demonstrate that the serum AFP level may be a serum marker of LPC in patients with ALI/ALF. A comparison of the serial changes in the AFP levels and PT-INR in our study patients showed impaired proliferation of LPC and delayed recovery of MH in the patients who died.
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Keisuke
K
Kakisaka
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Kojiro
K
Kataoka
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Mio
M
Onodera
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Akiko
A
Suzuki
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Kei
K
Endo
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Yoshinori
Y
Tatemichi
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Hidekatsu
H
Kuroda
Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan.
Kazuyuki
K
Ishida
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Yasuhiro
Y
Takikawa
donor; hepatic progenitor cell; liver progenitor cell; liver tissue damage