Aim: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.
Conclusion: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.
Aim
The prognosis of acute‐on‐chronic liver failure (ACLF) is extremely poor in comparison to acute liver failure (ALF). We aimed to establish methods for the early diagnosis of ACLF and its severity to identify the patients with a poor prognosis.
Methods
The laboratory data at admission of 30 ACLF and 46 ALF patients were compared. Three established prognosis prediction models (Model for End‐Stage Liver Disease [MELD]; MELD modified by serum sodium concentration, [MELD‐Na]; and the Japan hepatic encephalopathy prediction model [J‐HEPM]) were assessed using area under the receiver–operator curve (AUROC) values.
Results
No significant difference was found in the laboratory data of the two patient groups. J‐HEPM was able to predict the outcome of the ACLF subjects (AUROC = 0.93).
Conclusion
Although ACLF could not be differentially diagnosed from ALF at admission from the laboratory data alone, the J‐HEPM effectively predicted the prognosis of liver failure in patients with ACLF. These findings indicate that ACLF patients with high J‐HEPM scores require earlier and more intensive care than ALF patients.
We propose the appropriate timing to start high-dose corticosteroid therapy in patients with ALI/ALF; 40% of JHEPM probability, 1.53 of PT-INR, and 52% of PT because these values were theoretically discriminated at 98% coverage to the patients with coma. Because the study contained selection bias, the appropriate timing for therapy should be confirmed in a future prospective study.
Guest Editor's Introduction: This paper was originally presented by Z. Yamazaki at the first congress of the International Society for Artificial Organs on August 26, 1977. It was printed in Artificial Organs Vol. 2 (supp) 273–276, 1978, and reprinted here with permission. This is the first paper describing clinical application of a membrane plasma separator as a hepatic assist device. This plasma separator was a hollow fiber device developed by Asahi Medical, Inc., Japan. Mr. K. Kataoka, vice president of Asahi Medical, Inc. was responsible for the development of this plasma separator module. Dr. N. Inoue is the internist responsible for these patients. Thirteen patients with acute liver failure were treated by this apheresis system. Seven out of thirteen patients recovered; however, only three of them survived.
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