Late Increase of Peripheral CD34+ Cells Number during Acute Liver Failure Recovery.

Human Hematopoietic Stem Cells (HSC) of bone marrow origin are reported to transdifferentiate into various cell types, including cells of hepatic lineage, and to be involved in hepatic repopulation. As it has been previously reported in the course of myocardial infarction, we hypothesized that CD34+ cells would appear early in severe acute liver failure and could predict a favourable outcome. Methods: We quantified circulating CD34+ cells in peripheral blood of 146 patients without and with severe hepatic failure (HF) defined by factor V <50%: 20 acute hepatitis with HF, 26 acute alcoholic hepatitis with HF, 22 major right hepatectomy (6/23 developped HF) and 78 controls (31 healthy subjects, 23 cirrhosis, 24 cirrhosis with chronic HF). CD34+ cells were quantified by flow cytometry, according to ISHAGE guidelines in both one and dual platform approaches. Phenotypic and functional analyses were performed in selected cases. In case of acute HF, quantification was done every day until correction of liver function. One patient underwent liver transplantation. The number of circulating CD34+ cells was correlated with factor V level. Results were presented using median and range. Results : At inclusion, the numbers of CD34+ cells /mm3 were similar in different groups (healthy controls = 1.0 [0.1– 4.0]; cirrhosis = 0.9 [0.1–5.1]; cirrhosis with chronic HF = 1.0 [0.1–3.7]; alcoholic hepatitis with HF = 1.2 [0.1–6.0]; liver resection 24H after surgery = 0.8 [0.2–3.2]; acute hepatitis with HF = 0.7 [0.2–3.1]. For patients with acute hepatitis with HF, the number of CD34+ increased over time, from 0.7 [0.2–3.1] to 1.8 [0.5–9.6] at the 4th day after admission and was significantly (p <10–3) correlated with correction of factor V. There was no correlation between the number of CD34+ and the time between admission and onset of the disease. There was no significant increase over time in the hepatectomy group nor in the alcoholic hepatitis group. CD34+ cells detected during acute hepatitis regeneration presented an immature phenotype and coexpressed CD33, CD90, CD133, CD117, CD135 (FLT3-R), CD38, HLA-DR and not V-Cadherin. Clonogenic progenitor cell assays did not reveal specific features and correlation between number of CD34 and BFU-E colonies were in favour of their hematopoietic potentiality. Conclusion: By contrast with data reported in acute myocardial infarction in which early mobilisation of CD34+ cells was observed, we found that the increase of circulating CD34+ HSC is a late event occurring at the time of the recovery of liver function in acute severe hepatic failure. The hematopoietic potentiality of mobilized CD34+ cells suggests that they do not play a major role in liver repopulation in fulminant acute hepatitis.