Changes in Peripheral CD4+CD25 high Regulatory T Cells in the Acute-on-Chronic Liver Failure Patients with Plasma Exchan

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Changes in Peripheral CD4+CD25high Regulatory T Cells in the Acute-on-Chronic Liver Failure Patients with Plasma Exchange Treatment Wei-lin Mao,1 Yu-Feng Lou,1,3 Bo Ye,1 Sha Lin,1 Yue-mei Chen,2 and Yu Chen1,2

Abstract—The prevalence of CD4+CD25high regulatory T cells (Tregs) in patients with acute-onchronic liver failure (AoCLF) who received plasma exchange (PE) and/or medical treatment was investigated. One hundred five patients with AoCLF in two groups (PE plus routine-care, n=48 and routine-care, n=57) were enrolled in our study. In the PE group, there were 27 survivors (27/48) while, in the routine-care group, there were 18 survivors (18/57), both after 30 days treatment. Twenty-three healthy donors were used as the control group. Tregs were determined by flow cytometry serially. In the survivors, Tregs frequency were lower compared with the normal controls on admission and showed an up and down tendency; moreover, this frequency turned to the level as that in healthy subjects and was faster in the PE compared with the medical group while, among the nonsurvivors, Tregs stayed at a high level throughout the examination period. Importantly, an increased quantity of Tregs was associated with high mortality and reduced survival time of AoCLF patients. These data suggest that Tregs play a role in determining the patient’s fate toward either a favorable or unfavorable clinical course of disease, and PE may represent a reliable hepatic support device for AoCLF. KEY WORDS: regulatory T cells; acute-on-chronic liver failure; plasma exchange.

liver function. It can result from any type of liver disorder including viral hepatitis, cirrhosis, and liver damage from alcohol abuse or drugs. Acute-on-chronic liver failure (AoCLF) has been defined as acute deterioration of liver function in patients with previously well-compensated chronic liver disease over a period of 2–4 weeks, usually precipitated by gastrointestinal bleeding, infection, binge drinking, or surgery and is associated with progressive jaundice, hepatic encephalopathy, and/or hepatorenal syndrome and signs of multi-organ dysfunction [3]. AoCLF has been shown to carry poor prognosis, with an in-hospital mortality rate of over 70% if liver transplantation is not available [4]. It is now recognized that HBV was not directly cytopathic; host cellular immune responses play a pivotal role in HBV-related liver disease [5]. In recent years, much attention has been focused on the CD4+CD25+ regulatory T cell (Tregs) and its role in

INTRODUCTION Chronic hepatitis B virus (HBV) infection is a wellestablished cause of liver-related morbidity and mortality and represents a major global public health problem. It causes acute and chronic infections of the liver and is responsible for 1.2 million deaths annually [1]. Some patients develop abnormal liver functions or even liver failure during the lengthy course of chronic HBV infection [2]. Liver failure is characterized by severe deterioration in

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Department of Laboratory Medicine, First Affiliated Hospital, Zhejiang Universit