title: Changes in cellular proliferation and plasma products are associated with liver failure.
abstract: OBJECTIVE
  To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis.
  
  
  METHODS
  Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced self-limited AH and ALF. Thus, we worked with five groups: Hepatitis A virus (HAV)-induced self-limited acute hepatitis (HAV-AH), HAV-induced ALF (HAV-ALF), non-viral-induced self-limited acute hepatitis (non-viral AH), non-viral-induced acute liver failure (non-viral ALF), and healthy subjects (HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.
  
  
  RESULTS
  The levels of mitochondrial DNA (mtDNA) and the cytokines investigated [interleukin (IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology (P< 0.05). High plasma mtDNA and IL-10 were the best markers associated with ALF [mtDNA: OR = 320.5 (95%CI: 14.42-7123.33),P< 0.0001; and IL-10: OR = 18.8 (95%CI: 1.38-257.94),P= 0.028] and death [mtDNA: OR = 12.1 (95%CI: 2.57-57.07),P= 0.002; and IL-10: OR = 8.01 (95%CI: 1.26-50.97),P= 0.027]. In the cellular proliferation assay, NKbright, NKT and regulatory T cells (TReg) predominated in virus-specific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature.
  
  
  CONCLUSIONS
  mtDNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Juliana Gil
authors.initials: JG
authors.lastname: Melgaço
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Frederico Marianetti
authors.initials: FM
authors.lastname: Soriani
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Pedro Henrique Ferreira
authors.initials: PH
authors.lastname: Sucupira
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Leonardo Assaf
authors.initials: LA
authors.lastname: Pinheiro
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Yasmine Rangel
authors.initials: YR
authors.lastname: Vieira
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Jaqueline Mendes
authors.initials: JM
authors.lastname: de Oliveira
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Lia Laura
authors.initials: LL
authors.lastname: Lewis-Ximenez
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Cristina Carvalho Vianna
authors.initials: CC
authors.lastname: Araújo
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Lúcio Filgueiras
authors.initials: LF
authors.lastname: Pacheco-Moreira
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Gustavo Batista
authors.initials: GB
authors.lastname: Menezes
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Oswaldo Gonçalves
authors.initials: OG
authors.lastname: Cruz
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Claudia Lamarca
authors.initials: CL
authors.lastname: Vitral
authors.affiliation: Juliana Gil Melgaço, Leonardo Assaf Pinheiro, Claudia Lamarca Vitral, Departamento de Microbiologia e Parasitologia, Universidade Federal Fluminense, Niterói 20550-013, Brazil.
authors.forename: Marcelo Alves
authors.initials: MA
authors.lastname: Pinto
keywords: Acute liver failure; Cellular immune response; Cytokines; Hepatitis A virus; Mitochondrial DNA