P.042 Studies on the control of HBV infection in a mouse model of acute hepatitis B

2006 ◽  
Vol 36 ◽  
pp. S73
Author(s):  
M. Svorcova ◽  
A. Untergasser ◽  
U. Drebber ◽  
O. Utermoehlen ◽  
U. Protzer
2017 ◽  
Vol 11 (4) ◽  
Author(s):  
S. Rolland ◽  
L. Antonova ◽  
J. Powis ◽  
T. Murdoch ◽  
D. Wong ◽  
...  

Clinicians often assume that patients vaccinated for hepatitis B virus (HBV) have immunity. We report three cases of acute HBV infection in HBV-vaccinated HIV patients. These cases illustrate that patients at an elevated risk of HBV exposure presenting with acute hepatitis should be tested for HBV infection regardless of previous vaccination status.


1991 ◽  
Vol 174 (6) ◽  
pp. 1565-1570 ◽  
Author(s):  
A Penna ◽  
F V Chisari ◽  
A Bertoletti ◽  
G Missale ◽  
P Fowler ◽  
...  

The absence of readily manipulable experimental systems to study the cytotoxic T lymphocyte (CTL) response against hepatitis B virus (HBV) antigens has thus far precluded a definitive demonstration of the role played by this response in the pathogenesis of liver cell injury and viral clearance during HBV infection. To circumvent the problem that HBV infection of human cells in vitro for production of stimulator/target systems for CTL analysis is not feasible, a panel of 22 overlapping synthetic peptides covering the entire amino acid sequence of the HBV core (HBcAg) and e (HBeAg) antigens were used to induce and to analyze the HBV nucleocapsid-specific CTL response in nine patients with acute hepatitis B, six patients with chronic active hepatitis B, and eight normal controls. By using this approach, we have identified an HLA-A2-restricted CTL epitope, located within the NH2-terminal region of the HBV core molecule, which is shared with the e antigen and is readily recognized by peripheral blood mononuclear cells from patients with self-limited acute hepatitis B but less efficiently in chronic HBV infection. Our study provides the first direct evidence of HLA class I-restricted T cell cytotoxicity against HBV in humans. Furthermore, the different response in HBV-infected subjects who successfully clear the virus (acute patients) in comparison with patients who do not succeed (chronic patients) suggests a pathogenetic role for this CTL activity in the clearance of HBV infection.


2003 ◽  
Vol 38 ◽  
pp. 157-158
Author(s):  
K. Michitaka ◽  
N. Horiike ◽  
Y. Chen ◽  
H. Yatsuhashi ◽  
N. Kojima ◽  
...  

2014 ◽  
Vol 20 (3) ◽  
pp. 349-352 ◽  
Author(s):  
Margherita Macera ◽  
Nicolina Capoluongo ◽  
Michele Gambardella ◽  
Mario Starace ◽  
Carmine Minichini ◽  
...  

1991 ◽  
Vol 106 (2) ◽  
pp. 397-402 ◽  
Author(s):  
A. A. Papachristou ◽  
A. S. Dumas ◽  
V. C. Katsouyannopoulos

SUMMARYSerological markers and peak serum alanine aminotransferase (ALT) values of 140 in-patients with acute hepatitis, either type A (n= 90), or type B (n= 50) were prospectively assessed. In 23 out of the 90 patients with acute hepatitis A, evidence of previous experience with hepatitis B virus (HBV) was found, whereas 35 out of the 50 patients with acute hepatitis B had past contact with hepatitis A virus (HAV). The mean peak ALT values [S.D.] were significantly higher in hepatitis A patients with previous experience with HBV (1413 [704] i.u./l), when compared to those without such experience (842 [464] i.u./l, P < 0·001). Such a difference was not evident between acute hepatitis B patients, whether or not they had previous contact with HAV. We conclude that when acute hepatitis A is superimposed on past HBV infection an augmented transaminaemia, indicative of enhanced liver cell necrosis, takes place although a definite explanation is lacking. We suggest that individuals with markers of HBV infection should be early candidates for HAV immunization.


PEDIATRICS ◽  
1993 ◽  
Vol 91 (1) ◽  
pp. 150-152
Author(s):  
RENE ROMERO ◽  
RONALD E. KLEINMAN

Acute hepatitis B virus (HBV) infection in childhood is often subclinical. Fever, abdominal pain, anorexia, and jaundice are the most common findings in those 10% to 20% of children who are symptomatic.1 Rarely, urticarial rashes or arthralgias may precede these common symptoms and serum transaminase elevations.2 In this report, we describe the first case of isolated thrombocytopenia associated with acute HBV infection occurring in a child. The findings provide further supporting evidence for the ability of HBV to cause hematologic derangements. Since immune thrombocytopenic purpura (ITP) of childhood is a relatively common disorder, often following acute viral infections, isolated thrombocytopenia occurring in the setting of acute HBV infection can present diagnostic difficulties, with significant therapeutic implications.


2015 ◽  
Vol 89 (19) ◽  
pp. 10087-10096 ◽  
Author(s):  
Takuro Uchida ◽  
Nobuhiko Hiraga ◽  
Michio Imamura ◽  
Masataka Tsuge ◽  
Hiromi Abe ◽  
...  

ABSTRACTHepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are critical in eliminating infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by HBV-specific CTLs. After HBV inoculation in human hepatocyte-transplanted herpes simplex virus type-1 thymidine kinase-NOG mice, human peripheral blood mononuclear cells (PBMCs) were administered, and albumin, HBV DNA, alanine aminotransferase (ALT), and cytokine levels were analyzed. Histopathological and flow-cytometric analysis of infiltrating human immune cells were performed, and the efficacy of CTL-associated antigen-4 immunoglobulin (CTLA4Ig) against liver damage was evaluated. PBMC treatment resulted in massive hepatocyte damage with elevation of ALT, granzyme A, and gamma interferon and decrease in albumin and HBV DNA. The number of liver-infiltrating human lymphocytes and CD8-positive cells was significantly higher in HBV-infected mice. HBV-specific CTLs were detected by core and polymerase peptide-major histocompatibility complex-tetramer, and the population of regulatory T cells was significantly decreased in HBV-infected mice. Serum hepatitis B surface (HBs) antigen became negative, and HBs antibody appeared. CTLA4Ig treatment strongly inhibited infiltration of mononuclear cells. CTLA4Ig treatment will be used to treat patients who develop severe acute hepatitis B to prevent liver transplantation or lethality. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B.IMPORTANCEWithout liver transplantation, some HBV-infected patients will die from severe liver damage due to acute overreaction of the immune system. No effective treatment exists, due in part to the lack of a suitable animal model. An animal model is necessary to investigate the mechanism of hepatitis and to develop therapeutic strategies to prevent acute liver failure in HBV infection. We developed an animal model in which HBV-infected human hepatocytes are targeted by human HBV-specific CTLs. In this model, HBV-infected human hepatocytes were transplanted into severely immunodeficient NOG mice in order to reconstruct elements of the human immune system. Using this model, we found that CTL-associated antigen-4 immunoglobulin was able to suppress damage to HBV-infected hepatocytes, suggesting an approach to treatment. This animal model is useful for virological and immunological analysis of HBV infection and to develop new therapies for severe acute hepatitis B.


2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Femke Stelma ◽  
Sophie B Willemse ◽  
Robin Erken ◽  
Annikki de Niet ◽  
Marjan J Sinnige ◽  
...  

Abstract Background Acute hepatitis B virus infection in adults is generally self-limiting but may lead to chronicity in a minority of patients. Methods We included 9 patients with acute hepatitis B virus (HBV) infection and collected longitudinal follow-up samples. Natural killer (NK) cell characteristics were analyzed by flowcytometry. HBV-specific T-cell function was analyzed by in vitro stimulation with HBV peptide pools and intracellular cytokine staining. Results Median baseline HBV DNA load was 5.12 log IU/mL, and median ALT was 2652 U/mL. Of 9 patients, 8 cleared HBsAg within 6 months whereas 1 patient became chronically infected. Early time points after infection showed increased CD56bright NK cells and an increased proportion of cells expressing activation markers. Most of these had normalized at week 24, while the proportion of TRAIL-positive CD56bright NK cells remained high in the chronically infected patient. In patients who cleared HBV, functional HBV-specific CD8+ and CD4+ responses could be observed, whereas in the patient who developed chronic infection, only low HBV-specific T-cell responses were observed. Conclusions NK cells are activated early in the course of acute HBV infection. Broad and multispecific T-cell responses are observed in patients who clear acute HBV infection, but not in a patient who became chronically infected.


Sign in / Sign up

Export Citation Format

Share Document