Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection.
BACKGROUND
Chronic hepatitis C disease (CHC) follows an accelerated course in human immunodeficiency virus (HIV) coinfection. The reasons for this are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. We sought to compare the expression of Fas on hepatocytes and irreversible apoptosis of hepatocytes among patients with CHC with and without HCV/HIV coinfection.


METHODS
Fas-immunostained hepatocytes were semiquantified, and apoptotic hepatocytes were detected by staining caspase-cleaved cytokeratin 18 filaments and counted across the entire section of liver-biopsy specimens from HCV-infected patients with and without HCV/HIV coinfection.


RESULTS
One hundred thirty-four HCV/HIV-coinfected and 100 HCV-infected patients were included. HCV/HIV coinfection was associated with both diffuse distribution of Fas-stained hepatocytes (adjusted odds ratio [AOR], 7.4 [95% confidence interval {CI}, 3.8-14.4]) and with apoptotic hepatocyte counts greater than the median (AOR, 2.5 [95% CI, 1.5-4.5]). In HCV/HIV-coinfected patients, CD4+ cell nadir<200 cells/mL was associated with both Fas expression (AOR, 2.9 [95% CI, 1.3-6.8]) and hepatocyte apoptosis (AOR, 2.3 [95% CI, 1.1-4.9]).


CONCLUSIONS
HCV/HIV-coinfected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than do HCV-infected patients. However, low CD4+ cell nadirs in coinfected patients are associated with hepatocyte Fas expression and apoptosis.
Macias
Juan
J
Servicio de Medicina Interna, Hospital Universitario de Valme, Seville, Spain.
Japón
Miguel A
MA
Sáez
Carmen
C
Palacios
Rosa B
RB
Mira
José A
JA
García-García
José A
JA
Merchante
Nicolás
N
Vergara
Salvador
S
Lozano
Fernando
F
Gómez-Mateos
Jesús
J
Pineda
Juan A
JA
D000328:Adult; D017209:Apoptosis; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D002452:Cell Count; D003430:Cross-Sectional Studies; D005260:Female; D005355:Fibrosis / Q000473:pathology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019014:fas Receptor / Q000378:metabolism*
D019014:fas Receptor