Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection.
OBJECTIVE
To test the hypothesis that antigen-specific interferon (IFN)gamma responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV).


METHODS
Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy.


METHODS
We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFNgamma and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning.


RESULTS
There were significant negative correlations between inflammatory scores and IFNgamma production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFNgamma production in response to NS5 and summed HCV proteins. Higher IFNgamma production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFNgamma responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFNgamma response to Candida.


CONCLUSIONS
In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFNgamma responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation.
Graham
Camilla S
CS
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA. cgraham@bidmc.harvard.edu
Wells
Annalee
A
Liu
Tun
T
Sherman
Kenneth E
KE
Peters
Marion
M
Chung
Raymond T
RT
Bhan
Atul K
AK
Andersen
Janet
J
Koziel
Margaret James
MJ
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002175:Candida / Q000276:immunology; D005260:Female; D005355:Fibrosis; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000494:pharmacology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019562:Viral Load
D019380:Anti-HIV Agents; D018936:Hepatitis C Antigens; D016753:Interleukin-10; D007371:Interferon-gamma