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Soluble TNF Receptor II Levels Are Elevated in HCV/HIV Co-infection and Are Associated with Advanced Liver Fibrosis Stage
Margaret Shuhart*, M Chung, D Paschal, M Wener, D Gretch, and C Morishima
Univ of Washington, Seattle, US
Background:
Tumor
necrosis factor-alpha (TNF-α) has been implicated in the pathogenesis of
both hepatitis C (HCV) and HIV infections. However, its role in HCV/HIV co-infection
is not known. Plasma levels of soluble TNF receptors (sTNFR) I and II are
thought to reflect TNF-α activity. We tested the hypotheses that sTNFR I
and sTNFR II levels are increased in HCV/HIV-co-infected subjects when compared
to HCV-mono-infected subjects, and are correlated with liver disease.
Methods:
Plasma levels
(pg/mL) were measured using Biosource Multiplex antibody bead kits for sTNFR I,
sTNFR II, TNF-a and the
Luminex xMAP detection system in subjects with HCV/HIV co-infection,
HCV mono-infection, and seronegative controls. Assay sensitivity for TNF-α
was 10 pg/mL and <15 pg/mL for sTNFR I and II. Only 13% of
samples had detectable levels of TNF-α and were not analyzed further. Remaining
analyses were performed using the average values of duplicate wells for sTNFR I
and II, using the 2-sample t-test,
Spearman rank correlation, and ordered logistic regression.
Results:
Soluble TNFR I and II were highly correlated (r = 0.55, p<0.0001). Soluble TNFR I was significantly higher in both
HCV/HIV and HCV groups when compared to seronegative controls, but not
different between the HCV/HIV and HCV groups (see the table). Soluble TNFR II
was significantly higher in the HCV/HIV group when compared to the HCV and
seronegative groups. Although soluble TNFR II was inversely related to the CD4 T-cell
count (p = 0.001), no association was
found with HIV viral load. A higher sTNFR I or sTNFR II level was correlated
with higher liver fibrosis stage (p =
0.038 and 0.001, respectively). However, only sTNFR II was independently associated
with liver disease stage when both sTNFR were included in the model (sTNFR II p = 0.004, sTNFR I p = 0.47).
Conclusions: Soluble TNFR levels are elevated in HCV/HIV co-infection,
but only sTNFR II levels are significantly increased in comparison with HCV
mono-infection. Moreover, only levels of sTNFR II are independently associated
with liver fibrosis stage. These findings suggest that sTNFR II levels are
specifically influenced by HIV infection, and may have an important effect on
HCV liver disease.
|
Group (n)
|
sTNFR I*
(mean ± SD)
|
p-value (vs
SN)
|
sTNFR II**
(mean ± SD)
|
P-value
(vs SN)
|
|
Seronegative
(14)
|
828±290
|
|
840±317
|
|
|
HCV (26)
|
1212±770
|
0.03
|
1443±882
|
0.004
|
|
HCV/HIV (26)
|
1157±326
|
0.003
|
1914±569
|
<0.0001
|
*HCV/HIV vs HCV, p = 0.7
**HCV/HIV vs HCV, p = 0.03
|
