Hepatic peroxisome proliferator-activated receptor γ and α-mRNA expression in HCV-infected adults is decreased by HIV co-infection and is also affected by ethnicity

Shores, Nathan J.; Mendes-Corrêa, Maria Cássia; Maida, Ivana; Turner, JoLyn; High, Kevin P.; Babudieri, Sergio; Núãez, Marina

doi:10.6061/clinics/2015(12)05

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CLINICAL SCIENCE • Clinics 70 (12) • Dec 2015 • https://doi.org/10.6061/clinics/2015(12)05 copy

Hepatic peroxisome proliferator-activated receptor γ and α-mRNA expression in HCV-infected adults is decreased by HIV co-infection and is also affected by ethnicity

Authorship SCIMAGO INSTITUTIONS RANKINGS

OBJECTIVE:

To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression.

METHODS:

We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults.

RESULTS:

Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects.

CONCLUSION:

mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.

Nuclear Receptors; PPAR; Hepatitis C; HIV Infection; mRNA Expression; Liver Tissue

	HCV-Only	HCV & HIV	p-value
N	40	36	---
Age	47 (28-69)	49 (36-68)	0.4
Male sex	29 (72.5)	24 (67)	0.4
Weight	82 (53-130)	75 (51-121)	0.2
BMI	28 (18-36)	26 (17-37)	0.3
Race			0.003
White	29 (72.5)	12 (33)
Black	6 (15)	14 (39)
Mixed/Hispanic	4 (10)	10 (28)
Native American	1 (2.5)	0
Country			<0.0001
Brazil	9 (22.5)	21 (58)
Italy	12 (30)	0
USA	19 (47.5)	15 (42)
HCV genotype			0.5
1	34 (94)	30 (91)
2	0	1 (3)
3	1 (3)	2 (6)
4	1 (3)	0
HCV RNA, log₁₀	5.82 (3.16-7.00)	6.17 (5.1-7.59)	0.04
ALT	100 (15-351)	62 (15-213)	0.02
AST	93 (20-1,018)	47 (16-103)	0.1
METAVIR fibrosis score			0.6
F0	4 (10)	6 (17)
F1	14 (350	14 (39)
F2	14 (35)	13 (36)
F3	5 (12.5)	2 (5)
F4	3 (7.5)	1 (3)
METAVIR inflammation score			0.3
A0	1 (2.5)	5 (14)
A1	17 (42.5)	15 (42)
A2	17 (42.5)	11 (30)
A3	5 (12.5)	5 (14)
Steatosis			0.4
Unknown	9 (22.5)	7 (19.5)
None	18 (45)	19 (53)
Mild	6 (15)	8 (22)
Moderate	4 (10)	1 (3)
Severe	3 (7.5)	1 (3)
CD4	---	540 (260-1049)	---
CD4%	---	27 (15-44)	---
HIV RNA	---	177 (<50-1450)	---
HAART
No	---	3 (8)	---
AZT	---	11 (68)	---
Dideoxynucleosides	---	2 (6)	---
PI	---	20 (59)	---
DM	---	6 (17)	0.2
Current alcohol use	---	9 (26)	0.4
Cholesterol levels	169 (113-231)	159 (91-226)	0.4
Triglyceride levels	83 (37-2091	149 (55-428)	0.003

	Univariate analyses Beta (95% CI); p-value	Multivariate Analysis Beta (95% CI); p-value
HIV+	-0.175 ((-0.057) - (-0.007)); 0.1	-0.225 ((-0.064) - (0.001)); p=0.06
Age	-0.086(-0.003 - 0.001); 0.4
Male sex	-0.209 ((-0.067) - (0.003); 0.07
BMI	0.067 (-0.003 - 0.005); 0.6
Black race	0.272 (0.008 - 0.079); 0.02	0.225 (-0.008 - 0.080); 0.1
United States	0.333 (0.016 - 0.078); 0.003	0.197((-0.010) - 0.065)); 0.1
HCV-1 genotype	0.216 ((-0.006) - (0.126); 0.07
HCV RNA	-0.144 (0.000 - 0.000); 0.3
METAVIR F3/F4	-0.112((-0.068) - (0.024); 0.3
METAVIR A2/A3	0.063 ((-0.024) - (0.041)); 0.6
Steatosis (yes vs. no)	-0.105 ((-0.057) - (0.024)); 0.4
DM	0.054 ((-0.04) - (0.063)); 0.6
Alcohol use	0.120 ((-0.017) - (0.055)); 0.3
CD4 counts	-0.235 (0.000 - 0.000); 0.3
HIV RNA levels	0.112 (0.000 - 0.000); 0.7
HAART regimen
AZT	-0.337 ((-0.029) - (0.000)); 0.051
Dideoxynucleosides	0.029 ((-0.090) - (0.016)); 0.9
PI	-0.038 ((-0.052) - 0.042); 0.8

	Univariate analyses Beta (95% CI); p-value	Multivariate Analysis Beta (95% CI); p-value
HIV+	-0.330 ((-0.005) - (-0.001)); 0.004	-0.392 ((-0.005) - (-0.001)); p=.001
Age	-0.142 (0.000 - 0.000); 0.2
Male sex	-0.046 ((-0.003) - (0.002); 0.7
BMI	0.085 (0.000 - 0.000); 0.9
Black race	0.25 (0.000 - 0.005); 0.03	0.266 (0.000 - 0.005); 0.04
United States	0.333 (0.001 - 0.005); 0.003	0.166 ((-0.001) - 0.004)); 0.2
HCV-1 genotype	0.133((-0.002) - (0.006); 0.3
HCV RNA	-0.109 (0.000 - 0.000); 0.4
METAVIR F3/F4	-0.08 ((-0.004) - (0.002); 0.5
METAVIR A2/A3	0.128 ((-0.001) - (0.003)); 0.9
Steatosis (yes vs. no)	-0.051 ((-0.003) - (0.002)); 0.7
Diabetes	0.056 ((-0.002) - (0.004)); 0.6
Alcohol use	0.065 ((-0.002) - (0.003)); 0.5
CD4 counts	-0.07 (0.000 - 0.000); 0.7
HIV RNA levels	-0.017 (0.000 - 0.000); 0.9
HAART regimen
AZT	-0.297 ((-0.005) - (0.000)); 0.09
Dideoxynucleosides	-0.022 ((-0.006) - (0.005)); 0.9
PI	-0.06 ((-0.003) - 0.002); 0.7

Faculdade de Medicina / USP Rua Dr Ovídio Pires de Campos, 225 - 6 and., 05403-010 São Paulo SP - Brazil, Tel.: (55 11) 2661-6235 - São Paulo - SP - Brazil
E-mail: clinics@hc.fm.usp.br

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[1] Nunez M and High K conceived and designed the study. Shores N, Mendes-Correa MC, Maida I, Turner J and Babudieri S were responsible for the data acquisition. Nunez M, Shores N, High K, Turner J, Mendes-Correa MC and Maida I were responsible for the data analysis and interpretation. Nunez M, Shores N and Turner J were responsible for the manuscript drafting. Nunez M was responsible for the statistical analysis. Turner J was responsible for the technical and material support. Nunez M supervised the study. All authors have accepted the content of the manuscript.