Copyright
©The Author(s) 2017.
World J Virol. May 12, 2017; 6(2): 36-45
Published online May 12, 2017. doi: 10.5501/wjv.v6.i2.36
Published online May 12, 2017. doi: 10.5501/wjv.v6.i2.36
Table 1 Demographic, clinical and laboratory characteristics of the patients, according to the existence or not of significant liver fibrosis (≥ F2)
All patients (n = 158) | No fibrosis (n = 124) | Fibrosis (n = 34) | P value | |
Demography, epidemiology, anthropometry and habits | ||||
Age (yr) | 44.56 (43.20-45.92) | 44.50 (42.93-46.07) | 44.79 (41.96-47.63) | 0.9 |
Male, n (%) | 104 (65.8) | 78 (62.9) | 26 (76.5) | 0.14 |
Weight (kg) | 65.17 (62.88-67.46) | 64.46 (61.72-67.20) | 67.76 (64.03-71.50) | 0.24 |
Height (cm) | 164.4 (160.6-168.2) | 163.4 (158.5-168.2) | 168.2 (166.2-170.2) | 0.3 |
Body mass index (kg/m2) | 23.58 (23.10-24.05) | 23.48 (22.95-24.01) | 23.90 (22.75-25.0.6) | 0.5 |
Tobacco smokers, n (%) | 105 (66.5) | 78 (62.9) | 27 (79.4) | 0.07 |
Cannabis use, n (%) | 38 (24.1) | 22 (17.7) | 16 (47.1) | 0.0004 |
Alcohol intake, n (%)1 | 55 (35.0) | 43 (34.7) | 12 (36.4) | 0.9 |
IDU, n (%) | 58 (36.9) | 29 (23.6) | 29 (85.6) | < 0.0001 |
Men who have sex with men, n (%) | 28 (17.8) | 27 (22.0) | 1 (2.9) | 0.01 |
Heterosexual, n (%) | 67 (42.7) | 63 (51.2) | 4 (11.8) | < 0.0001 |
Transfusion, n (%) | 4 (2.5) | 4 (3.3) | 0 (0.0) | 0.3 |
HIV-related parameters | ||||
Current CD4 counts (cells/μL) | 581.5 (533.0-630.1) | 612.3 (555.8-668.8) | 469.6 (383.7-555.4) | 0.017 |
Nadir CD4 counts (cells/μL) | 201.8 (176.5-227.1) | 213.4 (183.4-243.4) | 159.7 (116.7-202.6) | 0.04 |
CD4 gain (cells/μL) | 379.7 (334.4-425.0) | 399.0 (345.4-452.6) | 309.9 (231.4-388.4) | 0.11 |
Undetectable HIV viral load, n (%) | 135 (85.4) | 109 (87.9) | 26 (76.5) | 0.09 |
HIV viral load (log copies/mL)2 | 2.996 (2.556-3.434) | 2.991 (2.407-3.575) | 3.006 (2.173-3.840) | 0.97 |
Years of HIV infection | 11.93 (11.12-12.73) | 11.31 (10.39-12.22) | 14.19 (12.70-15.68) | 0.003 |
Months on antiretroviral therapy | 114.3 (106.8-121.8) | 109.9 (101.3-118.5) | 130.2 (115.0-145.3) | 0.03 |
CDC clinical stage, n (%) | ||||
A | 84 (53.5) | 65 (52.8) | 19 (55.9) | 0.07 |
B | 23 (14.6) | 22 (17.9) | 1 (2.9) | |
C | 50 (31.8) | 36 (29.3) | 14 (41.2) | |
HCV-related parameters | ||||
HCV infection, n (%) | 57 (36.1) | 25 (20.2) | 32 (94.1) | < 0.0001 |
HCV viral load (log copies/mL) | 5.745 (5.504-5.985) | 5.524 (5.085-5.964) | 5.915 (5.649-6.181) | 0.11 |
Years of HCV infection | 22.46 (20.71-24.21) | 21.84 (18.96-24.72) | 22.94 (20.65-25.23) | 0.5 |
HCV genotype, n (%) | ||||
1 | 31 (54.4) | 14 (56.0) | 17 (53.1) | 0.7 |
2 | 2 (1.3) | 1 (4.0) | 1 (3.1) | |
3 | 15 (23.6) | 5 (20.0) | 10 (31.3) | |
4 | 9 (15.8) | 5 (20.0) | 4 (12.5) | |
Liver fibrosis parameters | ||||
Transient elastometry (kPa) | 7.53 (5.99-9.06) | 4.65 (4.45-4.85) | 18.02 (11.93-24.10) | < 0.0001 |
APRI | 0.633 (0.511-0.756) | 0.385 (0.346-0.423) | 1.541 (1.093-1.989) | < 0.0001 |
Forns | 4.412 (4.116-4.707) | 3.990 (3.734-4.246) | 5.949 (5.095-6.802) | 0.0001 |
FIB-4 | 1.475 (1.249-1.700) | 1.088 (0.985-1.191) | 2.884 (2.031-3.736) | 0.0002 |
YFPI3 | 0.584 (0.416-0.752) | 0.281 (0.222-0.340) | 0.821 (0.548-1.095) | 0.0004 |
Degree of liver fibrosis, n (%) | ||||
F0-F1 | 124 (78.5) | 124 (100) | 0 (0.0) | < 0.0001 |
F2 | 15 (9.5) | 0 (0.0) | 15 (44.1) | |
F3 | 10 (6.3) | 0 (0.0) | 10 (29.4) | |
F4 | 9 (5.7) | 0 (0.0) | 9 (26.5) | |
Laboratory parameters | ||||
Platelet count (/μL) | 222570 (211690-233450) | 236750 (225410-248090) | 169270 (147220-191330) | < 0.0001 |
Glucose (mg/dL) | 98.54 (95.25-101.84) | 98.00 (94.62-101.38) | 100.66 (90.92-110.39) | 0.5 |
Total cholesterol (mg/dL) | 195.01 (188.51-201.51) | 201.0 (193.8-208.3) | 173.0 (160.6-185.4) | 0.0004 |
HDL cholesterol (mg/dL) | 49.33 (46.88-51.78) | 49.42 (46.95-52.29) | 48.25 (42.02-54.48) | 0.7 |
LDL cholesterol (mg/dL) | 110.73 (104.68-116.77) | 116.97 (110.22-123.72) | 87.53 (76.91-98.16) | 0.0001 |
Triglycerides (mg/dL) | 199.79 (170.08-229.50) | 189.0 (157.5-220.5) | 241.7 (161.4-322.0) | 0.22 |
AST (UI/mL) | 40.89 (36.01-45.78) | 30.72 (28.30-33.13) | 78.00 (62.01-93.99) | < 0.0001 |
ALT (UI/mL) | 47.82 (40.54-55.09) | 36.91 (32.03-41.79) | 87.59 (62.16-113.02) | 0.0003 |
AST/ALT ratio | 1.011 (0.949-1.074) | 0.993 (0.927-1.059) | 1.079 (0.913-1.246) | 0.3 |
GGT (UI/mL) | 83.95 (66.61-101.29) | 59.73 (48.40-71.07) | 174.21 (110.61-237.81) | 0.001 |
Alkaline phosphatase (UI/mL) | 91.87 (85.09-98.65) | 90.72 (83.22-98.23) | 98.31 (81.46-115.17) | 0.4 |
MMP-2 (ng/mL) | 0.538 (0.442-0.654) | 0.482 (0.387-0.600) | 0.867 (0.579-1.300) | 0.02 |
MMP-3 (ng/mL) | 15.00 (13.24-17.01) | 14.36 (12.47-16.54) | 17.77 (14.45-23.49) | 0.18 |
MMP-8 (ng/mL) | 0.031 (0.023-0.041) | 0.029 (0.021-0.039) | 0.040 (0.020-0.078) | 0.4 |
MMP-9 (ng/mL) | 22.49 (18.81-26.90) | 23.19 (19.00-28.31) | 19.94 (13.01-30.58) | 0.5 |
MMP-10 (ng/mL) | 2.50 (1.66-3.75) | 2.163 (1.487-3.145) | 5.077 (0.938-27.469) | 0.12 |
TIMP-1 (ng/mL) | 50.56 (45.58-56.08) | 50.84 (45.43-56.88) | 49.49 (37.71-64.94) | 0.8 |
TIMP-2 (ng/mL) | 8.23 (7.16-9.46) | 7.62 (6.59-8.80) | 11.15 (7.55-16.45) | 0.03 |
TIMP-4 (ng/mL) | 0.040 (0.030-0.054) | 0.037 (0.027-0.051) | 0.054 (0.026-0.110) | 0. 3 |
Table 2 Genotypic frequencies of different single nucleotide polymorphisms according to liver fibrosis ≥ F2 and hepatitis C virus status
SNP | Genotype | No fibrosis n (%) | Fibrosis n (%) | P value | HIV mono-infected n (%) | HIV/HCV coinfected n (%) | P value |
MMP-1 -1607 1G/2G | 1G1G | 14 (20.3) | 4 (16.7) | 0.9 | 9 (16.1) | 9 (24.3) | 0.6 |
1G2G | 13 (18.8) | 5 (20.8) | 12 (21.4) | 6 (16.2) | |||
2G2G | 42 (60.9) | 15 (62.5) | 35 (62.5) | 22 (59.5) | |||
MMP-8 -799C/T | CC | 30 (27.0) | 6 (22.2) | 0.6 | 25 (26.3) | 11 (25.5) | 1 |
CT | 47 (42.4) | 10 (37.0) | 39 (41.1) | 18 (41.9) | |||
TT | 34 (30.6) | 11 (40.8) | 31 (32.6) | 14 (32.6) | |||
MMP-9 -1562 C/T | CC | 78 (81.2) | 28 (84.8) | 0.6 | 61 (83.6) | 45 (80.4) | 0.6 |
CT | 18 (18.8) | 5 (15.2) | 12 (16.4) | 11 (19.6) | |||
TT | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |||
MMP-13 -77A/G | AA | 89 (74.8) | 21 (61.8) | 0.14 | 70 (72.9) | 40 (70.2) | 0.7 |
AG | 30 (25.2) | 13 (38.2) | 26 (27.1) | 17 (29.8) | |||
GG | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |||
TNF-α -308 G/A | AA | 11 (11.3) | 4 (11.8) | 0.5 | 7 (9.5) | 8 (14.0) | 0.7 |
AG | 62 (63.9) | 18 (52.9) | 46 (62.1) | 34 (59.6) | |||
GG | 24 (24.7) | 12 (35.3) | 21 (28.4) | 15 (26.3) | |||
CCR5-Δ32 | wt/wt | 96 (80.0) | 30 (88.2) | 0.27 | 77 (79.4) | 49 (86.0) | 0.3 |
wt/Δ32 | 24 (20.0) | 4 (11.8) | 20 (20.6) | 8 (14.0) | |||
Δ32/Δ32 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Table 3 Liver fibrosis indexes according to the single nucleotide polymorphisms genotypes
SNP | Genotype | Transient elastometry | YFPI1 | APRI | Forns | FIB-4 |
MMP-1 -1607 1G/2G | 1G1G | 5.583 (4.600-6.567) | 0.346 (0.215-0.477) | 0.693 (0.192-1.195) | 3.719 (2.860-4.579) | 1.317 (0.723-1.911) |
1G2G | 5.911 (4.649-7.174) | 0.470 (0.250-0.691) | 0.488 (0.307-0.670) | 4.253 (3.430-5.077) | 1.092 (0.859-1.324) | |
2G2G | 8.781 (5.585-11.977) | 0.689 (0.378-1.001) | 0.675 (0.453-0.897) | 4.390 (3.914-4.867) | 1.479 (1.097-1.862) | |
P value | 0.3 | 0.3 | 0.7 | 0.4 | 0.5 | |
MMP-8 -799C/T | CC | 6.644 (3.736-9.553) | 0.633 (0.074-1.193) | 0.615 (0.411-0.819) | 4.510 (3.920-5.099) | 1.461 (1.058-1.864) |
CT | 5.628 (5.060-6.196) | 0.357 (0.275-0.439) | 0.453 (0.347-0.559) | 4.126 (3.701-4.551) | 1.145 (1.014-1.277) | |
TT | 7.729 (4.540-10.918) | 0.671 (0.376-0.965) | 0.768 (0.447-1.088) | 4.407 (3.825-4.989) | 1.603 (1.081-2.125) | |
P value | 0.4 | 0.19 | 0.1 | 0.5 | 0.15 | |
MMP-9 -1562 C/T | CC | 7.540 (5.810-9.269) | 0.527 (0.361-0.694) | 0.612 (0.475-0.749) | 4.370 (4.024-4.717) | 1.404 (1.163-1.645) |
CT | 11.178 (4.093-18.264) | 0.833 (0.229-1.437) | 0.867 (0.412-1.323) | 5.083 (4.024-6.142) | 2.043 (1.044-3.041) | |
TT | - | - | - | - | - | |
P value | 0.14 | 0.16 | 0.16 | 0.11 | 0.065 | |
MMP-13 -77A/G | AA | 7.217 (5.654-8.780) | 0.535 (0.358-0.712) | 0.623 (0.480-0.766) | 4.352 (3.993-4.711) | 1.462 (1.185-1.738) |
AG | 8.721 (4.646-12.798) | 0.700 (0.291-1.109) | 0.698 (0.426-0.970) | 4.588 (3.998-5.177) | 1.553 (1.109-1.998) | |
GG | - | - | - | - | - | |
P value | 0.4 | 0.4 | 0.6 | 0.5 | 0.7 | |
TNF-α -308 G/A | AA | 10.073 (1.300-18.849) | 0.656 (0.132-1.180) | 0.693 (0.135-1.250) | 4.331 (3.280-5.383) | 1.584 (0.693-2.475) |
AG | 8.086 (5.779-10.394) | 0.552 (0.336-0.767) | 0.675 (0.495-0.855) | 4.603 (4.174-5.033) | 1.575 (1.210-1.940) | |
GG | 7.514 (4.623-10.404) | 0.620 (0.228-1.012) | 0.701 (0.405-0.997) | 4.221 (3.513-4.929) | 1.466 (1.021-1.910) | |
P value | 0.7 | 0.9 | 0.99 | 0.6 | 0.9 | |
CCR5-Δ32 | wt/wt | 7.852 (5.998-9.707) | 0.590 (0.399-0.783) | 0.664 (0.525-0.803) | 4.439 (4.102-4.775) | 1.513 (1.264-1.762) |
wt/Δ32 | 6.521 (4.109-8.934) | 0.545 (0.232-0.858) | 0.539 (0.230-0.847) | 4.391 (3.684-5.098) | 1.335 (0.699-1.971) | |
Δ32/Δ32 | - | - | - | - | - | |
P value | 0.5 | 0.9 | 0.4 | 0.9 | 0.6 |
Table 4 Metalloproteases and their tissue inhibitors according to the single nucleotide polymorphisms genotypes
SNP | Genotype | MMP-2 | MMP-3 | MMP-8 | MMP-9 | MMP-10 | TIMP-1 | TIMP-2 | TIMP-4 |
MMP-1 -16071G/2G | 1G1G | 0.379 (0.195-0.736) | 16.69 (11.00-25.33) | 0.035 (0.013-0.095) | 19.93 (11.59-34.28) | 1.782 (0.350-9.071) | 41.73 (30.87-56.42) | 6.79 (4.52-10.21) | 0.031 (0.010-0.091) |
1G2G | 0.803 (0.409-1.575) | 19.87 (15.13-26.10) | 0.041 (0.012-0.134) | 22.35 (13.37-37.36) | 1.451 (0.417-5.047) | 54.07 (39.44-74.14) | 7.30 (4.49-11.87) | 0.047 (0.020-0.113) | |
2G2G | 0.609 (0.449-0.826) | 14.72 (11.57-18.73) | 0.027 (0.017-0.042) | 23.65 (17.07-32.76) | 3.345 (1.512-7.399) | 50.34 (42.16-60.10) | 8.39 (6.54-10.76) | 0.032 (0.019-0.053) | |
P value | 0.18 | 0.4 | 0.7 | 0.9 | 0.5 | 0.4 | 0.6 | 0.7 | |
MMP-8 799C/T | CC | 0.655 (0.473-0.908) | 15.96 (12.94-19.68) | 0.048 (0.025-0.090) | 29.93 (19.94-44.94) | 4.650 (1.354-15.97) | 61.60 (49.94-75.99) | 11.67 (8.59-15.85) | 0.041 (0.023-0.073) |
CT | 0.568 (0.409-0.787) | 13.05 (10.22-16.65) | 0.031 (0.018-0.054) | 21.30 (15.50-29.28) | 2.179 (1.201-3.953) | 47.17 (38.80-57.34) | 6.71 (5.50-8.18) | 0.035 (0.021-0.058) | |
TT | 0.432 (0.280-0.668) | 16.66 (13.35-20.81) | 0.020 (0.015-0.027) | 18.86 (14.03-25.37) | 1.623 (0.938-2.808) | 47.75 (40.75-55.94) | 8.12 (5.89-11.20) | 0.050 (0.030-0.084) | |
P value | 0.3 | 0.3 | 0.09 | 0.17 | 0.17 | 0.11 | 0.01 | 0.6 | |
MMP-9 1562 C/T | CC | 0.495 (0.385-0.637) | 15.42 (13.11-18.14) | 0.034 (0.024-0.049) | 22.39 (17.79-28.19) | 2.405 (1.462-3.957) | 52.23 (46.17-59.07) | 8.39 (7.18-9.80) | 0.037 (0.026-0.053) |
CT | 1.031 (0.853-1.246) | 18.15 (13.99-23.54) | 0.020 (0.008-0.047) | 22.97 (14.77-35.71) | 5.960 (0.666-53.34) | 46.55 (33.82-64.07) | 8.18 (4.40-15.21) | 0.058 (0.025-0.137) | |
TT | - | - | - | - | - | - | - | - | |
P value | 0.02 | 0.3 | 0.2 | 0.9 | 0.2 | 0.4 | 0.9 | 0.3 | |
MMP-13 77A/G | AA | 0.522 (0.419-0.650) | 15.62 (13.47-18.13) | 0.030 (0.022-0.041) | 23.06 (18.64-28.54) | 2.337 (1.380-3.957) | 53.30 (47.05-60.38) | 8.54 (7.21-10.12) | 0.050 (0.036-0.069) |
AG | 0.683 (0.458-1.017) | 14.37 (11.10-18.59) | 0.037 (0.019-0.071) | 22.96 (16.01-32.93) | 2.685 (1.215-5.931) | 48.10 (39.30-58.88) | 8.07 (6.09-10.68) | 0.031 (0.016-0.058) | |
GG | - | - | - | - | - | - | - | - | |
P value | 0.22 | 0.6 | 0.6 | 0.98 | 0.8 | 0.4 | 0.7 | 0.14 | |
TNF-α 308 G/A | AA | 0.730 (0.325-1.639) | 21.40 (14.72-31.13) | 0.039 (0.010-0.156) | 17.42 (8.16-37.21) | 0.804 (0.369-1.755) | 57.25 (37.28-87.92) | 13.14 (8.72-19.80) | 0.111 (0.054-0.227) |
AG | 0.558 (0.429-0.727) | 14.65 (11.96-17.95) | 0.031 (0.020-0.050) | 23.41 (17.78-30.83) | 4.460 (2.097-9.486) | 51.62 (43.92-60.66) | 8.39 (6.71-10.48) | 0.043 (0.028-0.064) | |
GG | 0.453 (0.281-0.732) | 16.54 (13.36-20.47) | 0.027 (0.018-0.040) | 23.62 (17.25-32.34) | 1.998 (0.879-4.542) | 46.63 (39.84-54.59) | 7.04 (5.36-9.26) | 0.023 (0.012-0.045) | |
P value | 0.4 | 0.24 | 0.8 | 0.7 | 0.065 | 0.6 | 0.1 | 0.02 | |
CCR5-Δ32 | wt/wt | 0.601 (0.484-0.747) | 15.75 (13.71-18.09) | 0.031 (0.022-0.043) | 21.55 (17.50-26.53) | 2.441 (1.482-4.020) | 50.72 (44.83-57.38) | 8.10 (6.95-9.45) | 0.041 (0.029-0.057) |
wt/Δ32 | 0.431 (0.286-0.652) | 13.64 (9.87-18.85)) | 0.032 (0.020-0.051) | 27.15 (18.55-39.73) | 2.662 (1.222-5.801) | 52.01 (42.66-63.42) | 9.44 (6.49-13.72) | 0.043 (0.021-0.088) | |
Δ32/Δ32 | - | - | - | - | - | - | - | - | |
P value | 0.15 | 0.4 | 0.9 | 0.3 | 0.9 | 0.9 | 0.4 | 0.9 |
Table 5 Correlations among metalloproteases, their tissue inhibitors and liver fibrosis parameters
MMP-3 | MMP-8 | MMP-9 | MMP-10 | TIMP-1 | TIMP-2 | TIMP-4 | TE | YFPI | APRI | Forns | FIB-4 | |
MMP-2 | 0.19 (0.04) | 0.21 (0.02) | 0.21 (0.02) | 0.20 (0.09) | 0.29 (0.002) | 0.29 (0.002) | 0.35 (0.0002) | 0.23 (0.016) | 0.30 (0.058) | 0.20 (0.03) | 0.19 (0.04) | 0.20 (0.03) |
MMP-3 | 0.29 (0.0006) | 0.30 (0.0006) | 0.15 (0.19) | 0.33 (0.0001) | 0.27 (0.002) | 0.38 (< 0.0001) | 0.09 (0.3) | 0.001 (0.99) | 0.16 (0.06) | 0.16 (0.06) | 0.10 (0.24) | |
MMP-8 | 0.69 (< 0.0001) | 0.25 (0.02) | 0.71 (< 0.0001) | 0.40 (< 0.0001) | 0.24 (0.005) | -0.02 (0.8) | -0.15 (0.3) | -0.01 (0.9) | 0.03 (0.8) | -0.03 (0.7) | ||
MMP-9 | 0.21 (0.06) | 0.71 (< 0.0001) | 0.16 (0.06) | 0.21 (0.01) | -0.21 (0.01) | -0.32 (0.02) | -0.17 (0.047) | -0.11 (0.2) | -0.20 (0.02) | |||
MMP-10 | 0.12 (0.3) | 0.22 (0.051) | 0.11 (0.3) | 0.01 (0.9) | -0.09 (0.7) | 0.12 (0.3) | -0.08 (0.5) | -0.03 (0.8) | ||||
TIMP-1 | 0.40 (< 0.0001) | 0.39 (< 0.0001) | 0.02 (0.8) | -0.04 (0.8) | -0.02 (0.8) | 0.07 (0.4) | 0.01 (0.9) | |||||
TIMP-2 | 0.33 (0.0001) | 0.28 (0.0009) | 0.25 (0.08) | 0.35 (< 0.0001) | 0.20 (0.018) | 0.36 (< 0.0001) | ||||||
TIMP-4 | 0.11 (0.2) | 0.03 (0.8) | 0.14 (0.12) | 0.06 (0.5) | 0.19 (0.03) | |||||||
TE | 0.94 (< 0.0001) | 0.75 (< 0.0001) | 0.59 (< 0.0001) | 0.82 (< 0.0001) | ||||||||
YFPI | 0.63 (< 0.0001) | 0.51 (0.0001) | 0.74 (< 0.0001) | |||||||||
APRI | 0.55 (< 0.0001) | 0.90 (< 0.0001) | ||||||||||
Forns | 0.67 (< 0.0001) |
Table 6 Independent predictors of different fibrosis indexes
TE | APRI | Forns | FIB-4 | YFPI | |
Higher MMP-2 levels | 0.001 | 0.0001 | 0.03 | 0.0009 | 0.004 |
Higher TIMP-2 levels | 0.016 | 0.0001 | 0.024 | 0.0002 | - |
Lower MMP-9 levels | 0.023 | 0.016 | - | 0.03 | 0.043 |
Lower current CD4 counts | - | 0.032 | 0.037 | 0.043 | - |
Older age | - | - | 0.004 | 0.05 | - |
% of the index accounted for by the model | 20.00% | 35.30% | 23.30% | 33.50% | 20.70% |
- Citation: Collazos J, Valle-Garay E, Suárez-Zarracina T, Montes AH, Cartón JA, Asensi V. Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunodeficiency virus-infected patients. World J Virol 2017; 6(2): 36-45
- URL: https://www.wjgnet.com/2220-3249/full/v6/i2/36.htm
- DOI: https://dx.doi.org/10.5501/wjv.v6.i2.36