Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

Table 1 Baseline characteristics of all patients treated with direct-acting antivirals n (%)

	All patients (n = 1068)	SVR12 not achieved (n = 138)	SVR12 achieved (n = 930)	P-value
Age (mean ± SE, yr)	61.8 ± 0.2	60.7 ± 0.5	62.0 ± 0.2	0.02
Sex
Male	97.5 (1041)	12.8 (133)	87.2 (908)	0.78
Female	2.5 (27)	18.500 (5)	81.50 (22)
Race/ethnicity
White	37.5 (400)	11.00 (44)	89.0 (356)	0.14
African American	37.5 (401)	14.70 (59)	85.3 (342)
Hispanic	15.1 (161)	16.80 (27)	83.2 (134)
Asian	0.70 (7)	14.30 (1)	85.700 (6)
Other	9.3 (99)	7.10 (7)	92.90 (92)
Fib4 < 3.25	64.6 (690)	9.1 (63)	90.9 (627)	< 0.01
Fib4 ≥ 3.25	35.4 (378)	19.80 (75)	80.2 (303)
Treatment naïve	79.5 (849)	16.4 (102)	83.6 (747)	0.09
Treatment experienced	20.5 (219)	16.40 (36)	83.6 (183)
HCV genotype
HCV genotype 1a	58.0 (619)	12.10 (75)	87.9 (544)	< 0.01
HCV genotype 1b	25.9 (277)	10.10 (28)	89.9 (249)
HCV genotype 2	7.9 (84)	21.40 (18)	78.60 (66)
HCV genotype 3	6.9 (74)	23.00 (17)	77.00 (57)
HCV genotype 4	1.2 (13)	0.00 (0)	100.0 (13)
HCV genotype 6	0.10 (1)	0.00 (0)	100.0 (1)
Treatment
PrOD	4.5 (48)	8.30 (4)	91.70 (44)	0.01
PrOD/RBV	17.6 (188)	14.40 (27)	85.6 (161)
Sofosbuvir/Ledipasvir	34.4 (367)	6.3 (23)	93.7 (344)
Sofosbuvir/Ledipasvir/RBV	13.4 (143)	13.30 (19)	86.7 (124)
Sofosbuvir/RBV	9.8 (105)	23.80 (25)	76.20 (80)
Sofosbuvir/Simeprevir	17.5 (187)	19.80 (37)	80.2 (150)
Other regimens	2.9 (30)	10.0 (3)	90.00 (27)
No HIV	96.7 (1033)	13.1 (135)	86.9 (898)	0.44
HIV	3.3 (35)	8.60 (3)	91.40 (32)
Duration of treatment
8 wk	19.9 (213)	6.6 (14)	93.4 (199)	< 0.01
12 wk	73.1 (781)	13.4 (105)	86.6 (676)
16 wk	2.8 (30)	40.00 (12)	60.00 (18)
24 wk	4.1 (44)	15.90 (7)	84.10 (37)
BMI < 30	66.5 (710)	12.50 (89)	87.5 (621)	0.60
BMI > 30	33.5 (358)	13.70 (49)	86.3 (309)
No HTN	43.7 (467)	13.30 (62)	86.7 (405)	0.76
HTN	56.3 (601)	12.60 (76)	87.5 (525)
No T2DM	85.6 (914)	12.4 (113)	87.6 (801)	0.15
T2DM	14.4 (154)	16.20 (25)	83.8 (129)
No HLD	58.1 (620)	14.50 (90)	85.5 (530)	0.70
HLD	41.9 (448)	10.70 (48)	89.3 (400)
No metabolic syndrome	87.1 (930)	13.0 (121)	87.0 (809)	0.84
Metabolic syndrome	12.9 (138)	12.30 (17)	87.7 (121)

PrODL: Ombitasvir/Paritaprevir/Ritonavir/Dasabuvir; Fib4: Fibrosis 4 score; RBV: Ribavirin; BMI: Body mass index; HTN: Hypertension; T2DM: Type 2 diabetes mellitus; HLD: Hyperlipidemia; SVR: Sustained virologic response; HCV: Hepatitis C virus.

Table 2 Baseline characteristics of patients with hepatitis C virus and type 2 diabetes mellitus

	All patients (n = 106)	SVR12 not achieved (n = 8)	SVR12 achieved (n = 98)	P-value
Age (mean ± SD, yr)	63.2 ± 0.5	59.6 ± 1.4	63.5 ± 0.5	0.04
Sex
Male	99.1 (105)	7.60 (8)	92.40 (97)	0.74
Female	0.90 (1)	0.00 (0)	100.0 (1)
Race/ethnicity
White	27.40 (29)	6.90 (2)	93.20 (27)	0.15
African American	36.80 (39)	5.10 (2)	94.90 (37)
Hispanic	25.50 (27)	11.1 (3)	88.90 (24)
Asian	1.90 (2)	50.0 (1)	50.00 (1)
Other	8.50 (9)	0.00 (0)	100.0 (9)
Cirrhosis
Yes	53.80 (57)	8.80 (5)	91.20 (52)	0.61
No	46.20 (49)	6.10 (3)	93.90 (46)
CTP class
CTP A	82.50 (47)	6.40 (3)	93.60 (44)	0.21
CTP B	14.00 (8)	25.0 (2)	75.0 (6)
CTP C	3.50 (2)	0.00 (0)	100.0 (2)
Treatment status
Naive	67.90 (72)	5.60 (4)	94.40 (68)	0.26
Experienced	32.10 (34)	11.8 (4)	88.20 (30)
HCV genotype
Genotype 1a	56.60 (60)	10.0 (6)	90.00 (54)	0.67
Genotype 1b	22.60 (24)	4.20 (1)	95.80 (23)
Genotype 2	12.30 (13)	0.00 (0)	100.0 (13)
Genotype 3	7.60 (8)	12.5 (1)	87.50 (7)
Genotype 4	0.90 (1)	0.00 (0)	100.0 (1)
Treatment regimen
Sofosbuvir/Simeprevir	39.60 (42)	7.10 (3)	92.90 (39)	0.96
Sofosbuvir/Ribavirin	17.00 (18)	5.60 (1)	94.40 (17)
PrOD	18.90 (20)	10.0 (2)	90.00 (18)
Sofosbuvir/Ledipasvir	24.50 (26)	7.70 (2)	92.30 (24)
Body mass index
Normal	15.10 (16)	6.20 (1)	93.80 (15)	0.78
Overweight	41.50 (44)	9.10 (4)	90.90 (40)
Obese	28.30 (30)	6.70 (2)	93.30 (28)
Severely obese	10.40 (12)	8.30 (1)	91.70 (11)
Very severely obese	4.70 (4)	0.00 (0)	100.0 (4)
Co-HIV infection	2.80 (3)	100.0 (3)	0.0 (0)	0.62
HTN	89.60 (95)	8.40 (8)	91.60 (87)	0.32
HLD	74.50 (79)	6.30 (5)	93.70 (74)	0.42
Metabolic syndrome	80.20 (85)	7.10 (6)	92.90 (79)	0.71

HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HTN: Hypertension; HLD: Hyperlipidemia; PrOD: Ombitasvir/Paritaprevir/Ritonavir/ Dasabuvir; SVR: Sustained virologic response; CTP: Child-Turcotte-Pugh.

Table 3 Mean hemoglobin A1c before and after hepatitis C virus treatment by hepatitis C virus genotype and sustained virologic response 12-wk status

Genotype	Before DAA	SE	After DAA	SE	P-value
Mean HbA1c of patients who did achieve SVR12
1a	7.5	0.19	6.68	0.14	0.001
1b	7.3	0.22	6.59	0.21	0.03
2	7.09	0.35	6.29	0.21	0.06
3	7.12	0.37	6.10	0.39	0.08
4	5.5	NA	5.30	NA	NA
Overall	7.35	0.13	6.55	0.11	< 0.01
Mean HbA1c of patients who did not achieve SVR12
1a	8.98	1.14	8.95	1.41	0.98
1b	6.4	NA	6.50	NA	NA
2	No observations
3	8.5	NA	8.70	NA	NA
4	No observations
Overall	8.6	0.89	8.61	1.08	0.99

HbA1c: Hemoglobin A1c; SVR12: Sustained virologic response 12 wk after treatment; DAA: Direct acting antiviral; SE: Standard error.

Table 4 Mean difference in hemoglobin A1c by hepatitis C virus genotype and direct acting antiviral treatment

	Average change HbA1c (SE)	P-value
HCV genotype
1a	-0.73 (0.13)	0.97
1b	-0.69 (0.20)
2	-0.79 (0.27)
3	-0.88 (0.51)
4	-0.20 (NA)
Treatment
Sofosbuvir/Simeprevir	-0.71 (0.16)	0.97
Sofosbuvir/Ribavirin	-0.77 (0.27)
PrOD	-0.66 (0.15)
Ledipasvir/Sofosbuvir	-0.80 (0.24)

HbA1c: Hemoglobin A1c; HCV: Hepatitis C virus; PrOD: Ombitasvir/Paritaprevir/Ritonavir/ Dasabuvir

Table 5 Components of metabolic syndrome on Sustained virologic response 12 wk after treatment

	Unadjusted OR (95%CI)	Adjusted OR (95%CI)
Obese	0.90 (0.62-1.31)	1.25 (0.82-1.90)
HTN	1.06 (0.74-1.52)	0.81 (0.51-1.28)
HLD	1.42 (0.97-2.10)	1.31 (0.87-1.97)
T2DM	0.72 (0.48-1.10)	0.82 (0.55-1.09)
Metabolic syndrome	1.04 (0.68-1.60)	1.81 (0.75-4.37)

HTN: Hypertension; HLD: Hyperlipidemia; T2DM: Type 2 diabetes mellitus.

Table 6 Odds ratio for a decrease of hemoglobin A1c > 0.5 among type 2 diabetes mellitus patients treated with direct acting antiviral

Predictor	Unadjusted OR (95%CI)	Adjusted OR (95%CI)
Age	1.03 (0.95-1.11)	1.07 (0.96-1.20)
Race/ethnicity
White1	1.58 (0.64-3.91)
African American	0.89 (0.32-2.43)	0.52 (0.13-2.06)
Hispanic	0.53 (0.18-1.57)	0.65 (0.16-2.66)
Asian	0.50 (0.02-8.85)	0.8 (0.04-10.01)
Other	0.83 (0.16-4.21)	0.98 (0.12-7.90)
Cirrhosis (by chart review)	0.62 (0.28-1.37)	0.59 (0.20-1.69)
Treatment naïve	0.84 (0.87-4.59)	2.61 (0.92-7.29)
HCV genotype
1a1	0.77 (0.35-1.71)
1b	1.33 (0.49-3.60)	0.79 (0.22-2.86)
2	1.50 (0.41-5.42)	6.75 (0.26-176.51)
3	0.66 (0.15-2.92)	3.81 (0.29-50.00)
Treatment regimen
Sofosbuvir/Simeprevir1	1.23 (0.55-2.75)
Sofosbuvir/Ribavirin	0.75 (0.27-2.09)	0.07 (0.003-1.50)
PrOD	1.60 (0.56-4.56)	0.71 (0.17-2.86)
Ledipasvir/Sofosbuvir	0.66 (0.27-1.62)	0.35 (0.09-1.36)
Overweight	1.36 (0.42-4.35)	0.89 (0.20-1.69)
Obese	1.55 (0.44-5.40)	1.10 (0.20-5.93)
Severely obese	1.08 (0.24-4.94)	0.41 (0.05-3.07)
Very severely obese	0.26 (0.21-3.06)	0.08 (0.003-2.07)
HTN	1.36 (0.38-4.80)	1.15 (0.15-8.86)
HLD	1.69 (0.69-4.09)	1.45 (0.29-7.26)
Metabolic syndrome	1.58 (0.60-4.15)	0.96 (0.10-9.19)
SVR12a	10.67 (1.76-64.7)	7.24 (1.22-42.94)

¹Reference group;

^aP < 0.05. HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HTN: Hypertension; HLD: Hyperlipidemia; SVR12: Sustained virologic response 12 wk post-treatment; PrOD: Ombitasvir/Paritaprevir/Ritonavir/ Dasabuvir.