Effects of hepatitis C virus genotypes and viral load on glucose and lipid metabolism after sustained virological response with direct-acting antivirals

Sparvoli, Jucéli Márcia Hendges; Sparvoli, Antonio Cardoso; Pereira, Afonso Alexandre; Paula, Ana Luisa Machado de; Garcia, Laís; Gonçalves, Carla Vitola

doi:10.1590/1806-9282.20221163

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Revista da Associação Médica Brasileira

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Original Article • Rev. Assoc. Med. Bras. 69 (5) • 2023 • https://doi.org/10.1590/1806-9282.20221163 copy

Effects of hepatitis C virus genotypes and viral load on glucose and lipid metabolism after sustained virological response with direct-acting antivirals

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

The objective of this study, carried out at the university hospital of the Federal University of Rio Grande, was to assess whether the treatment of chronic hepatitis C with direct-acting antivirals and the sustained virological response will affect the metabolic influences of the hepatitis C virus and whether these effects will vary according to genotypes and virus load.

METHODS:

This is an intervention pre-post study, carried out from March 2018 to December 2019, evaluating 273 hepatitis C virus patients treated with direct-acting antivirals. Inclusion criteria included being monoinfected with hepatitis C virus and achieving sustained virological response . Exclusion criteria included the presence of decompensated cirrhosis or co-infected with hepatitis B virus or human immunodeficiency virus. Genotypes, genotype 1 subtypes, and hepatitis C virus viral load were analyzed. Glucose metabolism was evaluated by the Homeostasis Model Assessment-insulin resistance indices: Homeostasis Model Assessment-β, TyG, and HbA1c, measured at the beginning of treatment and in sustained virological response. Statistical analysis with a T test by paired comparison of the means of the variables in the pretreatment and in the sustained virological response.

RESULTS:

Homeostasis Model Assessment-insulin resistance analysis: there were no significant differences between pretreatment and sustained virological response. Homeostasis Model Assessment-β analysis: significant increase in genotype 1 patients (p<0.028). TyG index analysis: significant increase in genotype 1b (p<0.017), genotype 3 (p<0.024), and genotype non-1 with low viral load (p<0.039). HbA1c analysis: significant decrease in genotype 3 (p<0.001) and genotype non-1 patients with low viral load (p<0.005).

CONCLUSION:

We detected significant metabolic influences after sustained virological response: impairment in lipid profile and improvements in the glucose metabolism. We found significant differences in genotype dependence, genotype 1 subtypes, and viral load.

KEYWORDS:
Genotype; Hepatitis C; Lipid metabolism; Insulin resistance; Viral load

		n (%)	Pretreatment	SVR	p-value
Age (mean±SD)			57.03 (±11.11)
	≤54 years	98 (35.9)
	55–64 years	113 (41.4)
	≥65 years	62 (22.7)
Color
	White	193 (70.7)
	Nonwhite	80 (29.3)
Genre
	Male	144 (52.7)
	Female	129 (47.3)
Weight (mean±SD)				73.54 (±14.69)	0.127
WC Abdominal (mean±SD)			73.21 (±14.72)	94.04 (±11.99)	0.206
	Adequate	73 (29.3)	94.38 (±11.87)
	Inadequate	200 (70.7)
BMI (mean±SD)			25.59 (±4.76)	27.73 (±4.84)	0.093
	≤24.9 (81)	81 (29.7)
	25–29.9 (116)	117 (42.9)
	≥30 (74)	75 (27.5)
Glycemic profile (mean±SD)			101.84 (±27.29)	107.79 (±31.70)	0.976
	With normal blood glucose	98 (35.9)
	With prediabetes	125 (45.8)
	With diabetes	50 (18.3)
Glycemic/genotypes (mean±SD)
	Genotype 1 (146)		105.02 (±21.01)	104.27 (±22.23)	0.541
	enotype 2 (38)		115.47 (±42.31)	116.00 (±37.23)	0.889
	Genotype 3 (87)		109.28 (±28.10)	110.25 (±40.57)	0.775
Profile triglycerides (mean±SD)
	Genotype 1 (146)		101.87 (±66.30)	105.30 (±66.47)	0.416
	Genotype 2 (38)		104.95 (±49.45)	109.51 (±54.57)	0.563
	Genotype 3 (87)		79.85 (±31.56)	100.94 (±76.15)	0.031
Laboratories (mean±SD)
	Total cholesterol		166.37 (±36.91)	185.52 (±38.41)	<0.001
	LDL		97.30 (±33.86)	111.80 (±36.66)	<0.001
	HDL		49.59 (±14.23)	50.26 (±13.66)	0.652
	Triglycerides		95.44 (±55.67)	104.47 (±67.50)	0.006

		HOMA-IR pretreatment Mean (SD)	HOMA-IR pretreatment 95%CI	HOMA-IR SVR Mean (SD)	HOMA-IR SVR 95%CI	p-value			HOMA-β pretreatment Mean (SD)	HOMA-β pretreatment 95%CI	HOMA-β SVR Mean (SD)	HOMA-β SVR 95%CI	p-value
Genotypes (G)							Genotype (G)
	Genotype 1 (146)	2.42 (±1.76)	2.13–2.72	2.65 (±1.87)	2.37–2.99	0.079		Genotype 1 (146)	89.29 (±62.85)	79.42–99.37	103.97 (±79.97)	91.27–117.30	0.028
	G1 a (67)	2.36 (±1.60)	2.02–2.79	2.53 (±1.83)	2.12–3.00	0.457		G1 a (67)	85.81 (±53.67)	73.25–99.82	98.27 (±91.03)	79.46–121.54	0.223
	G1 b (78)	2.63 (±2.44)	2.14–3.19	3.06 (±3.76)	2.34–3.94	0.098		G1 b (78)	91.12 (±62.94)	77.56–105.43	104.16 (±61.73)	90.66–117.47	0.086
	Genotype 2 (38)	2.75 (±2.03)	2.17–3.40	2.53 (±1.80)	2.00–3.10	0.323		Genotype 2 (38)	79.34 (±54.38)	63.93–99.16	72.78 (±43.84)	59.75–87.58	0.516
	Genotype 3 (87)	2.56 (±2.33)	2.09–3.14	2.96 (±3.50)	2.34–3.80	0.117		Genotype 3 (87)	87.51 (±56.82)	76.00–101.42	99.61 (±57.16)	87.76–11.01	0.058
Viral load (VL)		2.51 (±1.80)	2.22–2.84	2.68 (±2.05)	2.36–3.06	0.300	Viral load (VL)		87.85 (±65.71)	76.86–99.40	98.62 (±79.30)	86.28–113.14	0.147
	≥600,000 – High (132)	2.51 (±1.81)	2.22–2.85	2.69 (±2.06)	2.34–3.07	0.294		≥600,000 – High (132)	87.40 (±65.76)	77.61–98.48	99.23 (±79.29)	86.33–113.98	0.108
	≤599,999 – Low (131)	2.50 (±1.87)	2.09–2.93	2.76 (±1.80)	2.33-3.16	0.239		≤599,999 – Low (131)	92.17±70.27	77.17–108.12	110.80±94.10	90.41–134.05	0.089
Genotype 1 (G1)		2.31 (±1.66)	1.96–2.77	2.52 (±1.98)	2,10–3.07	0.148	Genotype 1 (G1)		85.15±52.49	72.99–99.07	96.34±60.84	82.02–110.66	0.050
	High VL (76)	2.54 (±1.74)	2.10–3.04	2.60 (±2.38)	2.38–3.29	0.813		High VL (76)	82.02±59.63	66.46–98.06	81.67±49.57	68.98–94.74	0.966
	Low VL (66)	2.67 (±2.57)	2.11–3.32	3.00 (±3.55)	2.35–3.85	0.181		Low VL (66)	87.40±53.29	75.30–100.29	99.14±57.62	86.12–114.00	0.080
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	High VL (55)							High VL (55)
	Low VL (70)							Low VL (70)
		TyG pretreatment Mean (SD)	TyG pretreatment 95%CI	TyG RVS Mean (SD)	TyG RVS 95%CI	p-value			HbA1c pretreatment Mean (SD)	HbA1c pretreatment 95%CI	HbA1c RVS Mean (SD)	HbA1c RVS 95%CI	p-value
Genotypes (G)							Genotypes
	Genotype 1 (144)	4.56 (±0.26)	4.52–4.60	4.58 (±0.27)	4.53–4.62	0.510		Genotype 1 (146)	5.63 (±0.92)	5.49–5.80	5.54 (±0.78)	5.42–5.69	0.144
	G1 a (66)	4.58 (±0.24)	4.51–4.63	4.56 (±0.31)	4.49–4.64	0.651		G1 a (68)	5.78 (±1.02)	5.54–6.04	5.69 (±0.98)	5.46–5.94	0.391
	G1 b (74)	4.51 (±0.25)	4.46–4.57	4.57 (±0.30)	4.51–4.64	0.017		G1 b (78)	5.59 (±0.77)	5.43–5.79	5.47 (±0.66)	5.33–5.61	0.155
	Genotype 2 (37)	4.63 (±0.31)	4,53–4.73	4.64 (±0.29)	4.54–4.74	0.771		Genotype 2 (38)	5.83 (±0.94)	5.56–6.15	5.91 (±1.05)	5.59–6.27	0.400
	Genotype 3 (83)	4.48 (±0.23)	4,43–4.52	4.54 (±0.33)	4.48–4.62	0.024		Genotype 3 (87)	5.85 (±1.06)	5.65–6.11	5.54 (±1.08)	5.34–5.79	0.001
Viral load (VL)		4.55 (±0.27)	4,51–4.60	4.56 (±0.31)	4.51–4.62	0.639	Viral load (VL)		5.71 (±0.91)	5.57–5.88	5.61 (±1.02)	5.44–5.80	0.117
	≥600,000 – High (128)	4.55 (±0.27)	4,50–4.60	4.56 (±0.31)	4.50–4.62	0.634		≥600,000 – High (132)	5.72 (±0.92)	5.56–5.88	5.61 (±1.03)	5.45–5.80	0.119
	≤599,999 – Low (127)	5.56 (±0.26)	4.50–4.62	4.55 (±0.27)	4.49–4.61	0.813		≤599,999 – Low (131)	5.68 (±0.97)	5.47–5.92	5.53 (±0.88)	5.35–5.75	0.108
Genotype 1 (G1)		4.56 (±0.26)	4.50–4.63	4.59 (±0.26)	4.52–4.65	0.389	Genotype (G1)		5.58 (±0.83)	5.40–5.79	5.52 (±0.63)	5.37–5.67	0.462
	G1+High VL (76)	4.54 (±0.28)	4.46–4.62	4.57 (±0.37)	4.47–4.67	0.323		G1+High VL (76)	5.78 (±0.84)	5.58–6.01	5.73 (±1.20)	5.44–6.05	0.609
	G1+Low VL (66)	4.51 (±0.26)	4.45–4.57	4.57 (±0.29)	4.51–4.64	0.039		G1+Low VL (66)	5.90 (±1.14)	5.65–6.19	5.59 (±0.99)	5.38–5.85	0.005
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	GN1+High VL (55)							GN1+High VL (55)
	GN1+Low VL (68)							GN1+Low VL (70)
		HOMA-IR pretreatment Mean (SD)	HOMA-IR pretreatment 95%CI	HOMA-IR SVR Mean (SD)	HOMA-IR SVR 95%CI	p-value			HOMA-β pretreatment Mean (SD)	HOMA-β pretreatment 95%CI	HOMA-β SVR Mean (SD)	HOMA-β SVR 95%CI	p-value
Genotypes (G)							Genotype (G)
	Genotype 1 (146)	2.42 (±1.76)	2.13–2.72	2.65 (±1.87)	2.37–2.99	0.079		Genotype 1 (146)	89.29 (±62.85)	79.42–99.37	103.97 (±79.97)	91.27–117.30	0.028
	G1 a (67)	2.36 (±1.60)	2.02–2.79	2.53 (±1.83)	2.12–3.00	0.457		G1 a (67)	85.81 (±53.67)	73.25–99.82	98.27 (±91.03)	79.46–121.54	0.223
	G1 b (78)	2.63 (±2.44)	2.14–3.19	3.06 (±3.76)	2.34–3.94	0.098		G1 b (78)	91.12 (±62.94)	77.56–105.43	104.16 (±61.73)	90.66–117.47	0.086
	Genotype 2 (38)	2.75 (±2.03)	2.17–3.40	2.53 (±1.80)	2.00–3.10	0.323		Genotype 2 (38)	79.34 (±54.38)	63.93–99.16	72.78 (±43.84)	59.75–87.58	0.516
	Genotype 3 (87)	2.56 (±2.33)	2.09–3.14	2.96 (±3.50)	2.34–3.80	0.117		Genotype 3 (87)	87.51 (±56.82)	76.00–101.42	99.61 (±57.16)	87.76–11.01	0.058
Viral load (VL)		2.51 (±1.80)	2.22–2.84	2.68 (±2.05)	2.36–3.06	0.300	Viral load (VL)		87.85 (±65.71)	76.86–99.40	98.62 (±79.30)	86.28–113.14	0.147
	≥600,000 – High (132)	2.51 (±1.81)	2.22–2.85	2.69 (±2.06)	2.34–3.07	0.294		≥600,000 – High (132)	87.40 (±65.76)	77.61–98.48	99.23 (±79.29)	86.33–113.98	0.108
	≤599,999 – Low (131)	2.50 (±1.87)	2.09–2.93	2.76 (±1.80)	2.33-3.16	0.239		≤599,999 – Low (131)	92.17±70.27	77.17–108.12	110.80±94.10	90.41–134.05	0.089
Genotype 1 (G1)		2.31 (±1.66)	1.96–2.77	2.52 (±1.98)	2,10–3.07	0.148	Genotype 1 (G1)		85.15±52.49	72.99–99.07	96.34±60.84	82.02–110.66	0.050
	High VL (76)	2.54 (±1.74)	2.10–3.04	2.60 (±2.38)	2.38–3.29	0.813		High VL (76)	82.02±59.63	66.46–98.06	81.67±49.57	68.98–94.74	0.966
	Low VL (66)	2.67 (±2.57)	2.11–3.32	3.00 (±3.55)	2.35–3.85	0.181		Low VL (66)	87.40±53.29	75.30–100.29	99.14±57.62	86.12–114.00	0.080
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	High VL (55)							High VL (55)
	Low VL (70)							Low VL (70)
		TyG pretreatment Mean (SD)	TyG pretreatment 95%CI	TyG RVS Mean (SD)	TyG RVS 95%CI	p-value			HbA1c pretreatment Mean (SD)	HbA1c pretreatment 95%CI	HbA1c RVS Mean (SD)	HbA1c RVS 95%CI	p-value
Genotypes (G)							Genotypes
	Genotype 1 (144)	4.56 (±0.26)	4.52–4.60	4.58 (±0.27)	4.53–4.62	0.510		Genotype 1 (146)	5.63 (±0.92)	5.49–5.80	5.54 (±0.78)	5.42–5.69	0.144
	G1 a (66)	4.58 (±0.24)	4.51–4.63	4.56 (±0.31)	4.49–4.64	0.651		G1 a (68)	5.78 (±1.02)	5.54–6.04	5.69 (±0.98)	5.46–5.94	0.391
	G1 b (74)	4.51 (±0.25)	4.46–4.57	4.57 (±0.30)	4.51–4.64	0.017		G1 b (78)	5.59 (±0.77)	5.43–5.79	5.47 (±0.66)	5.33–5.61	0.155
	Genotype 2 (37)	4.63 (±0.31)	4,53–4.73	4.64 (±0.29)	4.54–4.74	0.771		Genotype 2 (38)	5.83 (±0.94)	5.56–6.15	5.91 (±1.05)	5.59–6.27	0.400
	Genotype 3 (83)	4.48 (±0.23)	4,43–4.52	4.54 (±0.33)	4.48–4.62	0.024		Genotype 3 (87)	5.85 (±1.06)	5.65–6.11	5.54 (±1.08)	5.34–5.79	0.001
Viral load (VL)		4.55 (±0.27)	4,51–4.60	4.56 (±0.31)	4.51–4.62	0.639	Viral load (VL)		5.71 (±0.91)	5.57–5.88	5.61 (±1.02)	5.44–5.80	0.117
	≥600,000 – High (128)	4.55 (±0.27)	4,50–4.60	4.56 (±0.31)	4.50–4.62	0.634		≥600,000 – High (132)	5.72 (±0.92)	5.56–5.88	5.61 (±1.03)	5.45–5.80	0.119
	≤599,999 – Low (127)	5.56 (±0.26)	4.50–4.62	4.55 (±0.27)	4.49–4.61	0.813		≤599,999 – Low (131)	5.68 (±0.97)	5.47–5.92	5.53 (±0.88)	5.35–5.75	0.108
Genotype 1 (G1)		4.56 (±0.26)	4.50–4.63	4.59 (±0.26)	4.52–4.65	0.389	Genotype (G1)		5.58 (±0.83)	5.40–5.79	5.52 (±0.63)	5.37–5.67	0.462
	G1+High VL (76)	4.54 (±0.28)	4.46–4.62	4.57 (±0.37)	4.47–4.67	0.323		G1+High VL (76)	5.78 (±0.84)	5.58–6.01	5.73 (±1.20)	5.44–6.05	0.609
	G1+Low VL (66)	4.51 (±0.26)	4.45–4.57	4.57 (±0.29)	4.51–4.64	0.039		G1+Low VL (66)	5.90 (±1.14)	5.65–6.19	5.59 (±0.99)	5.38–5.85	0.005
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	GN1+High VL (55)							GN1+High VL (55)
	GN1+Low VL (68)							GN1+Low VL (70)

		HOMA-IR pretreatment Mean (SD)	HOMA-IR pretreatment 95%CI	HOMA-IR SVR Mean (SD)	HOMA-IR SVR 95%CI	p-value			HOMA-β pretreatment Mean (SD)	HOMA-β pretreatment 95%CI	HOMA-β SVR Mean (SD)	HOMA-β SVR 95%CI	p-value
Genotypes (G)							Genotype (G)
	Genotype 1 (146)	2.42 (±1.76)	2.13–2.72	2.65 (±1.87)	2.37–2.99	0.079		Genotype 1 (146)	89.29 (±62.85)	79.42–99.37	103.97 (±79.97)	91.27–117.30	0.028
	G1 a (67)	2.36 (±1.60)	2.02–2.79	2.53 (±1.83)	2.12–3.00	0.457		G1 a (67)	85.81 (±53.67)	73.25–99.82	98.27 (±91.03)	79.46–121.54	0.223
	G1 b (78)	2.63 (±2.44)	2.14–3.19	3.06 (±3.76)	2.34–3.94	0.098		G1 b (78)	91.12 (±62.94)	77.56–105.43	104.16 (±61.73)	90.66–117.47	0.086
	Genotype 2 (38)	2.75 (±2.03)	2.17–3.40	2.53 (±1.80)	2.00–3.10	0.323		Genotype 2 (38)	79.34 (±54.38)	63.93–99.16	72.78 (±43.84)	59.75–87.58	0.516
	Genotype 3 (87)	2.56 (±2.33)	2.09–3.14	2.96 (±3.50)	2.34–3.80	0.117		Genotype 3 (87)	87.51 (±56.82)	76.00–101.42	99.61 (±57.16)	87.76–11.01	0.058
Viral load (VL)		2.51 (±1.80)	2.22–2.84	2.68 (±2.05)	2.36–3.06	0.300	Viral load (VL)		87.85 (±65.71)	76.86–99.40	98.62 (±79.30)	86.28–113.14	0.147
	≥600,000 – High (132)	2.51 (±1.81)	2.22–2.85	2.69 (±2.06)	2.34–3.07	0.294		≥600,000 – High (132)	87.40 (±65.76)	77.61–98.48	99.23 (±79.29)	86.33–113.98	0.108
	≤599,999 – Low (131)	2.50 (±1.87)	2.09–2.93	2.76 (±1.80)	2.33-3.16	0.239		≤599,999 – Low (131)	92.17±70.27	77.17–108.12	110.80±94.10	90.41–134.05	0.089
Genotype 1 (G1)		2.31 (±1.66)	1.96–2.77	2.52 (±1.98)	2,10–3.07	0.148	Genotype 1 (G1)		85.15±52.49	72.99–99.07	96.34±60.84	82.02–110.66	0.050
	High VL (76)	2.54 (±1.74)	2.10–3.04	2.60 (±2.38)	2.38–3.29	0.813		High VL (76)	82.02±59.63	66.46–98.06	81.67±49.57	68.98–94.74	0.966
	Low VL (66)	2.67 (±2.57)	2.11–3.32	3.00 (±3.55)	2.35–3.85	0.181		Low VL (66)	87.40±53.29	75.30–100.29	99.14±57.62	86.12–114.00	0.080
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	High VL (55)							High VL (55)
	Low VL (70)							Low VL (70)
		TyG pretreatment Mean (SD)	TyG pretreatment 95%CI	TyG RVS Mean (SD)	TyG RVS 95%CI	p-value			HbA1c pretreatment Mean (SD)	HbA1c pretreatment 95%CI	HbA1c RVS Mean (SD)	HbA1c RVS 95%CI	p-value
Genotypes (G)							Genotypes
	Genotype 1 (144)	4.56 (±0.26)	4.52–4.60	4.58 (±0.27)	4.53–4.62	0.510		Genotype 1 (146)	5.63 (±0.92)	5.49–5.80	5.54 (±0.78)	5.42–5.69	0.144
	G1 a (66)	4.58 (±0.24)	4.51–4.63	4.56 (±0.31)	4.49–4.64	0.651		G1 a (68)	5.78 (±1.02)	5.54–6.04	5.69 (±0.98)	5.46–5.94	0.391
	G1 b (74)	4.51 (±0.25)	4.46–4.57	4.57 (±0.30)	4.51–4.64	0.017		G1 b (78)	5.59 (±0.77)	5.43–5.79	5.47 (±0.66)	5.33–5.61	0.155
	Genotype 2 (37)	4.63 (±0.31)	4,53–4.73	4.64 (±0.29)	4.54–4.74	0.771		Genotype 2 (38)	5.83 (±0.94)	5.56–6.15	5.91 (±1.05)	5.59–6.27	0.400
	Genotype 3 (83)	4.48 (±0.23)	4,43–4.52	4.54 (±0.33)	4.48–4.62	0.024		Genotype 3 (87)	5.85 (±1.06)	5.65–6.11	5.54 (±1.08)	5.34–5.79	0.001
Viral load (VL)		4.55 (±0.27)	4,51–4.60	4.56 (±0.31)	4.51–4.62	0.639	Viral load (VL)		5.71 (±0.91)	5.57–5.88	5.61 (±1.02)	5.44–5.80	0.117
	≥600,000 – High (128)	4.55 (±0.27)	4,50–4.60	4.56 (±0.31)	4.50–4.62	0.634		≥600,000 – High (132)	5.72 (±0.92)	5.56–5.88	5.61 (±1.03)	5.45–5.80	0.119
	≤599,999 – Low (127)	5.56 (±0.26)	4.50–4.62	4.55 (±0.27)	4.49–4.61	0.813		≤599,999 – Low (131)	5.68 (±0.97)	5.47–5.92	5.53 (±0.88)	5.35–5.75	0.108
Genotype 1 (G1)		4.56 (±0.26)	4.50–4.63	4.59 (±0.26)	4.52–4.65	0.389	Genotype (G1)		5.58 (±0.83)	5.40–5.79	5.52 (±0.63)	5.37–5.67	0.462
	G1+High VL (76)	4.54 (±0.28)	4.46–4.62	4.57 (±0.37)	4.47–4.67	0.323		G1+High VL (76)	5.78 (±0.84)	5.58–6.01	5.73 (±1.20)	5.44–6.05	0.609
	G1+Low VL (66)	4.51 (±0.26)	4.45–4.57	4.57 (±0.29)	4.51–4.64	0.039		G1+Low VL (66)	5.90 (±1.14)	5.65–6.19	5.59 (±0.99)	5.38–5.85	0.005
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	GN1+High VL (55)							GN1+High VL (55)
	GN1+Low VL (68)							GN1+Low VL (70)
		HOMA-IR pretreatment Mean (SD)	HOMA-IR pretreatment 95%CI	HOMA-IR SVR Mean (SD)	HOMA-IR SVR 95%CI	p-value			HOMA-β pretreatment Mean (SD)	HOMA-β pretreatment 95%CI	HOMA-β SVR Mean (SD)	HOMA-β SVR 95%CI	p-value
Genotypes (G)							Genotype (G)
	Genotype 1 (146)	2.42 (±1.76)	2.13–2.72	2.65 (±1.87)	2.37–2.99	0.079		Genotype 1 (146)	89.29 (±62.85)	79.42–99.37	103.97 (±79.97)	91.27–117.30	0.028
	G1 a (67)	2.36 (±1.60)	2.02–2.79	2.53 (±1.83)	2.12–3.00	0.457		G1 a (67)	85.81 (±53.67)	73.25–99.82	98.27 (±91.03)	79.46–121.54	0.223
	G1 b (78)	2.63 (±2.44)	2.14–3.19	3.06 (±3.76)	2.34–3.94	0.098		G1 b (78)	91.12 (±62.94)	77.56–105.43	104.16 (±61.73)	90.66–117.47	0.086
	Genotype 2 (38)	2.75 (±2.03)	2.17–3.40	2.53 (±1.80)	2.00–3.10	0.323		Genotype 2 (38)	79.34 (±54.38)	63.93–99.16	72.78 (±43.84)	59.75–87.58	0.516
	Genotype 3 (87)	2.56 (±2.33)	2.09–3.14	2.96 (±3.50)	2.34–3.80	0.117		Genotype 3 (87)	87.51 (±56.82)	76.00–101.42	99.61 (±57.16)	87.76–11.01	0.058
Viral load (VL)		2.51 (±1.80)	2.22–2.84	2.68 (±2.05)	2.36–3.06	0.300	Viral load (VL)		87.85 (±65.71)	76.86–99.40	98.62 (±79.30)	86.28–113.14	0.147
	≥600,000 – High (132)	2.51 (±1.81)	2.22–2.85	2.69 (±2.06)	2.34–3.07	0.294		≥600,000 – High (132)	87.40 (±65.76)	77.61–98.48	99.23 (±79.29)	86.33–113.98	0.108
	≤599,999 – Low (131)	2.50 (±1.87)	2.09–2.93	2.76 (±1.80)	2.33-3.16	0.239		≤599,999 – Low (131)	92.17±70.27	77.17–108.12	110.80±94.10	90.41–134.05	0.089
Genotype 1 (G1)		2.31 (±1.66)	1.96–2.77	2.52 (±1.98)	2,10–3.07	0.148	Genotype 1 (G1)		85.15±52.49	72.99–99.07	96.34±60.84	82.02–110.66	0.050
	High VL (76)	2.54 (±1.74)	2.10–3.04	2.60 (±2.38)	2.38–3.29	0.813		High VL (76)	82.02±59.63	66.46–98.06	81.67±49.57	68.98–94.74	0.966
	Low VL (66)	2.67 (±2.57)	2.11–3.32	3.00 (±3.55)	2.35–3.85	0.181		Low VL (66)	87.40±53.29	75.30–100.29	99.14±57.62	86.12–114.00	0.080
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	High VL (55)							High VL (55)
	Low VL (70)							Low VL (70)
		TyG pretreatment Mean (SD)	TyG pretreatment 95%CI	TyG RVS Mean (SD)	TyG RVS 95%CI	p-value			HbA1c pretreatment Mean (SD)	HbA1c pretreatment 95%CI	HbA1c RVS Mean (SD)	HbA1c RVS 95%CI	p-value
Genotypes (G)							Genotypes
	Genotype 1 (144)	4.56 (±0.26)	4.52–4.60	4.58 (±0.27)	4.53–4.62	0.510		Genotype 1 (146)	5.63 (±0.92)	5.49–5.80	5.54 (±0.78)	5.42–5.69	0.144
	G1 a (66)	4.58 (±0.24)	4.51–4.63	4.56 (±0.31)	4.49–4.64	0.651		G1 a (68)	5.78 (±1.02)	5.54–6.04	5.69 (±0.98)	5.46–5.94	0.391
	G1 b (74)	4.51 (±0.25)	4.46–4.57	4.57 (±0.30)	4.51–4.64	0.017		G1 b (78)	5.59 (±0.77)	5.43–5.79	5.47 (±0.66)	5.33–5.61	0.155
	Genotype 2 (37)	4.63 (±0.31)	4,53–4.73	4.64 (±0.29)	4.54–4.74	0.771		Genotype 2 (38)	5.83 (±0.94)	5.56–6.15	5.91 (±1.05)	5.59–6.27	0.400
	Genotype 3 (83)	4.48 (±0.23)	4,43–4.52	4.54 (±0.33)	4.48–4.62	0.024		Genotype 3 (87)	5.85 (±1.06)	5.65–6.11	5.54 (±1.08)	5.34–5.79	0.001
Viral load (VL)		4.55 (±0.27)	4,51–4.60	4.56 (±0.31)	4.51–4.62	0.639	Viral load (VL)		5.71 (±0.91)	5.57–5.88	5.61 (±1.02)	5.44–5.80	0.117
	≥600,000 – High (128)	4.55 (±0.27)	4,50–4.60	4.56 (±0.31)	4.50–4.62	0.634		≥600,000 – High (132)	5.72 (±0.92)	5.56–5.88	5.61 (±1.03)	5.45–5.80	0.119
	≤599,999 – Low (127)	5.56 (±0.26)	4.50–4.62	4.55 (±0.27)	4.49–4.61	0.813		≤599,999 – Low (131)	5.68 (±0.97)	5.47–5.92	5.53 (±0.88)	5.35–5.75	0.108
Genotype 1 (G1)		4.56 (±0.26)	4.50–4.63	4.59 (±0.26)	4.52–4.65	0.389	Genotype (G1)		5.58 (±0.83)	5.40–5.79	5.52 (±0.63)	5.37–5.67	0.462
	G1+High VL (76)	4.54 (±0.28)	4.46–4.62	4.57 (±0.37)	4.47–4.67	0.323		G1+High VL (76)	5.78 (±0.84)	5.58–6.01	5.73 (±1.20)	5.44–6.05	0.609
	G1+Low VL (66)	4.51 (±0.26)	4.45–4.57	4.57 (±0.29)	4.51–4.64	0.039		G1+Low VL (66)	5.90 (±1.14)	5.65–6.19	5.59 (±0.99)	5.38–5.85	0.005
Non-1 Genotype (GN1)							Non-1 Genotype (GN1)
	GN1+High VL (55)							GN1+High VL (55)
	GN1+Low VL (68)							GN1+Low VL (70)

	HOMA-IR pretreatment Média (SD)	HOMA-IR pretreatment IC 95%	HOMA-IR SVR Mean (SD)	HOMA-IR SVR IC 95%	p-valor		HOMA-β pretreatment Mean (SD)	HOMA-β pretreatment IC 95%	HOMA-β SVR Mean (SD)	HOMA-β SVR IC 95%	p-valor
Genotypes (G)						Genotype (G)
Genotype 1 (146)	2.42 (±1.76)	2.13 - 2.72	2.65 (±1.87)	2.37 - 2.99	0.079	Genotype 1 (146)	89.29 (±62.85)	79.42-99.37	103.97(±79.97)	91.27-117.30	0.028
G1 a (67)	2.36 (±1.60)	2.02 - 2.79	2.53 (±1.83)	2.12 - 3.00	0.457	G1 a (67)	85.81 (±53.67)	73.25-99.82	98.27(±91.03)	79.46-121.54	0.223
G1 b (78)	2.63 (±2.44)	2.14 - 3.19	3.06 (±3.76)	2.34 - 3.94	0.098	G1 b (78)	91.12 (±62.94)	77.56-105.43	104.16(±61.73)	90.66-117.47	0.086
Genotype 2 (38)	2.75 (±2.03)	2.17 - 3.40	2.53 (±1.80)	2.00 - 3.10	0.323	Genotype 2 (38)	79.34(±54.38)	63.93-99.16	72.78(±43.84)	59.75-87.58	0.516
Genotype 3 (87)	2.56 (±2.33)	2.09 - 3.14	2.96 (±3.50)	2.34 - 3.80	0.117	Genotype 3 (87)	87.51(±56.82)	76.00-101.42	99.61(±57.16)	87.76-11.01	0.058
Viral load (VL)						Viral load (VL)
≥ 600000 - High (132)	2.51 (±1.80)	2.22 - 2.84	2.68 (±2.05)	2.36 - 3.06	0.300	≥ 600000 - High (132)	87.85(±65.71)	76.86-99.40	98.62(±79.30)	86.28-113.14	0.147
≤ 599999- Low (131)	2.51 (±1.81)	2.22 - 2.85	2.69 (± 2.06)	2.34 - 3.07	0.294	≤ 599999- Low (131)	87.40(±65.76)	77.61-98.48	99.23(±79.29)	86.33-113.98	0.108
Genótipo 1 (G1)						Genotype 1 (G1)
High VL (76)	2.50 (±1.87)	2.09 - 2.93	2.76 (±1.80)	2.33 -3.16	0.239	High VL (76)	92.17 ±70.27	77.17-108.12	110.80 ± 94.10	90.41-134.05	0.089
Low VL (66)	2.31 (±1.66)	1.96 - 2.77	2.52 (±1.98)	2,10 - 3.07	0.148	Low VL (66)	85.15±52.49	72.99 - 99.07	96.34 ± 60.84	82.02 -110.66	0.050
Non-1 Genotype (GN1)						Non-1 Genotype (GN1)
High VL (55)	2.54 (±1.74)	2.10 - 3.04	2.60 (±2.38)	2.38 - 3.29	0.813	High VL (55)	82.02 ±59.63	66.46 - 98.06	81.67±49.57	68.98 - 94.74	0.966
Low VL (70)	2.67 (±2.57)	2.11 - 3.32	3.00 (±3.55)	2.35 - 3.85	0.181	Low VL (70)	87.40± 53.29	75.30- 100.29	99.14±57.62	86.12- 114.00	0.080
	TyG pretreatment Média (SD)	TyG pretreatment IC 95%	TyG RVS Mean (SD)	TyG RVS IC 95%	p-valor		HbA1c pretreatment Média (SD)	HbA1c pretreatment IC 95%	HbA1c RVS Mean (SD)	HbA1c RVS IC 95%	p-valor
Genotypes (G)						Genotypes
Genotype 1 (144)	4.56(±0.26)	4.52 - 4.60	4.58 (±0.27)	4.53 - 4.62	0.510	Genotype 1 (146)	5.63 (±0.92)	5.49 - 5.80	5.54 (±0.78)	5.42 - 5.69	0.144
G1 a (66)	4.58 (±0.24)	4.51 - 4.63	4.56 (±0.31)	4.49 - 4.64	0.651	G1 a (68)	5.78 (±1.02)	5.54 - 6.04	5.69 (±0.98)	5.46 - 5.94	0.391
G1 b (74)	4.51 (±0.25)	4.46 - 4.57	4.57 (±0.30)	4.51 - 4.64	0.017	G1 b (78)	5.59 (±0.77)	5.43 - 5.79	5.47 (±0.66)	5.33 - 5.61	0.155
Genotype 2 (37)	4.63 (±0.31)	4,53 - 4.73	4.64 (±0.29)	4.54 - 4.74	0.771	Genotype 2 (38)	5.83 (±0.94)	5.56 - 6.15	5.91 (±1.05)	5.59 - 6.27	0.400
Genotype 3 (83)	4.48 (±0.23)	4,43 - 4.52	4.54 (±0.33)	4.48 - 4.62	0.024	Genotype 3 (87)	5.85 (±1.06)	5.65 - 6.11	5.54 (±1.08)	5.34 - 5.79	0.001
Viral load (VL)						Viral load (VL)
≥ 600000 High (128)	4.55 (±0.27)	4,51 - 4.60	4.56 (±0.31)	4.51 - 4.62	0.639	≥ 600000 High (132)	5.71 (±0.91)	5.57 - 5.88	5.61 (±1.02)	5.44 - 5.80	0.117
≤ 599999 Low (127)	4.55 (±0.27)	4,50 - 4.60	4.56 (±0.31)	4.50 - 4.62	0.634	≤ 599999 Low (131)	5.72(±0.92)	5.56 - 5.88	5.61 (±1.03)	5.45 - 5.80	0.119
Genotype 1 (G1)						Genotype (G1)
G1 + High VL (76)	5.56 (±0.26)	4.50 - 4.62	4.55 (±0.27)	4.49 - 4.61	0.813	G1 + High VL (76)	5.68 (±0.97)	5.47 - 5.92	5.53 (±0.88)	5.35 - 5.75	0.108
G1 + Low VL (66)	4.56 (±0.26)	4.50 - 4.63	4.59 (±0.26)	4.52 - 4.65	0.389	G1 + Low VL (66)	5.58 (±0.83)	5.40 - 5.79	5.52 (±0.63)	5.37 - 5.67	0.462
Non-1 Genotype (GN1)						Non-1 Genotype(GN1)
GN1 + High VL (55)	4.54 (±0.28)	4.46 - 4.62	4.57 (±0.37)	4.47 - 4.67	0.323	GN1 + High VL (55)	5.78 (±0.84)	5.58 - 6.01	5.73 (±1.20)	5.44 - 6.05	0.609
GN1 + Low VL (68)	4.51 (±0.26)	4.45 - 4.57	4.57 (±0.29)	4.51 - 4.64	0.039	GN1 + Low VL (70)	5.90 (±1.14)	5.65 - 6.19	5.59 (±0.99)	5.38 - 5.85	0.005

Associação Médica Brasileira R. São Carlos do Pinhal, 324, 01333-903 São Paulo SP - Brazil, Tel: +55 11 3178-6800, Fax: +55 11 3178-6816 - São Paulo - SP - Brazil
E-mail: ramb@amb.org.br

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[1] *Corresponding author: juceli.sparvoli@gmail.com