Predictive factors associated with hepatitis C antiviral therapy response

Table 1 Risk factors associated with response (sustained virologic response 12) to first-generation direct acting antivirals in naive patients

	SVR12 rates (%)
	Boceprevir			Telaprevir
Predictive variables	PR48	BOCRGT	BOCPR48	PR48	T12PR48
Naïve	40	67	66	44	75
Mild-moderate fibrosis	38	67	67	47	118.5
Advanced fibrosis	38	41	52	33	62
Black race	23	42	53	25	62
HCVRNA viral load < 800.000 IU/mL	64	76	85	36	74
IL28B C/C	78	82	80	64	90
Il28B C/T	28	65	71	23	71
IL28B T/T	27	55	59	25	73
HCV genotype 1a	35	59	63	41	71
HCV genotype 1b	40	66	70	4	79
BMI < 25	47	58	67	44	83
BMI ≥ 30	33	48	66	41	71
Relapse	22	9	9	28	9

Data obtained, analyzed and adapted from Ref. [8,9,44]. PR48: Standard therapy with pegylated interferon plus ribavirin for 48 wk; BOCRGT: Boceprevir with therapy possibly shortened by response guided therapy; BOCPR48: Boceprevir with treatment fixed time for 48 wk; T12PR48: Telaprevir by 12 wk and standard therapy for 48 wk; IL28B: Interleukin-28B; BMI: Body mass index; HCV: Hepatitis C virus; SVR: Sustained virologic response.

Table 2 Risk factors associated with therapeutic response to first-generation direct acting antivirals in patients previously treated with pegylated interferon and ribavirin

	SVR rates (%)
	Boceprevir			Telaprevir
Predictive variables	PR48	BOCRGT	BOCPR48	PR48	T12PR48
Previous relapser	29	69	75	24	83
Previous partial-responder	7	40	52	15	59
Previous null responder				5	29
Mild-moderate fibrosis	23	63	68	16	76
Advanced fibrosis	13	44	68	11	49
Black race	8	61	63	10	55
HCVRNA viral load > 800.000 IU/mL (baseline)
IL28B C/C	46	79	77	29	79
Il28B C/T	17	61	73	16	60
IL28B T/T	50	55	72	13	61
HCV genotype 1a	24	5	61
HCV genotype 1b	22	65	73
BMI < 25	20	6	68
BMI ≥ 30	11	56	65
Relapse	15	59	54

Data obtained, analyzed and adapted from Ref. [40,41,44,45]. PR48: Standard therapy with pegylated interferon plus ribavirin for 48 wk; BOCRGT: Boceprevir with therapy possibly shortened by response guided therapy; BOCPR48: Boceprevir with treatment fixed time for 48 wk; T12PR48: Telaprevir by 12 wk and standard therapy for 48 wk; IL28B: Interleukin-28B; BMI: Body mass index; HCV: Hepatitis C virus; SVR: Sustained virologic response.

Table 3 Cupic study evaluation of the risk/benefit of the treatment cirrhotic patients with telaprevir or boceprevir triple therapy considering the chances of death or severe complications and sustained virologic response 12 according to cutoffs of serum albumin level and platelet count n (%)

Factors	Platelet count	Platelet count
	> 100000/mm3	≤100000/mm3
Serum albumin level > 35 g/L
Patients with severe complications or death)	19 (6.2)	9 (12.2)
SVR12	168 (54.9)	27 (36.5)
Serum albumin level > 35 g/L
Patients with severe complications or death	5 (16.1)	19 (51.4)
SVR12	9 (29.0)	10 (27.0)

Adapted from Hézode et al[50]. SVR12: Sustained virologic response at 12 wk after ending of treatment.

Table 4 Characteristics of the "New-wave" direct acting antivirals and the most important variables associated with sustained virological response

Drug	Characteristics	Resistance-associated	SVR predictive factors	OR1	P-value1
Sofosbuvir	Nucleotide analogue HCV NS5B	HCV mutation S282T	Genotype 1			McHutchison et al[15]
	Polymerase inhibitor		Cirrhosis: no vs yes	3.93	0.0018	Neutrino study
	Against all HCV genotypes		IL28B: CC vs CT/TT	7.99	0.006
			RBV exposure (mg/kg per day)	1.39	0.0005
			Genotypes 2 and 3
			HCV genotypes 2 vs 3	42.49	< 0.0001	Fission study
			Cirrhosis: no vs yes	2.94	0.005
			HCV RNA baseline: < vs≥ 6 Log IU/mL	2.33	0.009
			RBV exposure (mg/kg per day)	1.26	0.002
Simeprevir	NS3/4A serine protease inhibitor	Q80K-HCV subtype 1a	HCV 1a: Q80K: no vs yes	0.19	1.7 × 10-5	Jacobson et al[61]
	HCV genotype 1	R155K	F0-F2 vs F3-F4	2.09	0.029	Quest-1 study
		D168V - HCV subtype 1b	IL28B: CC vs CT/TT	5.11	1.3 × 10-4
			HCV RNA baseline: ≤vs > 800.000 IU/mL	3.13	0.028
Daclatasvir	NS5A replication complex inhibitor	NS3 polymorphisms	HCV genotype 1a vs 1b	2.82	0.025	Hézode et al[63]
	Against all HCV genotypes	NS5A-A30K	HCV genotypes 2 vs 3	1.31	0.740	Sulkowski et al[46]
Ledipasvir	HCV NS5A replication complex inhibitor					Afdhal et al[67]
	HCV genotype 1
ABT-450	NS3/4A protease inhibitor		Treatment vs placebo	7.19	4.3 × 20-11	Feld et al[70]
Ritonavir	HCV NS5A replication complex inhibitor
Ombitasvir	HCV NS5A inhibitor (Pangenotipic)		HCV genotype 1a
Dasabuvir	HCV NS5B RNA non-nucleoside polymerase inhibitor		Ribavirin: with vs without	3.50	0.038	Ferenci et al[69]
	HCV genotype 1

¹Statistical analyses were performed using Fisher’s test, two-tailed. An alpha error < 5% was considered. IL28B: Interleukin-28B; HCV: Hepatitis C virus; SVR: Sustained virologic response; RBV: Ribavirin.