Factors associated with success of telaprevir- and boceprevir-based triple therapy for hepatitis C virus infection

Table 1 Baseline characteristics of the study group

	n	Continuous variables: Median (IQR)/categorical variables: n (%)	Range
Telaprevir	223	172 (77)	-
Demographics and anthropometrics
Age, yr	223	57 (51-61)	22-74
Gender, male	223	144 (65)	-
Race, white	223	182 (82)	-
BMI, kg/m3, 17-24: Normal; 25-30: Overweight; > 30: Obesea	186	27.1 (24.5-30.7)	16.3-49.3
Past medical history
Diabetes	223	48 (22)	-
Depression	223	47 (21)	-
IL28B genotype	223
CC		20 (9)	-
CT		50 (22)	-
TT		21 (10)	-
Unknown		132 (59)	-
Treatment history	223
Naïve		68 (31)	-
Non-responder		95 (43)	-
Relapser		45 (20)	-
Intolerance		12 (5)	-
Unknown		3 (1)	-
HCV treatment related characteristics
HCV viral load, log IU/mL	221	6.31 (5.89-6.66)	3.07-7.64
Sub-genotype	223
1a		118 (53.5)	-
1b		72 (32)	-
1a/1b		1 (0.5)	-
Unknown		32 (14)	-
Laboratory tests
Hemoglobin, g/dL, female:12-15.5 g/dL; male: 13.5-17.5 g/dLa	220	14.3 (13.2-15.3)	9.2-18.2
AFP, ng/mL, 1.6-4.5 ng/mLa	158	6.85 (3.58-13.83)	0.80-208.60
Albumin g/dL, 3.5-4.9 g/dLa	219	4.20 (3.90-4.50)	2.60-5.30
AST, U/L, 1-50 U/La	221	62 (39-106)	19-324
ALT, U/L, 1-53 U/La	221	67 (44-107)	15-403
Platelets, × 103/μL, 150-450 × 103/μLa	223	152 (106-195)	14-365
Creatinine, mg/dL, 0.60-1.40 mg/dLa	205	0.91 (0.81-1.04)	0.58-10.2
Ferritin, ng/mL, 15-150 ng/mLa	54	184 (113-373)	22-893
eGFR, mL/min/1.73 m2 < 60 mL/min per 1.73 m2ab	204	88 (75-99)	6-125
Indication of liver fibrosis
APRI score	221	0.82 (0.43-1.82)	0.10-12.48
FIB-4 score	221	2.65 (1.77-5.66)	0.35-35.30
FIB-4, advanced fibrosis/cirrhosisc	221	98/221 (44)	-
Cirrhosis, biopsy	189	85/189 (45)	-
Transient elastography score, kPa	80	11.8 (7.2-20.3)	3.9-55.1
Cirrhosis, transient elastographyd	80	36/80 (45)	-
Cirrhosis, transient elastography/biopsy	202	96/202 (48)	-

^aNormal range;

^bEstimated glomerular filtration rate calculated with epidemiology formula;

^cFIB-4 score ≥ 3.25 kPa;

^dTransient elastography > 13.5 kPa. BMI: Body mass index; HCV: Hepatitis C virus; AFP: Alpha-fetoprotein; AST: Aspartate transaminase; ALT: Alanine transaminase; eGFR: Estimated glomerular filtration rate; APRI: Aspartate transaminase to platelet ratio index.

Table 2 Univariable and multivariable logistic regression for baseline factors associated with sustained virological response

	Univariable			Multivariablea
	OR	95%CI	P	OR	95%CI	P
Protease inhibitor, telaprevir	1.62	0.84-3.12	0.15	-	-	-
Age, yr	0.98	0.96-1.01	0.23	-	-	-
Gender, male	1.11	0.64-1.94	0.71	-	-	-
Race, white	3.12	1.41-6.90	< 0.01	5.92	2.34-14.96	< 0.01
Diabetes	0.43	0.21-0.87	0.02	-	-	-
Depression	1.58	0.83-3.02	0.17	-	-	-
BMI, kg/m2	0.98	0.93-1.04	0.52	-	-	-
IL28B, CC vs CT/TT	3.56	1.31-9.64	0.01	3.54	1.19-10.53	0.02
Treatment history, naïve/relapser	1.86	1.08-3.20	0.03	-	-	-
HCV viral load, log IU/mL	0.79	0.54-1.14	0.21	-	-	-
Sub-genotype, 1b (vs all other)	2.06	1.17-3.65	0.01	2.81	1.45-5.44	0.02
Hemoglobin, g/dL	1.03	0.86-1.23	0.78	-	-	-
AFP, ng/mL	0.95	0.92-0.98	< 0.01	-	-	-
Albumin, g/dL	2.56	1.33-4.92	< 0.01	-	-	-
AST, U/L	0.99	0.99-0.99	0.02	-	-	-
ALT, per U/L	1.00	0.99-1.01	0.61	-	-	-
Platelets, per × 104/µL	1.08	1.03-1.13	< 0.01	1.10	1.05-1.16	< 0.01
Creatinine, per mg/dL	0.8	0.42-1.53	0.50	-	-	-
Ferritin, per ng/mL	0.99	0.99-1.00	0.63	-	-	-
eGFR, per mL/min per 1.73 m2	1.00	0.99-1.02	0.65	-	-	-
APRI	0.84	0.70-1.02	0.08	-	-	-
FIB-4	0.91	0.83-0.99	0.02	-	-	-
APRI > 1.5	0.44	0.24-0.82	0.01	-	-	-
FIB-4 ≥ 3.25	0.39	0.22-0.68	< 0.01	-	-	-
Cirrhosis transient elastography/biopsy	0.5	0.29-0.87	0.01	-	-	-

^aModel includes platelets and no variable significantly correlated with platelets. BMI: Body mass index; HCV: Hepatitis C virus; AFP: Alpha-fetoprotein; AST: Aspartate transaminase; ALT: Alanine transaminase; eGFR: Estimated glomerular filtration rate; APRI: Aspartate transaminase to platelet ratio index.

Table 3 Comparison of on-treatment variables in the sustained virologic response and non- sustained virologic response group

	Total cohort Categorical: n (%) Continous: Median (IQR)	SVR (n = 94)	Fail to achieve SVR (n = 129)	P
Discontinuation due to adverse events	44/223 (20%)	13/94 (14%)	31/94 (24%)	0.06a
Change in ferritin from baseline to week 4 of treatment, ng/mL	91 (45-212)	146 (81-331)	62 (-20-175)	0.08b
Development of severe anemia	94/223 (42%)	54/94 (57%)	66/129 (51%)	0.35a
Change in eGFR from baseline to week 4c, mL/min per 1.73 m2	-4.41 (-14.87-3.23)	-6.59 (-16.98-0.52)	-1.68 (-13.99-5.00)	0.04b
Fast viral kinetics	139/223 (62%)	83/94 (88%)	56/129 (43%)	< 0.01a

^aχ² test;

^b Mann-Whitney test;

^c Estimated glomerular filtration rate calculated with epidemiology formula. SVR: Sustained virological response; eGFR: Estimated glomerular filtration rate.

Table 4 Univariable and multivariable logistic regression of factors associated with relapse

	Univariable			Multivariable
	OR	95%CI	P	OR	95%CI	P
Protease inhibitor, Telaprevir	0.41	0.15-1.10	0.08	-	-	-
Age, yr	1.00	0.96-1.05	0.95	-	-	-
Gender, female	1.36	0.53-3.48	0.52	-	-	-
Race, black	1.16	0.28-4.71	0.84	-	-	-
Diabetes	1.86	0.65-5.28	0.25	-	-	-
Depression	0.54	0.17-1.75	0.30	-	-	-
BMI, per kg/m2	0.98	0.88-1.10	0.76	-	-	-
IL28B, CC vs CT/TTa	-	-	-	-	-	-
Treatment history, naïve/relapser	1.10	0.45-2.72	0.84	-	-	-
HCV viral load, log IU/mL	1.74	0.80-3.78	0.16	-	-	-
Sub-genotype, 1a (vs all other)	6.26	1.75-22.45	0.01	5.15	1.40-18.97	0.01
Hemoglobin, g/dL	1.24	0.88-1.73	0.22	-	-	-
AFP, ng/mL	1.02	0.99-1.05	0.15	-	-	-
Albumin, g/dL	1.02	0.34-3.08	0.97	-	-	-
AST, U/L	1.01	1.00-1.02	0.06	-	-	-
ALT, U/L	1.00	0.99-1.01	0.23	-	-	-
Platelets, × 104/µL	0.95	0.89-1.02	0.19	-	-	-
Creatinine, mg/dL	1.41	0.72-2.74	0.31	-	-	-
Ferritin, ng/mL	1.00	0.99-1.01	0.26	-	-	-
eGFR, mL/min per 1.73 m2b	0.99	0.97-1.02	0.66	-	-	-
APRI score	1.16	0.94-1.43	0.17	-	-	-
FIB-4 score	1.03	0.94-1.13	0.49	-	-	-
APRI > 1.5	2.33	0.87-6.23	0.09	-	-	-
FiB-4 ≥ 3.25	2.77	1.12-6.86	0.03	2.77	1.07-7.22	0.04
Cirrhosis, transient elastography/biopsy	2.55	1.05-6.19	0.04	-	-	-

^aZero patients with IL28b CC genotype relapsed after completing treatment; ^bEstimated glomerular filtration rate calculated with epidemiology formula. BMI: Body mass index; HCV: Hepatitis C virus; AFP: Alpha-fetoprotein; AST: Aspartate transaminase; ALT: Alanine transaminase; eGFR: Estimated glomerular filtration rate; APRI: Aspartate transaminase to platelet ratio index.