Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection

Table 1 Patient characteristics, transmission route and co-morbidities n (%)

Patients	< 60 yr	≥ 60 yr	P value
Mean age	4558 (94.0)	301 (6.0)	< 0.0001
Gender			< 0.0001
Male	3001 (65.8)	133 (44.2)	-
Female	1557 (34.2)	168 (55.8)	-
Race
Caucasian	4373 (95.9)	289 (96.0)
African	78 (1.7)	6 (2.0)
Asian	88 (1.9)	5 (1.7)
Hispanic	16 (0.4)	1 (0.5)
Unknown/other	3 (0.1)	0
Genotype			< 0.0001
1	2614 (57.3)	245 (81.4)	-
2	258 (5.7)	27 (9.0)	-
3	1480 (32.5)	21 (7.0)	-
Others (4, 5, 6)	206 (4.5)	8 (2.6)
Initial viral load
> 1 Mio copies/mL	2659 (58.9)	193 (64.5)	0.0830
Thrombocytes (/μL)	221.259 (635-595000; SD 71.884)	186.433 (21000-557500; SD 70546)
Within normal range	3736 (85.1)	207 (72.9)
(140000-360000 c/μL)
Below normal range	503 (11.5)	72 (25.4)
(< 140000 c/μL)
Above normal range	150 (3.4)	5 (1.8)
(> 360000 c/μL)
GPT/ALT (U/L)	107 (4-1409; SD 103)	115 (20-591; SD 89)
Within normal range	882 (20.0)	27 (9.5)
(Male ≥ 50 U/L;
Female < 35 U/L)
Above normal range	3521 (80.0)	258 (90.5)
(Male ≥ 50 U/L;
Female ≥ 35 U/L)
GOT/AST (U/L)	74 (10-2880; SD 87)	92 (18-526; SD 71)
Within normal range	1530 (36.5)	43 (16.3)
(Male < 50 U/L;
Female < 35 U/L)
Above normal range	2658 (63.5)	221 (83.7)
(Male ≥ 50 U/L;
Female ≥ 35 U/L)
GGT (U/L)	96 (4-1871; SD 129)	111 (9-1240; SD 137)
Within normal range	2186 (50.2)	98 (35.4)
(Male < 66 U/L;
Female < 39 U/L)
Above normal range	2165 (49.8)	179 (64.6)
(Male ≥ 66 U/L;
Female ≥ 39 U/L)
INR
< 1.7	2758 (98.1)	182 (95.3)
1.7-2.3	31 (1.1)	4 (2.1)
> 2.3	22 (0.8)	5 (2.6)
Body mass index	25.2	26.5	0.000
(mean value)
Treatment naive	4038 (88.6)	253 (84.1)	0.0176
Estimated duration of infection (yr)	11.6	19.9	0.000
Histology available in Degree of Fibrosis	746 (16.4)	90 (29.9)	< 0.0001
P value adjusted			0.0003
(0-4 without unknown)
F0/1/2	533 (71.4)	48 (53.3)
F3/4	104 (14.0)	28 (31.1)
Unknown	109 (14.6)	14 (15.6)
APRI score			< 0.0001
< 1.5	3526 (85.7)	181 (70.2)
≥ 1.5	587 (14.3)	77 (29.8)
Duration of therapy	32.5	33.0	0.6250
(mean value) (wk)
Co-morbidities			0.6198
(with/none)
None	1792 (39.3)	114 (37.9)	-
With	2766 (60.7)	187 (62.1)	-
Cardiac	305 (6.7)	98 (32.6)	< 0.0001
Metabolic	204 (4.5)	53 (17.6)	< 0.0001
Drugs and alcoho	1469 (32.2)	10 (3.3)	< 0.0001
Psychogenic	768 (16.8)	26 (8.6)	< 0.0002
Skin	116 (2.5)	8 (2.7)	0.8500

Patient characteristics, transmission route and co-morbidities: multiple choice possible: comparison of patients < 60 years vs≥ 60 years with chronic hepatitis. APRI score: [(aspartate aminotransferase (AST) of the sample/reference AST) × 100]/thrombocyte count. Cardiac: pAVK, coronary heart disease, stenocardia, cardiac infarction, arterial vascular disease, hypertension. Psychogenic: depression, psychosis, attempted suicide. Drugs and alcohol: Active, former and substituted consumption. Metabolic: Diabetes, disorder in lipid metabolism. ALT: Alanine aminotransferase; INR: International Normalized Ratio.

Table 2 Rates and reasons for treatment discontinuation n (%)

	All genotypes		P value	OR (95%CI)	Genotype 1		P value	OR (95%CI)
	< 60 yr	≥ 60 yr			< 60 yr	≥ 60 yr
Treatment discontinuation	1402 (30.8)	144 (47.8)	0.000	2.065 (1.633-2.611)	985 (37.7)	134 (54.7)	0.000	1.996 (1.534-2.599)
Non-response	622 (13.6)	80 (26.6)	0.000	2.291 (1.750-2.999)	535 (20.5)	78 (31.8)	0.000	1.815 (1.365-2.414)
Lost to follow up	323 (7.1)	6 (2.0)	0.002	0.267 (0.118-0.603)	176 (6.7)	4 (1.6)	0.004	0.230 (0.085-0.625)
Adverse events	142 (3.1)	34 (11.3)	0.000	3.960 (2.670-5.873)	89 (3.4)	30 (12.2)	0.000	3.959 (2.558-6.126)
Of them due to intolerance RBV	49 (1.1)	19 (6.3)	0.000	6.200 (3.602-10.673)	35 (1.3)	16 (6.5)	0.000	5.148 (2.807-9.444)
Of them due to intolerance IFN	91 (2.0)	23 (7.6)	0.000	4.061 (2.530-6.519)	62 (2.4)	21 (8.6)	0.000	3.859 (2.309-6.448)
Patient request	210 (4.6)	22 (7.3)	0.035	1.633 (1.035-2.575)	127 (4.9)	21 (8.6)	0.013	1.836 (1.134-2.971)
Compliance	160 (3.5)	3 (1.0)	0.028	0.277 (0.088-0.872)	87 (3.3)	2 (0.8)	0.046	0.239 (0.058-0.977)
Co-morbidities	41 (0.9)	7 (2.3)	0.020	2.623 (1.167-5.898)	30 (1.1)	6 (2.4)	0.081
Death	12 (0.3)	3 (1.0)	0.039	3.814 (1.070-13.588)	10 (0.4)	3 (1.0)	0.061
Others	74 (1.6)	2 (0.7)	0.194		50 (1.9)	2 (0.8)	0.219

Rates and reasons for treatment discontinuation: multiple choice possible: comparison of patients < 60 years vs≥ 60 years with chronic hepatitis C. Others: Conspicuous blood results, hospitalisation, unexpected incident. RBV: Ribavirin; IFN: Interferon.

Table 3 Rates of dose modification n (%)

	All genotypes		P value	OR (95%CI)	Genotype 1		P value	OR (95%CI)
	< 60 yr(n = 4558)	≥ 60 yr(n = 301)			< 60 yr(n = 2614)	≥ 60 yr(n = 245)
No dose reduction	3933 (86.3)	208 (69.1)	0.000	2.814 (2.172-3.644)	2204 (84.3)	166 (67.8)	0.000	2.558 (1.918-3.412)
Reduction of RBV	286 (6.3)	55 (18.3)	0.000	1.827 (1.560-2.140)	190 (7.3)	47 (19.2)	0.000	1.74 (1.460-2.074)
Reduction of	224 (4.9)	20 (6.6)	0.183		129 (4.9)	17 (6.9)	0.173
pegINF α2a
Reduction of RBV and pegINF α2a	115 (2.5)	18 (6.0)	0.001	1.349 (1.138-1.600)	91 (3.5)	15 (6.1)	0.039	1.218 (1.010-1.470)

Rates of dose modification: Comparison of patients < 60 years vs≥ 60 years with chronic hepatitis C. RBV: Ribavirin; pegIFN: Pegylated interferon.

Table 4 Sustained virological response rates stratified for treatment history

Patients	< 60 yr	≥ 60 yr	P value
Mean age	4558 (94.0)	301 (6.0)	< 0.0001
Gender			< 0.0001
Male	3001 (65.8)	133 (44.2)	-
Female	1557 (34.2)	168 (55.8)	-
Race
Caucasian	4373 (95.9)	289 (96.0)
African	78 (1.7)	6 (2.0)
Asian	88 (1.9)	5 (1.7)
Hispanic	16 (0.4)	1 (0.5)
Unknown/other	3 (0.1)	0
Genotype			< 0.0001
1	2614 (57.3)	245 (81.4)	-
2	258 (5.7)	27 (9.0)	-
3	1480 (32.5)	21 (7.0)	-
Others (4, 5, 6)	206 (4.5)	8 (2.6)
Initial viral load
> 1 Mio copies/mL	2659 (58.9)	193 (64.5)	0.0830
Thrombocytes (/μL)	221.259 (635-595000; SD 71.884)	186.433 (21000-557500; SD 70546)
Within normal range	3736 (85.1)	207 (72.9)
(140000-360000 c/μL)
Below normal range	503 (11.5)	72 (25.4)
(< 140000 c/μL)
Above normal range	150 (3.4)	5 (1.8)
(> 360000 c/μL)
GPT/ALT (U/L)	107 (4-1409; SD 103)	115 (20-591; SD 89)
Within normal range	882 (20.0)	27 (9.5)
(Female < 35 U/L)
Above normal range	3521 (80.0)	258 (90.5)
(Male ≥ 50 U/L;
Female ≥ 35 U/L)
GOT/AST (U/L)	74 (10-2880; SD 87)	92 (18-526; SD 71)
Within normal range	1530 (36.5)	43 (16.3)
(Male < 50 U/L;
Female < 35 U/L)
Above normal range	2658 (63.5)	221 (83.7)
(Male ≥ 50 U/L;
Female ≥ 35 U/L)
GGT (U/L)	96 (4-1871; SD 129)	111 (9-1240; SD 137)
Within normal range	2186 (50.2)	98 (35.4)
(Male < 66 U/L;
Female < 39 U/L)
Above normal range	2165 (49.8)	179 (64.6)
(Male ≥ 66 U/L;
Female ≥ 39 U/L)
INR
< 1.7	2758 (98.1)	182 (95.3)
1.7-2.3	31 (1.1)	4 (2.1)
> 2.3	22 (0.8)	5 (2.6)
Body mass index	25.2	26.5	0.000
(mean value)
Treatment naive	4038 (88.6)	253 (84.1)	0.0176
Estimated duration of infection (yr)	11.6	19.9	0.000
Histology available in Degree of Fibrosis	746 (16.4)	90 (29.9)	< 0.0001
P value adjusted			0.0003
(0-4 without unknown)
F0/1/2	533 (71.4)	48 (53.3)
F3/4	104 (14.0)	28 (31.1)
Unknown	109 (14.6)	14 (15.6)
APRI score			< 0.0001
< 1.5	3526 (85.7)	181 (70.2)
≥ 1.5	587 (14.3)	77 (29.8)
Duration of therapy	32.5	33.0	0.6250
(mean value) (wk)
Co-morbidities			0.6198
(with/none)
None	1792 (39.3)	114 (37.9)	-
With	2766 (60.7)	187 (62.1)	-
Cardiac	305 (6.7)	98 (32.6)	< 0.0001
Metabolic	204 (4.5)	53 (17.6)	< 0.0001
Drugs and alcoho	1469 (32.2)	10 (3.3)	< 0.0001
Psychogenic	768 (16.8)	26 (8.6)	< 0.0002
Skin	116 (2.5)	8 (2.7)	0.8500

SVR: Sustained virological response.

Table 5 Sustained virological response rates stratified for genotype, APRI score and age

	APRI score	SVR n (%)	P
GT 1			χ2test
< 60 yr	< 1.5	936 (45.7)	0.000
	≥ 1.5	99 (31.2)
≥ 60 yr	< 1.5	40 (26.5)	0.476
	≥1 .5	12 (20.7)
GT 2/3
< 60 yr	< 1.5	799 (60.8)	0.000
	≥ 1.5	106 (43.6)
≥ 60 yr	< 1.5	18 (66.7)	0.526
	≥ 1.5	9 (52.9)

SVR: Sustained virological response.

Table 6 Multivariate logistic regression for fibrosis, age and ribavirin/peg-interferon adverse events as factors for sustained virological response

	Sig.	Exp (B)	95%CI for EXP(B)
			Lower	Upper
Fibrosis stage F4 vs Fibrosis stage F0, F1, F2, F3	0.004	0.717	0.573	0.897
Age 60 yr vs < 60 yr	0.003	0.427	0.243	0.750
Treatment discontinuation due to ribavirin adverse events	0.142
Treatment discontinuation due to Peg-IFN adverse events	0.998

IFN: Interferon.