Roeder C, Jordan S, Schulze zur Wiesch J, Pfeiffer-Vornkahl H, Hueppe D, Mauss S, Zehnter E, Stoll S, Alshuth U, Lohse AW, Lueth S. Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection. World J Gastroenterol 2014; 20(31): 10984-10993 [PMID: 25152602 DOI: 10.3748/wjg.v20.i31.10984]
Corresponding Author of This Article
Dr. Stefan Lueth, PD, Department of Medicine I, University Hospital Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. slueth@uke.de
Research Domain of This Article
Virology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Aug 21, 2014; 20(31): 10984-10993 Published online Aug 21, 2014. doi: 10.3748/wjg.v20.i31.10984
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
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
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)
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
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)
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
Citation: Roeder C, Jordan S, Schulze zur Wiesch J, Pfeiffer-Vornkahl H, Hueppe D, Mauss S, Zehnter E, Stoll S, Alshuth U, Lohse AW, Lueth S. Age-related differences in response to peginterferon alfa-2a/ribavirin in patients with chronic hepatitis C infection. World J Gastroenterol 2014; 20(31): 10984-10993