Inter-facility analysis of cohort clinical and demographic characteristics
A total of 238 patients [Hospital A: 142(59.7%) vs Hospital B: 96(40.3%)], treatment naïve patients, were enrolled for care from 2018–2021(94 (39.5%) ≤ 2019; 74(31.1%) = 2020; 70(29.4%) ≥2021). The median age at diagnosis was 59(IQR: 50–69) years. HCV/HIV and HCV/HBV co-infection was observed in 9(3.8%) and 3(1.3%) patients, respectively. The mean (± SD) hemoglobin (Hgb) and PLTs count was 14.3 (±1.7) g/dL and 181.9 (±92.3) x 109/µL, respectively. Moreover; anemia (Hgb < 12 g/dL in women and Hgb < 13 g/dL in men) was present in 12(5%) patients while 76(31.9%) patients had thrombocytopenia. According to FIB-4 score estimates, cirrhosis was highly likely in 81(34%) whereas 81 (34%) and 47(19.5%) had indeterminate and less likelihood of cirrhosis, respectively. See Table 1 for pairwise comparisons of means, medians and/or proportions in the two facilities.
Table 1. Demographic characteristics, patient history, and laboratory measurements at inclusion in the study among chronic Hepatitis-C infected individuals in Eritrea.
Characteristics
|
Population N (%)
|
Hospital A N (%)
|
Hospital B N (%)
|
p-value (χ2)
|
Age at Enrollment (Mean±SD)
|
59 ± 12.6
|
59 ± 12.7
|
60.5 ± 12.4
|
0.34b
|
<50 years
|
51(21.5)
|
34(24.1)
|
17(17.7)
|
0.25(2.761)
|
≥50-60 years
|
58(24.5)
|
37(26.2)
|
21(21.9)
|
>60 years
|
128(54.0)
|
70(49.6)
|
58(54.0)
|
Gender
|
Male
|
100 (42)
|
63 (44.4)
|
37 (38.5)
|
0.37 (0.798)
|
Female
|
138 (58)
|
79 (55.6)
|
59 (61.5)
|
Address
|
Central zone
|
199 (83.6)
|
119 (83.8)
|
23 (83.3)
|
0.92 (0.009)
|
Outside central zone
|
39 (16.3)
|
23 (16.2)
|
16 (16.7)
|
Enrollment year
|
≤ 2019
|
94 (39.5)
|
66 (46.4)
|
28 (29.2)
|
0.026 (7.3)
|
2020
|
74 (31.1)
|
38 (26.8)
|
36 (37.5)
|
≥ 2021
|
70 (29.4)
|
38 (26.8)
|
32 (33.3)
|
Marital status
|
Married
|
98 (83)
|
17 (60.7)
|
81 (91)
|
< 0.001 (21.5)
|
Single
|
19 (17.1)
|
11 (39.3)
|
11 (8.2)
|
DAA regimen
|
SOF/VEL
|
183 (76.9)
|
90 (63.4)
|
93 (96.9)
|
< 0.001
(36.3)
|
SOF/DCV
|
44 (18.5)
|
41 (28.9)
|
3 (3.1)
|
Not initiated on DAA
|
11 (4.6)
|
11 (7.7)
|
0
|
Median Baseline HCV RNA [IQR]) (Log10 IU/ml)
|
6.12 (5.5-6.5)
|
6.1 (5.7-6.6)
|
6 (5.4-6.5)
|
0.15a
|
HCV RNA (IU/ml)
|
|
|
|
|
<800,000
|
80(38.5)
|
49(61.2)
|
31(38.8)
|
0.37(0.982)
|
>800,000
|
128(61.5)
|
87(68.0)
|
41(32.0)
|
HBsAg
|
Positive
|
3 (1.3)
|
2 (1.4)
|
1 (1)
|
< 0.001 (27.9)
|
Negative
|
73 (30.7)
|
62 (43.7)
|
11 (11.5)
|
No data entry
|
162 (68.1)
|
78 (54.9)
|
84 (87.5)
|
HIV status
|
Positive
|
9 (3.8)
|
5 (3.6)
|
4 (4.2)
|
0.58 (0.29)
|
Negative
|
84 (35.8)
|
48 (34.5)
|
36 (37.5)
|
No data entry
|
142 (60.4)
|
86 (61.9)
|
56 (58.3)
|
Baseline Hematology
|
Hemoglobin (g/dL), mean ±SD
|
14.3 ± 1.7
|
14.3 ± 1.6
|
- (Only one)
|
|
Platelets (×109/µL), mean ±SD
|
181.9 ± 92.3
|
179.3 ± 68.9
|
190.5 ± 81.5
|
0.6b
|
Liver function test
|
AST (IU/L) [median (IQR)]
|
41 (29-75)
|
45 (30-68)
|
40 (29-65.8)
|
0.65a
|
ALT (IU/L) [median (IQR)]
|
33.5 (19.8-60.2)
|
31 (17-60)
|
37.5 (22-64.5)
|
0.1a
|
(FIB-4) Non-invasive Fibrosis Evaluation in Hepatitis C
|
Less likely
|
47 (19.5)
|
29 (26.4)
|
20 (23.5)
|
0.88 (0.246)
|
Intermediate
|
81 (34)
|
40 (36.4)
|
31 (36.5)
|
Highly likely
|
81 (34)
|
41 (37.3)
|
34 (40)
|
APRI score
|
0.5 (0.3-1.1)
|
0.5 (0.3-1.1)
|
0.5 (0.3-0.9)
|
0.5a
|
<0.5
|
118 (55.1)
|
68 (54.4)
|
50 (56.2)
|
0.7 (0.06)
|
>0.5
|
96 (44.9)
|
57 (45.6)
|
39 (43.8
|
Treatment response
|
Sustained virologic response
|
116 (92.8)
|
80 (95.2)
|
36 (87.8)
|
0.1 (1.3)
|
Treatment non-response
|
9 (7.5)
|
4 (4.8)
|
5 (12.2)
|
Median Duration of treatment (IQR) weeks
|
90 (60-114)
|
89 (60-97)
|
94 (66-177)
|
0.04a
|
Survival outcome
|
Positive outcome
|
153 (64.2)
|
101 (71.1)
|
52 (54.2)
|
0.01 (8)
|
Lost to follow up
|
67 (28.1)
|
34 (23.9)
|
33 (34.4)
|
Dead
|
18 (7.5)
|
7 (4.9)
|
11 (11.5)
|
Median duration of follow up, (IQR)
|
107 (60-239)
|
115 (89-275)
|
112 (69-181)
|
0.01a
|
Abbreviations: SOF+DCV: Sofosbuvir+Declatasavir; SOF+VEL: Sofosbuvir+Velpatasavir; HBsAg: Hepatitis B surface antigen; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; IQR: Interquartile range; SD: Standard deviation; DAA: Direct-acting antiretroviral therapy; HCV: Hepatitis C virus; RNA: Ribonucleic acid; HIV: Human Immunodeficiency virus.
Superscripts: a: Mann-Whitney U test; b: independent samples t-test
Specific host factors and Liver Fib-4 Score stages
Analysis of specific host factors and FIB-4 index uncovered a number of findings. Compared to participants with FIB-4>3.25 points, participants with FIB-4 <3.25 points were younger (50± 12 vs. 60±10 years, p-value<0.001); had lower median AST (IQR) (27(20-34) vs 66 (45-133) IU/L, p-value<0.001); higher baseline Hgb (14.7±1.7 g/dL) vs 13.6 ±1.6 g/dL) p-value <0.02; and Higher mean PLT counts (255(±99) x 109/µL) vs135(±48) x 109/µL), p-value<0.001. Significant differences were not observed across sex, ALT and baseline VL. Moreover; Majority of patients with cirrhosis (FIB-4 score >3.25) were initiated on SOF/VEL (77.9%). (Table 2).
Table 2: Host factors and Fib-4 Score stages among chronic Hepatitis-C infected individuals in Eritrea.
Characteristics
|
Cirrhosis less likely
|
Indeterminate
|
Cirrhosis highly likely
|
P-value
|
Male n (%)
|
21(23.3)
|
34(37.8)
|
35(38.9)
|
0.956
|
Age in years, mean(±SD)
|
50 (12)
|
60 (10)
|
64 (10)
|
<0.001a
|
Baseline AST (IU/L), median (IQR)
|
27 (20-34)
|
38 (30-52)
|
66 (45-133)
|
<0.001b
|
Baseline ALT (IU/L), median (IQR)
|
26 (17-47)
|
38 (20-60)
|
33 (21-76)
|
0.1b
|
PLT (×109/µL) count, mean (±SD)
|
255 (99)
|
198 (56)
|
135 (48)
|
<0.001a
|
Baseline Log10VL (IU/ML), median (IQR)
|
6.06 (5.3 – 6.6)
|
6.2 (5.7-6.6)
|
6 (5.6 -6.3)
|
0.2b
|
HGB (g/dL), mean (±SD)
|
14.7 (1.7)
|
14.8 (1.1)
|
13.6 (1.6)
|
0.02a
|
DAAT, SOF/VEL
|
38 (80.9%)
|
68 (85%)
|
60 (77.9%)
|
0.5c
|
DAAT, SOF/DCV
|
9 (19.9%)
|
12 (15%)
|
17 (22.1%)
|
Abbreviation: AST: Aspartate aminotransferase; ALT: Alanine aminotransferase. IQR: interquartile range.
Superscripts: a -One-way ANOVA, b- Kruskal-Wallis test
Outcomes of DAA Therapy
Out of 238 patients enrolled in the study, 227 were initiated on treatment. The median duration of treatment was 90 (IQR: 60-114) days. Of 227 patients who initiated treatment with DAAT, 125 (55%) patients had viral load at 12 weeks EOT whereas 102 patients had no viral load at 12 weeks EOT (54 were LTFU and 18 died before SVR12 while 19 patients were on treatment during the study period). Of the 125 patients with HCV RNA data post EOT, 116 (92.8%) had SVR12. According to the data, there was no statistical difference in SVR rates between the SOF/VEL and SOF/DCV groups (93.9% and 88.9% respectively, p-value=0.6). Moreover; 58 (96.7%) and 12 (85.7%) of patients on SOF+VEL and SOF+DOC with FIB-4 score < 3.25 attained SVR respectively. Among patients with a FIB-4 score > 3.25 (Cirrhosis), 27 (87.1%) of patients on SOF+VEL and 11 (100%) of patients on SOF+DOC attained SVR. No significant difference was identified in the rate of SVR between the FIB-4 ≤ 3.25 and FIB-4 > 3.25 groups (94.5% and 90.5%, respectively, p-value=0.4). (Figure 3).
Figure 3: SVR attainment by specific DAA combinations per specific Fib-4 categories.
a – Chi-square test
Pre- and Post-treatment values of specific variables
Pre-treatment and post-treatment analysis of specific laboratory variables demonstrated that AST and ALT, were significantly lower than pre-treatment values (41(IQR: 30-68) vs 30(IQR: 24-35), p-value<0.001) and (33(IQR: 20-60) vs 18(IQR: 14-26), p-value<0.001) respectively. Moreover; FIB-4 score and APRI score were significantly lower following treatment with DAA (2.1(IQR:1.4-4.1) vs 1.9 (IQR: 1.2-2.9), p-value=0.003) and (0.5(IQR: 0.3-1) vs 0.3 (IQR: 0.2-0.5), p-value<0.001 respectively. However, PLT count demonstrated limited improvement following treatment (Table 3).
Table 3: Alterations in Laboratory parameters in response to DAA among chronic Hepatitis-C infected individuals in Eritrea.
Characteristics
|
Pretreatment
|
Post-treatment
|
p-value
|
AST, median (IQR)
|
41(30-68)
|
30 (24-35)
|
<0.001a
|
ALT, median (IQR)
|
33(20-60)
|
18(14-26)
|
<0.001a
|
PLT count, mean (±SD)
|
185 (78)
|
180 (69)
|
0.4b
|
VL Log10, median (IQR)
|
6.15(5.56-6.58)
|
0.0(0.0-0.0)
|
<0.001a
|
FiB-4 Score
|
2.1 (1.4-4.1)
|
1.9 (1.2-2.9)
|
0.003a
|
APRI score
|
0.5 (0.3-1)
|
0.3 (0.2-0.5)
|
<0.001a
|
Abbreviations: AST: Aspartate aminotransferase; ALT: Alanine aminotransferase. IQR: interquartile range; VL: Viral load; SD: Standard deviation.
Superscripts: a- Wilcoxon signed-rank test, b- Paired Samples t-test
Loss to follow-up and Mortality in the HCV care cascade
Death occurred in 18 (7.5% (95% CI: 1.7-4.1) patients while 67 cases were LTFU (28.1%, 95%CI: 22.3-33.9). Analysis of the proportion of LTFU and death through HCV Cascade of Care demonstrated that 11(61.2%) deaths occurred before treatment completion and 7 (38.8%) occurred before SVR. In contrast, 11 (16.4%) LFTU occurred at a follow-up appointment after diagnosis; 28(41.7%) occurred before treatment completion; 26(38.8%) occurred before SVR and 2(2.9%) occurred post SVR care (Figure 4).
Figure 4: Proportion of loss to follow-up and Mortality in the Consensus HCV care cascade
Factors associated with Mortality and LTFU
Patients who died had a significantly shorter median duration on treatment with DAA of 31 days (IQR: 21-227) as compared to 90 days (IQR: 80-144) and 84 days (IQR: 42-92) for a positive outcome and LTFUs, respectively (p-value=0.002). Mortality was also associated with FIB-4 score > 3.25, ALT > 40 IU/L and AST > 40 IU/L. Similarly, Patients that died had significantly higher APRI scores as compared to LTFU and Positive outcomes. Moreover, mortality was associated with higher values of baseline AST (111.5 (IQR: 53-111.5) vs. 48.5 (IQR: 31.7-73.2) and 28 (IQR: 21.7-65.7) for a positive outcome and LTFU respectively; p-value<0.001. Majority (75 %) of patients that died received DAA for < 12 weeks. Moreover patients that died had a higher median FIB score, 6.9 (IQR: 4.5-6.9) as compared to positive outcome 3.1 (IQR: 1.6-6.2) and LTFU 1.3 (IQR: 0.9-6); p-value<0.001. In contrast, LTFU was higher in both patients who had not started treatment and had been on follow-up for ≤ 12 weeks while Fib-score was relatively lower as compared to positive outcome and Death (Table 4).
Table 4: Demographic characteristics, patient history, and laboratory measurements with treatment and follow-up outcome at inclusion time in the study among Hepatitis-C infected individuals in Eritrea
Characteristics
|
Positive outcome n (%)
|
LTFU (%)
|
Dead (%)
|
P-value
|
Gender
|
|
|
|
|
Male
|
61 (39.9)
|
30 (44.8)
|
9 (50)
|
0.61 (0.9)
|
Female
|
92 (60.1)
|
37 (55.2)
|
9 (50)
|
Age at enrollment, mean ±SD
|
58 (10)
|
50 (16)
|
58 (6)
|
0.34a
|
Address
|
|
|
|
|
Central Zone
|
131 (85.6)
|
55 (82.1)
|
13 (72.2)
|
0.3 (2.2)
|
Outside central zone
|
22 (14.4)
|
12 (17.9)
|
5 (27.8)
|
Enrollment year, median (IQR)
|
2019 (2019-2020)
|
2019 (2019-2019)
|
2018 (2018-2019
|
0.94b
|
<2020
|
62 (40.5)
|
25 (37.3)
|
7 (38.9)
|
0.76 (1.8)
|
2020
|
44 (28.8)
|
25 (37.3)
|
5 (27.8)
|
>2020
|
47 (30.7)
|
17 (25.4)
|
6 (33.3)
|
Marital status
|
|
|
|
|
Married
|
55 (77.5)
|
31 (93.9)
|
12 (92.3)
|
0.07 (5.2)
|
Single
|
16 (22.5)
|
2 (6.1)
|
1 (7.7)
|
Occupation
|
|
|
|
|
Employed
|
41 (58.6)
|
13 (43.3)
|
8 (66.7)
|
0.2 (2.6)
|
Unemployed
|
29 (41.4)
|
17 (56.7)
|
4 (33.3)
|
DAA regimen
|
|
|
|
|
SOF/VEL
|
118 (77.6)
|
50 (73.5)
|
14 (82.4)
|
<0.001 (25)
|
SOF/DCV
|
34 (23.4)
|
7 (10.2)
|
3 (17.6)
|
Not started on DAA
|
0 (0)
|
11 (16)
|
0
|
|
Treatment duration, median (IQR)
|
90 (80-144)
|
84 (42-92)
|
31 (26-227)
|
0.002b
|
≤ 12 weeks
|
110 (72.4)
|
39 (90.7)
|
9 (75)
|
0.003 (15.8)
|
13-24 weeks
|
32 (21.1)
|
1 (2.3)
|
0
|
> 24 weeks
|
10 (6.6)
|
3 (7)
|
3 (25)
|
HBsAg status
|
|
|
|
|
Positive
|
0
|
1 (1.5)
|
2 (11.1)
|
<0.001 (18.8)
|
Negative
|
53 (34.6)
|
17 (25.4)
|
3 (16.7)
|
No data entry
|
100 (65.4)
|
49 (73.1)
|
13 (72.2)
|
HIV status
|
|
|
|
|
Positive
|
6 (4)
|
2 (3)
|
1 (5.6)
|
0.8 (0.9)
|
Negative
|
52 (34.4)
|
27 (40.9)
|
5 (27.8)
|
No data entry
|
93 (61.6)
|
37 (56.1)
|
12 (66.7)
|
FIB-4 score
|
3.1 (1.6-6.2)
|
1.3 (0.9-6)
|
6.9 (4.5-6.9)
|
0.001b
|
Less likely
|
30 (20.8)
|
16 (32.7)
|
1 (6.3)
|
0.01 (13)
|
Indeterminate
|
62 (43.1)
|
16 (32.7)
|
3 (18.8)
|
Highly likely
|
52 (36.1)
|
17 (34.7)
|
12 (75)
|
APRI score
|
0.5 (0.3-1)
|
0.4 (0.2-0.8)
|
1.1 (0.8-2.5)
|
<0.001b
|
< 0.5
|
84 (57.9)
|
32 (62.7)
|
2 (11.1)
|
<0.001 (15.7)
|
> 0.5
|
61 (42.1)
|
19 (37.3)
|
16 (88.9)
|
Initial Serum HCV/RNA, median (IQR)
|
6.2 (5.6-6.5)
|
6 (5.4-6.5)
|
5.8 (4.9-6.2)
|
0.28b
|
Baseline hematology
|
|
|
|
|
Hemoglobin (g/DL), mean ±SD
|
14.4 (1.6)
|
14.3 (1.7)
|
12.3 (1.6)
|
0.14a
|
Platelet count ×109/µL, mean ±SD
|
181 (98)
|
188 (58)
|
133 (44)
|
0.49a
|
Baseline ALT (IU/L), median (IQR)
|
27.5 (19.7-57.7)
|
23 (13.2-39.5)
|
43.5 (35-43.5)
|
0.1
|
ALT < 40
|
82 (53.7)
|
33 (58.9)
|
6 (40)
|
0.39 (1.8)
|
ALT > 40
|
61 (42.7)
|
23 (41.1)
|
9 (60)
|
Baseline AST (IU/L), median (IQR)
|
48.5 (31.7-73.2)
|
28 (21.7-65.7)
|
111.5 (53-111.5)
|
<0.001b
|
AST < 40
|
77 (52)
|
30 (55.6)
|
0
|
<0.001 (17.8)
|
AST > 40
|
71 (48)
|
24 (44.4)
|
17 (100)
|
Duration of follow-up, median (IQR)
|
132 (91-264)
|
60 (2-121)
|
49 (14-228)
|
<0.001b
|
Abbreviations: SD: Standard Deviation; IQR: interquartile range; HBsAg: Hepatitis B surface antigen; HIV: Human immunodeficiency virus; HCV: Hepatitis C virus; ALT: alanine aminotransferase; ASP: Aspartate Aminotransferase; SOF+DCV: Sofosbuvir+Declatasavir; SOF+VEL: Sofosbuvir+Velpatasavir.
Superscripts: a- One-way ANOVA, b- Kruskal-Wallis test
Incidence rates, rate ratio and Kaplan-Meier survival estimates for mortality
Following 29,786 person-days of follow-up, incidence rate of death was 6.04 (95% CI: 3.8-9.5) per 10,000 person-days. Kaplan-Meier survival analysis demonstrated that patients enrolled in Hospital B had a significantly shorter mean duration of survival (548 days (95% CI: 403-694) vs 578 days (95% CI: 533-624), p-value=0.02) (Figure 5c) and RR of death, 3.3(95% CI: 1.1-10.1). Moreover, patients with FIB-4 scores ≥3.25 had a significantly shorter mean survival duration (472 days (95% CI: 402-542) (Figure 5d) and higher risk rate of mortality (732 days (95% CI: 732-732), p<0.001). Lastly, patients from outside central zone had a shorter mean duration of survival, 358 days (95% CI: 283-433) vs 623 days (95% CI: 547-669) for those from central zone, p <0.05) (See Table 5 for details). Patients overall survival curves for LTFU are displayed in figure 5a.
Table 5: Incidence rate and rate ratios of mortality, and Kaplan-Meier survival estimates among chronic Hepatitis-C patients in Eritrea
Cohort Characteristics
|
Person time (days)
|
death Events
|
Incidence of death per 10,000 PDs (95% CI)
|
Relative risk rates (95% CI)
|
Mean survival duration in days (95% CI)
|
P-value (log-rank)
|
Population
|
29786
|
18
|
6.04 (3.8-9.5)
|
|
|
-
|
Hospital
|
|
|
|
|
|
|
Hospital A
|
20253
|
7
|
3.4 (1.6-7.20
|
1
|
578 (533-624)
|
0.02 (5.4)
|
Hospital B
|
9533
|
11
|
11.5 (6.3-20.8)
|
3.3 (1.1-10.1)
|
548 (403-694)
|
Gender
|
|
|
|
|
|
|
Female
|
15691
|
9
|
5.7 (2.9-11)
|
1
|
526 (471-581)
|
0.91 (0.01)
|
Male
|
14095
|
9
|
6.3 (3.3-12.2)
|
1.01 (0.3-2.8)
|
585 (459-712)
|
Address
|
|
|
|
|
|
|
Central zone
|
25577
|
13
|
5 (2.9-8.7)
|
1
|
623 (547-669)
|
0.05 (3.6)
|
Outside central zone
|
4209
|
5
|
11.8 (4.9 -28.5)
|
2.3 (0.6-7)
|
358 (283-433)
|
Enrollment year
|
|
|
|
|
|
|
≤ 2019
|
14824
|
7
|
4.7 (2.2-9.9)
|
1
|
624 (563-720)
|
0.17 (3.53)
|
2020
|
9469
|
5
|
5.2 (2.1-12.6)
|
1.2 (0.3-4.1)
|
468 (392-544)
|
≥ 2021
|
5493
|
6
|
10.9 (4.9-24.3)
|
2.1 (0.6-6.70
|
477 (365-588)
|
Initial regimen
|
|
|
|
|
|
|
SOF/DCV
|
22969
|
15
|
6.5 (3.9-10.8)
|
1
|
134 (30-238)
|
0.157 (3.7)
|
SOF/VEL
|
6816
|
3
|
4.4 (1.4-13.6)
|
0.67 (0.12-2.4)
|
191 (113-270)
|
Treatment duration
|
|
|
|
|
|
|
≤ 12 weeks
|
17070
|
15
|
6.8 (4.1-11.30
|
1
|
79 (22-135)
|
0.1 (3.9)
|
13 and ≤ 24 weeks
|
7597
|
0
|
0
|
0
|
0
|
>24 weeks
|
4341
|
3
|
5.6 (1.8-17.4)
|
1 (0.2-3.80
|
319 (179-459)
|
AST
|
|
|
|
|
|
|
≤ 40IU/L
|
16406
|
|
0 (0)
|
|
0
|
< 0.001 (13.7)
|
> 40 IU/L
|
17612
|
17
|
7.4 (4.4-12)
|
|
144 (58-230)
|
ALT
|
|
|
|
|
|
|
≤ 40IU/L
|
18769
|
6
|
2.5 (1.1-6)
|
1
|
499 (457-542)
|
0.35 (0.86)
|
> 40 IU/L
|
15154
|
9
|
4.6 (2.3-9.1)
|
1.8 (0.5-6.3)
|
572 (444-699)
|
Non-invasive Fibrosis Evaluation in Hepatitis C (FIB-4)
|
|
|
|
Cirrhosis is not highly likely
|
20879
|
4
|
1.9 (0.7-5.1)
|
1
|
649 (537-761)
|
<0.001 (11.3)
|
Cirrhosis highly likely
|
12176
|
12
|
9.8 (5.5-17.30
|
5.1 (1.5-21.8)
|
472 (402-542)
|
Abbreviation: ALT: alanine aminotransferase; AST: Aspartate Aminotransferase; SOF+DCV: Sofosbuvir+Declatasavir; SOF+VEL: Sofosbuvir+Velpatasavir.
Incidence rates and Kaplan-Meier survival estimates for LTFU
The number of LTFU events was 67 events translating into an incidence rate of 1.1 (95% CI: 0.8-1.5) per 10,000 person-days. In the Kaplan-Meier analysis; patients enrolled at Hospital B had a shorter mean duration of survival, 304 days (95% CI: 215-392) vs 736 days (95%:515-956) in Hospital A, p<0.001 (Figure5a). Moreover, patients not initiated on DAA had significantly shorter mean survival duration than those on treatment, 169 days (95% CI: 1-458) vs 371 days (95% CI: 308-434) for patients on SOF/DCV and 830 days (95% CI: 659-1001) for patients on SOF/VEL, p <0.001 (Table 6). Patients overall survival curves for LTFU are displayed in figure 5b.
Table 6: Incidence rate and Kaplan-Meier survival estimates for LTFU among chronic Hepatitis-C patients in Eritrea
Cohort Characteristics
|
Person time (Days)
|
Events
|
Incidence of LTFU per 1000 PDs (95% CI)
|
Mean survival duration in days, 95% CI
|
P-value (log-rank)
|
Population
|
35490
|
67
|
1.1 (0.82-1.5)
|
|
-
|
Hospital
|
Hospital A
|
24719
|
34
|
0.78 (0.52-1.18)
|
736 (515-956)
|
0.008 (7)
|
Hospital B
|
10771
|
33
|
1.8 (1.2-2.7)
|
304 (215-392)
|
Gender
|
Male
|
17432
|
30
|
0.93 (0.6-1.45)
|
685 (448-921)
|
0.5 (0.45)
|
Female
|
18058
|
37
|
1.3 (0.85-1.86)
|
376 (312-439)
|
Address
|
Central zone
|
30604
|
55
|
1.04 (0.75-1.44)
|
700 (510-890)
|
0.45 (0.56)
|
Outside central zone
|
4886
|
12
|
1.3 (0.68-2.7)
|
267 (196-338)
|
Enrollment year
|
≤ 2019
|
18689
|
25
|
0.69 (0.42-1.13)
|
695 (460-929)
|
0.18 (3.4)
|
2020
|
11036
|
25
|
1.5 (0.95-2.4)
|
325 (248-401)
|
≥ 2021
|
5765
|
17
|
1.8 (1-3.2)
|
373 (264-482)
|
Initial regimen
|
SOF/DCV
|
26076
|
50
|
1.9 (1.4-2.5)
|
371 (308-434)
|
< 0.001 (27.7)
|
SOF/VEL
|
7862
|
7
|
0.8 (0.4-1.8)
|
830 (659-1001)
|
Not started
|
1552
|
10
|
6.4 (3.4-11.9)
|
169 (1-458)
|
Treatment duration
|
≤ 12 weeks
|
20454
|
39
|
1.8 (1.3-2.5)
|
364 (290-438)
|
<0.001 (16.1)
|
13 and ≤ 24 weeks
|
7884
|
1
|
1.2 (0.1-9)
|
563 (479-646)
|
>24 weeks
|
4382
|
3
|
5.6 (1.8-17.4)
|
457 (338-575)
|
AST
|
≤ 40mg/dL
|
16406
|
30
|
1.3 (0.84-1.95)
|
404 (342-466)
|
0.73 (0.1)
|
> 40 mg/dL
|
15242
|
24
|
0.7 (0.45-1.2)
|
389 (301-477)
|
ALT
|
≤ 40mg/dL
|
18335
|
33
|
1.3 (0.89-1.9)
|
565 (404-725)
|
0.26 (1.25)
|
> 40 mg/dL
|
13291
|
23
|
0.68 (0.39-1.2)
|
407 (316-498)
|
Non-invasive Fibrosis Evaluation in Hepatitis C (FIB-4)
|
Less likely
|
6232
|
16
|
1.6 (0.94-2.9)
|
270 (169-371)
|
0.22 (3)
|
Intermediate
|
13183
|
16
|
0.6 (0.33-1.24)
|
447 (374-521)
|
Highly likely
|
11300
|
17
|
0.81 (0.44-1.5)
|
396 (309-483)
|
Abbreviation: ALT: alanine aminotransferase; AST: Aspartate Aminotransferase; SOF+DCV: Sofosbuvir+Declatasavir; SOF+VEL: Sofosbuvir+Velpatasavir.
Independent predictors of LTFU in chronic hepatitis C patients in Eritrea
Table 7 presents unadjusted and adjusted hazards ratio for variable associated with LTFU in 238 chronic HCV patients followed from 2018-2021. In the adjusted model, independent predictors of LTFU included enrollment year (2020: aHR=2.2, 95% CI: 1-4.7; p value=0.04); Hospital (Hospital B: aHR = 2.2, 95% CI: 1-4.7; p value=0.03) and FIB-4 score (≥3.25: aHR=3.7, 95% CI: 1.2-11.5; p-value=0.02), (1.45-3.25 points: aHR=1.6 95% CI: 0.6-4.2; p-value=0.3).
Table 7: Cox proportional hazards of LTFU among chronic hepatitis C patients followed in ONRH and HNRH (2018-2021).
Characteristics
|
Unadjusted HR (95% CI)
|
p-value
|
Adjusted HR (95% CI)
|
p-value
|
Gender
|
Male
|
1 (Ref)
|
0.7
|
|
|
Female
|
1.1 (0.5-2.5)
|
|
|
Age at enrollment
|
1 (0.9-1.05)
|
0.7
|
|
|
Address
|
Maekel
|
1 (Ref)
|
0.3
|
|
|
Outside maekel
|
1.3 (0.7-2.5)
|
|
|
Hospital
|
|
|
|
|
Hospital A
|
1 (Ref)
|
|
1 (Ref)
|
|
Hospital B
|
1.9 (1.1-3.1)
|
0.01
|
2.2 (1-4.7)
|
0.03
|
Enrollment year
|
<2020
|
1 (Ref)
|
|
1 (Ref)
|
|
2020
|
1.6 (0.9-2.8)
|
0.09
|
2.1 (1-4.4)
|
0.04
|
>2020
|
1.7 (0.9-3.3)
|
0.08
|
2.5 (0.8-7.9)
|
0.1
|
HBsAg testing
|
Known
|
1 (Ref)
|
0.8
|
|
|
Not data entry
|
1 (0.4-2.6)
|
|
|
HIV status
|
Positive
|
1 (Ref)
|
|
|
|
Negative
|
2.1 (0.5-9.4)
|
0.2
|
|
|
No data entry
|
1.8 (0.4-7.8)
|
0.4
|
|
|
Baseline serum HCV RNA
|
1 (1-1.3)
|
0.3
|
|
|
DAAT regimen
|
SOF+VEL
|
1 (Ref)
|
0.06
|
|
|
SOF+DCV
|
0.4 (0.1-1)
|
|
Baseline ALT
|
1 (0.9-1)
|
0.9
|
|
|
Baseline AST
|
0.9 (0.9-1)
|
0.6
|
|
|
Non-invasive Fibrosis Evaluation in Hepatitis C (FIB-4)
|
Cirrhosis highly likely
|
1 (Ref)
|
|
1 (Ref)
|
|
Indeterminate
|
0.7 (0.4-1.5)
|
0.5
|
1.6 (0.6-4.2)
|
0.3
|
Cirrhosis less likely
|
1.5 (0.7-3.1)
|
0.2
|
3.7 (1.2-11.5)
|
0.02
|
Abbreviations: HBsAg: Hepatitis B surface antigen; HIV: Human immunodeficiency virus; HCV: Hepatitis C virus; ALT: alanine aminotransferase; ASP: Aspartate Aminotransferase; SOF+DCV: Sofosbuvir+Declatasavir; SOF+VEL: Sofosbuvir+Velpatasavir.
Figure 5: Kaplan-Meier curves for cumulative survival, LTFU and mortality of chronic HCV patients followed in the two major treatment centers in Eritrea from 2018-to 2021. Figure 5A: Overall cumulative proportion of death; Figure 5B: Overall cumulative proportion of LTFU; Figure 5C Cumulative proportion of survival by hospital Figure 5D: Cumulative mortality curve by FIB 4 score.