Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population and Study Design
2.2. Pre-LT DAA Therapy
2.3. Sample
2.4. Detection of Anti-HCV Antibodies
2.5. RT-PCR for HCV-RNA Detection
2.6. Immunosuppression Protocol
2.7. Follow-Up Parameters
2.8. Pathological Interpretation
2.9. Ethics
2.10. Statistics
3. Results
3.1. Patient Characteristics
3.2. Incidence of Allograft Injury: BCs and ACR
3.3. Fluctuation in Anti-HCV Antibody Titers and Allograft Injury
3.4. Multivariate Logistical Analysis of the Impact of Confounding Factors
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable, n (%)/Median ± SD | All Patients n = 153 | DAA Group n = 31 (20.3) | DAA-Naïve Group n = 122 (79.7) | p-Value |
---|---|---|---|---|
Sex, n (%) Male/female | 72 (47.7)/81 (52.3) | 12 (38.7)/19 (61.3) | 60 (49.6)/62 (50.4) | 0.28 |
Age at transplant (years), mean ± SD | 54.5 | 57.4 ± 7.5 | 57.2 ± 6.6 | 0.85 |
Follow-up (months), mean ± SD | 43.6 | 33.2 ± 18.6 | 46.1 ± 21.7 | 0.0029 |
Serum HCV RNA positive, n (%) | ||||
Pre-transplant | 70 (45.8) | 1 (3.2) | 69 (56.6) | <0.000001 |
Post-transplant | 61 (39.9) | 0 (0) | 61 (50) | <0.000001 |
HCV genotype, n (%) 1/2/3/6/undetected | 54 (35.3)/39 (25.5)/2 (1.3)/2 (1.3)/56 (36.6) | 8 (25.8)/10 (32.3)/1 (3.2)/0 (0)/12 (38.7) | 46 (37.7)/29 (23.8)/1 (0.8)/2 (1.6)/44 (36.1) | 0.19 |
AFP (ng/mL), mean ± SD | ||||
Pre-transplant | 14.1 ± 70.0 | 11.9 ± 21.4 | 14.7 ± 37.8 | 0.69 |
Post-transplant | 3.8 ± 7.3 | 4.2 ± 5.1 | 3.7 ± 3.2 | 0.52 |
Liver donor, n (%) Living donor/deceased donor | 136 (88.9)/17 (11.1) | 27 (87.1)/4 (12.9) | 109 (87.3)/13 (10.7) | 0.75 |
HCC diagnosed at LT, n (%) Absent/present | 80 (52.3)/73 (47.7) | 19 (61.3)/12 (38.7) | 61 (50)/61 (50) | 0.057 |
MELD score, mean ± SD | 18.0 ± 18.7 | 17.6 ± 9.6 | 18.2 ± 9.4 | 0.75 |
Liver explant pathology | ||||
Viable tumor identified, n (%) | 60 (39.2) | 18 (58.1) | 42 (34.4) | 0.11 |
Largest tumor (cm), mean ± SD | 2.9 ± 3.0 | 2.6 ± 1.1 | 2.9 ± 1.6 | 0.39 |
Number of lesions, mean | 2.5 | 2.3 ± 1.4 | 2.6 ± 1.8 | 0.52 |
Lymphovascular invasion, n (%) | 16 (10.5) | 3 (15.0) | 13 (22.8) | 0.47 |
Post-LT complications, n (%) | ||||
Biliary complication | 28 (18.3) | 10 (32.3) | 18 (14.8) | 0.028 |
Acute cellular rejection | 41 (26.8) | 8 (25.8) | 33 (27) | 0.56 |
Post-LT de novo HCC/recurrence, n (%) | 6 (3.9)/0 | 0 (0)/0 (0) | 6 (4.9)/0 (0) | 0.35 |
Category | Anti-HCV (+) n = 153 (%) | p-Value | |
---|---|---|---|
DAA Group n = 31 (20.3) | DAA-Naïve Group n = 122 (79.7) | ||
Positive BC | 10 (32.3) | 18 (14.8) | <0.05 |
Negative BC | 21 (67.7) | 104 (85.2) | |
Positive ACR | 8 (25.8) | 33 (27.1) | >0.05 |
Negative ACR | 23 (74.2) | 89 (73.0) |
Variable/Median ± SD | BCs (+) (n = 28) | BCs (−) (n = 125) | p-Value | ACR (+) (n = 41) | ACR (−) (n = 112) | p-Value |
---|---|---|---|---|---|---|
Age (years) | 58.0 ± 5.9 | 57.0 ± 6.9 | 0.49 | 59.6 ± 5.3 | 56.3 ± 7.0 | 0.0065 |
Sex (M/F) | 14/14 | 59/66 | 0.84 | 20/21 | 53/59 | 1.00 |
Pre-LT DAA use (Yes/no) | 10/18 | 21/104 | 0.036 | 8/33 | 23/89 | 1.00 |
Graft warm ischemic time (min) | 35.4 ± 4.9 | 37.9 ± 6.7 | 0.16 | 36.3 ± 4.6 | 37.8 ± 7.0 | 0.33 |
Graft cold ischemic time (min) | 71.1 ± 96.9 | 51.9 ± 64.6 | 0.33 | 34.3 ± 10.5 | 62.8 ± 81.4 | 0.09 |
Post-LT day 30 | ||||||
AST (U/L) | 67.9 ± 78.2 | 63.5 ± 211.5 | 0.91 | 53.6 ± 40.8 | 68.2 ± 224.5 | 0.69 |
ALT (U/L) | 84.5 ± 96.0 | 53.6 ± 98.6 | 0.13 | 70.7 ± 58.3 | 55.2 ± 109.4 | 0.40 |
Total bilirubin (mg/dL) | 0.92 ± 0.75 | 1.53 ± 7.14 | 0.65 | 0.97 ± 1.3 | 1.58 ± 7.5 | 0.61 |
Albumin (g/dL) | 4.13 ± 0.47 | 4.11 ± 0.48 | 0.84 | 4.0 ± 0.59 | 4.1 ± 0.42 | 0.21 |
INR | 1.00 ± 0.16 | 1.08 ± 0.34 | 0.30 | 1.03 ± 0.2 | 1.07 ± 0.35 | 0.50 |
Category | DAA Group n = 31 (%) | DAA-Naïve Group n = 122 (%) | ||
---|---|---|---|---|
Anti-HCV Ab titer | 28.05 ± 33.96 a | 10.50 ± 39.93 a’ | ||
Upregulation n = 25 (80.7) | Downregulation n = 6 (19.3) | Upregulation n = 85 (69.7) | Downregulation n = 37 (30.3) | |
37.58 ± 30.18 b | −11.66 ± 14.02 c | 27.97 ± 25.45 b’ | −29.62 ± 38.37 c’ |
Category | BCs n = 28 (%) | ACR n = 41 (%) | ||||||
---|---|---|---|---|---|---|---|---|
Anti-HCV Ab titer (S/CO ratio) | Upregulation n = 19 (67.9) | Downregulation n = 9 (32.1) | Upregulation n = 29 (70.7) | Downregulation n = 12 (29.3) | ||||
25.13 ± 25.39 a | −20.39 ± 27.08 a’ | 18.71 ± 18.81 b | −23.18 ± 23.55 b’ | |||||
DAA (+) n = 9 (47.4) | DAA (−) n = 10 (52.6) | DAA (+) n = 1 (11.1) | DAA (−) n = 8 (88.9) | DAA (+) n = 7 (24.1) | DAA (−) n = 22 (75.9) | DAA (+) n = 1 (8.3) | DAA (−) n = 11 (91.7) | |
34.87 ± 24.41 c | 16.36 ± 24.08 c’ | −2.55 | −22.63 ± 28.05 | 34.07 ± 27.44 d | 13.82 ± 11.34 d’ | −23.14 | −23.18 ± 24.71 |
Category n (%) | DAA Group 31 (20.2) | DAA-Naïve Group 122 (79.7) | p-Value |
---|---|---|---|
∆Anti-HCV Ab titer following LT, mean ± SD | 28.05 ± 33.96 | 10.50 ± 39.93 | 0.013 |
Post-LT positive fluctuation in anti-HCV titer, mean ± SD | 37.58 ± 30.18 | 27.97 ± 25.45 | 0.714 |
Post-LT negative fluctuation in anti-HCV titer, mean ± SD | −11.66 ± 14.02 | −29.62 ± 38.37 | 0.43 |
Post-LT positive fluctuation in anti-HCV titer, n (%) | 6 (19.3) | 37 (30.3) | 0.27 |
Post-LT negative fluctuation in anti-HCV titer, n (%) | 25 (80.7) | 85 (69.7) |
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Lin, S.-H.; Wu, K.-T.; Wang, C.-C.; Huang, K.-T.; Hsu, L.-W.; Eng, H.-L.; Chiu, K.-W. Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury. Antibodies 2024, 13, 7. https://doi.org/10.3390/antib13010007
Lin S-H, Wu K-T, Wang C-C, Huang K-T, Hsu L-W, Eng H-L, Chiu K-W. Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury. Antibodies. 2024; 13(1):7. https://doi.org/10.3390/antib13010007
Chicago/Turabian StyleLin, Shu-Hsien, Kun-Ta Wu, Chih-Chi Wang, Kuang-Tzu Huang, Li-Wen Hsu, Hock-Liew Eng, and King-Wah Chiu. 2024. "Immune Responses to Anti-Hepatitis C Virus Antibodies during Pre-Liver Transplantation Direct-Acting Antiviral Therapy in Hepatitis C Virus-Infected Recipients Associated with Post-Liver Transplantation Allograft Injury" Antibodies 13, no. 1: 7. https://doi.org/10.3390/antib13010007