Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Endpoints of Study
2.2. Statistical Analysis
3. Results
Adverse Events and Safety Profile
4. Discussion
4.1. Limitations
4.2. Future Directions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variable | Baseline (n = 108) |
---|---|
Age, y, mean (SD) | 53.5 (12.2) |
Sex, n (%) | |
M | 68 (63.0) |
F | 40 (37.0) |
Nationality, n (%) | |
Italian | 67 (62.0) |
Romanian | 22 (20.4) |
Other | 19 (17.6) |
BMI, median [IQR] | 24.3 [22.7–26.6] |
Cirrhosis, n (%) | 85 (89.5) |
Stiffness (kPa), median [IQR] | 12.8 [9.8–17.6] |
Fibrosis stage, n (%) | |
Absence | 7 (6.5) |
Mild | 22 (20.4) |
Advanced | 63 (58.3) |
Not performed | 16 (14.8) |
CAP (db/m), mean (SD) | 214.7 (57.6) |
Steatosis stage, n (%) | |
S0 | 49 (45.4) |
S1 | 7 (6.5) |
S2 | 7 (6.5) |
S3 | 5 (4.6) |
Not performed/available | 40 (37.0) |
History of HCC, n (%) | 9 (8.3) |
Active | 4 (3.7) |
Previous interferon, n (%) | 38 (35.2) |
HDV RNA (UI/mL), median [IQR] | 42,660 [3205–367,420] |
HBV DNA not detected, n (%) | 89 (82.4) |
HBV treatment, n (%) | |
Entecavir | 52 (48.1) |
Tenofovir | 56 (51.9) |
HCV treated, n (%) | 9 (8.3) |
HIV positive, n (%) | 5 (4.6) |
Progression Time | ||||||
---|---|---|---|---|---|---|
Time 0 (Baseline) | Time 1 (=6 Months) | |||||
Variable | Responder (n = 59) | Non-Responder (n = 49) | p | Responder (n = 59) | Non-Responder (n = 49) | p |
PLT × 103 (U/mL), median [IQR] | 103.0 [78.0–153.0] | 121.0 [80.0–183.0] | 0.411 | 121.0 [80.0–183.0] | 125.0 [95.0–170.0] | 0.784 |
ALT (U/mL), median [IQR] | 67.0 [44.0–116.3] | 75.0 [47.8–125.3] | 0.274 | 31.5 [24.0–36.5] | 45.5 [34.0–64.0] | 0.001 |
AST (U/mL), median [IQR] | 66.0 [46.5–91.0] | 66.0 [48.8–99.0] | 0.772 | 32.5 [28.0–38.0] | 43.0 [33.0–50.0] | 0.021 |
ALP (U/mL), median [IQR] | 88.0 [68.3–114.3] | 91.0 [72.0–119.0] | 0.858 | 82.0 [72.3–97.8] | 87.0 [65.8–110.5] | 0.996 |
GGT (U/mL), median [IQR] | 59.0 [34.3–84.0] | 63.0 [29.8–91.3] | 0.939 | 37.0 [23.3–52.3] | 40.5 [29.5–70.5] | 0.226 |
Albumin (g/dL), median [IQR] | 3.9 [3.6–4.2] | 4.1 [3.8–4.4] | 0.020 | 4.1 [3.9–4.4] | 4.1 [3.8–4.4] | 0.598 |
γ globulin (g/dL), median [IQR] | 1.9 [1.5–2.2] | 1.9 [1.4–2.4] | 0.659 | 1.5 [1.2–1.8] | 1.7 [1.2–1.9] | 0.880 |
INR, median [IQR] | 1.2 [1.1–1.4] | 1.1 [1.0–1.2] | 0.002 | 1.1 [1.1–1.2] | 1.1 [1.0–1.2] | 0.648 |
eGFR (mL/min/1.73 m2), median [IQR] | 86.7 [69.3–98.5] | 88.2 [78.0–98.6] | 0.392 | 90.2 [74.3–100.7] | 88.1 [75.0–100.6] | 0.776 |
Vitamin D (ng/dL), median [IQR] | 14.3 [11.0–21.6] | 32.6 [19.1–39.7] | 0.001 | 20.0 [14.9–29.2] | 38.5 [16.4–47.0] | 0.248 |
HBsAg (U/mL), median [IQR] | 5722.0 [720.0–10,466.7] | 4968.6 [887.0–9608.0] | 0.813 | 8000.0 [1258.0–10,887.5] | 9427.7 [4431.8–15,568.0] | 0.188 |
APRI Score, median [IQR] | 1.5 [1.0–2.4] | 1.5 [0.8-2.5] | 0.731 | 1.0 [0.5–2.4] | 1.3 [0.8–1.3] | 0.144 |
FIB-4, median [IQR] | 3.7 [2.3–5.5] | 2.9 [1.8–5.8] | 0.205 | 2.7 [1.6–4.1] | 2.7 [1.5–4.6] | 0.895 |
HDV RNA (UI/mL), median [IQR] | 29,800.0 [3100.0–375,000.0] | 45,160.0 [3683.0–363,815.5] | 0.615 | 0.0 * [0.0–291.0] | 14,090.0 [1750.5–69,483.8] | <0.001 |
Univariable Analysis | Multivariable Analysis | |||||||
---|---|---|---|---|---|---|---|---|
Parameter | OR | 95% CI | p | OR | 95% CI | p | ||
Age | 1.03 | 0.99 | 1.07 | 0.051 | 1.02 | 0.95 | 1.10 | 0.509 |
Sex | 1.41 | 0.64 | 3.12 | 0.391 | ||||
M | ||||||||
F | ||||||||
Nationality | ||||||||
Italian | 1 | |||||||
Romanian/Other | 0.30 | 0.13 | 0.68 | 0.004 | 0.32 | 0.03 | 3.54 | 0.355 |
BMI | 1.04 | 0.94 | 1.15 | 0.451 | ||||
Cirrhosis | 0.79 | 0.32 | 1.95 | 0.606 | ||||
Stiffness | 1.04 | 0.99 | 1.09 | 0.100 | ||||
History of HCC | 0.78 | 0.20 | 3.11 | 0.726 | ||||
Previous interferon | 0.60 | 0.15 | 2.47 | 0.479 | ||||
HBV DNA | 1.00 | 0.99 | 1.01 | 0.638 | ||||
PLT | 0.99 | 0.98 | 1.01 | 0.823 | ||||
ALT | 0.99 | 0.99 | 1.01 | 0.312 | ||||
AST | 1.00 | 0.99 | 1.01 | 0.846 | ||||
ALP | 1.00 | 0.99 | 1.01 | 0.909 | ||||
GGT | 0.99 | 0.98 | 1.01 | 0.606 | ||||
Albumin | 0.32 | 0.12 | 0.84 | 0.020 | 1.36 | 0.15 | 12.28 | 0.935 |
γ globulin | 0.80 | 0.31 | 2.03 | 0.634 | ||||
INR | 1.57 | 0.86 | 2.68 | 0.245 | ||||
eGFR | 0.99 | 0.97 | 1.02 | 0.357 | ||||
HBsAg | 1.01 | 0.99 | 1.01 | 0.479 | ||||
APRI score | 0.99 | 0.76 | 1.28 | 0.929 | ||||
FIB-4 | 1.02 | 0.90 | 1.17 | 0.717 | ||||
Vitamin D | 0.92 | 0.87 | 0.98 | 0.013 | 0.93 | 0.88 | 1.02 | 0.182 |
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Rinaldi, L.; Viganò, M.; Ciancio, A.; Caturano, A.; Messina, V.; Niro, G.A.; Capoluongo, N.; Loglio, A.; Marinaro, L.; Marrone, A.; et al. Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study. Viruses 2025, 17, 251. https://doi.org/10.3390/v17020251
Rinaldi L, Viganò M, Ciancio A, Caturano A, Messina V, Niro GA, Capoluongo N, Loglio A, Marinaro L, Marrone A, et al. Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study. Viruses. 2025; 17(2):251. https://doi.org/10.3390/v17020251
Chicago/Turabian StyleRinaldi, Luca, Mauro Viganò, Alessia Ciancio, Alfredo Caturano, Vincenzo Messina, Grazia Anna Niro, Nicolina Capoluongo, Alessandro Loglio, Letizia Marinaro, Aldo Marrone, and et al. 2025. "Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study" Viruses 17, no. 2: 251. https://doi.org/10.3390/v17020251
APA StyleRinaldi, L., Viganò, M., Ciancio, A., Caturano, A., Messina, V., Niro, G. A., Capoluongo, N., Loglio, A., Marinaro, L., Marrone, A., Claar, E., Russello, M., Ciracì, E., Gentilucci, U. V., Pace Palitti, V., Acierno, C., Cosentino, C., Mormone, A., Cotugno, R., ... Izzi, A. (2025). Assessment of Response and Safety of Bulevirtide Treatment in Patients with Chronic Delta Virus Infection: The ARISTOTLE Pilot Observational Study. Viruses, 17(2), 251. https://doi.org/10.3390/v17020251