Risk Factors of Glecaprevir/Pibrentasvir-Induced Liver Injury and Efficacy of Ursodeoxycholic Acid
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Treatment and Follow-Up
2.3. Assessment of GP-Induced Liver Injury
2.4. Assessment of Efficacy of Add-On UDCA for GP-Induced Liver Injury
2.5. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. SVR and GP-Induced Liver Injury
3.3. Risk Factors Contributing to GP-Induced Liver Injury
3.4. Efficacy of Add-On UDCA for GP-Induced Liver Injury
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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N = 236 | |
---|---|
Age, years (range) | 70 (14–94) |
≥75 years | 85 (36%) |
Sex, male/female | 132/104 |
Height, cm (range) | 161.0 (133.2–180) |
Weight, kg (range) | 58 (29.6–140.5) |
Body mass index, kg/m2 (range) | 22.8 (15.6–58.5) |
Cirrhosis | 78 (33%) |
Genotype (1/2/3/4/5/6/unknown) | 132/101/1/0/0/1/1 |
HCV-RNA (logIU/mL) | 6.3 (2.1–7.6) |
History of HCC treatment | 28 (12%) |
History of IFN-based therapy | 24 (10%) |
History of DAA treatment | 13 (6%) |
White blood cells (/mm3) | 5180 (1200–11,700) |
Hemoglobin (g/dL) | 13.7 (7.8–17.3) |
Platelets (×104/mm3) | 17.9 (5.1–96.7) |
AST (U/L) | 39 (13–432) |
ALT (U/L) | 36 (8–558) |
ALP (U/L) | 87 (35–303) |
γ-GT (U/L) | 37 (7–748) |
PT (%) | 97 (12–141) |
Alb (g/dL) | 4.1 (2.3–5.2) |
TB (mg/dL) | 0.8 (0.3–2.6) |
ALBI grade (1/2/3) | 154/80/2 |
N = 236 | |
---|---|
Occurrence of liver dysfunction | 146 (62%) |
Liver injury grade | |
AST elevation (Grade 1/2/≥3) | 7 (6/1/0) |
ALT elevation (Grade 1/2/≥3) | 14 (13/1/0) |
ALP elevation (Grade 1/2/≥3) | 60 (60/0/0) |
γ-GT elevation (Grade 1/2/≥3) | 4 (2/1/1) |
TB elevation (Grade 1/2/≥3) | 118 (75/34/9) |
Time to liver injury | |
AST elevation after 2/4/6/8/10/12 weeks | 2/2/2/0/0/1 |
ALT elevation after 2/4/6/8/10/12 weeks | 8/1/2/1/1/1 |
ALP elevation after 2/4/6/8/10/12 weeks | 31/14/6/7/1/1 |
γ-GT elevation after 2/4/6/8/10/12 weeks | 2/1/0/0/1/0 |
TB elevation after 2/4/6/8/10/12 weeks | 94/12/7/5/0/0 |
Management of liver injury | |
Treatment discontinuation due to hyperbilirubinemia | 1 |
Dose reduction due to hyperbilirubinemia | 1 |
Add-on UDCA for hyperbilirubinemia | 21 |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
Factors | p | OR | 95% CI | p | OR | 95% CI |
Age (per 1-year increase) | <0.001 | 1.056 | 1.033–1.079 | 0.005 | 1.044 | 1.013–1.076 |
Sex (female) | 0.209 | 1.408 | 0.826–2.402 | |||
Height (per 1-cm increase) | 0.005 | 0.960 | 0.932–0.987 | 0.614 | 1.028 | 0.923–1.145 |
Weight (per 1-kg increase) | 0.002 | 0.971 | 0.953–0.990 | 0.351 | 0.939 | 0.822–1.072 |
BMI (per 1-kg/m2 increase) | 0.040 | 0.939 | 0.885–0.997 | 0.341 | 1.179 | 0.840–1.655 |
Cirrhosis | 0.103 | 1.614 | 0.908–2.870 | |||
History of HCC treatment | 0.133 | 1.992 | 0.810–4.896 | |||
History of IFN-based therapy | 0.343 | 1.563 | 0.621–3.930 | |||
History of DAA treatment | 0.085 | 0.363 | 0.115–1.148 | |||
HCV-RNA (per 1-logIU/mL increase) | 0.528 | 1.090 | 0.834–1.424 | |||
White blood cells (per 1/mm3 increase) | 0.043 | 1.000 | 1.000–1.000 | 0.829 | 1.000 | 1.000–1.000 |
Hemoglobin (per 1-g/dL increase) | 0.139 | 0.893 | 0.768–1.037 | |||
Platelets (per 1 × 104/mm3 increase) | 0.008 | 0.946 | 0.908–0.986 | 0.623 | 0.989 | 0.946–1.034 |
AST (per 1-IU/L increase) | 0.175 | 0.996 | 0.990–1.002 | |||
ALT (per 1-IU/L increase) | 0.039 | 0.995 | 0.991–1.000 | 0.659 | 0.999 | 0.992–1.005 |
ALP (per 1-IU/L increase) | 0.914 | 1.000 | 0.993–1.006 | |||
γ-GT (per 1-IU/L increase) | 0.016 | 0.996 | 0.993–0.999 | 0.093 | 0.997 | 0.993–1.001 |
PT (per 1% increase) | 0.022 | 0.979 | 0.962–0.997 | 0.305 | 0.989 | 0.969–1.010 |
Alb (per 1-g/dL increase) | 0.013 | 0.467 | 0.256–0.852 | 0.676 | 1.302 | 0.377–4.492 |
TB (per 1-mg/dL increase) | <0.001 | 10.668 | 3.640–31.267 | <0.001 | 14.700 | 3.941–54.822 |
ALBI grade (≥2) | 0.001 | 2.836 | 1.552–5.184 | 0.482 | 1.501 | 0.484–4.653 |
Univariate | Multivariate | |||||
---|---|---|---|---|---|---|
Factors | p | OR | 95% CI | p | OR | 95% CI |
Age (per 1-year increase) | 0.009 | 1.038 | 1.010–1.068 | 0.614 | 1.010 | 0.974–1.047 |
Sex (female) | 0.747 | 0.896 | 0.459–1.749 | |||
Height (per 1-cm increase) | 0.066 | 0.969 | 0.937–1.002 | |||
Weight (per 1-kg increase) | 0.024 | 0.970 | 0.944–0.996 | 0.575 | 0.984 | 0.931–1.040 |
BMI (per 1-kg/m2 increase) | 0.045 | 0.911 | 0.831–0.998 | 0.683 | 0.963 | 0.803–1.154 |
Cirrhosis | 0.006 | 2.563 | 1.306–5.028 | 0.195 | 1.771 | 0.746–4.205 |
History of HCC treatment | 0.136 | 1.977 | 0.806–4.847 | |||
History of IFN-based therapy | 0.448 | 0.614 | 0.175–2.161 | |||
History of DAA treatment | 0.332 | 0.359 | 0.045–2.839 | |||
HCV-RNA (per 1-logIU/mL increase) | 0.106 | 0.773 | 0.566–1.056 | |||
White blood cells (per 1/mm3 increase /mm3) | 0.064 | 1.000 | 1.000–1.000 | |||
Hemoglobin (per 1-g/dL increase) | 0.080 | 0.852 | 0.712–1.019 | |||
Platelets (per 1 × 104/mm3 increase) | 0.026 | 0.938 | 0.886–0.992 | 0.554 | 0.980 | 0.920–1.045 |
AST (per 1-IU/L increase) | 0.789 | 0.999 | 0.991–1.007 | |||
ALT (per 1-IU/L increase) | 0.312 | 1.004 | 0.996–1.011 | |||
ALP (per 1-IU/L increase) | 0.914 | 1.000 | 0.993–1.006 | |||
γ-GT (per 1-IU/L increase) | 0.335 | 0.998 | 0.993–1.002 | |||
PT (per 1% increase) | 0.019 | 0.976 | 0.957–0.996 | 0.157 | 0.985 | 0.963–1.006 |
Alb (per 1-g/dL increase) | 0.023 | 0.451 | 0.227–0.896 | 0.958 | 1.033 | 0.313–3.411 |
TB (per 1-mg/dL increase) | 0.001 | 5.024 | 1.932–13.069 | 0.004 | 5.132 | 1.679–15.683 |
ALBI grade (≥2) | 0.001 | 2.834 | 1.494–5.377 | 0.651 | 1.320 | 0.396–4.392 |
Add-On UDCA Group (n = 21) | No UDCA Group (n = 18) | |||
---|---|---|---|---|
Total Bilirubin (mg/dL) | p | Total Bilirubin (mg/dL) | p | |
At onset | 3.0 (1.9–5.9) | 2.0 (1.6–3.5) | ||
After 2 weeks | 1.9 (0.8–3.7) | <0.001 | 2.0 (1.0–3.3) | 0.690 |
After 4 weeks | 2.1 (1.0–4.1) | <0.001 | 2.2 (0.6–3.5) | 0.950 |
After 6 weeks | 1.6 (1.1–4.3) | <0.001 | 1.8 (0.8–3.6) | 0.363 |
After 8 weeks | 1.8 (0.7–3.4) | 0.012 | 1.9 (1.4–3.6) | 0.500 |
After 10 weeks | 1.7 (1.0–3.5) | 0.018 | 1.9 (1.2–5.2) | 0.465 |
Δ Total Bilirubin | Add-On UDCA Group (n = 21) | No UDCA Group (n = 18) | p |
---|---|---|---|
After 2 weeks | −1.1 (−3.8–0.0) | −0.1 (−1.3–0.8) | <0.001 |
After 4 weeks | −1.0 (−4.7–−1.0) | 0.0 (−1.3–1.8) | <0.001 |
After 6 weeks | −1.2 (−4.6–0.7) | −0.2 (−1.5–0.8) | 0.004 |
After 8 weeks | −1.4 (−5.2–−0.4) | 0.2 (−0.4–1.8) | 0.002 |
After 10 weeks | −1.4 (−4.3–−0.5) | 0.3 (−0.6–2.6) | 0.012 |
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Tamai, H.; Okamura, J. Risk Factors of Glecaprevir/Pibrentasvir-Induced Liver Injury and Efficacy of Ursodeoxycholic Acid. Viruses 2023, 15, 489. https://doi.org/10.3390/v15020489
Tamai H, Okamura J. Risk Factors of Glecaprevir/Pibrentasvir-Induced Liver Injury and Efficacy of Ursodeoxycholic Acid. Viruses. 2023; 15(2):489. https://doi.org/10.3390/v15020489
Chicago/Turabian StyleTamai, Hideyuki, and Jumpei Okamura. 2023. "Risk Factors of Glecaprevir/Pibrentasvir-Induced Liver Injury and Efficacy of Ursodeoxycholic Acid" Viruses 15, no. 2: 489. https://doi.org/10.3390/v15020489
APA StyleTamai, H., & Okamura, J. (2023). Risk Factors of Glecaprevir/Pibrentasvir-Induced Liver Injury and Efficacy of Ursodeoxycholic Acid. Viruses, 15(2), 489. https://doi.org/10.3390/v15020489