Abstract
Introduction
Current guidelines discourage the use of direct-acting antiviral (DAA) containing protease-inhibitor (PI) in advanced HCV cirrhosis. We aimed to compare the real-world tolerability of PI vs. non-PI DAA regimens in this population.
Methods
We identified advanced cirrhosis patients treated with DAA from the REAL-C registry. The primary outcome was significant worsening or improvement in CPT or MELD scores following DAA treatment.
Results
From the REAL-C registry of 15,837 patients, we included 1077 advanced HCV cirrhosis patients from 27 sites. 42% received PI-based DAA. Compared to non-PI group, the PI group was older, had higher MELD and higher percentage with kidney disease. Inverse probability of treatment weighting (IPTW; matching on age, sex, history of clinical decompensation, MELD, platelet, albumin, Asia site, Asian ethnicity, hypertension, hemoglobin, genotype, liver cancer, ribavirin) was used to balance the two groups. In the IPTW-matched cohorts, the PI and non-PI groups had similar SVR12 (92.9% vs. 90.7%, p = 0.30), similar percentages of significant worsening in CTP or MELD scores at posttreatment week 12 and 24 (23.9% vs. 13.1%, p = 0.07 and 16.5% vs. 14.6%, p = 0.77), and similar frequency of new HCC, decompensating event, and death by posttreatment week 24. In multivariable analysis, PI-based DAA was not associated with significant worsening (adjusted odds ratio = 0.82, 95% CI 0.38–1.77).
Conclusion
Tolerability and treatment outcomes were not significantly different in advanced HCV cirrhosis treated with PI-based (vs. non-PI) DAA up to CTP-B or MELD score of 15. Safety of PI-based DAA in those with CTP-C or MELD beyond 15 awaits further data.
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Abbreviations
- DAA:
-
Direct-acting antivirals
- HCV:
-
Hepatitis C virus
- SVR:
-
Sustained virologic response
- PI:
-
Protease inhibitors
- MELD:
-
Model for end-stage-liver disease
- CTP:
-
Child–Turcotte–Pugh
- IPTW:
-
Inverse probability of treatment weighting
- REAL-C:
-
Real-World Evidence from the Asia Pacific Rim Liver Consortium for HCV
- USA:
-
United States of America
- HE:
-
Hepatic encephalopathy
- HCC:
-
Hepatocellular carcinoma
- OR:
-
Odds ratio
- CI:
-
Confidence interval
- SD:
-
Standard deviation
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Acknowledgements
We would like to acknowledge Kaohsiung Medical University Research Center Grant: Center for Liquid Biopsy and Cohort Research KMHK-DK(C)111006 and KMHK-DK(C)111004 for supporting Dr. Ming-Lung Yu.
Funding
The study is supported in part by an investigator-initiated research grant from Gilead Sciences to Stanford University. The funding body has no role in study design, data collection, data interpretation, manuscript writing and the decision to publish.
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Guarantor of the article: MHN. Specific author contributions: study design: YJW, ST, and MHN. Data collection: all the authors. Data analysis: ST, YJW and MHN. Data interpretation: all the authors. Drafting of the article: YJW, ST and MHN. Study concept and study supervision: MHN.
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WYJ: Speaker: Gilead and AbbVie; MHN: research support: Pfizer, Enanta, Gilead, Exact Sciences, Vir Biotech, Helio Health, National Cancer Institute, Glycotest, B.K. Kee Foundation; Consulting and/or Advisory Board: Intercept, Exact Science, Gilead, GSK, Eli Lilly, Laboratory of Advanced Medicine, Janssen; AN: Speaker fee and research grant: Gilead and AbbVie; LSG: Advisory Board: Gilead Sciences, Roche, GSK, Janssen, Grifols, Assembly, Arbutus, Abbott, Sysmex; Speakers Bureau: Gilead Sciences, Abbott, Janssen; Educational/research funding: Abbott, Merck Sharpe and Dohme, Gilead Sciences, Sysmex GW: Speakers’ fees: Abbott, Abbvie, Ascletis, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen and Roche; Research grant: Gilead Sciences; MA: Speakers’ fees: AbbVie, Gilead; Research grant: AbbVie; CHT: Speaker: Abbvie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, and Bayer; HT: Abbie, Astellas Pharma and Sysmex Corporation; KT: Speaker: Abbie; EO: Speakers’ fees: Abbvie, Gilead Sciences; Research grant: Gilead Sciences; WLC: Speaker: Gilead, AbbVie, BMS, PharmaEssentia; Member of Advisory Board: Gilead, AbbVie, BMS, Pharma Essentia; HT: AbbVie, Gileads, Bayer, Eisai, MSD, Janssen; MFY: Advisory board member/consultant for and/or received research funding: AbbVie, Aligos Therarpeutics, AiCuris, Antios Therapeutics, Arrowhead Pharmaceuticals, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Bluejay Therapeutics, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, and Hoffmann-La Roche, Vir Biotechnology; YML: Consultant: Abbvie, Abbott, BMS, Gilead, Merck and Roche diagnostics; Speaker: Abbvie, Abbott, BMS, Gilead, IPSEN, Merck and Roche; YU: Speakers’ fees: Abbvie Inc, Research grant: Gilead Sciences, Abbvie; ME: Speakers’ fee: AbbVie; FJ: Speaker fees: Gilead Sciences, MSD and Ascletis, Consulting or advisory board: Gilead Sciences and MSD; YT: Speakers’ fee: Gilead Sciences, Fujirebio Inc, AbbVie, Research grants: Janssen, Gilead, Board of Trustees of the Leland Stanford Junior University, AbbVie.
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All the procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted and ethical approval was obtained from Stanford University, Stanford, California, USA and each participating site.
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Wong, Y.J., Tran, S., Huang, CF. et al. Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study. Hepatol Int 17, 1150–1161 (2023). https://doi.org/10.1007/s12072-023-10547-4
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DOI: https://doi.org/10.1007/s12072-023-10547-4