Back to Search
Start Over
Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation.
- Source :
-
Journal of hepatology [J Hepatol] 2021 Dec; Vol. 75 (6), pp. 1312-1322. Date of Electronic Publication: 2021 Jul 29. - Publication Year :
- 2021
-
Abstract
- Background & Aims: Cases of acute liver injury (ALI) have been reported among chronic HCV-infected patients receiving protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, but no analyses have compared the risk of ALI in patients receiving PI- vs. non-PI-based DAAs. Thus, we compared the risk of 3 ALI outcomes between patients (by baseline Fibrosis-4 [FIB-4] group) receiving PI-based or non-PI-based DAAs.<br />Methods: We conducted a cohort study of 18,498 patients receiving PI-based DAA therapy (paritaprevir/ritonavir/ombitasvir±dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) matched 1:1 on propensity score to those receiving non-PI-based DAAs (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). During exposure to DAA therapy, we determined development of: i) alanine aminotransferase (ALT) >200 U/L, ii) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and iii) hepatic decompensation. We used Cox regression to determine hazard ratios (HRs) with 95% CIs for each ALI outcome within groups defined by baseline FIB-4 (≤3.25; >3.25).<br />Results: Among patients with baseline FIB-4 ≤3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR 3.98; 95% CI 2.37-6.68), but not severe hepatic dysfunction (HR 0.67; 95% CI 0.19-2.39) or hepatic decompensation (HR 1.01; 95% CI 0.29-3.49), compared to those receiving non-PI-based regimens. For those with baseline FIB-4 >3.25, those receiving PIs had a higher risk of ALT >200 U/L (HR, 2.15; 95% CI 1.09-4.26), but not severe hepatic dysfunction (HR, 1.23 [0.64-2.38]) or hepatic decompensation (HR, 0.87; 95% CI 0.41-1.87), compared to those receiving non-PI-based regimens CONCLUSION: While risk of incident ALT elevations was increased in those receiving PI-based DAAs in both FIB-4 groups, the risk of severe hepatic dysfunction and hepatic decompensation did not differ between patients receiving PI- or non-PI-based DAAs in either FIB-4 group.<br />Lay Summary: Cases of liver injury have been reported among patients treated with protease inhibitor-based direct-acting antivirals for hepatitis C infection, but it is not clear if the risk of liver injury among people starting these drugs is increased compared to those starting non-protease inhibitor-based therapy. In this study, patients receiving protease inhibitor-based treatment had a higher risk of liver inflammation than those receiving a non-protease inhibitor-based treatment, regardless of the presence of pre-treatment advanced liver fibrosis/cirrhosis. However, the risk of severe liver dysfunction and decompensation were not higher for patients treated with protease inhibitor-based regimens.<br />Competing Interests: Conflict of interest D.B. has received research support to the NIH AIDS Clinical Trials Group (ACTG) from Abbvie and Regeneron for an ACTG-sponsored trial. All other authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.<br /> (Published by Elsevier B.V.)
- Subjects :
- Aged
Antiviral Agents pharmacology
Cohort Studies
Female
Humans
Liver Failure, Acute blood
Male
Middle Aged
Propensity Score
Proportional Hazards Models
Protease Inhibitors administration & dosage
Retrospective Studies
Risk Factors
Transaminases blood
United States
United States Department of Veterans Affairs organization & administration
United States Department of Veterans Affairs statistics & numerical data
Antiviral Agents classification
Liver Failure, Acute drug therapy
Protease Inhibitors pharmacology
Transaminases analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 75
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 34333102
- Full Text :
- https://doi.org/10.1016/j.jhep.2021.07.021