Highlights
- •Comparative analysis of 18,498 initiators of PI-based DAAs matched on propensity score to 18,498 initiators of non-PI-based DAAs to assess risk of three acute liver injury endpoints, according to advanced hepatic fibrosis/cirrhosis status by FIB-4.
- •Propensity score-matched hazard ratios of ALT >200 U/L were higher for PI than non-PI initiators in those with and without baseline advanced hepatic fibrosis/cirrhosis (i.e., FIB-4 >3.25 and FIB-4 ≤3.25, respectively).
- •No differences in propensity score-matched hazard ratios of severe hepatic dysfunction or hepatic decompensation were observed between PI and non-PI-based DAA initiators, regardless of baseline advanced hepatic fibrosis/cirrhosis status by FIB-4.
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.
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).
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.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: July 28, 2021
Accepted:
July 18,
2021
Received in revised form:
July 14,
2021
Received:
December 23,
2020
Identification
Copyright
Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
