Torgersen, Jessie, Newcomb, Craig W., Carbonari, Dena M., Rentsch, Christopher T., Park, Lesley S., Mezochow, Alyssa, Mehta, Rajni L., Buchwalder, Lynn, Tate, Janet P., Bräu, Norbert, Bhattacharya, Debika, Lim, Joseph K., Taddei, Tamar H., Justice, Amy C., and Lo Re III, Vincent
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. 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). 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 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. 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. [Display omitted] • 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. [ABSTRACT FROM AUTHOR]