Jessie Torgersen

Risk of Acute Liver Injury Associated with Protease Inhibitor-Based Direct-Acting Antiviral Therapy for Hepatitis C

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Jessie Torgersen, Epidemiology


J Torgersen1, C Newcomb1, D Carbonari1, C Rentsch2, L Park3, A Mezochow1, R Mehta4, L Buchwalder4, J Tate4, N Bräu5, D Bhattacharya6, J Kim4, T Taddei4, A Justice4, V Lo Re, III1

  1. University of Pennsylvania Perelman School of Medicine
  2. London School of Hygiene & Tropical Medicine
  3. Stanford University School of Medicine
  4. Yale School of Medicine
  5. Icahn School of Medicine at Mount Sinai
  6. David Geffen School of Medicine at UCLA


Cases of acute liver injury (ALI) have been reported among chronic hepatitis C virus-infected initiators of protease inhibitor (PI)-based direct-acting antiviral (DAA) regimens, predominately with decompensated cirrhosis. No comparative analyses have evaluated whether initiators of PI versus non-PI-based DAAs have higher risk of ALI events, stratified by advanced hepatic fibrosis/cirrhosis status.

We conducted a cohort study including 20,872 initiators of PI-based (paritaprevir/ritonavir/ombitasvir +/- dasabuvir, elbasvir/grazoprevir, glecaprevir/pibrentasvir) and 54,315 initiators of non-PI-based DAA therapies (sofosbuvir/ledipasvir, sofosbuvir/velpatasvir) in the 1945-1965 Veterans Birth Cohort (2014-2019). We determined development of: 1) alanine aminotransferase (ALT) >200 U/L, 2) severe hepatic dysfunction (coagulopathy with hyperbilirubinemia), and 3) hepatic decompensation, all within 12 months of DAA initiation. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals of each outcome in PI versus non-PI initiators, stratified by baseline advanced hepatic fibrosis/cirrhosis status by FIB-4.

Among persons with baseline FIB-4 ≤3.25, PI initiators had higher risk of ALT >200 U/L (HR, 3.75 [2.74-5.15]), but not severe hepatic dysfunction (HR, 1.51 [0.57-4.04]) or hepatic decompensation (HR, 0.59 [0.26-1.37]), compared to non-PI-initiators. For those with baseline FIB-4 >3.25, PI initiators did not have significantly higher risk of ALT >200 U/L (HR, 1.68 [0.89-3.19]), severe hepatic dysfunction (HR, 0.79 [0.46-1.37]), or hepatic decompensation (HR, 0.78 [0.45-1.35]) than non-PI initiators.

While risk of incident ALT elevations was increased among PI-based DAA initiators with FIB-4 ≤3.25, risk of severe hepatic dysfunction and hepatic decompensation did not differ between PI and non-PI-based DAA initiators in either FIB-4 stratum.


acute liver injury, protease inhibitor, direct-acting antivirals, hepatitis C

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