Real-world treatment outcome with protease inhibitor direct-acting antiviral in advanced hepatitis C cirrhosis: a REAL-C study

Hepatol Int. 2023 Oct;17(5):1150-1161. doi: 10.1007/s12072-023-10547-4. Epub 2023 Jun 5.


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.

Keywords: Cirrhosis; Direct-acting antiviral; Effectiveness; Hepatitis C virus; Outcome; Protease inhibitor; Real world; Tolerability; Treatment.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Hepacivirus / genetics
  • Hepatitis C* / drug therapy
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Liver Cirrhosis / complications
  • Liver Neoplasms* / drug therapy
  • Protease Inhibitors / adverse effects
  • Sustained Virologic Response
  • Treatment Outcome


  • Antiviral Agents
  • Protease Inhibitors