Telaprevir or boceprevir triple therapy in patients with chronic hepatitis C and varying severity of cirrhosis

Abstract

Background: Risks and benefits of protease inhibitor (PI) (telaprevir or boceprevir) triple therapy in hepatitis C virus (HCV)-infected patients with mildly decompensated cirrhosis, including those wait-listed for liver transplantation (LT), are incompletely known.

Aim: To assess virological responses and safety of PI triple therapy in patients with mildly decompensated Child-Pugh (CP) CP ≥6 vs. compensated (CP = 5) cirrhosis.

Methods: Multicentre cohort of 160 adults with cirrhosis treated with peginterferon/ribavirin (peg-IFN/RBV) plus telaprevir (69%) or boceprevir (31%), comparing outcomes between those with CP = 5 and CP ≥6.

Results: Patients, 47% with CP ≥6 cirrhosis (CP range 6-10), received PI triple therapy for a targeted duration of 48 weeks. The cohort was median age 59 years, 32% female, 59% genotype 1a, 35% previous null/partial responders. Sustained virological response at 12 weeks (SVR12) was achieved by 35% of patients with CP ≥6 vs. 54% of those with CP = 5 (P = 0.02). CP = 5, achievement of rapid virological response and genotype 1b/other, independently predicted SVR12. Compared to those with CP = 5, patients with CP ≥6 had more peg-IFN dose reductions, eltrombopag use, transfusions and hospitalisations to manage adverse events (all P < 0.05). Overall, 67 (42%) discontinued treatment early. Nine wait-listed patients were treated for a median of 97 days (IQR 60-160) prior to liver transplantation and five achieved post-LT SVR.

Conclusions: In the presence of mild decompensation (Child-Pugh ≥6), SVR12 rates with protease inhibitor triple therapy are significantly reduced and adverse events increased. Thus, treatment with protease inhibitor triple therapy, if judged as necessary, should be undertaken with close monitoring and awareness of the significant risks.

Figure 1

Virological outcomes of patients with compensated and mildly decompensated cirrhosis with telaprevir or boceprevir triple therapy.

Figure 2

Outcomes of patients receiving telaprevir or boceprevir triple therapy prior to liver transplantation. Graphical representation of the nine wait-listed patients treated prior to liver transplantation. The x-axis is time in days with lead-in to the left of the vertical line and triple therapy to the right. The number 1–9 along the y-axis identifies each patient. Also along the y-axis, each patient is identified as having HCC vs. no HCC and as having compensated (CP = 5) or mildly decompensated (CP ≥6) cirrhosis. All nine patients were treated with telaprevir-based triple therapy. On the right, we represent those that achieved post-LT SVR12 with ‘YES’ and those who did not with ‘NO’.