3D + R Lowers Liver Morbidity, Mortality Risks in HCV GT1 Post-Transplant

SAN FRANCISCO, CA—Patients with recurrent hepatitis C virus (HCV) genotype 1 (GT1) infection treated with the "3D+R" regimen post-transplant have a substantially lower likelihood of experiencing compensated or decompensated cirrhosis and death compared with the standard of care, 48 weeks of pegylated interferon plus ribavirin, or no treatment, a study reported at The Liver Meeting® 2015.

In fact, pegylated interferon plus ribavirin, compared with the 3D+R treatment—ombitasvir/paritaprevir/ritonavir, dasabuvir, and ribavirin—"is associated with a 26-fold greater risk of compensated cirrhosis and decompensated cirrhosis over a lifetime, and a 47% greater mortality risk over 10 years," reported Sammy Saab, MD, MPH, from Pfleger Liver Institute, UCLA, Los Angeles, CA.

Among patients who receive 48 weeks of pegylated interferon plus ribavirin, dose reduction occurs in approximately 70% due to side effects such as anemia, and only 30% achieve sustained virologic response (SVR), Dr. Saab and colleagues noted.

"Without effective treatment, HCV recurrence affects 75% to 90% of post-transplant recipients and liver fibrosis progresses faster in this population," they added.

The 3D+R interferon-free regimen recently was approved in the US for use in post-transplant patients with HCV GT1 infection. To elicit a better understanding of the long-term impact of 3D+R on liver outcomes and mortality relative to standard of care, the investigators assessed lifetime risks of liver morbidity and mortality in post-transplant patients with HCV GT1 recurrence who received no treatment, 48 weeks of pegylated interferon plus ribavirin, or the 3D+R regimen.

A two-phase Markov health state model calculated outcomes over a lifetime horizon for patients with a median age of 60 years, 79% male, with recurrent HCV GT1 and mild-to-moderate liver disease (METAVIR fibrosis stage F0–F2).

In the first phase, patients were assigned to one of the three treatment options for 24 weeks and, in the second phase, their disease-state progression was followed through compensated cirrhosis, decompensated cirrhosis, and death. Researchers extracted transition rates from published literature derived sustained virologic response (SVR) rates from clinical trial results of 3D+R and pegylated interferon plus ribavirin.

In addition, lifetime risks of compensated cirrhosis, decompensated cirrhosis, and 10-year all-cause mortality were analyzed.

Study authors found that the HCV GT1 liver transplant patients treated with 3D+R had substantially lower lifetime risks of liver morbidity and all-cause mortality than patients treated with pegylated interferon plus ribavirin or no treatment.

The estimated lifetime risk of developing compensated cirrhosis in untreated patients was 63.3%, 51.5% in the pegylated interferon plus ribavirin group, and 1.9% in the 3D+R group. The estimated lifetime risk of developing decompensated cirrhosis was 55.6%, 45.3%, and 1.7%, respectively. All-cause mortality over a 10-year horizon was 29.5% in the no treatment group, 27.4% in the pegylated interferon plus ribavirin group, and 18.6% in the 3D+R treatment group.

"Average life expectancy with 3D+R treatment was 5 years longer compared with no treatment, and 4.2 years longer" when compared with 48 weeks of pegylated interferon plus ribavirin treatment, they reported.

"This analysis provides an assessment of long-term outcomes in the rapidly evolving HCV treatment landscape for a patient population with a large unmet need," Dr. Saab and colleagues concluded.

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