Direct-acting antiviral regimen produced high SVR among liver transplant recipients with HCV

BOSTON — Liver transplant recipients with hepatitis C virus infection genotype 1 achieved sustained virologic response after 12 weeks of therapy with a regimen of three direct-acting antivirals, with ribavirin, according to data presented at The Liver Meeting.

“HCV recurrence is associated with an aggressive disease force. We know that recurrent cirrhosis leading to graft failure occurs in 20% to 30% of recipients within 5 years. However, it is difficult to predict which patients may have a recurrent course of the disease,” Parvez S. Mantry, MD, Medical Director, Liver Institute Research; Medical Director Hepatobiliary Tumor Program, Methodist Health System, Dallas, said in his presentation. “This multi-targeted, interferon-free regimen of ABT 450-[ritonavir], ombitasvir, dasabuvir and ribavirin achieved high response rates in immunosuppressed liver transplant recipients with recurrent HCV genotype 1 infection. This phase 2 study in liver transplant recipients with mild to moderate liver fibrosis shows that antiviral therapy may offer clinical benefit before the acceleration of fibrosis to advanced liver disease and its associated complications in this difficult-to-treat population.”

In an ongoing open-label phase 2 trial, 34 liver transplant recipients with recurrent HCV genotype 1 infection and without cirrhosis received 150 mg ABT-450/100 mg ritonavir (AbbVie/Enanta), 25 mg of ombitasvir and 250 mg of dasabuvir plus ribavirin (dosage based on investigator recommendation) for 24 weeks. Lower calcineurin inhibitor (CNI) dosing was advised due to inhibitor interactions of the study regimen: 0.5 mg of tacrolimus once weekly or 0.2 mg every 3 days and cyclosporine dosed at one-fifth the daily pre-study dose once daily, according to the abstract.

All patients achieved a rapid virologic response and end of treatment response; 97.1% of patients achieved a sustained virologic response (SVR) at 4 weeks, 97.0% achieved SVR12 and 93.3% achieved SVR24. No patients experienced breakthrough during treatment and one patient relapsed. Lower CNI dosage led to stable levels of CNI.

The most common adverse events were fatigue (50.0%) and headache (44.1%). One patient achieved SVR12 then discontinued treatment after week 18 due to adverse events, including moderate rash, memory impairment and anxiety. No acute rejections were observed in any of the patients during the study.

Paul Y. Kwo

"Recurrent hepatitis C post-liver transplantation has historically been difficult to treat, and we have considered post-liver-transplant patients a special population in need of new treatment strategies," researcher Paul Y. Kwo, MD, professor of medicine at the Indiana University School of Medicine and HCV Next Editorial Board member, said in a press release. "What this study showed is that this special population is no longer special. We can treat them as successfully as if they haven't had a liver transplant with drugs that are well tolerated and without risk of rejection.”

For more information:

Mantry PS. Abstract 198. Presented at: The Liver Meeting, Nov. 7-11, 2014; Boston, MA.

Disclosures: See the abstract for a full list of relevant financial disclosures.