Direct-Acting Antivirals Prove Long-Acting on HCV Infection after Liver Transplant

Direct-acting antiviral (DAA) treatment of HCV infection after liver transplant (LT) was associated with persistent improvement in hepatic function, fibrosis and survival rate, in a recently published long-term study.

Although the effectiveness of DAAs for HCV infection is well documented, relatively little is known about long-term outcomes in patients treated after LT, according to the investigators.

“The safety and efficacy of DAAs after LT are widely accepted, but only a few studies have described the long-term impact of viral eradication on liver function and survival after LT,” explained lead author Martina Gambato, MD, Multivisceral Transplant and Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale-Università Padova, Padova, Italy, and colleagues.

To evaluate the long-term impact of sustained virologic response (SVR) on fibrosis progression and survival in patients treated for HCV after LT, the investigators conducted a retrospective cohort study of the 3 year period following DAA treatment of consecutive patients (median 51-month follow-up), drawn from records of the NAVIGATORE web-based platform, or the DAA compassionate use program in Italy between May 2014 and January 2019.

Baseline staging of the RT-PCR confirmed HCV liver disease was established by liver biopsy or transient elastography (TE).The presence of cirrhosis was determined by at least one of the following: biopsy-proven fibrosis METAVIR stage 4; presence of esophageal varices, or liver stiffness measurement ≥12 kPa.The severity of cirrhosis was measured with the model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores.Clinical and laboratory test results were captured every 4 weeks during the treatment period, and at 3, 6, 12, 24 weeks and 36 months after the end of treatment (EoT). After viral eradication, TE was performed at least 1 year after the EoT.

The investigators identified 135 patients treated with DAAs after LT with sufficient record of outcome for inclusion. All patients received DAA treatment based on available DAA regimens and according to Italian and European guidelines.Those in the DAA compassionate use program (44%), however, received a regimen of sofosbuvir 400mg daily with ribavirin 1000 to 1200mg for 24 weeks, which the investigators considered suboptimal.

Gambato and colleagues point out that the overall SVR rate at 12 weeks of 78.7% following the first DAA regimen in this cohort with LT was lower than has been reported in most studies of treatment unrelated to transplant, and lowered further by the rate in the compassionate use program.Retreatment, however, resulted in an overall 96% SVR12.

In their long-term follow-up, the investigators found that the transaminase levels and platelet counts improved at EoT, and maintained that trend over the 3 years; and they confirmed a significant decrease in liver stiffness.Given that there has been debate over whether initial reduction in stiffness might reflect resolution of hepatic inflammation rather than regression of fibrosis, the investigators only considered liver stiffness measurements performed at least 1 year after EoT.

“For the first time, we were able to report a long-term improvement in liver stiffness in patients with advanced liver fibrosis at the baseline (64%),” Gambato and colleagues indicated.

They also found that that half of the patients with advanced fibrosis at the baseline demonstrated regression in fibrosis stages <2.This, they indicate, “led to a change in the management and surveillance of these patients.”