Friday, August 5, 2016

HCV RNA Persists in Liver After Interferon-Free Treatment Regimens

HCV RNA Persists in Liver After Interferon-Free Treatment Regimens
By Reuters Staff
| August 04, 2016

NEW YORK (Reuters Health) - Hepatitis C virus (HCV) RNA persists in two-thirds of liver explants from patients who were treated with interferon-free regimens, researchers report.

Patients awaiting liver transplant receive antiviral treatment to eradicate the virus in serum and liver in order to prevent HCV graft infection. The duration of treatment needed to accomplish this in patients with advanced cirrhosis using interferon-free regimens is unknown.

Dr. Xavier Forns from the University of Barcelona, Spain, and colleagues assessed the presence of HCV RNA in liver explants from 39 HCV-infected patients treated with an interferon-free regimen (median duration, 17 weeks) on the waiting list for liver transplant and analyzed whether its presence was associated with relapse after liver transplantation.

Although most patients (68%) had undetectable serum HCV RNA by the fourth week of treatment, HCV RNA was present in 26 out of 39 liver explants (67%), the team reports in Gastroenterology, online June 30.

Patients with HCV RNA-positive liver explants received a shorter course of treatment than did those with HCV RNA-negative explants (14 vs. 21 weeks, p=0.014) and had HCV RNA undetectable in serum for a shorter period of time (61 vs. 99 days, p=0.013).

Most patients (33/39, 85%) had sustained virological response after liver transplant, but six patients had recurrent HCV infection after transplant.

HCV RNA was detected in 67% of liver explants both from patients with and without recurrent HCV infection after liver transplant, but the intrahepatic HCV RNA concentration was significantly higher in those who relapsed than in those who achieved posttransplant sustained virological response.

Explant HCV RNA concentrations did not differ between individuals treated with sofosbuvir plus ribavirin and those treated with more than one direct antiviral agent (DAA).

The two patients who relapsed despite having an HCV RNA-negative explant carried HCV resistant variants both at baseline and at relapse.

"Our study demonstrates that despite the use of effective DAAs, residual HCV RNA remains present in liver explants of a significant proportion of HCV-infected patients treated on the waitlist, despite undetectable HCV RNA in serum," the researchers conclude. "Nevertheless, its presence does not seem to be associated with virological relapse after transplantation, except in cases with high liver HCV RNA concentrations."

"The presence of non-functional HCV RNA or a down regulation of the intrahepatic interferon pathway unable to clear residual HCV RNA might explain our findings," they speculate.

No commercial funding was reported for the study, but several co-authors work for Gilead Sciences or have other ties to the company.

Dr. Forns did not respond to a request for comments.


Gastroenterology 2016.

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