Advent of DAAs accompanied by dramatic improvement in survival after HCV-related liver transplant

Survival among people with hepatitis C virus (HCV) undergoing liver transplant has improved significantly since the introduction of direct-acting antivirals (DAAs), investigators from Catalonia report in the Journal of Hepatology. Thanks to DAAs, there was also a decrease in the number of people with HCV needing a liver transplant.

“Although not unexpected considering the efficacy of these drugs, our findings suggest for the first time that the main problem of LT [liver transplant] programmes around the world, hepatitis C recurrence, will no longer impact on patient and graft survival,” write the authors. “These results support and recognise those public health programmes that have permitted widespread access to DAA to hepatitis C patients with advanced liver disease, and encourage the policies aimed to expand the access to all patients with HCV infection.”

DAAs have revolutionised the care and prognosis of people with chronic HCV infection. Well tolerated, the therapy can achieve cure rates in excess of 90%, even in people with decompensated cirrhosis.

In Western countries, HCV is the main cause of referral for liver transplant.

Investigators in Catalonia wanted to see if the use of DAAs was having an impact on composition of waiting lists for liver transplant and on short-term post-transplant survival.

They therefore analysed data for all patients admitted to the liver transplant waiting list in Catalonia between 2008 and 2016. This time period was divided into two periods: 2008 to 2013, when HCV therapy was based on interferons; and 2014 to 2016, when DAAs were used. The authors charted changes in reasons for liver transplant and post-transplant survival.

A total of 1483 people were admitted to the liver transplant waiting list.

The proportion of people for whom HCV-related disease was given as the reason for transplant fell significantly from 47% in 2008 to 35% in 2016. The sharpest falls in HCV-related indications occurred in 2015 and 2016.

In contrast, the number of admissions to the list for reasons other than HCV remained stable, or in the case of non-alcoholic steatohepatitis (NASH), increased significantly.

Closer study of HCV-related indications showed that decompensated cirrhosis accounted for 47% of admissions in 2008, falling to 24% in 2016.

Between 2008 and 2013, 7% of people with HCV were HCV RNA negative at the time of inclusion in the waiting list. Of the people with detectable HCV viral load at the time of admission, 13% received antiviral therapy. A sustained virological response (SVR) was observed in 46% of those receiving interferon and ribavirin therapy and in 80% of people taking a first-generation DAA in addition to these drugs.

In the DAA era, a fifth of people were already HCV RNA negative at the time of admission to the waiting list, with 53% of viraemic patients taking DAAs while awaiting transplantation. An SVR was observed in 91% of these individuals.

Improvements in liver function after SVR meant that ten were removed from the transplant list. Records of the people who were not treated before transplantation showed that 87% received DAAs after receiving a new liver with 96% attaining an SVR.

Over the period of the study, 1114 people underwent transplant. Overall three-year survival in the entire cohort increased from 82% to 91%. This improvement was due to improved survival among people with HCV, which increased from 76% to 91%. In contrast, survival remained stable among non-HCV patients.

“We have demonstrated for the first time that the availability of DAAs is associated with significant improvements in survival after liver transplantation in HCV-infected LT candidates…it is clear that DAA therapy will dramatically change the scenario of LT, potentially contributing to long-term improvements in survival,” conclude the authors. “In addition, DAAs are associated with a decrease in indication for LT related to HCV, which is notably changing the composition of waiting lists.”