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Is DAA treatment for hepatitis C reducing the need for liver transplants?
Liz Highleyman, 2017-01-27 07:30:00
People successfully treated for hepatitis are less likely to need liver transplants and less likely to die while on a transplant waiting list, according to studies presented at the 2016 AASLD Liver Meeting in November. A related analysis looked at the optimal timing of treatment for people awaiting transplants in order to avoid 'MELD purgatory'.
Over years or decades chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis, hepatocellular carcinoma (HCC), hepatic decompensation and the need for a liver transplant. In recent years hepatitis C has been a leading indication for liver transplantation in Europe and the US.
Successful hepatitis C treatment can slow or halt liver disease progression. Direct-acting antivirals (DAA) used in interferon-free regimens have made treatment easier, faster and much more effective. All-oral DAA treatment has only been widely available since 2014, but it may be starting to have an effect on how many people with hepatitis C need liver transplants.
Donghee Kim and colleagues of Stanford University School of Medicine looked at mortality among people living with hepatitis C with decompensated cirrhosis awaiting liver transplants before and after the introduction of DAA therapy.
This analysis included more than 20,000 adult liver transplant candidates with end-stage liver disease identified from the US national Organ Procurement and Transplantation Network (OPTN) database.
Cohort 1 (n = 6002 including 2410 with HCV) consisted of individuals on a waiting list as of 1 January 2004, cohort 2 (n = 6598 including 2416 with HCV) was made up of those listed as of 1 January 2009 and cohort 3 (n = 8779 including 2783 with HCV) consisted of those listed as of 1 January 2014 – the last of which had DAAs available after sofosbuvir (Sovaldi) was introduced at the end of 2013.
Overall, 35% of the transplant candidates had hepatitis C. Roughly 30% had alcoholic liver disease in all cohorts, but the proportion with non-alcoholic steatohepatitis (NASH) rose over time, from 0.3% in cohort 1 to 9.9% in cohort 2 and 17.2% in cohort 3. In both the HCV and non-HCV populations more than half were men and patient age increased over time. In both populations the average MELD score was higher – indicating worse liver function impairment – in cohort 3 (14) than in cohorts 1 and 2 (13).
More people with HCV withdrew from the waiting list over time (6.3% in cohort 1, 4.2% in cohort 2 and 2.7% in cohort 3), and more did so because they improved enough to no longer need a transplant (0.3%, 1.6% and 2.2%, respectively). In the non-HCV population, overall withdrawal rose from 3.3% in cohort 1 to 6.2% and 6.9% in cohorts 2 and 3, and the proportion withdrawing due to improved condition followed a similar pattern (1.0%, 2.8% and 3.0%, respectively).
Nearly two-thirds of people with HCV in all three cohorts were alive one year after the study start date (64.1% in cohort 1, 63.1% in cohort 2 and 63.5% in cohort 3). About 12% in all three HCV cohorts died while on the waiting list (11.8%, 11.5% and 11.5%, respectively). One-year survival and death rates were similar in the non-HCV population.
The one-year mortality rate while on the waiting list was 10% lower for people with HCV in cohort 2 compared to cohort 1, and 22% lower for cohort 3 compared to cohort 2 – a statistically significant difference. Among the non-HCV population there was only a non-significant 3% reduction in the risk of death between cohorts 2 and 3, suggesting better hepatitis C treatment might help explain the greater improvement seen in the HCV population.
This pattern was more marked for people with HCV with the highest baseline MELD liver function scores (> 20), for whom the risk of death was 43% lower for cohort 3 compared to cohort 2, again statistically significant. In the non-HCV population the death rate for people with high MELD was 16% lower, a non-significant trend.
Looking at changes in MELD scores over time, the researchers found that scores rose less in both the HCV and non-HCV population with low baseline MELD in the most recent cohort. But the greatest improvement was seen among people with HCV with baseline scores > 20: those in cohort 1 saw a +4.39 point annual increase, compared with +3.70 in cohort 2 and +2.40 in cohort 3, suggesting reduced disease progression. Among the non-HCV population with high MELD scores, the annual change did not differ significantly.
These findings, the researchers concluded, show "improved survival and disease severity for HCV-positive liver transplant candidates in the DAA era, driven by patients with high MELD."