2 research outputs found
Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network.
Background
Few data are available on the virological and clinical outcomes of advanced liver disease
patients retreated after first-line DAA failure.
Aim
To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in
the advanced liver disease stage.
Methods
Data on HCV genotype, liver disease severity, and first and second line DAA regimens were
prospectively collected in consecutive patients who reached the 12-week post-treatment
and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centersResults
Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve
SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis.
The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir\ub1ribavirin),
whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or
other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a
second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with
sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs \ub1ribavirin. Among these, 69 (96%)
patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5\u201314
months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12
(16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%),
whereas it did not change in the remaining 60 patients. Following the retreatment SVR12
(median time of 6 months; range: 3\u201312 months), the Child-Pugh class improved in 17
(23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and
from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of patients who were retreated, 3 (4%) had undergone OLT
before retreatment (all reached SVR12 following retreatment) and 2 (2.8%) underwent OLT
after having achieved retreatment SVR12. Two (70%) of the 3 patients who failed to achieve
SVR12 after retreatment, and 2 (2.8%) of the 69 patients who achieved retreatment SVR12
died from liver failure (Child-Pugh class deteriorated from B to C) or HCC complications.
Conclusions
Failure rate following the first DAA regimen in patients with advanced disease is similar to or
lower than that reported in clinical trials, although the majority of patients were treated with
suboptimal regimens. Interim findings showed that worsening of liver function after failure, in
terms of Child Pugh class deterioration, was improved by successful retreatment in about
one third of retreated patients within a short follow-up period; however, in some advanced
liver disease patients, clinical outcomes (Child Pugh class, HCC development, liver failure
and death) were independent of viral eradication