High real-world efficacy of elbasvir/grazoprevir (EBR/GZR) in genotype 1 (GT1) infected patients with and without liver cirrhosis: results from the German Hepatitis C Registry (DHC-R)

Background:

In the past, HCV treatment was less successful in patients (pts) with liver cirrhosis. In pts with GT1 and GT4 infection EBR/GZR has demonstrated high efficacy across clinical studies. Information about the real-world efficacy of EBR/GZR in pts with liver cirrhosis is still scarce. Therefore, we investigated the real-world utilization and effectiveness of EBR/GZR treatment regimens in pts with and without cirrhosis in a large GT1 cohort of the German Hepatitis C Registry.

Methods:

From September 2016 until August 2017, 527 patients (pts) with GT1 infection were treated at physician discretion with EBR/GZR +/- ribavirin (RBV) for 12 to 16 weeks in 110 medical practices and hospital outpatient departments. Cirrhosis was reported on histological or non-invasive estimation. The primary outcome was per protocol sustained virologic response at 12 or 24 weeks post treatment (SVR12 or SVR24).

Results:

92 pts with cirrhosis (17.5%) and 435 pts without cirrhosis (82.5%) received EBR/GZR-based treatment and showed the following characteristics (cirrhosis vs. non-cirrhosis): mean age 60 vs. 52 years, male gender 63 vs. 62%, mean BMI 28 vs. 25, GT1a 35 vs. 34%, baseline viral load > 800.000 IU/mL 52 vs. 57%, gamma-GT elevation 72 vs. 48%, bilirubin elevation 17 vs. 5%, Quick's test < 80% (37 vs. 6%), platelet count < 150/nL (54 vs. 10), APRI score> 2 (24 vs. 6%), opioid substitution 10 vs. 12%, HIV co-infection 5 vs. 5%, renal dysfunction 10 vs. 11% and treatment-naïve 66 vs. 78%. Cirrhotic pts showed a higher frequency of co-morbidities such as cardiovascular disease (59 vs. 30%), diabetes mellitus (23 vs. 7%) and gastrointestinal disease (28 vs. 4%) thereby receiving more frequent outpatient medications than non-cirrhotic pts (88 vs. 68%). Most frequently used drugs were agents acting on renin-angiotensin system (48 vs. 23%), beta blocker (37 vs. 20%), drugs for acid-related disorders (29 vs. 14%) and diuretics (27 vs. 10%). In both populations, 92% of pts were treated with EBR/GZR and only 8% with EBR/GZR+RBV. At data extraction, SVR results were available from 433 pts. Per protocol SVR was 98.8% (79/80) and 98.3% (347/353) in pts with and without cirrhosis, respectively. One cirrhotic patient who failed treatment had Child B cirrhosis (off-label treatment). SVR rates of GT1a and GT1b infected pts with cirrhosis were 100% (27/27) and 98.1% (52/53), and in pts without cirrhosis 97.3% (107/110) and 98.8% (238/241).

Conclusions:

In German real-world, GT1 infected pts with cirrhosis are older, suffer more frequently from cardiovascular, metabolic and gastrointestinal co-morbidities and need more frequent co-medications. Despite these limitations, EBR/GZR-based treatment of cirrhotic pts results in high SVR rates of 98% in GT1b and 100% in GT1a infection. Moreover, SVR in Child A cirrhosis was 100%. These findings are comparable to SVR rates of 97% and 99% in GT1a and GT1b infection without cirrhosis. The majority of patients are treated with EBR/GZR (92%) in the absence of RBV.