Evaluation of efficacy and safety of interferon-free "3D" regimen among patients with non-compensated cirrhosis caused by HCV genotype 1b infection.

Objective: The first interferon-free regimen became available in Russia in 2015. It brought hope to HCV Gt1 patients with cirrhosis for whom interferonbased schemes found to be non-effective or contraindicated. 3D therapy was the only available etiotropic option for them. New safety data published after the start of our study significantly limited usage of this regimen among patients with non-compensated cirrhosis. The aim of this study was to evaluate efficacy and safety of the 3D interferon-free regimen among HCV Gt1b patients with non-compensated cirrhosis. Method: 66 patients (26 males and 40 females) with HCV Gt1b and non-compensated cirrhosis were enrolled. All of them were treated with ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks. Ribavirin was discontinued after 4 weeks of therapy due to onset of new data on the efficacy of 3D regimen without ribavirin in Turquoise III study published in September 2015 before the change of package insert. Child-Pugh score was assessed before the start of antiviral therapy as follows: 21 patients (31,8%) - 9 points, 11 patients (16,7%) - 8 points, 34 patients (51,5%) - 7 points. The key method used to evaluate study results was modified intent-to-treat (mITT) analysis because number of analyzed patients within treatment period changed after withdrawal caused by safety reasons but followed by assessment of efficacy among patients who discontinued treatment. Per protocol (PP) method was also used in addition to mITT. Results: Aviremia after 14 days of treatment was reached among 35 out of 65 patients (53,8%), rapid virologic response - among 79,7% patients (51/64). Each patient who received full 12-week course of treatment (n=60) including those who discontinued due to safety reasons (n=3) between 14th and 30th days of therapy reached SVR12 and SVR24. Assessment of Child-Pugh score in 6 months after EOT demonstrated decrease by 3-4 points among 21 patients (33,9%) and by 1-2 points among 35 patients. 66,1% patients reached clinical improvement in MELD score. Treatment discontinuation was caused by progression of hepatic encephalopathy and/or jaundice (4 cases). Those adverse events regressed among majority of patients after discontinuation of therapy. 3 deaths were reported (bacterial endocarditis, progression of hepatic encephalopathy and bleeding from gastric ulcers) during treatment period and 1 death in follow-up period due to progression of hepatocellular carcinoma. Conclusion: 3D therapy was effective in 100% patients (mITT) with HCV GT1b and non-compensated cirrhosis both among those who completed full therapy course and those who discontinued the therapy due to safety reasons. Safety analysis demonstrated that the rate of severe adverse events was comparable with natural course of HCV-infection in patients on non-compensated cirrhotic stage without antiviral treatment. [ABSTRACT FROM AUTHOR]