Virological failures of primary interferon-free therapy in patients with chronic HCV RNA viremia and successful repeated interferon-free therapy

Abstract

Objective. Description of clinical forms of chronic HCV infection in the observed patients, clarifications of options and causes of virological failures of primary interferon-free therapy (DAAT/1) and the results of repeated interferon-free treatment (DAAT/2).Materials and methods. 8 patients with chronic RNA HCV viremia (subtypes 1b+/–1a and 3а/3ab) were prospectively observed who suffered a virological failure of primary interferon-free therapy with original inhibitors in the form of relapse of RNA HCV viremia and aviremic low-level replication RNA HCV in PBMCs (peripheral mononuclears), but then achieved HCV eradication with a repeated course of interferon-free therapy.Results. Two variants of virological failures of primary interferon-free therapy were noted — relapse of RNA HCV viremia and aviremic low-level replication of RNA HCV in PBMCs. A number of unfavorable prognosis signs (individual clinical and laboratory syndromes and laboratory parameters) were revealed, which were observed in most patients who did not achieve HCV eradication using primary interferon-free therapy with antiviral drugs: HCV-associated syndromes of low-grade systemic inflammation (LGSI), benign lymphoproliferation and autoantibody production, a high level viral load of HCV RNA viral load in blood plasma, HBV-coinfection without HBsAg and cirrhosis of the liver in the outcome of chronic hepatitis C. The target result of repeated interferon-free therapy, confirmed by the sustainable virological response after 12 weeks after the end of the treatment (SVR12), was achieved in all «losers» of primary interferon-free therapy.Conclusion. The unfavorable prognostic signs identified in the majority of «losers» of primary interferon-free therapy in the form of individual clinical and laboratory syndromes and laboratory parameters may be associated with potential virological inefficiency of therapy. Based on logistic regression analysis, the value of each of the identified features for predicting different outcomes of primary interferon-free therapy in a large group of patients with HCV is shown. Pangenotypic combinations of GLE/PIB+SOF+/–RBV and VEL/SOF+RBV inhibitors have shown their high antiviral efficacy in the treatment of relapse of RNA HCV viremia and aviremic low-level replication of RNA HCV in peripheral mononuclears for all the patients for whom primary interferon-free therapy was unsuccessful.