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Introduction. The options of antiviral therapy (AVT) in the stages of severe liver fibrosis and cirrhosis (LC) as well as in the patients with comorbidities for the long time were limited to the standard therapy by pegilated interferon (peg-IFN) in combination to ribavirin (RBV). Before official registration of interferon-free treatment modes in 2015 experience of the application was limited to clinical trials or treatment within early approach programs. Aim of investigation. To analyze the efficacy of PTV for chronic hepatitis C within the named patient program of expanded access to daclatasvir. Material and methods. Approval of Ministry of Healthcare of the Russian Federation to import of drugs was received for the treatment of 101 HCV-infected patients with compensated LC, who, been untreated had an urgent need for effective therapy, with estimated life expectancy less than 12 months, in 12 centers of the Russian Federation. The patients with 1b HCV genotype received treatment by combination of daclatasvir and asunaprevir 100 mg, patients with 2 and 3 HCV genotypes, and those with 1b HCV genotype after the liver transplantation received daclatasvir to sofosbuvir combination. Results. Sustained virologic response for 24 wks (SVR24) in early approach program was 89% (83 of 93) of patients with severe liver disease who urgently needed effective treatment with estimated life expectancy of less than 12 months if been untreated. In group of the patients receiving treatment mode of daclatasvir + asunaprevir the frequency of SVR24 achievement was 90%. Of 93 patients who underwent complete treatment course no severe adverse effects were registered. During treatment infrequent nonspecific adverse events, such as a headache and fatigue were observed. No significant elevation of alanine transaminase and aspartate aminotransferase activity, or bilirubin level were detected. Conclusions. Daclatasvir combination to asunaprevir or sofosbuvir demonstrated high efficacy, including that at treatment of patients with poor prognostic signs.

Aim. To estimate efficacy and safety of direct antiviral drugs for hepatitis C treatment in donor lung recipients. Key points. The first cases in Russian literature and one of the first-ever cases of hepatitis C treatment by direct antiviral agents in lung transplant recipients are presented. Combined therapy by asunaprevir and daclatasvir for 24 weeks resulted in sustained virologic response. No significant adverse effects on drug to drug interactions, except for mild and controllable alteration of tacrolimus blood level, were noted. Conclusion. Daclatasvir and asunaprevir combination is effective and safe treatment mode for hepatitis C in donor lung recipients

Aim of investigation. To estimate efficacy and safety of narlaprevir (NVR) with ritonavir (RTV), pegilated interferon (peg-IFN) and ribavirin (RBV) at treatmentnaïve and earlier treated noncirrhotic patients with chronic hepatitis C caused by the 1st virus genotype in double blind placebo-controlled 3rd phase study (PIONEER). Material and methods. The main group received NVR (200 mg od orally) in combination to RTV (100 mg) and pegIFN/RBV for 12 weeks that was followed by peg-IFN/ RBV for 12 weeks. Comparison group received pegIFN/ RBV for 48 weeks, for the first 12 weeks in combination to placebo. Results. The sustained virologic response in 24 weeks after treatment termination (SVR24) in the main group (NVR/RTV, PEG IFN/RBV)) was achieved in 89.1% (163/183) of treatment-naïve and 69.7% (69/99) of earlier treated patients. SVR24 was achieved in 86.5% (32/37) of patients with relapse after previous peg-IFN/ RBV treatment course. The viral load decreased for the mean of 5.3 log10 in 2 weeks and 5.9 log10 in 4 weeks of treatment in the main group vs 1.5 log10 in 2 weeks and 2.5 log10 in 4 weeks in comparison group. In treatment-naïve patients from the main group SVR24 was achieved in 90.8% at initial METAVIR F0-F2 liver fibrosis stage and in 75% at F3 liver fibrosis stage. In those who were previously treated by peg-IFN/RBV, in the main group SVR-24 was attained in 72.6% at liver fibrosis stage F0-F2 and in 53.3% with F3 liver fibrosis stage. NVR/RTV addition to peg-IFN/RBV treatment did not alter safety profile as compared to peg-IFN/RBV therapy. Conclusions. In PIONEER study the narlaprevir combination therapy was characterized by high efficacy, convenience of administration and favorable safety profile.

Aim of investigation. To estimate frequency of late relapses and clinical outcomes in patients with chronic hepatitis C (CHC) with sustained virologic response (SVO) achievement at antiviral therapy (AVT).Material and methods. Overall 208 patients with CHC, including 12 at the stage of liver cirrhosis (LC), who achieved SVO were investigated. Mean duration of the follow-up was 56,1±35,4 months. Standard clinical and laboratory investigation and evaluation of RNA HCV was carried out. In 114 patients RNA HCV and DNA HBV in blood serum and peripheral mononuclear blood cells were studied by polymerase chain reaction (PCR) with fluorescent hybridization detection in «real time» mode (sensitivity of 10 IU/ml for HCV and 5 IU/ml for HBV).Results. In 3 (1,5%) patients late (i.e. over 6 months after AVT) relapses of HCV-infection were observed. Application of ultraresponsive PCR method allowed to reveal relapse half a year prior to its clinical and laboratory manifestation in 2 cases. No data on latent HCVinfection was obtained not in a single case, including patients with relapse of cryoglobulinemia syndrome. A principal cause of elevation of alanine transaminase activity was non-alcoholic steatohepatitis. In one LC patient development of esophageal varicose veins was detected. There were no cases of decompensation of LC, hepatocellular carcinoma and death due to liver disease.Conclusion. At patients who have achieved SVO as a result of AVT, late relapses of HCV-infection are rare and in the majority no disease progression was found. Relapses of cryoglobulinemia syndrome were observed, but data on presence of latent HCV-infection were not received. Highly sensitive PCR methods are rational for assessment of SVO.

Aim of investigation. To estimate risk of development of liver function decompensation, hepatocellular carcinoma (HCC) development and prognostic factors of liver-related mortality in patients with chronic viral mixed-hepatitis.Material and methods. 82 patients with hepatitis D, 56 – with hepatitis B+C and 20 – with hepatitis B+C+D, followed-up from Jan 2002 to Dec 2011, were included in the study. Results. During follow-up, decompensation occurred in 45.1, 8.9 and 62.5% of patients with compensated liver cirrhosis in groups D, BC and BCD, respectively. The 5-year risk of decompensation was 62%, 27% and 60%. HCC developed in 5.7% of patients, high AFP being the only predictor of HCC. The 5-year risk of HCC was 3.8%, 3.5% and 0%, respectively. 17.1%, 1.8% and 20% of patients died in groups D, BC and BCD, respectively, 5-year survival rate was 90%, 97% and 82%.Conclusions. In patients with chronic viral mixed hepatitis it is decompensation with liver failure development that determines prognosis and is principal cause of liver-related mortality in the most cases, not HCC development.

Aim of investigation. To study the functional changes of cardio-vascular system in patients with viral liver diseases.Material and methods. Overall 150 patients with hepatitis virus C-associated liver diseases, including 80 patients with chronic hepatitis and 70 – with liver cirrhosis (LC) have been included in original study. All patient underwent electro- and echocardiography, and Reberg test with calculation of sodium filtration fraction. At ECG analysis corrected Q-T (Q-Tс) interval was calculated by Bazett's formula.Results. In LC patients elongation of Q–Tc interval (432±21 ms) was revealed in comparison to patients with hepatitis (412±20 ms, р

The aim of review. Studying of effect of antiviral therapy on regression of fibrosis in chronic hepatitis B.Original positions. Article presents analysis of the largest investigations estimating effect of interferon α and nucleoside/nucleotide analogues on development of liver fibrosis. Decrease of severity of fibrosis (for prophylaxis of liver cirrhosis and hepatocellular carcinoma development) is one of the basic criteria of efficacy of treatment of chronic liver diseases. Now various strategies of influence on fibrosis are discussed, including elimination of etiological factor, suppression of inflammation and specific antifibrotic therapy.Conclusion. Successful antiviral therapy at chronic hepatitis B (continuous suppression of replication of virus and activity of inflammation in the liver) results in regression of fibrosis, including cirrhotic stage, and is associated with improvement of patients’ survival rate.

The aim of review. To analyze efficacy of antiviral therapy of various duration in patients with chronic hepatitis C (CHC).Original positions of the report. According to published data viremia dynamics has important prognostic value during treatment, which allows to consider it as one of important factors determining duration and efficacy of treatment along with virus genotype. Poor efficacy of the latter, especially at patients with the 1-st HCV genotype, high cost and risk of the serious undesirable effects cause necessity to individualize antiviral therapy at CHC, improve risk/benefit ratio.Conclusion. At CHC patients with the rapid virologic response (absence of viremia at the 4-th week) it is possible to limit duration of treatment by pegilated interferon and ribavirin in the case of the 1-st HCV genotype to 24 wks, in the case of the 2 and 3-rd genotypes to 12–16 wk. In patients with the 3-rd HCV genotype without rapid virologic response and in patients with the 1-st HCV genotype and slow virologic response treatment probably should be prolonged to 48 and 72 wks respectively.