[Assessment of the possible impact of hepatitis viruses on the development and course of autoimmune liver diseases].

BACKGROUND: Despite the well-studied pathogenesis, the etiology of autoimmune liver disease (AILD) remains unknown. AIM: To determine the significance of hepatitis A, B, C and E viruses in the development and progression of AILD. MATERIALS AND METHODS: A single-center case-control study included 139 patients with AILD: autoimmune hepatitis - AIH (n=46), primary biliary cholangitis - PBS (n=74), primary sclerosing cholangitis - PSC (n=19). Median age 56 years, IQR 48-65 years. 125 patients - without liver disease - control group (median age 55 years, IQR 46-65 years). Testing of blood serum samples for anti-HAV IgG, anti-HEV IgG, HBsAg, anti-HBc IgG, anti-HCV was carried out by solid-phase ELISA. All patients underwent fibroelastography. Needle liver biopsy - 70 patients: AIH (n=37), PBC (n=28) and PSC (n=5). RESULTS: Ab(IgG) to HAV and HBV were detected in patients with AILD significantly more often than in the control group (74.8% vs 54.4%; p<0.001). An increased risk of developing AILD was established in patients with the presence of antibodies to HAV, HBV and HEV (OR 2.491, CI 95% [1.481-4.190]). The highest risk of developing PBC was found in patients with antibodies to HAV and HBV (OR 3.008, 95% CI [1.633-5.542] and OR 2.515, 95% CI [1.242-5.093]). In patients with severe liver fibrosis (F3-F4 according to METAVIR), antibodies to HAV and HBV were detected significantly more often than in patients with F0-F2 [85% vs 65%; p=0.008]. CONCLUSION: In our work, we have demonstrated the relationship of past hepatitis A, B, E and AILD, as well as the high risk of developing severe fibrosis in patients with AILD and markers of hepatitis A and B viruses indicates the possible involvement of these viruses in the pathogenesis of AILD.

[Efficacy and safety of narlaprevir/ritonavir and daclatasvir non interferon combination in population of Russian patients with chronic hepatitis C].

AIM: Evaluate efficacy and safety of a combination of direct - acting antivirals narlaprevir/ritonavir with daclatasvir in patients with viral hepatitis C. MATERIALS AND METHODS: The study enrolled adult patients with HCV genotype 1b infection without demonstrated NS5A resistance - associated substitutions Y93C/H/N/S and/or L31F/M/V/I. Patients were treated with narlaprevir 200 mg QD, ritonavir 100 mg QD and daclatasvir 60 mg QD. Treatment duration was 12 weeks. Proportion of patients achieving sustained virological response 12 weeks after treatment (SVR12) was the primary efficacy endpoint. RESULTS AND DISCUSSION: In total, 105 (75.0%) patients were treatment with the study combination. Patients' age varied from 21 to 69 years, the mean age being 43.2±10.9 years. There were slightly more women (55.2%), and 69 patients (65.7%) had comorbidities. SVR 12 was 89.5% (95% CI 82.0-94.7%). In 10 of 11 patients with treatment failures NS5A resistance - associated substitutions in residues 31 and/or 93 were found, as well as less clinically relevant substitutions L28M, P58S, R30Q, Q62K. Adverse events (AEs) were found in less than one half of patients (45 patients, or 42.9% in the safety population). Almost all recorded AEs were mild to moderate. CONCLUSION: Efficacy of treatment with a combination of narlaprevir/ritonavir and daclatasvir in treatment - naïve patients with HCV genotype 1b was close to 90%. This combination was found to be safe and well - tolerated.

[Hepatic decompensation associated with an interferon-free antiviral therapy in patients with HCV-cirrhosis].

Today, there is no complete clarity about the pathogenetic mechanisms of the hepatic decompensation in patients with HCV-cirrhosis during the course of direct-acting antiviral (DAAs) therapy. The current article describes several clinical observations of decompensation (with the development of liver failure and portal hypertension) in cirrhotic patients during the course of DAAs-therapy of hepatitis C. The authors present contemporary views and their own assumptions about the possible mechanisms of the hepatic decompensation associated with DAAs-therapy in patients with liver cirrhosis.

Hepatic decompensation associated with an interferon-free antiviral therapy in patients with HCV-cirrhosis.

Today, there is no complete clarity about the pathogenetic mechanisms of the hepatic decompensation in patients with HCV-cirrhosis during the course of direct-acting antiviral (DAAs) therapy. The current article describes several clinical observations of decompensation (with the development of liver failure and portal hypertension) in cirrhotic patients during the course of DAAs-therapy of hepatitis C. The authors present contemporary views and their own assumptions about the possible mechanisms of the hepatic decompensation associated with DAAs-therapy in patients with liver cirrhosis.

[Resistance to protease inhibitors and efficiency of antiviral therapy in patients with chronic hepatitis C].

AIM: To clarify the role of virus resistance in the efficiency of antiviral therapy with protease inhibitors (PIs) chronic hepatitis C (CHC) patients, with moderate sensitivity to interferon-α. MATERIALS AND METHODS: Eight Caucasian patients (4 men and 4 women) aged 21 to 65 years (median 52.5 years) with genotype 1b hepatitis C virus (HCV) infection were included in the study. Two patients were diagnosed with liver cirrhosis; 4 had been ineffectively treated with peginterferon in combination with ribavirin. None of the patients had obesity and/or insulin resistance. All the 8 patients received triple therapy with PIs (boceprevir (n=3), telaprevir (n=4), and simeprevir (n=1)) and as a result failed to achieve a sustained virologic response. All the participants were studied to identify mutations in HCV NS3/4A region. RESULTS: Five of the 8 patients were found to have mutations in HCV NS3/4A region (substantially reducing drug susceptibility in 3 cases). CONCLUSION: In CHC patients who are moderately sensitive to interferon-α and receive therapy with PIs, resistance to the latter is critically important for the efficiency of therapy and the timely identification of resistance mutations can contribute to the choice of an optimal treatment policy.

[Hepatitis C virus genotype 3: that simple, yet that complex (corrected)].

The data on natural course of chronic viral hepatitis C infection (HCV) and the efficacy of antiviral treatment depending on virus genotype are summarized in the article. The significance of virus genotype in progression of liver fibrosis and liver steatosis is discussed. It is pointed out that chronic HCV infection caused by genotype 3 is characterized by a more aggressive clinical course of disease and less favorable prognosis. Optimal approaches to the management of patients with genotype 3 of chronic HCV infection as well as perspectives of antiviral therapy in this group of patients are discussed in the article. [corrected].