[Assessment of body mass index in patients with chronic hepatitis C who received an effective antiviral therapy].

AIM: To evaluate the body mass index (BMI) in patients with chronic hepatitis C (CHC) with different stages of liver fibrosis and steatosis who received effective antiviral therapy (AVT). MATERIALS AND METHODS: The study included 278 CHC patients with a sustained virologic response (SVR) at the end of treatment. In addition to assessing the investigational data to determine the clinical status of the patient, we calculated BMI (following the World Health Organization guidelines) and determined the severity of liver fibrosis (F) and steatosis (S) using transient elastography. The patients were assessed at the start of antiviral therapy, after ≥6 months from the moment SVR was confirmed, and then every 12 to 24 months. RESULTS: By the end of the study, the mean patient age was 49 years, 53% of them were men, and 34% of the patients were obese. Excessive weight gain was registered in 17% (n=48) of the cases, with 60% newly diagnosed with Class 1 to 2 obesity. Both before the start of AVT and years after reaching SVR, the mean BMI corresponded to the reference pre-obesity values, the liver steatosis was significantly more often absent in normal BMI; on the contrary, fatty liver (predominantly S2 to S3) was registered in individuals with elevated BMI (p<0.0001). After the long-term period following a successful therapy, Stage F4 liver fibrosis patients were mainly diagnosed with obesity (80% versus 44% before AVT; p=0.0010). CONCLUSION: The high proportion of patients with elevated BMI and liver steatosis seen years after a successful CHC therapy indicates a continued risk of progression of chronic liver disease. Such patients should be advised on how important it is to change their lifestyle to reduce overweight and prevent weight gain. We also need long-term assessments of how liver steatosis changes over time and what are the outcomes associated with post-SVR increase in BMI.

[Prevalence of hepatitis B and C viral infection according to the data on fetal outcomes in Moscow in 2015-2017]. / Rasprostranennost' infektsii, vyzvannoi virusami gepatita V i S, po materialam letal'nykh iskhodov v Moskve v 2015-2017 gg.

OBJECTIVE: To elucidate the prevalence of hepatitis B and C viral infection among the people who died in Moscow in 2015-2017, by studying the primary medical records of a representative sample of fatal outcomes, followed by the mathematical extrapolation of the data obtained to the total number of all deaths. MATERIAL AND METHODS: The 2015-2017 primary medical documentations from 8 therapeutic-and-preventive establishments with morbid anatomy units in the administrative districts and from 2 infectious diseases hospitals of the Moscow Healthcare Department were studied. The sample of those who died was 11.8-12.1% of the total number of all-cause deaths in Moscow during these years and was representative at a 0.95 confidence probability and a ±5% confidence interval. The Bernoulli theorem and the Laplace function for the 95% confidence probability were used to extrapolate the obtained data to the number of all those who died in these years. RESULTS: The mortality rates associated with acute viral hepatitis B and C were 0.04-0.07 and 0-0.008, respectively, per 100,000 population, which corresponds to the official statistical data. The mortality rates for chronic viral hepatitis and liver cirrhosis in their outcomes, including hepatocellular carcinomas in their presence, exceeded the official statistical data by many times, accounting for 0.5-1.6 and 10.4-12.1 persons with viral hepatitis B and C, respectively, per 100,000 population and rose by 22.5% over 3 years. The rates obtained for hepatitis B virus were 1.7-5.6 lower, and those for hepatitis C virus were, on the contrary, 1.3-1.5 times higher than average in the European Union countries. There was a manifold (7.4-24-fold) prevalence of hepatitis C virus in the etiology of chronic liver damage. The mortality from liver cirrhosis of alcoholic and unknown etiology was 14.4-19.5 persons per 100,000 population and declined by 21% over 3 years. The percentage of deaths caused by acute viral hepatitis was 0.5% per 100,000 population in Moscow in 2017; that caused by chronic viral hepatitis, including liver cirrhosis in the outcome and hepatocellular carcinoma, which had developed in their presence, was 46.3%; and that of liver cirrhosis of alcoholic and unspecified etiology was 48.7% of the total number of all liver lesions. CONCLUSION: The study of primary medical records of a representative sample of fatal outcomes, followed by the mathematical extrapolation of the data obtained to the number of all deaths, makes it possible to objectively estimate the burden of mortality from hepatitis B and C viral infection.

[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.

[The efficiency of antiviral therapy in patients with chronic -hepatitis C infected with hepatitis C virus recombinants].

The review gives the data available in the literature in the efficiency of treatment in patients with chronic hepatitis C infected with hepatitis C virus.(HCV) recombinants, by applying various antiviral therapy regimens. The low efficiency of treatment with- pegylated interferons (PEG IFN) + ribavirin (RIB) and sofosburin (SOF) +RIB in this patient group (a sustained virologic response was achieved in 22 and 30.7%, respectively) compared with the efficiency of treatment (87-97 and 83-97%, respectively) inpatients infected with HCV genotype 2 does not allow the 2015 EASL HCV genotype 2 treatment regimens to be used in. such patients. In this connection, subtyping genotype 2 isolates by NS5B sequencing should be introduced into clinical laboratory practice to successfully detect recombinant HCVs and to enhance the efficiency of antiviral therapy.

[Analysis of ineffective antiviral therapy with pegylated interferon and ribavirin in a patient with chronic hepatitis C infected with HCV genotype 2].

The paper describes a case of ineffective dual antiviral therapy (pegylated interferon and ribavirin) in a patient with chronic hepatitis C infected with hepatitis C virus (HCV) genotype 2 according to the data from the use of a commercial test system. Analysis of the predictors of failure of antiviral therapy (AVT) (the HCV recombinant variant RF2k/1b, a high viral load before the start of therapy, an unfavorable IL-28B genotype, a high body mass index, and a need for a lower ribavirin dose after 12 weeks of AVT because of adverse reactions for less than 4 weeks) in this patient has shown that no virological response is mainly associated with the presence of the HCV recombinant variant, the treatment effectiveness of which is comparable with that in HCV genotype 1 and obesity. In this connection, when HCV genotype 2 is identified, sequencing the NS5B region of the HCV genome is additionally recommended to rule out the virus recombinant strain and, if it is detected, highly effective interferon-free therapy with direct-acting antivirals is indicated.

[Possibilities of using cepeginterferon alpha-2b in double (cepeginterferon alfa-2b and ribavirin) and triple (simeprevir, cepeginterferon alpha-2b, and ribavirin) antiviral therapy regimens for chronic hepatitis C. A review of clinical trials and experience of everyday clinical practice]. / Vozmozhnosti primeneniia tsepeginterferona al'fa-2b v sostave dvukh- (tsepeginterferon al'fa-2b i ribavirin) i trekhkomponentnoi (simeprevir, tsepeginterferon al'fa-2b i ribavirin) skhem protivovirusnoi terapii khronicheskogo gepatita S. Obzor klinicheskikh issledovanii i opyta povsednevnoi klinicheskoi praktiki.

Since the incidence of chronic hepatitis C (CHC) increases steadily, the priority of national health care is to provide antiviral therapy (AVT) for the maximum number of patients infected with hepatitis C virus (HCV). The regimens including pegylated interferons (PEG-IFN) are still in demand in the Russian Federation. A number of clinical trials have been conducted to evaluate the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b), an original PEG-IFN-α developed in the Russian Federation. Their results have shown that cePEG-IFN alpha-2b in the two-component AVT regimen has at least no less clinical efficacy than PEG-IFN alpha-2b and PEG-INF alpha-2a in HCV monoinfected and HCV/HIV co-infected patients. The pooled analysis of data has indicated that the use of cePEG-IFN alpha-b in combination with ribavirin allows an average of 80% of the patients with HCV genotypes 2 and 3 and 62% of those with HCV genotype 1 to achieve a sustained virological response (SVR). In clinical practice when the two-component AVT regimen (cePEG-IFN alpha-b and ribavirin) was used in patients with early-stage CHC and mild fibrosis, SVR was recorded in 90.7% of the patients with HCV genotype 2/3 and in 75% of those with HCV genotype 1. The experience in using cePEG-IFN alpha-2b as a component of the three-component AVT regimen (simeprevir, cePEG IFN alfa-2b, and ribavirin) has been published. The observational program manly covered young patients with mild or moderate fibrosis. SVR was observed in 94% of the patients. Another paper describes the experience with the triple AVT therapy (simeprevir, cePEG-IFN alfa-2b, and ribavirin) in 22 patients, the majority of whom had advanced fibrosis. SVR was recorded in 71.4% of those who had completed treatment. Thus, an individual approach and assessment of predictive response factors to two- or three-component AVT regimens including cePEG-IFN alpha 2b can achieve successful treatment outcomes in most patients with CHC, which is, in some cases, more economically sound than interferon-free regimens used as first-line therapy.

Hepatitis B virus genetic typing using mass-spectrometry.

Mini-sequencing with subsequent result registration using MALDI-ToF mass-spectrometry was employed for hepatitis B virus genetic typing in Russian population. This approach was employed for hepatitis B virus genetic typing in HBsAg-positive patients with chronic hepatitis B, hepatitis of combined etiology and hepatic cirrhosis and allowed to show the prevalence of D genotype (83.3%) in all groups of patients. Other hepatitis B virus genotypes: genotype A (5.9%), genotype C (3.6%), and mixed infection with D and C (7.2%) were also found in patients with chronic hepatitis B and hepatic cirrhosis. All genotypes were found in patients with chronic hepatitis B and hepatic cirrhosis. Chronic hepatitis of combined etiology was noted only in patients with genotype D. Possibility of detection of mixed infection with hepatitis B viruses of various genotypes is a distinct advantage of mini-sequencing approach over direct nucleotide sequence evaluation for hepatitis B virus genetic typing.