Репозиторий Университета

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Objective An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%. Patients and methods In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing. Results At baseline, patients had Child-Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent. Conclusion In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks' treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To evaluate the incidence and prevalence of hepatitis C in Russia and estimate the impact of hepatitis C virus on liver cirrhosis, hepatocellular carcinoma and liver-related mortality before the implementation of the national program for the elimination of viral hepatitis. Materials and methods. We analyzed statistical data on the incidence of hepatitis C in Russia in 2001–2017, the incidence, prevalence and mortality rates from liver cirrhosis and malignant liver tumors in 2011–2015. An analysis of the incidence and prevalence of HCV was carried out in various age-sex groups. The structure of genotypes of the hepatitis C virus was determined in patients at different stages of liver fibrosis and with different levels of viral load. Results. In 2017, 50 798 cases of HCV were registered in Russia (34.6 per 100 thousand of the population). As of January 1, 2017, the total number of patients with chronic hepatitis C under medical observation was 591 830 (405 per 100 thousand population). The incidence rate of fibrosis and cirrhosis in Russia in 2015 was 12.7 per 100000 population (18640 cases), the total number of registered patients – 75.9 per 100 thousand population (110951 people). The incidence rate of malignant liver tumors in 2015 was 5.5 per 100 thousand population (8083 cases), the total number of patients on dispensary observation was 5.0 per 100 thousand population (7360 people). In 2015, the estimated number of deaths from liver cirrhosis and hepatocellular carcinoma in the outcome of chronic hepatitis C was 14 792 and 1635, respectively. Conclusion. Hepatitis C is the main cause of liver cirrhosis (excluding alcoholic etiology), hepatocellular carcinoma and liver-related mortality in Russia. To reduce the prevalence of HCV and mortality from liver cirrhosis and primary liver cancer, it is necessary to provide all patients with HCV with antiviral drugs.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The first interferon-free regimen became available in Russia in 2015. It brought hope to HCV Gt1 patients with cirrhosis for whom interferon-based 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.

© 2018 Media Sphera Publishing Group. All rights reserved. Ascites and hydrothorax may be the symptoms of congestive heart failure and do not always reflects presense of the decompensated liver cirrhosis. Clinical examination of patient with chronic hepatitis C which cyanosis of the lips, cervival veins pulsation, a triple heart rhythm indicated on pathology of the heart (constrictive pericarditis), which was confirmed by instrumental methods. Congestive heart failure has lead to the congestive liver in a young female patient. Regression of all the symptoms of heart failure occurred after surgical treatment (pericardectomy).

© 2018 Russian Transplant Society. All Rights Reserved. Blood level of transforming growth factor beta 1 (TGF-β1) is associated with liver function and immune homeostasis, which suggests it as a potential biomarker for immunosuppressant tacrolimus dose requirement at liver transplantation (LT). Aim. To evaluate diagnostic efficacy of TGF-β1 blood level at determination of individual tacrolimus dose requirement in children at LT. Materials and methods. 89 children with end stage liver disease aged from 3 to 73 months were examined. Children underwent living related LT, then the recipients received 2–3 component immunosuppressive therapy, including tacrolimus. Blood concentration of tacrolimus and TGF-β1 was measured by ELISA. Results. TGF-β1 blood level in children before LT was significantly lower than in healthy children: 3.7 (1.3–8.4) and 19.3 (12.6–25.5) ng/ml, p = 0.001. A month after LT, its concentration increased to 8.1 (1.8–15.3) ng/ml (p = 0.02). A year after LT, the cytokine level remained higher than before transplantation: 6.6 (1.9–12.6) ng/ml, p = 0.01. TGF-β1 level did not correlate with tacrolimus blood concentration, determined 12 hours after the last administration of the drug, neither a month, nor a year after transplantation. At the same time, the cytokine level one month after LT was associated with a tacrolimus daily dose one year after the operation (r = –0.23, p = 0.04). In the recipients, who received smaller daily doses (0.4–2.5 mg) of tacrolimus, TGF-β1 level was higher than in those receiving large doses (3.0–6.0 mg) of the drug: 9.1 (2.6–16.2) ng/ml vs. 4.2 (1.3–9.2) ng/ ml, p = 0.04. Evaluation of diagnostic efficacy of the TGF-β1 level as a test for the detection of tacrolimus dose requirement showed that the area under the ROC curve (AUC) was 0.66 ± 0.07; 95% CI [0.53–0.79], the sensitivity and specificity of the test were 60 and 74% at threshold value 6.7 ng/ml. Relative risk of higher tacrolimus dose requirement was 3.14 ± 0.48; 95% CI [1.24–7.96]. Conclusion. TGF-β1 blood level in one month after LT less than 6.7 ng/ml is 3 times higher risk factor of tacrolimus dose requirement more than 3.0 mg per day. The likehood of the test is 66%, the sensitivity and specificity – 60 and 74%.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To study clinico-epidemiological characteristics of patients with CHC and to evaluate clinical, economic and other parameters related to their treatment. Patients and methods. The study is conducted in 10 countries in Central and Eastern Europe involving 1.500-2000 patients with chronic HCV infection, aged 18 years and older not current receiving treatment for hepatitis and seeking for care in a routine clinical visit to physician. After enrollment, patients are observed until the end of HCV treatment. The study includes three consecutive phases. At the phase 1 epidemiological data for the patients seeking for care is being collected at the single visit. Patients for whom antiviral IFN-containing treatment is planned to be started within 12 weeks from the first visit were included into the second phase. During phase 2 patients are being assessed on-treatment for HRQoL changes over time, the impact of HCV and treatment on work productivity, activities of daily living and resource utilization. Interim results presented in this paper reflect epidemiologic characteristics of HCV patients collected during the first phase of MOSAIC study on the territory of Russia. Results. Data from 492 patients were collected in 15 study centers in Russia. 441 patients (377 treatment naïve, 64 experienced) entered the study, 51 patients were considered non-participants. 161 patients did not start treatment within 12 weeks after enrollment. Patients were of white race, 57% males and 43% females, aged between 19 and 74 years, with median age 37.0 (IQR 31-47 years). Median time since HCV diagnosis was 2.0 years. 30 (6.8%) patients had clinically compensated liver cirrhosis, 40% of patients had unknown cirrhosis status. The most common viral genotypes were Gt1 and Gt3 – 55.6% and 37.6% of patients, respectively. Among patients with known viral load HCV RNA level at enrollment was ≤ 800.000 IU/ml in 53% of patients and > 800.000 IU/ml in 47% of patients. Twelve (4.3%) treated patients had extra-hepatic symptoms of liver disease, no association was found between liver cirrhosis and presence of extra-hepatic manifestations (p = 0.3534). 14.5% of patients were treatment experienced, 88.9% of them had only one course of antiviral therapy in the past. Relapse was the most common reason of therapy failure observed in 50% (32/64) patients.17.5% of HCV patients have concomitant diseases; the most common are cardiovascular diseases (5,7%), other liver diseases (5%) and diabetes mellitus (2,9%), the latter is associated with the presence of liver cirrhosis (p = 0.0125). Among studied parameters (gender, age, HCV genotype and pre-treatment status) age was an only significant predictor of liver cirrhosis development, odds increase with every 10 years of increment (OR 2.005 [95% CI 1.407; 2.858], ROC 0.732, p = 0.0001). Conclusion. Epidemiology of patients with HCV infection was investigated in the first phase of MOSAIC international observational study on the territory of Russia and described in the present article. Сlinical, humanistic and economic burden of anti-HCV treatment based on MOSAIC data will be presented in future publications.

Background

Small intestinal bacterial overgrowth (SIBO) was detected in cirrhosis in many studies. The aim is to perform a systematic review and meta-analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO with features of cirrhosis.

Methods

PUBMED search (until 14 January 2018) was performed. Specific search terms were: ‘(cirrhosis) AND (SIBO OR bacterial overgrowth)’. Studies not relating to cirrhosis or SIBO, animal studies, and non-original articles were excluded. A meta-analysis of all studies was performed using a random-effects model.

Results

117 references were identified by the PUBMED search. 3 references were added after handsearching the reference lists of all the articles. 99 references were excluded. 21 studies (included in total 1264 cirrhotics and 306 controls) remained for qualitative analysis and quantitative synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8–47.1), while the prevalence of SIBO for controls was 10.7% (95% CI 5.7–19.0). OR 6.83 (95% CI 4.16–11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001). SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001), and was not associated with hypocoagulation. Further studies are required to clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt hepatic encephalopathy in past, esophageal varices and systemic inflammation.

Conclusion

Small intestinal bacterial overgrowth is more often detected in cirrhosis than in healthy persons and is associated with some features of cirrhosis.

Background

Small intestinal bacterial overgrowth (SIBO) was detected in cirrhosis in many studies. The aim is to perform a systematic review and meta-analysis on the prevalence of SIBO in cirrhosis and on the relationship of SIBO with features of cirrhosis.

Methods

PUBMED search (until 14 January 2018) was performed. Specific search terms were: ‘(cirrhosis) AND (SIBO OR bacterial overgrowth)’. Studies not relating to cirrhosis or SIBO, animal studies, and non-original articles were excluded. A meta-analysis of all studies was performed using a random-effects model.

Results

117 references were identified by the PUBMED search. 3 references were added after handsearching the reference lists of all the articles. 99 references were excluded. 21 studies (included in total 1264 cirrhotics and 306 controls) remained for qualitative analysis and quantitative synthesis. Prevalence of SIBO for cirrhosis was 40.8% (95% CI 34.8–47.1), while the prevalence of SIBO for controls was 10.7% (95% CI 5.7–19.0). OR 6.83 (95% CI 4.16–11.21; p < 0.001). Prevalence of SIBO for decompensated cirrhosis was higher than prevalence of SIBO for compensated cirrhosis (50.5% vs. 31.2%; p < 0.001). SIBO in cirrhosis was associated with ascites (p < 0.001), minimal hepatic encephalopathy (p = 0.001), bacterial translocation (p = 0.026), spontaneous bacterial peritonitis (p = 0.008), prolonged orocecal transit time (p < 0.001), and was not associated with hypocoagulation. Further studies are required to clarify the relationship of SIBO with hyperbilirubinemia, hypoalbuminemia, overt hepatic encephalopathy in past, esophageal varices and systemic inflammation.

Conclusion

Small intestinal bacterial overgrowth is more often detected in cirrhosis than in healthy persons and is associated with some features of cirrhosis.