Репозиторий Университета

© 2017 Elsevier Masson SAS A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC50dark/IC50light ratio of 11–18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. Purpose. A special place among liver diseases is occupied by various tumors and tumor-like lesions. In recent years in clinical practice the possibilities of correct diagnosis have increased significantly as a result of the introduction of advanced diagnostic equipment and wide usage of various contrast agents at studies of the abdominal cavity using the ultrasound method (US), multislice computed tomography (MSCT) and magnetic resonance imaging (MRI). In addition, the differential diagnosis of benign and malignant lesions has been simplified even when the size of the lesions is less than 1 cm. This scientific review describes the capabilities of the "routine" method of the liver diagnostics – US, as well as the latest techniques that are being introduced into the modern practice such as: US with intravenous contrast enhancement, US elastography and perfusion CT and MRI. The advantages of each method are presented as well as the limitations of their use in clinical practice.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. This lecture for the system of postgraduate medical education analyzes causes, types, key links of pathogenesis, and manifestations of the main typical forms of liver pathology-liver failure, hepatic coma, jaundice, cholemia, acholia, cholelithiasis, and their complications in children. To control the retention of the lecture material, case problems and multiple-choice tests are given.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. Purpose. To improve diagnostics and effectiveness of treatment in patients with unresectable cholangiocarcinoma complicated by obstructive jaundice. Materials and methods. A total of 28 patients (100%) with unresectable or functionally inoperable cholangiocarcinomas complicated by obstructive jaundice were diagnosed and treated. All patients underwent percutaneous drainage of the ducts under the ultrasound control and fluoroscopy. After reduction of jaundice video fluorescent diagnostic was performed. There was used a special module for that, by means of which a video fluorescent image of the bile ducts tumor was obtained and the degree of photosensitizer accumulation in the tissues was determined. Following photosensitizers were used: Photosens, Radachlorin (Russia) and Photolon (Belorussia). After the videofluorescence diagnostics photodynamic therapy of tumor stricture was conducted. Photodynamic therapy was performed using a fiber-optic system, if necessary, a controllable balloon catheter on the distal segment was used allowing to conduct therapy throughout the stricture more evenly. For the restoration of biliary evacuation nitinol stents were used. Results. In all patients a videofluorescent image of the bile duct tumor was obtained and a high degree of photosensitizer accumulation was determined. At the same time 23 patients (82%) had a malignant lesion confirmed morphologically. The effectiveness of combined treatment in unresectable cholangiocarcinoma was evaluated by life expectancy, the highest was 29 months (mean 14±5 months), but some of patients were under dynamic control for a period of 6 to 17 months. Conclusions. Usage of interventional treatment methods for patients with cholangiocarcinoma complicated by obstructive jaundice improves liver function and decreases jaundice. The combined use of minimally invasive technologies with fluorescent diagnostics and photodynamic therapy allows to increase the median life expectancy and improve the quality of patient’s life.

© 2018 Nutritec. All Rights Reserved.  The aim of this study was to examine the effect of polyphenol quercetin on morphological changes in nonalcoholic fatty liver disease (NAFLD) in rats fed high-fructose diet. Material and methods. For 20 weeks animals (n=8 in each group) of the 1 st group were given standard diet and water; the 2 nd group - standard diet and 20% fructose solution; the 3 rd group - standard diet with quercetin supplementation (0.1%) and 20% fructose solution. Formalin-fixed and paraffin-embedded liver samples were sectioned, stained (hematoxilin and eosin, Van Gieson's stain), evaluated with the use of the SAF and NAS scales. Results and discussion. Histological assessment did not reveal pathology in the structure of the liver of the 1 st group rats (SOAOFO; NAS - 0, fibrosis - 0). The 2 nd group rat livers disclosed micro-, mid- and macrovesicular steatosis, inflammation without ballooning, pericellular and periportal fibrosis (S2A1F2; NAS - 3, fibrosis - 2). Quercetin-treated rats exhibited in liver significantly less steatosis without significant changes in inflammation and fibrosis features (S1A1F2; NAS - 2, fibrosis - 2) compared with rats of the 2 nd group. Conclusion. The data obtained demonstrate the ability of quercetin to inhibit the development of NAFLD in rats fed a diet with a high content of fructose, by reducing the severity of hepatostatosis.

Liver resection remains the method of choice for treatment of colorectal liver metastases with good long-term results. Regional lymph nodes involvement is significant negative prognostic factor. Moreover, it has been considered as a contraindication for liver resection for a long time. The role of lymphadenectomy remains controversial. Current state of this problem is reviewed in the article. Liver regional lymph nodes involvement takes place in 10-20% of cases. PET/CT is the most sensitive method of preoperative diagnosis. Involvement of liver regional lymph nodes is currently not absolute contraindication for liver resection. Routine lymphadenectomy does not make sense, and, perhaps, is justified only within scientific trials for more accurate disease staging. Indications for lymphadenectomy are suspicious changes of lymph nodes revealed by preoperative visualization methods or by intraoperative exploration. Modern chemotherapy regimens allow to reconsider the prognostic importance of liver regional lymph node metastases and to extend indications for liver resections.

© 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 Russian Transplant Society. All rights reserved. Aim. To establish the ability of the total RNA extracted from the body’s bone marrow cells (BMCs), in which liver tissue was damaged, to serve as a carrier of targeted regenerative signals to this organ. Materials and methods. By method of adoptive transfer in rats (n = 37) the mitotic and proliferative activity of liver and kidney cells were studied in intact recipients after intraperitoneal injection: the mononuclear BMCs – 2,5×106; 5,0×106; 3,5×107 cells – group 1 and the total RNA of the same BMCs (30μg/100g of weight) – group 2 from donors in 12 hours after 70–75% of hepatectomy; in group 3 (control), a saline solution was injected. RNA from BMCs was extracted by the method developed by the «Evrogen» firm (Russia) with the reagent Extract RNA. Results. In group 2 in 48 and 72 h. there was the increasing of mitotic and proliferative cell activity in the liver, but not in the kidneys (control of the specificity of regenerative signals); in group 1 there was no transfer of regenerative signals to these organs. Conclusion. The authors believe that the total RNA from BMCs, activated by hepatectomy, accumulates targeted (hepatospecific) regeneration signals, but they are perceived only when RNA has been obtained by the damaged tissue.

© 2018 Russian Transplant Society. All rights reserved. Chronic HCV infection is the leading cause of liver transplantation in adults in developed countries. Unfortunately, the reinfection of the graft inevitably occurs in all patients with persistent replication of the virus. Against the background of the necessary immunosuppressive therapy, the progression of the disease accelerates, leading to rapid decompensation of the liver. Antiviral therapy significantly improves the results of transplantation, but the use of standard interferon-based regimens is associated with low efficacy (no more than 30% for the most common 1 genotype of the virus) and poor tolerance. The article describes new interferon-free oral regimens used to treat the recurrence of HCV infection of 1 genotype.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. To demonstrate the effectiveness of volumetric multispiral computer tomography at the planning of focal liver masses treatment. To present visual 3D reconstructions of the liver, its vessels and focal masses. Material and methods. A group of patients included 25 patients with different focal liver masses. The age of the patients was from 29 to 83 years (mean age 62.1 years). Each patient had MSCT of abdomen with intravenous contrast injection. The following diagnoses were made according to the results of the examination, most of which were subsequently confirmed histologically: hemangioma-3 (12%), focal nodular hyperplasia-2 (8%), abscess-1 (4%), hepatocellular carcinoma-2 (8 %), cysts-4 (16%), metastases-13 (52%) cases. Results. Three-dimensional modeling allows effectively and without distortion to combine all the phases of contrasting in a single image, which gives complete information about the anatomical features affected by the pathological process of the liver. Conclusion. Processing DICOM images with the construction of 3D models of the liver helps the surgeon at the planning of surgical treatment, improves the spatial perception of the anatomical relationship of the organ, its vessels and pathological formations. However, three-dimensional modeling requires additional time and its clinical significance remains insufficiently studied.

AIM: To develop predictive model for hepatic insufficiency in obstructive jaundice.MATERIAL AND METHODS: Obstructive jaundice was modeled by the author's method on 48 mini pigs, while morpho-functional features of erythrocytes were studied by using of INTEGRA Aura atomic force microscope (NT-MDT, Zelenograd, Russia). Histological specimens were stained with hematoxylin and eosin. Discriminant analysis was used to create predictive model for hepatic insufficiency.RESULTS: Mathematical model of hepatic insufficiency prediction has been developed. Sensitivity and specificity of this model were 94.1% and 74.2% respectively. Total percentage of correct predictions was 81.3%.CONCLUSION: Severe obstructive jaundice contributes erythrocyte's transformation from biconcave to dome-shaped followed by changes of its physical properties. Erythrocyte's volume and activity of cytolysis enzymes are the most informative to predict hepatic insufficiency. Our model allows us to diagnose this complication at early stages and to correct pre-, intra- and postoperative therapy.

© 2018 Vitebsk State Medical University. All rights reserved. Objective: To study the ultrastructural changes in the liver mitochondria in experimental diffuse purulent peritonitis against the background of the metabolic support. Methods: The morphometric evaluation of the rabbit liver mitochondria electron microscopic images (n=55) was performed in experimental diffuse purulent peritonitis. The obtained electron diffraction patterns were estimated using the ImageJ 1.45s program, in which the number of mitochondria sections, the number of intermithochondrial contacts and the number of damaged and intact mitochondria were counted. The average area, perimeter, and specific volume (measured in %) were calculated for the undamaged mitochondrial profiles. Metabolic agents with energotropic properties, phosphocreatine preparations containing creatine phosphate and preparations containing the succinic acid, niacinamide, inosine diphosphate and riboflavin were used. Results: Electron microscopic analysis of mitochondria of hepatocytes made it possible to reveal significant changes in their structure, caused by the development of purulent peritonitis. Morphometric evaluation of electron diffraction patterns showed changes in the quantitative and qualitative characteristics of mitochondria: the ratio of the damaged and intact mitochondria, their size, perimeter and specific volume of all groups. The use of metabolic support permitted to reduce the negative effect of purulent peritonitis in the postoperative period, which is exerted on the liver mitochondria, in comparison with the control group of animals that did not receive any metabolic support. Conducting a comparative analysis revealed a higher efficacy of the metabolic agent containing the succinic acid, niacinamide, inosine diphosphate and riboflavin, which resulted in more intensive restoration of the mitochondrial membrane structure. Conclusions: The development of purulent peritonitis is accompanied by a violation of the ultrastructural organization of the liver mitochondria in all studied groups. Metabolic correction allows restoring the membrane structure of mitochondria, and as the result improving the energy supply of cells to combat the negative consequences of endotoxicosis in peritonitis.

© 2018 Russian Transplant Society. All Rights Reserved. HCV infection is one of the most common causes leading to the development of terminal liver diseases – cirrhosis and hepatocellular carcinoma, the main treatment for which is orthotopic liver transplantation. However, with continued virus replication, 100% reinfection occurs, which leads to the rapid progression of cirrhosis of the graft and the loss of its function. Standard interferon-containing therapy is ineffective for HCV infection, especially genotype 1, both before and after transplantation, and also has a wide range of adverse events. The article presents the successful experience of treating the recurrence of HCV infection 1 genotype in a patient who underwent liver transplantation and several courses of ineffective antiviral therapy.

© 2018 Russian Transplant Society. All Rights Reserved. Aim. To study the efficacy and safety of the use of paritaprevir, ritonavir, ombitasvir and dasabuvir in combination or without ribavirin in liver recipients with recurrence of HCV 1 genotype after transplantation. Materials and methods. The study included 46 patients after orthotopic liver transplantation with recurrence of HCV 1 genotype. 37 patients completed a 24-week course of antiviral therapy, including paritaprevir, ritonavir, ombitasvir and dasabuvir in combination or without ribavirin. The effectiveness of the therapy was calculated as the proportion of patients who achieved aviremia 12 weeks after the end of the course of treatment. The safety of therapy was assessed by the number of adverse events that occurred during the course of antiviral therapy. Results. A sustained virologic response at 12 weeks after the end of the course of antiviral therapy, including paritaprevir, ritonavir, ombitasvir and dasabuvir, reached 100% of the recipients of the liver. Reduction in the intensity of cytolytic and cholestatic syndromes was noted at week 4 of therapy. Adverse events were recorded in 56.7% of the subjects, mostly they were not severe and were stopped on their own. Acute cellular rejection of the transplant developed in 1 patient (2.7%). There have been no cases of irreversible liver transplant dysfunction or death of the recipient. The conclusion. The use of paritaprevir, ritonavir, ombitasvir and dasabuvir is safe and effective in the treatment of relapse of HCV infection of 1 genotype after liver transplantation.

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. Purpose. To show the difficulty of diagnosis and treatment of atypical course of tuberculous empyema, when the process was complicated by tuberculosis of the chest, destruction of the diaphragm and penetration into the liver. Results. After chest MSCT scan, tuberculosis was suspected. The patient successfully underwent surgery: Pleurectomy with chest wandering abscess excision, resection of the VII rib and abdominal wandering abscess excision combined with the diaphragm and liver resection. The postoperative period was uncomplicated. During examination 4 years after surgery the patient was in a satisfactory condition, has ability to work, was transferred to group III dispensary tuberculosis registration. Discussion. Diagnosis and treatment of pleural empyema in some cases is difficult and, sometimes, requires differentiation from the oncological process. We have not found cases of tuberculous empyema spread of in the abdominal cavity with penetration into the liver in the literature. Conclusion. MSCT scan allowed to timely diagnose the atypical course of tuberculous empyema.

© 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. Aim. To analyse the status and trends in the development of organ donation and organ transplantation in the Russian Federation according to 2017 data. Materials and methods. The survey of heads of transplantation centers was conducted. A comparative analysis of the data obtained in the dynamics of years, between individual subjects of the Russian Federation, the centers of transplantation is performed. Results. According to the register in 2017 in Russia there were only 41 centers for kidney transplantation, 24 liver and 16 hearts. The waiting list for kidney transplantation in 2017 included 5,531 potential recipients, which is approximately 13.8% of the total number of 40,000 patients receiving dialysis. The level of donor activity in 2017 was 3.8 per million of the population, while the share of multiorgan seizures was 66.5%, the average number of organs received from one effective donor was 2.8. In 2017, the level of kidney transplantation was 8.0 per million of the population, the liver transplantation index was 3.0 per million of the population; the rate of heart transplantation is 1.7 per million of the population. In 2017 the number of transplants in Russia increased by 11.3% compared to 2016. There are 11 transplantation centers on the territory of Moscow and the Moscow Region, and half of all kidney transplants and 70% of all liver and heart transplantations are performed. The number of patients with transplanted organs in the Russian Federation is approaching 13,000. Conclusion. In the Russian Federation there is a strong tendency to increase the number of effective donors and to increase the number of organ transplants, and the number of transplant centers is also increasing. In recent years, the country has created prerequisites for the development of organ donation and transplantation: the regulatory and legal framework, public donation funding, material and technical base, etc. In the coming years, positive experience and organizational patterns of organ donation and transplantation from successful regions in Other subjects of the Russian Federation for building effective programs. The leading role in this process should be played by the Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs.

© 2018 Media Sphera Publishing Group. All rights reserved. The review demonstrated results and prospects of non-pharmacological and drug therapy patients with liver disease, not associated with a viral infection. The presented data emphasize the relevance of studying the problem of effective therapy of diseases of the liver and its role in improving the course and outcomes of liver disease.

© 2018 Dynasty Publishing House. All rights reserved. The article presents a clinical case of a patient with genetically confirmed Alagille syndrome (ALGS) with marked delay of physical development that did not correspond to the severity of liver damage. Alagille syndrome (ALGS) is a rare hereditary disease with underlying hypoplasia of the intrahepatic bile ducts manifested by cholestasis syndrome in the first weeks of life. Developmental delay is characteristic for cholestatic diseases of the liver, including ALGS, which is conditioned by impaired absorption of fats and fat-soluble vitamins in the intestines. But growth delay and underweight in this syndrome often do not correlate with the severity of cholestatis syndrome, and causes of their development remain unstudied. Cholestatis syndrome was moderate, and clinical signs of liver cirrhosis were absent. Intense skin itching, greatly disturbing not only the baby's wake period but also sleep, along with marked height and weight deficit were indications for liver transplantation at the age of 4 years, after which a fast normalisation of the parameters of physical development was noted. This clinical case study permits to hypothesize that developmental delay in children with ALGS is conditioned by chronic cholestatic liver damage, irrespective of the severity of its clinical presentation.

© 2018 Russian Transplant Society. All rights reserved. Donor organs shortage leads to extending criteria for deceased liver donation in the whole world. Aim: To compare results of deceased donor liver transplantation (DDLT) depending of donor age over 60 years old. Materials and methods: The study includes 390 DDLT from January 2010 to November 2017. All liver donors separated by age for two groups: I - 60 years and older (n = 26); II - younger than 60 years (n = 364). All donors were standardized by demographic, laboratory fi ndings and inotropic drug requirement. Results: no difference between both groups in severity of ischemia-reperfusion injury, ICU or in-hospital staying (median 2 and 7,5 days respectively) was found. There is also no difference between biliary or vascular complication rate. 5-year actuarial survival rate found no difference between both groups (I: 70%: II: 76%, p = 0,54). Conclusion. Using grafts from donors older than 60 years don't worsen early and late results of DDLT. Care should be taken to avoid other risk factors (cold ischemia time, warm ischemia time).