DIRECT-ACTING ANTIVIRALS FOR HEPATITIS C DO NOT AFFECT THE RISK OF DEVELOPMENT OR THE OUTCOME OF HEPATOCELLULAR CARCINOMA.

HCV infection and its complications, especially hepatocellular carcinoma, is a substantial public health burden. In 2015 "Nationwide hepatitis C elimination program" was launched in Georgia. According to the protocol, patients with HCC also receive DAA antiviral treatment. We study the effect of the different DAA therapy regiments on the incidence or recurrence of HCC and its prognosis. Overall, 408 patients were recruited in Georgian-French Joint Hepatology Clinic HEPA between April 2015-March 2016. The selection criteria were as follows: 1 - age 50-65 years; 2. Liver fibrosis level F3-F4 or cirrhosis at least 15 years of disease history; 3. HCV positive diagnosed by PCR method, whatever the level of viral load and genotype; 4. absence of previous complications of cirrhosis (ascites, gastrointestinal bleeding or HCC; 5. Child-Pugh class A or B; and 6. absence of severe extrahepatic disease. Essential clinical and biological parameters were recorded. Clinical monitoring and management of adverse events were performed on a regular base. HCV All patients included in the study received anti-HCV treatment with direct-acting antivirals (DAAs) within the national hepatitis C elimination program in accordance with national protocols. During April 2015-March 2016 treatment was provided with sofosbuvir (SOF) in combination with ribavirin (RBV), with or without pegylated interferon (IFN). Since March 2016, ledipasvir/sofosbuvir (LDV/SOF) was prescribed to all patients with or without RBV depending on the HCV genotype, level of fibrosis, and previous treatment experience. In conclusion, we find that neither different DAA regimens nor different treatment duration affects HCC risk after antiviral treatment. Moreover, there are no significant changes in mortality rate due to HCC in these groups. Therefore, it can be concluded, that HCC status is not a contraindication for DAA treatment, especially at the early stages of cancer, when a tumor is curative.

Investigation of functional activity human dental pulp stem cells at acute and chronic pulpitis.

UNLABELLED: It is already recognized that together with the other connective tissues organ-specific progenic stem cells are also found in postnatal dental pulp. This group of undifferentiated cells is only 1% of total cell population of the pulp. The aim of the study was the identification of stem cells in human dental pulp, detection of their localization and assessment of functional activity during inflammation process and/or at norm. The obtained results showed that at acute pulpitis the pulp stroma is hypocellular in comparison with the norm but cells proliferative activity is low. CD 133 and NCAM (CD 56) positive stem cells were found in perivascularl space of the pulp stroma and in Hohle layer. At process prolongation and transition to the chronic phase pulp stroma is hypercellular, the cells with large, rounded or oval-shaped nuclei with clear chromatin appear together with fibroblasts. They are distributed as about entire thickness of the stroma as especially Hohle layer. In such cells higher proliferative activity (Ki67 expression) was observed. The cells in the mentioned proliferation phase are intensively marked by CD133, the rate of which is high in Hohle layer and along it. A large number of NCAM (CD 56) positive cells appear in pulp stroma. CONCLUSIONS: During pulpitis an involvement of stem cells into the process of reparative dentinogenesis should be conducted stepwise. In acute cases of the disease, stem cell perivascularl mobilization and proliferation and its migration to Hohle layer occur in response to irritation /stimulation. Chronification of the process leads not only to the migration of stem cells to the periphery of the pulp but also s their В«maturationВ¼ (increase of NCAM expression in the stem cells), which causes an increase the number of dentin producing active odontoblasts and initiation of reparative dentinogenesis.

Unknown bile ductuli accompanying hepatic vein tributaries (experimental study).

Studying Ductular reaction (DR) at early stages after common bile duct ligation (CBDL) in rats we revealed some ductular profiles (DPs) of unusual location - accompanying different caliber tributaries of hepatic veins (THV) including central and sub-lobular venules. We investigated the essence and genesis of these atypically located ductuli. 28 Wistar Rat livers were studied histologically and immunohistochemically in norm and after 6, 12 and 24 hours of CBDL. Biliary system of part of the animals was preliminary injected by Indian Ink. After CBDL the number of DPs including the ones accompanying large and small THV was increased. The diameters of DPs found immediately at central and sublobular veins were varying from 5 to 15 mВµ and of DPs located in the adventitia of the large THV are varying from 10 to 30 mВµ. The cell of these DPs were CK19, CK7 and OV6 positive, but Ki-67 negative, what confirms their belonging to cholangiocytes but denies their proliferative genesis. In the sites of crossing of different size portal tracts (PT) and THV with integration of their connective tissue sheaths were revealed some biliary ducts/ductules dislocated from PT towards the THV and situated within their adventitia. The Indian Ink injected via CBD was found in both - portal and perivenous DPs as well as in bile canaliculi, what confirms their inter-continuity. The biliary ductules dislocated from PT toward THV may accompany hepatic venous pathways reversely up to central venules. These finest ductuli having spare function are likely to communicate with bile canaliculi.

New model of veno-venous bypass for management of anhepatic phase in experimental study on dogs.

Blood is shunted from the inferior vena cava and portal vein to the superior vena caval system to prevent congestion in the lower parts of the body during the anhepatic phase (AP) of liver transplantation. It leads to overload in the superior vena caval system retarding cranial outflow due to a nonphysiological blood redistribution. To overcome this problem, we developed a new bypass in dogs: blood is shunted from the inferior (caudal) vena cava and portal vein to the suprahepatic inferior (caudal) vena cava. This model was compared with traditional one with or without a pump. Blood pressure and flow parameters were estimated during 3 hours of AP in four groups of four dogs each. The current study showed that a nontraditional scheme of venous bypass reduced circulatory complications during AP, especially in the cranial vena caval system, although a low rate of congestion remains in the caudal vena cava and portal vein systems. Whereas the same scheme using a pump effectively prevented congestion in all of the systems: cranial, caudal, and portal. We concluded that application of a nontraditional bypass scheme, providing venous blood return into suprahepatic part of caudal vena cava, can be considered to be a method of choice for experimental liver transplantation.

Experimental liver autotransplantation with novel scheme of veno-venous bypass as a model of liver denervation and delymphatization.

The impact of denervation and delymphatization (DD) on liver tissue remains a topic of major interest in liver transplantation, as the organ or its part continues to function well. Various chemical and/or surgical interventions have been developed to achieve in situ liver denervation and delymphatization, but it is evident that DD can be achieved only through "ectomia", ie, complete isolation of the organ from adjacent and connected structures. This Study describes a liver DD model based on a technique of autotransplantation (replantation), maximally preventing ischemia in the transplanted (replanted) graft and dyscirculatory complications in the recipient. Experiments were performed on eight male mongrel dogs. Venous reservoir and roller pumps were used in a forced nontraditional bypass scheme. Autotransplantation was performed by step-by-step dissection of the suprahepatic, infrahepatic, and portal structures, leading to DD, with subsequent recovery of the blood vessel and bile duct. DD was achieved successfully with stable hemodynamic parameters during all surgery periods. All animals survived. This model of liver autotransplantation lead to DD of the organ. It was characterized by hemodynamic stability of the liver as well as of the whole body at every stage of the surgery, proffering liver DD for experimental studies.

Unusual types of smooth muscle tumors of uterine corpus: case reports and literature review.

Classification of a smooth muscle neoplasm as benign or malignant is straightforward. Morphologic and biologic diversity makes smooth muscle neoplasia a diagnostic dilemma for pathologists but fascinating area of study. We report three cases of unusual types of smooth muscle tumors of uterine corpus: 1) highly cellular leiomyoma; 2) cotyledonoid dissecting leiomyoma (CDL) and 3) poorly differentiated leiomyosarcoma. Diagnostic pathology of the uterine smooth muscle tumors hides pitfalls. Some of the tumor type requires ancillary techniques to establish correct diagnosis. In case of CDL only gross and/or histopathologic features can clarify the question. There are number of cases, were the complex methods must be utilized.

Ductular reaction at the early terms of common bile duct ligation in the rats.

Ductular reaction (DR) in bile duct ligated rats generally appears from 2nd day after biliary obstruction (BO). However, we show that increased amount of ductular profiles is evident already in 6 hours after BDL. The study aims to explain the origin of such an early DR in response to BO. Male Lewis rats were subjected to common bile duct ligation (CBDL) for 3, 6, 12 and 24 hours and sham operation. Liver samples were studied histologically, immunohistochemically (Ki67, pan-Cytokeratin /AE1 + AE3/ and OV-6) and by immunoblotting analyses. It appeared that number of ductular profiles increase in time-related manner after BO. These ductular profiles are formed by biliary epitheliocyte-like cells; No mitotic activity was revealed. Part of hepatocytes reveals pan-Cytokeratin positivity on 12 and 24 hours after BO. Total cytokeratins content at 24 hours after CBDL was 37% higher in comparison with control data. The significant increase was observed for the cytokeratins with molecular weights: 61, 56 and 40 KDa. Thus, early DR after BDL is mediated by widening of the existed finest biliary ramifications and is not associated with proliferation activities. This DR is accompanied by differentiation of hepatocytes toward bile duct-like cells.