scholarly journals Different Timing of Cholangiocyte and Hepatocyte Damage in Liver Preservation: Time to Implement Donor Interventions and New Preservation Techniques to Prevent Ischemic-type Biliary Lesions

2021 ◽  
Vol 105 (7) ◽  
pp. e77-e78
Author(s):  
Damiano Patrono ◽  
Marinella Zanierato ◽  
Alfonso Wolfango Avolio ◽  
Renato Romagnoli
2009 ◽  
Vol 47 (01) ◽  
Author(s):  
L Ciuclan ◽  
C Stump ◽  
I Ilkavets ◽  
H Weng ◽  
MV Singer ◽  
...  

2009 ◽  
Vol 47 (09) ◽  
Author(s):  
LI Ciuclan ◽  
S Ehnert ◽  
I Ilkavets ◽  
H Weng ◽  
H Gaitantzi ◽  
...  

2018 ◽  
Vol 17 (2) ◽  
pp. 117-121
Author(s):  
Sun Maw-Sheng ◽  
Liang Chun-Ya ◽  
Hsieh Po-Chun ◽  
Kuo Chan-Yen

Apoptosis of hepatocyte, under ischemia/reperfusion (IR) conditions, has been identified as an essential process in the progression of liver transplantation. Under these conditions, mitochondria can become a threat to the cell because of their capacity to generate reactive oxygen species (ROS). Additionally, ROS overproduction may induce inflammation. As ROS accumulation appears to cause hepatocyte damage or death, there has been considerable interest in identifying the candidate natural products involved and in developing strategies to reduce oxidative stress. In this study, we use Danshensu as a candidate product to speculate whether has the protective effect on apoptotic hepatocyte upon IR. To speculate the apoptotic phenomena was reversed by Danshensu, we detected the p53, cleaved-caspase 3 expression by western blotting, as well as caspase-3 activity. Additionally, we analyzed the ROS levels by 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining. We also detected the cell viability by WST-1. Results showed that Danshensu alleviated hypoxia-caused cell apoptosis via ROS overproduction. We suggested that Danshensu is a good strategy for treating hepatocyte damage upon IR.


2020 ◽  
Vol 20 (9) ◽  
pp. 720-727
Author(s):  
Jianguo Qiu ◽  
Wei Tang ◽  
Chengyou Du

Background: Immune checkpoint modulators, such as the programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor, cytotoxic T-Lymphocyte-associated antigen 4 (CTLA-4) inhibitor have been investigated with encouraging results for hepatocellular carcinoma (HCC). However, the safety of this strategy in patients with previous liver transplantation (LT) is not well studied. Objective: To explore the safety and feasibility of immune checkpoints inhibitors in recurrent and metastatic HCC patients on a background of LT. Methods: A case of recurrent, refractory, metastatic HCC after LT, where PD-1 inhibitor was initiated, was described and related literature was reviewed. Results: There was complete remission in lung metastases and the partial radiological response of metastatic retroperitoneal lymph node to the drug with no liver graft rejection after 13 cycles of PD- 1 inhibitor injection. PD-1inhibitor, at least in this patient, was verified to play an important role in controlling tumor progression and prolonging patient survival. Conclusions: This novel drug might be a useful method to allow doctors to guarantee a better chance for long-term survival in recurrent, metastatic HCC patients with the previous LT. However, it should be used with caution in allograft recipients due to the risk of acute graft rejection, further larger, prospective studies are needed to determine optimal immunomodulatory therapy to achieve optimal anti-tumor efficacy with transplant liver preservation.


2021 ◽  
pp. 56-62
Author(s):  
N. R. Matkovska ◽  
N. H. Virstiuk ◽  
I. O. Kostitska

Abstract. In Ukraine, among the causes of death because of digestive tract diseases, alcoholic liver disease (ALD) has the second place. Due to the significant prevalence of obesity and the growing incidence of ALD, methods are being sought to prevent the progression of the pathological process in the liver, the occurrence of complications and to improve the quality of life of such patients. The aim of the study: to examine the effect of complex treatment with ademethionine, arginine glutamate and rosuvastatin on changes in lipid and carbohydrate metabolism in patients with alcoholic liver cirrhosis (ALC) in combination with obesity. Methods. The study included 156 patients diagnosed with ALC in combination with obesity, including 18 women and 138 men aged (45.3±8.9) years and a median duration of disease (5.1±2.8) years. Patients were divided into subgroups depending on the stage of Child-Pugh decompensation and depending on the applied treatment. Results. At the stage of decompensation, lipid metabolism and leptin levels were low, which indicates the depletion of body fat depots as the disease progresses. It may be due to the progression of the liver dysfunction, as it is actively involved in regulating the formation, destruction and accumulation of fats. Changes in carbohydrate metabolism in patients with ALC in combination with obesity were characterized by a significant increase in IRI, HOMA-IR index and a decrease in the QUICKI index, indicating the presence of insulin resistance (p<0.05). In determining the adipocytokine values, it was found that in decompensated liver function, the leptin rates decreased and the levels of adiponectin increased. Higher leptin content in the stage of compensation and subcompensation is also associated with increased secretion of adipose tissue. At the stage of decompensation, fat depots are depleted, so leptin levels are reduced. This decrease is directly related to the Child-Pugh and MELD scores. Adiponectin levels were decreased in the stage of compensation and increased with the progression of the disease and correlated with disease severity and the MELD score. It is thought that an increased adiponectin level indicates the level of anti-inflammatory reaction in response to hepatocyte damage. Significant deterioration in carbohydrate metabolism, adiponectin and leptin in patients receiving basic treatment was accompanied by deterioration of their condition and increased the risk of 3-month mortality. After the course of treatment in patients of group receiving ademethionine, arginine, glutamate and rosuvastatin at the stage of compensation and subcompensation, the rates of lipid, carbohydrate metabolism, adiponectin and leptin significantly improved and differed from those in patients receiving basic treatment and combination of basic treatment, ademethionine and arginine glutamate (p<0.05). At the stage of decompensation in the scheme with the inclusion of rosuvastatin it was possible to normalize the levels of HDL cholesterol, VLDL cholesterol, atherogenic coefficient and leptin, reduce the levels of adiponectin, IRI, HOMA-IR, HbA1c and increase the QUICKI index, which was accompanied by a decrease in Child-Pugh severity score and 3 month mortality MELD score. Conclusions. In patients with ALC in combination with obesity, the inclusion in the treatment of ademethionine, arginine glutamate and rosuvastatin helps to improve the course of the disease according to the lipid and carbohydrate metabolism, Child-Pugh and MELD scores.


Author(s):  
Bote G. Bruinsma ◽  
James H. Avruch ◽  
Pepijn D. Weeder ◽  
Gautham V. Sridharan ◽  
Basak E. Uygun ◽  
...  

2015 ◽  
Vol 93 (8) ◽  
pp. 625-631 ◽  
Author(s):  
Yan Hu ◽  
Ning Zhang ◽  
Qing Fan ◽  
Musen Lin ◽  
Ce Zhang ◽  
...  

Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5–10 μmol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.


2013 ◽  
Vol 4 (5) ◽  
pp. 763 ◽  
Author(s):  
Yuan Yuan ◽  
Si-Jia Wu ◽  
Xin Liu ◽  
Lu-Lu Zhang

1995 ◽  
Vol 268 (6) ◽  
pp. G997-G1003 ◽  
Author(s):  
T. Ohuchi ◽  
K. Tada ◽  
K. Akamatsu

Injury to hepatocytes most likely occurs via disturbances in the microcirculation. The role of vasoconstriction due to the effect of endogenous endothelin-1 (ET-1) in the development of galactosamine (GalN)- and lipopolysaccharide (LPS)-induced liver injury was investigated. Using the multiple indicator dilution technique, we measured the volume of the hepatic sinusoids and the apparent Disse space as indicators of overall hepatic microcirculation. Serum purine nucleoside phosphorylase activity as a marker of damage to nonparenchymal cells increased and the volume of the sinusoids and the Disse space decreased prior to hepatocyte damage in rats treated intraperitoneally with GalN and LPS. Moreover, the amount of ET-1 release was elevated. When livers from untreated rats were perfused with ET-1 in a recirculating system, hepatocyte damage was observed similar to experiments with GalN and LPS. A monoclonal anti-endothelin antibody, AwETN40, diminished the extent of liver injury caused by GalN and LPS in isolated perfused rat liver. The present study suggests that vasoconstriction is an early event in GalN- and LPS-induced liver injury and that the development of hepatocyte damage is mediated via microcirculatory disturbances due to endogenous ET-1.


2009 ◽  
Vol 57 (15) ◽  
pp. 6584-6589 ◽  
Author(s):  
Irena Palíková ◽  
Kateřina Valentová ◽  
Ivana Oborná ◽  
Jitka Ulrichová

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