Treatment of liver failure in rats with end-stage cirrhosis by transplantation of immortalized hepatocytes

Hepatology ◽  
2002 ◽  
Vol 36 (2) ◽  
pp. 386-394 ◽  
Author(s):  
Jin Cai ◽  
Masahiro Ito ◽  
Hideo Nagata ◽  
Karen A. Westerman ◽  
Daryl LaFleur ◽  
...  
2021 ◽  
pp. 1-4
Author(s):  
Fatima Farid Mir ◽  
Anjan Madasu ◽  
Hani Humad ◽  
Asim Noor Rana

Fifteen-month-old male child, known to have a congenital bone marrow failure syndrome, presented in a state of shock with severe lactic acidosis following a brief episode of vomiting. Hospital stay was complicated by recurrent bouts of metabolic acidosis and progressive hepatic failure. Blood mitochondrial DNA sequencing revealed a large heteroplasmic 4,977 bp mitochondrial deletion (approximately 40% of all mitochondrial copies) suggestive of Pearson marrow-pancreas syndrome. By virtue of natural disease course, within a month of admission child succumbed to end-stage liver failure with multi-organ failure and died.


2021 ◽  
Vol 11 ◽  
Author(s):  
Tongdi Fang ◽  
Guo Long ◽  
Dong Wang ◽  
Xudong Liu ◽  
Liang Xiao ◽  
...  

ObjectiveTo establish a nomogram based on inflammatory indices and ICG-R15 for predicting post-hepatectomy liver failure (PHLF) among patients with resectable hepatocellular carcinoma (HCC).MethodsA retrospective cohort of 407 patients with HCC hospitalized at Xiangya Hospital of Central South University between January 2015 and December 2020, and 81 patients with HCC hospitalized at the Second Xiangya Hospital of Central South University between January 2019 and January 2020 were included in the study. Totally 488 HCC patients were divided into the training cohort (n=378) and the validation cohort (n=110) by random sampling. Univariate and multivariate analysis was performed to identify the independent risk factors. Through combining these independent risk factors, a nomogram was established for the prediction of PHLF. The accuracy of the nomogram was evaluated and compared with traditional models, like CP score (Child-Pugh), MELD score (Model of End-Stage Liver Disease), and ALBI score (albumin-bilirubin) by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).ResultsCirrhosis (OR=2.203, 95%CI:1.070-3.824, P=0.030), prothrombin time (PT) (OR=1.886, 95%CI: 1.107-3.211, P=0.020), tumor size (OR=1.107, 95%CI: 1.022-1.200, P=0.013), ICG-R15% (OR=1.141, 95%CI: 1.070-1.216, P<0.001), blood loss (OR=2.415, 95%CI: 1.306-4.468, P=0.005) and AST-to-platelet ratio index (APRI) (OR=4.652, 95%CI: 1.432-15.112, P=0.011) were independent risk factors of PHLF. Nomogram was built with well-fitted calibration curves on the of these 6 factors. Comparing with CP score (C-index=0.582, 95%CI, 0.523-0.640), ALBI score (C-index=0.670, 95%CI, 0.615-0.725) and MELD score (C-ibasedndex=0.661, 95%CI, 0.606-0.716), the nomogram showed a better predictive value, with a C-index of 0.845 (95%CI, 0.806-0.884). The results were consistent in the validation cohort. DCA confirmed the conclusion as well.ConclusionA novel nomogram was established to predict PHLF in HCC patients. The nomogram showed a strong predictive efficiency and would be a convenient tool for us to facilitate clinical decisions.


2019 ◽  
Vol 28 (9-10) ◽  
pp. 1116-1122 ◽  
Author(s):  
Wei Zhou ◽  
Erek D. Nelson ◽  
Anan A. Abu Rmilah ◽  
Bruce P. Amiot ◽  
Scott L. Nyberg

Owing to the increasing worldwide burden of liver diseases, the crucial need for safe and effective interventions for treating end-stage liver failure has been a very productive line of inquiry in the discipline of hepatology for many years. Liver transplantation is recognized as the most effective treatment for end-stage liver disease; however, the shortage of donor organs, high medical costs, and lifelong use of immunosuppressive agents represent major drawbacks and demand exploration for alternative treatments. Stem cell-based therapies have been widely studied in the field of liver diseases and are considered to be among the most promising therapies. Herein, we review recent advances in the application of stem cell-related therapies in liver disease with the aim of providing readers with relevant knowledge in this field and inspiration to spur further inquiry.


2018 ◽  
Vol 315 (3) ◽  
pp. G374-G384 ◽  
Author(s):  
Zhen Tian ◽  
Yi Chen ◽  
Naijuan Yao ◽  
Chunhua Hu ◽  
Yuchao Wu ◽  
...  

Liver sinusoids serve as the first line of defense against extrahepatic stimuli from the intestinal tract. Hepatic stellate cells (HSCs) are pericytes residing in the perisinusoidal space that integrate cytokine-mediated inflammatory responses in the sinusoids and relay these signals to the liver parenchyma. Oxidative stress has been shown to promote inflammation during acute liver failure (ALF). Whether and how oxidative stress is involved in HSC inflammation during ALF remains unclear. Level of systemic oxidative stress is reflected by superoxide dismutase (SOD). Thus, ALF patients were recruited to investigate the correlation between plasma SOD levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from ALF patients who had undergone liver transplantation. SOD2 expression and HSCs activation were investigated by immunohistochemistry. Inflammation, mitophagy, and apoptosis were investigated by immunoblot analysis and flow cytometry in HSCs treated with lipopolysaccharide (LPS) and reactive oxygen species (ROS) donors. The plasma SOD level was significantly increased in patients with ALF compared with those with cirrhosis (444.4 ± 23.58 vs. 170.07 ± 3.52 U/ml, P < 0.01) and was positively correlated with the Model for End-Stage Liver Disease-Na score ( R2 = 0.4720, P < 0.01). In vivo observations revealed that SOD2 immunostaining was increased in ALF patients and mice models, and in vitro experiments demonstrated that LPS/ROS promoted inflammation via inhibiting mitophagy. Moreover, the regulation of inflammation was apoptosis independent in HSCs. LPS-induced increases in oxidative stress promote inflammation through inhibiting mitophagy in HSCs during the process of ALF, providing a novel strategy for the treatment of patients with ALF. NEW & NOTEWORTHY Here we demonstrate that the serum superoxide dismutase (SOD) level is significantly increased in patients with acute liver failure (ALF), and, correlated with the Model for End-Stage Liver Disease-Na score, SOD level dropped in the remission stage of ALF. We identify that, in liver tissue from ALF patients and mice models, manganese-dependent SOD was overexpressed, and show lipopolysaccharide/H2O2 inhibits mitophagy via reactive oxygen species in hepatic stellate cells (HSCs). We show that inhibited mitophagy promotes inflammation in HSCs, whereas mitophagy inducer rescues HSCs from lipopolysaccharide-induced inflammation.


Author(s):  
Ximena Soler ◽  
Lori A Aronson ◽  
Gillian Derrick

Liver transplantation is an established therapy in pediatric end-stage liver failure. Blood loss during orthotopic liver transplantation (OLT) is highly variable. Massive hemorrhage and transfusion of blood products, with its related consequences, is a well-known complication of this operation.


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