Activated and nonactivated MSCs increase survival in humanized mice after acute liver injury through alcohol binging.

The ability of the liver to regenerate after injury makes it an ideal organ to study for potential therapeutic interventions. Mesenchymal stem cells (MSCs) possess self-renewal and differentiation properties, as well as anti-inflammatory properties that make them an ideal candidate for therapy of acute liver injury. The primary aim of this study is to evaluate the potential for reversal of hepatic injury using human umbilical cord-derived MSCs. Secondary aims include comparison of various methods of administration as well as comparison of activated versus nonactivated human umbilical cord stem cells. To induce liver injury, humanized mice were fed high-cholesterol high-fat liquid diet with alcohol binge drinking. Mice were then treated with either umbilical cord MSCs, activated umbilical cord MSCs, or a placebo and followed for survival. Blood samples were obtained at the end of the binge drinking and at the time of death to measure alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Histology of all mouse livers was reported at time of death. Activated MSCs that were injected intravenously, intraperitoneally, or both routes had superior survival compared with nonactivated MSCs and with placebo-treated mice. AST and ALT levels were elevated in all mice before treatment and improved in the mice treated with stem cells. Conclusion: Activated stem cells resulted in marked improvement in survival and in recovery of hepatic chemistries. Activated umbilical cord MSCs should be considered an important area of investigation in acute liver injury.

Pancreatic complications following orthotopic liver transplantation.

During fiscal year 1986, 40 out of 196 patients (21%) developed hyperamylasemia following orthotopic liver transplantation. The placement of a retropancreatic aortohepatic arterial interposition graft was associated with hyperamylasemia (p < 0.025). Eight patients (20%) developed clinically significant acute pancreatitis and its sequelae; abscesses and pseudocysts each in 2. Pancreatitis was attributable to the retropancreatic arterial graft in 4, viral infection in 2 and obstruction of the pancreatic duct in 1 patient. All 4 patients with arterial graft-related pancreatitis exhibited poor graft function immediately postoperatively, of whom 2 required retransplantation - both of which failed to function. Five patients died (63%); 2 from primary graft non-function, 2 due to sepsis and 1 from systemic cytomegalovirus infection. We conclude that acute pancreatitis after liver transplantation is a life-threatening complication which is often associated with graft non-function.

Causas de muerte posterior al transplante hepático en niños tratados con ciclosporina y esteroides / Causes of death after liver transplantation in children treated with ciclosporine and steroides

Se analiza una serie de 227 niños sometidos a trasplante ortotópico de hígado entre marzo de 1980 y febrero de 1986. Fallecieron durante el período en estudio 70 pacientes (31,7%); 9 fueron excluidos del análisis (4 murieron dentro de las primeras 24 hs. postoperatorias y 5 cuyo deceso ocurrió fuera de nuestra institución). La insuficiencia hepática por trombosis arterial, falla primaria del funcionamiento del hígado o rechazo inmunológico del mismo, motivó 25 muertes de los 61 restantes, 21 murieron por sepsis generalizada, mientras que 7 fallecieron por sangrado incontrolable y 8 fueron atribuidas a un variado grupo de causas. Los índices de mortalidad de los pacientes sometidos a 1, 2 y 3 trasplante fueron del 20, 38 y 50% respectivamente. El 85,2% de las muertes se produjo durante el 1er. semestre posterior al trasplante hepático inicial. La insuficiencia hepática fue la principal causa de muertes tempranas y las tardías se debieron en su mayoría a sepsis. El estudio de las causas de muerte posterior al trasplante hepático, revela que ciertos avances en determinadas áreas conducirán a mejores resultados.

Hiperprolactinemia y regeneración hepática / Hyperprolactinemia and liver regeneration

Se investigó en ratas el efecto regenerativo hepático de la hiperprolactinemia. En el grupo experimental se implantaron isoinjertos de hipófisis por debajo de la cápsula renal, igual procedimiento fue simulado en el grupo control. Dos semanas más tarde, ambos grupos fueron sometidos a una hepatectomía del 70 %. Los animales se sacrificaron a los 6, 24 y 48 hs. después de la hepatectomía parcial y los hígados remanentes se utilizaron para determinar los niveles ornitin-decarboxilasa y timidin-quinasa, como también la relación peso hepático/peso corporal. Los resultados obtenidos demostraron que la hiperprolactinemia no posee efectos regenerativos en hígados de ratas sometidas a resección.

Hepatic artery thrombosis following pediatric liver transplantation: Assessment of blood flow measurement in allografts.

The purpose of this study was to define parameters which could be predictive of hepatic artery thrombosis, which continues to be a major complicating factor in pediatric liver transplantation. The hepatic blood flow of 14 pediatric liver patients (15 grafts) who weighed less than 15 kg was measured electromagnetically during orthotopic liver transplantation. The results of blood flow determination and the clinical data in 7 patients (8 grafts) who developed hepatic artery thrombosis were compared with those of 7 control patients. All patients with a hepatic arterial flow of less than 60 ml/min developed hepatic artery thrombosis (4/8 vs. 0/7; p < 0.05), and the patients with hepatic artery thrombosis exhibited higher total hepatic and portal vein flow per 100 gram of liver tissue (262 vs. 136 ml/min; p < 0.001 and 222 vs. 80 ml/min; p < 0.025, respectively) as well as longer cold preservation time (384 vs. 326 min; p < 0.025). The results of our study suggest that hepatic arterial flows of less than 60 ml/min are critical for the development of hepatic artery thrombosis, and that portal venous overflow and increased preservation times may contribute to the development of hepatic artery thrombosis.

Causes of death after liver transplantation in children treated with cyclosporine and steroids.

Two-hundred-and-twenty-seven children underwent orthotopic liver transplantation between March 1980 and March 1986. Seventy (31 %) patients died during the study period. Four patients who died within 24 hours of the initial liver transplant and 5 patients who died outside of our institution were excluded from the analysis. Liver failure, related to either thrombosis of the hepatic artery, primary non-function of the graft or rejection accounted for 25 of the remaining 61 deaths. In 21 patients death was related to overwhelming sepsis while 7 patients died from excessive bleeding. Eight of the deaths were due to a miscellaneous group of causes. Twenty percent of the 150 patients who received a single liver transplant died compared to a death rate of 50% in patients who underwent three transplants. Eighty-five percent of the deaths occurred within 6 months after the initial liver transplant. Liver failure was the cause in the majority of the early deaths whereas the later deaths were more likely to be due to sepsis. This detailed analysis of the causes of death after pediatric liver transplantation in a large group of patients has revealed that advances in certain areas could lead to even better results.

Evidence for hyperacute rejection of human liver grafts: The case of the canary kidneys.

Sequential liver and kidney transplantation from the same donor was performed in 2 patients. The kidney in Patient 1, which was transplanted after the liver, was hyperacutely rejected and removed 6 hours later. The first liver as well as another liver transplanted 3 days later developed widespread hemorrhagic necrosis. Although the cytotoxic crossmatch of preoperative recipient serum with both donors was negative, patchy widespread IgM and C(1q) deposits were found in all 3 organs. In Patient 2, who had a strongly positive cytotoxic crossmatch with his donor, the liver suffered a massive but reversible injury, while the kidney never functioned. Both patients developed a coagulopathy a few minutes after liver revascularization. The kidneys in these cases had served like the canaries which miners once used to detect a hostile environment and their presence made more understandable how an indolent version of hyperacute rejection of the liver can take place.