Liver Progenitor Cells in Massive Hepatic Necrosis—How Can a Patient Survive Acute Liver Failure?

Massive hepatic necrosis is the most severe lesion in acute liver failure, yet a portion of patients manage to survive and recover from this high-risk and harsh disease syndrome. The mechanisms underlying recovery remain largely unknown to date. Recent research progress highlights a key role of liver progenitor cells, the smallest biliary cells, in the maintenance of liver homeostasis and thus survival. These stem-like cells rapidly proliferate and take over crucial hepatocyte functions in a severely damaged liver. Hence, the new findings not only add to our understanding of the huge regenerative capability of the liver, but also provide potential new targets for the pharmacological management of acute liver failure in clinical practice.

Differences of liver CT perfusion of blunt trauma treated with therapeutic embolization and observation management

Massive hepatic necrosis after therapeutic embolization has been reported. We employed a 320-detector CT scanner to compare liver perfusion differences between blunt liver trauma patients treated with embolization and observation. This prospective study with informed consent was approved by institution review board. From January 2013 to December 2016, we enrolled 16 major liver trauma patients (6 women, 10 men; mean age 34.9 ± 12.8 years) who fulfilled inclusion criteria. Liver CT perfusion parameters were calculated by a two-input maximum slope model. Of 16 patients, 9 received embolization and 7 received observation. Among 9 patients of embolization group, their arterial perfusion (78.1 ± 69.3 versus 163.1 ± 134.3 mL/min/100 mL, p = 0.011) and portal venous perfusion (74.4 ± 53.0 versus 160.9 ± 140.8 mL/min/100 mL, p = 0.008) were significantly lower at traumatic parenchyma than at non-traumatic parenchyma. Among 7 patients of observation group, only portal venous perfusion was significantly lower at traumatic parenchyma than non-traumatic parenchyma (132.1 ± 127.1 vs. 231.1 ± 174.4 mL/min/100 mL, p = 0.018). The perfusion index between groups did not differ. None had massive hepatic necrosis. They were not different in age, injury severity score and injury grades. Therefore, reduction of both arterial and portal venous perfusion can occur when therapeutic embolization was performed in preexisting major liver trauma, but hepatic perfusion index may not be compromised.

Hepatotoxicity of Two Progoitrin-Derived Nitriles in New Zealand White Rabbits

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic, causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

Hepatotoxicity of Two Progoitrin-Derived Nitriles in New Zealand White Rabbits

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede (Brassica spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

Structural Organization of the Liver in the Presence of Pig Hepatosis

The structural organization of the liver in hepatosis and its clinical and morphological manifestation in pigs were studied. In animals with reduced vitality, the liver underwent deep microscopic and ultrastructural changes. At hepatic steatosis, the liver had a cellular structure, many lipid vacuoles and the damage of mitochondrial membranes of a granular endoplasmic reticulum appeared in hepatocytes. Proteinosis was characterized by impaired of lobular structure, with protein swelling of the cytoplasm of hepatocytes and Disse’s spaces expansion, significant decrease of glycogen; mitochondrial swelling and the appearance of lysosomal vacuoles in the hepatocyte. In massive hepatic necrosis, hepatocyte dystrophy was noted, significant histochemical decrease of glycogen, lysis of the hepatocyte granule endoplasmic reticulum, pycnosis of the hepatocyte nucleus, and in general necrobiotic changes in the liver cells.

Fatal hepatic sarcocystosis in a free-ranging grizzly bear cub associated with Sarcocystis canis–like infection

We describe herein fatal hepatic sarcocystosis in a free-ranging grizzly bear ( Ursus arctos horribilis) cub with apicomplexan infection of the liver and brain, both demonstrating 100% homology for Sarcocystis canis and S. arctosi. Fatal hepatic sarcocystosis in dogs has been etiologically associated with intrahepatic schizonts of S. canis. In black and polar bears, a S. canis–like organism produces schizonts in the liver and massive hepatic necrosis. Although intramuscular sarcocysts, taxa S. arctosi and S. ursusi, have been described in healthy brown and black bears, respectively, they have not been detected in bears with hepatic sarcocystosis, to our knowledge, and it is currently unknown whether bears represent an aberrant or intermediate host.