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Liver support system

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Liver support system

A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins (liver dialysis), or providing additional replacement of the metabolic functions of the liver through the inclusion of hepatocytes to the device (bioartificial liver device). A diachysis machine is used for acute care i.e. emergency care, as opposed to a dialysis machine which are typically used over the longer term. These systems are being trialed to help people with acute liver failure (ALF) or acute-on-chronic liver failure.

The primary functions of the liver include removing toxic substances from the blood, manufacturing blood proteins, storing energy in the form of glycogen, and secreting bile. The hepatocytes that perform these tasks can be killed or impaired by disease, resulting in acute liver failure (ALF) which can be seen in person with previously diseased liver or a healthy one.

In hyperacute and acute liver failure, the clinical picture develops rapidly with progressive encephalopathy and multiorgan dysfunction such as hyperdynamic circulation, coagulopathy, acute kidney injury and respiratory insufficiency, severe metabolic alterations, and cerebral edema that can lead to brain death. In these cases the mortality without liver transplantation (LTx) ranges between 40-80%. LTx is the only effective treatment for these patients although it requires a precise indication and timing to achieve good results. Nevertheless, due to the scarcity of organs to carry out liver transplantations, it is estimated that one third of patients with ALF die while waiting to be transplanted.

On the other hand, a patient with a chronic hepatic disease can suffer acute decompensation of liver function following a precipitating event such as variceal bleeding, sepsis and excessive alcohol intake among others that can lead to a condition referred to as acute-on-chronic liver failure (ACLF).

Both types of hepatic insufficiency, ALF and ACLF, can potentially be reversible and liver functionality can return to a level similar to that prior to the insult or precipitating event.

LTx has shown an improvement in the prognosis and survival with severe cases of ALF. Nevertheless, cost and donor scarcity have prompted researchers to look for new supportive treatments that can act as "bridge" to the transplant procedure. By stabilizing the patient's clinical state, or by creating the right conditions that could allow the recovery of native liver functions, both detoxification and synthesis can improve, after an episode of ALF or ACLF.

Three different types of supportive therapies have been developed: bio-artificial, artificial and hybrid liver support systems (Table 2).

Bioartificial liver devices are experimental extracorporeal devices that use living cell lines to provide detoxification and synthesis support to the failing liver. Bio-artificial liver (BAL) Hepatassist 2000 uses porcine hepatocytes whereas ELAD system employs hepatocytes derived from human hepatoblastoma C3A cell lines. Both techniques can produce, in fulminant hepatic failure (FHF), an improvement of hepatic encephalopathy grade and biochemical parameters. Potential side effects that have been documented include immunological issues (porcine endogenous retrovirus transmission), infectious complications, and tumor transmigration.

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