*5.1.1 Acute liver failure*

Regardless of the etiology of liver damage, apoptosis and hepatocyte necrosis are generated, which allows the release of damage-associated molecular patterns (DAMPs), such as micro-RNA 122, high mobility protein 1 (HMGB1), Keratin 18, which bind to toll-like receptors (TLR4) of Kupffer cells, which induces the release of cytokines.

Activation of the Kupffer cells induces the release of cytokines, which stimulates the recruitment of monocytes and induces an intrahepatic inflammatory phenotype, with sequestration of platelets and amplifying the inflammatory response. The inflammatory process is not limited to the liver, this induces a systemic inflammatory response (SIRS), and a counterregulatory mechanism called compensatory antiinflammatory response syndrome (CARS) is induced, the latter conditions a state of immunomodulation, which explains the high risk of infections, risk of sepsis, multiorgan failure, and worsening of encephalopathy (**Figure 3**) [9].

Neopterin formed by macrophages, monocytes, and activated dendritic cells has been described; it is considered a marker of inflammation in ALF due to

#### **Figure 3.**

*A) Regardless of the etiology of the liver injury, the release of DAMPs is generated, recognized by the TLR4 of Kupffer cells. B) Activated Kupffer cells release cytokines, which stimulate monocyte migration, amplifying the inflammatory response within the liver. C) Inflammation is not limited to this organ and generates SIRS; likewise, a counterregulatory mechanism (CARS) is stimulated, which leads to a state of immunoparalysis and increases the risk of infections. D) Albumin in its oxidized form contributes to the perpetuation of the inflammatory state. E) Damage to the stellate cells of the hepatic sinusoids decreases the release of ADAMTS 13, increases the expression of VWF multimers, favors platelet aggregation that predisposes to the formation of microthrombi, and, together with the increase in monocyte and macrophage trafficking, alters hepatic circulation.*

*Artificial Liver Support Systems DOI: http://dx.doi.org/10.5772/intechopen.109843*

acetaminophen. It is evident that the increase in neopterin and sCD163 correlates with SIRS, greater clinical severity measured by SOFA score, and with the requirement of liver transplantation [10]. The aforementioned supports the increase in mononuclear cell activity and the increase in the inflammatory response in ALF.

Acute liver failure has great potential to develop multi-organ complications (cerebral, respiratory, metabolic, hematological, hemodynamic, infectious, and renal) despite supportive management, many of them do not stabilize and lead to an increase in mortality. In this critical condition, extracorporeal liver support therapies are used until the recovery of liver function, which, in some series, reaches 60% of acute patients and without reaching transplantation [11].

#### *5.1.2 Acute chronic liver failure*

It represents the spectrum of chronic liver disease without cirrhosis or with compensated or decompensated cirrhosis, in which a hepatic or extrahepatic precipitating factor triggers a persistent inflammatory response that induces the development.

TNF alpha and activated stellate cells, allowing nitric oxide secretion, further damage hepatocytes and cause splanchnic vasodilation. The endothelin released from endothelial cells decreases the expression of cluster of differentiation (CD) and human leukocyte anti-DR (HLA), conditions an environment of TL reg inhibition, and lowers LTH 17 activation. This conditions a state of "Ineffective Immunity," dysfunctional cells, decreased phagocytic activity, increased anti-inflammatory cytokines, and release of reactive oxygen species (ROS) [12].

ACLF conditions a SIRS state in the first 7 days from the onset of the symptoms and after 10–14 days, a state of immunosuppression due to anti-inflammatory

#### **Figure 4.**

*A) In chronic liver disease without cirrhosis and in compensated or decompensated cirrhosis, they generate the favorable environment for the arrival of PAMPs in the enterohepatic circulation, mitochondrial stress, apoptosis, and necrosis typical of liver disease, regardless of the etiology, allowing the release of DAMPs. Both molecules bind to TRL4 receptors of Kupffer cells, which are activated and release cytokines with hepatic and systemic impact. B) The intrahepatic inflammatory response and the release of chemokines induce chemotaxis of monocytederived macrophages from the systemic circulation to the liver at sites of injury. C) Albumin in the oxidized form contributes to the perpetuation of the inflammatory state. D) Damage to the stellate cells of the hepatic sinusoids decreases the release of ADAMTS 13 and increases the expression of VWF multimers that favors platelet aggregation and stimulates phagocytosis of these molecules by macrophages, increasing cell size and increasing the number of cells. Cell traffic contributes to lower liver perfusion.*

cytokines (CARS) is generated, increasing the risk of sepsis, septic shock, and multiple organ failure (**Figure 4**) [13].

The severity of ACLF measured by CLIF-SOFA has a direct relationship with mortality. The measures used in the management with crystalloid solutions and human albumin, and the use of vasoactive agents are a necessity to meet the hemodynamic objectives, anti-encephalopathy measures, and anti-cerebral edema. The need for transfusion of blood products and the support of mechanical ventilation and infection control represent the supportive management of these patients. Many of them, despite the optimization of the measures implemented, require extracorporeal liver support therapy, which, as in acute liver failure, has the clear objective of limiting the inflammatory response that perpetuates cell damage, decreasing macrophage activation that conditions the permanent inflammatory response.
