**3.1 Definition and etiology**

324 Liver Transplantation – Basic Issues

For invasive procedures, the INR can be temporarily corrected with recombinant Factor VIIa (Novo-7) at a dose of 40 μg/kg. Such therapy reduces the INR to below 1.5 within 30 minutes of administration, and allows approximately 90-120 minutes for the performance of invasive procedures. Vitamin K may reduce the INR if malnutrition is contributing to

Despite the coagulopathic state observed in ALF, anticoagulant proteins such as protein C and S are reduced, and patients are at risk of venous thrombotic complications. Therefore, venous thromboembolism prophylaxis with subcutaneous heparin or lowmolecular weight heparin formulations should be considered despite the presence of

*Acute kidney injury* in ALF usually results from impaired renal perfusion or direct renal insults. Hepatorenal syndrome, which occurs in the setting of portal hypertension and chronic liver disease, does not occur in ALF. Management of acute kidney injury includes avoidance of additional nephrotoxic insults, as well as supportive measures. In order to avoid increases in intracranial pressure and significant fluid shifts, if renal replacement therapy is necessary, continuous renal replacement therapy (CRRT) is preferred over

*Infections* occur in ALF from functional immunosuppression. Patients are susceptible to overwhelming bacterial and fungal sepsis, although clinical signs of infection may be absent. Empiric antibacterial and antifungal therapy should be considered in the setting of advanced hepatic encephalopathy, shock, or for patients listed for transplantation. Associated sepsis and septic shock are managed with broad-spectrum antibiotics, vasoactive

*Respiratory disturbances,* including acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), are frequent manifestations of ALF. In the setting of ALI and ARDS, lungprotective strategies with low tidal volume (6 cc/kg ideal body weight) ventilator settings and mild permissive hypercapnea are recommended. Hypoxemic respiratory failure portends a poor prognosis and is treated supportively. Severe hypercapnea, bronchoscopy, and patient-ventilator asynchrony can exacerbate intracranial hypertension; titration of the set respiratory rate to compensate for hypercapnea, as well as adequate sedation and analgesia to improve synchrony, are imperative. Neuromuscular-blocking paralytic agents

may be necessary if patient-ventilator asynchrony persists despite adequate sedation.

*Metabolic derangements* result both from impaired hepatic metabolic function and resulting multi-organ failure. Consequences include lactic acidosis and disturbances in arterial pH,

coagulopathy.

coagulopathy.

**2.4.3 Renal impairment** 

conventional hemodialysis.

agent support and high-dose corticosteroids.

**2.4.5 Pulmonary complications** 

**2.4.6 Metabolic derangements** 

**2.4.4 Infections** 

Acute on chronic liver failure (ACLF), or decompensated cirrhosis, occurs when cirrhosis of any etiology is complicated by the development and sequelae of portal hypertension. Longstanding portal hypertension results from intrahepatic resistance to portal flow, and increased portal inflow from inappropriate splanchnic vasodilation. These pathophysiologic changes result in splanchnic and systemic derangements, including the development of gastroesophageal varices, hepatic encephalopathy, pulmonary decompensation, and hepatorenal syndrome. Given the importance of splanchnic vasodilation in the pathophysiology of ACLF, pharmacologic therapy with splanchnic vasoconstrictors plays a central role in the therapy of ACLF.

Etiologies of cirrhosis are numerous, and include alcoholic steatosis, chronic viral hepatitis, metabolic diseases (e.g. non-alcoholic fatty liver disease, hemachromatosis, wilson disease), autoimmune hepatitis and cholestatic liver diseases ( e.g. primary biliary cirrhosis and primary sclerosing cholangitis).
