severe liver disease. Intrinsic pulmonary dysfunction in patients with severe liver disease, such as emphysema or asthma has the same incidence as in patients without liver disease. The severity of these irreversible diseases should be considered when accepting a patient for transplantation. However, some lung dysfunction is the direct result of liver disease. Restrictive pulmonary disease can be the result of tense ascites or pleural effusion, which is especially common on the right side.

Hepatopulmonary syndrome is a condition that is unique to severe liver disease: it is the result of abnormally dilated precapillaries and capillaries in the pulmonary circulation, leading to significant ventilation/perfusion mismatch and hypoxia. Dilated capillaries are more common in the bases of the lungs, leading to orthodeoxia (lower arterial pO2 in the upright position). Oxygen administration improves oxygenation, which should not occur in situations with right-to-left shunting. However, injection of agitated saline (echogenic contrast) during echocardiography shows the contrast in the left atrium and ventricle about 3-4 cardiac cycles after their presence in the right atrium or ventricle, suggesting the presence of an intrapulmonary right-to-left shunt. This combination is unique to hepatopulmonary syndrome. Thus, the condition is confirmed by contrast-enhanced echocardiography, and pulmonary angiography or radionuclide scanning is rarely necessary to confirm the diagnosis. The presence of the hepatopulmonary syndrome is not a contraindication to liver transplantation, because the syndrome is reversible after successful transplantation, although many have a prolonged recovery in the intensive care unit.

Central Nervous System

Cerebral function can be affected because of an excess of metabolites that are normally metabolized by the liver or because of abnormal metabolites. Hepatic encephalopathy, common in acute fulminant failure, has been attributed to abnormal ammonia metabolites. However, other factors contribute to hepatic encephalopathy: cerebral edema, changes in neurotransmitter concentrations and blood-brain barrier function, decreased cerebral metabolic rate, uncoupling of cerebral blood flow, and increased intracranial pressure. By itself, encephalopathy is not a contraindication to liver transplantation, but if severe it may require tracheal intubation for airway protection. Seizures and subarachnoidal bleeding also can affect consciousness. Evaluation includes the use of computed tomography scans of the head, electroencephalography, transcranial Doppler blood flow determination, and epidural intracranial pressure determination.

Renal System

Renal dysfunction may be the result of hypovolemia, acute tubular necrosis, terminal renal disease, or hepatorenal syndrome. The hepatorenal syndrome is caused by abnormal distribution of renal blood flow, due to hormonal imbalances, resulting in low urine output, a low urinary sodium concentration (< 5 mmol/L) and a high urine/plasma creatinine ratio. The hepatorenal syndrome is reversible after successful transplantation. Patients with non-reversible renal failure should be considered for combined liver-kidney transplantation.

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