Section 4: Subspecialty Management
Chapter 55: Organ Transplantation

Pathophysiology and Management of End-Stage Liver Disease

Considering the numerous synthetic and metabolic functions of the liver (Ch. 17), the manifestations of end-stage liver disease extend to virtually every other organ system. The central nervous system may be affected by encephalopathy ranging from mild confusion to deep coma. This may be exacerbated by electrolyte abnormalities, such as hyponatremia, and worsened by GI bleeding. In fulminant hepatic failure, encephalopathy must be distinguished from cerebral edema, which may require CT scanning. Circulation is usually hyperdynamic with reduced systemic vascular resistance and increased cardiac output, and low–normal blood pressure, despite reduced plasma volume.

Pulmonary gas exchange may be adversely affected by atelectasis from abdominal distention and pleural effusion. The hepatopulmonary syndrome is characterized by intrapulmonary shunting from arteriovenous communications, which is a generalized feature of chronic liver failure. Hypoxemia may be significant, although routine causes of gas-exchange problems are more common.

Renal dysfunction is common and results from diuretic use, intravascular volume depletion, and the hepatorenal syndrome. Azotemia from the hepatorenal syndrome, which is reversible with transplantation, must be distinguished from renal dysfunction resulting from profound hypovolemia, common with aggressive diuretic use and hemorrhage.

Endocrine manifestations include glucose intolerance, although hepatic glycogen depletion may lead to chronic hypoglycemia; coagulopathy, resulting from diminished clotting factor production (particularly I [fibrinogen], II [prothrombin], V, VII, IX, and X); thrombocytopenia from hypersplenism and from low production owing to a lack of thrombopoietin; and reduced hepatic clearance of fibrinolysins and tissue plasminogen activators.

When end-stage liver disease destroys the normal hepatic architecture, portal hypertension follows, and engorged venous collateral vessels develop in the abdominal and GI tract walls, mesentery, and retroperitoneum. Hemorrhage is common from esophageal varices, and arteriovenous communications contribute to the pathologically decreased systemic vascular resistance and intrapulmonary shunting. 115  The latter leads to intractable hypoxemia, exacerbated by pleural effusions and atelectasis. Ascites develops as a result of chronic venous hypertension, diminished albumin synthesis, and sodium and water retention from unmetabolized aldosterone and antidiuretic hormone. Treatment usually consists of diuretics, which may exacerbate electrolyte and acid-base derangements and intravascular volume depletion.

PA hypotension occurs in about 2 percent of patients who present for liver transplantation. 116  Moreover, the hepatopulmonary syndrome, consisting of hypoxemia, pulmonary vasodilation, and hepatic dysfunction, occurs in approximately 30 percent of potential transplant recipients. 116  Currently, outcome studies are being conducted to better define outcome (survival) and costs of performing liver transplantation in patients with these syndromes. 116