Definition

Cirrhosis is a progressive and ultimately fatal syndrome of hepatic failure.

Pathophysiology

Chronic alcoholism is the most common cause of cirrhosis (Laënnec’s cirrhosis) in the United States. Cirrhosis is also caused by biliary obstruction, chronic hepatitis, right-sided heart failure, α₁-antitrypsin deficiency, Wilson disease, and hemochromatosis. Anatomic alterations secondary to hepatocyte necrosis are the primary cause of the deterioration that occurs in liver function.

Over time, the liver parenchyma is replaced by fibrous and nodular tissue, which distorts, compresses, and obstructs normal portal venous blood flow. Portal hypertension develops and impairs the ability of the liver to perform various metabolic and synthetic processes. Obstructive engorgement of vessels within the portal system ultimately results in transmission of increasing backpressure within the splanchnic circulation. Therefore, splenomegaly, esophageal varices, and right-sided heart failure ensue in addition to deterioration in liver function.

The development of esophageal varices places the patient at risk for spontaneous, severe upper gastrointestinal hemorrhage. Fluid sequestration resulting from ascites causes consequent alteration in intravascular fluid dynamics and alteration in the renin–angiotensin system. Subsequent reduction in renal perfusion results in eventual renal failure in conjunction with hepatic failure (hepatorenal syndrome). Failure of the liver to clear nitrogenous compounds (ammonia) from the blood contributes to the development of progressive mental status changes (caused by encephalopathy), ultimately leading to coma.

Clinical manifestations

The clinical manifestations of cirrhosis may not be strongly correlated with the severity of the disease process. Patients may have severe liver disease without overt jaundice and ascites. However, the eventual development of jaundice and ascites is observed in most patients as the disease process progresses. Other signs of severe liver disease include gynecomastia, spider angiomata, palmar erythema, and asterixis. Hepatic fibrosis results from the presence of other diseases; portal hypertension ensues, along with its sequelae. These diseases include Budd-Chiari syndrome (vena cava or hepatovenous obstruction), idiopathic portal fibrosis (Banti syndrome), schistosomiasis, and certain rare congenital fibrotic disorders. Venous occlusive disease secondary to metastases, primary hepatic neoplasia, or thromboembolism is also associated with portal hypertension.

Diagnostic and laboratory results

Laboratory changes in the presence of portal hypertension include a hematocrit of 30% to 35%; hyponatremia resulting from increased secretion of antidiuretic hormone; blood urea nitrogen greater than 20 mg/dL; and elevated plasma bilirubin, transaminases, and alkaline phosphatase concentrations.

Treatment

Treatment is supportive until liver transplantation can be undertaken. Variceal bleeding involves replacement of blood loss, vasopressin infusion (0.1–0.9 units/min intravenously), balloon tamponade (Sengstaken-Blakemore tube), endoscopic sclerosis, or the transjugular intrahepatic portosystemic shunt–stent procedure to stop the bleeding. If bleeding does not stop or recurs, emergency surgical procedures such as shunts (portocaval or splenorenal), esophageal transection, or gastric devascularization may be needed. Coagulopathies should be corrected by replacing clotting factors with fresh-frozen plasma (FFP) or cryoprecipitate. Platelet transfusions should be performed preoperatively for counts less than 100,000 mm³. Preservation of renal function involves avoiding aggressive diuresis while correcting acute intravascular fluid deficits with colloid infusions.

Anesthetic considerations

The dosage of muscle relaxants should be reduced, depending on hepatic elimination (e.g., pancuronium, vecuronium) because of reduced plasma clearance. Cisatracurium may be the relaxant of choice. The duration of action of succinylcholine may be prolonged as a result of reduced levels of pseudocholinesterase. Half-lives of opioids may be prolonged, leading to prolonged respiratory depression. Regional anesthesia may be used in patients without thrombocytopenia or coagulopathy if hypotension is avoided (perfusion to the liver becomes highly dependent on hepatic arterial blood flow). After removal of large amounts of ascitic fluid, colloid fluid replacement may be necessary to prevent hypotension. Whole blood may be preferable to packed red blood cells when replacing blood loss. Coagulation factors and platelet deficiencies should be corrected with FFP and platelet transfusions, respectively. Citrate toxicity can occur in these patients because of impaired metabolism of the citrate anticoagulant in blood products. Intravenous calcium should be given to reverse the negative inotropic effects of a reduction in serum ionized calcium levels. For patients with esophageal varices, placement of a nasogastric tube or esophageal can cause rupture and uncontrolled bleeding.

Therapeutic modalities for portal hypertension

Pharmacologic management of patients with portal hypertension and acute variceal bleeding is considered secondary to endoscopic treatment and traditionally consists of intravenous infusion of vasopressin or somatostatin. Vasopressin is a splanchnic vasoconstrictor but may also induce undesirable systemic vasoconstriction. Infusion of vasopressin is initiated at 0.1 to 0.4 U/min. Concurrent infusion of nitroglycerin, titrated at 40 mcg/min, may be used to attenuate coronary arterial vasoconstriction and to control systolic blood pressure at 100 to 110 mmHg. In the presence of profound variceal exsanguination and hemodynamic instability, vasopressin may be used in conjunction with mechanical compression of bleeding esophageal varices provided by insertion of a triple-lumen Sengstaken-Blakemore tube. Use of this device also requires endotracheal intubation for airway support and for prevention of pulmonary aspiration.

Octreotide, a somatostatin analog, has been shown to be equally as effective as vasopressin in pharmacologic control of variceal bleeding. Infused at 50 mcg/hr, octreotide acts as a potent and reversible inhibitor of gastrointestinal peptide hormone activity, thereby decreasing gut motility and venous return to the portal circulation. Octreotide has also been shown to be equally as efficacious as sclerotherapy in acute treatment of variceal hemorrhage. Endoscopic sclerotherapy, usually performed with the patient under intravenous titrated sedation, has been recognized as the treatment of choice in definitive correction of variceal bleeding. Sclerotherapy is accomplished endoscopically by injection of a thrombosing agent either directly into the bleeding variceal or through creation of a fibrotic overlayer over the varix, accomplished by injection of the sclerosing agent proximal to the paravariceal mucosa. A course of treatments is usually necessary to reduce the incidence of rebleeding. Rebleeding, however, continues to be problematic in this subset of patients, with an incidence of up to 60%.

Definition

Hepatic failure occurs when massive necrosis of liver cells results in the development of a life-threatening loss of functional capacity that exceeds 80% to 90%. Hepatic failure can result from acute or chronic liver disease.

Incidence

The major causes of hepatic failure in the United States are related to the effects of viral hepatitis or drug-related liver injury. Each year, an estimated 2000 cases of hepatic failure in the United States are related to viral hepatitis. This accounts for 1% of all deaths and 6% of all liver-related deaths.

Pathophysiology

The following box is a categoric list of the potential causes of hepatic failure.

Diagnostic and laboratory findings

Most proteins associated with the promotion or inhibition of coagulation are synthesized in the liver. When one is reviewing laboratory data, special attention should be given to coagulation studies, liver function studies, complete blood count, electrolytes, glucose, blood urea nitrogen, and creatinine.

A 12-lead electrocardiogram (ECG) should be performed to rule out any possible cardiac arrhythmias related to acidemia, electrolyte abnormalities, or hypoxemia associated with hepatic failure. The patient with liver failure is at risk for the development of acid–base derangements. Respiratory alkalosis may result from hyperventilation related to an abnormality of central regulation. Respiratory acidosis may be caused by endotoxins, increased intracranial pressure, or pulmonary sequelae, which depress respiratory centers. Metabolic acidosis is also possible, related to substantial tissue damage and decreased clearance of lactic acid by the failing liver.

The hypoxemia associated with liver failure can be attributed to aspiration, atelectasis, infection, hypoventilation, or their combinations. Results of chest radiography should be obtained to rule out evidence of pulmonary edema or adult respiratory distress syndrome. Listed in the following table is a guide to laboratory results in liver failure.