Clinical cirrhosis

Cirrhosis is the end stage of all chronic liver diseases. It kills about 26,000 people every year in the United States making it the 12^th leading cause of death overall and the 8^th leading cause of death in men. But although cirrhosis is widwspread managing it still posses a challenge to emergency physicians because the disease affects every body system. It not only causes a range of unique diseases but also makes treating common diseases more difficult.

Most cases of cirrhosis are preventable, with alcohol and viral infections causing the majority of them. Nonalcoholic fatty liver disease may develop as a result of obesity, diabetes, hypertriglyceridemia, or profound weight loss after jejunoileal bypass surgery. Mortality rates in alcoholic liver disease are higher than those in other causes causes of cirrhosis in the United States.

How cirrhosis develops. Cirrhosis is a progressive liver fibrosis with nodular regeneration and distortion of hepatic architecture. This distorted architecture causes resistance to portal flow that leads to portal hypertension. As a result, blood is shunted away from the liver. The body’s attempt to compensate this leads to local production of vasodilators, like nitric oxide, that induce splanchnic arterial vasodilation and collateral vein formation, causing blood to be diverted to the systemic circulation and development of a hyperdynamic circulatory system.

Splanchnic vasodilation is the most important factor in the development od ascites. Eventually, visodilation becomes so severe that the effective circulating blood volume decreases and arterial pressure drops. This leads to activation of the sympathetic nervous and retin-angiotestin-aldosterone systems resulting in sodium and fluid retention. Also, the combination of splanchnic arterial vasodilation and portal hypertension alters intestinal capillary permeability and pressure facilitating the accumulation of retained fluid within the abdominal cavity and further increasing fluid retention.

Clinical profile. About 40% of patients with cirrhosis are asymptomatic. This is because 80 to 90% of the liver parenchyma must be destroyed before the clinical manifestations of liver failure and cirrhosis develop. Once ascites or gastrointestinal bleeding develops, cirrhosis is considered decompensated. Half of all patients with cirrhosis and ascites will die within two years if they do not receive an orthotopic liver transplant.

Jaundice, palmar erythema, hepatomegaly, splenomegaly, or ascites may be discovered on abdominal examination depending on how far the disease has progressed. Tremor of the hands may be present in cases of hepatic encephalopathy. Abdominal ultrasonography is the first-line radiographic study for diagnosing cirrhosis. Therapy consists of sodium restriction, diuretics (spironolactone, furosemide), and abstention from alcohol. Fluid restriction is unnecessary unless serum sodium is less than 125 mEq/L, although it may help control ascites and minimize the amount of diuretic required.

Common complications. Cirrhosis is an immunocompromised state. As more and more damage is done to the liver its synthetic function begins to decline. This problem is compounded by increased sympathetic tone causing a decrease in gut motility. This in its turn promotes bacterial stasis and overgrowth which leads to an overpopulation of enteric gram-negative bacteria. Intestinal submucosal edema from portal hypertension increases intestinal capillary permeability and compromises the protective integrity of the mucosal barrier. The above problems combined with the failure of antibacterial defense mechanisms to microorganisms and toxins from the blood often have disastrous results in the body including sepsis.

Another common problem associated with cirrhosis is malnutrition due to anorexia, poor diet, malabsorption, and an altered metabolic state. Malnutrition also decreases the risk of infection. Bleeding can occur secondary to decreased production of clotting factors. In addition, patients with cirrhosis are prone to hypoglycemia due to decreased hepatic glycogen storage.

Special treatment considerations. Because of the unusual physiologic mechanisms of their disease patients with cirrhosis do not respond to traditional therapies for common problems. Early goal-directed therapy, intensive insulin therapy, and other sepsis treatments have been shown to decrease mortality in the general population but have not been tried on patients with cirrhosis.

Hypotension from sepsis or other causes of shock may be refractory to catecholamine administration in patients with cirrhosus because of sympathetic desensitization. Priliminary evidence shows that vasopressin may improve refractory shock in these patients. Terlipressin has been extremely beneficial in treating hepatorenal syndrome and has shown great promise in treating acute liver injury with hypotension and severe lactic acidosis resistant to volume expansion as well as catecholamine-resistant septic shock. This drug is still in phase III clinical trials in the United States.

Marked adrenal insufficiency almost always occurs in patients with cirrhosis and severe sepsis and can lead to circulatory collapse. Steroids should be considered early in the course of therapy. In addition, septic patients with cirrhosis are more prone to developing disseminated intravascular coagulopathy (DIC) than the general population so early vigilant monitoring is suggested. Distinguishing DIS from hepatic coagulopathy can be difficult because fibrinogen levels may be low, high, or normal in cirrhosis. Early monitoring for trends in these laboratory values may help differentiate DIC from hepatic coagulopathy.

Some drugs should be avoided in patients with cirrhosis. Nonsteroidal anti-inflammatory drugs cause a decrease in renal perfusion. In addition, iodinated contrast agents given for computed tomography or other imaging studies may cause renal vasoconstriction when administered intravascularly. Nitrovasodilators or substances inhibiting angiotensin II action may be used to treat portal hypertension but they shunt blood away from the kidneys and may include renal dysfunction in patients with cirrhosis and ascites. They should not ne used by emergency physicians because they may precipitate prerenal failure.

Finally, 33 to 46% of patients with cirrhosis have gallstones, a higher incidence than in the general population. Keep this in mind, especially when patients present with abdominal pain. Traditional laboratory results, such as liver function test, may not be helpful in delineating this diagnosis. If gallstones are strongly suspected, an abdominal ultrasound should be performed.

Variceal bleeding: most feared complication. Variceal bleeding is one of seven unique complications that may occur with cirrhosis. The others are spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, cirrhotic cardiomyopathy, hepatopulmonary syndrome, and portopulmonary hepertension.

Patients can lose massive amounts of dlood rapidly with variceal bleeding, making it the cirrhosis complication physicians fear most. The situation is further complicated by impared platelet function and coagulopathy. About 50% of patients with cirrhosis develop varices.

Once varices have been identified, profilaxis with40 mg of oral propranolol twice a day is recommended. If propranolol is contraindicated or not tolerated 20 mg of oral isosorbid mononitrate twice a day may be used, but patients must be monitored closely for renal failure. Beta blockers should never be started during acute bleeding in patients with cirrhosis.

When patients present to the emergency department with variceal bleeding the mainstays of therapy are correcting hypovolemia, achieving hemostasis, and preventing complications. Upper gastrointestinal hemorrhage from esophageal varices may be massive and patients may have trouble protecting their airway. If airway compromise seems likely early intubation is recommended.

There is no mortality benefit in using both medical and endoscopic management for an initial bleeding. Each of these therapies reduces the risk of bleeding by 40-50%. Endoscopy is a reasonable choice for the first rebleeding but surgical placement of a transjugular intrahepatic portosystemic shunt (TIPS) must be strongly considered.

There is a significant decrease in mortality when antibiotics are implemented early in the course of variceal hemorrhage so prophylaxis with norfloxacin should begin as soon as possible.