Management Miscellaneous		Hepatic encephalopathy is the most serious complication of end-stage liver disease. There are several known precipitating factors. Pathogenesis is unclear, but presumably relates to toxins that normally would be rendered harmless in the liver. Symptoms include altered consciousness, disorientation and a variety of abnormal neurologic signs. There is no diagnostic laboratory test. Elevated ammonia levels are characteristic, but not always seen. Spinal fluid is usually normal. EEG is abnormal but not diagnostic. Treatment centers on known precipitating factors. Protein intake is severely reduced. Various measures are undertaken to reduce ammonia production by gut bacteria. These include lactulose as a laxative, cleansing enemas, and Flagyl to decrease the gut bacteria. Neomycin is no longer recommended because of its potential ototoxic and nephrotoxic effects. Newer therapies include addition of branched-chain amino acids to TPN and use of Flumazenil, a benzodiazepine-GABA antagonist. Urgent liver transplant may be required. Coagulopathy can be due to several reasons. Factors II, V, VII, IX, X and fibrinogen are all synthesized in the liver and all may be low in cholestasis. Factor VII is the first to decrease because of its short half-life, so monitoring of prothrombin time is essential. Fibrinogen usually declines only in severe disease. Vitamin-K dependent factors (II, VII, IX and X) also decrease early because of the fat malabsorption associated with cholestatic diseases. The anticoagulants, protein C, protein S and antithrombin III, are also made in the liver. Fibrin and tissue plasminogen activator are ordinarily removed from the circulation by the liver. Abnormality in any or all of these processes may lead to increased bleeding. Disseminated intravascular coagulation is unusual and may be a sign of sepsis. However, thrombocytopenia commonly occurs from hypersplenism. Hepatorenal syndrome is a poorly understood disorder involving the onset of renal failure in the context of severe liver disease. Most commonly in pediatrics, it occurs with Alagille syndrome, hereditary tyrosinemia and polycystic kidney/liver disease. The diagnostic criteria have been specified, although they are not pathognomonic. Physiologically, there is severe renal vasoconstriction with decreased renal blood flow, especially to the cortex. This is superimposed on the typical hemodynamic changes seen in end-stage liver disease - decreased systemic vascular resistance, increased cardiac output and decreased systemic blood pressure. The exact etiology of the vasoconstriction is unknown, although many mediators (nitric oxide, endothelins, renal prostaglandins, renin, catecholamines) have been implicated. Dialysis is the treatment of choice while awaiting liver transplant, which is curative. Without transplant, mortality is > 70% in adult studies. Less commonly seen is hepatopulmonary syndrome, a triad of hypoxia, liver disease and intrapulmonary vasodilatation. Its onset is usually heralded by the appearance of cyanosis and digital clubbing in a patient with chronic liver disease. Because the pulmonary vasodilatation is more pronounced at the lung bases, there is a characteristic fall in pO2 when standing. As with hepatorenal syndrome, the exact mediators involved in the pulmonary vasodilatation are not known. The only definitive treatment is liver transplant, although the results are not as encouraging as in hepatorenal syndrome. Return to top of page