Hepatic Synthetic Function

The incidence of viral resistance to lamivudine increases with the duration of therapy in patients with chronic hepatitis B (11). However, the effect of viral resistance on hepatic synthetic function has not been well defined. In 38 patients (26 with cirrhosis) in an open study there was an initial antiviral response in all patients (hepatitis B virus DNA became undetectable by a hybridization assay), and nine of 22 (41%) hepatitis B e antigen-positive patients underwent hepatitis B e antigen seroconversion. In 29 patients with undetectable serum hepatitis B viral DNA at the end of the study, the mean serum albumin concentration rose from 40 to 43 g/1, corresponding to a yearly increase of 1.85 g/1 this was largely attributable to an increase in the cirrhotic patients. Resistance to lamivudine developed in nine patients. Suppression of viral replication by lamivudine improves hepatic synthetic function in chronic hepatitis B patients, but emergence of drug resistance is associated with a rapid fall in serum albumin. 

The prothrombin time, which is a measure of the activities of certain coagulation factors made by (he liver, is sometimes used as an indicator of hepatic synthetic function. Prothrombin has a very short half-life, and an increased prothrombin time may be the earliest indicator of hepatocellular damage. 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

The resulting resistance to blood flow results in portal hypertension and the development of varices and ascites. Hepatocyte loss and intrahepatic shunting of blood results in diminished metabolic and synthetic function, which leads to hepatic encephalopathy (HE) and coagulopathy. 

Albumin and coagulation factors are markers of hepatic synthetic activity and are used to estimate hepatocyte functioning in cirrhosis. 

Because of its wide range and diversity of synthetic functions, the liver may be considered to be the body s factory, taking raw materials and producing many compounds some of which are exported for use in other tissues. This section describes the syntheses of proteins, lipids and lipoproteins, ketones, urea and haem. Not all of these pathways are unique to the liver, but all illustrate important points of hepatic function. 

The important uses of laboratory tests in acute hepatitis are to identify individuals with fulminant hepatic failure, document recovery, and determine clearance of any infectious agents. The most important tests in determining extent of injury are not plasma activities of cytosolic enzymes, but evidence of impaired liver function. The most important indicator of prognosis in acute hepatitis is impairment in synthetic functions of which PT is a widely accepted indicator. In acute viral or alcoholic hepatitis, PT more than 15... 

Routine liver tests include alkaline phosphatase, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), and y-glutamyl transpeptidase (GGT). Additional markers of hepatic synthetic activity include albumin and prothrombin time. Liver function tests are... 

These proteins are markers of hepatic synthetic activity and are therefore used to estimate the level of functioning hepatocytes in cirrhosis. They are employed in the Child-Pugh scoring system for liver disease. Albumin levels can be affected by a number of factors, including the patient s nutritional status, acute illnesses, which result in redistribution of albumin, and protein losses from renal and intestinal sources. 

Cardiac index and blood pressure must be sufficient to ensure adequate organ perfusion, as assessed by alert mental status, creatinine clearance sufficient to prevent metabolic azotemic complications, hepatic function adequate to maintain synthetic and excretory functions, a stable heart rate and rhythm, absence of ongoing myocardial ischemia or infarction, skeletal muscle and skin blood flow sufficient to prevent ischemic injury, and normal arterial pH (7.34 to 7.47) with a normal serum lactate concentration. These goals are most often achieved with a cardiac index greater than 2.2 L/min/m2, a mean arterial blood pressure greater than 60 mm Hg, and PAOP of 25 mm Hg or greater. 

The liver is involved in a variety of both synthetic and catabolic functions, including metabolism of amino acids, lipids, carbohydrates, protein synthesis and detoxification [ 1 ]. These metabolic functions are performed mainly by hepatocytes, although the liver is made of three major cell types (hepatocytes, biliary epithelial cells and Kupffer cells). Exerting many different metabolic functions, the liver contains several different and specific enzymes, leakage of which into the bloodstream occurs in hepatic diseases. 

As CHCs and POCs are metabohsed by the liver their use may adversely affect this patient, who has severely compromised liver function. CHC or POC methods should not be advocated in this case. This patient s synthetic and metabohc function is significantly impaired and therefore the metabohsm of CHCs could be affected, precipitating adverse drug reactions such as jaundice, hepatitis and cholestasis. 

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