Hepatitis

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(1) An overview of hepatitis: part 1
The UK is the only major developed country showing an increase in the number of deaths from all forms of liver disease, including hepatitis. In part 1, Gareth Nickless focuses on non-viral hepatitis and drug use in liver dysfunction
(PDF 110K)

Pharmaceutical Journal 2008;280:411-414 (5 April 2008)

(2) An overview of hepatitis: part 2
In part 2 of this overview of hepatitis, Gareth Nickless looks at viral hepatitis and its treatment
(PDF 80K)

Pharmaceutical Journal 2008;280:477-480 (19 April 2008)



Definitions

Cholestasis Impaired bile flow. This can be intra- or extra-hepatic (eg, gallstones blocking the bile duct) and may or may not be associated with hepatitis.

Cirrhosis of the liver A progressive disease of the liver (as a result of diffuse damage to hepatic parenchymal cells) associated with fibrosis, nodular formation and altered architecture. There is associated failure of hepatocyte function and resistance to hepatic blood flow.

Compensated liver disease Where a patient has known chronic liver damage but is asymptomatic, either because of prescribed medicines or because there is enough healthy liver tissue to carry our normal functions

Decompensated liver disease Where a patient with compensated liver disease suddenly develops symptoms

Liver function tests

Bilirubin Bilirubin is a by-product of haem metabolism that is conjugated by the hepatocytes and transported to the bile ducts to form bile salts. When the liver is damaged, however, this function is impaired and bilirubin levels rise, leading to jaundice. Although a raised bilirubin indicates that something is wrong, it is not always a sign of liver disease.

For example, in auto-immune haemolytic anaemia haemolysis will result in a larger quantity of bilirubin for the liver to process and, in patients with gallstones biliary obstruction can prevent conjugated bilirubin from reaching the gall bladder.

Alkaline phosphatase Alkaline phosphatase (ALP) is found in the epithelial cells that line branches of the bile duct. Raised levels are commonly seen in intra- and extra-hepatic cholestasis. ALP is also produced in the bone so conditions such as Paget’s disease can complicate the interpretation of ALP results.

Transaminase enzymes Transaminases (alanine aminotransferase [ALT] and aspartase aminotransferase [AST]) are the enzymes that are most specific to the liver. Levels are most likely to be raised during acute hepatocellular damage (ie, in acute hepatitis) but are usually normal in patients with cholestasis.

In patients with gallstones in the common bile duct a mixed picture of both cholestasis and hepatitis (ie, raised hepatic and biliary enzymes) may be seen.

However, in patients with cirrhosis of the liver ALT and AST levels may be normal, or only marginally raised, because there is little remaining healthy liver tissue left to damage.

Gamma glutaryltransferase Gamma glutaryltransferase (GGT) is found in high concentrations in the bile ducts and raised levels may be seen in patients presenting with cholestasis or cirrhosis. Unlike ALP, GGT is not present in bone so can be used to ascertain whether or not a high ALP result is due to bone disease.

Patients prescribed drugs with enzyme-inducing properties (eg, phenytoin) can also have a raised GGT level, as will patients who have consumed a large amount of alcohol close to the blood test.

Albumin Albumin levels are useful in assessing the synthetic function of the liver. However, because plasma half-life is approximately 20 days, it takes at least a week for levels to fall below the reference range in a patient with liver damage. This result is, therefore, more useful for looking for chronic liver damage.

It should also be remembered that other processes can cause a more rapid reduction in albumin levels (eg, the catabolic effects of infection).

Prothrombin time Prothrombin time (and thus international normalised ratio) may be increased in a patient with hepatobiliary disease for two reasons. First, vitamin K absorption may be impaired due to absence of bile in the gut and, secondly, the damaged hepatocytes will be unable to synthesise adequate clotting factors.

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