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Key Stage 5 biology I Lesson Plan 6 – LIVER DISEASE Alcoholic Liver Disease Alcoholic liver disease is caused by the excessive consumption of alcohol and is the major cause of liver disease in western countries. Because the liver is the main organ involved in breaking alcohol down into water and carbon dioxide it is most prone to developing alcohol related problems. The Stages of Liver Disease Alcoholic liver disease is a broad term that actually refers to a number of more specific conditions. Steatosis, otherwise known as fatty liver, is the first stage of liver disease and is basically the accumulation of fat in the liver cells. These appear under a microscope as large fatty globules and can also be caused by diabetes, obesity and starvation. Steatosis caused by alcohol intake can usually be reversed by reducing or completely stopping alcohol consumption. However, 20 to 30 percent of people developing steatosis and continuing to drink excessively will go on to develop the next stage of liver disease; alcoholic hepatitis. At this stage liver function tests such as those for bilirubin and albumin are usually normal, tests for aspartate amino-transferase (AST) and alkaline phosphatase (ALP) may show slight increases and g-glutamyl transferase (GGT) levels will invariably be elevated. Alcoholic hepatitis can occur when those cells affected by steatosis suffer an acute inflammatory reaction. This reaction is not directly related to the quantity of alcohol being consumed and some people seem more prone to it than others. The inflammation is called alcoholic steatonecrosis and is thought to predispose sufferers to develop liver fibrosis. As with steatosis, this condition can usually be reversed by reducing or completely stopping alcohol consumption. However, even with complete abstinence the condition can take up to six months to resolve. At this stage bilirubin levels can reach between 300 and 500 μmol/L and GGT levels can rise substantially. The levels of albumin in the blood serum will fall. Alcoholic hepatitis will progress to liver fibrosis and cirrhosis in 25 to 30 per cent of cases. Cirrhosis is a late stage of liver disease characterised by fibrosis and alterations to the structure of the liver. Biochemical abnormalities include a low serum albumin and elevated levels of bilirubin and AST. AST levels may reach up to 300 IU/L (International Units per litre). Alcoholic cirrhosis is often progressive and can lead to total liver failure. The later stages of cirrhosis are irreversible but can usually be managed with the appropriate treatments for long periods of time. Patients who manage to abstain from alcohol at this stage have a five year survival rate of between 60 and 70 per cent, which falls to 40 per cent for those who continue to drink. Hepatocellular carcinoma (malignant liver cancer) occurs in 10 per cent of stable cirrhotics and is usually fatal within six months. Resource Sheet 6.2 Key Stage 5 biology I Lesson Plan 6 – LIVER DISEASE Resource Sheet 6.2 Managing Liver Disease Recognising alcoholic liver disease in its early stages is very important. Patients presenting with anorexia, nausea, diarrhoea, tenderness in the area of the right lower chest below the diaphragm and elevated levels of GGT are prime candidates for alcoholic liver disease. The most important therapy in the early stages of alcoholic liver disease is simply abstinence from alcohol and a nutritious diet. Drugs such as diazepam and chlordiazepoxide can be used to treat withdrawal symptoms. The different stages of alcoholic liver disease will lead to a variety of different symptoms. For example, patients with chronic liver disease will often become hyperglycemic due to insulin resistance. Patients suffering liver failure, on the other hand, will become hypoglycemic as the liver loses its ability to make glucose (gluconeogenesis) and depletes its glycogen stores. Patients with severe alcoholic hepatitis will need hospital treatment as they will usually have some significant metabolic abnormalities. These can include: • Hypomagnesemia - low levels of magnesium in the blood • Hypokalemia - low levels of potassium in the blood • Metabolic acidosis - a blood pH of less than 7.35 • Ketoacidosis - a life-threatening condition in which ketones, which result from the breakdown of fat for energy, accumulate in the bloodstream and the pH of the blood decreases. Alcoholic hepatitis can be treated with corticosteroids and amino acid supplements can be given intravenously to treat protein malnourishment. Cirrhosis itself is irreversible so therapy is directed at relieving the complications of liver failure and in particular high blood pressure in the portal vein (portal hypertension). Portal hypertension can cause stretching of the veins at the base of the oesophagus. These are called oesophageal varices and if they burst the bleeding can be fatal. To treat this condition a portacaval shunt is created surgically between the portal vein and the inferior vena cava to allow blood from the abdominal organs to bypass the liver. A liver transplant, however, remains the only option for those patients with end stage alcoholic cirrhosis. The ethical issues around using such a scarce resource as a healthy transplant-ready liver for a disease which is widely considered to be self-inflicted are still hotly debated. Splenic vein Portal vein Inferior vena cava Renal vein Diagram 1. A portacaval shunt Key Stage 5 biology I Lesson Plan 6 – LIVER DISEASE Liver Function Tests There are a range of blood tests that can be carried out on patients with suspected liver disease. Here are some of them: mALB – Albumin. Normal range 35 – 48 IU/L (International Units per Litre) Albumin is synthesised by the liver and will decrease if the liver is damaged. mAST – Aspartate Amino-Transferase. Normal range 12 – 40 IU/L This enzyme is produced by hepatocytes, leaking out if the cells are damaged. Therefore the level will rise in a damaged liver. High levels of AST can also be present due to myocardial infarct (heart attack). mALP – Alkaline Phosphatase. Normal range 30 – 95 IU/L This enzyme is produced by the biliary ducts of the liver and will leak into the blood if the cells are damaged. However it is also present in bone and placenta and renal and intestinal damage can also result in elevated levels in the blood. mGGT – g-Glutamyl Transferase. Normal range 3- 28 IU/L This enzyme is specific to liver cells and production rises due to alcohol toxicity. It can be elevated by even very minor liver dysfunction. mALT – Alanine Transaminase. Normal range 10 – 40 IU/L (male), 7 – 35 IU/L (female) This enzyme is involved in the metabolism of the amino acid alanine in the liver. Injury to the liver results in ALT leaking out into the blood. ALT is the most sensitive marker for liver cell damage. When making a diagnosis the ratio of AST to ALT can be useful to investigate as a ratio of AST:ALT higher than 2:1 is usually a sure sign of advanced alcoholic liver disease. mTbil – Total Bilirubin. Normal range 3 - 20 μmol/L Bilirubin is a product of the breakdown of haemoglobin from red blood cells. The liver is responsible for clearing the blood of bilirubin so elevated levels of bilirubin are a sign that the liver may not be functioning as it should. Resource Sheet 6.2