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This disease is caused by mutations that lead to copper accumulation in the liver (excretory disorder) and the brain. This results in neuropsychiatric symptoms and movement disorders. The diagnosis is made by the presence of a very low serum ceruloplasmin level (plasma copper binding protein), increased copper excretion in the urine (> 100 pg/24 hours) and by the presence of copper accumulation at the edge of the cornea, the so-called Kayser-Fleischer ring.

Patients may also present with acute liver failure (ALF) in which unconjugated bilirubin is markedly elevated. This is due to the release of copper from the tissue, which leads to hemolysis. Familial screening should be performed by detecting the gene mutation. The treatment aims to bind copper and increase urinary excretion. For this purpose, D-penicillamine (750 to 1 g/day) is used with supplements of pyridoxine (vitamin B6) (250 mg/week).

This is a congenital abnormality in the structure of the alpha-antitrypsin produced, such that the aberrant isoenzyme is not excreted from the liver cell. The accumulation in the hepatocytes gives rise to neonatal cholestasis in the newborn. In adulthood it gives rise to cirrhosis, but together with alcohol can cause premature development of cirrhosis.

Plasma deficiency can lead to early emphysema at the age of 18 to 30. The diagnosis is made by the dosage of the alpha-1-antitrypsin protein. However, this is usually increased secondary to cirrhosis. The diagnosis is also made by staining the aberrant enzyme in the hepatocyte on liver biopsy and ultimately detecting the gene mutation. There is currently no specific therapy. A smoking ban should be imposed and prevention of lung infections is important. In case of symptomatic cirrhosis, a liver transplant should be performed.

Porphyrias are a group of metabolic diseases caused by a dysfunction or defect in one of the enzymes of heme biosynthesis. This leads to the accumulation of toxic heme precursors. There are genetic and acquired forms. The most common form is porphyria cutanea tarda. It occurs in 0.5 to 1 in 10,000 cases. The pathogenesis is caused by the accumulation of porphyrins in the liver and is further provoked by various factors, such as alcohol and oral contraception. Typical are sunlight toxicity of the skin and dark red urine if it has been in the urethra for a while. Biochemically there is an increased iron saturation and increased ferritin. The treatment consists mainly of avoiding provoking factors. In case of iron overload, bloodletting must be performed (chelation).

There is a whole list of rare hereditary disorders that affect the liver and are called 'metabolic' diseases. These are diseases in which something goes wrong in the metabolism due to a genetic defect. This can be in the production, combustion or storage of sugars (glycogenesis), in the processing of amino acids (for example tyrosinemia), in the production, storage or processing of fats and in the breakdown of old cells and their membranes (Gaucher disease).

This concerns alcoholic and non-alcoholic liver disease.

Alcohol abuse is one of the leading causes of liver disease in the West. Alcohol abuse does not lead to liver disease in everyone, but the risk of cirrhosis increases the longer and the more alcohol is consumed. Recent guidelines speak of problematic alcohol use when someone consumes more than 10 units of alcohol per week, where a unit is approximately 10g of ethanol. This is the equivalent of one glass of lager, one glass of wine or a shot of spirits.

Alcohol abuse can affect other organs besides the liver and cause the following diseases: acute and chronic pancreatitis, polyneuropathy, gout, cardiomyopathy, neurological disorders such as Korsakoff syndrome (confabulations with memory disorders) and Wernicke syndrome (confusion with ataxia and impaired eye coordination). Finally, alcohol abuse gives an increased risk of oral, pharyngeal, laryngeal and esophageal carcinomas, especially if the patient also smokes.

The damage of alcohol to the body occurs according to various factors, such as race and gender. For example, the Japanese quickly form an increased concentration of acetaldehyde, which leads to 'flushing'. Alcohol is more harmful to women for several reasons:

- alcohol is not fat-soluble and women have more fat mass. As a result, they have a smaller volume of distribution, which allows them to reach high blood alcohol concentrations more quickly;

- women have less alcohol hydrogenase;

- estrogens have a synergistic effect on oxidative stress and inflammation.

There is also an increased risk of developing alcoholic cirrhosis after gastric bypass, due to the reduced alcohol dehydrogenase activity in the stomach and underlying non-alcoholic fatty liver disease. Prevention is extremely important, alcohol abuse must be detected early and actively recognized. Specific questionnaires have been developed for this (CAGE and AUDIT-C).

There are currently no good routine tests to detect chronic alcohol abuse. The alcohol levels found in the blood during blood tests and/or breath tests quickly become negative. The most accurate technique is to detect alcohol metabolites (ethyl glucuronide) in the hair, which give an idea of ​​the alcohol abuse in the past three months. In the urine they give an idea of ​​the alcohol intake in the last few days. There are different stages of alcohol abuse. Abuse occurs in 20% of the population. The person involved then suffers on a physical, social and mental level. 5% of the population has an addiction, which is characterized by tolerance (having to drink more and more to get the same effect) and withdrawal symptoms.

Delirium tremens

Delirium tremens is a withdrawal symptom. It usually occurs within 6 to 24 hours to 5 days after stopping alcohol. It makes the patient very anxious and irritated. It is accompanied by hallucinations and leads to serious restlessness. Clinical examination reveals a rapid, fine tremor. This can lead to epilepsy and coma. Today, treatment consists of placing the patient in a quiet (dark) room and administering tranquilizers. The following are used: diazepam (10 mg/4 to 8 hours), clorazepate (three times 10 to 20 mg/day) or haloperidol (5 to 10 mg intramuscularly or intravenously, then 1 to 10 mg/day depending on agitation). If glucose is given by infusion, 10 g of vitamin B1 is added. There is currently no adequate medication for alcohol dependency in patients with advanced liver disease. Disulfiram is contraindicated in cirrhosis. There is little experience in patients with cirrhosis with other products, acamprosate or naltrexone.

Presents with increased gamma-glutamyltransferase (gamma-GT) and an enlarged hyperreflective liver on ultrasound.

Alcohol abuse leads to steatosis in the liver (accumulation of triglycerides in hepatocytes). This condition causes few symptoms. Clinical examination reveals a large, fairly soft liver. The lab suggests alcohol abuse: increased gamma-GT, increased MCV (volume of erythrocytes), increased triglycerides and an increase in uric acid. There will be more aspartate aminotransferases than alanine aminotransferases (AST > ALT). A large hyperreflective liver is found on radiology.

In the differential diagnosis of hepatic steatosis, the following conditions must be excluded:

- non-alcoholic fatty liver disease (NAFLD)

- unbalanced parenteral nutrition;

- malnutrition due to anorexia nervosa;

- bariatric surgery by means of jejuno-ileal short-circuiting;

- medically indicated conditions (including corticosteroids and cordarone);

- acute gestational steatosis.

The prognosis is favorable after stopping alcohol and the abnormalities can disappear after six weeks.

Presents with a marked increase in y-GT, accompanied by jaundice and an enlarged hyperreflective liver.

ASH occurs in a third of heavy drinkers and is usually already superimposed on alcoholic cirrhosis.

The symptoms and biochemistry are determined by the severity of the alcoholic static hepatitis. A severe form is characterized by:

- chachexia;

- icterus;

- leukocytosis and a low platelet count (also due to suppression by alcohol);

- a moderately increased amount of transaminases: about 100 IU/l;

- AST > ALT;

- very high y_GT, as well as Fe saturation and ferritin (differential diagnosis with primary hemochromatosis).

The prognosis is unfavorable if the Maddrey score is higher than 32. This is based on the prothrombin time (PT) and the amount of bilirubin. The patient can then evolve into acute or chronic liver failure.

Treatment consists of: stopping alcohol, preventing delirium tremens, administering vitamin B1 and providing sufficient calorie-rich food (enteral nutrition if necessary). If the Maddrey score is higher than or equal to 32, prednisolone must be administered for one month, to be stopped if the Lille score does not decrease after one week. This score is based on, among other things, the amount of bilirubin.

Presents with abnormal liver tests in patients with metabolic syndrome.

Non-alcoholic fatty liver disease is a manifestation of the metabolic syndrome, which is characterized by:

- abdominal obesity (waist circumference >= 94 centimeters for men and >= 80 centimeters for women);

- insulin resistance (fasting glycemia >= 110);

- hyperlipidemia;

- arterial hypertension.

The pathophysiology is complex. It involves an overload of the adipose tissue (especially visceral), which leads to a dysfunction of this adipose tissue. This results in the release of free fatty acids, which accumulate in the hepatocytes and are converted into triglycerides, which overload the hepatocytes. The patients are usually free of complaints. The diagnosis is therefore made on the basis of routine laboratory tests. This mainly involves an increase in y-GT, with or without a slight increase in transaminases and alkaline phosphatases. Biochemically, an isolated increase in serum ferritin is found in a number of these patients. An enlarged hyperreflective liver can be seen on an ultrasound.

Two stages are distinguished:

- non-alcoholic steatosis: does not lead to complicated liver disease;

- non-alcoholic steatohepatitis (NASH): can lead to cirrhosis in 20% of patients after 20 years.

The distinction is made using a liver biopsy.

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