Liver

Methods of Examination

Sonography
Sonography , or ultrasound scanning, is the most important non-invasive imaging technique for the diagnosis of liver and gall-bladder problems. Sonography is called for in a circumscribed set of liver conditions. Stones, cystic changes and solid conditions as small as 3 to 5 mm can be detected. Doppler sonography allows us to distinguish solid and cystic structures, as well as those where blood-flow is present. A further diagnostic advantage of ultrasound is that it permits the low-risk, sonographically guided removal of tissue samples (biopsies ).

Computerised Tomography (CT) and Magnetic Resonance Imaging (MRI)
The indications for CT and MRI are the same as those for sonography. A particular advantage of CT and MRI is the degree of contrast in the imaging, especially for cystic formations and solid tumours of the liver such as adenomas , haemangiomas and primary cancer of the liver (hepatoma).

Arteriography
The imaging of the hepatic vessels is carried out in connection with liver transplant investigations, for the definitive diagnosis of a liver tumour and for treating tumours of the liver.

Histology
The diagnosis is completed by removing a tissue sample (liver biopsy). This is indicated in the case of all unclear, diffuse or focal liver parenchyma conditions.

2. Major Disorders of the Liver

Numerous congenital and acquired disorders can affect the liver and produce similar symptoms. The main groups are briefly as follows:
1. Viral hepatitis. Hepatitis A is for the most part harmless; a vaccine is available. Hepatitis B is a large-scale global killer: 300,000,000 people are affected, and one million die every year. A vaccine is available and is urgently recommended. Hepatitis C is also very common: it is assumed that globally 100,000,000 people are infected with Hepatitis C. At the present time a vaccine is unfortunately not available.
2. Alcoholic liver disease.
3. Congenital liver disorders. Haemochromatosis is a very common hereditary illness: around 20,000 Swiss are affected. Other congenital liver disorders are Wilson's disease (too much copper), and alpha-1 antitrypsin deficiency. Cystic fibrosis can also affect the liver.
4. Autoimmune liver disease.
5. Cirrhosis of the liver.
6. Liver tumours, including cancer of the liver.

1. Viral Hepatitis

Hepatitis A Viral Infection

1. Definition
Acute inflammation of the liver, generally self-healing, caused by an enteral RNA (ribo-nucleic acid) virus transmitted from the intestine or bowel. Previously this was a disease affecting primarily children and young people, but now, on account of the high standard of hygiene in western countries, the infection is increasingly attacking the adult population.

2. Symptoms and Signs
Clinically, most acute hepatitis infections are characterised through a gastro-enteric pre-stage ('stomach flu') which is frequently followed by an icteric phase (jaundice). This begins with a darkening of the colour of the urine and a yellowing of the eyes and the mucous membranes.

3. Complications and Risks
Hepatitis A is a self-healing illness. Fulminant life-threatening incidences are extremely rare (0.01%). The treatment in such cases is liver transplantation.

4. Diagnosis and Preliminary Investigation
The diagnosis is established on the basis of clinical and laboratory tests. Laboratory results show that in addition to an increased amount of liver enzymes the patient's blood always contains antibodies against the hepatitis A virus.

5. Therapy / Treatment / Prevention
No specific therapy is called for. For preventive measures a live vaccine is available for those visiting risk areas such as Asia, Africa, Central America and the Middle East. The injections of 1 ml each time are administered after the first injection at intervals of 2 to 4 weeks and 6 to 12 months. The success rate is greater than 95%.

Hepatitis B Virus Infection

1. Definition
Acute inflammation of the liver, caused by a DNA virus transmitted through human contact during sexual relations or during birth (only humans can carry the hepatitis B virus). Hepatitis B is one of the biggest global killers: 300,000,000 people are affected, and one million die every year. In contrast to hepatitis A there is no reciprocal relationship of the infection rate with the age of the groups examined; in connection with rising drug abuse among 15 to 29 year-olds, however, a certain increase in HBV infected persons is apparent. The frequency of hepatitis B is increasing in the case of partners of HBV infected persons, which means that the disease is probably sexually transmitted. The period from infection to appearance of symptoms (the incubation period) amounts to between 4 and 6 weeks.

2. Symptoms and Signs
Mostly of a general nature, such as pain in the upper abdomen, loss of appetite, feelings of malaise, vomiting. Jaundice (icterus) is not always present. A diagnosis which excludes hepatitis A is not possible without recourse to laboratory tests (see below).

3. Complications and Risks
Large scale progress studies show that 90% of hepatitis B infections result in a spontaneous recovery free from complications. Fewer than 1% of all cases develop into a fulminant form: an emergency transplantation is required in such cases. In around 10% of cases the infection leads to a chronic condition (chronic persistent or chronic acute hepatitis). Cirrhosis of the liver (see below) occurs in fewer than 1% of the cases. Primary liver cell carcinoma appears primarily in the case of patients with chronic developments, especially when accompanied by an additional harmful factor, such as a further infection by the hepatitis C virus or alcohol.

4. Diagnosis and Preliminary Investigation
The diagnosis of a hepatitis virus infection is established through certain laboratory tests (serological examinations). The positive nature of the blood serum tests is dependent on the course of the disease (e.g. the development of chronic hepatitis).

5. Therapy / Treatment / Prevention
Treatment of acute hepatitis B infection is not necessary. Bed rest has no effect on the course of the illness. Most patients attempt to avoid excessive physical activity anyway. Patients with a fulminant condition require a liver transplantation. In cases of chronically active hepatitis a treatment with Interferon leads to an elimination of the virus in ca. 40 to 50% of cases. Patients treated successfully are less likely to develop cirrhosis of the liver and liver carcinoma. Before the start of treatment, a liver biopsy is always indicated so as to permit an exact mapping of the extent of the disorder. A live vaccine is available which consists of purified, genetically engineered synthesised vaccine substances manufactured from human plasma. The live vaccine is repeated after 4 weeks and 6 months. The result of the vaccination is monitored by demonstrating the presence of antibodies against the virus. The vaccine titre should be higher than 100 IU, otherwise an additional vaccination will be required.

6. After-care
After-care is necessary for HBV infected patients with a chronic liver inflammation, since they have a high risk of developing cirrhosis of the liver and liver carcinoma. This after-care, which takes place in the Institute of Clinical Pharmacology / Hepatology of the Inselspital, includes the clinical monitoring and the laboratory parameter tests which permit an early diagnosis of the development of cirrhosis or carcinoma of the liver. An early diagnosis of these disorders provides for better treatments.

Hepatitis C Virus Infection

1. Definition
An infection of the liver caused by an RNA virus. This leads to inflammation of the liver (hepatitis). The hepatitis C virus is transmitted through blood products, drug abuse (contaminated needles) and minor injuries (caused by razors, tooth-brushes, etc.). Sexual transmission, insofar as it occurs at all, is extremely rare, as is transmission from mother to child. Expectant mothers with hepatitis C can give birth normally and breast-feed their children. Hepatitis C is very common: it is assumed that globally there are 100,000,000 people infected by it. .

2.Symptoms and Signs
Most patients are unaware of the infection. Fatigue and an occasional tenderness in the upper right abdominal cavity can be present.

3. Complications and Risks
If the illness becomes chronic (i.e. if it lasts longer than a year), it can eventually lead to the formation of scar tissue in the liver (cirrhosis). This process can take between 10 and 30 years. Patients with cirrhosis of the liver can develop cancer of the liver 30 years after the infection; this is quite rare in Switzerland, however. It is estimated that in Switzerland 0.5 to 1 % of the population have hepatitis C, i.e. 35,000 to 70,000 people are affected. It is not known how many of these will develop serious complications (cirrhosis or cancer of the liver). On the basis of various studies, it can be estimated that each year 200 to 300 patients will develop serious complications.

4. Diagnosis and Preliminary Investigation
The family physician can diagnose hepatitis C by the presence of a liver inflammation and by arranging a test for the relevant antibodies. Additional factors which provide important information, especially before the onset of treatment, are the determination of the virus titre, the identification of the genetic type of the virus and a liver biopsy (histology).

5. Therapy and Treatment
The treatment of choice today is the combination of Interferon + Ribavirin. This produces a recovery rate in up to 75 % of the patients. Interferon (IFN) comprises a group of proteins produced by the body as a defensive response to virus infection. Interferon is currently produced through a process of genetic engineering. The major adverse reaction is a sort of 'flu', with fever, aching joints and fatigue. The majority of patients can continue to work normally during therapy. More recent substances, so-called 'virostatics' ('antibiotics' aimed at viruses) can lead to recovery in 50% of patients when used in combination with Interferon. Ribavirin and Amantadine belong to the virostatics, and are presently being tested clinically. For patients with cirrhosis of the liver and severe complications the recommended treatment today is transplantation. This procedure is carried out in Berne at the Clinic for Visceral and Transplant Surgery. Patients with liver cancer can be successfully treated through an operation if the cancer is detected in the early stages.

After-care
After-care is necessary for HCV infected patients with a chronic liver inflammation, since they have a high risk of developing cirrhosis of the liver and liver carcinoma. This after-care, which takes place in the Institute of Clinical Pharmacology / Hepatology of the Inselspital, includes the clinical monitoring and the laboratory parameter tests which permit an early diagnosis of the development of cirrhosis or carcinoma of the liver. An early diagnosis of these disorders provides for better treatments.

2. Alcoholic Liver Disease

1.Definition
Alcoholic liver disease is a chronic disorder of the liver which can result from persistent high consumption of alcohol. Alcoholic liver disorders range from excess fat accumulation to alcohol-induced hepatitis and cirrhosis of the liver.

2. Symptoms and Signs
The main incidence is to be found in patients with alcoholic hepatitis. The symptoms are numerous. They include loss of appetite, nausea, vomiting and weight loss, as well as severe symptoms such as kidney failure, bleeding in the digestive tract and mental problems. Excessive fat and cirrhosis are mostly not symptomatic, and become apparent through their complications (see below).

3. Complications and Risks
Increased alcohol consumption can lead to cirrhosis and cancer of the liver.

4. Diagnosis and Preliminary Investigation
The diagnosis of alcoholic liver disease is established through a study of the case history and by excluding other causes.

5. Therapy, Treatment and Prevention
The best treatment is abstinence from alcohol. The complications of alcoholic liver disease, in particular cirrhosis of the liver, are treated in the appropriate manner.

3. Congenital Liver Disorders / Heamochromatosis

1. Definition
Haemochromatosis is the most common hereditary disease of adults. One in every 10 to 12 people is a healthy carrier of a defective gene, and one of every 400 to 600 people contract the disease. On the basis of the frequency of the gene, we must assume that in Switzerland the number of affected patients is from 17,500 to 20,000. The defective gene causes an uncontrolled absorption of dietary iron and leads to an excessive accumulation of the heavy metal in various organs.

2. Symptoms and Sign
The first symptoms can be apparent in the liver, the joints, the pancreas or other glands. The symptoms are frequently not clear-cut, and the proper diagnosis might not be made if the family physician does not consider the possibility of this disorder. Liver signs are fatigue and upper abdominal cavity tenderness; joints can be inflamed and painful; pancreas symptoms are diabetes (thirst, increased urination); other affected glands could result in impotence.

3. Complications and Risks
Late consequences can affect similar organs to those mentioned above. Cirrhosis (scarring) of the liver can develop. This can in turn lead to various complications, including internal bleeding, excessive abdominal fluid causing swelling (ascites), jaundice (icterus), and liver cancer. Pancreas: diabetes mellitus with all its late complications. Heart: irregular heart-beat, heart failure. Skin: dark pigmentation.

4. Clarification and Preliminary Investigation
The first step is a simple blood test (for iron and iron binding capacity). If the results show levels to be higher than normal, a molecular genetic examination is carried out; in 85% of cases this will reveal whether the disease is present. In some circumstances a liver biopsy is required; this involves the use of a needle for the removal of a small sample of liver tissue which is examined under a microscope to determine the quantity of iron present. If haemochromatosis is diagnosed, it is of the utmost importance that all other family members be examined in order that timely therapeutic measures can be taken to prevent damage to organs.

5. Therapy and Treatment
The excess iron is removed through regular venesection (blood-letting) . The fact that effective treatment is available underlines the absolute need of an early diagnosis. Early detection allows all organ damage to be avoided!

4. Autoimmune Liver Diseases

1. Definition
Liver disorders with unclear causes. It is suspected that autoimmune responses (a form of self-destruction) come into play. Autoimmune disorders include autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Autoimmune hepatitis is especially common among young women. 90% of the cases of primary biliary cirrhosis affect middle-aged women. 70% of cases of primary sclerosing cholangitis affect men, and the disorder is associated with a chronic inflammation of the intestine.

2. Symptoms and Signs
The symptoms vary according to the stage of the disease. Autoimmune hepatitis can be acute, with signs of liver inflammation. Primary biliary cirrhosis and primary sclerosing cholangitis are usually symptom-free at the outset. The main symptom is itching, followed later by signs of liver cirrhosis (excessive abdominal fluid, jaundice).

3. Complications and Risks
Cirrhosis of the liver will eventually appear in the late stages of all autoimmune liver disorders.

4. Diagnosis and Preliminary Investigation
The diagnosis of autoimmune liver disease is usually established through the examination of liver tissue (biopsy). Additional examinations include laboratory tests for determining specific antibodies; the diagnosis of primary sclerosing cholangitis requires an ERCP procedure.

5. Therapy and Treatment
Depending on the stage the disease has reached, drug therapies are possible. The definitive treatment for all autoimmune liver disorders is transplantation.

5. Cirrhoses of the Liver

1. Definition
Cirrhosis of the liver is characterised by a scarring of the liver. The scarring leads to a loss of normal structure (the formation of nodules) and to an increase of connective tissue. Many diseases lead to liver cirrhosis: viral hepatitis (see also hepatitis B and hepatitis C), alcohol, autoimmune disorders, inherited metabolic problem, including haemochromatosis.

2. Symptoms and Signs
Many patients are completely unaware that they have cirrhosis. Others complain of fatigue or of symptoms related to the basic disorder. In most cases the disease is noticed on account of its complications.

3. Complications and Risks
Internal bleeding (for example from varicose veins in the oesophagus, the so-called oesophageal varices), abdominal dropsy (ascites), jaundice (icterus), hepatic encephalopathy (a self-poisoning caused by the liver's failure to filter toxic substances coming from the intestine), muscular atrophy and cramps. Cirrhosis, however, is not a cause of death of many patients.

4. Diagnosis and Preliminary Investigation
The diagnosis is mostly established on the basis of the symptoms caused by the complications.

5. Therapy and Treatment
The complications of cirrhosis can be treated: bleeding through endoscopic procedures (sclerosis and ligation of varicose veins), radiology (TIPS), surgery, drugs (beta-blockers). Diuretics are used to treat the excessive fluid of ascites. Encephalopathy is also treated with drugs. Diet (low in salt, generally high in protein, frequent but small meals, avoidance of alcohol). If appropriate and applicable the underlying disease can be treated. At present the only possibility for a cure is a liver transplant. Ongoing medical research is actively seeking successful drug therapies.

6. Liver Cell Carzinoma

1. Frequency and Cause
Malignant growths of the liver stem in ca 80 to 90% of cases directly from the liver cells and are designated as liver cell cancer. Liver cell cancer is at present one of the most common forms of cancer with an uneven geographical distribution. In Asia it constitutes, with a share of 20 to 30%, the most common of all malignant tumours, whereas in Europe and North America it accounts for only 1 to 2% of such malignancies. Nevertheless the frequency of liver cell cancer is increasing in Europe; in the past 15 years its rate has doubled among women and risen by 50% among men. Liver cell cancer usually originates as a consequence of a chronic liver disorder which has led to cirrhosis (scarring of the liver); this in turn may have been caused by a virus (hepatitis B or C), excessive alcohol consumption, fungus toxins such as aflatoxin , or an inherited disease like haemochromatosis.

2. Symptoms and Signs
Frequently the patient notices nothing. Small liver growths are often discovered only in the course of routine examinations. The first symptoms are pain in the upper abdomen and loss of weight. When excessive abdominal water, jaundice or a perceptible growth are present, the disease is already at an advanced stage.

3. Complications and Risks
Liver cell cancer can begin in the liver in blood and lymph vessels, but can also start in bile ducts and spread to other parts of the liver, to the abdominal cavity, the lungs and elsewhere. If left untreated, this condition can lead to the patient's death within one year of diagnosis.

4. Diagnosis and Preliminary Investigation
Ultrasound, computerised tomography and magnetic resonance imaging are the most important imaging procedures for detecting small liver cell cancers. A so-called tumour-marker, injected into the blood, can be useful for the detection of liver cell cancers.

5. Therapy and Treatment
Only an early and complete removal of the liver tumour offers the prospect of a cure. Since the liver can grow and recover even after the operative removal of up to 70% of its tissue, extended liver operations are now capable of success. When the tumour is removed totally, 5 year survival rates are achieved in 25 to 40% of cases. In the case of existing damage and function loss in the liver, however, such as is the case with, e.g., liver cirrhosis, the technical possibilities of removing liver tissue are severely limited. In these cases, particularly when the tumour is still small, a liver transplantation occasionally offers the chance of a cure. If an operation is not possible, the patient can still often be helped even though a cure is no longer possible. In such cases an injection of pure alcohol directly into the tumour, or the administration of chemotherapy via the hepatic arteries can arrest or retard the growth of the tumour.