Symptoms and causes

Symptoms

Liver diseases are a common problem and a major cause of death. Symptoms can be very diverse and range from just discrete blood abnormalities to rapidly evolving liver failure. Because the liver has a large reserve of liver cells (a half-healthy liver provides sufficient liver function) and also easily forms new liver cells (regeneration), symptoms often occur only at an advanced stage of the chronic disease.

Causes

Causes of liver damage are numerous and can be divided into:
- Viral hepatitis e.g. hepatitis A, B, C, D, E
- Auto-immune diseases of the liver and bile ducts e.g. auto-immune hepatitis, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)-
- Nutritional causes e.g. non-alcoholic fatty liver
- Metabolic hereditary causes e.g. hemochromatosis
- Intoxications e.g. due to certain medications

Patients may:
- have no symptoms (only abnormal liver labs)
- develop acute hepatitis
- develop acute liver failure
- develop chronic liver disease with evolution towards liver cirrhosis and portal hypertension
- hepatocellular carcinoma.

Diagnosis and treatment

How is the liver function assessed?

Liver function is evaluated by clinical examination and is based on certain biological parameters. Scoring systems help liver specialists determine the severity of the liver disease and whether a liver transplant is necessary. Two systems are used regularly:

- Model of end-stage liver disease or MELD: A score used to determine the severity of a chronic liver disease based on three blood parameters (bilirubin, creatinine and prothrombin time). This helps physicians to assign organs for transplantation. The higher the MELD score, the more serious the liver disease and the higher the patient is positioned on the transplant waiting list (See also Bilirubin, Creatinine, Prothrombin, Prothrombin Time and Transplantation).

- Child-Pugh score: A score that is used to make a prognosis of chronic liver diseases (especially liver cirrhosis) and to estimate the progression of liver cirrhosis. The score lies between 5 and 15 and is based on five parameters: albumin and bilirubin values, prothrombin time, ascites and hepatic encephalopathy. Patients who have 5 or 6 points obtain a Child-Pugh score of A. This means that they have compensated liver cirrhosis but that the liver is still functioning well. Scores of 7-9 points and >9 points indicate decompensated liver cirrhosis and correspond to Child-Pugh score B and Child-Pugh score C; respectively.

The higher the scores, the more serious the condition and the worse the prognosis.

The MELD score quantifies terminal liver diseases in a transplantation setting. The calculation is based on three test results: bilirubin, creatinine and INR. (Kuntz/Kuntz ยท Hepatology, Textbook and Atlas.)

The Child-Pugh score is used to determine the prognosis of chronic liver disease and includes the clinical assessment of ascites, encephalopathy and several test results: bilirubin, albumin and prothrombin time. (Child, CG, III, Turcotte, JG. Surgery and Portal Hypertension. In: The Liver and portal hypertension, Child, CG III (Eds), W.B. Saunders, Philadelphia 1964. p. 50; Hepatology. 1987;7(4):660; Scand J Gastroenterol. 1989;24(3):269.)

A few terms

Bilirubin: A yellow to orange breakdown product of red blood cells that is excreted in bile and urine. An increased concentration of bilirubin in bodily fluids indicates liver damage; this means that the liver cells do not secrete bile or it indicates a blockage of the bile ducts.

Creatinine: a breakdown product of phosphocreatine. The amount of creatinine produced (in relation to the muscle mass) and the amount excreted daily in the urine remain fairly constant, except in patients who have kidney and muscle disorders. For them, the creatinine concentration in the urine is elevated. The creatine concentration is therefore used to detect and monitor renal insufficiency.

International Normalised Ratio or INR: a standardised measure of blood clotting time.

Albumin
: this protein, which is produced by the liver, is the most common protein in human blood. It plays a key role in regulating intravascular osmotic pressure and in the transport of various substances in the blood. The albumin concentration in the blood is normally monitored by the hepatologist (liver specialist). A reduction in this concentration may be a consequence of liver failure.

Prothrombin
: a coagulation factor involved in the coagulation process. Prothrombin is found in the blood and is produced in the liver. A reduction in the prothrombin value is proportional to the degree of hepatic insufficiency. Prothrombin time, or PT, is a laboratory test that examines how quickly a person's blood coagulates.

How are liver diseases treated?

The treatment of liver diseases depends on their cause and severity. More information can be found in the overview of individual liver diseases.

This presentation contains more detailed explanations on liver fibrosis, liver cirrhosis and complications such as portal hypertension, encephalopathy, ascites and oesophageal varicose veins
.

What are chronic liver diseases and what are their causes?

Liver disorders can be hereditary or they can be caused by factors that damage the liver, such as viruses (e.g. the hepatitis C virus or HCV), toxins, medication, alcohol abuse or autoimmune disorders. Liver disease is characterised by the formation of liver lesions (i.e. damaged liver cells) resulting from the progressive breakdown of liver tissue due to inflammation. The liver disease is considered chronic if it persists for at least six months and is characterised by repeated lesion formation and regeneration. This process can lead to liver fibrosis and, eventually, to liver cirrhosis. The latter condition is characterised by the breakdown of liver tissue, liver fibrosis and lumpy regeneration. As liver disease progresses, more and more scar tissue is formed, making it difficult for the liver to function [1-2]. The consequences of serious liver failure, such as portal hypertension with bleeding varicose veins, encephalopathy, jaundice and ascites, can be life-threatening.

[1] Lim Y.S. and Kim W.R., Clin Liver Dis. 2008; 12(4):733-46.
[2] Huang P.L. Dis Model Mech. 2009 May-June; 2(5-6):231-7.

A few more terms:

Liver fibrosis: The excess formation of fibrotic connective tissue (scar tissue) in response to trauma or organ damage. In liver fibrosis, scar tissue and nodules will gradually replace normal liver tissue, disrupting the normal liver structure and function. This scarring is caused by chronic inflammation of the liver. The degree of liver fibrosis is determined by the severity of the liver damage. Liver cirrhosis is the last stage of progressive liver fibrosis (See also Liver cirrhosis).

Liver cirrhosis: an advanced stage of a pathological disorder caused by long-term damage to the liver in which functional liver cells (hepatocytes) die off. Liver cirrhosis is characterised by a disturbed liver structure. Fibrotic scarring is associated with the unstructured formation of nodules when the liver attempts to regenerate the dead cells. Live cirrhosis can reduce life expectancy and make the patient more susceptible to several complications. If the liver becomes further damaged, liver cirrhosis evolves from a compensated to a decompensated form, and the patient has symptoms of severe liver failure: portal hypertension with bleeding varicose veins, encephalopathy, jaundice or ascites.

Portal hypertension: elevated blood pressure (>12 mm Hg) in the portal vein. The main cause of portal hypertension is an obstruction of the blood circulation in the liver, such as nodules in liver cirrhosis. This condition can have serious consequences, such as ascites, oesophageal varices and haemorrhoids (See also Ascites, oesophageal varices).

Oesophageal varices (oesophageal varices): these are enlarged and abnormally swollen veins in the oesophagus (which connects the throat to the stomach). They lead to a permanent and pathological change of the vessel walls. Usually, we find oesophageal varices in patients who have severe liver disease. In this case, they are the result of the portal hypertension caused by liver cirrhosis. In an attempt to compensate for the blood supply to the liver, the blood flows to smaller vessels, which may leak and rupture. This can cause life-threatening bleeding (See Portal hypertension and liver cirrhosis).

Hepatic encephalopathy: neuropsychiatric disorders in patients who have liver failure, often characterised by cognitive (mental) problems, confusion and a changed level of consciousness.

Ascites: fluid accumulation in the abdominal cavity. A terminal liver disease in combination with portal hypertension can lead to the development of ascites.

Are chronic liver diseases common?

Yes, these conditions are common.

Little has been written about the number of people suffering from liver cirrhosis (prevalence) and the number of newly diagnosed liver cirrhosis patients per year (incidence). Available data suggest that about 0.1% of the European population has liver cirrhosis. This corresponds to 14-26 new cases per 100,000 inhabitants per year and about 170,000 deaths per year. There are, however, major differences within Europe.

Liver cirrhosis can be caused by a viral infection (viral hepatitis e.g. hepatitis B or C) or have a non-viral cause. Causes include exposure to certain chemicals, an autoimmune disease (e.g. autoimmune hepatitis), excessive alcohol consumption or fatty liver.

What are the symptoms of a chronic liver disease?

Many patients suffering from a chronic liver disease do not exhibit any symptoms. If there are any symptoms, they often remain very vague, such as fatigue, itching, nausea, upper right abdominal pain, jaundice, asthenia, muscle pain, joint pain and/or anorexia. However, most symptoms can have different underlying causes. If the condition continues, more specific symptoms may occur. The symptoms are usually associated with hepatic insufficiency, portal hypertension and extrahepatic manifestations. The latter are complications due to the liver disease, but concern other organs.

A few more difficult words

Asthenia: general fatigue and weakness, characterised by a lack of energy and strength.

Anorexia: an eating disorder characterised by a reduced sense of hunger and a reduced appetite. The disorder may have a psychological cause, but is also common in patients suffering from certain acute and/or chronic diseases.

Extrahepatic manifestations: all symptoms, signs or sensations caused by a liver disease that affect organs other than the liver, e.g. the nervous system, immune system, circulatory system, respiratory system, reproductive system, urinary system, endocrine system, lymphatic system, digestive system, musculoskeletal system and skin.

What is the difference between liver fibrosis and liver cirrhosis?

A chronic liver disease is accompanied by constant inflammation of the liver, also known as hepatitis. Chronic inflammation causes liver lesions (i.e. damaged liver cells). During the healing process, fibrotic tissue provides a basis for closing the wound. As the disease progresses, liver fibrosis increases. This is measured by the Metavir score, which ranges from stage F0 (no liver fibrosis) to F4 (liver cirrhosis). Stage F4 is also called liver cirrhosis, the final stage of progressive liver fibrosis. Regenerative nodules and an altered structure of the liver tissue are characteristics of liver cirrhosis [1-3].

[1] Bedossa P. et al, Hepatology 1994; 20(1 Pt1): 15-20.

[2] Poynard T. et al, BMC Gastroenterology 2010, 10: 40.

[3] Sebastiani G. et al, World J Gastroenterol. 2014, 20(32): 11033-53.

Metavir: A scoring system based on the histopathological assessment of a liver biopsy to evaluate the degree of inflammation (A0-A3) and the fibrotic stage (F0-F4). Metavir stages F0-F1 correspond to mild liver damage, metavir stage F2 to significant liver fibrosis of the portal fields and metavir stages F3-F4 to advanced liver fibrosis, pre-liver cirrhosis or liver cirrhosis.

Which factors can influence the progression of liver fibrosis?

Genetic factors may play a role in the progression of liver fibrosis, but there are also other factors, such as alcohol consumption, the viral infection that caused the liver disease, diabetes mellitus and the patient's age, gender and weight. In patients who have hepatitis C, the progression of hepatic fibrosis is strongly influenced by age, alcohol consumption and male gender [1-3].

[1] Poynard T. et al, Lancet 2003;362(9401):2095-100.

[2] Poynard T. and Afdhal, N., AntiVir Ther 2010;15(3):281-91.

[3] Poynard T. et al. Lancet 1997; 349(9055):825-32.

Is liver cirrhosis reversible?

In some cases, liver cirrhosis is partially reversible. However, there is as yet no evidence of a complete cure for liver cirrhosis (i.e. a return to normal liver structure) [1].

[1] Povero D. et al, Histol Histopathol. 2010;25(8):1075-91.

Do I have to follow a special diet if I have a chronic liver disease?

It is advisable not to drink alcohol and to follow a balanced diet, especially for patients suffering from gall bladder problems and gallstones. Be sure to ask your physician for advice on a healthy diet.

Diagnosis

Liver diseases are detected based on the patient's medical history (anamnesis), clinical examinations, blood analysis, imaging (ultrasound, CT scan, MRI scan, endoscopic examination) and tissue examination after a liver puncture. The sequence of these technical examinations and the conversations about the results will be the subject of a careful discussion between the patient and the physician.

How are chronic liver diseases treated?

Treatment depends on the cause and severity of the chronic liver disease. More information can be found in the overview of individual liver diseases and under liver fibrosis/liver cirrhosis.

Treatment centres and specialisations

Digestive Centre

Latest publication date: 21/01/2021
Supervising author: Dr Vanderstraeten Erik