Cirrhosis is a chronic disease of the liver in which liver tissue is replaced by connective tissue, resulting in the loss of liver function. Cirrhosis is caused by damage from toxins (including alcohol), metabolic problems, chronic viral hepatitis or other causes. Cirrhosis is sometimes referred to by its obsolete eponym Laennec's cirrhosis after René Laënnec. Cirrhosis is irreversible but treatment of the causative disease will slow or even halt the damage. The following codes are used with International Statistical Classification of Diseases and Related Health Problems. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... Medicine In medicine, a persistent and lasting condition is said to be chronic (from Greek chronos). ... The liver is an organ in vertebrates, including humans. ... Connective tissue is any type of biological tissue with an extensive extracellular matrix and often serves to support, bind together, and protect organs. ... A toxin, in a scientific context, is a biologically produced substance that causes injury to the health of a living thing on contact or absorption, typically by interacting with biological macromolecules such as enzymes and receptors. ... Bottles of cachaça, a Brazilian alcoholic beverage. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos), the Greek word for change, or overthrow (Etymonline)), is the biochemical modification of chemical compounds in living organisms and cells. ... A virus is a small particle that infects cells in biological organisms. ... Hepatitis is a gastroenterological disease, featuring inflammation of the liver. ... An eponym is a person, whether real or fictitious, whose name has (or is thought to have) given rise to the name of a particular place, tribe, discovery, or other item. ... René-Théophile-Hyacinthe Laënnec (February 17, 1781- August 13, 1826), French physician; inventor of the stethoscope. ...

Cirrhosis may refer to chronic interstitial inflammation of any tissue, but is rarely used for other diseases than cirrhosis of the liver.

Symptoms

Initial symptoms

Early symptoms include red palms, spider angioma (red spots on the upper body), hypertrophy of the parotid glands, and fibrosis of tendons in the hands. Clubbing may develop. Angiomas are benign tumors that are made up of small blood vessels. ... Hypertrophy is the increase of the size of an organ. ... The parotid gland is the largest of the salivary glands. ... Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue. ... // Introduction A tendon or sinew is a tough band of fibrous connective tissue that connects muscle to bone. ... In medicine, clubbing (or digital clubbing) is a deformity of the fingers and fingernails that is associated with a number of diseases, mostly of the heart and lungs. ...

Many people with cirrhosis have no symptoms in the early stages of the disease. However, as scar tissue replaces healthy cells, liver function starts to fail and a person may experience the following symptoms:

• exhaustion
• fatigue
• loss of appetite
• nausea
• weakness
• weight loss
• abdominal pain

Nausea (Greek Ναυτεία) is the sensation of unease and discomfort in the stomach with an urge to vomit. ... In the context of physical health, weight loss is the process of losing body weight, usually by losing fat. ... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ...

Complications

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

• Bruising and bleeding due to decreased production of coagulation factors.
• Jaundice due to decreased processing of bilirubin.
• Itching due to bile products deposited in the skin.
• Hepatic encephalopathy - the liver does not clear ammonia and related nitrogenous substances from the blood, which affect cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
• Sensitivity to medication due to decreased metabolism of the active compounds.
• Hepatocellular carcinoma is primary liver cancer, commonly caused by cirrhosis. It has a high mortality rate.
• Portal hypertension - blood normally carried from the intestines and spleen through the portal vein flows more slowly and the pressure increases; this leads to the following complications:
  • Ascites - fluid leaks through the vasculature into the abdominal cavity.
  • Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. These blood vessels may become enlarged and are more likely to burst.
• Problems in other organs. Cirrhosis can cause immune system dysfunction, leading to infection. Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis). Cirrhosis can also lead to impotence, kidney dysfunction and renal failure (hepatorenal syndrome) and osteoporosis.

A bruise or contusion or ecchymoses is a kind of injury, usually caused by blunt impact, in which the capillaries are damaged, allowing blood to seep into the surrounding tissue. ... Hemorrhage (alternate spelling is Haemorrhage) is the medical term referring to the presence of blood in the interstitial tissues. ... The coagulation of blood is a complex process during which blood forms solid clots. ... Jaundice, technically known as icterus, is yellowing of the skin, sclera (the white of the eyes) and mucous membranes caused by increased levels of bilirubin in the system. ... Bilirubin is a yellow breakdown product of haem (heme in American English). ... An itch (Latin: pruritus) is a sensation felt on an area of skin that makes a person or animal want to scratch it. ... Hepatic encephalopathy is a condition (usually caused by liver cirrhosis and its resultant portal hypertension) where brain cells are damaged by a build-up of toxic substances in the blood. ... Ammonia is a compound of nitrogen and hydrogen with the formula NH3. ... Hepatocellular carcinoma (HCC, also called hepatoma or liver cancer) is a primary malignancy (cancer) of the liver. ... In medicine, portal hypertension is hypertension (high blood pressure) in the portal vein and its branches. ... The portal vein is a major vein in the human body draining blood from the digestive system and its associated glands. ... In medicine (gastroenterology), esophageal varices are extreme dilations of sub mucosal veins in the mucosa of the esophagus in diseases featuring portal hypertension, secondary to cirrhosis primarily. ... An infection is the detrimental colonization of a host organism by a foreign species. ... Spontaneous bacterial peritonitis is a form of peritonitis that occurs in patients with cirrhosis. ... Impotence or, more clinically, erectile dysfunction is the inability to develop or maintain an erection of the penis for satisfactory sexual intercourse regardless of the capability of ejaculation. ... Renal failure is the condition where the kidneys fail to function properly. ... Hepatorenal syndrome (HRS) is liver failure that results in concomitant renal failure. ... Osteoporosis is a disease of bone in which the amount of bone is decreased and the strength of trabecular bone is reduced, cortical bone becomes thin and bones are susceptible to fracture. ...

Causes

Cirrhosis has many possible causes; sometimes more than one cause are present in the same patient. In the Western World, chronic alcoholism and hepatitis C are the most common causes.

• Alcoholic liver disease (ALD). Alcoholic cirrhosis develops after more than a decade of heavy drinking in 15% of all alcoholics. There is great variability in the amount of alcohol needed to cause cirrhosis (3-4 drinks a day in some men and 2-3 in some women). Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates.
• Chronic hepatitis B (with or without D agent). The hepatitis B virus is probably the most common cause of cirrhosis worldwide, especially South-East Asia, but it is less common in the United States and the Western world. Hepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is dependant on the presence of hepatitis B, but accelerates cirrhosis in co-infection.
• Chronic hepatitis C. The hepatitis C virus ranks with alcohol as a major cause of chronic liver disease and cirrhosis. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis.
• Autoimmune hepatitis. This disease is caused by the immune system attacking the liver and causing inflammation, damage, and eventually scarring and cirrhosis.
• Inherited diseases. These interfere with the way the liver produces, processes, and stores enzymes, proteins, metals, and other substances the body needs to function properly.
  • Alpha 1-antitrypsin deficiency
  • Hemochromatosis (iron accumulation)
  • Wilson's disease (copper accumulation)
  • Galactosemia
  • Glycogen storage diseases
  • Cystic fibrosis
• Non-alcoholic steatohepatitis (NASH). In NASH, fat builds up in the liver and eventually causes scar tissue. This type of hepatitis appears to be associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications.
• Diseases that lead to chronic obstruction of the bile ducts. Accumulated bile damages liver tissue:
  • In babies, blocked bile ducts are most commonly caused by biliary atresia, a disease in which the bile ducts are absent or injured.
  • In adults, the most common cause is primary biliary cirrhosis, a disease in which the ducts become inflamed, blocked, and scarred.
  • Secondary biliary cirrhosis can happen after gallbladder surgery if the ducts are inadvertently tied off or injured.
• Drugs or toxins.
• Repeated bouts of heart failure with liver congestion.
• Certain parasitic infections (like schistosomiasis).

Originally known as serum hepatitis, Hepatitis B has only been recognized as such since World War II, and has caused current epidemics in parts of Asia and Africa. ... Hepatitis D is a disease caused by a small circular RNA virus (Hepatitis delta virus); this virus is replication defective and therefore cannot propagate in the absence of another virus. ... Originally known as serum hepatitis, Hepatitis B has only been recognized as such since World War II, and has caused current epidemics in parts of Asia and Africa. ... Hepatitis C is a form of hepatitis (liver inflammation) caused by a virus, the Hepatitis C virus (HCV). ... In medicine (gastroenterology), hepatitis is any disease featuring inflammation of the liver. ... Alpha 1-antitrypsin deficiency (A1AD or Alpha-1) is a genetic disorder caused by reduced levels of alpha 1_antitrypsin in the blood. ... Haemochromatosis, also spelled hemochromatosis, is a hereditary disease characterized by improper processing by the body of dietary iron which causes iron to accumulate in a number of body tissues, eventually causing organ dysfunction. ... Wilsons disease is an autosomal recessive hereditary disease, with an incidence of about 1 in 30,000. ... Galactosemia is a rare genetic metabolic disorder which affects an individuals ability to properly digest the sugar galactose. ... Glycogen storage disease is any one of several inborn errors of metabolism that result from enzyme defects that affect the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. ... As its name signifies, Non-alcoholic steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. ... A bile duct is any of a number of long tube-like structures that carry bile. ... Biliary atresia is a rare condition in newborn children in which the biliary tract between the liver and the intestine is blocked or absent. ... A drug is any substance that can be used to modify a chemical process or processes in the body, for example to treat an illness, relieve a symptom, enhance a performance or ability, or to alter states of mind. ... A toxin, in a scientific context, is a biologically produced substance that causes injury to the health of a living thing on contact or absorption, typically by interacting with biological macromolecules such as enzymes and receptors. ... Skin vesicles created by the penetration of Schistosoma. ...

Diagnosis

The doctor may diagnose cirrhosis on the basis of symptoms, the medical history, a physical examination and laboratory tests. For example, during a physical examination, the doctor may notice that the liver feels harder or larger than usual and order blood tests that can show whether liver disease is present. The term symptom (from the Greek syn = con/plus and pipto = fall, together meaning co-exist) has two similar meanings in the context of physical and mental health: A symptom may loosely be said to be a physical condition which shows that one has a particular illness or disorder (see... In medicine, physical examination, or clinical examination, is the process by which the physician investigates the body of a patient for signs of disease . ...

If looking at the liver is necessary to check for signs of disease, the doctor might order a computerized axial tomography (CAT) scan, ultrasound, magnetic resonance imaging (MRI), or a scan of the liver using a radioisotope (a harmless radioactive substance that highlights the liver).

A liver biopsy will confirm the diagnosis. For a biopsy, the doctor uses a needle to take a tiny sample of liver tissue, then examines it under the microscope for scarring or other signs of disease. A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... 1852 microscope Compound microscope made by John Cuff in 1750 A microscope (Greek: micron = small and scopos = aim) is an instrument for viewing objects that are too small to be seen by the naked or unaided eye. ...

Pathology

Macroscopically, the liver is initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm and the color is often yellow (if associates steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular and mixed cirrhosis. In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. The mixed cirrhosis consists in a variety of nodules with different sizes. Microscopically, cirrhosis is characterized by regeneration nodules, surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. Biliary tract, central vein and the radiar pattern of hepatocytes are absent. Fibrous septa are important and may present inflammatory infiltrate (lymphocytes, macrophages) If it is a secondary biliary cirrhosis, biliary ducts are damaged, proliferated or distended - bile stasis. These dilated ducts contain inspissated bile which appear as bile casts or bile thrombi (brown-green, amorphous). Bile retention may be found also in the parenchyma, as the so called "bile lakes". 1 In cellular pathology, steatosis is a condition which is a marker of sublethal cellular injury. ...

Pathophysiology

The liver plays a vital role in synthesis of proteins (e.g. albumin, clotting factors and complement), detoxification and storage (e.g. vitamin A). In addition, it participates in the metabolism of lipids and carbohydrates. You may be looking for albumen, or egg white. ... The coagulation of blood is a complex process during which blood forms solid clots. ... The complement system is a complex biochemical cascade of the immune system, leading to cytolysis, chemotaxis, opsonization and inflammation, it can mark pathogens for phagocytosis. ... Retinol, the dietary form of vitamin A, is a fat-soluble, antioxidant vitamin important in vision and bone growth. ... Figure 1: Structure of a Lipid. ... Carbohydrates (literally hydrates of carbon) are chemical compounds that act as the primary biological means of storing or consuming energy, other forms being fat and protein. ...

Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are still fully reversible.

The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma, blocking the portal flow of blood through the organ and disturbing normal function. Iredale (2003) summarises the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile and obstructs blood flow in the circulation. In addition, it secretes TGF-β₁, which leads to a fibrotic response and proliferation of connective tissue. Furthermore, it disturbs the balance between matrix metalloproteinases and the naturally occurring inhibitors (TIMP 1 and 2), leading to matrix breakdown and replacement by connective tissue-secreted matrix. The parenchyma are the functional parts of an organ in the body (i. ... In neuroscience, stellate cells are inhibitory interneurons found within the molecular layer of the cerebellum. ... Retinol, the dietary form of vitamin A, is a fat-soluble, antioxidant vitamin important in vision and bone growth. ... Transforming growth factor (TGF) is one of many characterized growth factors that exist in nature. ... Connective tissue is any type of biological tissue with an extensive extracellular matrix and often serves to support, bind together, and protect organs. ... Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, which are capable of collectively degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules. ... In biology, the word matrix is used for the material between animal or plant cells, or generally the material (or tissue) in which more specialized structures are embedded, and also specifically for one part of the mitochondrion. ...

The fibrous tissue forms nodes, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. Portal hypertension is responsible for most severe complications of cirrhosis. The spleen is a ductless, vertebrate gland that is not necessary for life but is closely associated with the circulatory system, where it functions in the destruction of old red blood cells and removal of other debris from the bloodstream, and also in holding a reservoir of blood. ... A 250 ml bag of newly collected platelets. ...

Treatment

Liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. Close follow-up is often necessary. Alcohol and acetaminophen, as well as other potentially damaging substances, are discouraged. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). High-protein food increases the nitrogen balance and may increase encephalopathy; this is therefore eliminated as much as possible from the diet. Acetaminophen (USAN) or paracetamol (INN), is a popular analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. ...

Treatment exists of elimination of the causes and preventing complications:

• Elimination of causes: alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with medications to remove the copper.
• Preventing complications. Diuretics may be necessary to suppress ascites. Antibiotics will be prescribed for infections, and various medications can help with itching. Laxatives decrease risk of encephalopathy. For portal hypertension, propranolol is a commonly used agent to lower blood pressure over the portal system.

In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the portal vein. A diuretic is any drug that tends to increase the flow of urine from the body (diuresis). ... Propranolol (Inderal®) is a non-selective beta blocker (i. ...

If complications cannot be controlled or when the liver ceases functioning, a liver transplant is necessary. Survival from liver transplantation has been improving over the 1990s and is now around 90%, depending largely on the severity of disease in the recipient. Transplantation necessitates the use of immune suppressants (cyclosporine or tacrolimus). // Events and trends The 1990s are generally classified as having moved slightly away from the more conservative 1980s, but otherwise retaining the same mindset. ... Cyclosporine, Ciclosporin (INN), or cyclosporin (former BAN), is an immunosuppressant drug. ... Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug. ...

Epidemiology

In the United States, cirrhosis is the twelfth leading cause of death by disease, killing about 26,000 people each year. As it is a chronic disease with often frequent and severe complications, the cost of cirrhosis in terms of quality of life, hospital admissions, and lost productivity is high.

References

• National Digestive Diseases Information Clearinghouse (NDDIC) article Cirrhosis of the Liver NIH Publication No. 04-1134, December 2003
• Iredale JP. Cirrhosis: new research provides a basis for rational and targeted treatments. BMJ 2003;327:143-7. Fulltext.PMID 12869458
• Photos at: Atlas of Pathology

The British Medical Journal (BMJ) is a medical journal published weekly in the United Kingdom by the British Medical Association (BMA). ...