Cirrhosis

Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as

Diagnosis is based on blood tests, medical imaging, and liver biopsy.^[2][1]

Cirrhosis affected about 2.8 million people and resulted in 1.3 million deaths in 2015.[4]^[5] Of these deaths, alcohol caused 348,000 (27%), hepatitis C caused 326,000 (25%), and hepatitis B caused 371,000 (28%).^[5] In the United States, more men die of cirrhosis than women.^[1] The first known description of the condition is by Hippocrates in the fifth century BCE.^[17] The term "cirrhosis" was derived in 1819 from the Greek word "kirrhos", which describes the yellowish color of a diseased liver.^[18]

Signs and symptoms

Cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge.^[8] Some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea.^[8] Early signs may also include redness on the palms known as palmer erythema.^[10] People may also feel discomfort in the right upper abdomen around the liver.^[8]

As cirrhosis progresses, symptoms can include neurological changes.^[8] This can consist of cognitive impairments, confusion, memory loss, sleep disorders, and personality changes.^[8]Steatorrhea or presence of undigested fats in stool is also a symptom of cirrhosis.^[19]

Worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (

• Spider angiomata or spider nevi happen when there is dilatation of vasculature beneath the skin surface.^[20] There is a central, red spot with reddish extensions that radiate outward. This creates a visual effect that resembles a spider. It occurs in about one-third of cases.^[20] The likely cause is an increase in estrogen.^[20] Cirrhosis causes a rise of estrogen due to increased conversion of androgens into estrogen.^[21]
• Palmar erythema, a reddening of the palm below the thumb and little finger, is seen in about 23% of cirrhosis cases, and results from increased circulating estrogen levels.^[22]
• Gynecomastia, or the increase of breast size in men, is caused by increased estradiol (a potent type of estrogen).^[23] This can occur in up to two-thirds of cases.^[24]
• Hypogonadism signifies a decreased functionality of the gonads.^[25] This can result in impotence, infertility, loss of sexual drive, and testicular atrophy. A swollen scrotum may also be evident.^[26]
• Liver size can be enlarged, normal, or shrunken in people with cirrhosis.^[27] As the disease progresses, the liver will typically shrink due to the result of scarring.^[28]
• increased levels of bilirubin, which may also cause the urine to be dark-colored.^[29]

Liver cirrhosis makes it hard for blood to flow in the portal venous system.^[30] This resistance creates a backup of blood and increases pressure.^[30] This results in portal hypertension. Effects of portal hypertension include:

• Ascites is a build-up of fluid in the peritoneal cavity in the abdomen^[31]
• An enlarged spleen in 35–50% of cases^[6]
• Esophageal varices and gastric varices result from collateral circulation in the esophagus and stomach (a process called portacaval anastomosis).^[32] When the blood vessels in this circulation become enlarged, they are called varices. Varices are more likely to rupture at this point.^[7] Variceal rupture often leads to severe bleeding, which can be fatal.^[32]
• paraumbilical collateral veins due to portal hypertension.^[30] Blood from the portal venous system may be forced through the paraumbilical veins and ultimately to the abdominal wall veins. The created pattern resembles the head of Medusa, hence the name.^[7]
• Cruveilhier-Baumgarten bruit is bruit in the epigastric region (on examination by stethoscope).^[33] It is due to extra connections forming between the portal system and the paraumbilical veins.^[33]

• bleeding can result from decreased production of clotting factors^[36]
• Hepatic encephalopathy (HE) occurs when ammonia and related substances build up in the blood.^[36] This build-up affects brain function when they are not cleared from the blood by the liver. Symptoms can include unresponsiveness, forgetfulness, trouble concentrating, changes in sleep habits, or psychosis. One classic physical examination finding is asterixis.^[24] This is the asynchronous flapping of outstretched, dorsiflexed hands.^[24] Fetor hepaticus is a musty breath odor resulting from increased dimethyl sulfide and is a feature of HE.^[37]
• Sensitivity to medication can be caused by decreased metabolism of the active compounds
• Acute kidney injury (particularly hepatorenal syndrome)^[24]
• Cachexia associated with muscle wasting and weakness ^[36]

Causes

Cirrhosis has many possible causes, and more than one cause may be present.

• AST and ALT blood levels are both elevated, but at less than 300 IU/liter, with an AST:ALT ratio > 2.0, a value rarely seen in other liver diseases.^[42] In the United States, 40% of cirrhosis-related deaths are due to alcohol.^[24]
• In
  steroids.^[43][44] Though similar in signs to alcoholic liver disease, no history of notable alcohol use is found. Blood tests and medical imaging are used to diagnose NAFLD and NASH, and sometimes a liver biopsy is needed.^[31]
• Chronic hepatitis C, an infection with the hepatitis C virus, causes inflammation of the liver and a variable grade of damage to the organ.^[36] Over several decades, this inflammation and damage can lead to cirrhosis. Among people with chronic hepatitis C, 20–30% develop cirrhosis.^[36][24] Cirrhosis caused by hepatitis C and alcoholic liver disease are the most common reasons for liver transplant.^[24] Both hepatitis C and hepatitis B–related cirrhosis can also be attributed with heroin addiction.^[45]
• Chronic hepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis.^[36] Hepatitis D is dependent on the presence of hepatitis B and accelerates cirrhosis in co-infection.^[36]

Less common causes

• In
  anti-mitochondrial antibodies.^[46]
• Primary sclerosing cholangitis is a disorder of the bile ducts that presents with pruritus, steatorrhea, fat-soluble vitamin deficiencies, and metabolic bone disease. A strong association with inflammatory bowel disease is seen, especially ulcerative colitis.^[24]
• lymphocytes. This causes inflammation and eventually scarring as well as cirrhosis. Findings include elevations in serum globulins, especially gamma globulins.^[24]
• pseudogout, or cardiomyopathy, All of these are due to signs of iron overload.^[24][36]
  Family history of cirrhosis is common as well.
• Kayser-Fleischer rings in the cornea and altered mental status.^[43][36]
• Indian childhood cirrhosis is a form of neonatal cholestasis characterized by deposition of copper in the liver ^[36][47]
• autosomal co-dominant disorder of low levels of the enzyme alpha-1 antitrypsin^[24]
• Cardiac cirrhosis is due to chronic right-sided heart failure, which leads to liver congestion ^[24]
• Galactosemia^[48]
• Glycogen storage disease type IV^[36]
• Cystic fibrosis^[24]
• Hepatotoxic drugs or toxins, such as acetaminophen (paracetamol), methotrexate, or amiodarone^[36]

Pathophysiology

The liver plays a vital role in the synthesis of proteins (for example, albumin, clotting factors and complement), detoxification, and storage (for example, of vitamin A and glycogen). In addition, it participates in the metabolism of lipids and carbohydrates.^{[citation needed]}

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 fully reversible.^{[citation needed]}

The pathological hallmark of cirrhosis is the development of scar tissue that replaces

As this cascade of processes continues, fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, and enlarged, resulting in its retention of platelets, which are needed for normal blood clotting. Portal hypertension is responsible for the most severe complications of cirrhosis.^{[citation needed]}

Diagnosis

The diagnosis of cirrhosis in an individual is based on multiple factors.^[24] Cirrhosis may be suspected from laboratory findings, physical exam, and the person's medical history. Imaging is generally obtained to evaluate the liver.^[24] A liver biopsy will confirm the diagnosis; however, is generally not required.^[36]

Imaging

Rarely are diseases of the bile ducts, such as primary sclerosing cholangitis, causes of cirrhosis.^[36] Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) may aid in the diagnosis.^[36]

Lab findings

The best predictors of cirrhosis are ascites, platelet count < 160,000/mm³, spider angiomata, and a Bonacini cirrhosis discriminant score greater than 7 (as the sum of scores for platelet count,

• Thrombocytopenia, typically multifactorial, is due to alcoholic marrow suppression, sepsis, lack of folate, platelet sequestering in the spleen, and decreased thrombopoietin.^[42] However, this rarely results in a platelet count < 50,000/mL.^[67]
• Aminotransferases AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferase levels do not preclude cirrhosis.^[42]
• Alkaline phosphatase – slightly elevated but less than 2–3 times the upper limit of normal.^{[citation needed]}
• Gamma-glutamyl transferase – correlates with AP levels. Typically much higher in chronic liver disease from alcohol.^[67]
• Bilirubin levels are normal when compensated, but may elevate as cirrhosis progresses.^{[citation needed]}
• Albumin levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver.
• Prothrombin time increases, since the liver synthesizes clotting factors.
• Globulins increase due to shunting of bacterial antigens away from the liver to lymphoid tissue.
• Serum sodium levels fall(hyponatremia) due to inability to excrete free water resulting from high levels of ADH and aldosterone.
• Leukopenia and neutropenia are due to splenomegaly with splenic margination.^{[citation needed]}
• Coagulation defects occur, as the liver produces most of the coagulation factors, thus coagulopathy correlates with worsening liver disease.
• Glucagon is increased in cirrhosis.^[24]
• Vasoactive intestinal peptide is increased as blood is shunted into the intestinal system because of portal hypertension.
• Vasodilators are increased (such as nitric oxide and carbon monoxide) reducing afterload with compensatory increase in cardiac output, mixed venous oxygen saturation.^[68]
• Renin is increased (as well as sodium retention in kidneys) secondary to a fall in systemic vascular resistance.^[69]

FibroTest is a biomarker for fibrosis that may be used instead of a biopsy.^[70]

Other laboratory studies performed in newly diagnosed cirrhosis may include:

• Serology for hepatitis viruses,
  ANA, anti-smooth muscle, antimitochondria
  , anti-LKM)
• Ferritin^[71][72] and transferrin saturation: markers of iron overload as in hemochromatosis, copper and ceruloplasmin: markers of copper overload as in Wilson's disease
• Immunoglobulin
  levels (IgG, IgM, IgA) – these immunoglobins are nonspecific, but may help in distinguishing various causes.
  • IgG level is elevated in chronic hepatitis, alcoholic and autoimmune hepatitis. It's slow and sustained increase is seen in viral hepatitis.
  • IgM significantly increased in primary biliary cirrhosis and moderately increased in viral hepatitis and cirrhosis.
  • IgA is increased in alcoholic cirrhosis and primary biliary cirrhosis.^{[citation needed]}
• Cholesterol and glucose
• Alpha 1-antitrypsin

Markers of inflammation and immune cell activation are typically elevated in cirrhotic patients, especially in the decompensated disease stage:

• C-reactive protein (CRP)^[73]
• Procalcitonin (PCT)^[73]
• Presepsin^[74]
• soluble CD14^[73]
• soluble CD163^[75]
• soluble CD206 (mannose receptor)^[76]
• soluble TREM-1^[77]

A recent study identified 15 microbial biomarkers from the gut microbiota.^[78] These could potentially be used to discriminate patients with liver cirrhosis from healthy individuals.

Pathology

The

• 
  No fibrosis, but mild zone 3 steatosis, in which collagen fibres (pink–red, arrow) are confined to portal tracts (P) (Van Gieson's stain)^[84]
• 
  Histopathology of steatohepatitis with mild fibrosis in the form of fibrous expansion (Van Gieson's stain)^[84]
• 
  Histopathology of steatohepatitis with moderate fibrosis, with thin fibrous bridges (Van Gieson's stain)^[84]
• 
  Histopathology of steatohepatitis with established cirrhosis, with thick bands of fibrosis (Van Gieson's stain)^[84]
• 
  Trichrome stain

  , showing cirrhosis as a nodular texture surrounded by fibrosis (wherein collagen is stained blue).

As cirrhosis can be caused by many different entities which injure the liver in different ways, cause-specific abnormalities may be seen. For example, in

• 
  Micronodular cirrhosis, with diffuse areas of pallor
• 
  Pale macronodules of cirrhosis
• 
  Cirrhosis leading to hepatocellular carcinoma

Grading

The severity of cirrhosis is commonly classified with the

The Child-Pugh score is a validated predictor of mortality after a major surgery.[88] For example, Child class A patients have a 10% mortality rate and Child class B patients have a 30% mortality rate while Child class C patients have a 70–80% mortality rate after abdominal surgery.^[88] Elective surgery is usually reserved for those in Child class A patients. There is an increased risk for child class B individuals and they may require medical optimization. Overall, it is not recommended for Child class C patients to undergo elective surgery.^[88]

In the past, the Child-Pugh classification was used to determine people who were candidates for a liver transplant.^[88] Child-Pugh class B is usually an indication for evaluation for transplant.^[90] However, there were many issues when applying this score to liver transplant eligibility.^[88] Thus, the MELD score was created.

The

MELD-Plus is a further risk score to assess severity of chronic liver disease. It was developed in 2017 as a result of a collaboration between Massachusetts General Hospital and IBM.^[95] Nine variables were identified as effective predictors for 90-day mortality after a discharge from a cirrhosis-related hospital admission.^[95] The variables include all Model for End-Stage Liver Disease (MELD)'s components, as well as sodium, albumin, total cholesterol, white blood cell count, age, and length of stay.^[95]

The

Key prevention strategies for cirrhosis are population-wide interventions to reduce alcohol intake (through pricing strategies, public health campaigns, and personal counseling), programs to reduce the transmission of viral hepatitis, and screening of relatives of people with hereditary liver diseases.[97]

Little is known about factors affecting cirrhosis risk and progression. However, many studies have provided increasing evidence for the protective effects of coffee consumption against the progression of liver disease. These effects are more noticeable in liver disease that is associated with alcohol use disorder. Coffee has antioxidant and antifibrotic effects.

Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. A recommended diet consists of high-protein, high-fiber diet plus supplementation with branched-chain amino acids.[99] Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of constipation. Carvedilol increases survival benefit for people with cirrhosis and portal hypertension.^[100]Diuretics in combination with low salt diet reduce fluid in body which helps reduce oedema.^[101]

Alcoholic cirrhosis caused by alcohol use disorder 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.^{[citation needed]}

Cirrhosis caused by Wilson's disease is treated by removing the copper which builds up in organs.^[2] This is carried out using chelation therapy such as penicillamine. When the cause is an iron overload, iron is removed using a chelation agent such as deferoxamine or by bloodletting.^{[citation needed]}

As of 2021, there are recent studies studying drugs to prevent cirrhosis caused by

Regardless of the underlying cause of cirrhosis, consumption of alcohol and other potentially damaging substances is discouraged. There is no evidence that supports the avoidance or dose reduction of paracetamol in people with compensated cirrhosis; it is thus considered a safe analgesic for said individuals.^[105]

People who are at risk of being exposed to hepatitis A and hepatitis B should consider vaccines against these diseases.^{[citation needed]}

Treating the cause of cirrhosis prevents further damage; for example, giving oral antivirals such as

People with cirrhosis or liver damage are often advised to avoid drugs that could further harm the liver.[107] These include several drugs such as anti-depressants, certain antibiotics, and NSAIDs (like ibuprofen).^[107] These agents are hepatotoxic as they are metabolized by the liver. If a medication that harms the liver is still recommended by a doctor, the dosage can be adjusted to aim for minimal stress on the liver.^{[citation needed]}

Lifestyle

According to a 2018 systematic review based on studies that implemented 8 to 14 week-long exercise programs, there is currently insufficient scientific evidence regarding either the beneficial or harmful effects of physical exercise in people with cirrhosis on all-cause mortality, morbidity (including both serious and non-serious adverse events), health-related quality of life, exercise capacity and anthropomorphic measures.^[108] These conclusions were based on low to very low quality research, which imposes the need to develop further research with higher quality, especially to evaluate its effects on clinical outcomes.^{[citation needed]}

Transplantation

If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%. The survival rate depends largely on the severity of disease and other medical risk factors in the recipient.^[109] In the United States, the MELD score is used to prioritize patients for transplantation.^[110] Transplantation necessitates the use of immune suppressants (ciclosporin or tacrolimus).

Decompensated cirrhosis

Manifestations of decompensation in cirrhosis include gastrointestinal bleeding, hepatic encephalopathy, jaundice or ascites. In patients with previously stable cirrhosis, decompensation may occur due to various causes, such as constipation, infection (of any source), increased alcohol intake, medication, bleeding from esophageal varices or dehydration. It may take the form of any of the complications of cirrhosis listed below.

People with decompensated cirrhosis generally require admission to a hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment – often with diuretics, antibiotics, laxatives or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline.^[111] Administration of saline is avoided, as it would add to the already high total body sodium content that typically occurs in cirrhosis. Life expectancy without liver transplant is low, at most three years.

Palliative care

Palliative care is specialized medical care that focuses on providing patients with relief from the symptoms, pain, and stress of a serious illness, such as cirrhosis. The goal of palliative care is to improve quality of life for both the patient and the patient's family and it is appropriate at any stage and for any type of cirrhosis.^[112]

Especially in the later stages, people with cirrhosis experience significant symptoms such as abdominal swelling, itching, leg edema, and chronic abdominal pain which would be amenable for treatment through palliative care.^[113] Because the disease is not curable without a transplant, palliative care can also help with discussions regarding the person's wishes concerning health care power of attorney, do not resuscitate decisions and life support, and potentially hospice.^[113] Despite proven benefit, people with cirrhosis are rarely referred to palliative care.^[114]

Immunity

Cirrhosis is known to cause immune dysfunction in numerous ways. It impedes the immune system from working normally.^{[citation needed]}

Bleeding and blood clot risk

Cirrhosis can increase the risk of bleeding. The liver produces various proteins in the

The American Gastroenterological Association (AGA) provided recommendations in 2021 in regards to coagulopathy management of cirrhotic patients in certain scenarios.^[115]

• The AGA does not recommend for extensive pre-procedural testing, including repeated measurements of PT/INR or platelet count before patients with stable cirrhosis undergo common gastrointestinal procedures. Nor do they suggest the routine use of blood products, such as platelets, for bleeding prevention.^[115] Cirrhosis is stable when there are no changes in baseline abnormalities of coagulation lab values.
• For patients with stable cirrhosis and low platelet count undergoing common low-risk procedures, the AGA does not recommend the routine use of
  thrombopoietin receptor agonists for bleeding prevention.^[115]
• In hospitalized patients who meet standard guidelines for clot prevention, the AGA suggests standard prevention.[115]
• The AGA does not recommend in routine screening for portal vein thrombosis. If there is a portal vein thrombosis, the AGA suggests treatment by anticoagulation.^[115]
• In the case of cirrhosis with atrial fibrillation, the AGA recommends using anticoagulation over no anticoagulation.^[115]

Complications

Ascites

Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention).

Where salt restriction and the use of diuretics are ineffective then paracentesis may be the preferred option.^[117] This procedure requires the insertion of a plastic tube into the peritoneal cavity. Human serum albumin solution is usually given to prevent complications from the rapid volume reduction. In addition to being more rapid than diuretics, 4–5 liters of paracentesis is more successful in comparison to diuretic therapy.^[116]

Esophageal and gastric variceal bleeding

For portal hypertension, nonselective beta blockers such as propranolol or nadolol are commonly used to lower blood pressure over the portal system. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting (TIPS) is occasionally indicated to relieve pressure on the portal vein. As this shunting can worsen hepatic encephalopathy, it is reserved for those patients at low risk of encephalopathy. TIPS is generally regarded only as a bridge to liver transplantation^[118] or as a palliative measure.^{[citation needed]} Balloon-occluded retrograde transvenous obliteration can be used to treat gastric variceal bleeding.^[119]

Hepatic encephalopathy is a potential complication of cirrhosis.^[24] It may lead to functional neurological impairment ranging from mild confusion to coma.^[24] Hepatic encephalopathy is primarily caused by the accumulation of ammonia in the blood, which causes neurotoxicity when crossing the blood-brain barrier. Ammonia is normally metabolized by the liver; as cirrhosis causes both decreased liver function and increased portosystemic shunting (allowing blood to bypass the liver), systemic ammonia levels gradually rise and lead to encephalopathy.^[123]

Most pharmaceutical approaches to treating hepatic encephalopathy focus on reducing ammonia levels.^[124] Per 2014 guidelines,^[125] the first-line treatment involves the use of lactulose, a non-absorbable disaccharide which decreases the pH level of the colon when it is metabolized by intestinal bacteria. The lower colonic pH causes increased conversion of ammonia into ammonium, which is then excreted from the body.^[126] Rifaximin, an antibiotic that inhibits the function of ammonia-producing bacteria in the gastrointestinal tract,^[127] is recommended for use in combination with lactulose as prophylaxis against recurrent episodes of hepatic encephalopathy.^{[125][128][129]}

In addition to pharmacotherapy, providing proper hydration and nutritional support is also essential.^[124] Appropriate quantities of protein uptake is encouraged.^[130] Several factors may precipitate hepatic encephalopathy, which include alcohol use, excess protein, gastrointestinal bleeding, infection, constipation, and vomiting/diarrhea.^[124] Drugs such as benzodiazepines, diuretics, or narcotics can also precipitate encephalopathic events.^[124] A low protein diet is recommended with gastrointestinal bleeding.^[130]

The severity of hepatic encephalopathy is determined by assessing the patient's mental status. This is generally a subjective assessment, although several attempts at creating criteria to help standardize this assessment have been published. One example is the West Haven criteria, reproduced below.

Hepatorenal syndrome

Hepatorenal syndrome is a serious complication of end-stage cirrhosis when kidney damage is also involved.^[132]

Spontaneous bacterial peritonitis

People with ascites due to cirrhosis are at risk of spontaneous bacterial peritonitis.

Portal hypertensive gastropathy

Cirrhosis can cause immune system dysfunction, leading to infection. Signs and symptoms of infection may be nonspecific and are more difficult to recognize (for example, worsening encephalopathy but no fever).^[134] Moreover, infections in cirrhosis are major triggers for other complications (ascites, variceal bleeding, hepatic encephalopathy, organ failures, death).^{[134][75][77]}

Hepatocellular carcinoma

Each year, approximately one million deaths are due to complications of cirrhosis, making cirrhosis the 11th most common cause of death globally.^[138] Cirrhosis and chronic liver disease were the tenth leading cause of death for men and the twelfth for women in the United States in 2001, killing about 27,000 people each year.^[139]

The cause of cirrhosis can vary; alcohol and non-alcoholic fatty liver disease are main causes in western and industrialized countries, whereas viral hepatitis is the predominant cause in low and middle-income countries.^[138] Cirrhosis is more common in men than in women.^[140] The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.

Globally, age-standardized disability-adjusted life year (DALY) rates have decreased from 1990 to 2017, with the values going from 656.4 years per 100,000 people to 510.7 years per 100,000 people.^[141] In males DALY rates have decreased from 903.1 years per 100,000 population in 1990, to 719.3 years per 100,000 population in 2017; in females the DALY rates have decreased from 415.5 years per 100,000 population in 1990, to 307.6 years per 100,000 population in 2017.^[141] However, globally the total number of DALYs have increased by 10.9 million from 1990 to 2017, reaching the value of 41.4 million DALYs.^[141]

Etymology

The word "cirrhosis" is a neologism derived from Greek: κίρρωσις; kirrhos κιρρός, meaning "yellowish, tawny" (the orange yellow colour of the diseased liver) and the suffix -osis, i.e. "condition" in medical terminology.^{[142][143][144]} While the clinical entity was known before, René Laennec gave it this name in an 1819 paper.^[18]

See also

References