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| {{Infobox_Disease | | | {{Infobox_Disease | |
| Name = {{PAGENAME}} | | | Name = {{PAGENAME}} | |
| Image = Cirrhosis 030.jpg | | | Image = Cirrhosis 030.jpg | |
| Caption = Gross, natural color of liver and stomach view from external surfaces, micronodular cirrhosis and hemorrhagic gastritis (as the surgeon would see these in natural color). <br> <small> [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology] </small> | | | Caption = Gross, natural color of liver and stomach view from external surfaces, micronodular cirrhosis and hemorrhagic gastritis (as the surgeon would see these in natural color). <br> <small> [http://www.peir.net Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology] </small> | |
| DiseasesDB = 2729 |
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| ICD10 = {{ICD10|K|70|3|k|70}}, {{ICD10|K|71|7|k|70}}, {{ICD10|K|74||k|70}} |
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| ICD9 = {{ICD9|571}} |
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| ICDO = |
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| OMIM = |
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| MedlinePlus = |
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| MeshID = D008103 |
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| }} | | }} |
| {{SI}}
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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| {{CMG}} | | {{Cirrhosis}} |
| '''Associate Editor-In-Chief:''' {{CZ}}
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| ==Overview==
| | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
| '''Cirrhosis''' is a consequence of chronic [[liver]] [[disease]] characterized by replacement of liver [[Tissue (biology)|tissue]] by fibrotic [[scar]] tissue as well as regenerative [[Nodule (medicine)|nodules]], leading to progressive loss of liver function. Cirrhosis is most commonly caused by [[alcoholism]] and [[hepatitis C]], but has many other possible causes. | |
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| [[Ascites]] (fluid retention in the abdominal cavity) is the most common complication of cirrhosis and is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are [[hepatic encephalopathy]] (confusion and coma) and bleeding from [[esophageal varices]]. Cirrhosis is generally irreversible once it occurs, and treatment generally focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a [[liver transplant]].
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| ==Historical Perspective==
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| ===Etymology===
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| The word "cirrhosis" is a neologism that derives from Greek ''kirrhos'', meaning "tawny" (the orange-yellow colour of the diseased liver). While the clinical entity was known before, it was [[René Laennec]] who gave it the name "cirrhosis" in his 1819 work in which he also describes the stethoscope.<ref>Roguin A. Rene Theophile Hyacinthe Laennec (1781-1826): the man behind the stethoscope. ''Clin Med Res'' 2006;4:230-5. PMID 17048358.</ref>
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| ==Pathophysiology==
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| The liver plays a vital role in synthesis of proteins (e.g. [[serum albumin|albumin]], [[coagulation|clotting factors]] and [[complement system|complement]]), detoxification and storage (e.g. [[vitamin A]]). In addition, it participates in the metabolism of [[lipid]]s and [[carbohydrate]]s.
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| 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.
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| 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. Recent research shows the pivotal role of [[Ito cell|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 (called [[myofibroblast]]) and obstructs blood flow in the circulation. In addition, it secretes [[TGF beta 1|TGF-β<sub>1</sub>]], which leads to a fibrotic response and proliferation of [[connective tissue]]. Furthermore, it disturbs the balance between [[matrix metalloproteinase]]s and the naturally occurring inhibitors (TIMP 1 and 2), leading to [[matrix (biology)|matrix]] breakdown and replacement by connective tissue-secreted matrix.<ref>Iredale JP. Cirrhosis: new research provides a basis for rational and targeted treatments. [[British Medical Journal|BMJ]] 2003;327:143-7. [http://bmj.bmjjournals.com/cgi/content/full/327/7407/143 Fulltext.] PMID 12869458.</ref>
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| The fibrous tissue bands (septa) separate hepatocyte nodules, 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 [[platelet]]s. Portal hypertension is responsible for most severe complications of cirrhosis.
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| == Causes ==
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| === Common Causes ===
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| Cirrhosis has many possible causes; sometimes more than one cause is present in the same patient. In the Western World, chronic alcoholism and hepatitis C are the most common causes.
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| * ''[[Alcoholic liver disease]]'' (ALD). Alcoholic cirrhosis develops in 15% of individuals who drink heavily for more than a decade. There is great variability in the amount of alcohol needed to cause cirrhosis (as little as 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. Patients may also have concurrent [[alcoholic hepatitis]] with fever, hepatomegaly, jaundice, and anorexia. AST and ALT are both elevated but less than 300 IU/L with a AST:ALT ratio > 2.0, a value rarely seen in other liver diseases. [[Liver biopsy]] may show hepatocyte necrosis, Mallory bodies, neutrophilic infiltration with perivenular inflammation.
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| * ''Chronic [[hepatitis C]]''. Infection with this virus causes inflammation of and low grade damage to the liver that over several decades can lead to cirrhosis. Can be diagnosed with serologic assays that detect hepatitis C antibody or viral RNA. The enzyme immunoassay, EIA-2, is the most commonly used screening test in the US.
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| * ''Chronic [[hepatitis B]]''. 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 dependent on the presence of hepatitis B, but accelerates cirrhosis in co-infection. Chronic hepatitis B can be diagnosed with detection of HBsAG > 6 months after initial infection. HBeAG and HBV DNA are determined to assess whether patient will need antiviral therapy.
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| * ''[[Non-alcoholic fatty liver disease|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. This disorder is similar to that of alcoholic liver disease but patient does not have an alcohol history. Biopsy is needed for diagnosis.
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| * ''[[Primary biliary cirrhosis]]''. May be asymptomatic or complain of fatigue, pruritus, and non-jaundice skin hyperpigmentation with hepatomegaly. There is prominent alkaline phosphatase elevation as well as elevations in cholesterol and bilirubin. Gold standard diagnosis is antimitochondrial antibodies with liver biopsy as confirmation if showing florid bile duct lesions. It is more common in women.
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| * ''[[Primary sclerosing cholangitis]]''. PSC is a progressive cholestatic disorder presenting with pruritus, steatorrhea, fat soluble vitamin deficiencies, and metabolic bone disease. There is a strong association with inflammatory bowel disease (IBD), especially ulcerative colitis. Diagnosis is best with contrast cholangiography showing diffuse, multifocal strictures and focal dilation of [[bile duct]]s, leading to a beaded appearance. Non-specific serum immunoglobulins may also be elevated.
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| * ''[[Autoimmune hepatitis]]''. This disease is caused by the immunologic damage to the liver causing inflammation and eventually scarring and cirrhosis. Findings include elevations in serum globulins, especially gamma globulins. Therapy with prednisone +/- azathioprine is beneficial. Cirrhosis due to autoimmune hepatitis still has 10-year survival of 90%+. There is no specific tool to diagnose autoimmune but it can be beneficial to initiate a trial of corticosteroids.
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| * ''[[Hereditary hemochromatosis]]''. Usually presents with family history of cirrhosis, skin hyperpigmentation, diabetes mellitus, pseudogout, and/or cardiomyopathy, all due to signs of [[Iron overload disorder|iron overload]]. Labs will show fasting transferrin saturation of > 60% and ferritin > 300 ng/mL. Genetic testing may be used to identify ''HFE'' mutations. If these are present, biopsy may not need to be performed. Treatment is with [[Venipuncture|phlebotomy]] to lower total body iron levels.
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| * ''[[Wilson's disease]]''. Autosomal recessive disorder characterized by low serum ceruloplasmin and increased hepatic copper content on liver biopsy. May also have [[Kayser-Fleischer ring]]s in the cornea and altered mental status.
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| * ''[[Alpha 1-antitrypsin deficiency]]'' (AAT). Autosomal recessive disorder. Patients may also have COPD, especially if they have a history of [[tobacco smoking]]. Serum AAT levels are low. Recombinant AAT is used to prevent lung disease due to AAT deficiency.
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| * ''Cardiac cirrhosis''. Due to chronic right sided heart failure which leads to liver congestion.
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| * [[Galactosemia]]
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| * [[Glycogen storage disease type IV]]
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| * [[Cystic fibrosis]]
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| * [[Hard and soft drugs|Drug]]s or [[toxin]]s
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| * Certain parasitic infections (such as [[schistosomiasis]])
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| ===Miscellaneous syndromes===
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| * [[Cruveilhier-Baumgarten syndrome]]
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| * [[Haemosiderosis]]
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| * Steatohepatitis, non-alcoholic
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| ===Biochemical abnormalities===
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| * [[Cholestatic jaundice]]
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| ===Congenital conditions===
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| * [[Biliary atresia]]
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| ===Mendelian inherited conditions===
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| * Carbohydrate-deficient glycoprotein syndrome type 1b
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| * [[Caroli disease]]
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| * [[Hemochromatosis]]
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| * [[Sickle cell disease]]
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| ===Autosomal dominant conditions===
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| * [[Alagille syndrome]]
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| * [[Porphyria cutanea tarda]] type 2 (familial)
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| ===Autosomal recessive conditions===
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| * [[Alpers disease]]
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| * [[Alpha-1-antitrypsin deficiency]]
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| * [[Alström syndrome]]
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| * [[Berardinelli lipodystrophy syndrome]]
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| * Carbohydrate deficient glycoprotein syndrome type 1a
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| * Cerebrohepatorenal syndrome
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| * Cholestasis-oedema syndrome, Norwegian type
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| * Cholesterol ester storage disease
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| * Cystic fibrosis
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| * Galactosemia type 1
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| * Glycogenosis type 3
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| * Glycogenosis type 4
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| * Hepatic venoocclusive disease with immunodeficiency
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| * Indian familial childhood cirrhosis
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| * Keratitis-ichthyosis-deafness syndrome, autosomal recessive
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| * Polycystic kidney disease, autosomal recessive
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| * Tyrosinaemia type 1
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| * Wilson disease
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| ===Cardiac and vascular conditions===
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| * Cardiac failure, right sided
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| * Hepatic vein thrombosis
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| ===Autoimmune conditions===
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| * Primary biliary cirrhosis
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| * Primary sclerosing cholangitis
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| ===Trauma, mechanical and physical conditions===
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| * Bile duct stricture
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| ===Helminths and helminthic conditions===
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| * Fasciola hepatica
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| * Schistosoma haematobium
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| * Schistosoma japonicum
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| * Schistosoma mansoni
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| Protozoa and protozoal conditions
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| * Visceral leishmaniasis
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| ===Viruses and viral conditions===
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| * Hepatitis B
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| * Hepatitis C
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| ===Iatrogenic conditions===
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| * Graft versus host disease
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| * Parenteral nutrition
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| ===Drugs, hormones and mediators===
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| * Ethanol
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| * Isoniazid
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| * Methotrexate
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| * Methyldopa
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| * Methyldopate
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| === Causes in Alphabetical Order <ref>Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016</ref> <ref>Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X</ref>===
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| * [[Abetalipoproteinemia]]
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| * [[Alpha-1 Antitrypsin Deficiency]]
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| * Autoimmune cholangiopathy
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| * Autoimmune hepatitis
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| * [[Budd-Chiari Syndrome]]
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| * Congenital hepatic fibrosis
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| * [[Constrictive pericarditis]]
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| * [[Cor Pulmonale]]
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| * [[Cystic Fibrosis]]
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| * [[Drug]]s, [[toxin]]s
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| * [[Galactosemia]]
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| * [[Glycogen-storage disease]]
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| * [[Granulomatous]] [[cirrhosis]]
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| * [[Hemochromatosis]]
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| * Hereditary [[fructose intolerance]]
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| * Hereditary tyrosinosis
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| * [[Hypervitaminosis A]]
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| * Indian childhood cirrhosis
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| * [[Mitral Stenosis]]
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| * Nutritional
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| * [[Porphyria cutanea tarda]]
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| * Posthepatic cirrhosis
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| * Postnecrotic cirrhosis
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| * [[Primary Biliary Cirrhosis]]
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| * [[Primary sclerosing cholangitis]]
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| * [[Sarcoidosis]]
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| * [[Schistosomiasis]]
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| * Secondary biliary cirrhosis
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| * [[Sickle Cell Disease]]
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| * [[Steatohepatitis]]
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| * [[Thalassemia]]
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| * [[Tricuspid insufficiency]]
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| * [[Viral Hepatitis]]
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| * [[Wilson's Disease]]
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| ==Differential Diagnosis==
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| {|
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| |-style="background:silver; color:black"
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| | '''Differential Diagnosis''' || '''Useful Findings'''
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| |-style="background:silver; color:black"
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| | '''Alcoholic cirrhosis''' || '''History EtOH, AST/ALT > 2'''
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| |- style="background:silver; color:black"
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| | '''Chronic Hepatits C Virus (HCV)''' || '''HCV AB'''
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| |-style="background:silver; color:black"
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| | '''Primary Biliary Cirrhosis (PBC)''' || '''Elevated alk phos, AMA+'''
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| |-style="background:silver; color:black"
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| | '''Primary sclerosing cholangitis''' || '''History inflammatory bowel disease (IBD), ANA or ASMA or P-ANCA+'''
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| |-style="background:silver; color:black"
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| | '''Autoimmune hepatitis''' || '''Hypergammaglobulinemia, ANA/ASMA +'''
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| |-style="background:silver; color:black"
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| | '''Chronic Hepatitis B Virus''' || '''HBsAg+, HBeAg may be +'''
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| |-style="background:silver; color:black"
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| | '''Hemochromatosis''' || '''Family history+, Fe/TIBC and ferritin elevated'''
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| |-style="background:silver; color:black"
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| | '''Wilson’s disease''' || '''Family history+, young age, low ceruloplasmin'''
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| |-style="background:silver; color:black"
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| | '''Alpha-1-antitrypsin (AAT) deficiency''' || '''Family history+, young age, low serum AAT'''
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| |}
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| ==Epidemiology and Demographics==
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| Cirrhosis and chronic liver disease were the 10th leading cause of death for men and the 12th for women in the United States in 2001, killing about 27,000 people each year.<ref>Anderson RN, Smith BL. Deaths: leading causes for 2001. ''Natl Vital Stat Rep'' 2003;52:1-85. PMID 14626726.</ref> Also, the cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.
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| Established cirrhosis has a 10-year mortality of 34-66%, largely dependent on the cause of the cirrhosis; alcoholic cirrhosis has a worse prognosis than primary biliary cirrhosis and cirrhosis due to hepatitis. The risk of death due to all causes is increased twelvefold; if one excludes the direct consequences of the liver disease, there is still a fivefold increased risk of death in all disease categories.<ref>Sorensen HT, Thulstrup AM, Mellemkjar L, Jepsen P, Christensen E, Olsen JH, Vilstrup H. Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: a nationwide cohort study in Denmark. ''J Clin Epidemiol'' 2003;56:88-93. PMID 12589875.</ref>
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| Little is known on modulators of cirrhosis risk. Studies have recently suggested that coffee consumption may protect against cirrhosis, especially alcoholic cirrhosis.<ref name=Klatsky>Klatsky AL, Morton C, Udaltsova N, Friedman GD. Coffee, cirrhosis, and transaminase enzymes. ''Arch Intern Med'' 2006;166:1190-5. PMID 16772246.</ref>
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| ==Diagnosis==
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| The [[Gold standard (test)|gold standard]] for diagnosis of cirrhosis is a ''liver biopsy'', through a [[percutaneous]], transjugular, [[laparoscopic]], or fine-needle approach. Histologically cirrhosis can be classified as micronodular, macronodular, or mixed, but this classification has been abandoned since it is nonspecific to the etiology, it may change as the disease progresses, and serological markers are much more specific. However, a biopsy is not necessary if the clinical, laboratory, and radiologic data suggests cirrhosis. Furthermore, there is a small but significant risk to liver biopsy, and cirrhosis itself predisposes for complications due to liver biopsy.<ref>{{cite journal |last=Grant |first=A |coauthors=Neuberger J |year=1999 | title=Guidelines on the use of liver biopsy in clinical practice |journal=Gut |volume=45 |issue=Suppl 4 |pages=1-11 |id=PMID 10485854 |url=http://gut.bmj.com/cgi/content/full/45/suppl_4/IV1|quote=The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68,000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding. }}</ref>
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| ==Symptoms and signs==
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| The following signs and symptoms may occur in the presence of cirrhosis or as a result of the complications of cirrhosis. Many are nonspecific and may occur in other diseases and do not necessarily point to cirrhosis. Likewise, the absence of any does not rule out the possibility of cirrhosis.
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| * ''[[Spider angioma]]ta'' or ''spider nevi''. Vascular lesions consisting of central arteriole surrounded by many smaller vessels due to an increase in [[estradiol]]. These occur in about 33% of cases.<ref name="pmid10423070">{{cite journal |author=Li CP, Lee FY, Hwang SJ, ''et al'' |title=Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function |journal=Scand. J. Gastroenterol. |volume=34 |issue=5 |pages=520-3 |year=1999 |pmid=10423070 |doi=}}</ref>
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| * ''[[Palmar erythema]]''. Exaggerations of normal speckled mottling of the palm, due to altered sex hormone metabolism.
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| * ''Nail changes''.
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| ** ''Muehrcke's nails'' - paired horizontal bands separated by normal color due to [[hypoalbuminemia]] (low production of [[human serum albumin|albumin]]).
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| ** ''Terry's nails'' - proximal two thirds of the nail plate appears white with distal one-third red, also due to hypoalbuminemia
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| ** ''[[Clubbing]]'' --- Angle between the nail plate and proximal nail fold > 180 degrees
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| * ''[[Hypertrophic osteopathy|Hypertrophic osteoarthropathy]]''. Chronic proliferative periostitis of the long bones that can cause considerable pain.
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| * ''[[Dupuytren's contracture]]''. Thickening and shortening of palmar fascia that leads to flexion deformities of the fingers. Thought to be due to fibroblastic proliferation and disorderly collagen deposition. It is relatively common (33% of patients).
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| * ''[[Gynecomastia]]''. Benign proliferation of glandular tissue of male breasts presenting with a rubbery or firm mass extending concentrically from the nipples. This is due to increased estradiol and can occur up to 66% of patients.
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| * ''[[Hypogonadism]]''. Manifested as impotence, infertility, loss of sexual drive, and testicular atrophy due to primary gonadal injury or suppression of hypothalamic or pituitary function.
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| * ''Liver size''. Can be [[hepatomegaly|enlarged]], normal, or shrunken.
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| * ''[[Splenomegaly]]''. Due to congestion of the red pulp as a result of portal hypertension.
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| * ''[[Ascites]]''. Accumulation of fluid in the peritoneal cavity giving rise to flank dullness (needs about 1500 mL to detect flank dullness).
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| * ''[[Caput medusae|Caput medusa]]''. In portal hypertension, the umbilical vein may open. Blood from the portal venous system may be shunted through the periumbilical veins into the umbilical vein and ultimately to the abdominal wall veins, manifesting as caput medusa.
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| * ''Cruveilhier-Baumgarten murmur''. Venous hum heard in epigastric region due to collateral connections between portal system and the remnant of the umbilical vein in portal hypertension.
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| * ''[[Fetor hepaticus]]''. Sweet pungent smell in breath due to increased [[dimethyl sulfide]] due to severe portal-systemic shunting.
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| * ''[[Jaundice]]''. Yellow discoloring of the skin, eye, and mucus membranes due to increased bilirubin (at least 2-3 mg/dL or 30 mmol/L). Urine may also appear dark.
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| * ''[[Asterixis]]''. Bilateral asynchronous flapping of outstretched, dorsiflexed hands seen in patients with hepatic encephalopathy.
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| * ''Other''. Weakness, fatigue, anorexia, weight loss.
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| ===Lab findings===
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| The following findings are typical in cirrhosis:
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| * ''[[Transaminase|Aminotransferase]]s'' - AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferases do not preclude cirrhosis.
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| * ''[[Alkaline phosphatase]]'' - usually slightly elevated.
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| * ''[[Gamma-glutamyl transpeptidase|GGT]]'' -- correlates with AP levels. Typically much higher in chronic liver disease from alcohol.
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| * ''[[Bilirubin]]'' - may elevate as cirrhosis progresses.
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| * ''[[Albumin]]'' - levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver
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| * ''[[Prothrombin time]]'' - increases since the liver synthesizes clotting factors.
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| * ''[[Globulin]]s'' - increased due to shunting of bacterial antigens away from the liver to lymphoid tissue.
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| * ''Serum [[sodium]]'' - [[hyponatremia]] due to inability to excrete free water resulting from high levels of [[vasopressin|ADH]] and [[aldosterone]].
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| * ''[[Thrombocytopenia]]'' - due to both congestive [[splenomegaly]] as well as decreased [[thrombopoietin]] from the [[liver]]. However this rarely results in platelet count < 50,000/mL.
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| * ''[[Leukopenia]] and [[neutropenia]]'' - due to [[splenomegaly]] with splenic margination.
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| * ''[[Coagulation]] defects'' - the [[liver]] produces most of the coagulation factors and thus coagulopathy correlates with worsening liver disease.
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| Other laboratory studies performed in newly diagnosed [[cirrhosis]] may include:
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| * Serology for [[hepatitis]] viruses, [[autoantibody|autoantibodies]] ([[Anti-nuclear antibody|ANA]], anti-smooth muscle, [[Anti-mitochondrial antibody|anti-mitochondria]], anti-LKM)
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| * [[Ferritin]] and [[transferrin saturation]] (markers of iron overload), [[copper]] and [[ceruloplasmin]] (markers of copper overload)
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| * [[Immunoglobulin]] levels (IgG, IgM, IgA) - these are non-specific but may assist in distinguishing various causes
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| * [[Cholesterol]] and [[glucose]]
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| * [[Alpha 1-antitrypsin]]
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| === Electrolyte and Biomarker Studies ===
| | {{CMG}}; {{AE}} {{Cherry}} |
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| * Prothrombin time, albumin
| | {{SK}} Cirrhosis of liver; hepatic fibrosis; hepatic sclerosis |
| * Platelets
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| * Lytes/Creatinine (Cr)
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| *:* Hyponatremia suggests severe disease
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| ===Imaging=== | | == [[Cirrhosis overview|Overview]] == |
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| ''[[Medical ultrasonography|Ultrasound]]'' is routinely used in the evaluation of cirrhosis, where it may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension and [[Budd-Chiari syndrome]] (by assessing flow in the hepatic vein).
| | == [[Cirrhosis historical perspective|Historical Perspective]] == |
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| A new type of device, the FibroScan (transient elastography), uses elastic waves to determine liver stiffness which theoretically can be converted into a liver score based on the METAVIR scale. The FibroScan produces an ultrasound image of the liver (from 20-80mm) along with a pressure reading (in kPa.) The test is much faster than a biopsy (usually last 2.5-5 minutes) and is completely painless. It shows reasonable corellation with the severity of cirrhosis.<ref>{{cite journal |author=Foucher J, Chanteloup E, Vergniol J, ''et al'' |title=Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study |journal=Gut |volume=55 |issue=3 |pages=403-8 |year=2006 |pmid=16020491 |doi=10.1136/gut.2005.069153}}</ref>
| | == [[Cirrhosis classification|Classification]] == |
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| Other tests performed in particular circumstances include abdominal [[Computed tomography|CT]] and liver/bile duct [[Magnetic resonance imaging|MRI]] ([[Magnetic resonance cholangiopancreatography|MRCP]]).
| | == [[Cirrhosis pathophysiology|Pathophysiology]] == |
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| ===Endoscopy=== | | == [[Cirrhosis causes|Causes]] == |
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| [[Gastroscopy]] (endoscopic examination of the [[esophagus]], stomach and [[duodenum]]) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. If these are found, prophylactic local therapy may be applied (sclerotherapy or banding) and [[beta blocker]] treatment may be commenced. | | == [[Cirrhosis differential diagnosis|Differentiating Cirrhosis from other Diseases]] == |
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| ===Computer Tomography=== | | == [[Cirrhosis epidemiology and demographics|Epidemiology and Demographics]] == |
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| <gallery>
| | == [[Cirrhosis risk factors|Risk Factors]] == |
| Image: CT_abdomen_-_liver_cirrhosis_-_01.jpg|Liver cirrhosis as seen on an axial [[computed tomography|CT]] of the abdomen.
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| </gallery>
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| ===MRI=== | | == [[Cirrhosis screening|Screening]] == |
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| <gallery>
| | == [[Cirrhosis natural history, complications and prognosis|Natural History, Complications and Prognosis]] == |
| Image:Cirrhosis-001.jpg|T2
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| Image:Cirrhosis-002.jpg|T2
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| </gallery>
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| ===Other Diagnostic Modalities=== | | == Diagnosis == |
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| If biliary pathology ([[primary sclerosing cholangitis]] - [[PSC]]) is suspected, [[Endoscopic retrograde cholangiopancreatography|ERCP]] may be performed.
| | [[Cirrhosis history and symptoms|History and Symptoms]] | [[Cirrhosis physical examination|Physical Examination]] | [[Cirrhosis laboratory findings|Laboratory Findings]] | [[Cirrhosis electrocardiogram|Electrocardiogram]] | [[Cirrhosis chest x ray|Chest X Ray]] | [[Cirrhosis CT|CT]] | [[Cirrhosis MRI|MRI]] | [[Cirrhosis echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Cirrhosis other imaging findings|Other Imaging Findings]] | [[Cirrhosis other diagnostic studies|Other Diagnostic Studies]] | [[Cirrhosis Clinical prediction rules|Clinical prediction rules]] |
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| Generally [[Magnetic resonance cholangiopancreatography|MRCP]] (MRI of biliary tract and pancreas) is sufficient for diagnosis, but ERCP allows for particular interventions, such as placement of a biliary [[stent]] or extraction of gallstones.
| | == Treatment == |
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| ===Pathology===
| | [[Cirrhosis medical therapy|Medical Therapy]] | [[Cirrhosis surgery|Surgery]] | [[Cirrhosis primary prevention|Primary Prevention]] | [[Cirrhosis secondary prevention|Secondary Prevention]] | [[Cirrhosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Cirrhosis future or investigational therapies|Future or Investigational Therapies]] |
| Macroscopically, the liver may be 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 ([[René Laennec|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.
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| Microscopically, cirrhosis is characterized by regeneration nodules, surrounded by fibrous septa. In these nodules, regenerating hepatocytes are disorderly disposed. Portal tracts, central veins and the radial 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".<ref>[http://www.pathologyatlas.ro/Cirrhosis.html Pathology atlas], "cirrhosis".</ref>
| | ==Case Studies== |
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| ==Grading==
| | [[Cirrhosis case study one|Case #1]] |
| The severity of cirrhosis is commonly classified with the [[Child-Pugh score]]. This score uses [[bilirubin]], [[human serum albumin|albumin]], [[prothrombin time|INR]], presence and severity of [[ascites]] and [[Hepatic encephalopathy|encephalopathy]] to classify patients in class A, B or C; class A has a favourable prognosis, while class C is at high risk of death. It was devised in 1964 by Child and Turcotte and modified in 1973 by Pugh ''et al''.<ref>Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. ''Br J Surg'' 1973;60:646-9. PMID 4541913.</ref>
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| More modern scores, used in the allocation of [[liver transplant]]s but also in other contexts, are the [[Model for End-Stage Liver Disease]] (MELD) score and its pediatric counterpart, the [[Pediatric end-stage liver disease|Pediatric End-Stage Liver Disease]] ([[PELD]]) score.
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| ==Treatment==
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| Traditionally, liver damage from cirrhosis cannot be reversed, but treatment could stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Close follow-up is often necessary. Antibiotics will be prescribed for infections, and various medications can help with itching. Laxatives, such as [[lactulose]], decrease risk of constipation; their role in preventing encephalopathy is limited.
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| ===Treating underlying causes===
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| 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 [[chelation therapy]] (e.g. [[penicillamine]]) to remove the copper.
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| ===Preventing further liver damage===
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| Regardless of underlying cause of cirrhosis, alcohol and [[acetaminophen]], as well as other potentially damaging substances, are discouraged. Vaccination of susceptible patients should be considered for [[Hepatitis A]] and [[Hepatitis B]].
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| === Chronic Pharmacotherapies ===
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| ==== Varices ====
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| * Endoscopic screening in all cirrhotic patients
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| * If varices present--treat with propranolol or nadolol
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| ==== Hepatocellular Cancer ====
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| * Incidence 1-6%/year in HCV-, HBV-, EtOH-related cirrhosis
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| * Screening frequency & benefit controversial
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| * Serum alpha-fetoprotein (AFP) every 6 months (~60% sensitive, ~90% specific)
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| * Ultrasound every 6 months (~75% sensitive, ~90% specific)
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| ===Preventing complications===
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| ====Ascites====
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| {{main|Ascites}}
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| Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). [[Diuretic]]s may be necessary to suppress [[ascites]].
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| ====Esophageal variceal bleeding====
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| {{main|Esophageal varices}}
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| 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 shunt]]ing is occasionally indicated to relieve pressure on the portal vein. As this can worsen encephalopathy, it is reserved for those at low risk of encephalopathy, and is generally regarded only as a bridge to liver transplantation or as a palliative measure.
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| ====Hepatic encephalopathy====
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| {{main|Hepatic encephalopathy}}
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| High-protein food increases the [[Blood urea nitrogen|nitrogen balance]], and would theoretically increase [[encephalopathy]]; in the past, this was therefore eliminated as much as possible from the diet. Recent studies show that this assumption was incorrect, and high-protein foods are even ''encouraged'' to maintain adequate nutrition.
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| ====Hepatorenal syndrome====
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| {{main|Hepatorenal syndrome}}
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| The [[hepatorenal syndrome]] is defined as a urine sodium less than 10 mmol/L and a [[serum creatinine]] > 1.5 mg/dl (or 24 hour [[creatinine clearance]] less than 40 ml/min) after a trial of volume expansion without diuretics.<ref name="pmid3297907">{{cite journal |author=Ginés P, Arroyo V, Quintero E, ''et al'' |title=Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study |journal=Gastroenterology |volume=93 |issue=2 |pages=234-41 |year=1987 |pmid=3297907 |doi=}}</ref>
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| ====Spontaneous bacterial peritonitis====
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| {{main|Spontaneous bacterial peritonitis}}
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| Cirrhotic patients with [[ascites]] are at risk of [[spontaneous bacterial peritonitis]].
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| ===Transplantation===
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| {{main|Liver transplantation}}
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| 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%, depending largely on the severity of disease and other medical problems in the recipient.<ref> [http://www.emedicinehealth.com/liver_transplant/page11_em.htm E-medicine liver transplant outlook and survival rates]</ref> In the United States, the [[Model for End-Stage Liver Disease|MELD score]] ([http://www.unos.org/resources/meldPeldCalculator.asp online calculator])<ref name="pmid2682175">{{cite journal |author=Cosby RL, Yee B, Schrier RW |title=New classification with prognostic value in cirrhotic patients |journal=Mineral and electrolyte metabolism |volume=15 |issue=5 |pages=261-6 |year=1989 |pmid=2682175 |doi=}}</ref> is used to prioritize patients for transplantation. Transplantation necessitates the use of immune suppressants ([[ciclosporin]] or [[tacrolimus]]).
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| ===Decompensated cirrhosis===
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| 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 above.
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| Patients with decompensated cirrhosis generally require admission to [[hospital]], with close monitoring of the [[fluid balance]], mental status, and emphasis on adequate nutrition and medical treatment - often with [[diuretic]]s, [[antibiotic]]s, [[laxative]]s and/or [[enema]]s, [[thiamine]] and occasionally [[glucocorticoid|steroids]], [[acetylcysteine]] and [[pentoxifylline]]. Administration of [[Saline (medicine)|saline]] is generally avoided as it would add to the already high total body sodium content that typically occurs in cirrhosis.
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| ==Complications==
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| As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.
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| * [[Bruising]] and [[hemorrhage|bleeding]] due to decreased production of [[coagulation]] factors.
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| * Jaundice due to decreased processing of [[bilirubin]].
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| * [[Itch]]ing ([[pruritus]]) due to bile products deposited in the skin.
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| * [[Hepatic encephalopathy]] - the liver does not clear [[ammonia]] and related nitrogenous substances from the blood, which are carried to the brain, affecting cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, or changes in sleep habits.
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| * Sensitivity to medication due to decreased metabolism of the active compounds.
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| * [[Hepatocellular carcinoma]] is primary liver cancer, a frequent complication of cirrhosis. It has a high mortality rate.
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| * [[Portal hypertension]] - blood normally carried from the intestines and spleen through the [[hepatic portal vein]] flows more slowly and the pressure increases; this leads to the following complications:
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| ** Ascites - fluid leaks through the vasculature into the abdominal cavity.
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| ** [[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.
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| * Problems in other organs.
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| ** Cirrhosis can cause immune system dysfunction, leading to [[infection]]. Signs and symptoms of infection may be aspecific are more difficult to recognize (e.g. worsening encephalopathy but no fever).
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| ** Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines ([[spontaneous bacterial peritonitis]]).
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| ** [[Hepatorenal syndrome]] - insufficient blood supply to the kidneys, causing [[acute renal failure]]. This complication has a very high mortality (over 50%).
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| ** [[Hepatopulmonary syndrome]] - blood bypassing the normal lung circulation (shunting), leading to [[cyanosis]] and [[dyspnea]] (shortness of breath), characteristically worse on sitting up.<ref name=PHD>Rodriguez-Roisin R, Krowka MJ, Herve P, Fallon MB; ERS Task Force Pulmonary-Hepatic Vascular Disorders (PHD) Scientific Committee. Pulmonary-Hepatic vascular Disorders (PHD). ''Eur Respir J'' 2004;24:861-80. PMID 15516683.</ref>
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| ** [[Portopulmonary hypertension]] - increased blood pressure over the lungs as a consequence of portal hypertension.<ref name=PHD/>
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| == Risk Stratification and Prognosis==
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| {|
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| |-style="background:silver; color:black"
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| | '''Well-Compensated, no EtOH''' || '''35% mortality at 2 years'''
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| |-style="background:silver; color:black"
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| | '''Onset of Ascites''' || '''50% mortality at 2 years'''
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| |- style="background:silver; color:black"
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| | '''Variceal bleeding''' || '''65% mortality at 1 year (35% short-term mortality)'''
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| |}
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| == Primary Prevention ==
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| * Education about hepatotoxins:
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| *:* EtOH
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| *:* Acetaminophen
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| *:* Herbals
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| * Maintenance of adequate caloric intake: 2000-3000 kcal/d
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| * Hepatitis A Virus vaccination, Pneumovax
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| ==Pathological Findings==
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| [http://www.peir.net Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
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| <gallery>
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| Image:Cirrhosis 001.jpg|Cirrhosis: Gross, external view of micronodular cirrhosis
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| Image:Cirrhosis 002.jpg|Cirrhosis: Gross, cut section of previous one (an excellent example)
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| Image:Cirrhosis 003.jpg|Cirrhosis: Gross, close-up image
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| Image:Cirrhosis 004.jpg|Macronodular cirrhosis and hepatoma
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 005.jpg|Cirrhosis: Gross, close-up, natural color (an excellent example)
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| Image:Cirrhosis 006.jpg|Cirrhosis: Gross, close-up (an excellent example)
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| Image:Cirrhosis 007.jpg|Cirrhosis: Gross, close-up view
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| Image:Cirrhosis 008.jpg|Micronodular cirrhosis: Gross, external view (an excellent example)
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 009.jpg|Micronodular cirrhosis: Gross, close-up image
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| Image:Cirrhosis 010.jpg|Micronodular cirrhosis: Gross (an excellent example)
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| Image:Cirrhosis 011.jpg|Macronodular cirrhosis: Gross, natural color (perfect color for cirrhosis), close-up, an excellent example
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| Image:Cirrhosis 012.jpg|Cirrhosis with portocaval shunt: Gross, severe cirrhosis with extensive liver necrosis due to thrombosis of portocaval shunt (well shown)
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 013.jpg|Endstage cirrhosis: Gross, natural color, close-up (an excellent example)
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| Image:Cirrhosis 014.jpg|Endstage cirrhosis: Gross, natural color, close-up view is an excellent example for nodules of yellow-orange liver tissue and broad irregular bands of fibrosis
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| Image:Cirrhosis 015.jpg|Endstage cirrhosis: Gross, natural color, close-up cut surface, very well shown nodules of yellow and necrotic opaque liver tissue with broad and irregular bands of fibrosis (an excellent example)
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| Image:Cirrhosis 016.jpg|Macronodular cirrhosis: Gross, natural color, external view of liver and very enlarged spleen (liver has variable size nodules up to about 2 cm)
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 017.jpg|Macronodular cirrhosis: Gross, natural color, cut surface, large irregular bands of fibrosis with variable size liver cell nodules up to about 8 mm and all necrotic appears to be an end stage liver disease.
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| Image:Cirrhosis 018.jpg|Macronodular cirrhosis: Gross, natural color view of frontal sections of liver and spleen showing a contracted macronodular liver and an enlarged spleen as large as the liver
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| Image:Cirrhosis 019.jpg|Macronodular cirrhosis: Gross, natural color slab of liver
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| Image:Cirrhosis 020.jpg|Fatty change and early cirrhosis: Gross, natural color, rather close-up image showing typical fatty color, and in lighting at lower right of micrography micronodularity is evident (quite good example)
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 021.jpg|Cirrhosis with portal vein thrombosis: Gross, natural color, sectioned liver with portal vein exposed and filled with red thrombus. A good example of end stage cirrhosis.
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| Image:Cirrhosis 022.jpg|Endstage cirrhosis with lobular necrosis: Gross, natural color, very close-up view (an excellent example of alcoholic cirrhosis)
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| Image:Cirrhosis 023.jpg|Micronodular cirrhosis: Gross, natural color view of whole liver through capsule with obvious cirrhosis (note to quite large liver)
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| Image:Cirrhosis 024.jpg|Micronodular cirrhosis: Gross, natural color, view of whole liver showing external surface typical cirrhotic liver (history of alcoholism)
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 025.jpg|Lung: Idiopathic Interstitial Fibrosis: Gross, natural color, an excellent photo of lung cirrhosis (close-up view)
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| Image:Cirrhosis 026.jpg|Endstage cirrhosis: Gross, natural color, slice of liver. Portal vein is opened to show size and patency.
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| Image:Cirrhosis 027.jpg|Endstage cirrhosis: Gross, natural color, severe cirrhosis with bile stasis
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| Image:Cirrhosis 028.jpg|Portal Vein Thrombosis with cirrhosis: Gross, close-up, micronodular cirrhosis with portal vein thrombosis
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| </gallery>
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| <gallery>
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| Image:Cirrhosis 029.jpg|Lung: Hematite: Gross, natural color, external view of "pulmonary cirrhosis" with typical hematite color
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| Image:Cirrhosis 030.jpg|Gross, natural color of liver and stomach view from external surfaces, micronodular cirrhosis and hemorrhagic gastritis (as the surgeon would see these in natural color)
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| </gallery>
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| ==Mikroscopic Images==
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| ===Chronic active hepatitis - Cirrhosis===
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| {{#ev:youtube|CzKGvWZrUpU}}
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| ===Micronodular cirrhosis===
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| {{#ev:youtube|CV8OYeIUXko}}
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| ===Primary biliary cirrhosis===
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| {{#ev:youtube|Jj8ozr_IttM}}
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| ==References==
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| {{Reflist|2}}
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| ==External links==
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| *[http://digestive.niddk.nih.gov/ddiseases/pubs/cirrhosis/ Cirrhosis of the Liver] at the National Digestive Diseases Information Clearinghouse (NDDIC). NIH Publication No. 04-1134, December 2003.
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| *[http://www.nlm.nih.gov/medlineplus/cirrhosis.html] at the National Library of Medicine and the National Institutes of Health. Medline Plus: Cirrhosis -- also called: Hepatic fibrosis
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