Cirrhosis Classification and external resources
Cirrhosis leading to hepatocellular carcinoma (autopsy specimen).
ICD-10	K70.3, K71.7, K74.
ICD-9	571
DiseasesDB	2729
eMedicine	med/3183  radio/175
MeSH	D008103

Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules (lumps that occur as a result of a process in which damaged tissue is regenerated),^[1][2][3] leading to progressive loss of liver function. The liver is a vital organ in the human body and is present in Vertebrates and some other animals A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Tissue is a cellular organizational level intermediate between cells and a complete organism Scars (also called cicatrices) are areas of fibrous tissue that replace normal Skin (or other tissue after injury In Medicine, a nodule refers to a relatively hard roughly spherical abnormal structure Cirrhosis is most commonly caused by alcoholism and hepatitis C, but has many other possible causes. Alcoholism is a term with multiple and sometimes conflicting definitions Hepatitis C is a blood-borne infectious disease that is caused by the Hepatitis C virus ( HCV) affecting the Liver.

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. In Medicine ( Gastroenterology) ascites (also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices. Hepatic encephalopathy (sometimes hepatoencephalopathy) is a potentially-reversible Neuropsychiatric abnormality in the setting of Liver failure, whether In Medicine ( Gastroenterology) esophageal varices are extremely dilated sub-mucosal Veins in the Esophagus. 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. Liver transplantation or hepatic transplantation is the replacement of a diseased Liver with a healthy liver Allograft.

The word "cirrhosis" derives from Greek kirrhos, meaning "tawny" (the orange-yellow colour of the diseased liver). The Ancient Greek language is the historical stage in the development of the Hellenic language family spanning the Archaic (c 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. René-Théophile-Hyacinthe Laennec ( February 17, 1781 - August 13, 1826) was a French Physician and inventor of the Stethoscope The stethoscope (from Greek στηθοσκόπιο, of στήθος stéthos - chest and σκοπή skopé - examination) is an acoustic ^[4]

Contents 1 Signs and symptoms 2 Complications 3 Causes 4 Diagnosis 4.1 Lab findings 4.2 Imaging 4.3 Endoscopy 4.4 Pathology 5 Grading 6 Pathophysiology 7 Treatment 7.1 Treating underlying causes 7.2 Preventing further liver damage 7.3 Preventing complications 7.3.1 Ascites 7.3.2 Esophageal variceal bleeding 7.3.3 Hepatic encephalopathy 7.3.4 Hepatorenal syndrome 7.3.5 Spontaneous bacterial peritonitis 7.4 Transplantation 7.5 Decompensated cirrhosis 8 Epidemiology 9 References 10 External links

Signs and symptoms

Some of 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.

• Spider angiomata or spider nevi. A spider angioma (also known as a nevus araneus, spider nevus, or vascular spider) is a type of Angioma found slightly below the skin's Vascular lesions consisting of a central arteriole surrounded by many smaller vessels due to an increase in estradiol. Estradiol (17β-estradiol (also oestradiol) is a Sex hormone. These occur in about 1/3 of cases. ^[5]
• Palmar erythema. Palmar Erythema is reddening of the palms at the Thenar and Hypothenar eminences Exaggerations of normal speckled mottling of the palm, due to altered sex hormone metabolism.
• Nail changes.
  • Muehrcke's nails - paired horizontal bands separated by normal color due to hypoalbuminemia (low production of albumin). Hypoalbuminemia is a medical condition where levels of albumin in Blood serum are abnormally low Human serum albumin is the most abundant Protein in Human Blood plasma.
  • Terry's nails - proximal two thirds of the nail plate appears white with distal one-third red, also due to hypoalbuminemia
  • Clubbing - angle between the nail plate and proximal nail fold > 180 degrees
• Hypertrophic osteoarthropathy. Terry's nails is a physical finding in which fingernails and/or toenails appear white with a characteristic "ground glass" appearance with no lunula. In Medicine, clubbing, finger clubbing, or digital clubbing is a deformity of the Fingers and fingernails that is associated with a Hypertrophic osteopathy is a bone disease secondary to disease in the lungs Chronic proliferative periostitis of the long bones that can cause considerable pain. Shin splints is a general term used to refer to a painful condition in the shins.
• Dupuytren's contracture. Dupuytren's contracture (also known as Morbus Dupuytren or Dupuytren's disease, and sometimes misspelled as Dupuytren's constricture is a fixed Flexion 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).
• Gynecomastia. Gynecomastia, or gynaecomastia, ˌgaɪnəkoʊˈmæstiə is the development of abnormally large Mammary glands in Males resulting in breast enlargement which 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 in up to 66% of patients.
• Hypogonadism. Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes) Manifested as impotence, infertility, loss of sexual drive, and testicular atrophy due to primary gonadal injury or suppression of hypothalamic or pituitary function.
• Liver size. Can be enlarged, normal, or shrunken. Hepatomegaly is the condition of having an enlarged Liver. It is a nonspecific medical sign having many causes which can broadly be broken down into Infection
• Splenomegaly (increase in size of the spleen). Splenomegaly is an enlargement of the Spleen, which usually lies in the left upper quadrant (LUQ of the Human abdomen. Due to congestion of the red pulp as a result of portal hypertension.
• Ascites. In Medicine ( Gastroenterology) ascites (also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more Accumulation of fluid in the peritoneal cavity giving rise to flank dullness (needs about 1500 mL to detect flank dullness). It may be associated with hydrocele and penile flomation (swelling of the penile shaft) in men. A hydrocele denotes a pathological accumulation of Serous fluid in a bodily cavity
• Caput medusa. Caput medusae is the appearance of distended and engorged Paraumbilical veins which are seen radiating from the Umbilicus across the abdomen to join Systemic 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.
• Cruveilhier-Baumgarten murmur. Venous hum heard in epigastric region (on examination by stethoscope) due to collateral connections between portal system and the remnant of the umbilical vein in portal hypertension.
• Fetor hepaticus. Fetor hepaticus or foetor hepaticus (see spelling differences) also known as breath of the dead, is a condition seen in Portal hypertension Musty odor in breath due to increased dimethyl sulfide. Dimethyl sulfide (DMS or methylthiomethane is an organosulfur compound with the formula (CH32S
• Jaundice. Jaundice, also known as icterus (attributive adjective "icteric" is yellowish discoloration of the Skin, sclerae (whites of the eyes 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.
• Asterixis. Asterixis (also called the flapping tremor) is a Tremor of the wrist when the wrist is extended (dorsiflexion sometimes said to resemble a bird flapping its wings Bilateral asynchronous flapping of outstretched, dorsiflexed hands seen in patients with hepatic encephalopathy.
• Other. Weakness, fatigue, anorexia, weight loss.

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. Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby
• Jaundice due to decreased processing of bilirubin. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism.
• Itching (pruritus) due to bile products deposited in the skin. Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch
• 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. Hepatic encephalopathy (sometimes hepatoencephalopathy) is a potentially-reversible Neuropsychiatric abnormality in the setting of Liver failure, whether Ammonia is a compound with the formula N[[hydrogen H3]] It is normally encountered as a Gas with a characteristic pungent Odor
• Sensitivity to medication due to decreased metabolism of the active compounds.
• Hepatocellular carcinoma is primary liver cancer, a frequent complication of cirrhosis. Hepatocellular carcinoma (HCC also called hepatoma) is a primary malignancy (cancer of the Liver. It has a high mortality rate.
• 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:
  • Ascites - fluid leaks through the vasculature into the abdominal cavity. In Medicine, portal hypertension is Hypertension (high blood pressure in the Portal vein and its branches The hepatic portal vein (often portal vein for short is a Portal vein in the human body that drains blood from the Digestive system and its associated
  • Esophageal varices - collateral portal blood flow through vessels in the stomach and esophagus. In Medicine ( Gastroenterology) esophageal varices are extremely dilated sub-mucosal Veins in the 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. An infection is the detrimental Colonization of a host Organism by a foreign Species. Signs and symptoms of infection may be aspecific are more difficult to recognize (e. g. worsening encephalopathy but no fever).
  • Fluid in the abdomen (ascites) may become infected with bacteria normally present in the intestines (spontaneous bacterial peritonitis). Spontaneous bacterial peritonitis (SBP is a form of Peritonitis that occurs in patients with Cirrhosis.
  • Hepatorenal syndrome - insufficient blood supply to the kidneys, causing acute renal failure. Hepatorenal syndrome (HRS refers to Acute renal failure that occurs in the setting of Cirrhosis or Fulminant Liver failure, sometimes also associated Acute renal failure ( ARF) also known as acute kidney failure or acute kidney injury, is a rapid loss of Renal function due to damage to the This complication has a very high mortality (over 50%).
  • Hepatopulmonary syndrome - blood bypassing the normal lung circulation (shunting), leading to cyanosis and dyspnea (shortness of breath), characteristically worse on sitting up. In Medicine, hepatopulmonary syndrome is a Syndrome of Shortness of breath and Hypoxemia (low oxygen levels in the blood of the arteries caused Cyanosis is a blue coloration of the Skin and mucous membranes due to the presence of deoxygenated Hemoglobin in Blood vessels near the skin surface Dyspnea or dyspnoea (pronounced disp-nee-ah, IPA /dɪsp'niə/ from Latin dyspnoea, from Greek dyspnoia from ^[6]
  • Portopulmonary hypertension - increased blood pressure over the lungs as a consequence of portal hypertension. Portopulmonary hypertension is the coexistence of Portal hypertension and Pulmonary hypertension. ^[6]

Causes

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.

• Alcoholic liver disease (ALD). Alcoholic liver disease is the major cause of Liver disease in Western countries (in Asian countries viral Hepatitis is the major cause 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. The liver is a vital organ in the human body and is present in Vertebrates and some other animals Patients may also have concurrent alcoholic hepatitis with fever, hepatomegaly, jaundice, and anorexia. Alcoholic hepatitis is Hepatitis (inflammation of the liver due to excessive intake of alcohol. 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. A biopsy (in Greek: βίος life and όψη look/appearance is a Medical test involving the removal of cells or tissues
• Chronic hepatitis C. Hepatitis C is a blood-borne infectious disease that is caused by the Hepatitis C virus ( HCV) affecting the Liver. 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.
• 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.
• Non-alcoholic steatohepatitis (NASH). Non-alcoholic fatty liver disease ( NAFLD) is fatty inflammation of the Liver when this is not due to excessive alcohol use 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.
• Primary biliary cirrhosis. Primary biliary cirrhosis is an Autoimmune disease of the Liver marked by the slow progressive destruction of the small bile ducts ( Bile canaliculi) within 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.
• Primary sclerosing cholangitis. Primary sclerosing cholangitis ( PSC) is a chronic liver disease caused by progressive Inflammation and scarring of the Bile ducts of the liver 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 ducts, leading to a beaded appearance. A bile duct is any of a number of long tube-like structures that carry Bile. Non-specific serum immunoglobulins may also be elevated.
• Autoimmune hepatitis. Anomalous presentation of Human leukocyte antigen (HLA class II on the surface of Hepatocytes possibly due to Genetic predisposition or Acute liver infection 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.
• Hereditary hemochromatosis. Haemochromatosis, also spelled hemochromatosis (see spelling differences) also called siderophilia Usually presents with family history of cirrhosis, skin hyperpigmentation, diabetes mellitus, pseudogout, and/or cardiomyopathy, all due to signs of iron overload. In Medicine, iron overload disorders are Diseases caused by the accumulation of Iron in the body 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 phlebotomy to lower total body iron levels. In medicine venipuncture or venepuncture (also known as phlebotomy, venesection, blood draw, drawing blood or taking blood
• Wilson's disease. Wilson's disease or hepatolenticular degeneration is an Autosomal recessive Genetic disorder in which Copper accumulates in tissues Autosomal recessive disorder characterized by low serum ceruloplasmin and increased hepatic copper content on liver biopsy. May also have Kayser-Fleischer rings in the cornea and altered mental status. Kayser-Fleischer rings (KF rings are dark rings that appear to encircle the iris of the Eye.
• Alpha 1-antitrypsin deficiency (AAT). Alpha 1-antitrypsin deficiency ( α1-antitrypsin deficiency, A1AD or Alpha-1) is a Genetic disorder caused by defective production of Alpha Autosomal recessive disorder. Patients may also have COPD, especially if they have a history of tobacco smoking. Tobacco Smoking is the inhalation of smoke from burned dried or cured leaves of the Tobacco plant most often in the form of a Cigarette. Serum AAT levels are low. Recombinant AAT is used to prevent lung disease due to AAT deficiency.
• Cardiac cirrhosis. Nutmeg liver is the pathological appearance of the liver caused by Chronic passive congestion of the liver secondary to Right heart failure. Due to chronic right sided heart failure which leads to liver congestion.
• Galactosemia
• Glycogen storage disease type IV
• Cystic fibrosis
• Drugs or toxins
• Certain parasitic infections (such as schistosomiasis)

Diagnosis

The gold standard for diagnosis of cirrhosis is a liver biopsy, through a percutaneous, transjugular, laparoscopic, or fine-needle approach. Galactosemia is a rare genetic metabolic disorder which affects an individual's ability to properly metabolize the sugar Galactose. Glycogen storage disease type IV is a very rare Hereditary Metabolic disorder. Cystic fibrosis (also known as CF, mucoviscoidosis, or mucoviscidosis) is a hereditary disease affecting the exocrine (mucus glands of the lungs Hard and soft drugs are loose categories of non-prescription Psychoactive drugs This distinction is used in both official and casual discourse A toxin ( Greek:, toxikon, lit (poison for use on arrows is a Poisonous substance produced by living cells or organisms that is active at very low Schistosomiasis (also known as bilharzia, bilharziosis or snail fever) is a Parasitic disease caused by several species of fluke In Medicine, a gold standard test or criterion standard test is a Diagnostic test or benchmark that is regarded as definitive In Surgery, percutaneous pertains to any medical procedure where access to inner organs or other tissue is done via needle-puncture of the skin rather than by using an "open" Laparoscopic surgery, also called Minimally invasive surgery (MIS, bandaid surgery, Keyhole surgery, or pinhole surgery 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. ^[7]

Lab findings

The following findings are typical in cirrhosis:

• Aminotransferases - AST and ALT are moderately elevated, with AST > ALT. In Biochemistry, a transaminase or an aminotransferase is an Enzyme that Catalyzes a type of reaction between an Amino acid and an However, normal aminotransferases do not preclude cirrhosis.
• Alkaline phosphatase - usually slightly elevated. Alkaline phosphatase ( ALP) ( is a Hydrolase Enzyme responsible for removing Phosphate groups from many types of molecules including
• GGT – correlates with AP levels. Typically much higher in chronic liver disease from alcohol.
• Bilirubin - may elevate as cirrhosis progresses. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism.
• 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. Albumin (Latin albus white refers generally to any Protein with water Solubility, which is moderately soluble in concentrated salt solutions and experiences The prothrombin time ( PT) and its derived measures of prothrombin ratio ( PR) and international normalized ratio ( INR) are measures
• Globulins - increased due to shunting of bacterial antigens away from the liver to lymphoid tissue. Globulin is one of the two types of serum Proteins the other being albumin.
• Serum sodium - hyponatremia due to inability to excrete free water resulting from high levels of ADH and aldosterone. Sodium (ˈsoʊdiəm is an element which has the symbol Na( Latin natrium, from Arabic natrun) atomic number 11 atomic mass 22 Hyponatremia ( British: hyponatraemia) is an Electrolyte disturbance (disturbance of the salts in the blood in which the Sodium ( Natrium Arginine vasopressin ( AVP) also known as vasopressin, argipressin or antidiuretic hormone ( ADH) is a Hormone found in Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water
• Thrombocytopenia - due to both congestive splenomegaly as well as decreased thrombopoietin from the liver. Thrombopoietin (leukemia virus oncogene ligand megakaryocyte growth and development factor, also known as THPO, is a Glycoprotein Hormone produced However, this rarely results in platelet count < 50,000/mL.
• Leukopenia and neutropenia - due to splenomegaly with splenic margination. Leukopenia (or leukocytopenia, or leucopenia, from Greek λευκό -white and πενία -deficiency is a decrease in the number of Neutropenia (adjective neutropenic) from Latin Prefix neutro- and Greek Suffix -πενία (deficiency is
• Coagulation defects - the liver produces most of the coagulation factors and thus coagulopathy correlates with worsening liver disease. Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby

Other laboratory studies performed in newly diagnosed cirrhosis may include:

• Serology for hepatitis viruses, autoantibodies (ANA, anti-smooth muscle, anti-mitochondria, anti-LKM)
• Ferritin and transferrin saturation (markers of iron overload), copper and ceruloplasmin (markers of copper overload)
• Immunoglobulin levels (IgG, IgM, IgA) - these are non-specific but may assist in distinguishing various causes
• Cholesterol and glucose
• Alpha 1-antitrypsin

Imaging

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. Hepatitis (plural hepatitides) implies injury to the Liver characterized by the presence of Inflammatory cells in the tissue of An autoantibody is an Antibody (a type of Protein) manufactured by the Immune system that is directed against one or more of the individual's own proteins Anti-nuclear antibodies ( ANA s also known as anti-nuclear factor or ANF) are antibodies directed against contents of the cell nucleus Anti-mitochondrial antibodies (AMA are Antibodies ( Immunoglobulins) formed against Mitochondria, primarily mitochondria in cells of the Ferritin is a Globular protein complex consisting of 24 protein subunits and is the main intracellular iron storage protein in both Prokaryotes Transferrin saturation, measured as a percentage is a Medical laboratory value Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 Ceruloplasmin (or caeruloplasmin) is officially known as ferroxidase or iron(IIoxygen oxidoreductase. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily Cholesterol is a Lipid found in the Cell membranes and transported in the Blood plasma of all Animals It is an essential component of mammalian Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. alpha 1-Antitrypsin or α1-antitrypsin ( A1AT) is a Glycoprotein and generally known as serum trypsin inhibitor. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension and Budd-Chiari syndrome (by assessing flow in the hepatic vein). In Medicine ( Gastroenterology and Hepatology) Budd-Chiari syndrome is the clinical picture caused by Occlusion of the Hepatic vein

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. ^[8]

Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI (MRCP). Computed tomography (CT is a Medical imaging method employing Tomography. Magnetic resonance cholangiopancreatography ( MRCP) is a Medical imaging technique which uses Magnetic resonance imaging to visualise the biliary

Endoscopy

Gastroscopy (endoscopic examination of the esophagus, stomach and duodenum) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. In Anatomy of the Digestive system, the duodenum is a hollow jointed tube about 25-30 cm (10-12 in long connecting the Stomach to the Jejunum If these are found, prophylactic local therapy may be applied (sclerotherapy or banding) and beta blocker treatment may be commenced. Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias

Rarely diseases of the bile ducts, such as primary sclerosing cholangitis, can be causes of cirrhosis. Primary sclerosing cholangitis ( PSC) is a chronic liver disease caused by progressive Inflammation and scarring of the Bile ducts of the liver Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) can show abnormalities in these patients, and may aid in the diagnosis. Endoscopic retrograde cholangiopancreatography ( ERCP) is a technique that combines the use of Endoscopy and Fluoroscopy to diagnose and treat certain problems Magnetic resonance cholangiopancreatography ( MRCP) is a Medical imaging technique which uses Magnetic resonance imaging to visualise the biliary

Pathology

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). In cellular Pathology, steatosis (also called fatty change, fatty degeneration or adipose degeneration) is the process describing 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. René-Théophile-Hyacinthe Laennec ( February 17, 1781 - August 13, 1826) was a French Physician and inventor of the Stethoscope 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. 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. "^[9]

Grading

The severity of cirrhosis is commonly classified with the Child-Pugh score. In Medicine ( Gastroenterology) the Child-Pugh score (sometimes the Child-Turcotte-Pugh score) is used to assess the prognosis of chronic liver disease This score uses bilirubin, albumin, INR, presence and severity of ascites and 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. Bilirubin (formerly referred to as hematoidin) is the yellow breakdown product of normal Heme Catabolism. Human serum albumin is the most abundant Protein in Human Blood plasma. The prothrombin time ( PT) and its derived measures of prothrombin ratio ( PR) and international normalized ratio ( INR) are measures In Medicine ( Gastroenterology) ascites (also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more Hepatic encephalopathy (sometimes hepatoencephalopathy) is a potentially-reversible Neuropsychiatric abnormality in the setting of Liver failure, whether It was devised in 1964 by Child and Turcotte and modified in 1973 by Pugh et al. ^[10]

More modern scores, used in the allocation of liver transplants 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 (PELD) score. Liver transplantation or hepatic transplantation is the replacement of a diseased Liver with a healthy liver Allograft. The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of Chronic liver disease. Pediatric end-stage liver disease ( PELD) is a disease severity scoring system for children under 18 years of age

The hepatic venous pressure gradient, i. e. the difference in venous pressure between afferent and efferent blood to the liver, also determines severity of cirrhosis, although hard to measure. Blood pressure is also the title of a short story by Damon Runyan in Guys and Dolls and Other Stories A value of 16 mm or more means a greatly increased risk of dying. ^[11]

Pathophysiology

The liver plays a vital role in synthesis of proteins (e. g. albumin, clotting factors and complement), detoxification and storage (e. Serum albumin, often referred to simply as albumin, is the most abundant Plasma protein in humans and other Mammals Albumin is essential for maintaining Coagulation is a complex process by which Blood forms Clots It is an important part of Hemostasis (the cessation of blood loss from a damaged vessel whereby The complement system is a Biochemical cascade that helps clear Pathogens from an organism g. vitamin A). Vitamin A refers to a family of similarly shaped molecules the Retinoids. In addition, it participates in the metabolism of lipids and carbohydrates. Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Carbohydrates (from ' Hydrates of Carbon ' or saccharides ( Greek σάκχαρον meaning " Sugar " are the most

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. Parenchyma is a term used to describe a bulk of a substance It is used in different ways in Animals and in Plants. Recent research shows the pivotal role of stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Ito cells, also known as hepatic stellate cells, lipocytes, or fat-storing cells, are Pericytes found in the Perisinusoidal space Vitamin A refers to a family of similarly shaped molecules the Retinoids. Damage to the hepatic parenchyma leads to activation of the stellate cell, which becomes contractile (called myofibroblast) and obstructs blood flow in the circulation. A Myofibroblast is a cell that is in between a Fibroblast and a Smooth muscle cell in differentiation In addition, it secretes TGF-β₁, which leads to a fibrotic response and proliferation of connective tissue. Transforming growth factor beta 1 or TGF-β1 is a polypeptide member of the Transforming growth factor beta superfamily of Cytokines It is a secreted protein Connective tissue is one of the four types of tissue in traditional classifications (the others being epithelial, Muscle, and Nervous 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. Matrix metalloproteinases (MMPs are Zinc -dependent Endopeptidases other family members are Adamalysins Serralysins and Astacins In Biology, matrix (plural matrices) is the material between animal or plant cells, the material (or tissue in which more specialized structures are embedded ^[12]

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 platelets. The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red Splenomegaly is an enlargement of the Spleen, which usually lies in the left upper quadrant (LUQ of the Human abdomen. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved Portal hypertension is responsible for most severe complications of cirrhosis.

Treatment

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. Lactulose is a synthetic Sugar used in the treatment of Constipation and Hepatic encephalopathy, a complication of Liver disease.

Treating underlying 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 chelation therapy (e. Wilson's disease or hepatolenticular degeneration is an Autosomal recessive Genetic disorder in which Copper accumulates in tissues Chelation therapy is the administration of chelating agents to remove Heavy metals from the body g. penicillamine) to remove the copper. Penicillamine is a Pharmaceutical of the chelator class It is sold under the trade names of Cuprimine and Depen.

Preventing further liver damage

Regardless of underlying cause of cirrhosis, alcohol and acetaminophen, as well as other potentially damaging substances, are discouraged. Paracetamol ( INN) (ˌpærəˈsiːtəmɒl -ˈsɛtə- or acetaminophen ( USAN) is a widely-used Analgesic and Antipyretic Medication Vaccination of susceptible patients should be considered for Hepatitis A and Hepatitis B. Hepatitis A, (formerly known as infectious hepatitis) is an acute Infectious disease of the Liver caused by Hepatitis A virus which is

Preventing complications

Ascites

Main article: Ascites

Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). In Medicine ( Gastroenterology) ascites (also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more Diuretics may be necessary to suppress ascites. A diuretic is any Drug that elevates the rate of urination ( Diuresis) In Medicine ( Gastroenterology) ascites (also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more

Esophageal variceal bleeding

Main article: Esophageal varices

For portal hypertension, propranolol is a commonly used agent to lower blood pressure over the portal system. In Medicine ( Gastroenterology) esophageal varices are extremely dilated sub-mucosal Veins in the Esophagus. Propranolol ( INN) is a non-selective Beta blocker mainly used in the treatment of Hypertension. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the portal vein. A transjugular intrahepatic portosystemic shunt, also TIPS, is an artificial channel in the Liver from the Portal vein to a Hepatic 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.

Hepatic encephalopathy

Main article: Hepatic encephalopathy

High-protein food increases the nitrogen balance, and would theoretically increase encephalopathy; in the past, this was therefore eliminated as much as possible from the diet. Hepatic encephalopathy (sometimes hepatoencephalopathy) is a potentially-reversible Neuropsychiatric abnormality in the setting of Liver failure, whether Nitrogen balance is the measure of Nitrogen output subtracted from nitrogen input Encephalopathy /ɛnˌsɛfəˈlɒpəθi/ literally means Disease of the Brain. Recent studies show that this assumption was incorrect, and high-protein foods are even encouraged to maintain adequate nutrition.

Hepatorenal syndrome

Main article: Hepatorenal syndrome

The hepatorenal syndrome is defined as a urine sodium less than 10 mmol/L and a serum creatinine > 1. Hepatorenal syndrome (HRS refers to Acute renal failure that occurs in the setting of Cirrhosis or Fulminant Liver failure, sometimes also associated Hepatorenal syndrome (HRS refers to Acute renal failure that occurs in the setting of Cirrhosis or Fulminant Liver failure, sometimes also associated Creatinine is a break-down product of Creatine phosphate in Muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass 5 mg/dl (or 24 hour creatinine clearance less than 40 ml/min) after a trial of volume expansion without diuretics. Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. ^[13]

Spontaneous bacterial peritonitis

Main article: Spontaneous bacterial peritonitis

Cirrhotic patients with ascites are at risk of spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis (SBP is a form of Peritonitis that occurs in patients with Cirrhosis. In Medicine ( Gastroenterology) ascites (also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more Spontaneous bacterial peritonitis (SBP is a form of Peritonitis that occurs in patients with Cirrhosis.

Transplantation

Main article: Liver transplantation

If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Liver transplantation or hepatic transplantation is the replacement of a diseased Liver with a healthy liver Allograft. Liver transplantation or hepatic transplantation is the replacement of a diseased Liver with a healthy liver Allograft. 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. ^[14] In the United States, the MELD score (online calculator)^[15] is used to prioritize patients for transplantation. The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of Chronic liver disease. Transplantation necessitates the use of immune suppressants (ciclosporin or tacrolimus). Ciclosporin (ˌsaɪkləˈspɔrən cyclosporine ( USAN) or cyclosporin (former BAN) is an Immunosuppressant drug widely Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after allogenic Organ transplant to reduce the

Decompensated cirrhosis

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. Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that An infection is the detrimental Colonization of a host Organism by a foreign Species. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease It may take the form of any of the complications of cirrhosis listed above.

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 diuretics, antibiotics, laxatives and/or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline. A hospital is an institution for Health care providing treatment by specialised staff and equipment and often but not always providing for Fluid balance is the concept of Human homeostasis that the amount of Fluid lost from the body is equal to the amount of fluid taken in A diuretic is any Drug that elevates the rate of urination ( Diuresis) In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Laxatives (or purgatives) are foods compounds or drugs taken to induce bowel movements or to loosen the stool most often taken to treat Constipation. An enema (plural enemata or enemas) is the procedure of introducing liquids into the Rectum and colon via the Anus. For the similarly spelled pyrimidine see Thymine Thiamin or thiamine, also known as Vitamin B1 Glucocorticoids (GC are a class of Steroid hormones characterised by an ability to bind with the glucocorticoid receptor ( GR) and trigger similar effects Acetylcysteine ( rINN; ˌæsɛtəlˈsɪstiːn əˌsɛtəl- also known as N -acetylcysteine or N -acetyl-L-cysteine (abbreviated Pentoxifylline is the International Nonproprietary Name (INN of a drug sold by Aventis under the name Trental Administration of saline is generally avoided as it would add to the already high total body sodium content that typically occurs in cirrhosis. In Medicine, saline (also saline solution) is a general term referring to a sterile solution of Sodium chloride (table Salt) in water

Epidemiology

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. ^[16] Also, the cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.

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. ^[17]

Little is known on modulators of cirrhosis risk, apart from other diseases that cause liver injury (such as the combination of alcoholic liver disease and chronic viral hepatitis, which may act synergistically in leading to cirrhosis). Studies have recently suggested that coffee consumption may protect against cirrhosis, especially alcoholic cirrhosis. ^[18]

References

External links

• Cirrhosis of the Liver at the National Digestive Diseases Information Clearinghouse (NDDIC). NIH Publication No. 04-1134, December 2003.
• [1] at the National Library of Medicine and the National Institutes of Health. Medline Plus: Cirrhosis – also called: Hepatic fibrosis

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