cirrhosis cirrhosis cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. over time, scar tissue can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. the disease typically develops slowly over months or years. early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen. as the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin. the fluid build-up in the abdomen develop spontaneous infections. more serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer. cirrhosisother namescirrhosis of the liver, hepatic cirrhosiscross-section of human liver with cirrhosispronunciation/sɪˈroʊsɪs/ specialtygastroenterology, hepatologysymptomstiredness, itchiness, swelling in the lower legs, jaundice, easily bruising, fluid build-up in the abdomencomplicationsspontaneous bacterial peritonitis, hepatic encephalopathy, dilated veins in the esophagus, liver cancerusual onsetover months or yearsdurationlong termcausesalcoholic liver disease, hepatitis b, hepatitis c, non-alcoholic steatohepatitisdiagnostic methodblood tests, medical imaging, liver biopsypreventionvaccination (such as hepatitis b), avoiding alcohol, losing weight, exercising, low-carbohydrate diet, controlling hypertension and diabetes may help in those with nafld or nashtreatmentdepends on underlying causefrequency2.8 million (2015)deaths1.3 million (2015) cirrhosis is most commonly caused by alcoholic liver disease, non-alcoholic steatohepatitis (nash – the progressive form of non-alcoholic fatty liver disease), heroin abuse, chronic hepatitis b, and chronic hepatitis c. heavy drinking over a number of years can cause alcoholic liver disease. liver damage has also been attributed to heroin usage over an extended period of time as well. nash has a number of causes, including obesity, high blood pressure, abnormal levels of cholesterol, type 2 diabetes, and metabolic syndrome. less common causes of cirrhosis include autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis that disrupts bile duct function, genetic disorders such as wilson's disease and hereditary hemochromatosis, and chronic heart failure with liver congestion. diagnosis is based on blood tests, medical imaging, and liver biopsy. hepatitis b vaccine can prevent hepatitis b and the development of cirrhosis, but no vaccination against hepatitis c is available. no specific treatment for cirrhosis is known, but many of the underlying causes may be treated by a number of medications that may slow or prevent worsening of the condition. hepatitis b and c may be treatable with antiviral medications. avoiding alcohol is recommended in all cases. autoimmune hepatitis may be treated with steroid medications. ursodiol may be useful if the disease is due to blockage of the bile duct. other medications may be useful for complications such as abdominal or leg swelling, hepatic encephalopathy, and dilated esophageal veins. if cirrhosis leads to liver failure, a liver transplant may be an option. cirrhosis affected about 2.8 million people and resulted in 1.3 million deaths in 2015. of these deaths, alcohol caused 348,000, hepatitis c caused 326,000, and hepatitis b caused 371,000. in the united states, more men die of cirrhosis than women. the first known description of the condition is by hippocrates in the fifth century bce. the term "cirrhosis" was derived in 1819 from the greek word "kirrhos," which describes the yellowish color of a diseased liver. signs and symptoms person with cirrhosis and associated pain in the right upper region of the abdomen cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge. some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea. people may also feel discomfort in the right upper abdomen around the liver. as cirrhosis progresses, symptoms can include neurological changes. this can consist of cognitive impairments, confusion, memory loss, sleep disorders, and personality changes. worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (edema) and abdomen (ascites). other signs of advancing disease include itchy skin, bruising easily, dark urine, and yellowing of the skin. liver dysfunction these features are a direct consequence of liver cells not functioning: spider angiomata or spider nevi happen when there is dilatation of vasculature beneath the skin surface. there is a central, red spot with reddish extensions that radiate outward. this creates a visual effect that resembles a spider. it occurs in about one-third of cases. the likely cause is an increase in estrogen. cirrhosis causes a rise of estrogen due to increased conversion of androgens into estrogen. palmar erythema presents as reddish palms below the thumb and little finger. this is seen in about 23% of cirrhosis cases. this is a result of increased estrogen. gynecomastia, or the increase of breast size in men, is caused by increased estradiol (a potent type of estrogen). this can occur in up to two-thirds of cases. hypogonadism signifies a decreased functionality of the gonads. this can result in impotence, infertility, loss of sexual drive, and testicular atrophy. a swollen scrotum may also be evident. liver size can be enlarged, normal, or shrunken in people with cirrhosis. as the disease progresses, the liver will typically shrink due to the result of scarring. jaundice is the yellowing of the skin. it can additionally cause yellowing of mucous membranes notably of the white of the eyes. this phenomenon is due to increased levels of bilirubin, which may also cause the urine to be dark-colored. portal hypertension liver cirrhosis makes it hard for blood to flow in the portal venous system. this resistance creates a backup of blood and increases pressure. this results in portal hypertension. effects of portal hypertension include: ascites is a build-up of fluid in the peritoneal cavity in the abdomen an enlarged spleen in 35 to 50% of cases esophageal varices and gastric varices result from collateral circulation in the esophagus and stomach (a process called portacaval anastomosis). when the blood vessels in this circulation become enlarged, they are called varices. varices are more likely to rupture at this point. variceal rupture often leads to severe bleeding, which can be fatal. caput medusae are dilated paraumbilical collateral veins due to portal hypertension. blood from the portal venous system may be forced through the paraumbilical veins and ultimately to the abdominal wall veins. the created pattern resembles the head of medusa, hence the name. cruveilhier-baumgarten bruit is bruit in the epigastric region (on examination by stethoscope). it is due to extra connections forming between the portal system and the paraumbilical veins. other nonspecific signs some signs that may be present include changes in the nails (such as muehrcke's lines, terry's nails, and nail clubbing). additional changes may be seen in the hands (dupuytren's contracture) as well as the skin/bones (hypertrophic osteoarthropathy). advanced disease as the disease progresses, complications may develop. in some people, these may be the first signs of the disease. bruising and bleeding can result from decreased production of clotting factors hepatic encephalopathy (he) occurs when ammonia and related substances build up in the blood. this build-up affects brain function when they are not cleared from the blood by the liver. symptoms can include unresponsiveness, forgetfulness, trouble concentrating, changes in sleep habits, or psychosis. one classic physical examination finding is asterixis. this is the asynchronous flapping of outstretched, dorsiflexed hands. fetor hepaticus is a musty breath odor resulting from increased dimethyl sulfide and is a feature of he. sensitivity to medication can be caused by decreased metabolism of the active compounds acute kidney injury (particularly hepatorenal syndrome) cachexia associated with muscle wasting and weakness causes cirrhosis has many possible causes, and more than one cause may be present. history taking is of importance in trying to determine the most likely cause. globally, 57% of cirrhosis is attributable to either hepatitis b (30%) or hepatitis c (27%). alcohol use disorder is another major cause, accounting for about 20-40% of the cases. common causes hepatitis c viral particles and the liver alcoholic liver disease (ald, or alcoholic cirrhosis) develops for 10–20% of individuals who drink heavily for a decade or more. alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates. this injury happens through the formation of acetaldehyde from alcohol. acetaldehyde is reactive and leads to the accumulation of other reactive products in the liver. people with ald may also have concurrent alcoholic hepatitis. associated symptoms are fever, hepatomegaly, jaundice, and anorexia. ast and alt blood levels are both elevated, but at less than 300 iu/liter, with an ast:alt ratio > 2.0, a value rarely seen in other liver diseases. in the united states, 40% of cirrhosis-related deaths are due to alcohol. in non-alcoholic fatty liver disease (nafld), fat builds up in the liver and eventually causes scar tissue. this type of disorder can be caused by obesity, diabetes, malnutrition, coronary artery disease, and steroids. though similar in signs to alcoholic liver disease, no history of notable alcohol use is found. blood tests and medical imaging are used to diagnose nafld and nash, and sometimes a liver biopsy is needed. chronic hepatitis c, an infection with the hepatitis c virus, causes inflammation of the liver and a variable grade of damage to the organ. over several decades, this inflammation and damage can lead to cirrhosis. among patients with chronic hepatitis c, 20–30% develop cirrhosis. cirrhosis caused by hepatitis c and alcoholic liver disease are the most common reasons for liver transplant. both hepatitis c and hepatitis b-related cirrhosis can also be attributed with heroin addiction. chronic 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 and accelerates cirrhosis in co-infection. less common causes in primary biliary cholangitis (previously known as primary biliary cirrhosis), the bile ducts become damaged by an autoimmune process. this leads to liver damage. patients may have no symptoms. while other people could present with fatigue, pruritus, or skin hyperpigmentation. the liver is typically enlarged which is referred to as hepatomegaly. rises in alkaline phosphatase, cholesterol, and bilirubin levels occur. patients are usually positive for anti-mitochondrial antibodies. primary sclerosing cholangitis is a disorder of the bile ducts that presents with pruritus, steatorrhea, fat-soluble vitamin deficiencies, and metabolic bone disease. a strong association with inflammatory bowel disease is seen, especially ulcerative colitis. autoimmune hepatitis is caused by an attack of the liver by lymphocytes. this causes inflammation and eventually scarring as well as cirrhosis. findings include elevations in serum globulins, especially gamma globulins. hereditary hemochromatosis usually presents with skin hyperpigmentation, diabetes mellitus, pseudogout, or cardiomyopathy, all of these are due to signs of iron overload. family history of cirrhosis is common as well. wilson's disease is an autosomal recessive disorder characterized by low ceruloplasmin in the blood and increased copper of the liver. copper in the urine is also elevated. patients may also have kayser-fleischer rings in the cornea and altered mental status. indian childhood cirrhosis is a form of neonatal cholestasis characterized by deposition of copper in the liver alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder of low levels of the enzyme alpha-1 antitrypsin cardiac cirrhosis is due to chronic right-sided heart failure, which leads to liver congestion galactosemia glycogen storage disease type iv cystic fibrosis hepatotoxic drugs or toxins, such as acetaminophen (paracetamol), methotrexate, or amiodarone pathophysiology the liver plays a vital role in the synthesis of proteins (for example, albumin, clotting factors and complement), detoxification, and storage (for example, of vitamin a and glycogen). in addition, it participates in the metabolism of lipids and carbohydrates. cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. if the cause is removed at this stage, the changes are fully reversible. the pathological hallmark of cirrhosis is the development of scar tissue that replaces normal tissue. this scar tissue blocks the portal flow of blood through the organ, raising the blood pressure and disturbing normal function. research has shown the pivotal role of the stellate cell, that normally stores vitamin a, in the development of cirrhosis. damage to the liver tissue from inflammation leads to the activation of stellate cells, which increases fibrosis through