Cirrhosis is a late stage of liver fibrosis, which has led to widespread destruction of normal liver architecture. Cirrhosis is characterized by regenerative nodules that are surrounded by dense connective tissue. It is often associated for years with no or only nonspecific symptoms (eg. As loss of appetite, fatigue, weight loss). Late manifestations of cirrhosis are portal hypertension, ascites, and when decompensation occurs, liver failure. To help diagnose a liver biopsy is often required. Cirrhosis is usually regarded as irreversible. The treatment is symptomatic.
Cirrhosis is a leading cause of death worldwide causes of cirrhosis are similar to those of fibrosis (see table: medical conditions and medications that can cause hepatic fibrosis).. In developed countries, the vast majority of cases is caused by chronic Alkoholabususoder chronic hepatitis C. In parts of Asia and Africa the main cause is often a chronic hepatitis B. (Properties of hepatitis viruses for additional information about hepatitis B and C) The classification of cirrhosis of unknown etiology as cryptogenic cirrhosis is becoming increasingly rare as many specific causes are identified (eg. B . chronic hepatitis C, steatohepatitis). Damage to the biliary tract can also lead to cirrhosis, as is the case with mechanical biliary obstruction, primary biliary cirrhosis and primary sclerosing cholangitis.
Cirrhosis is a late stage of liver fibrosis, which has led to widespread destruction of normal liver architecture. Cirrhosis is characterized by regenerative nodules that are surrounded by dense connective tissue. It is often associated for years with no or only nonspecific symptoms (eg. As loss of appetite, fatigue, weight loss). Late manifestations of cirrhosis are portal hypertension, ascites, and when decompensation occurs, liver failure. To help diagnose a liver biopsy is often required. Cirrhosis is usually regarded as irreversible. The treatment is symptomatic. Cirrhosis is a leading cause of death worldwide causes of cirrhosis are similar to those of fibrosis (see table: medical conditions and medications that can cause hepatic fibrosis).. In developed countries, the vast majority of cases is caused by chronic Alkoholabususoder chronic hepatitis C. In parts of Asia and Africa the main cause is often a chronic hepatitis B. (Properties of hepatitis viruses for additional information about hepatitis B and C) The classification of cirrhosis of unknown etiology as cryptogenic cirrhosis is becoming increasingly rare as many specific causes are identified (eg. B . chronic hepatitis C, steatohepatitis). Damage to the biliary tract can also lead to cirrhosis, as is the case with mechanical biliary obstruction, primary biliary cirrhosis and primary sclerosing cholangitis. Pathophysiology There are two primary factors: liver fibrosis regenerating liver cells in response to tissue damage and loss inducing growth factors, hepatocellular hyperplasia (formation of regenerative nodules) and an arterial formation (angiogenesis). Among the substances that regulate the growth, include cytokines and growth factors liver (epithelial growth factor, hepatocyte growth factor, transforming growth factor ?, tumor necrosis factor). Insulin, glucagon and the intrahepatic vasculature determine the form and location of regenerative nodules. Angiogenesis results in the formation of new vessels into the connective tissue sheath which surrounds the regenerative nodules. These vessels combine hepatic artery and portal vein with the Lebervenolen and provide in this way again intrahepatic circulation forth. However, only a relatively small Blufluss can be done by this cycle compared to normal liver. As a result, the portal venous pressure rises. Such circulation disorders contribute to portal hypertension, the verstärtk, because the regenerative nodules compress the hepatic venules. The speed with which the fibrosis develops into cirrhosis and the morphology of cirrhosis vary from patient to patient. Presumably, the reason for these differences is the extent of exposure to the harmful stimulus and the individual response to it. Complications The portal hypertension is the most common serious complication of cirrhosis and can even cause complications, including GI bleeding from the esophagus, stomach, rectal varices and portalhypertensive gastropathy ascites Acute kidney injury (hepatorenal syndrome kidney and electrolyte changes) Pulmonary hypertension (portopulmonale hypertension) ascites is a risk factor for a spontaneous bacterial peritonitis. Portopulmonale hypertension can manifest with symptoms of heart failure. The complications of portal hypertension tend to have significantly increased morbidity and mortality. Cirrhosis can cause more cardiovascular complications. Vasodilation, intrapulmonary right-left shunts and a mismatch between perfusion and ventilation can lead to hypoxia (hepatopulmonary syndrome). The progressive loss of liver architecture affects the function, leading to liver failure. This manifests as coagulopathy, acute renal failure (hepatorenal syndrome) and hepatic encephalopathy. The hepatocytes secrete less bile and thus contribute to cholestasis and jaundice. Less bile in the intestine leading to malabsorption of dietary fat (triglycerides) and fat-soluble vitamins. The malabsorption of vitamin D may contribute to osteoporosis. Malnutrition is common. It is due to anorexia with reduced food intake or in patients with alcoholic liver disease, malabsorption due to pancreatic insufficiency. Blood disorders are common. Anemia usually results bleeding from hypersplenism, chronic gastrointestinal, folic acid deficiency (particularly in patients with alcoholism) and hemolysis. Cirrhosis results in reduced formation of prothrombotic and antithrombotic factors. Hypersplenism and altered expression of thrombopoietin contribute to thrombocytopenia. Thrombocytopenia and reduced formation of clotting factors can make the blood clotting unpredictable, resulting in an increased risk for both bleeding and for thromboembolism (even if the INR is usually increased). Leukopenia are also common; it is mediated by hypersplenism and altered expression of erythropoietin and granulocyte colony stimulating factors. Tips and risks thromboembolic complications should be considered in patients with cirrhosis, even at elevated INR. Hepatocellular carcinoma is a common complication of cirrhosis, especially in the case of those caused by chronic hepatitis B or C, hemochromatosis, alcohol abuse, alpha 1-antitrypsin deficiency, or glycogen storage disease wurde.Histopathologie Cirrhosis is characterized by regenerative nodules and fibrosis. Liver nodules incompletely formed, nodes without fibrosis (nodular regenerative hyperplasia) and congenital hepatic fibrosis (diffuse fibrosis without regenerative nodules) are not a true cirrhosis. A distinction is one micronodular from a makronodulären cirrhosis. The micronodular cirrhosis is characterized by uniform small nodules (<3 mm in diameter) and wide connective tissue strands characterized. The nodes typically lack the lobular organization; the terminal (central) venous and portal fields are destroyed. Over time, often a macronodular cirrhosis develops. The nodes vary in size (3 mm to 5 cm in diameter) and have partly a relatively normal lobular organization of portal fields and terminal venules on. Width connective tissue strands of different thickness surrounding the large knot. From the collapse of the normal liver architecture is expected when there are concentrated in the connective tissue scar numerous portal tracts. A mixed cirrhosis (incomplete septal cirrhosis) combines elements of mikronodulären makronodulären and cirrhosis. The distinction between these morphological types of cirrhosis is of limited clinical relevance. Symptoms and signs A cirrhosis can remain asymptomatic for years. One third of patients never develop symptoms. Often the first symptoms are non-specific; They include general fatigue (due to cytokine release), anorexia, malaise and weight loss (see Table: Common symptoms and discomfort due to complications of cirrhosis). The liver is typically palpable firm consistency and with a blunt edge; but it can also be small and not palpable. Node can not grope in general. Clinical signs suggestive of chronic liver disease or in an alcohol abuse, but are not specific to a cirrhosis, umfasen decrease in muscle, palmar, enlargement of the parotid gland, white nails, clubbing, Dupuytren's contracture, spider nevi (<10 are normal ), gynecomastia, axillary hair loss, testicular atrophy, and peripheral neuropathy. Once complications of cirrhosis develop inexorably follows decompensation. Common symptoms and discomfort due to complications of cirrhosis symptom or sign Possible cause abdominal distention ascites abdominal pain with fever or hepatic encephalopathy (rarely with peritoneal signs) bacterial peritonitis Spontaneous calf pain or turgors, symptoms of a pulmonary embolism thromboembolism clubbing Hepatopulmonary syndrome confusion, lethargy Hepatic encephalopathy dyspnea, hypoxia syndrome Hepatopulmonary Portopulmonale hypertension tiredness, paleness anemia due to bleeding, hypersplenism, malnutrition with deficiency of folic acid (or iron or vitamin B12), chronic illness or effects of alcohol consumption (eg. B. Bone marrow suppression), fluid overload, oliguria, symptoms of kidney failure hepatorenal syndrome fragility (due to a fall caused from the state or from a lower height) osteoporosis symptoms of infection leukopenia jaundice cholestasis petechiae, purpura, bleeding thrombocytopenia aufgr by splenomegaly and portal hypertension or the direct effects of alcohol on the bone marrow coagulopathy due to hepatic impairment and / or vitamin K deficiency pruritus, cholestasis Xanthelasmen Rectal bleeding Rectal varices Portal hypertension splenomegaly Steatorrhea fat malabsorption upper gastrointestinal bleeding esophageal varices Portal hypertensive gastropathy diagnostic liver function tests, coagulation tests, blood count and serological tests for evaluation of viral causes, if necessary Biopsy (z. B. with unclear clinical and non-invasive investigations or if the result of a biopsy can alter the treatment) Sometimes ultrasound elastography or magnetic resonance angiography to identify the cause by clinical evaluation, routine testing for common causes and selective examinations for rarer causes General Procedure the suspicion of the presence of cirrhosis, patients with manifestations of their usual complications (see table: common symptoms and discomfort due to complications of cirrhosis), particularly portal hypertension or ascites. Early cirrhosis should be considered in patients with non-specific symptoms or characteristic laboratory abnormalities that have been discovered by chance during a laboratory examination, especially in patients who have a disease or take a medicine that could cause fibrosis. The clarification is designed to detect the cirrhosis and complications and its cause to ermitteln.Labortests At the beginning of the diagnostic workup are liver function tests, coagulation parameters, blood counts and serological testing for viral causes (eg. As hepatitis B and C). However, laboratory tests alone can only reinforce the suspicion of cirrhosis, but they did not confirm or rule. A liver biopsy is always necessary when a clear diagnosis would lead to better management and earnings. The test results may be normal or non-specific expression changes that occur with complications of cirrhosis or in alcoholism. ALT and AST levels are often slightly increased. Alkaline phosphatase and ?-glutamyl transpeptidase (GGT) are often normal; elevated levels indicate a cholestasis or biliary obstruction. Bilirubin is usually within the normal range, but is increased if the cirrhosis progresses, especially in primary biliary cirrhosis. Decreased serum albumin and a prolonged prothrombin time reflect a decreased liver synthesis power that can usually be observed in end-stage disease. In poor nutritional status albumin may also be low. Serum globulins are increased with inflammatory component at a cirrhosis and other liver diseases. Anemia occurs frequently and is usually normocytic with a high red blood cell distribution width. Often, the anemia is multifactorial; causative factors are chronic gastrointestinal bleeding (usually lead to microcytic anemia), folic acid deficiency (leading to macrocytic anemia, v. a. alcohol abuse), hemolysis and hypersplenism. About the blood can be a leukopenia, thrombocytopenia or pancytopenia nachweisen.Bildgebende diagnostics conventional imaging methods are not very sensitive or specific with regard to the diagnosis of cirrhosis itself, but can often detect its complications. Ultrasound elastography and magnetic resonance elastography are useful in the detection of early cirrhosis, when the results of conventional imaging are ambiguous and portal hypertension is not clear. In advanced cirrhosis, ultrasonography shows a small nodular liver. Sonography also recognizes a portal hypertension and ascites. The CT can detect a nodular architecture, but has no advantage over sonography. Leberszintigramme with 99Tc-sulfur colloid can show an irregular uptake in the liver and increased uptake in spleen and bone marrow. MRI is more expensive than other imaging tests and has little Vorteile.Identifizierung the cause Determining the specific cause of cirrhosis requires important clinical information from the history and examination and selective diagnostics. Alcohol is the most likely cause (increased GOT stronger than GPT) in patients with a documented history of alcoholism and clinical findings such as gynecomastia, spider nevi (telangiectasias) and testicular atrophy at the same time existing laboratory evidence of a corresponding liver damage and liver enzyme induction (significantly increased GGT). Fever, a painful pressure hepatomegaly and jaundice may indicate an alcoholic hepatitis. The detection of hepatitis B surface antigen (HBsAg) and IgG antibodies against hepatitis B (IgG anti-HBc) the existence of a chronic hepatitis B. confirmed the detection of serum antibodies to hepatitis C (anti-HCV) and HCV-RNA can on close hepatitis C virus infection. Most doctors also perform routine tests on the following interference from: autoimmune hepatitis: due to high antinuclear antibody titer (a low titer is non-specific and does not always require further studies) and confirmed by hypergammaglobulinemia and the detection of other autoantibody (eg smooth muscle antibodies. or antibodies against liver / kidney microsomal type 1) hemochromatosis: confirmed by elevated serum Fe and transferrin saturation and possibly by genetic testing Alpha-1-antitrypsin deficiency: confirmed by a low alpha-1 Antitrypsinspiegel in serum and genotyping Clinical calculator: diagnostic criteria for autoimmune hepatitis If these causes are not confirmed are to think of other causes: for detection of anti-mitochondrial Antik rpern (at 95%), there is a suspicion of primary biliary cirrhosis. Using magnetic resonance cholangiopancreatography (MRCP) proven strictures and dilatation of the intrahepatic and extrahepatic bile ducts suggest a primary sclerosing cholangitis. Reduced Serumcoeruloplasmin and corresponding results of copper analyzes may indicate Wilson's disease. Obesity and diabetes in the history point to nonalcoholic steatohepatitis (NASH). Liver biopsy if clinical criteria and noninvasive tests are inconclusive is to perform a liver biopsy in general. For example, if a clinical suspicion of a well-compensated cirrhosis is and the imaging is not unique, a biopsy should be performed to confirm the diagnosis. The sensitivity of the liver biopsy is almost 100%. Not alcohol-related fatty liver (NASH) can be seen on ultrasound Untersuchunge. A (NASH), often associated with obesity, diabetes or the metabolic syndrome, but requires to confirm a liver biopsy. In obvious cases of cirrhosis with significant coagulopathy, portal hypertension, ascites and liver failure, a biopsy is not necessary unless the results would change the management of the disease. In patients with coagulation disorders and thrombocytopenia of transjugular access the safest for the biopsy. If this approach is used, the pressures can be measured and thus the pressure gradient calculated transsinusoidale werden.Überwachung All patients with cirrhosis should be screened regardless of the cause regularly for hepatocellular carcinoma. Currently an abdominal ultrasound is recommended every 6 months; if instructions are found on hepatocellular carcinoma, a contrast-enhanced MRI or a three-phase CT of the abdomen should be made (contrast enhanced CT with separate arterial and venous phase images). Contrast-enhanced sonography appears promising as an alternative to CT or MRI, but is still being investigated in studies in the United States. An upper endoscopy to test for gastroesophageal varices should be performed if the diagnosis is made and then every 2-3 years. Positive results may require treatment or more frequent endoscopic surveillance. Prognosis The prognosis is often poor in individual cases to predict. It depends on factors such as etiology, severity of disease, existence of complications, coexisting diseases, individual factors and response to therapy from. Patients who continue their alcohol consumption, even in small amounts, have a poor prognosis. The Child-Turcotte-Pugh classification takes into account clinical symptoms and laboratory results for the assessment of the severity of the disease, the operational risk and the overall prognosis (see Table: Child-Turcotte-Pugh classification and interpretation of the Child-Turcotte-Pugh classification). Clinical calculator: Child-Pugh classification on the severity of liver disease Child-Pugh classification Turcotte-Clinical and laboratory data of the abnormality degree Points scored * encephalopathy (Grade ) none 1 1-2 2 3-4 3 Ascites None 1 low (or under control by diuretics) 2 min. Moderate, despite treatment diuretics 3 Albumin (g / dl)> 3.5 1 2.8-3.5 2 <2.8 3 Bilir ubin (mg / dl) <1 2 2-3 2> 3 3 PT (sec extended) <4 1 4-6 2> 6 3, or instead of PT INR <1.7 1 1.7-2.3 2> 2.3 3 * degree of risk based on the total number of points: low risk (A): 5-6 moderate risk (B): 7-9 high risk (C ): 10-15 the encephalopathy is classified based on symptoms: grade 1: insomnia, decreased concentration, depression, anxiety or irritability Grade 2 drowsiness, disorientation, poor short-term memory, unusual behavior Grade 3: somnolence, dizziness, amnesia, anger, paranoia or bizarre behavior Grade 4: coma interpretation of the Child-Turcotte-Pugh classification points risk (degrees) survival rate (%) 1 -year survival 2-year survival 5-6 low (A) 100 85 7-9 moderate (B) 80 60 10-15 High (C) 45 35 However, there are in the Child-Pugh classification Turcotte restrictions; For example, the assessment of the severity of ascites and encephalopathy is subjective; interrater reliability of the results is thus reduced. In contrast, the MELD estimates (Model for End-Stage Liver Disease) scores the severity of end stage liver disease, regardless of the cause, solely on the basis of objective results of laboratory tests from: serum creatinine, serum total bilirubin and INR. The MELD score is used to determine candidates for the distribution of available organs liver transplant. Variants of the MELD scores are occasionally used for other purposes (eg. As to estimate the 90-day mortality risk in patients with alcoholic hepatitis, for predicting postoperative mortality risk in patients with cirrhosis). A variant, including serum sodium (MELDNa) ??has been extensively studied, but is not commonly used in the US in the clinic. Clinical Calculator: MELD score for end stage liver disease (NOT appropriate for patients aged under 12 years) Clinical Calculator: MELDNa score for end stage liver disease (not suitable for patients under 12 years) The MELD score should in patients with hepatocellular carcinoma are calculated differently. For 12- to 17-year-old patient with disturbance of the urea cycle, organic acidemia or hepatoblastoma the MELD score is set to 30th Higher MELD scores indicate a higher risk. the corresponding PELD (Pediatric End-Stage Liver Disease) credit score is calculated for patients <12 years: higher PELD score values ??represent a higher risk. Clinical Calculator: PELD score for end stage liver disease (patients under 12 years) therapy adjunctive therapy Generally, treatment is supportive and consists of stopping the corresponding potentially damaging drugs, good nutrition (including vitamin substitution.) And the treatment of the underlying diseases and complications. The dose of drugs that are metabolized in the liver should be reduced accordingly. Any alcohol consumption and potentially hepatotoxic substances must be avoided. In patients who continue to alcohol abuse despite cirrhosis, can be expected withdrawal symptoms during hospitalization. Patients should be vaccinated against viral hepatitis A and B, unless there is already immune protection. Patients with varicose veins require treatment to prevent bleeding (portals Hypertension: Therapy). There is no evidence in favor of a treatment of small esophageal varices. Medium and large esophageal varices should be treated prophylactically with non-selective beta-blockers or endoscopic banding (ligation). If an endoscopic gastric varices are not accessible to banding and do not respond to non-selective beta blocker, a ballonverschließende retrograde transvenous obliteration or endoscopic Cyanoacrylatinjektion can be performed. The creation of a transjugular intrahepatic portosystemic shunt (TIPS, therapy) should in patients with complications of portal hypertension, including ascites and recurrent variceal bleeding, considered unresponsive to standard treatments. Liver transplantation is indicated in patients with end stage liver disease or hepatocellular carcinoma. Das Sterberisiko ohne Lebertransplantation übersteigt das Transplantationsrisiko (z. B. perioperative Komplikationen, dauerhafte Immunsuppression) ab einem MELD-Score von mehr als etwa 15. Bei einem Score ? 15 oder klinisch dekompensierter Zirrhose sollten die Patienten also an ein Transplantationszentrum überwiesen werden. Wichtige Punkte Morbidität und Mortalität bei Zirrhose sind üblicherweise auf ihre Komplikationen (z. B. Komplikationen der portalen Hypertension, Leberversagen, hämatologische Probleme) zurückzuführen. Eine Leberbiopsie sollte dann gemacht werden, wenn eine klare Diagnose zu einem besseren Management und Ergebnis führen würde. Alle Patienten mit Zirrhose sollten auf Autoimmunhepatitis, hereditäre Hämochromatose und Alpha-1-Antitrypsinmangel sowie auf die häufigsten Ursachen, die alkoholische und die Virushepatitis, untersucht werden. Alle Patienten sollten regelmäßig auf