Alcoholic Liver Disease

Alcohol consumption in Western countries is substantial. Among adults in the United States about 4.6% meet the DSM-IV criteria for alcohol abuse and 3.8% for alcohol dependence (alcohol-related diseases and rehabilitation). The male to female ratio is 2: 1. among the liver damage caused by alcohol abuse

(See also the American College of Gastroenterology 2010 practice guidelines Alcoholic Liver Disease) Alcohol consumption in Western countries is substantial. Among adults in the United States about 4.6% meet the DSM-IV criteria for alcohol abuse and 3.8% for alcohol dependence (alcohol-related diseases and rehabilitation). The male to female ratio is 2: 1. To the liver damage caused by alcohol abuse include fatty liver (> 90%) Alcoholic hepatitis (10-35%) cirrhosis (10-20%) A hepatocellular carcinoma may also in patients with cirrhosis, especially with coexisting iron accumulation, develop. Risk Factors The main risk factors associated with alcoholic liver disease are quantity and duration of alcohol consumption (usually> 8 years) Gender Genetic and metabolic properties obesity amount of alcohol In affected individuals is generally a linear correlation between amount and duration of alcohol consumption and the development of liver disease. The alcohol content is calculated by multiplying the volume of the drink (in ml) by the percentage of alcohol. For example, in 45 ml of a 40% strength beverage of alcohol content of 18 ml. Each ml contains about 0.79 g of alcohol. Although the values ??may vary, the volume content of alcohol of most beers is 2- 7%, in the majority of wine 10-15%. So 12 oz beer between about 5 and 20 g contain alcohol, 5 oz of wine between about 12 and 18 g and 1 1/2 oz shot about 14 g. The risk of liver disease increases significantly for men who drink> 40g, in particular> 80 g alcohol / day (eg., About 2-8 mugs of beer, 3-6 shot brandy or 3-6 glasses of wine) for a period > 10 years. To develop cirrhosis, the consumer usually must be> 80 g / day over a period of> 10 years. If the consumption is higher than 230 g / day over 20 years, the risk of cirrhosis is about 50%. But only some alcohol-dependent people develop liver disease. So the consumption of different amounts of alcohol does not explain fully the variations in the formation of a liver Erkan Kung why to accept the influence of additional factors ist.Geschlecht women are more susceptible to alcoholic liver disease even after adjustment of the height. half the current amount for men – – in women is from a quantity of 20 g of alcohol per day, the risk of developing alcoholic liver damage increased. A possible reason for this could be that women have less alcohol dehydrogenase in their stomach lining causing more intact alcohol liver erreicht.Genetische factors The alcoholic liver disease often comes before family, may play genetic factors (eg. As a lack of cytoplasmic enzymes to alcohol elimination) a Rolle.Ernährungszustand a diet rich in unsaturated fatty acids increases the risk factors as well as Fettleibigkeit.Andere Other risk factors include iron accumulation in the liver (which need not necessarily be associated with the absorption of iron) and an existing hepatitis C virus infection. Pathophysiology of alcohol absorption and metabolism of alcohol (ethanol) is rapidly absorbed in the stomach and small intestine. Alcohol can not be saved. A small amount is broken down in transit through the stomach lining. However, the largest amount is metabolized in the liver, especially by alcohol dehydrogenase (ADH), but also by cytochrome P-450 2E1 (CYP2E1), and the enzyme microsomal oxidation system (MEOS). The ADH pathway includes the following metabolic processes: ADH, a cytoplasmic enzyme oxidizes alcohol into acetaldehyde. Genetic ADH polymorphisms contribute to individual differences in alcohol levels in the blood after drinking the same, but not to the vulnerability of developing alcoholic liver disease. Acetaldehyde dehydrogenase (ALDH), a mitochondrial enzyme oxidizes acetaldehyde to acetate. Chronic alcohol use increases the acetate formation. Asians have lower ALDH, are more susceptible to toxic acetaldehyde effects that are similar to those of disulfiram which inhibits ALDH. These oxidative reactions hydrogen is formed, the nicotinamide adenine dinucleotide (NAD) to NADH reduced and the redox potential (NADH / NAD) increased in the liver. The increased redox potential inhibits fatty acid oxidation and gluconeogenesis, whereby the accumulation of fat in the liver is promoted. Chronic alcoholism induced MEOS (mainly in the endoplasmic reticulum), whereby its activity is enhanced. The most important enzyme that is involved is CYP2E1. The induced MEOS system can contribute 20% to the alcohol metabolism. Characterized harmful reactive O2 species are generated leading to oxidative stress and the formation of O2-free radicals in the liver führen.Fettansammlung fat (triglycerides) can accumulate in hepatocytes for the following reasons: Export of fat in the liver is reduced because the hepatic fatty acid oxidation and lipoprotein decreases. Increased fat storage, as a result of a decreasing hepatic fat export the peripheral lipolysis and triglyceride synthesis increases, leading to hyperlipidemia. The accumulation of fat in the liver increases the susceptibility to oxidative Leberschädigung.Endotoxine alcohol in the intestine alters the permeability of the gut, resulting in the increasing absorption of endotoxins, are released from bacteria in the gut. In response to endotoxins (which can not detoxify the damaged liver) it comes to the release of free radicals from liver macrophages (Kupffer cells), the oxidative liver damage verstärken.Oxidative damage Oxidative stress is increased by consumption of alcohol-induced hypermetabolism of liver lipid peroxidation induced free radicals alcohol-related malnutrition-induced reduction of protective antioxidant (z. B. glutathione, vitamin a and e) binding of alcohol oxidation products, such as acetaldehyde, are induced on liver cell proteins thereby neoantigens and inflammation accumulation of neutrophils and other white blood cells, the damage caused by lipid peroxidation and neo-antigens is induced release of inflammatory cytokines from leucocytes, a possible accumulation of iron in the liver increase the oxidative damage. Iron can with alcoholic liver disease by supplying ferrous wine – often these iron accumulation moderate – accumulate. This condition must be differentiated werden.Resultierende of hereditary hemochromatosis inflammation, cell death and fibrosis following factors can worsen the inflammation: cellular necrosis and apoptosis cause the loss of hepatocytes and subsequent tests of liver regeneration contribute to the development of liver fibrosis. Stellat- (Ito) cells proliferate and are transformed into myofibroblasts, which produce type I collagen or extracellular matrix. This results in a narrowing of the sinusoids and terminal liver veins, which contributes to the decrease in liver perfusion and the creation of portal hypertension. Fibrosis narrows the hepatic venules, which affects the liver perfusion, thus contributing to a portal Hypertnesion. The increasing liver fibrosis caused a nodular liver conversion and thus can lead to cirrhosis of the liver. Pathology fatty liver, alcoholic hepatitis and cirrhosis are often seen as separate progressive manifestations of alcoholic liver disease, but often occur simultaneously. The fatty liver (steatosis) is the initial and most common result of excessive alcohol consumption. Fatty liver is potentially reversible. When makrovesikuläre obesity fat is deposited as large triglyceride drop and displaces the Hepatozytenkerne. This is most pronounced in perivenular hepatocytes and leads to an enlargement of the liver. The alcoholic hepatitis (steatohepatitis) is a combination of fatty liver and a diffuse inflammation of the liver accompanied with liver cell necrosis (often focal). This pattern of damage can be pronounced with each varying severity. The damaged hepatocytes have a granular cytoplasm and are swollen (ballooning) or containing fibrillar proteins in the cytoplasm (Mallory or alcoholic hyaline bodies). Severely damaged hepatocytes are necrotic. These processes can lead to narrowing of sinusoids and terminal hepatic veins and the development of liver cirrhosis. It can also be a cirrhosis present. Under an alcoholic cirrhosis is meant an advanced liver disease, which is characterized by the final stage of hepatic fibrosis with destruction of normal liver architecture. The fat content may vary. An alcoholic hepatitis can coexist. The experiment a compensatory liver regeneration leads to the formation of relatively small nodes (micronodular cirrhosis). As a result, usually the liver shrinks. (-: pathophysiology cirrhosis macronodular cirrhosis) in the course of wider septa, which lead to the formation of nodes greater in the liver develop. Symptoms and discomfort symptoms usually occur in patients in the third or fourth decade of life, severe complications occur about a decade later. The fatty liver is often asymptomatic. In one third of patients, the liver is enlarged and soft, but generally not sensitive to pressure. The alcoholic hepatitis ranges from a mild reversible to life-threatening disease. Most patients with moderate running disease are malnourished and have fatigue, fever, jaundice, pain in the right upper abdomen and a pressure-sensitive liver enlargement on. At approximately 40% of patients, the condition deteriorated rapidly after admission with light (z. B. increasing jaundice) to severe (z. B. ascites, portosystemic encephalopathy, variceal bleeding, liver failure, coagulopathy) complications. While other manifestations of liver cirrhosis may occur. Compensated liver cirrhosis may be asymptomatic. The cirrhotic liver is usually small. If the cirrhotic liver is enlarged, it should be checked whether a fatty liver disease or a liver lesion is present. Symptoms range from which an alcoholic hepatitis to the complications of end-stage liver disease, such as portal hypertension (often with esophageal varices and upper gastrointestinal bleeding, splenomegaly, ascites and portosystemic encephalopathy). Portal hypertension can lead to intrapulmonary arteriovenous shunt with hypoxemia (hepatopulmonary syndrome), which can cause cyanosis and clubbing. Furthermore, acute renal failure due to the progressively decreasing renal blood flow may develop (hepatorenal syndrome). Hepatocellular carcinoma develops in 10-15% of patients with alcoholic cirrhosis. In the context of chronic alcoholism, a Dupuytren’s contracture, spider nevi, myopathy and peripheral neuropathy can develop. In men, chronic alcohol abuse may signs of hypogonadism and feminization (z. B. gynecomastia, testicular atrophy, changes in the pubic hair) cause. Malnutrition can cause multiple vitamin deficiencies (eg. As folic acid and vitamin B) Parotisvergrösserung and nail changes. In alcoholics, a Wernicke’s encephalopathy and Korsakoff’s psychosis may develop, which are mainly due to the thiamine deficiency. Pancreatitis is common. At about> 25% of alcoholics hepatitis C virus infection has been recorded. This combination accelerates the progression of liver disease. In patients with alcohol abuse and fatty liver, a Zieve syndrome (hyperlipidemia, hemolytic anemia and jaundice) can rarely be detected. Diagnosis Confirmed history of alcohol consumption liver (function) parameters and blood count If necessary. Liver biopsy alcohol is believed to be the cause of liver disease in patients who regularly consume large amounts of alcohol, in particular> 80 g / day. If there is more than the consumption of alcohol the patient uncertainty, anamnesis should be confirmed by family members. Patients can be screened with the CAGE questionnaire on alcohol disease (need to C ut down, Annoyed by critiscism, G uilty about drinking, and need for a morning eye-opener). There is no specific test for the diagnosis of alcoholic liver disease. The determination of liver function parameters (prothrombin time, albumin, bilirubin) and the blood can be a sign of advanced liver damage and anemia seen. The transaminases is usually moderate (<300 I.E./l) and does not reflect the extent of liver damage resist. Above all, a GOT-increase in normal or only slightly elevated GPT increase is recorded, resulting in a ratio of AST / ALT ? 2 results. A possible reason for the low GPT is a nutrient deficiency of vitamin B6, which is needed for the function of the enzyme discussed. Its effect on the GOT is less pronounced. The increase in gamma glutamyl transferase (GGT) may be more due to an alcohol-induced enzyme induction and less on cholestasis, liver damage or medication. A serum albumin degradation is usually attributed to malnutrition, but may indicate a lack of hepatic synthesis capacity in the context of an acute or chronic liver failure. Macrocytosis (MCV> 100 fL) is an expression of alcoholic damage to the bone marrow. Macrocytic anemia is due to the lack of folic acid as a result of malnutrition common in alcoholism before. Parameters of the severity of liver disease are: serum bilirubin showing the secretory function prothrombin time or INR, which reflect the hepatic synthesis performance A Thromobozytopenie may be caused by direct alcohol toxic damage of the bone marrow or by splenomegaly in portal hypertension. Neutrophil leukocytosis may result from an alcoholic hepatitis, wherein a concurrent infection (particularly pneumonia and spontaneous bacterial peritonitis) should be considered. Imaging methods of the liver are routinely not needed for diagnosis. If they are performed for other reasons, the abdominal ultrasonography or computed tomography may indicate a fatty liver or demonstrate splenomegaly, portal hypertension or ascites. Transient elastography measures the liver stiffness and thus detect advanced fibrosis. Through this non-invasive method of liver biopsy for evaluation of advanced liver fibrosis and associated therewith forecast can possibly be avoided. The significance of this process is derzeitg further investigated in studies. In patients with suspected alcoholic liver disease should other (additional) causes of liver disease, v. a. Be clarified viral hepatitis. Because the features of fatty liver, cirrhosis and Alkoholihepatitis overlap, it is more useful to describe the precise findings to assign a patient to a specific category, which can only be determined by a liver biopsy. Not all experts agree on the indications for liver biopsy. The following indications for liver biopsy were proposed: Unclear clinical diagnosis (. Eg unclear, persistently elevated transaminases despite abstinence from alcohol) Clinical suspicion of> 1 cause of liver disease clarify the extent of liver damage and prognosis (eg alcohol plus viral hepatitis.) the biopsy may provide clues to the cause of Lebererkranung. At the same extent (e.g. inflammatory activity and fibrosis stage) of liver injury can be determined. If an iron deposit is observed, a determination of iron in the liver tissue as well as a genetic analysis to exclude hereditary hemochromatosis should be excluded as the cause. should multiply every 6 months an annual abdominal ultrasonography and, if necessary, an alpha-fetoprotein measurement performed to rule out hepatotozelluläres cancer (hepatocellular carcinoma: Screening) in patients with liver cirrhosis.. Prognosis The prognosis is essentially determined by the extent of hepatic fibrosis and inflammation. Alcohol-related liver injury in particular fatty liver and inflammation may regress when alcohol is avoided. With abstinence, the fatty liver can fully recover within 6 weeks. Fibrosis and cirrhosis are usually irreversible. Certain biopsy findings (z. B. neutrophils and perivenular fibrosis) indicate a worse prognosis. To assess the severity and prognosis of alcohol-toxic liver disease usually liver function parameters such as prothrombin time, and bilirubin and creatinine are considered (to assess the existence of hepatorenal syndrome). For prognosis estimation with alcoholic liver disease Maddrey score can be used, which is calculated by the formula: Clinical computer: Hepatitis-discrimination function for corticosteroid therapy in alcoholic hepatitis For this formula bilirubin is measured in mg / dl (converted divided by bilirubin in .mu.mol / l through 17). A value of> 32 is connected to a high short-term mortality (35% of patients without encephalopathy and 45% of patients with encephalopathy after a month deceased) connected. Other prognostic scores are the MELD (Model for End-Stage Liver Disease) scores of the Glasgow score for alcoholic hepatitis and the Lille model. In patients ? 12 years of MELD score is calculated using the following formula: Clinical Calculator: MELD score for end stage liver disease (NOT appropriate for patients aged under 12 years) If cirrhosis and its complications (ascites, bleeding) manifesting once have the 5-year survival rate is about 50%; survival is higher in abstinent patients and lower when the patient continues drinkt. The coexistence of iron accumulation or chronic hepatitis C increases the risk for development of hepatocellular carcinoma. Therapy abstinence concomitant treatment and corticosteroids (par) enteral nutrition in severe alcoholic hepatitis If necessary. Transplantation alcohol abstinence restriction is the mainstay of treatment; it prevents further liver damage and leads to life extension. Because the compliance in these patients can be problematic, a multidisciplinary treatment strategy should be sought. Behavioral therapy and psychosocial co-supervision may help motivate patients. This should rehabilitation programs, support groups (alcohol-related diseases and rehabilitation: maintenance therapy) as well as a motivation boost serving co-supervision by doctors and psychologists are considered. Drug therapy for the treatment of withdrawal symptoms may be necessary. Here opioid antagonists appear (for example, naltrexone) and medications that gamma-aminobutyric acid receptors change (for example, baclofen) to have a short-term benefit. Disulfiram inhibits the aldehyde dehydrogenase, thereby acetaldehyde is accumulated; this causes in alcohol within 12 h after administration of disulfiram Errröten and other unpleasant Effekte.Begleitmaßnahmen The focus of the treatment is to accompanying measures. A nutrient-rich diet with added vitamins (v. A. B vitamins) is important during the first few days of alcohol abstinence. The alcohol withdrawal may require the administration of benzodiazepines (eg. Diazepam). In patients with advanced alcoholic liver disease, excessive sedation can induce a portosystemic encephalopathy and should therefore be avoided. Severe acute alcoholic hepatitis usually requires hospitalization, often intensive medical care is necessary (parenteral nutrition, treatment of complications such. As infections, bleeding from esophageal varices, portosystemic encephalopathy, Korsakoff’s psychosis, Niereninsufizienz, electrolyte derailments, portal hypertension , ascites, hepatic failure – improve see elsewhere in the MSD Manual) .Spezifische treatment corticosteroids (such as prednisolone 40 mg / day for 4 weeks followed by ausschleichender dosage) which results in patients with severe acute alcoholic hepatitis, no. have infections, gastrointestinal bleeding, kidney failure and pancreatitis. Than corticosteroids and enteral nutrition few specific treatments are clearly established. Antioxidants (eg., S-adenosyl-l-methionine, phosphatidylcholine, Metadoxine) show a beneficial effect in terms of improving liver damage, but must be found in other studies. Drugs that act on cytokines, particularly TNF-alpha, and thus reduce the inflammation that led to different results in smaller studies. Pentoxifylline, a phosphodiesterase inhibitor, which inhibits TNF-? synthesis, has provided various results of clinical trials in patients with severe alcoholic hepatitis. The use of anti-TNF-alpha antibodies (z. B. infliximab, etanercept) is to be considered that there may be severe infections occur, so the risk outweigh the benefits. Medication to reduce fibrosis (z. B. colchicine, penicillamine), and drugs that are given to normalize the hypermetabolism associated with alcoholic liver disease (eg. As propylthiouracil), have no proven benefit. A positive effect of antioxidants such as silymarin (milk thistle) and vitamin A and E has not been proven yet. A liver transplant may be considered if the allocation criteria are met. With liver transplantation, the 5-year survival rates are comparable to those of non-alcoholic liver disease, up to 80% in patients with no active liver damage and 50% for alcoholic hepatitis. The majority of transplant programs provides for a six-month phase of abstinence prior to transplantation, otherwise hold up to 50% of patients after transplant their drinking habits again; recent data suggest that an earlier transplant has a survival benefit, but at present this procedure is not standard in the treatment. Key points The risk of liver disease increases significantly for men> 40 g, in particular> 80 g alcohol / day (eg., About 2-8 mugs of beer, 3-6 glasses of wine or liquor) over a period of> 10 take years to him; the risk for women increases significantly when they take about half of it to him. Patients are screened with the CAGE questionnaire, doubts about the alcohol consumption of the patient should be made, interviewing family members can be considered. To forecast assessment should adverse histologic findings (eg. As neutrophils, perivenular fibrosis) and the use of a formula (for example, Maddrey score, MELD [Model for End-Stage Liver Disease] credit score) are considered. The importance of abstinence has highlighted offered supportive care and considered hospitalization and corticosteroids are given to patients with severe acute alcoholic hepatitis. A transplant can be drawn in abstinent patients into consideration.

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