Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basic therapeutic principle in alcoholic liver diseases in general and in alcoholic hepatitis in particular is the consequent withdrawal of alcohol intake. Basic therapy of more complicated causes includes well balanced nutrition and symptomatic treatment according to the known principles of hepatology and intensive care medicine. Infusions with glucose-glucagon-insulin, or the administration of silymarin, and in individual cases of glucocorticoids seems to be justified as additional treatment. The therapy with S-adenosyl-L-methionine is promising, but clear evidence of the therapeutic effect has to be supplied by clinical studies. Liver transplantation should be taken into consideration in prognostically infaust cases.
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PMID:[Therapy of alcoholic hepatitis]. 160 97

Alcoholic hepatitis presents as an acute hepatitis in an alcoholic. No specific laboratory tests for alcoholic hepatitis exist. Therefore, the diagnosis must be based on the clinical presentation, histology and exclusion of other causes of a similar clinical picture such as viruses and drugs. Patients with elevated bilirubin, encephalopathy and coagulopathy have a poor prognosis. Steroids, infusion of insulin and glucagon, supplementation of amino-acids and other experimental therapies do not appear to be helpful with the exception of steroids which may benefit the sickest patients. Long-term prognosis depends on the extent of cirrhotic changes present after the acute episode and on the drinking habits of the patient.
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PMID:[Alcoholic hepatitis]. 162 Dec 33

Severe alcoholic hepatitis is still a therapeutic challenge. It has been recently advocated that a 3-wk infusion with insulin and glucagon reduces its short-term mortality rate. A multicenter, randomized, single-blind, sequential trial was designed to compare this treatment with placebo. The triangular boundary was defined with alpha = 0.05, beta = 0.10 and estimated survival at 4 wk of 50% with placebo, 75% with treatment. Patients with biopsy-proven severe alcoholic hepatitis (presence of one or more of three criteria: encephalopathy, prothrombin activity less than or equal to 50%, bilirubinemia greater than or equal to 100 mumol/L) were randomized into two groups; one treatment group received an infusion (12 hr/day) of an association of insulin (30 IU) and glucagon (3 mg), and a control group received an infusion of glucose. Treatments were administered during a 3-wk period, and the mortality rate was noted at 4 wk. The decision to discontinue the trial was reached on the basis of results from the first 44 patients. Overall results were assessed in the 72 patients included at the time of this decision (treatment group: n = 37; control group: n = 35). Fifty-three patients had cirrhosis. No significant differences were noted between the two groups at inclusion on the basis of clinical, laboratory and histological criteria. The mortality rate was not significantly different in the two groups; 10 patients (27%) in the treatment group and 5 patients (14%) in the control group died. Causes of death were similar in the two groups and consisted primarily of gastrointestinal hemorrhage, hepatic failure and infectious events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon: a multicenter sequential trial. 172 3

Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease.
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PMID:Alcoholic liver disease. 222 93

Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon.
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PMID:Alcoholic hepatitis: pathogenesis and approaches to treatment. 223 74

A randomized, double-blind, controlled trial of insulin and glucagon infusion was conducted in 50 patients with acute alcoholic hepatitis. Twenty-five treatment patients received 24 U regular insulin and 2.4 mg glucagon over 12 h daily for 3 wk. Twenty-five control patients received 200 ml dextrose solution in identical bottles over the same time period. Six control and 2 treatment patients died from liver failure during study, and another treatment patient died from hypoglycemia. In the 34 patients with prothrombin times greater than 3 s prolonged, fewer deaths occurred among the insulin- and glucagon-infused patients (p less than 0.10). Clinical features of liver disease on entry into the study were similar in the two groups, and total serum bilirubin and prothrombin time improved more rapidly in the treatment group (p less than 0.05). Insulin and glucagon infusion is a promising treatment of alcoholic hepatitis and merits further study in the most severely ill patients.
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PMID:A randomized clinical trial of insulin and glucagon infusion for treatment of alcoholic hepatitis: progress report in 50 patients. 701 49

The past decade has witnessed major gains in our understanding of the pathogenesis and therapy of alcoholic liver disease. The molecular biology of alcohol-metabolizing enzymes is well understood. Older concepts of liver injury, e.g., hypermetabolism, generation of free radicals, mitochondrial and microtubular dysfunction, and impairment of liver regeneration by ethanol, have been studied in greater detail. The fibrotic response to alcoholic liver injury has been explored, revealing complex interrelationships between the nonparenchymal cells of the liver and showing the importance of cytokines in regulating these cells. New mechanisms of injury have been appreciated, most prominently the association between hepatitis C infection and alcoholic liver disease, and the formation of protein-acetaldehyde adducts in the liver of alcohol-fed subjects. A new animal model of alcoholic liver injury, the alcohol infusion rat model developed by French and Tsukomoto, promises to provide a relatively simple model for researchers. The clinical management of alcoholic liver disease continues to evolve. Focal fatty change is recognized as a variant of alcoholic fatty liver. Nonalcoholic steatohepatitis has been described as a mimic of alcoholic liver disease, and may provide insight into the mechanisms of perivenular liver injury. The presence of perivenular fibrosis may predict at an early stage which patients are at risk for serious liver injury. Nutritional and corticosteroid therapy of alcoholic hepatitis are now established. Other therapies such as propylthiouracil, glucagon plus insulin infusion, and colchicine have been studied in large trials. Alcoholic liver disease can now be treated in selected cases by liver transplantation.
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PMID:Recent developments in alcoholism:the liver. 823 24

Alcoholic hepatitis is a multisystem disease seen in individuals who chronically abuse alcohol. When severe, it is associated with a very high mortality rate, with nearly 50% of severely affected persons dying within 1 month of hospitalization. Primary therapy is complete alcohol abstinence and supportive care. Corticosteroids have been shown to be beneficial in a subset of severely ill patients with alcoholic hepatitis and concomitant hepatic encephalopathy. Pentoxifylline has been shown to improve short-term survival rates. Other pharmacologic interventions, including colchicine, propylthiouracil, calcium channel antagonists, and insulin with glucagon infusions, have not been proven to be beneficial. Nutritional supplementation with high-calorie, high-protein diets does not improve mortality rates. Orthotopic liver transplantation is highly controversial in this population of patients and currently is not indicated as definitive treatment. Extracorporeal liver support devices are still in their developmental stage and are only experimental.
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PMID:Alcoholic Hepatitis. 1169 77

Alcoholic hepatitis is a potentially life-threatening complication of alcoholic abuse, typically presenting with symptoms and signs of hepatitis in the presence of an alcohol use disorder. The definitive diagnosis requires liver biopsy, but this is not generally required. The pathogenesis is uncertain, but relevant factors include metabolism of alcohol to toxic products, oxidant stress, acetaldehyde adducts, the action of endotoxin on Kupffer cells, and impaired hepatic regeneration. Mild alcoholic hepatitis recovers with abstinence and the long-term prognosis is determined by the underlying disorder of alcohol use. Severe alcoholic hepatitis is recognized by a Maddrey discriminant function >32 and is associated with a short-term mortality rate of almost 50%. Primary therapy is abstinence from alcohol and supportive care. Corticosteroids have been shown to be beneficial in a subset of severely ill patients with concomitant hepatic encephalopathy, but their use remains controversial. Pentoxifylline has been shown in one study to improve short-term survival rates. Other pharmacological interventions, including colchicine, propylthiouracil, calcium channel antagonists, and insulin with glucagon infusions, have not been proven to be beneficial. Nutritional supplementation with available high-calorie, high-protein diets is beneficial, but does not improve mortality. Orthotopic liver transplantation is not indicated for patients presenting with alcoholic hepatitis who have been drinking until the time of admission, but may be considered in those who achieve stable abstinence if liver function fails to recover.
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PMID:Pathogenesis and management of alcoholic hepatitis. 1467 60