Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ageing of the liver mainly affects the sinusoids and the Kupffer cells. Pseudocapillarization, manifested by reduced sinusoidal fenestration and subendothelial collagen deposition, causes a reduction in oxygen-dependent hepatocyte functions such as oxidative drug metabolism. The liver mass in old people is somewhat reduced and the liver blood flow is diminished. This causes a reduction in the clearance of rapidly cleared drugs, but the clearance of slowly cleared drugs is not affected. The overall capacity of the liver to regenerate is maintained in old people. Therefore, hepatic resections for hepatocellular carcinoma can be carried out in non-cirrhotic elderly people. For liver transplantations, biological age is more important than calendar age. Transplantations in frail old people and in elderly people with very poor liver function are associated with increased morbidity and limited survival. In relatively healthy old people, the results are as good as those in younger age groups. An increased prevalence of hepatitis C associated cirrhosis and hepatocellular carcinoma in the elderly population is to be expected, at least in the next 20 years. There is a high prevalence of gallstones among old people, in particular among females. For symptomatic choledocholithiasis in elderly patients, endoscopic bile duct clearance does not necessarily need to be followed by cholecystectomy.
Best Pract Res Clin Gastroenterol 2002 Feb
PMID:Liver disease in the elderly. 1197 34

Iron overload in body tissues can cause complications such as cirrhosis, cardiomyopathy, diabetes, hypogonadism and arthritis. In populations of northern European descent, most iron overload is due to hereditary haemochromatosis (HHC), a genetic condition that causes increased iron absorption. HHC can be treated or prevented by regular phlebotomy treatments. Some experts have called for population screening for HHC, so that early phlebotomy treatment can be initiated. Two screening tests are available: measurement of the serum iron transferrin saturation (Tf%) and genetic testing for HFE mutations. However, both methods have low positive predictive values. Current data suggest that most people at risk are unlikely to develop clinical symptoms and that the population prevalence of clinical complications of HHC is low, arguing against population screening. Two other prevention strategies are available. (1) Health provider education, to heighten awareness of HHC as an explanation for symptoms and signs seen in early iron overload including unexplained fatigue, joint pain, palpitations, abdominal pain, elevated liver function tests, hepatomegaly and elevated serum ferritin. (2) Family-based testing after a diagnosis of HHC, to ensure that relatives are evaluated for evidence of iron overload. More research is also needed to identify the factors that increase risk for disease in persons with excess iron uptake, to determine whether moderate iron overload is a health risk and to evaluate the causes of iron overload other than HHC.
Best Pract Res Clin Haematol 2002 Jun
PMID:Hereditary haemochromatosis: a realistic approach to prevention of iron overload disease in the population. 1240 10

Understanding the pathogenesis of non-alcoholic steatohepatitis has recently assumed great importance with the recognition that it has the potential to progress to fibrosis and cirrhosis. The 'two-hit' model of pathogenesis was proposed in 1998, with the first 'hit' - steatosis - increasing the sensitivity of the liver to the second 'hits' mediating liver injury. The main aim of this chapter is to review this model in the light of studies that have been published over the subsequent 4 years. Particular attention will be focused on the role of insulin resistance and recent advances in our understanding of the basic cellular mechanisms linking obesity and insulin resistance. Based on this information I will propose a modification of the two-hit model that places more emphasis on the role of free fatty acids. This model will provide the basis for further research and enable the rational design of treatment strategies.
Best Pract Res Clin Gastroenterol 2002 Oct
PMID:Pathogenesis of steatohepatitis. 1240 38

Animal models of hepatic steatosis and steatohepatitis have improved our understanding of the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Three models, genetically obese ob/ob mice, lipoatrophic mice and normal rats fed choline-deficient, methionine-restricted diets, have been particularly informative. All support the multiple 'hit' hypothesis for NAFLD pathogenesis that suggests that fatty livers are unusually vulnerable to oxidants and develop steatohepatitis when secondary insults generate sufficient oxidants to cause liver cell death and inflammation. Steatohepatitis, in turn, increases sensitivity to other insults that induce hepatic fibrosis, promoting the evolution of cirrhosis. Early during NAFLD pathogenesis, inhibitor kappa kinase beta (IKKbeta), an enzyme that induces tumour necrosis factor alpha (TNFalpha) and other proinflammatory cytokines, is activated and this causes insulin resistance. Inhibition of IKKbeta or TNFalpha improves insulin sensitivity, steatosis and steatohepatitis in animals, suggesting novel strategies to prevent and treat early NAFLD in humans.
Best Pract Res Clin Gastroenterol 2002 Oct
PMID:Animal models of steatohepatitis. 1240 39

Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20-40% in obese patients. Since NASH is associated with obesity, prevalence has been predicted to increase along with the arsent epidemic of obesity and type II diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in 25% and 10% in these patients respectively over a 10-year period. This is of particular concern given the increasing recognition of NASH in children. Treatment consists of treating obesity and its co-morbidities; diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in body weight. Bariatric surgery is indicated in selected patients.A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.
Best Pract Res Clin Gastroenterol 2002 Oct
PMID:Steatohepatitis in obese individuals. 1240 42

Steatohepatitis in children occurs in the childhood version of non-alcoholic fatty liver disease (NAFLD), as a result of hepatotoxicity and with certain genetic/metabolic diseases. Until recently, NAFLD was considered to be rare in children. It is now recognized as an important childhood liver disease, especially because childhood obesity is much more common. Children with NAFLD may present as young as 4 years old; males tend to predominate; fibrosis is often found on liver biopsy and cirrhosis has been reported. Treatment for childhood NAFLD currently consists of weight reduction plus regular aerobic exercise; vitamin E may be an effective adjunctive therapy. Drug hepatotoxicity and genetic/metabolic diseases that can cause fatty liver, such as Wilson's disease and cystic fibrosis, must be excluded since treatment is radically different. Other causes of chronic hepatitis, such as chronic viral hepatitis, must also be excluded. Multisystemic inherited diseases with hyperinsulinaemia plus insulin resistance may have NAFLD as hepatic involvement and should be identified.
Best Pract Res Clin Gastroenterol 2002 Oct
PMID:Steatohepatitis in children. 1240 43

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.
Best Pract Res Clin Endocrinol Metab 2002 Dec
PMID:Obesity and liver disease. 1246 16

Chronic viral hepatitis is a common disease. More than 500 million people have chronic viral hepatitis worldwide. These diseases are due to chronic infection with hepatitis B virus, hepatitis D virus or hepatitis C virus. Chronic viral hepatitis is responsible for severe complications: cirrhosis and hepatocellular carcinoma, which are responsible for major morbidity and mortality worldwide. The prognosis of chronic viral hepatitis depends on the rate of progression of fibrosis, which varies widely from one patient to another. Some factors, such as gender, age, alcohol consumption and immune status, influence the progression of fibrosis. In recent years, treatment of chronic viral hepatitis has markedly improved-especially in chronic hepatitis C, with more than 50% of patients having a sustained response with the combination of pegylated interferon and ribavirin. Also, in chronic hepatitis B, new drugs are available, or being evaluated, and combination therapy could dramatically change future therapeutic strategies.
Best Pract Res Clin Gastroenterol 2003 Apr
PMID:Transition of care between paediatric and adult gastroenterology. Chronic viral hepatitis. 1267 18

Autoimmune hepatitis (AIH) is a rare chronic disease of the liver with an excellent prognosis under medical therapy capable of reaching complete remission. The diagnosis of AIH relies on the exclusion of viral, metabolic, genetic and toxic aetiologies of chronic hepatitis, or hepatic injury. Autoantibodies contribute to the diagnosis of AIH and have led to the serological subclassification into three distinct types. Also, immunogenetic associations suggest heterogeneity of the syndrome of AIH. Treatment is not based on serological types but is uniformly employed for all subtypes of AIH. Although 90% of patients respond to treatment, immunosuppressive drugs used in transplant medicine have been employed for patients with treatment failure. New drugs, such as budenoside, are being evaluated for the long-term treatment of AIH with a reduction in steroid side-effects. Liver transplantation is an established treatment option for patients who fail to reach remission and progress to cirrhosis and liver failure. In Europe, about 4% of cirrhotic patients with the diagnosis of AIH undergo transplantation. The diagnosis and awareness of the disease is designed to reduce mortality and morbidity.
Best Pract Res Clin Gastroenterol 2003 Apr
PMID:Transition of care between paediatric and adult gastroenterology. Autoimmune hepatitis. 1267 20

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. Interactions between acetaldehyde, reactive oxygen and nitrogen species, inflammatory mediators and genetic factors appear to play prominent roles in the development of ALD. The cornerstone of therapy for ALD is lifestyle modification, including drinking and smoking cessation and losing weight, if appropriate. Nutrition intervention has been shown to play a positive role on both an inpatient and outpatient basis. Corticosteroids are effective in selected patients with alcoholic hepatitis and pentoxifylline appears to be a promising anti-inflammatory therapy. Some complementary and alternative medicine agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Treatment of the complications of ALD can improve quality of life and, in some cases, decrease short-term mortality.
Best Pract Res Clin Gastroenterol 2003 Aug
PMID:Advances in alcoholic liver disease. 1282 59


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