Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As obesity prevalence rises, there is evidence that fatty liver disease can act synergistically with other chronic liver diseases to aggravate parenchymal injury. This is characterized best in chronic hepatitis C, where steatosis is caused by viral and metabolic effects. There is evidence that steatosis and its metabolic abnormalities also exacerbate other diseases, such as alcoholic liver disease, hemochromatosis, and, possibly, drug-induced liver disease. The pathogenesis seems related to increased susceptibility of steatotic hepatocytes to apoptosis, enhanced oxidative injury, and altered hepatocytic regeneration. Data suggest that active management of obesity may improve liver injury and decrease the progression of fibrosis in patients who have other chronic liver diseases.
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PMID:Steatosis as a cofactor in other liver diseases: hepatitis C virus, alcohol, hemochromatosis, and others. 1754 78

The prevalence of type 2 diabetes is higher in patients who have liver diseases, such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease, and cirrhosis. The development of diabetes in patients with cirrhosis is well recognized, but evidence is emerging that the development of chronic liver disease and progression to cirrhosis may occur after the diagnosis of diabetes and that diabetes plays a role in the initiation and progression of liver injury. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases; the effect of diabetes on the severity of disease; the potential mechanisms whereby coexistent diabetes exacerbates progression of hepatic fibrosis; and the impact of obesity, insulin resistance, and type 2 diabetes on clinical outcomes.
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PMID:Impact of diabetes on the severity of liver disease. 1790 49

This article describes the grading and staging systems used in the clinical context for non-neoplastic liver diseases (chronic and autoimmune hepatitis, fatty liver and steatohepatitis, medicinal toxic liver damage, iron storage disease and gall duct diseases). Fibrotic parenchymal alterations can also be assessed as well as livers planned for transplantation, with respect to possible rejection reactions. The basis for the histopathological diagnostic procedure is the liver biopsy. The consistent and correct use of the histological scores is obligatory in the diagnostic assessment of non-neoplastic liver diseases. Different scores are available for the various liver diseases. These are qualitative and quantitative scores based on empiricism and the practical relevance has been effectively proven. Grading describes the inflammatory activity and staging the extent of fibrosis or structural disorders up to liver cirrhosis. In many instances staging is the histopathological criteria for the prognosis assessment and is, therefore, decisive for therapy indications and therapy initiation.
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PMID:[Quality and quantity in hepatopathology. Diagnostic and clinically relevant grading for non-tumourous liver diseases]. 1821 Jan 14

A persistent increase in non-virus non-alcohol related aminotransferase levels can have multiple causes, which differ in terms of prevalence and clinical importance. In the general population, the most frequent cause is non-alcoholic hepatic steatosis, which can evolve into steato-hepatitis and cirrhosis. The treatment for steatosis and non-alcoholic steato-hepatitis consists of modifying lifestyles, whereas the effectiveness of drug treatment remains to be determined. Other much less frequent (yet not rare) causes of persistent non-virus non-alcohol related elevations in aminotransferase levels are celiac disease and hemochromatosis, whereas autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and alpha-1-anti-trypsin deficit are rare. Given that some of these conditions are susceptible to treatment, early diagnosis is important. No epidemiological data are available for evaluating the prevalence of elevated aminotransferase levels correlated with the toxicity of drugs or other xenobiotics, including herbal products. The present document, created by a panel of experts based on a systematic review of scientific evidence, is mainly geared towards physicians working in General Medicine and Transfusion Centres, who generally represent the first contact of persons with elevated aminotransferase levels. The document includes suggestions for diagnosing causes of persistent non-virus non-alcohol related increases in aminotransferase levels, considering the frequency and response to treatment. The conditions requiring specialized visits are also indicated.
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PMID:Consensus recommendations for managing asymptomatic persistent non-virus non-alcohol related elevation of aminotransferase levels: suggestions for diagnostic procedures and monitoring. 1839 1

Gastrointestinal complications of diabetes include gastroparesis, intestinal enteropathy (which can cause diarrhea, constipation, and fecal incontinence), and nonalcoholic fatty liver disease. Patients with gastroparesis may present with early satiety, nausea, vomiting, bloating, postprandial fullness, or upper abdominal pain. The diagnosis of diabetic gastroparesis is made when other causes are excluded and postprandial gastric stasis is confirmed by gastric emptying scintigraphy. Whenever possible, patients should discontinue medications that exacerbate gastric dysmotility; control blood glucose levels; increase the liquid content of their diet; eat smaller meals more often; discontinue the use of tobacco products; and reduce the intake of insoluble dietary fiber, foods high in fat, and alcohol. Prokinetic agents (e.g., metoclopramide, erythromycin) may be helpful in controlling symptoms of gastroparesis. Treatment of diabetes-related constipation and diarrhea is aimed at supportive measures and symptom control. Nonalcoholic fatty liver disease is common in persons who are obese and who have diabetes. In persons with diabetes who have elevated hepatic transaminase levels, it is important to search for other causes of liver disease, including hepatitis and hemochromatosis. Gradual weight loss, control of blood glucose levels, and use of medications (e.g., pioglitazone, metformin) may normalize hepatic transaminase levels, but the clinical benefit of aggressively treating nonalcoholic fatty liver disease is unknown. Controlling blood glucose levels is important for managing most gastrointestinal complications.
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PMID:Gastrointestinal complications of diabetes. 1861 80

Nonalcoholic steatohepatitis (NASH) was described by Ludwig mainly in obese, middle-aged women, often associated with diabetes mellitus and hyperlipidemia. In the recent years, NASH was found to be associated with male, nonobese, nondiabetic patients and with liver iron overload, which led to the hypothesis of iron playing a role in NASH pathogenesis. Increased ferritin with normal transferrin saturation is frequently found in fatty liver patients, but it reflects iron overload only in those patients in which it persists despite an appropriate diet. Insulin resistance hepatic iron overload (IR-HIO) is a new condition of hepatic iron overload, characterized by hyperferritinemia with normal or slightly increased transferrin saturation in the absence of hemochromatotic gene mutations. Although patients with IR-HIO have a high prevalence of insulin resistance-related metabolic disorders, the relationship of IR-HIO and NASH is unclear. Two characteristics allow differentiation of IR-HIO from genetic haemochromatosis: iron overload is heterogeneous from one hepatocyte to another in the periportal area, and sinusoidal iron is distributed throughout the lobule. In IR-HIO, fibrosis develops at a much lower hepatic iron burden than in genetic haemochromatosis, and sinusoidal iron, steatosis and inflammation could represent the histological mark of activity and progression of liver disease in IR-HIO.
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PMID:[Involvement and role of iron in nonalcoholic steatohepatitis]. 1929 96

A 57-year-old white woman had serum ferritin 793 ng/mL, HFE C282Y homozygosity, elevated serum angiotensin-converting enzyme (ACE) levels, 3+ hepatocyte iron, cirrhosis, hepatic granulomas, and portal hypertension. Her 37-year-old son had ferritin 869 ng/mL, C282Y/wt, elevated ACE levels, 2+ hepatocyte iron, bridging fibrosis, and hepatic granulomas. Her daughters had HFE C282Y/H63D and C282Y/wt, respectively; neither had a hemochromatosis phenotype, sarcoid, or severe liver disease. All 4 subjects had nonalcoholic hepatic steatosis. Sarcoid did not segregate with the human leukocyte antigen-A and -B haplotype shared by the proband, her son, and 1 daughter. Phlebotomy to achieve iron depletion in the proband and her son yielded 1.6 and 1.5 g iron, respectively; their ACE levels remained elevated. We reviewed previous reports of 4 patients with hemochromatosis and sarcoid. We conclude that a combination of sarcoid, steatosis, and excessive hepatocyte iron caused cirrhosis or hepatic fibrosis in the proband and her son.
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PMID:HFE hemochromatosis and hepatic sarcoid. 1944 63

Heterozygosity for p.Cys282YTyr is not ordinarily associated with a hemochromatosis phenotype, unless associated in the compound heterozygous state with other HFE mutations. The aims of the study were to identify factors responsible for iron overload in patients who were only heterozygous for p.Cys282Tyr at first genetic testing. Since 2001, twelve p.Cys282Tyr heterozygous patients with iron overload, defined by increased transferrin saturation, serum ferritin and hepatic iron stores, were identified. Four patients showed rare nonsense or missense HFE mutations in the compound heterozygous state with p.Cys282Tyr. One mutation (p.Gln233X) was never described before. The other 8 patients did not carry any other causal mutations in iron-related genes, but showed a very high prevalence of hepatic steatosis and steato-hepatitis, and metabolic alterations. Serum ferritin levels did not differ between the two groups, but transferrin saturation, hepatic iron amount and distribution significantly did. These last indices should be then strongly considered to decide for additional genetic characterization in p.Cys282Tyr heterozygotes. Our results also highlights the influence of metabolic alterations on serum iron indices and pattern of hepatic iron accumulation.
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PMID:Genetic and metabolic factors are associated with increased hepatic iron stores in a selected population of p.Cys282Tyr heterozygotes. 2011 27

Diabetes insipidus is a rare disorder in pregnant women, predating pregnancy or appearing for the first time during gestation. In pregnancy it usually affects women with HELLP syndrome or acute fatty liver of pregnancy and results from the reduced hepatic degradation of placental vasopressinase leading to its increased activity. Although infiltrative diseases have been found to cause diabetes insipidus in non-pregnant population, very few studies showed that these disorders may manifest for the first time during gestation. We describe here the case of transient diabetes insipidus in two subsequent pregnancies of a female with hemochromatosis. The first symptoms of this disease appeared for the first time at the beginning of the third trimester of her second pregnancy, and diagnosis was established on the basis of typical clinical presentation, confirmed by a water deprivation test. Diabetes insipidus resulted from the increased activity of vasopressinase, caused by hemochromatosis-induced liver dysfunction, the presence of which was confirmed between the pregnancies by liver biopsy and identification of the HFE gene mutation. Subsequent desferrioxamine treatment resulted in a less severe clinical course of diabetes insipidus in the last patient's pregnancy. In both pregnancies, the patient was successfully treated with oral desmopressin, which is resistant to degradation by placental vasopressinase. Although unrecognized pituitary disorders may pose a serious health problem to the mother and fetus, hemochromatosis-induced diabetes insipidus, as the case of our patient demonstrates, if effectively diagnosed and treated, cannot be regarded as a contraindication for pregnancy.
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PMID:Recurrent pregnancy-induced diabetes insipidus in a woman with hemochromatosis. 2095 66

Mitochondria are the main energy source in hepatocytes and play a major role in extensive oxidative metabolism and normal function of the liver. This key role also assigns mitochondria a gateway function in the center of signaling pathways that mediate hepatocyte injury, because impaired mitochondrial functions affect cell survival and contribute to the onset and perpetuation of liver diseases. Altered mitochondrial functions have indeed been documented in a variety of chronic liver diseases including alcohol-induced liver disease, nonalcoholic fatty liver disease, viral hepatitis, primary and secondary cholestasis, hemochromatosis, and Wilson's disease. Major changes include impairment of the electron transport chain and/or oxidative phosphorylation leading to decreased oxidative metabolism of various substrates, decreased ATP synthesis, and reduced hepatocyte tolerance towards stressing insults. Functional impairment of mitochondria is often accompanied by structural changes, resulting in organelle swelling and formation of inclusion in the mitochondrial matrix. Adequate mitochondrial functions in hepatocytes are maintained by mitochondrial proliferation and/or increased activity of critical enzymes. The assessment of mitochondrial functions in vivo can be a useful tool in liver diseases for diagnostic and prognostic purposes, and also for the evaluation of (novel) therapeutic interventions.
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PMID:Mitochondria in chronic liver disease. 2126 63


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