Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
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There are limited data on nonalcoholic fatty liver disease (NAFLD) from India. The clinicopathological profile of Indian patients with NAFLD may be different from that of Western patients. One hundred NAFLD patients with increased liver enzymes were prospectively evaluated for clinical presentation, associated diseases, overweight/obesity, central obesity (n=54), presence of diabetes mellitus, lipid abnormalities, insulin resistance (n=39), metabolic syndrome (n=54), serum iron, serum ferritin, and transferrin saturation (n=60), and HFE gene mutations (n=30). Risk factors for the grade and stage of the disease on histology were studied in 38 biopsy-proven patients. Patients were treated with lifestyle modifications and ursodeoxycholic acid (UDCA). Seventeen nonresponder patients were treated with metformin. The majority of patients were males (n=70). Twenty percent of patients were overweight, 68% had obesity, and 78% had central obesity. Abnormal cholesterol, HDL, and triglycerides were present in 36%, 66%, and 53% of patients, respectively. Twelve percent of patients had diabetes mellitus and 16% patients had various associated diseases. All 22 (100%) patients studied by ITT and all but 1 (98%) studied by HOMA-IR were found to have reduced insulin sensitivity and 50% were found to have metabolic syndrome by the modified ATP III criteria. Two (3%) patients were found to have high serum iron, 4 (7%) patients had high ferritin, 5 (8%) patients had increased transferrin saturation, and 4 (13%) patients were found to be heterozygotes for H63D HFE gene mutation. Twenty patients of 38 (53%) had histological evidence of NASH (class 3=6, class 4=14). The other 18 (47%) qualified for class I (n=1) or class II (n=17) NAFLD. Four (10.5%) patients had bridging fibrosis and none had evidence of cirrhosis liver. Seventy-four (74%) patients achieved a biochemical response to lifestyle modification and UDCA. All 17 patients treated with metformin had a reduction in ALT level and 10 (59%) of them had normalization of their enzymes. We conclude that the clinicopathological profile of NAFLD in Indian patients is different from that in the West.
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PMID:The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. 1742 Sep 51

Obesity has emerged as a significant global health problem in the pediatric population. Pediatric liver disease is a serious complication of childhood obesity. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from fat in the liver--simple steatosis, NASH/ steatohepatitis--fat with in.ammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. The important message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.
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PMID:Non-alcoholic fatty liver disease and childhood obesity. 1747 88

In the United States, obesity among adults and overweight among children and adolescents have increased markedly since 1980. Among adults, obesity is defined as a body mass index of 30 or greater. Among children and adolescents, overweight is defined as a body mass index for age at or above the 95th percentile of a specified reference population. In 2003-2004, 32.9% of adults 20-74 years old were obese and more than 17% of teenagers (age, 12-19 y) were overweight. Obesity varies by age and sex, and by race-ethnic group among adult women. A higher body weight is associated with an increased incidence of a number of conditions, including diabetes mellitus, cardiovascular disease, and nonalcoholic fatty liver disease, and with an increased risk of disability. Obesity is associated with a modestly increased risk of all-cause mortality. However, the net effect of overweight and obesity on morbidity and mortality is difficult to quantify. It is likely that a gene-environment interaction, in which genetically susceptible individuals respond to an environment with increased availability of palatable energy-dense foods and reduced opportunities for energy expenditure, contributes to the current high prevalence of obesity. Evidence suggests that even without reaching an ideal weight, a moderate amount of weight loss can be beneficial in terms of reducing levels of some risk factors, such as blood pressure. Many studies of dietary and behavioral treatments, however, have shown that maintenance of weight loss is difficult. The social and economic costs of obesity and of attempts to prevent or to treat obesity are high.
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PMID:The epidemiology of obesity. 1749 5

The prevalence of non-alcoholic steatohepatitis has increased in the last years, paralleling the increasing incidence of overweight and obesity in the general population and related comorbidities. It is expected that in near future, non-alcoholic steatohepatitis will be responsible for a large number of subjects with chronic liver disease due to fatty liver Because of this, treatment options for fatty liver are necessary. To date, the cornerstone of treatment is based in weight reduction, with diet and increased physical activity, although reports indicating that insulin sensitizers and medications that reduce oxidative stress may hold promise for the treatment of this condition. This article reviews the most important aspects of treatment of non-alcoholic steatohepatitis.
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PMID:[Therapeuric aspects of NAFLD. A literature review]. 1754 83

Polycystic ovary syndrome (PCOS) affects 6-7% of reproductive-aged women. Although the diagnostic criteria for PCOS have been debated, it is frequently characterized by hyperandrogenism (hirsutism, acne, male-pattern hair loss), oligo-anovulation, and polycystic ovaries on ultrasound. The reproductive and metabolic complications associated with the syndrome can be serious, so a comprehensive approach to the evaluation and treatment of affected women is important. Menstrual cycle control is necessary to prevent endometrial hyperplasia, and this can be accomplished with hormonal contraception, progesterone therapy, and weight loss (if overweight). In women desiring pregnancy, commonly used ovulation induction therapies include weight loss, clomiphene citrate, and/or metformin. Cosmetic issues such as hirsutism, acne and male-pattern hair loss can be challenging to cope with. Treatment options include estrogen-containing hormonal contraceptive agents, antiandrogens, and topical agents. More permanent hair reduction can be achieved with electrolysis and laser therapy. Evaluation of metabolic complications includes risk assessment for diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease. Women with PCOS should also be screened for sleep apnea, as this has been reported to occur more commonly in women with PCOS. Finally, mental health issues such as depression and eating disorders may be present. Many of the complications associated with PCOS can be managed with therapeutic lifestyle change, including a healthy diet, exercise, weight loss (if overweight), and psychological support. Pharmacological therapies are also available to effectively regulate menstrual cycles and manage cosmetic complications. This article will review the current diagnostic and therapeutic strategies in PCOS.
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PMID:Comprehensive clinical management of polycystic ovary syndrome. 1759 39

Current knowledge on gamma glutamyl transpeptidase (gammaGTP) was reviewed. This enzyme, which is mainly expresses on the cell surface, is thought to participate in catalyzing glutathione breakdown, resulting in the formation of cystein, a thiol compound exerting antioxidant effects. The most important role of this enzyme in vivo seems to recover cystein from extracellular glutathione to preserve intracellular homeostasis of oxidative stress. Increase in environmental oxidative stress may induce this enzyme via NFkB. However, its excessive induction may contrary raise oxidative stress and cause subsequent organ injuries since cysteinylglycine, an intermediate of the glutathione breakdown, affects the iron metabolism, resulting in the production of free radicals. Recently, there are multiple lines of evidence that the development of hypertension, hyperlipidemia, diabetes mellitus is associated with increased serum gammaGTP levels. The oxidative stress derived from gammaGTP may participate in the development of these morbid conditions and would account for these associations. However, since subjects associated with excessive drinking and overweight, two major factors increasing serum gammaGTP level are usually suffering from hypertension, hyperlipidemia, diabetes mellitus, it is most likely that the associations are attributed to excessive drinking and overweight. We recently demonstrated that level of serum gammaGTP is inversely associated with that of serum adiponectin, a sort of adipocytokines. In that abnormalities of adipocytokines including adiponectin cause hypertension, hyperlipidemia, diabetes mellitus as well as fatty liver that is associated with increased gammaGTP level, the status of adipocytokines may stand behind the associations among these factors in obese subjects. Moreover, we demonstrated that serum gammaGTP level is inversely associated with subjects' statuses of lifestyles evaluated by Breslow's lifestyle index, suggesting that serum gammaGTP activity could be a tool for screening of subjects with unhealthy lifestyles. In that unhealthy lifestyles cause various morbid conditions designated as lifestyle-related diseases that is thought to comprehend metabolic syndrome and/or alcohol-related diseases, such screening and intervention in their correction should be significant to prevent their development. The consensus currently reached is that increased serum gammaGTP activity is associated with increased mortality. In that excessive drinking, obesity, as well as improper lifestyle elevate serum gammaGTP activity meanwhile cause various morbid conditions that make lifespan shorter, the view is not surprising.
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PMID:[Gamma glutamyl transpeptidase (gammaGTP) in the era of metabolic syndrome]. 1766 41

Nonalcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the United States and involves a spectrum of progressive histopathologic changes. Common risk factors associated with NAFLD include obesity, diabetes, and hyperlipidemia. Although most patients with NAFLD have simple hepatic steatosis, a significant number develop nonalcoholic steatohepatitis, which may progress to fibrosis, cirrhosis, or end-stage liver disease. There is increasing evidence that NAFLD is a common feature in patients with the cardiometabolic syndrome, a onstellation of metabolic, cardiovascular, renal, and inflammatory abnormalities in which insulin resistance is thought to play a key role in end-organ pathogenesis. NAFLD is usually diagnosed after abnormal liver chemistry results are found during routine laboratory testing. No therapy has been proven effective for treating NAFLD/nonalcoholic steatohepatitis. Expert opinion emphasizes the importance of exercise, weight loss in obese and overweight individuals, treatment of hyperlipidemia, and glucose control.
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PMID:Nonalcoholic steatohepatitis and the cardiometabolic syndrome. 1767 1

Overweight and obesity among children and adolescents are increasing. Fatty liver disease (FLD) is an emerging problem in this age group. We investigated prevalence of overweight and non-invasive FLD and associated clinical characteristics in a representative population-based sample of 378 children and adolescents aged 12-20 years who were randomly selected from the general population in Leutkirch, Southern Germany. Overweight was defined as having a body mass index above the 90th percentile for the respective age and sex. About 15% of female (29 out of 194) and 12% of male participants (22/182) were overweight. Among females, only one non-overweight individual showed signs of FLD but in more than one third of the overweight males (8/22) signs of FLD were present. Overweight subjects in general had an unfavourable lipid profile and abnormal concentrations of obesity-related hormones such as significantly lower concentrations of adiponectin and increased levels of inflammatory markers including C-reactive protein and fibrinogen. Overweight males with signs of FLD showed even more severe altered metabolic responses compared to those who were overweight without signs of liver injury. FLD was not explained by alcohol consumption or other chronic liver disease. In this sample of children and adolescents representative of the general population a high prevalence of non-alcoholic fatty liver disease (NAFLD) is found in overweight males. These individuals showed the most severe metabolic alterations compared to non-overweight and overweight individuals without NAFLD indicating even higher risk for future overweight and obesity-related diseases such as type 2 diabetes and cardiovascular disease.
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PMID:Prevalence of non-alcoholic fatty liver and characteristics in overweight adolescents in the general population. 1789 81

Antiretroviral medications have significantly improved the prognosis of subjects infected by human immunodeficiency virus (HIV). However, long-term complications of these drugs are increasingly recognized as significant causes of morbidity and mortality. Non-alcoholic fatty liver disease (NAFLD), which can evolve into non-alcoholic steato-hepatitis (NASH), cirrhosis and ultimately hepatic failure is one of the more often observed complications in the current clinical practice and the correlation with liver enzyme elevations is controversial. Multiple factors have been considered as possibly correlated to this event in the HIV-infected population, including metabolic abnormalities (such as hyperlipidaemia, hyperglycaemia and being overweight), chronic inflammation, concurrent infection with hepatitis C and B viruses, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTI). HIV-associated syndromes such as lactic acidosis and lypodystrophy are frequently associated with fatty liver disease and a mitochondrial injury has been considered as its possible pathogenetic factor. In particular, treatment containing stavudine and didanosine have proven to be the most commonly implicated in the occurrence of mitochondrial abnormalities. Epidemiologic data to better define the role of predictive factors and drugs associated with the development of NAFLD are still lacking. Furthermore, it remains unclear the better therapeutic management for this condition, even if the current best therapeutic option for NAFLD is the treatment of the underlying disease. Other studies are mandatory to better elucidate the pathogenesis of NAFLD and the optimal therapeutic strategy for the underlying conditions.
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PMID:Steatohepatitis in HIV-infected subjects: pathogenesis, clinical impact and implications in clinical management. 1789 69

Obesity has emerged as one of the most serious public health concerns in the 21st century. Obese children tend to become obese adults. The dramatic rise in pediatric obesity closely parallels the rapid increase in the prevalence of adult obesity. As overweight children become adults they face the multitude of health problems associated with obesity at younger ages. The morbidity and mortality associated with obesity continue to increase. Obesity is one of the leading causes of preventable death. Complications of obesity include cardiovascular risks, hypertension, dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus and impaired glucose tolerance, acanthosis nigricans, hepatic steatosis, premature puberty, hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis and pseudotumor cerebri. Genetic and molecular and environmental factors play an important role in the assessment and management of obesity.
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PMID:Obesity: genetic, molecular, and environmental aspects. 1800 Sep 69


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