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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of incidental elevation of liver enzymes in North America and Europe. Risk factors for NAFLD include body mass index of 25 kg/m2 or greater, central obesity and diabetes mellitus. The spectrum of disease is variable, ranging from simple steatosis with benign prognosis, to non-alcoholic steatohepatitis and cirrhosis, conferring increase in morbidity and mortality. The primary abnormality or 'first hit' in patients with NAFLD is insulin resistance leading to hepatic steatosis. The second hit involves multiple proinflammatory cytokines resulting in non-alcoholic steatohepatitis. Treatment is aimed at aggressive risk factor control and weight loss. Currently, there are no pharmacological agents recommended in the treatment of NAFLD, although preliminary studies suggest promising agents in the future.
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PMID:Non alcoholic fatty liver disease: a clinical approach and review. 1669 1

Nonalcoholic fatty liver disease is a common condition associated with metabolic syndrome. It is the most common cause of elevated liver enzymes in U.S. adults, and is diagnosed after ruling out other causes of steatosis (fatty infiltration of liver), particularly infectious hepatitis and alcohol abuse. Liver biopsy may be considered if greater diagnostic and prognostic certainty is desired, particularly in patients with diabetes, patients who are morbidly obese, and in patients with an aspartate transaminase to alanine transaminase ratio greater than one, because these patients are at risk of having more advanced disease. Weight loss is the primary treatment for obese patients with nonalcoholic fatty liver disease. Medications used to treat insulin resistance, hyperlipidemia, and obesity have been shown to improve transaminase levels, steatosis, and histologic findings. However, no treatments have been shown to affect patient-oriented outcomes.
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PMID:Nonalcoholic fatty liver disease. 1677 Sep 27

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.
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PMID:Long-term follow-up of patients with NAFLD and elevated liver enzymes. 1700 14

Nonalcoholic fatty liver disease (NAFLD) is linked to the metabolic syndrome. The aim of the present study is to determine the effect of the metabolic syndrome on left ventricular (LV) geometry and function using as a model patients with NAFLD. Thirty-eight patients with NAFLD, less than 55 years of age and with a normal exercise test, were compared with an age and sex-matched control group. Patients with diabetes mellitus, hypertension, and body mass index>40 were excluded. A complete echocardiographic study including tissue Doppler imaging (TDI) was performed. The following parameters were assessed by echo Doppler: peak velocities of early (E) and late (A) diastolic filling, E/A ratio, flow propagation velocity (Vp). Using TDI early diastolic velocity (E'), and systolic velocity (S') of mitral annulus were obtained. The patients with NAFLD had a significantly higher body mass index (31.4+/-5 vs. 26.4+/-4 kg/m, P=0.01), higher glucose (100.6+/-13 vs. 83.0+/-10 mg/dL, P=0.01), and triglyceride levels (126.5+/-44 vs. 206.5+/-67 mg/dL, P<0.001). Increased thickness of the intraventricular septum, posterior wall (11.03+/-2.2 vs. 8.9+/-2.9 mm, P=0.001; 8.5+/-1.7 vs. 9.7+/-2.3 mm, P=0.04), and larger LV mass and LV mass/height (160.7+/-58.7 vs.115.3+/-35.4 g, P=0.001 and 92.6+/-29.5 vs. 69.2+/-19.8 g/m, P=0.001, respectively) were found in NAFLD group. LV systolic function was similar in both groups. Patients with NAFLD had a lower E (73.6+/-11.0 vs. 86.4+/-20.0 cm/s, P<0.006) and E/A ratio (1.0+/-0.3 vs. 1.76+/-0.8 P<0.0001). Moreover, the Vp and the E' on TDI were significantly lower compared with the control group (49.0+/-9.7 vs. 74.7+/-18.4 cm/s, P<0.0001 and 10.3+/-2.0 vs. 13.8+/-1.7 cm/s, P<0.0001, respectively). On multivariate analysis the E' on TDI was the only independent parameter associated with NAFLD. In conclusion, patients with NAFLD in the absence of morbid obesity, hypertension, and diabetes have mildly altered LV geometry and early features of left ventricular diastolic dysfunction. Early diastolic velocity on TDI was found to be the only index that could identify the patients with NAFLD and metabolic syndrome.
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PMID:Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment. 1706 17

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized medical condition that may progress to hepatic cirrhosis with liver failure. The pathologic picture resembles that of alcohol-induced liver injury, but it occurs in patients who do not abuse alcohol. NAFLD is more common among patients with evidence of insulin resistance. NAFLD refers to a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. The clinical implications of NAFLD are derived mostly from its common occurrence in the general population, specifically in obese individuals, and its potential to progress to cirrhosis and liver failure. It is difficult to propose a treatment strategy for NAFLD because its pathogenesis is poorly understood; however, the most commonly associated clinical features of obesity, diabetes mellitus, lipid disorders, and hypertension deserve therapeutic interventions independent of NAFLD. It is also not known if and how treatment of these other conditions affects the natural history of NAFLD, particularly in the long term.
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PMID:Nonalcoholic Fatty liver disease and obesity. 1724 48

Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.
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PMID:Nonalcoholic fatty liver disease. 1747 59

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

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the US, and obesity is the most common cause of NAFLD. Obesity and NAFLD are associated with hyperlipidemia, type 2 diabetes, and hypertension, all components of the metabolic syndrome. The purpose of this study was to examine the incidence of NAFLD among morbidly obese patients undergoing bariatric surgery and to determine if advanced liver disease can be predicted by demographics, comorbidities, and/or preoperative biochemical profiles. 135 nonconsecutive patients (109 female, average age 46) with mean body mass index (BMI) 50 (SD 7.6) who underwent liver biopsies during bariatric surgery were studied. Patient data including age, BMI, comorbidities, and preoperative liver function tests were analyzed against liver biopsy pathology. 86% of patients had abnormal liver biopsy results. 60% of patients had steatosis, and 27% had advanced liver disease (7% steatohepatitis, 16% fibrosis, and 4% cirrhosis). Patients were grouped according to liver biopsy pathology. Group A included patients with normal results and steatosis only. Group B included those patients with advanced liver disease:steatohepatitis, fibrosis, and cirrhosis. Of 37 patients in group B, 27% had abnormal preoperative liver function tests (LFTs) compared to 10% of patients in group A (p = 0.022). Patients in group B were more likely to have preoperative hyperlipidemia (p = 0.020) and were also found to have a significantly higher BMI (p = 0.042). Diabetes mellitus, male gender, and age were not predictive of advanced liver disease on liver biopsy, with p = 0.056, p = 0.074, p = 0.26, respectively. Liver disease is common in the morbidly obese. More than one quarter of morbidly obese patients undergoing bariatric surgery have advanced liver disease. Patients with increased preoperative LFTs, hyperlipidemia, and increased BMI are more likely to have non-alcoholic steatohepatitis, fibrosis, or cirrhosis on liver biopsy during weight loss surgery. Diabetes, male gender, and age did not predict advanced liver disease.
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PMID:Laparoscopic bariatric surgery: what else are we uncovering? Liver pathology and preoperative indicators of advanced liver disease in morbidly obese patients. 1747 22

The risk factors and settings for non-alcoholic fatty liver disease (NAFLD) in Asians are reviewed comprehensively. Based particularly on large community-based studies using ultrasonography, case-control series and prospective longitudinal studies, the prevalence of NAFLD in Asia is between 12% and 24%, depending on age, gender, locality and ethnicity. Further, the prevalence in China and Japan has nearly doubled in the last 10-15 years. A detailed analysis of these data shows that NAFLD risk factors for Asians resemble those in the West for age at presentation, prevalence of type 2 diabetes mellitus (T2DM) and hyperlipidemia. The apparent differences in prevalence of central obesity and overall obesity are related to criteria used to define waist circumference and body mass index (BMI), respectively. The strongest associations are with components of the metabolic syndrome, particularly the combined presence of central obesity and obesity. Non-alcoholic fatty liver disease appears to be associated with long-standing insulin resistance and likely represents the hepatic manifestation of metabolic syndrome. Not surprisingly therefore, Asians with NAFLD are at high risk of developing diabetes and cardiovascular disease. Conversely, metabolic syndrome may precede the diagnosis of NAFLD. The increasing prevalence of obesity, coupled with T2DM, dyslipidemia, hypertension and ultimately metabolic syndrome puts more than half the world's population at risk of developing NAFLD/non-alcoholic steatohepatitis/cirrhosis in the coming decades. Public health initiatives are clearly imperative to halt or reverse the global 'diabesity' pandemic, the underlying basis of NAFLD and metabolic syndrome. In addition, a perspective of NAFLD beyond its hepatic consequences is now warranted; this needs to be considered in relation to management guidelines for affected individuals.
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PMID:What are the risk factors and settings for non-alcoholic fatty liver disease in Asia-Pacific? 1756 27

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifestation of the metabolic syndrome, its prevalence is high in obese people and in patients who have type 2 diabetes-insulin resistance is one of the key elements of the pathogenesis of NAFLD. This disease is often asymptomatic in the absence of decompensated cirrhosis, but should be suspected in patients with elevated aminotransferase levels or radiological evidence of a fatty liver or hepatomegaly. Liver fibrosis is associated with age over 50 years, obesity, diabetes and high triglyceride levels. Liver biopsy is the only way to assess the histologic features of necrotic inflammation and fibrosis that define nonalcoholic steatohepatitis and to determine its probable prognosis. The prognosis is good for pure steatosis, whereas the presence of necrotic inflammation is associated with a significant risk of progression to cirrhosis and, possibly, hepatocellular carcinoma. Lifestyle changes, such as dietary modifications and exercise, are recommended. To date, there have been very few randomized, placebo-controlled trials of drug treatments for NAFLD.
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PMID:Nonalcoholic fatty liver disease: from pathogenesis to patient care. 1751 90


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