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Nonalcoholic fatty liver disease (NAFLD) is becoming an increasing cause of chronic liver damage. The decision of start a medical treatment is based on the documented risk of progression to cirrhosis and liver cancer, when steatohepatitis (NASH) occurs. The therapy of this syndrome requires, as obviously, some considerations on the natural history of the condition, on the efficacy and safety of various therapeutic options, as well as on the costs. Treatment of patients with NAFLD has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipemia. Weight loss improves insulin sensitivity, and NASH may resolve with weight reduction. Insulin resistance seems to be the common denominator in many cases of NAFLD. Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone). The last two decades have witnessed a considerable progress in the understanding of the mechanisms respon-sible for the fibrogenic progression of chronic liver diseases. Several drugs believed to be hepatoprotective or antifibrotic agent as UDCA, betaine, vitamin E, lecithin, beta-carotene and selenium have been used in patients with NASH. Silybin is the main component of silymarin that is absorbed when linked whith a phytosome. This substance reduces in rats the lipid-peroxidation and the activaction of hepatic stellate cells. In humans, some non controlled data show that silybin is able to reduce insulin resistance, liver steatosis and plasma markers of liver fibrosis.
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PMID:The treatment of NAFLD. 1623 94

Nonalcoholic fatty liver disease (NAFLD) is a fatty liver disease occurring in patients without alcohol consumption. It includes a broad spectrum of liver disease, from fatty infiltration, inflammation and fibrosis, to cirrhosis, usually having obesity, hyperlipidemia, and diabetes mellitus as its etiology. NAFLD-related cirrhosis has rarely been reported in Taiwan. We herein report a 41-year-old male patient with nonalcoholic fatty liver cirrhosis (NAFLC), with the first clinical manifestation being bleeding esophageal varices (EV). The patient was obese with diabetes mellitus, but without hyperlipidemia or any history of drinking alcohol. The laboratory tests, abdominal sonography, and computed tomography revealed a typical case of liver cirrhosis. The pan-endoscopy disclosed EV with red-color sign. EV ligation was performed successfully to stop the bleeding. When the patient was in a stabilized clinical condition, a liver biopsy showed a typical histologic finding of NAFLD. Most of the cases of NAFLC reported in the literature have silent signs and symptoms. Sudden onset of the EV as the first clinical manifestation, as in this case, is rare. This case reminds us that NAFLD may indeed induce severe liver impairment, such as liver cirrhosis. Liver biochemical tests and abdominal sonography should be considered in patients with overt obesity and diabetes.
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PMID:Nonalcoholic fatty liver disease manifesting esophageal variceal bleeding. 1668

Nonalcoholic fatty liver disease(NAFLD) is recognized as a cause of potentially progressive liver damage. NAFLD is often associated with metabolic syndrome that comprises central obesity, insulin resistance, and hyperlipidemia. Among these, severer forms with histopathological features of increasing ballooned hepatocytes and fibrosis are defined as nonalcoholic steatohepatitis (NASH). The natural history of NASH is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. Since central obesity and insulin resistance are most likely involved in the pathogenesis, justification of life style including physical exercise and nutritional counseling is essential for the treatment of NASH.
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PMID:[Treatment of NASH: nutritional counseling and physical exercise]. 1676 22

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

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease are independently associated. Due to the efficacy of 3-hydroxy 3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the prevention of cardiovascular disease, increasing interest has been shown in establishing the safety of these drugs in NAFLD. In this study, the relationship between statin use, hepatic triglyceride content (HTGC), and serum alanine aminotransferase (ALT) levels was examined in 2,264 Dallas Heart Study participants who were using no lipid-lowering agent (n = 2,124) or using only a statin for lipid management (n = 140). Statin use was not associated with a greater frequency of hepatic steatosis (38% vs. 34%) or elevated serum ALT (15% vs. 13%) by a pair-matched analysis. Statin use was also not associated with a greater prevalence of elevated serum ALT among subjects with hepatic steatosis (n = 638). This finding persisted when controlling for possible sample bias as a result of current prescribing practices for statins. Among subjects with serum lipid abnormalities who were not using a statin, hepatic steatosis was present in 60% of those with mixed hyperlipidemia and 83% of those with both mixed hyperlipidemia and an elevated serum ALT. In conclusion, statin use was not associated with a higher frequency of hepatic steatosis or serum ALT abnormalities, even among those with hepatic steatosis. Individuals meeting criteria for statin therapy are likely to have coexistent hepatic steatosis.
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PMID:Statins and hepatic steatosis: perspectives from the Dallas Heart Study. 1687 75

Obesity is now prevailing worldwide, coincident with the increase of hepatic steatosis. Metabolic syndrome with obesity and hypertension, hyperlipidemia, and impaired glucose tolerance is one of the most frequent life-threatening diseases and non-alcoholic steatohepatitis is believed to be a hepatic expression of this syndrome. Non-alcoholic steatohepatitis is prevalent and well characterized in Caucasians, but little is known about non-alcoholic steatohepatitis in Asia-Oceania. Obesity will be a serious social problem in Asia-Oceania in the next two decades and we need to prevent the increase of this syndrome. Therefore, it is extremely important to know about non-alcoholic steatohepatitis based on racial differences, because this syndrome is likely to be a multi-factorial syndrome resulting from different combinations of susceptibility genes superimposed on different environmental factors. Because hepatic steatosis is the first step in the development of not only metabolic syndrome but also non-alcoholic steatohepatitis, the genetic background of Japanese NASH patients was investigated and a measure to assess fatty acid beta-oxidation in the liver in vivo was developed.
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PMID:In vivo imaging of hepatic fatty acid metabolism in patients with non-alcoholic steatohepatitis using semiquantitative 123I-labeled branched-chain fatty acid analog. 1695 79

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

Non-alcoholic fatty liver disease (NAFLD) is often associated with features of the metabolic syndrome, carrying an increased risk to develop non-alcoholic steatohepatitis (NASH), the inflammatory form of liver steatosis. Epidemiological data confirm that obesity, diabetes, hypertension and hyperlipidemia are frequently found in NAFLD and worsen its prognosis because of increased risk of fibrotic evolution, eventually leading to liver cirrhosis. Recent studies confirm the close relationship between the metabolic syndrome and liver steatosis, and further support the detrimental role of oxidative stress and lipid peroxidation, which are pathophysiological processes present in both conditions. Novel diagnostic tools and life style modifications together with targeted therapeutic actions are urgently needed for the management of liver dysfunction in course of metabolic syndrome.
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PMID:Non-alcoholic fatty liver disease in the metabolic syndrome. 1762 52

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


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