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To aid understanding of markers of disease and predictors of outcome in alcohol-exposed systems, we undertook a literature survey of more than 700 articles to view the morphological characteristics and the clinical and experimental epidemiology of the Mallory body. Mallory bodies are filaments of intermediate diameter that contain intermediate filament components (e.g., cytokeratins) observable by conventional light microscopy or immunohistochemical methods, identical in structure regardless of initiating factors or putative pathogenesis. Although three morphological types can be identified under electron microscopy (with fibrillar structure parallel, random or absent), they remain stereotypical manifestations of hepatocyte injury. A summary of the conditions associated with Mallory bodies in the literature and their validity and potential etiological relationships is presented and discussed, including estimates on the combined light microscopic and immunohistochemical prevalences and kinetics. Emphasis is placed on proper confounder control (in particular, alcohol history), which is highly essential but often inadequate. These conditions include (mean prevalence of Mallory bodies in parentheses): Indian childhood cirrhosis (73%), alcoholic hepatitis (65%), alcoholic cirrhosis (51%), Wilson's disease (25%), primary biliary cirrhosis (24%), nonalcoholic cirrhosis (24%), hepatocellular carcinoma (23%), morbid obesity (8%) and intestinal bypass surgery (6%). Studies in alcoholic hepatitis strongly suggest a hit-and-run effect of alcohol, whereas other chronic liver diseases show evidence of gradual increase in prevalence of Mallory bodies with severity of hepatic pathology. Mallory bodies in cirrhosis do not imply alcoholic pathogenesis. Obesity, however, is associated with alcoholism and diabetes, and Mallory bodies are only present in diabetic patients if alcoholism or obesity complicates the condition. In addition, case studies on diseases in which Mallory bodies have been identified, along with pharmacological side effects and experimental induction of Mallory bodies by various antimitotic and oncogenic chemicals, are presented. Mallory bodies occur only sporadically in abetalipoproteinemia, von Gierke's disease and focal nodular hyperplasia and during hepatitis due to calcium antagonists or perhexiline maleate. Other conditions and clinical drug side effects are still putative. Finally, a variety of experimental drugs have been developed that cause Mallory body formation, but markedly different cell dynamics and metabolic pathways may raise questions about the relevance of such animal models for human Mallory body formation. In conclusion, the Mallory body is indicative but not pathognomonic of alcohol involvement. A discussion on theories of development and pathological significance transcending the clinical frameworks will be presented in a future paper.
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PMID:The Mallory body: morphological, clinical and experimental studies (Part 1 of a literature survey). 792 9

This study reports a clinicopathological analysis of 105 patients whose liver histology showed a pattern of alcohol-like steatohepatitis. There were 32 nonalcoholic, 21 asymptomatic ambulatory, and 52 hospitalized alcoholic hepatitis patients. Female sex, obesity, and diabetes predominated in nonalcoholics. Clinical and laboratory presentation were similar in nonalcoholics and ambulatory alcoholics, but different from the hospitalized alcoholics. Histology showed an increasing degree of severity of hepatocellular damage, Mallory bodies, neutrophil and mononuclear infiltration, and pericellular and portal fibrosis from the nonalcoholics to the hospitalized alcoholics, with ambulatory alcoholics displaying an intermediate degree of severity. Steatosis and glycogenated nuclei were prevalent in the obese, diabetic nonalcoholics, of whom 47% had significant fibrosis and 8% cirrhosis, the latter present in 38% and 89% of ambulatory and hospitalized alcoholic hepatitis (P = 0.0001), respectively. In asymptomatic subjects with suspected liver disease, a liver biopsy is the only way of establishing the type and severity of liver lesions.
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PMID:Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients. 856 53

Nonalcoholic steatohepatitis, along with other forms of nonalcoholic fatty liver disease, is a chronic liver disease that is attracting increasing significance. It is a clinicopathologic syndrome that was originally described in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. This typical patient profile has been expanded and is now recognized to occur even in normal weight males without overt abnormalities in carbohydrate metabolism. Although originally believed to be a benign clinical entity, nonalcoholic steatohepatitis is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. It is important to emphasize that nonalcoholic steatohepatitis is best considered one type of a larger spectrum of nonalcoholic fatty liver disease that is a consequence of insulin resistance and ranges from fat alone to fat plus inflammation, fat plus ballooning degeneration, and nonalcoholic steatohepatitis, the latter being the most serious form. As with any disease, the clinical importance of nonalcoholic steatohepatitis is related to its prevalence and natural history. Recent studies using different methodologies indicate that in the general population the prevalence of fatty liver and nonalcoholic steatohepatitis is approximately 20% and 3%, respectively. These prevalence rates are increased in certain subpopulations such as obesity and type II diabetes. Of greater concern is the recognition that cirrhosis and liver-related deaths occur in approximately 20% and 8% of these patients, respectively, over a 10-year period. Risk factors for these adverse clinical symptoms include patients older than the age of 45, the presence of diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio > 1 and hepatic histology. However, a number of important unresolved issues must be clarified before the true natural history of this disease can be fully understood.
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PMID:Clinical features and natural history of nonalcoholic steatosis syndromes. 1129 93

In the past year, some relevant papers related to the diagnosis of malnutrition and its pathogenesis in cirrhosis have been published. The value of anthropometrics in the nutritional assessment of end-stage cirrhotic patients has been reinforced. Also, the role of bioelectrical impedance analysis in these patients has been redefined. Several papers have investigated the relationship between leptin and malnutrition in chronic liver disease, particularly the role of alcoholism in hyperleptinaemia, and the importance of protein-bound leptin in these patients. In other papers, the impact of both undernutrition and obesity on the outcome of liver transplantation has been investigated. Two randomized, controlled trials on enteral nutrition in liver disease have been published in this period. One of them deals with a clinical situation (i.e. severe alcoholic hepatitis) associated with a high mortality rate, whereas the second is the first controlled trial in the field of preoperative nutrition in liver transplantation. Finally, some papers provide further arguments in the dilemma of which route of nutrition (enteral or parenteral) is better in cirrhosis.
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PMID:Nutritional aspects of liver disease and transplantation. 1170 97

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a relatively prevalent disorder (ie, occurring in 3% of adults) that may progress to cirrhosis in 15% to 40% of those who are afflicted. NASH is a subset of a broader diagnostic category, nonalcoholic fatty liver disease, a term applied to a condition involving the presence of excess fat in the liver with or without inflammation and cellular injury. A diagnosis of NASH is established by the presence of morphologic changes on liver biopsy similar to those seen in alcoholic hepatitis, including hepatocellular fat accumulation, evidence of lobular inflammation and cell injury, and in some cases, progressive fibrosis. Obesity and type 2 diabetes, two conditions associated with insulin resistance, are major risk factors for the development of NASH. Accumulating evidence suggests that the hyperinsulinemia associated with insulin resistance may be important in the pathogenesis of NASH. Clinical trials will now determine whether treatment of insulin resistance is an effective therapy for NASH.
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PMID:Evolving pathophysiologic concepts in nonalcoholic steatohepatitis. 1182 39

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that occurs in patients with no significant alcohol consumption; it is not histologically different from alcoholic hepatitis because it presents macrovesicular steatosis, hepatocellular necrosis, mixed inflammatory infiltrate, and various stages of fibrosis in addition Mallory bodies in some patients. Some authors have even described NASH as a benign disease; however, it is presently considered a potentially serious disease that may evolve into liver cirrhosis and probably, liver cancer. It is more often related to female sex, obesity, and dyslipidemia, although it may be present in other population groups and associated with other factors. Its origin may be multifactorial, including insulin resistance, protein glycation, oxidative stress, and others. The disease may be asymptomatic and found in routine physical exams when the patient shows increased aminotransferases with no other explanation. At present the only specific diagnosis procedure is liver biopsy. The sole available current treatment is body weight control, normalizing glucose and lipid blood levels, as well as the administration of some medication, as illustrated in the subsequent article.
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PMID:[Non-alcoholic steatohepatitis]. 1221 35

Non alcoholic fatty liver disease (NAFLD) and its more agressive form, non alcoholic steatohepatitis (NASH) are entities that are becoming subject of interest of the medical community in general, especially because of the increased prevalence of diabetes and obesity in the world population. There is solid evidence linking NAFLD with the so called metabolic syndrome or syndrome X, to the point of accepting hepatic steatosis and its spectrum as one more element of the latter, along with diabetes, hipertension, hypertriglyceridemia and obesity. Insulin resistance seems to be the common link between these entities. Clinical evaluation of every patient with abnormal aminotransferase levels should take into account non alcoholic fatty liver and its spectrum, especially if the subject is obese or diabetic. Despite the important developments in the field of imaging, currenty the only way to differentiate NASH from simple NAFLD is by performing a liver biopsy, which should be discussed extensively with the patient. The prognosis of simple NAFLD is generally benign, but if there is fibrosis, ballooning of the hepatocytes, inflammation and Mallory bodies there is risk to progression to cirrhosis. Liver histology in NAFLD is indistinguishable from alcoholic hepatitis, although the clinical course is generally more benign. Despite this long and protracted clinical course, an important number of subjects have complications of cirrhosis including hepatocellular carcinoma, and many patients require a liver transplantation. There is no specific treatment for this condition, although every therapeutic regimen should include a gradual and supervised weight reduction, a balanced diet and exercise, as well as correction of precipitant factors. There is currently no specific pharmacologic treatment for NASH or NAFLD. Current body of evidence and some pilot studies suggest that the future might be concentrated in agents improving insulin resistance. Meanwhile, we should do our best to study the prevalence of NAFLD in our country and, when clinically pertinent, study histologically those patients with high risk of fibrosis.
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PMID:[Non-alcoholic fatty liver]. 1276 15

Hepatic steatosis is a consequence of both obesity and ethanol use. Nonalcoholic steatosis (NASH) resemble alcoholic steatosis and steatohepatitis. Both exhibit increased hepatocellular triglycerides(TG), reflecting an increase in long chain fatty acids (LCFA). LCFA enter cells by both facilitated transport and passive diffusion. A driving force for both is the plasma unbound LCFA concentration ([LCFAu]). In both obese rodents and obese patients, adipocyte LCFA uptake via both facilitated transport and diffusion is increased. However, the LCFA uptake Vmax in hepatocytes is not increased in obese animals. Nevertheless, total LCFA uptake in obese rodents is increased ~3-fold, reflecting increased plasma LCFA concentrations. With advancing obesity, resistance to the antilipolytic effects of insulin results in increased lipolysis within the omental fat depot, a consequent further rise in portal venous LCFA, and an even greater rise in portal [LCFAu]. This causes a further increase in hepatocellular LCFA uptake, increased intracellular generation of reactive oxygen species (ROS), and transition from simple steatosis to NASH. By contrast, in rodent hepatocytes and in human hepatoma cell lines, ethanol up-regulates the LCFA uptake Vmax. Consequently, although plasma LCFA are unaltered, hepatocellular LCFA uptake in ethanol-fed rats is also increased~3-fold, leading to increased ROS generation and evolution of alcoholic hepatitis. Thus, while increased hepatic LCFA uptake contributes to the pathogenesis of both NASH and alcoholic hepatitis,the underlying mechanisms differ. Recognizing these mechanistic differences is important in developing strategies for both prevention and treatment of these conditions.
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PMID:Lipid metabolism in hepatic steatosis. 1533 Oct 68

Nonalcoholic steatohepatitis is an acquired liver disease, usually metabolic characterised by histologic lesions with steatosis, intralobular necrosis and inflammatory infiltrates. Liver biopsy findings are identical to those seen in alcoholic hepatitis. Nonalcoholic steatohepatitis is increasingly reported in industrial countries because of an increase of the prevalence of obesity and diabetes which are the most common risk factors of this disease. The diagnosis of nonalcoholic steatohepatitis is based on a confrontation between clinical and anatomic data and an exclusion of an excessive intake of alcohol and other hepatic disease. Liver biopsy has a prognosis and histologic benefit especially when there is risk factors of fibrosis. This disease is potentially severe with a potential risk for progression to cirrhosis. Progress in pathogenesis is noted but no definite therapy exist. The aim of this review is to indicate current knowledge for the gravity of nonalcoholic steatohepatitis and its consequence and to understand the pathogenesis to prevent cirrhosis.
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PMID:[Non alcoholic steatohepatitis: an emergent and potentially serious pathology]. 1551 46

NASH is an important form of chronic liver disease that is increasingly recognized. The diagnosis is secured by biopsy findings with similarities to alcoholic hepatitis in a patient with a confirmed history of abstinence. Obesity is a major risk factor, but the disease also occurs in the nonobese. In 20% to 40% of patients the disease can progress to various stages of fibrosis and ultimately cause cirrhosis and death from end-stage liver disease. For this reason, recognition of NASH is important, and establishing the diagnosis provides a further impetus for performing a liver biopsy as part of the evaluation of unexplained liver abnormalities. The mainstay of treatment is weight reduction in the obese. For those individuals who are not obese, continued observation is the only option currently available. Patients who develop decompensated cirrhosis should be considered for liver transplantation unless advanced age or other underlying medical illnesses are a problem. With the increasing knowledge about the pathophysiology of hepatic steatosis, it is hoped that better diagnostic tests for specific causes of NASH will be available and lead to efficacious therapy.
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PMID:Nonalcoholic steatohepatitis. 1556 51


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