Features of Nonalcoholic Steatosis Syndromes
Features of Nonalcoholic Steatosis Syndromes
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.
In 1980, Ludwig and colleagues gave the name nonalcoholic steatohepatitis (NASH) to a formerly recognized clinicopathologic syndrome that occurred in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. In these typical patients from the original description, hepatomegaly and mild abnormalities of liver function tests were common clinical findings. The liver biopsy specimens were characterized by the presence of striking macrovesicular fatty changes and evidence of focal necrosis with mixed inflammatory infiltrates and Mallory bodies. Fibrosis was present in most specimens, with 15% of the patients having cirrhosis. These authors concluded that the cause of NASH was unknown and no effective therapy currently existed. To a large extent, these conclusions remain valid today. However, progress has been made in our understanding of NASH in a number of different areas, perhaps no more importantly than in the recognition that NASH is not a benign clinical entity but rather a common disease with serious clinical sequelae.
However the histologic criteria required for inclusion in NASH studies have varied. Some studies required only the presence of macrovesicular steatosis with parenchymal inflammation. Although such findings meet the literal definition of steatohepatitis, such a definition would include cases with benign steatosis and nonspecific reactive inflammation and could encompass other diseases such as Wilson's disease, steroid treatment, autoimmune liver disease, and many of the secondary causes of fatty liver shown in Table 1. More important, these milder histologic forms bear no similarity to alcoholic hepatitis, which must include fibrosis, neutrophilic inflammation, and hepatocyte damage (ballooning degeneration) with or without Mallory hyaline. In addition, as discussed in the following, these milder forms of nonalcoholic fatty liver disease have a benign clinical course as compared with cases that resemble alcoholic hepatitis which may progress to cirrhosis and cause liver-related deaths. We believe (and in agreement with other authors) that the term NASH should be restricted to cases that meet the histologic criteria for the diagnosis of alcoholic hepatitis.
Therefore, NASH should be considered as a type (albeit the most severe form) of a larger spectrum of nonalcoholic fatty liver disease (NAFLD) that is a consequence of insulin resistance with histological findings ranging from (1) fat alone to (2) fat plus inflammation to (3) fat plus ballooning degeneration to (4) fat plus alcoholic hepatitis-like lesions (sinusoidal fibrosis and polymorphonuclear infiltrates, with or without Mallory hyalin). Only types 3 and 4 should be considered as NASH.
Macrovesicular fatty liver (or steatosis) is a common finding that has been observed in a wide range of clinical conditions. Table 1 displays a proposed classification of NAFL into two types: the primary type, which is caused by the conditions associated with insulin resistance, and the secondary type, which is caused by drugs, surgical procedures, and a variety of miscellaneous disorders. An adequate review of all the causes of NAFL listed in Table 1 is beyond the scope and intent of this article. Therefore, this discussion will be focused on the clinical characteristics and the natural history of primary NAFL.
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.
In 1980, Ludwig and colleagues gave the name nonalcoholic steatohepatitis (NASH) to a formerly recognized clinicopathologic syndrome that occurred in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. In these typical patients from the original description, hepatomegaly and mild abnormalities of liver function tests were common clinical findings. The liver biopsy specimens were characterized by the presence of striking macrovesicular fatty changes and evidence of focal necrosis with mixed inflammatory infiltrates and Mallory bodies. Fibrosis was present in most specimens, with 15% of the patients having cirrhosis. These authors concluded that the cause of NASH was unknown and no effective therapy currently existed. To a large extent, these conclusions remain valid today. However, progress has been made in our understanding of NASH in a number of different areas, perhaps no more importantly than in the recognition that NASH is not a benign clinical entity but rather a common disease with serious clinical sequelae.
However the histologic criteria required for inclusion in NASH studies have varied. Some studies required only the presence of macrovesicular steatosis with parenchymal inflammation. Although such findings meet the literal definition of steatohepatitis, such a definition would include cases with benign steatosis and nonspecific reactive inflammation and could encompass other diseases such as Wilson's disease, steroid treatment, autoimmune liver disease, and many of the secondary causes of fatty liver shown in Table 1. More important, these milder histologic forms bear no similarity to alcoholic hepatitis, which must include fibrosis, neutrophilic inflammation, and hepatocyte damage (ballooning degeneration) with or without Mallory hyaline. In addition, as discussed in the following, these milder forms of nonalcoholic fatty liver disease have a benign clinical course as compared with cases that resemble alcoholic hepatitis which may progress to cirrhosis and cause liver-related deaths. We believe (and in agreement with other authors) that the term NASH should be restricted to cases that meet the histologic criteria for the diagnosis of alcoholic hepatitis.
Therefore, NASH should be considered as a type (albeit the most severe form) of a larger spectrum of nonalcoholic fatty liver disease (NAFLD) that is a consequence of insulin resistance with histological findings ranging from (1) fat alone to (2) fat plus inflammation to (3) fat plus ballooning degeneration to (4) fat plus alcoholic hepatitis-like lesions (sinusoidal fibrosis and polymorphonuclear infiltrates, with or without Mallory hyalin). Only types 3 and 4 should be considered as NASH.
Macrovesicular fatty liver (or steatosis) is a common finding that has been observed in a wide range of clinical conditions. Table 1 displays a proposed classification of NAFL into two types: the primary type, which is caused by the conditions associated with insulin resistance, and the secondary type, which is caused by drugs, surgical procedures, and a variety of miscellaneous disorders. An adequate review of all the causes of NAFL listed in Table 1 is beyond the scope and intent of this article. Therefore, this discussion will be focused on the clinical characteristics and the natural history of primary NAFL.
Source...