Steatohepatitis
Encyclopedia
Steatohepatitis is a type of liver disease
, characterized by inflammation
of the liver
with concurrent fat
accumulation in liver ("steato", meaning fat, "hepatitis
", meaning inflammation of the liver). Mere deposition of fat in the liver is termed steatosis
, and together these constitute fatty liver
changes.
Classically seen in alcoholic
s as part of alcoholic liver disease
, steatohepatitis also is frequently found in people with diabetes and obesity
and it is related to metabolic syndrome
. When not associated with excessive alcohol
intake, it is referred to as non-alcoholic steatohepatitis, or NASH and is the progressive form of the relatively benign Non-alcoholic fatty liver disease
. Steatohepatitis of either etiology
may progress to cirrhosis
, and NASH is now believed to be a frequent cause of unexplained cirrhosis (at least in Western societies). NASH is also associated with Lysosomal Acid Lipase Deficiency
.
), mixed lobular inflammation, ballooning degeneration
of hepatocyte
s (sometimes with identifiable Mallory bodies), glycogen
ated hepatocyte nuclei, and pericellular fibrosis
. The "chicken wire" pattern of the pericellular fibrosis, which affects portal areas only secondarily in later stages, is very characteristic and is identified on trichrome stain
s.
, exercise, and antiglycemic drug
s may alter the course of the disease. A randomized controlled trial
found that "pioglitazone
led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis".
As of 2007, no treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake.. However, Vitamin E can improve some symptoms of NASH and was superior to insulin sensitizer in one large study. In the Pioglitazone
versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, for patients with NASH but without diabetes mellitus, the use of very high dosages of vitamin E (800 IU/day) for four years was associated with a significantly higher rate of improvement than placebo (43% vs. 19%) in the primary outcome. The primary outcome was an improvement in certain histological features as measured by biopsy—but it did not improve fibrosis. Pioglitazone, an insulin sensitizer, improved some features of NASH but not the primary outcome, and resulted in a significant weight gain (mean 4.7 kilograms) which persisted after pioglitazone was discontinued.
concluded that "liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis."
. Its relevance and high prevalence were recognized mainly in the 1990s. Some think that NASH is a diagnosis of exclusion, and that many cases may be in fact be due to other causes.
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
, characterized by inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
of the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
with concurrent fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
accumulation in liver ("steato", meaning fat, "hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
", meaning inflammation of the liver). Mere deposition of fat in the liver is termed steatosis
Steatosis
In cellular pathology, steatosis is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm...
, and together these constitute fatty liver
Fatty liver
Fatty liver, also known as fatty liver disease , is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis...
changes.
Classically seen in alcoholic
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
s as part of alcoholic liver disease
Alcoholic liver disease
Alcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...
, steatohepatitis also is frequently found in people with diabetes and obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
and it is related to metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
. When not associated with excessive alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
intake, it is referred to as non-alcoholic steatohepatitis, or NASH and is the progressive form of the relatively benign Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is one cause of a fatty liver, occurring when fat is deposited in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states...
. Steatohepatitis of either etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
may progress to cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, and NASH is now believed to be a frequent cause of unexplained cirrhosis (at least in Western societies). NASH is also associated with Lysosomal Acid Lipase Deficiency
Lysosomal Acid Lipase Deficiency
Lysosomal Acid Lipase Deficiency happens when the body does not produce enough active LAL enzyme. Under normal conditions, the body produces an enzyme called lysosomal acid lipase . This enzyme plays an important role in breaking down fatty material in the body...
.
Pathophysiology
Steatohepatitis is characterized microscopically by hepatic fat accumulation (steatosisSteatosis
In cellular pathology, steatosis is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm...
), mixed lobular inflammation, ballooning degeneration
Ballooning degeneration
In histopathology, ballooning degeneration, formally ballooning degeneration of hepatocytes, is a form of liver parenchymal cell death....
of hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
s (sometimes with identifiable Mallory bodies), glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
ated hepatocyte nuclei, and pericellular fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
. The "chicken wire" pattern of the pericellular fibrosis, which affects portal areas only secondarily in later stages, is very characteristic and is identified on trichrome stain
Trichrome stain
A trichrome stain is a stain including three colored components. See trichrome article for more information.Types include:* Gömöri trichrome stain* Lillie's trichrome* Masson's trichrome stain...
s.
Treatment
Recent studies suggest that dietDiet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
, exercise, and antiglycemic drug
Anti-diabetic drug
Anti-diabetic medications treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents...
s may alter the course of the disease. A randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found that "pioglitazone
Pioglitazone
Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic action.Pioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe,"Glizone" and "Pioz" in India by Zydus CND and USV respectively and Zactos in Mexico by Takeda...
led to metabolic and histologic improvement in subjects with nonalcoholic steatohepatitis".
As of 2007, no treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake.. However, Vitamin E can improve some symptoms of NASH and was superior to insulin sensitizer in one large study. In the Pioglitazone
Pioglitazone
Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic action.Pioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe,"Glizone" and "Pioz" in India by Zydus CND and USV respectively and Zactos in Mexico by Takeda...
versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, for patients with NASH but without diabetes mellitus, the use of very high dosages of vitamin E (800 IU/day) for four years was associated with a significantly higher rate of improvement than placebo (43% vs. 19%) in the primary outcome. The primary outcome was an improvement in certain histological features as measured by biopsy—but it did not improve fibrosis. Pioglitazone, an insulin sensitizer, improved some features of NASH but not the primary outcome, and resulted in a significant weight gain (mean 4.7 kilograms) which persisted after pioglitazone was discontinued.
Prognosis
A retrospective cohort studyCohort study
A cohort study or panel study is a form of longitudinal study used in medicine, social science, actuarial science, and ecology. It is an analysis of risk factors and follows a group of people who do not have the disease, and uses correlations to determine the absolute risk of subject contraction...
concluded that "liver failure is the main cause of morbidity and mortality in NASH-associated cirrhosis. The prognosis is either similar or less severe than HCV-cirrhosis."
History
NASH was first described in 1980 in a series of patients of the Mayo ClinicMayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
. Its relevance and high prevalence were recognized mainly in the 1990s. Some think that NASH is a diagnosis of exclusion, and that many cases may be in fact be due to other causes.
See also
- Alcoholic liver diseaseAlcoholic liver diseaseAlcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...
- Non-alcoholic fatty liver diseaseNon-alcoholic fatty liver diseaseNon-alcoholic fatty liver disease is one cause of a fatty liver, occurring when fat is deposited in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states...
- Steatosis hepatitisFatty liverFatty liver, also known as fatty liver disease , is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis...
- Lysosomal acid lipase deficiencyLysosomal Acid Lipase DeficiencyLysosomal Acid Lipase Deficiency happens when the body does not produce enough active LAL enzyme. Under normal conditions, the body produces an enzyme called lysosomal acid lipase . This enzyme plays an important role in breaking down fatty material in the body...
- Hepatitis C Long-Term Outcomes of Cirrhosis in Nonalcoholic Steatohepatitis Compared With Hepatitis C