Non-alcoholic fatty liver disease
Encyclopedia
Non-alcoholic fatty liver disease (NAFLD) is one cause of a fatty liver
, occurring when fat is deposited (steatosis
) 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 (e.g. diabetes mellitus type 2
) such as weight loss, metformin
and thiazolidinedione
s. Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD this being regarded as a major cause of cirrhosis
of the liver of unknown cause.
, and dull right-upper-quadrant abdominal discomfort
. Mild jaundice
may be noticed although this is rare. More commonly NAFLD is diagnosed following abnormal liver function tests
during routine blood tests. By definition, alcohol
consumption of over 20 g/day (about 25 ml/day) excludes the condition.
NAFLD is associated with insulin resistance
and metabolic syndrome
(obesity
, combined hyperlipidemia
, diabetes mellitus (type II)
and high blood pressure
).
showing steatosis
. An ultrasound may also be used to exclude gallstone
problems (cholelithiasis). A biopsy
(tissue examination) of the liver
is the only test widely accepted as definitively distinguishing NASH from other forms of liver disease and can be used to assess the severity of the inflammation
and resultant fibrosis
.
Non-invasive diagnostic tests have been developed, such as FibroTest
, that estimates liver fibrosis, and SteatoTest, that estimates steatosis, however their use has not been widely adopted. Apoptosis has been shown to be the mechanism of hepatocyte destruction and caspase-cleaved cytokeratin 18 (M30-Apoptosense ELISA
) in serum/plasma is often elevated in patients with NASH.
Other diagnostic tests are available. Relevant blood tests include erythrocyte sedimentation rate
, glucose
, albumin
, and renal function
. Because the liver is important for making proteins used in coagulation
some coagulation related studies are often carried out especially the INR (international normalized ratio). Blood tests (serology
) are usually used to rule out viral hepatitis
(hepatitis A, B, C, EBV
, CMV
and herpes viruses), rubella
, and autoimmune related diseases. Hypothyroidism
is more prevalent in NASH patients which would be detected by determining the TSH
.
It has been suggested that in cases involving overweight patients whose blood tests do not improve on losing weight and exercising that a further search of other underlying causes be undertaken. This would also apply to those with fatty liver that are very young or not overweight or insulin-resistant. In addition those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those that present with moderate to advanced fibrosis or cirrhosis.
). A liver can remain fatty without disturbing liver function, but by varying mechanisms and possible insults to the liver may also progress to outright inflammation
of the liver. When inflammation occurs in this setting, the condition is then called NASH. Over time, up to 20 percent of patients with NASH may develop cirrhosis
. Cigarette smoking is not associated with an increased risk of developing NASH.
The exact cause of NAFLD is still unknown. However, both obesity
and insulin resistance
probably play a strong role in the disease process. The exact reasons and mechanisms by which the disease progresses from one stage to the next are not known.
One debated mechanism proposes a "second hit", or further injury, enough to cause change that leads from hepatic steatosis to hepatic inflammation. Oxidative stress
, hormonal imbalances, and mitochondrial
abnormalities are potential causes for this "second hit" phenomenon
.
Polymorphisms
(genetic variations) in the single-nucleotide polymorphisms (SNPs) T455C and C482T in APOC3 are associated with fatty liver disease, insulin resistance
, and possibly hypertriglyceridemia
. 95 healthy Asian Indian men and 163 healthy non-Asian Indian men around New Haven, Connecticut were genotyped for polymorphisms in those SNPs. 20% homogeneous wild both loci. Carriers of T-455C, C-482T, or both (not additive) had a 30% increase in fasting plasma apolipoprotein C3, 60% increase in fasting plasma triglyceride and retinal fatty acid ester, and 46% reduction in plasma triglyceride clearance. Prevalence of non-alcoholic fatty liver disease was 38% in carriers, 0% wild (normal). Subjects with fatty liver disease had marked insulin resistance.
This is challenging as most children with NAFLD are asymptomatic with few showing abdominal pain. Currently, liver biopsy is considered the gold standard for diagnosing NAFLD. However, this method is invasive, costly and bears greater risk for children, and noninvasive screening and diagnosing methods would have significant public health implications for children with NAFLD.
The only treatment shown to be truly effective in childhood NAFLD is weight loss.
levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints:.
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.
In a study using the NHANES III
dataset, it has been shown that mild alcohol consumption (one glass of wine
a day) reduces the risk of NAFLD by half.
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...
, occurring when fat is deposited (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...
) in 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...
not due to excessive alcohol use
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...
. It is related to insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
and the 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...
and may respond to treatments originally developed for other insulin-resistant states (e.g. diabetes mellitus type 2
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
) such as weight loss, metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
and thiazolidinedione
Thiazolidinedione
The thiazolidinediones , also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.- Mechanism of action :...
s. Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD this being regarded as a major cause of 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...
of the liver of unknown cause.
Symptoms and associations
Most patients with NAFLD have few or no symptoms. Patients may complain of fatigue, malaiseMalaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, and dull right-upper-quadrant abdominal discomfort
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
. Mild jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
may be noticed although this is rare. More commonly NAFLD is diagnosed following abnormal liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
during routine blood tests. By definition, 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....
consumption of over 20 g/day (about 25 ml/day) excludes the condition.
NAFLD is associated with insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
and 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...
(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...
, combined hyperlipidemia
Combined hyperlipidemia
In medicine, combined hyperlipidemia is a commonly occurring form of hypercholesterolemia characterised by increased LDL and triglyceride concentrations, often accompanied by decreased HDL...
, diabetes mellitus (type II)
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
and high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
).
Secondary causes
NAFLD can also be caused by some medications:- AmiodaroneAmiodaroneAmiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...
- Antiviral drugAntiviral drugAntiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s (nucleoside analogues) - AspirinAspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
rarely as part of Reye's syndromeReye's syndromeReye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar . The classic features are liver damage, aspirin use and a viral infection...
in children - CorticosteroidCorticosteroidCorticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s - MethotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
- TamoxifenTamoxifenTamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
- Tetracycline
Diagnosis
Common findings are elevated liver enzymes and a liver ultrasoundMedical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
showing 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...
. An ultrasound may also be used to exclude gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
problems (cholelithiasis). A biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(tissue examination) 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...
is the only test widely accepted as definitively distinguishing NASH from other forms of liver disease and can be used to assess the severity of the 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...
and resultant 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...
.
Non-invasive diagnostic tests have been developed, such as FibroTest
FibroTest
FibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases...
, that estimates liver fibrosis, and SteatoTest, that estimates steatosis, however their use has not been widely adopted. Apoptosis has been shown to be the mechanism of hepatocyte destruction and caspase-cleaved cytokeratin 18 (M30-Apoptosense ELISA
M30-Apoptosense ELISA
M30 Apoptosense® ELISA is an enzyme-linked immunosorbent assay developed for the detection of soluble caspase-cleaved keratin 18 .-History:...
) in serum/plasma is often elevated in patients with NASH.
Other diagnostic tests are available. Relevant blood tests include erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
, glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
, and renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
. Because the liver is important for making proteins used in coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
some coagulation related studies are often carried out especially the INR (international normalized ratio). Blood tests (serology
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
) are usually used to rule out viral 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"...
(hepatitis A, B, C, EBV
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
, CMV
CMV
CMV is a three-letter abbreviation with multiple meanings, as described below:* Calima Aviación, ICAO airline designator* Cauliflower mosaic virus, although more commonly abbreviated as CaMV...
and herpes viruses), rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
, and autoimmune related diseases. Hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
is more prevalent in NASH patients which would be detected by determining the TSH
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
.
It has been suggested that in cases involving overweight patients whose blood tests do not improve on losing weight and exercising that a further search of other underlying causes be undertaken. This would also apply to those with fatty liver that are very young or not overweight or insulin-resistant. In addition those whose physical appearance indicates the possibility of a congenital syndrome, have a family history of liver disease, have abnormalities in other organs, and those that present with moderate to advanced fibrosis or cirrhosis.
Pathophysiology
NAFLD is considered to cover a spectrum of disease activity. This spectrum begins as fatty accumulation in the liver (hepatic 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...
). A liver can remain fatty without disturbing liver function, but by varying mechanisms and possible insults to the liver may also progress to outright 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. When inflammation occurs in this setting, the condition is then called NASH. Over time, up to 20 percent of patients with NASH may develop 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...
. Cigarette smoking is not associated with an increased risk of developing NASH.
The exact cause of NAFLD is still unknown. However, both 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 insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
probably play a strong role in the disease process. The exact reasons and mechanisms by which the disease progresses from one stage to the next are not known.
One debated mechanism proposes a "second hit", or further injury, enough to cause change that leads from hepatic steatosis to hepatic inflammation. Oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
, hormonal imbalances, and mitochondrial
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
abnormalities are potential causes for this "second hit" phenomenon
Phenomenon
A phenomenon , plural phenomena, is any observable occurrence. Phenomena are often, but not always, understood as 'appearances' or 'experiences'...
.
Dietary Influences
Soft drink (SD) consumption—specifically high-fructose corn syrup SD consumption—has become a major concern in public health. 80% of NAFLD patients with or without metabolic syndrome had excessive intake of SD (>500 cm3/day or >12 teaspoons/day added sugar) compared to the 17% healthy controls (P-value <0.001; Confidence Interval=95%). This included Coca-Cola (both regular and diet) and fruit juices as the most common SD sources. Another study suggests that 31 g/day in SD sugar intake raises the odds ratio for NAFLD to 1.45 times with 95% confidence. Metabolically, phosphorylation of fructose by fructokinase is specific and not rate-limited causing human hepatic ATP depletion. Ultimately, this leads to lipogenesis, which increases NAFLD risk.Genetics
Indian men have a high prevalence of non-alcoholic fatty liver disease. Two genetic mutations for this susceptibility have been identified, and these mutations provided clues to the mechanism of NASH and related diseases.Polymorphisms
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
(genetic variations) in the single-nucleotide polymorphisms (SNPs) T455C and C482T in APOC3 are associated with fatty liver disease, insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
, and possibly hypertriglyceridemia
Hypertriglyceridemia
In medicine, hypertriglyceridemia denotes high blood levels of triglycerides, the most abundant fatty molecule in most organisms. It has been associated with atherosclerosis, even in the absence of hypercholesterolemia . It can also lead to pancreatitis in excessive concentrations In medicine,...
. 95 healthy Asian Indian men and 163 healthy non-Asian Indian men around New Haven, Connecticut were genotyped for polymorphisms in those SNPs. 20% homogeneous wild both loci. Carriers of T-455C, C-482T, or both (not additive) had a 30% increase in fasting plasma apolipoprotein C3, 60% increase in fasting plasma triglyceride and retinal fatty acid ester, and 46% reduction in plasma triglyceride clearance. Prevalence of non-alcoholic fatty liver disease was 38% in carriers, 0% wild (normal). Subjects with fatty liver disease had marked insulin resistance.
Pediatric Population
Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) was first reported in 1983. It is currently the primary form of liver disease among children. NAFLD has been associated with the metabolic syndrome, which is a cluster of risk factors that contribute to the development of cardiovascular disease and type 2 diabetes mellitus. Studies have demonstrated that abdominal obesity and insulin-resistance in particular are thought to be key contributors to the development of NAFLD. Because obesity is becoming an increasingly common problem worldwide, the prevalence of NAFLD has been increasing concurrently. Moreover, boys are more likely to be diagnosed with NAFLD than girls with a ratio of 2:1. Studies have suggested that progression toward a more advance stage of disease among children is dependent on age and presence of obesity. This finding is consistent with previous studies in adults demonstrating the same association between age and obesity, and liver fibrosis. Early diagnosis of NAFLD in children may help prevent the development of liver disease during adulthood.This is challenging as most children with NAFLD are asymptomatic with few showing abdominal pain. Currently, liver biopsy is considered the gold standard for diagnosing NAFLD. However, this method is invasive, costly and bears greater risk for children, and noninvasive screening and diagnosing methods would have significant public health implications for children with NAFLD.
The only treatment shown to be truly effective in childhood NAFLD is weight loss.
Epidemiology
The prevalence of non-alcoholic fatty liver disease ranges from 9 to 36.9% of the population in different parts of the world. Approximately 23% of the United States population suffers from non-alcoholic fatty liver, and continues to trend upward. The prevalence of non-alcoholic fatty liver disease is higher in Hispanics, which can be attributed to high rates of obesity and type 2 diabetes in Hispanic populations. Non-alcoholic fatty liver disease is also more common among men than women in all ages groups until age 60, where the prevalence between sex equalize. This is due to the protective nature of estrogen.Treatment
A large number of treatments for NAFLD have been studied. While many appear to improve biochemical markers such as alanine transaminaseAlanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints:.
- Treatment of nutrition and excessive body weight:
- Nutritional counseling: Diet changes have shown significant histological improvement.
- Weight loss: gradual weight loss may improve the process in obese patients; rapid loss may worsen NAFLD. The negative effects of rapid weight loss are controversial: the results of a meta-analysis showed that the risk of progression is very low.https://www.aasld.org/eweb/DynamicPage.aspx?webcode=07LMPR_Bariatric
- A recent meta-analysis presented at the Annual Meeting of American Association for Study of Liver Diseases(AASLD) reported that weight-loss surgery leads to improvement and or resolution of NASH in around 80 % of patients.http://www.medpagetoday.com/Pediatrics/Obesity/tb/7270
- Insulin sensitisers (metforminMetforminMetformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
and thiazolidinedioneThiazolidinedioneThe thiazolidinediones , also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.- Mechanism of action :...
s) have shown efficacy in some studies. - ursodeoxycholic acid and lipid-lowering drugs, have little benefit.
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.
In a study using the NHANES III
National Health and Nutrition Examination Survey
The National Health and Nutrition Examination Survey is a survey research program conducted by the National Center for Health Statistics to asses the health and nutritional status of adults and children in the United States, and to track changes over time. The survey combines interviews and...
dataset, it has been shown that mild alcohol consumption (one glass of wine
Wine
Wine is an alcoholic beverage, made of fermented fruit juice, usually from grapes. The natural chemical balance of grapes lets them ferment without the addition of sugars, acids, enzymes, or other nutrients. Grape wine is produced by fermenting crushed grapes using various types of yeast. Yeast...
a day) reduces the risk of NAFLD by half.
See also
- Fatty liverFatty 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...
includes both non-alcoholic and 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... - 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...
External links
- Medscape article on NASH.
- MEDICINENET article on Steatosis.
- NIH page on Nonalcoholic Steatohepatitis
- British Medical Journal article on the diagnosis and initial management of non-alcoholic fatty liver disease