What are Fatty Liver, NAFLD, and NASH?
Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis (NASH), to cirrhosis (irreversible, advanced scarring of the liver). All of the stages of NAFLD have in common the accumulation of fat (fatty infiltration) in the liver cells (hepatocytes). In NASH, the fat accumulation is associated with varying degrees of inflammation (hepatitis) and scarring (fibrosis) of the liver.
The term nonalcoholic is used because NAFLD and NASH occur in individuals who do not consume excessive amounts of alcohol. Yet, in many respects, the histological picture of NAFLD (when we look at a biopsy piece of liver under the microscope) is similar to what can be seen in liver disease that is due to excessive intake of alcohol. As we shall see, however, the clinical circumstances in NAFLD and NASH are very different from those in alcoholic liver disease (ALD).
The NAFLD spectrum is thought to begin with and progress from its simplest stage, called simple fatty liver (steatosis). That is, fatty liver is the initial abnormality in the spectrum of NAFLD. Simple fatty liver involves just the accumulation of fat in the liver cells with no inflammation or scarring.
The fat is actually composed of a particular type of fat (triglyceride) that accumulates in tiny sacs within the liver cells. This accumulation of fat in liver cells is not the same as the fat cells (adipocytes) that constitute our body fat. Fatty liver is a harmless (benign) condition, which means that it, by itself, does not cause any significant liver damage.
The next stage and degree of severity in the NAFLD spectrum is NASH. Fortunately, only a fraction of patients with simple fatty liver will develop NASH. As mentioned, NASH involves the accumulation of fat in the liver cells as well as inflammation of the liver. The inflammatory cells can destroy the liver cells (hepatocellular necrosis).
In the terms “steatohepatitis” and “steatonecrosis”, steato refers to fatty infiltration, hepatitis refers to inflammation in the liver, and necrosis refers to destroyed liver cells. Strong evidence suggests that NASH, in contrast to simple fatty liver, is not a harmless condition. This means that NASH can ultimately lead to scarring of the liver (fibrosis) and then irreversible, advanced scarring (cirrhosis). Cirrhosis that is caused by NASH is the last and most severe stage in the NAFLD spectrum.
Much is not yet known about NASH and NAFLD. For example, as discussed below, the progression from each of the different stages of NAFLD is not well understood. Moreover, even liver specialists still do not agree on the exact microscopic definition of NASH.
Nevertheless, individuals who develop any of the three stages of NAFLD (fatty liver, NASH, or cirrhosis) share common risk factors. Accordingly, fatty liver and NASH are described in this article as part of the spectrum of NAFLD. Remember, NAFLD refers to the entire spectrum beginning with fatty liver, progressing through NASH, and ending with cirrhosis. NASH is that stage of the spectrum that involves fat accumulation (steatosis), inflammation (hepatitis), and scarring (fibrosis) in the liver.
Indeed, there are many other causes of fat accumulation in the liver besides NAFLD. However, NAFLD and NASH are considered the primary fatty liver diseases. The secondary fatty liver diseases include those that occur in other types of liver disease. Thus, alcoholic liver disease (ALD) is the most frequent secondary fatty liver disease. Secondary fatty liver can also occur in chronic viral hepatitis C (HCV), chronic viral hepatitis B (HBV), chronic autoimmune hepatitis (AIH), and Wilson’s disease. (In AIH, the body’s immune defense system mistakenly attacks its own liver. In Wilson’s disease, an accumulation of copper injures the liver.) In all of these secondary fatty liver diseases, fatty liver is associated with other liver abnormalities distinct from NAFLD and is thought to result from liver cell injury.
Another type of secondary fatty liver disease is unrelated to other specific liver diseases. In these cases, the accumulation of liver fat is due to disturbances in the body’s processing (metabolism) of fat (lipid) rather than to direct injury to the liver cells. Such causes include certain drugs (e.g., prednisone), some gastrointestinal operations (bariatric surgery) for obesity, malnutrition, and genetic defects in proteins that process (metabolize) lipids. As described below, all of the secondary causes of fatty liver disease must be ruled out before attempting to establish the diagnosis of NAFLD. This is why NAFLD is considered a diagnosis of exclusion.
Liver specialists (hepatologists) actually recognized what is now called NASH in the 1970’s, but it was described under different names. In 1980, Dr. J. Ludwig from the Mayo Clinic in Rochester, Minnesota made an astute observation. He noted that certain individuals who share common features (obesity, diabetes, and elevated cholesterol) had a liver disease that closely resembled alcoholic liver disease (ALD). However, these patients drank no alcohol whatsoever. So, Dr. Ludwig was the first to coin the term nonalcoholic steatohepatitis (NASH). For many years, however, NASH was thought by most doctors to be a totally harmless condition. Or, it was considered an innocent bystander that was associated with other liver diseases (especially viral hepatitis). In fact, during those years, simple fatty liver (steatosis) and NASH were considered to be equivalent processes.
The discovery of the hepatitis C virus (HCV) played an accidental role in the recognition of the clinical significance of NASH. Up until 1990, individuals who had hepatitis with signs similar to those of viral hepatitis A or B (but with negative blood tests for both) were said to have non-A-non-B viral hepatitis. Then, in 1990 the hepatitis C virus was discovered. In the years that followed, the ways by which HCV is spread (blood transfusion and intravenous drug use) and its effects on the liver were recognized. It turned out that a great majority of non-A-non-B viral hepatitis cases were in fact due to HCV. There remained, however, some individuals whose tests were negative for HCV as well as for other types of liver disease. Only then did researchers realize that for many of these individuals, NASH was the culprit. This realization has since led to a flurry of interest and research regarding NASH and to the understanding that it is not a harmless condition.
Clinical studies and basic research on NAFLD are still in their infancy as compared to other common liver diseases, such as ALD and HCV. As a result, we continue to have an incomplete understanding of the natural history of NAFLD. Moreover, we do not know much about the processes responsible for the progression from simple fatty liver to NASH and NASH to cirrhosis.
The NAFLD spectrum is probably the most common disease of the liver in the United States. Although precise information on the number of cases of NAFLD and NASH is limited, estimates have been made. Moreover, information is available on which individuals are at risk to develop NAFLD and NASH.
To date, no data are available on the incidence (number of new cases per year) of NAFLD or NASH in the United States, or anywhere else in the world for that matter. To determine the incidence of this disease, long-term studies in populations at risk will be needed. Such data collection has only just begun in several medical centers.
We do have data, however, on theprevalence (number of cases observed at one time) of NAFLD and NASH in cross-sections of populations at risk. Therefore, knowing which individuals are at risk is important. In this regard, a large body of evidence now supports the concept that NAFLD is associated with a condition called insulin resistance, which is described in more detail below. Suffice it to say at this point that diabetes mellitus type 2 (DM2) and, in addition, especially the overweight condition and obesity are the most recognizable features of insulin resistance.
As just indicated, obesity is linked closely to NAFLD. Therefore, to get a grasp on the frequency of NAFLD and NASH and the impact of obesity on NAFLD in the population, one has to understand how obesity is defined. A calculation of the body mass index (BMI) is a method that can be used to determine degrees of obesity.
The BMI is calculated by dividing a person’s weight in kilograms by his or her height in meters squared (kg/m2). In the non-metric system, BMI = (lbs/inches2) x 703. In adults, normal weight is defined as a BMI between 20 and 25, overweight from 25 to 30, obesity from 30 to 35, significant obesity from 35 to 40, morbid obesity from 40 to 45, super obesity from 45 to 50, and super-morbid obesity greater than 50.
In addition to the BMI method, obesity can be described according to the distribution of body fat. Fat can be distributed predominantly either to the hips (gynoid or pear-shaped) or to the abdomen (central, android, or apple-shaped). An abdominal predominance of fat is the most commonly observed type of obesity in insulin resistance. Abdominal obesity is defined in men by a waist-to-hip circumference ratio greater than 1.0 or a waist circumference greater than 40 inches (102 centimeters). In women, abdominal obesity is defined by a waist-to-hip ratio greater than 0.8 or a waist circumference greater than 35 inches (88 centimeters). In fact, simple waist measurements alone seem to be the best predictor of the type of body fat distribution that is most closely associated with insulin resistance.
The normal limits that have been established for the BMI and waist circumference are not based on considerations of appearance. Rather, they are based on the significant risk of developing complications due to being overweight (BMI-related morbidity), such as coronary artery heart disease and diabetes. In children, however, normal ranges of the BMI vary according to age and gender. Furthermore, up until the age of 16, the upper limits for the normal BMI are lower than 25. Therefore, in children, the degree of overweight is more often expressed as a percentage above ideal body weight
As could be expected, primary NAFLD is observed principally in developed countries. In these societies, a sedentary lifestyle and high calorie, sugar, and fat diets lead to DM2 and obesity.
Thus, in developed countries, the overall prevalence of NAFLD in the population is estimated to be approximately 20%, and that of NASH 3%. The prevalence of each is presumably much higher in obese and diabetic persons. The reason for this presumption is that upwards of 55% of patients with NASH have DM2 and 95% are obese. Thus, the prevalence of simple fatty liver in obese persons can be estimated to be approximately 90% and that of NASH in obese persons to be 20%. NASH is typically a disease of middle-aged overweight women with predominantly central (abdominal) fat distribution. However, there are also increasing reports of NASH related to obesity in men and even in pediatric populations.
The Center for Disease Control reports that currently, approximately one half of the US adultpopulationisoverweight (BMI>25) and one quarter of the US adult populationisobese(BMI>30). Projecting the prevalence of NAFLD and NASH in the obese subpopulation to the entire population would suggest that upwards of 29 million Americans have NAFLD and 6.4 million of these persons have NASH.
These estimates, however, are very general. Another way to guesstimate is to study the relationship between the BMI and elevated liver enzymes (serum transaminases). You see, elevated transaminases can be caused by NAFLD in obese individuals. Thus, as compared to a normal BMI of less than or equal to 25, the risk of having elevated transaminases for men is roughly 2 times greater for a BMI of 25-30, 4 times greater for a BMI of 30-35, 5 times greater for a BMI of 35-40, and 6 times greater for a BMI greater than 40. For women, the risk is 2 times greater for a BMI of 25-30, 2.5 times greater for a BMI of 30-35, 4 times greater for a BMI of 35-40, and 5 times greater for a BMI greater than 40.
The bottom line is that currently, NAFLD is the most prevalent liver disease in the Unites States, representing an estimated 24% of cases of liver disease.
The exact cause of NASH is still unknown. Strong evidence, however, supports the concept that the process common to all stages of primary fatty liver disease (NAFLD) is insulin-resistance. A number of other factors may be involved as well in causing NAFLD and NASH and in progressing through the stages of NAFLD.
Insulin resistance is a state wherein normal signaling pathways that convey biochemical messages between insulin and its target cells are disrupted. As a result, the insulin does not exert its normal or full effects. Put another way, the body is resistant to the effects of insulin.
What does insulin normally do? Well, the pancreas secretes varying amounts of insulin during the day in response to food intake. Insulin works to maintain blood sugar (glucose) at normal levels. Thus, insulin prevents blood glucose from becoming too elevated. If insulin does not work in this way, high blood sugars and diabetes would occur. Insulin is a hormone that acts on the receptors of cells to trigger the complex biochemical reactions that control blood sugar. The cells targeted by insulin are mainly the fat cells (adipocytes), muscle cells (striated myocytes), and the liver cells (hepatocytes).
In insulin resistance, a defect in these insulin receptors causes insulin to be less effective than it normally would be. Thus, the pancreas must produce more insulin than normal in order to maintain normal blood glucose levels. Initially in this process, the increased insulin levels are sufficient to maintain normal blood glucose. In these patients, however, although the blood glucose is normal, the condition of being overweight or obesity are still clues that they are insulin resistant. At this juncture, only sophisticated blood tests (such as the euglycemic clamp test) can detect insulin resistance at the biochemical level.
As the insulin resistance progresses, even very high levels of insulin become ineffective. This degree of insulin resistance leads to elevated blood sugars and diabetes mellitus, type 2 (DM2). DM2 is usually managed by diet, exercise, and medication (see treatment section) that increases insulin sensitivity (the opposite of insulin resistance). If the process proceeds unchecked, however, the pancreas can no longer secrete insulin. Then, the patients require insulin injections, which condition is referred to as insulin-dependent DM2. Insulin resistance and DM2 are very different from diabetes mellitus type 1 (DM1), which is also called juvenile-onset diabetes. In DM1, a defect in insulin secretion occurs early on in life and requires immediate and ongoing treatment with insulin.
Insulin resistance can also surface early in life when it is due to congenital genetic abnormalities in the insulin receptors. More often, however, as described above, it becomes evident later in life as a result of acquired obesity. A sedentary lifestyle and a diet rich in carbohydrates, sugars, and fats also promote insulin resistance. Moreover, the degree of insulin resistance increases with a greater BMI and abdominal fat (that is, big waists). Elevated lipids (LDL cholesterol and triglycerides) are also associated with insulin resistance.
Insulin resistance leads to changes in the processing (metabolism) of sugar (glucose) and fat (lipid) in the liver, muscles, and fat cells (adipocytes). The result of these changes is an increased uptake (infiltration and accumulation) of triglyceride fat into the liver cells. The triglycerides are absorbed from the diet as well as channeled from abdominal fat and peripheral muscles. These large quantities of triglyceride fat are then stored in tiny sacs (vesicles) inside the liver cells.
So, this is how a fatty liver develops. In fact, it has been shown that as the BMI increases, so does the amount of fat in the liver.
Almost all patients with NASH are insulin resistant to some degree. However, only a minority of patients who are insulin resistant develop NASH. While an increased amount of fat in the liver may in itself lead to inflammation (see below), no evidence suggests that insulin resistance alone can lead to NASH.
The process whereby liver inflammation and death of liver tissue develop in NASH remains to be clearly explained. Several theories, however, have been advanced.
First, it is possible that the accumulation of fat in the liver alone could lead to the development of NASH. According to this theory, the large quantity of fat in the liver is thought to be a source of peroxidation (removal of electrons from molecules). Peroxidation thereby generates so-called free radicals. These free radicals then damage proteins and organelles (small structures within a cell) in the liver cells. Finally, this damage leads to cell death and/or an inflammatory cell cascade that removes the afflicted cells. In other words, the fat could be thought of as potential fuel waiting to be ignited.
However, a growing body of work in animal models of fatty liver suggests a two-hit hypothesis. With this theory, the first hit is the fatty liver (steatosis). Then, a second event, orsecond hit, leads to the development of NASH. Multiple potential second hits have been suggested.
Small hormones (cytokines), such astumor necrosis factor-alpha, which is secreted by cells and involved in inflammation, may induce cell death and even increase insulin resistance.
Intracellular organelles (mitochondria) that provide energy to the cell may malfunction and thereby cause a decrease in cell energy and lead to cell death.
Enzymes (cytochromes) that are involved in multiple metabolic pathways may lead to increased peroxidation and its consequences, as described above.
Receptors in the cell nucleus that are involved in triggering the effects of insulin (peroxisome proliferator activating receptors, PPAR) may fail and thus lead to insulin resistance, inflammation of the liver, and scarring of the liver.
Finally, recent research suggests that leptin resistance may contribute to the development of NASH. Think of this theory as analogous to the process of insulin resistance. Leptin is a very small hormone that is secreted by the brain, fat, and stomach cells in response to eating. Its main effect is to curb the appetite.
Patients with NASH have abnormally elevated levels of leptin but experience no loss of appetite. That is, they are resistant to the appetite-curbing effect of leptin. The leptin also helps control the processes of inflammation and scarring within the liver cells. Furthermore, interestingly enough, leptin also increases insulin sensitivity. But the fact that patients with NASH are insulin resistant supports the idea that the leptin receptors are malfunctioning.
The development of severe, irreversible scarring of the liver (cirrhosis) in NASH is even more poorly understood than the development of liver inflammation and death of liver tissue, as discussed above. Cirrhosis may simply develop over time as a result of chronic inflammation and repair, or may be due to yet a third hit.
As with chronic viral hepatitis and alcoholic liver disease (ALD), not all patients with NAFLD are at equal risk of developing substantial liver injury. Thus, not all diabetic and obese patients will develop a fatty liver, and not all patients with a fatty liver will develop NASH. Finally, not all patients with NASH will develop cirrhosis. This varying susceptibility of individuals to these diseases coupled with multiple disease-producing pathways suggests that the cause of primary NASH is a multi-faceted process. The cause is thought to involve altered lipid metabolism that results from environmental factors and genetic predisposition.
Many more years of research will be required to fully understand the cause of NASH.The symptoms of NAFLD and NASH are identical. They are very bland (not dramatic) and non-specific (can also be observed in other diseases). They can occur at any adult age and, in children, usually appear after 10 years of age.
Actually, most patients have no symptoms. They may, however, experience occasional, vague right upper-quadrant abdominal pain (below the rib-cage on the right side). This pain characteristically is dull and aching, without a predictable pattern of occurrence.
It is not an intense, sudden, and severe pain, as might occur with, for example, gallstones. The abdominal pain in NAFLD and NASH is thought to be due to the stretching of the liver covering (capsule) when the liver enlarges and/or when there is inflammation in the liver.
In contrast to ALD, HBV, and HCV, symptoms of severe, acute (rapid onset) liver failure (due to intense hepatitis) are not observed in NAFLD or NASH. The symptoms and signs of liver failure include yellowing of the skin (jaundice), intense fatigue, loss of appetite, nausea, vomiting, and confusion.
The classic signs of insulin resistance dominate the physical exam in NAFLD and NASH. As mentioned above, obesity (especially abdominal obesity) is the most frequent finding. In addition, patients with long-standing DM2 may have complications from the diabetes, such as retinopathy (abnormal blood vessels in the eye), kidney (renal) failure, and coronary artery heart disease. Elevated blood pressure (hypertension) is frequent.
Acanthosis nigricans, a dark pigmentation of the skin of the armpits and neck, can be a sign of insulin resistance and is frequently seen in children with NASH. When the liver is palpated (felt by the doctor), it usually feels normal. However, when very large amounts of fat accumulate in the liver, it can be become quite large with a soft, rounded edge that can be easily felt by the doctor.
The cirrhosis stage of NAFLD usually occurs later in life (age 50 to 60 years), presumably after many years of NASH. Frequently at this stage, patients have insulin dependent DM2. (With ALD or HBV, in contrast, cirrhosis can sometimes develop over a short period of time and, therefore, occur earlier in life.) NASH patients with cirrhosis can be without symptoms (asymptomatic) if diagnosed early. However, they can have typical signs of compensated or decompensated cirrhosis.
The signs of compensated cirrhosis include a large, hardened liver, small, star-shaped vessels (spider angiomata) on the skin of the upper torso, blotchy redness on the palms (palmar erythema), whitened nails, thin silky hair, loss of body hair, prominent veins on the abdomen (abdominal collateral veins), irregular or absent menstruation in pre-menopausal women, and small testes and enlarged, sometimes painful breasts (gynecomastia) in men.
The signs of decompensated cirrhosis include all the above except that the liver may be shrunken and there may be swelling of the legs (edema), accumulation of fluid in the abdomen (ascites), bleeding from veins in the esophagus (varices), and mental confusion (hepatic encephalopathy).
Fatty liver has also been described in several medical syndromes (groupings of abnormalities). For example, fatty liver occurs in polycystic ovarian syndrome, in which polycystic ovaries are associated with obesity, excessive hair (hirsutism), and insulin resistance. Congenital lipodystrophy syndromes, which are rare disorders in which the fat in the torso and extremities shifts to the abdomen, are also associated with an enlarged fatty liver.
The complications of NASH include cirrhosis (also considered the last stage of NAFLD) and primary liver cancer (hepatocellular carcinoma, HCC).
The risk of developing cirrhosis in a patient with NASH is still uncertain and varies perhaps from 8% to 15%. Up to now, very few studies have followed patients over sufficient periods of time to actually document the progression of NASH to cirrhosis. There is indirect evidence, however, that NASH can lead to cirrhosis For example, in some patients, at the time of an initial diagnosis of NASH made by liver biopsy, cirrhosis is already present, along with the usual signs of NASH.
Nonetheless, it is important to understand that in most instances when cirrhosis develops, the fatty infiltration disappears (regresses) along with the inflammation. Cirrhosis in NASH with loss of fat and inflammation is referred to as burned-outcirrhosis. This situation may result from less fat coming to the liver by way of the portal vein (the vessel that brings blood from the intestines to the liver). In addition, a decrease in insulin secretion (with the development of insulin dependent DM2) causes the triglyceride fats to leave the liver.
Furthermore, more and more reports indicate that at least 50% of cases of cryptogeniccirrhosis (cirrhosis due to unidentified causes) occur in the setting of previous long-standing obesity and/or DM2. These observations suggest that insulin-resistance, hence NASH, was often the basis of what was called cryptogenic cirrhosis. In fact, the number of liver transplantations for presumed NASH-related cirrhosis is on the rise.
The high rate of recurrent NASH developing in the new livers of patients receiving liver transplants for cryptogenic cirrhosis further confirms the causal role of NASH. Finally, a study from France suggests that patients with NASH have a similar risk of developing cirrhosis as do patients with HCV. As indicated above, however, the progression to cirrhosis in NASH is thought to be slow and the cirrhosis diagnosis is typically made in patients in their sixties.
There are also reports of primary liver cancer (hepatocellular carcinoma, HCC) occurring in patients with NASH-related cirrhosis. Indeed, the incidence of HCC in NASH cirrhosis appears to be similar to that observed in HCV cirrhosis (1-2% per year). The process that causes liver cancer to form in NASH cirrhosis is unknown and has not yet been studied.
HCC may develop as a result of liver repair and regrowth (hepatocellular regeneration) without any factor specifically related to NASH. Some authors, however, have suggested that insulin resistance in this situation may promote the development of liver cancer.
In the absence of any specific clinical or biochemical signs, NASH remains a diagnosis that is made after excluding other causes of fatty liver and other causes of elevated liver enzymes.
The most frequent biochemical abnormality in the blood in NASH is persistent, mild to moderately elevated transaminases (ALT and AST). Transaminases are the liver enzymes that are most often elevated in the various types of hepatitis. (Remember that hepatitis refers to inflammation of the liver.) In NASH, their levels tend to fluctuate from month to month, and most often the ALT is greater than the AST.
This is different from alcoholic liver disease (ALD), in which the AST is usually greater than the ALT. Indeed, this fortuitous finding often leads to initially considering the diagnosis of NAFLD or NASH. Unfortunately, however, no biochemical test or imaging procedure can differentiate simple fatty liver from NASH.
Most of the other liver blood tests (e.g., bilirubin and alkaline phosphatase) are usually normal in patients with NASH. Gammaglutamyltranspeptidase (GGTP), however, is typically moderately elevated. Serum ferritin (a protein involved in iron storage and inflammation) can be significantly elevated, but transferrin saturation is usually normal. These iron studies suggest the presence of only mild, if any, deposition of iron in the liver (iron overload).
Abnormal biochemistry tests associated with insulin resistance include elevated total cholesterol, low-density lipoprotein (LDL, the so-called bad cholesterol), triglycerides, and blood sugar and decreased high-density lipoprotein (HDL, the good cholesterol). The diagnosis of NAFLD or NASH can be considered after excluding other causes of mild elevations of transaminases, such as alcoholic liver disease, drug-induced hepatitis, chronic HBV or HCV, autoimmune hepatitis, genetic hemochromatosis, alpha-1-antitrypsin deficiency, and Wilson’s disease.
Drugs than can promote fatty liver (secondary NAFLD) and even features of NASH include prednisone, amiodarone (Cordarone), tamoxifen (Nolvadex), methotrexate (Rheumatrex, Trexall), and nonsteroidal anti-inflammatory drugs (NSAIDS). A difficult diagnostic situation may be encountered in patients who are taking cholesterol-lowering drugs of the statin type. The reason for this difficulty is that statins frequently raise transaminases without producing any significant liver injury.
In this situation, NAFLD can be suspected if the ALT remains elevated long after stopping the medication. However, if the statin drug is responsible, the ALT will return to normal soon after stopping the drug. Ideally, before initiating statin therapy, liver enzymes should be determined, especially in patients at high-risk for NAFLD.
A good quality liver ultrasound can be highly sensitive (detects all fatty livers) and specific (detects only fatty livers) in diagnosing fatty liver. The classic ultrasound finding with a fatty liver is a hyperechoic (bright) liver. Ultrasound, however, needs a skilled operator and its sensitivity decreases with increased abdominal fat.
Computerized tomography (CT) scan performs well in detecting fatty liver and can even measure the degree of fat infiltration. This technique, however, is hampered by any liver iron deposition that may be associated with NAFLD. Magnetic resonance imaging (MRI) is the overall best imaging exam for fatty liver, but also remains the most expensive. Nevertheless, no imaging procedure can in itself establish the diagnosis of NASH.
Thus, a presumptive diagnosis of NAFLD can be made in an individual based on the following criteria.
Clinical and/or biochemical signs of insulin resistance
Chronically (long duration) elevated ALT
Signs of fatty liver on ultrasound
Exclusion of other causes of elevated ALT and fatty liver
Only a liver biopsy, however, can establish a definite diagnosis and determine the severity of the condition.
To make the diagnosis of NAFLD or NASH, the doctor must fully consider the possible role of alcohol in the patient’s liver disease. This consideration requires detailed interviewing of the patient. The patient must also be honest in reporting alcohol use to the doctor. Unfortunately, this is not always the case. More