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Steatosis / Nonalcoholic Fatty Liver Disease

Definition :
Nonalcoholic fatty liver disease (NAFLD) describes a range of conditions involving the liver that affect people who drink little or no alcohol.

The mildest type is simple fatty liver (steatosis), an accumulation of fat within your liver that usually causes no liver damage. A potentially more serious type, nonalcoholic steatohepatitis (NASH), is associated with liver-damaging inflammation and, sometimes, the formation of fibrous tissue. In some cases, this can progress either to cirrhosis, which can produce progressive, irreversible liver scarring, or to liver cancer.

Nonalcoholic fatty liver disease affects all age groups, including children. Most often, it's diagnosed in middle-aged people who are overweight or obese, and who may also have diabetes and elevated cholesterol and triglyceride levels.

With the increasing incidence of obesity and diabetes in Western countries, nonalcoholic fatty liver disease has become a growing problem. Although its true prevalence is unknown, some estimates suggest it may affect as many as one-third of American adults.

Because early-stage nonalcoholic fatty liver disease rarely causes any symptoms, it's often detected because of abnormal results of liver tests done for unrelated issues. Treatments for nonalcoholic fatty liver disease include weight loss, exercise, improved diabetes control and the use of cholesterol-lowering medications.

Causes :
It's unclear exactly what causes nonalcoholic fatty liver disease. But many researchers believe that metabolic syndrome — a cluster of disorders that increase the risk of diabetes, heart disease and stroke — likely plays an important role in its development. Signs and symptoms of metabolic syndrome include :
  • Obesity, particularly around the waist (abdominal obesity)
  • High blood pressure (hypertension)
  • One or more abnormal cholesterol levels — high levels of triglycerides, a type of blood fat, or low levels of high-density lipoprotein (HDL) cholesterol, the "good" cholesterol
  • Resistance to insulin, a hormone that helps to regulate the amount of sugar in your blood

Of these, insulin resistance may be the most important trigger of simple fatty liver (steatosis) and nonalcoholic steatohepatitis (NASH). Because both conditions can remain stable for many years, causing little harm, researchers have proposed that a "second hit" to the liver may trigger a progression to cirrhosis. Possible triggers include bacterial infections, hormonal abnormalities or an accumulation of excess iron in the liver caused by hemochromatosis.

It's also unclear exactly how a liver becomes fatty. The fat may come from other parts of your body, or your liver may absorb an increased amount of fat from your intestine. Another possible explanation is that your liver loses its ability to change fat into a form that can be eliminated. But one thing's certain: The eating of fatty foods, by itself, doesn't produce a fatty liver.

Researchers suspect that there may be a genetic component to the disorder, and are investigating whether genes play a role in the development of nonalcoholic fatty liver disease or if genes may affect the severity of the disorder.

Risk Factor :
Although the cause of nonalcoholic fatty liver disease is unclear, the condition is associated with many risk factors. The three most important ones are closely related to metabolic syndrome and insulin resistance :

  • Overweight and obesity. Your risk increases with every pound of excess weight. More than 70 percent of people with nonalcoholic steatohepatitis (NASH) are obese. Overweight is defined as having a body mass index between 25 and 29.9; obesity is defined as having a body mass index of 30 or higher.
  • Diabetes. When your body becomes resistant to the effects of insulin or your pancreas doesn't produce enough insulin to maintain a normal blood sugar (glucose) level, this can damage many organs in your body, including your liver . As many as three in four people with NASH also have diabetes.
  • Hyperlipidemia. High cholesterol levels and elevated triglycerides are common in people who develop NASH. It's estimated that up to 80 percent of people with NASH have hyperlipidemia.

Other risk factors include :

  • Abdominal surgery. Operations to remove large sections of the small intestine (small bowel resection), treat obesity (gastric bypass) or bypass parts of the small intestine (jejunal bypass) often lead to rapid weight loss, which may increase your risk of nonalcoholic fatty liver disease.
  • Medications. These include oral corticosteroids (prednisone, hydrocortisone, others), synthetic estrogens (Premarin, Ortho-Est, others) for menopause, amiodarone (Cordarone, Pacerone) for heart arrhythmias, tamoxifen for breast cancer and methotrexate Rheumatrex, Trexall), an immune-suppressing medication for rheumatoid arthritis.
  • Other conditions. These include Wilson's disease, a hereditary condition that affects copper levels; Weber-Christian disease, which affects nutrient absorption; and abetalipoproteinemia, a rare congenital disorder that affects the ability to digest fat. Inherited metabolic disorders that increase the risk of cirrhosis include galactosemia, a rare disorder that affects the way the body metabolizes milk sugar (lactose), and glycogen storage diseases, which prevent glycogen, the stored form of glucose, from being formed or released when your body requires it.

When to seek medical advice :
If you're experiencing any of the symptoms of nonalcoholic fatty liver disease — fatigue, malaise and a dull ache in your upper right abdomen — see your doctor. Make an appointment for a screening if you have risk factors for nonalcoholic fatty liver disease such as obesity, diabetes and hyperlipidemia.

Symptoms
:
You may not have signs and symptoms of simple fatty liver (steatosis) or nonalcoholic steatohepatitis (NASH). When symptoms do occur, they are usually vague and nonspecific and may include :

  • Fatigue
  • Malaise
  • A dull ache in your upper right abdomen, a possible sign of an enlarged liver

At a more advanced stage, such as cirrhosis, nonalcoholic fatty liver disease may cause :

  • Lack of appetite
  • Weight loss
  • Nausea
  • Small, red spider veins under your skin or easy bruising
  • Weakness
  • Fatigue
  • Yellowing of your skin and eyes and dark, cola-colored urine
  • Bleeding from engorged veins in your esophagus or intestines
  • Loss of interest in sex
  • Fluid in your abdominal cavity (ascites)
  • Itching on your hands and feet and eventually on your entire body
  • Swelling of your legs and feet from retained fluid (edema)
  • Mental confusion, such as forgetfulness or trouble concentrating (encephalopathy)
  • Liver failure
Diagnosis:
Because early-stage nonalcoholic fatty liver disease seldom causes signs and symptoms, your doctor may discover it during a routine medical examination. Many cases are detected after doctors order liver tests to monitor people taking cholesterol-lowering drugs.

Before diagnosing nonalcoholic fatty liver disease, your doctor may order blood tests for other conditions that cause liver damage, such as hepatitis B and C. He or she will also inquire about your current and past alcohol consumption. Excess alcohol consumption — three or more drinks a day for men and two or more drinks a day for women — can also cause fatty liver and steatohepatitis.

If your doctor suspects nonalcoholic fatty liver disease, you're likely to have certain tests, including :

  • Liver-function test. A damaged liver releases certain enzymes. If this blood test shows that these enzymes are mildly elevated, it may be a sign that you have liver damage.
  • Ultrasound (ultrasonography). This noninvasive test uses sound waves to produce a picture of internal organs, including your liver. Abdominal ultrasound is painless and usually takes less than 30 minutes. While you lie on a bed or examining table, a technician applies a conductive gel to your abdomen and places a hand-held device (transducer) on the area, moving the transducer along your skin to locate your liver and adjacent organs. The transducer emits sound waves that are reflected from your liver and transformed into a computer-generated image.
  • Computerized tomography (CT). This test uses X-rays to produce cross-sectional images of your body.
  • Magnetic resonance imaging (MRI). Instead of X-rays, MRI creates images using a magnetic field and radio waves. Sometimes a contrast dye may be used. The test can take from 15 minutes to an hour. You may find an MRI scan to be more uncomfortable than a CT scan. That's because you'll likely be reclining on a stretcher enclosed in a tube with very little space above you or beside you. The thumping noise the machine generates also is disturbing to some people.
  • A liver biopsy. Although other tests can provide a great deal of information about the extent and type of liver damage, a biopsy is the only way to definitively diagnose nonalcoholic fatty liver disease. Your doctor may perform this procedure if you are over age 45 and you are obese or have diabetes. Additionally, your doctor is more likely to order this test if your liver function tests don't go back to normal after treatment. In this procedure, a small sample of tissue is removed from your liver and examined under a microscope. Your doctor is likely to use a thin cutting needle to obtain the sample. Needle biopsies are relatively simple procedures requiring only local anesthesia, but your doctor may choose not to do one if you have bleeding problems or severe abdominal swelling (ascites). Risks include bruising, bleeding and infection.

Complications :
It's difficult to predict the course of nonalcoholic fatty liver disease in any one person. Most people with simple fatty liver (steatosis) or nonalcoholic steatohepatitis (NASH) don't develop serious liver problems. Without treatment, however, these conditions can lead to cirrhosis and liver failure in some people. This risk is highest in people older than 45 who are affected by obesity, diabetes or both. Some estimates suggest that as many as one in four people with nonalcoholic fatty liver disease may develop serious liver disease within 10 years. In some cases, a liver transplant may be the only option.

Treatment:
The best treatment for you depends on the underlying cause of your nonalcoholic fatty liver disease. Preferred treatments include :
  • Weight loss and exercise. If your body mass index is above 25, a diet and exercise program may reduce the amount of accumulated fat in your liver. The most effective diet is rich in fiber and low in calories and saturated fat, with total fat accounting for no more than 30 percent of total calories. But go slowly. Aim to lose 10 percent of your body weight over six months, because rapid weight loss may lead to a worsening of liver disease. Even if you aren't overweight or obese, a healthy diet and daily physical activity may reduce inflammation, lower elevated levels of liver enzymes and decrease insulin resistance.
  • Diabetes control. Strict management of diabetes with diet, medications or insulin lowers blood sugar, which may prevent further liver damage. It may also reduce the amount of accumulated fat in your liver.
  • Cholesterol control. Controlling elevated levels of cholesterol and triglycerides with diet, exercise and cholesterol-lowering medications may help stabilize or reverse nonalcoholic fatty liver disease.
  • Avoidance of toxic substances. If you have nonalcoholic fatty liver disease — especially nonalcoholic steatohepatitis (NASH) — don't drink alcohol. Also avoid medications and other substances that can cause liver damage. Talk to your doctor about which drugs to avoid.

Under investigation
There's no standard medical treatment specifically for nonalcoholic fatty liver disease. Several possible treatments are under investigation, but so far none has proved effective. These approaches include :

  • Vitamins E and C. Since both vitamins are antioxidants, it's thought that they may reduce liver damage caused by oxidants, unstable oxygen molecules that damage cell membranes.
  • Ursodiol (Actigall). Most commonly used to treat gallstones, this drug decreases production of bile acids, which may in theory help lower elevated levels of liver enzymes in people with liver disease.
  • Other medications. Researchers are studying the effects of several medications on insulin resistance and nonalcoholic fatty liver disease in people with and without diabetes. These include metformin (Glucophage, Glucophage XR), pioglitazone (Actos), rosiglitazone (Avandia) and betaine (Cystadane). Another drug being investigated is orlistat (Xenical), a medication that blocks the absorption of some of the fat from your food. Early results indicate that orlistat may reduce the amount of fat in the liver.
  • Bariatric surgery. While abdominal weight-loss surgery coupled with rapid weight loss has been implicated as contributing to the development of NASH, some research suggests that bariatric surgery combined with modest weight loss may reduce the inflammation and scarring associated with NASH.

Prevention:
Your best defense against nonalcoholic fatty liver disease is to maintain a healthy weight and normal cholesterol and blood sugar levels. This strategy, along with avoiding excess alcohol and other substances that could be harmful to your liver, can help reduce your risk of liver disease.

 
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
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