Fatty Liver And Non-Alcoholic Steatohepatitis (NASH)

There should be little or no fat in a healthy liver. For most people, carrying a little fat in the liver causes no problems. Fatty liver is the name given to a condition in which you have too much fat in your liver. This is caused by the build-up of fats called triglycerides. These are the most common fats in our bodies. They belong to a group of fatty, waxy substances called lipids that your body needs for energy and cell growth.

We get triglycerides from our diet and they are also made in the liver. The liver processes triglycerides and controls their release. It combines them with special proteins to form tiny spheres called lipoproteins which it sends into the bloodstream to circulate among the cells of your body. When this process is interrupted and the flow of triglycerides to the liver is increased, their release, or ‘secretion’, from the liver is slowed down. This is what leads to the build-up of fat in your liver cells. 

Until recently fatty liver was considered rare and relatively harmless. It was not thought to progress to chronic (long-term) or serious liver disease.

Today it is one of the most common forms of liver disease and is known to lead to advanced conditions. In the majority of cases fatty liver does not cause any harm but for an increasing number of people the effects of having fat in their liver over a long period may lead to inflammation causing swelling and tenderness (hepatitis) and then to scarring (fibrosis).

In some people, this can progress to a condition known as cirrhosis, which can be life threatening.

Clinical knowledge about fatty liver is still coming together but common risk factors are obesity, diabetes and drinking too much alcohol. While the relationship between these factors is not fully known, they can be considered triggers for progression to other types of liver disease.

If alcohol is the cause of fatty liver it is called alcoholic liver disease (ALD). This leaflet is for people worried about fatty liver that is not caused by alcohol. This is known as non alcoholic fatty liver disease (NAFLD).

What is the difference between NAFLD and NASH?

Non alcoholic fatty liver disease (NAFLD) is actually a term for a wide range of conditions characterised by the build-up of fat in the liver cells of people who do not drink alcohol excessively.

At one end of this range is simple fatty liver, or steatosis. This is the stage where fat is first detected in the liver cells and is generally regarded as benign (harmless).

Non alcoholic steatohepatitis (NASH) is a significant development in NAFLD. This is a more aggressive condition that may cause scarring to the liver and can progress to cirrhosis. Cirrhosis causes irreversible damage to the liver and is the most severe stage in NAFLD.

In simple terms it may be easiest to think of NAFLD as having the following stages:

1. fatty liver

2. a form of hepatitis known as non alcoholicsteatohepatitis (NASH)

3. fibrosis

4. cirrhosis

5. Alcohol

NAFLD is almost the same as alcoholic liver disease (ALD) and shares the same stages, with alcoholic hepatitis occurring in place of steatohepatitis (NASH).

In practical terms the only difference between the two conditions – NAFLD and ALD – is that the latter is caused by drinking too much and the former by all other causes.

NAFLD can affect a wide range of people. In general, the older you are the more chance there is that you may have the condition. NAFLD is typically seen in people aged around 50 and more commonly in men than women.

It is hard to be precise about how many people have some form of NAFLD but it is estimated that one in five people (20%) in the UK have the earliest stages of NALFD, or steatosis.

People most at risk of NAFLD are those who:

• are obese

• have insulin resistance, associated with diabetes

• have hypertension (high blood pressure)

• have hyperlipidaemia (too much cholesterol and triglyceride in their blood)

• are taking certain drugs prescribed for other conditions

• have been malnourished, starved or given food intravenously

Non alcoholic steatohepatitis (NASH)

Non alcoholic steatohepatitis (NASH) is a more advanced form of NAFLD in which there is inflammation in and around the fatty liver cells. This may cause swelling of your liver and discomfort or pain around it. If you place your right hand over the lower right hand side of your ribs it will cover the area of your liver.

With intense, on-going inflammation a build up of scar tissue may form in your liver. This process is known as fibrosis, and can lead to cirrhosis. NASH is now considered to be one of the main causes of cirrhosis.

Cirrhosis is usually the result of long-term, continuous damage to the liver. This is where irregular bumps, known as nodules, replace the smooth liver tissue and the liver becomes harder. The effect of this, together with continued scarring from fibrosis, means that the liver will run out of healthy cells to support normal functions. This can lead to complete liver failure.

NASH should be distinguished from acute fatty liver disease, which may occur during pregnancy or with certain drugs or toxins (poisons). This condition is very rare and may lead rapidly to liver failure.

Signs and 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 the 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)

Causes

It's unclear 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 — may play an important role in its development. 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 so-called "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). Since 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 viral infections, an accumulation of excess iron in the liver (hemochromatosis) and moderate consumption of alcohol.

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, won't produce a fatty liver.  

Risk Factors

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 the 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 30; obesity 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, it can damage many organs in your body, including the liver. Up to 75 percent of people with NASH also have diabetes.

• Hyperlipidemia. As many as 80 percent of people with NASH have elevated cholesterol and triglyceride levels.

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. Losing more than one or two pounds a week, even from dieting, may increase your risk of nonalcoholic fatty liver disease.

• Chronic infection with hepatitis C or B. Most people with hepatitis C became infected through blood transfusions received before 1992, the year improved blood-screening tests became available. Intravenous drug use with contaminated needles is now the leading risk factor for hepatitis C. In the United States, hepatitis B is usually transmitted sexually or through contaminated needles. Long-term infection with hepatitis C slowly damages the liver, with cirrhosis developing in 20 percent of people 20 or more years after infection. The older you are when you're infected with the hepatitis C virus, the more likely you are to develop cirrhosis.

• Medications. These include oral corticosteroids (prednisone, hydrocortisone, others), synthetic estrogens (Premarin, Ortho-Est, others) for menopause, amiodarone (Cordarone, Pacerone) for heart arrhythmias, tamoxifen (Nolvadex) for breast cancer, diltiazem (Dilacor XR, Cardizem, others) for high blood pressure, anti-retroviral drugs such as indinavir (Crixivan) for infections related to HIV/AIDS, and methotrexate (Rheumatrex, Folex), an immune-suppressing medication for rheumatoid arthritis. In rare cases, cirrhosis may result from a severe reaction to amiodarone or methotrexate.

• 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 the body requires it.

Screening and 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 also will inquire about your alcohol consumption during the past five years. 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:

• A liver-function blood test. A damaged liver releases certain enzymes. If the 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 the 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 the 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 also 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 on either side. The thumping noise the machine generates is also 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. 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 may lead to cirrhosis and liver failure in some individuals. 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

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