Fatty Liver Disease

Picture of the liver, the largest gland in the body

Non-alcoholic fatty liver disease is characterized by increased accumulation of fat, especially triglycerides, in the liver cells. It is normal for the liver to contain some fat and by itself, this causes no symptoms.

In some patients, the excess fat can cause inflammation called steatohepatitis (steato=fat+hepar=liver +itis=inflammation), although there is no relationship between the amount of fat present and the potential for inflammation. Steatohepatitis can lead to cirrhosis (fibrosis, scarring, and hardening of the liver). There is also an association with liver cancer (hepatocellular carcinoma).

For the majority of patients, NAFLD is a benign disease and is not associated with any symptoms. It is only when the liver manifests signs of inflammation, either NASH or alcoholic steatohepatitis, that the patient may experience symptoms. As with other types of hepatitis, the initial symptoms are non-specific and include malaise, fatigue, and upper abdominal fullness and discomfort.

If steatohepatitis progresses to cirrhosis, symptoms of liver failure may develop. Symptoms of liver failure include:

• jaundice (because of the accumulation of bilirubin),
• ascites and edema (swelling of the body) due to decreased protein production by the liver,
• increased bruising, and
• associated mental confusion.

Fatty liver can be classified as alcohol and non-alcohol related. Alcohol is a direct toxin to the liver and can cause inflammation. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic related steatohepatitis (NASH) are markedly different illnesses and there are many potential causes that are linked to fat accumulation in the liver.

Some of the causes of fatty liver include:

• Diet: Consumption of excess calories in the diet (the excess caloric intake overwhelms the liver's ability to metabolize fat in a normal fashion, which results in fat accumulation in the liver).
• Diseases: Fatty liver is also associated with type II diabetes, obesity, high triglyceride levels in the blood, celiac disease, and Wilson's disease (abnormality of copper metabolism).
• Medical conditions: Rapid weight loss and malnutrition.
• Medications: Medications such as tamoxifen (Soltamox), amiodarone injection (Nestorone), amiodarone oral (Cordarone, Pacerone), and methotrexate (Rheumatrex Dose Pack, Trexall) are associated with NAFLD.

There is evidence to suggest the presence of an association between insulin resistance and the development of NAFLD. In this situation, although the body makes adequate insulin, the ability of cells to adequately use that insulin to metabolize glucose is abnormal. The relative excess of glucose is then stored as fat and can accumulate in the liver.

Physical Exam and Medical History

When concern exists for the presence of fatty liver disease, the health care practitioner will try to find the underlying cause and risk factors. Questions may be asked regarding alcohol consumption, medication use (both prescription and over-the-counter), and past medical history, especially concerning a previous history of viral hepatitis (the most common are A, B, and C), and immunizations against infectious hepatitis. Screening for diabetes may be appropriate.

Physical examination may reveal an enlarged liver that can be palpated or felt in the abdomen below the right rib margin. Otherwise, it may require the development of cirrhosis to elicit abnormalities on physical examination. These may initially include jaundice or a yellowish tinge to the skin and eyes, muscle wasting, hair thinning, abnormal skin blood vessels called spider angiomata, and splenomegaly (enlarged spleen).

Blood Tests

Blood tests may be helpful as screening tests for liver inflammation, although liver function studies such as serum transaminases (AST, ALT) may be normal or elevated and not necessarily related to the severity of the liver disease. Other liver tests such as alkaline phosphatase and bilirubin are often normal. Serum ferritin (a measure of iron storage) may be abnormal. In patients with NAFLD and NASH, cholesterol levels including triglycerides are often elevated.

Imaging Studies

Ultrasound of the liver can reveal patterns suggestive of fatty infiltration of the liver. Computerized tomography (CT scan) and magnetic resonance imaging (MRI scan) are also useful in the evaluation of fatty liver.

Liver Biopsy

The definitive diagnosis of fatty liver disease can only be confirmed by liver biopsy, where a needle is inserted into the liver through the abdominal wall to obtain a piece of tissue that is analyzed under the microscope.

The treatment of fatty liver disease is to decrease the potential risk exposures to the liver.

• Avoiding alcohol: For those with alcoholic liver disease, abstaining from alcohol is a must.
• Lifestyle changes: For those with NALFD or NASH, appropriate diet, weight loss, diabetes control, and cholesterol/triglyceride control are important both for treatment and to prevent the progression of the disease from NAFLD to NASH, and from NASH to cirrhosis. Patients with celiac disease who maintain a strict gluten-free diet can reverse fat accumulation in the liver.
• Exercise: Cardiovascular exercise can help promote weight loss and weight training can increase muscle mass. This not only improves metabolism and promotes weight loss, but the increase in muscle mass helps to sensitize the cells to insulin and reduces insulin resistance.

The patient and doctor should work together to formulate a plan that involves lifestyle changes. A balanced diet, an increase in physical activity and exercise, and medication if needed to control cholesterol and blood sugar levels can minimize the risk factors that lead to fat infiltration of liver cells.

Though there is much research underway, presently there are no medications proven to be effective in fatty liver disease; however, medications to control and lower cholesterol and triglyceride levels can be used in association with diet and exercise.

Patients with fatty liver disease should be seen routinely in follow-up visits to their doctor in order to monitor their liver function and progression to more serious liver abnormalities. Since losing weight, diet, and physical activity are the most important tools in minimizing the risk of fatty liver disease and are the most effective treatments, consultations with a dietician and a physical trainer may be appropriate.

Since fatty liver disease is asymptomatic until liver inflammation occurs, the diagnosis is often made incidentally. The doctor may note a slightly enlarged liver on physical examination, or screening blood tests may show mild abnormalities of liver function.

Patients who have abdominal swelling, jaundice, and easy bruising should seek medical care, though the cause may not necessarily be steatohepatitis or cirrhosis.

Fatty liver disease is a preventable illness with the institution of a healthy lifestyle including a well-balanced diet, weight control, avoidance of excess alcohol consumption, and a regular physical exercise program. This does not guarantee success in disease prevention as some people may still develop liver disease.

Research studies are underway to better understand, prevent, and control fatty liver disease. There is ample evidence to suggest that NAFLD, NASH, and alcoholic steatohepatitis are reversible, and progression to cirrhosis is preventable. Numerous research trials are being carried out to understand the factors responsible for fat accumulation in the liver and to explore medications both new and old, that may be effective in treatment.