Prof Dato’ Dr K.L Goh, University Malaya Medical Centre, Kuala Lumpur
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The diagnosis of "fatty liver" is commonly encountered today. With the popularity of routine blood screening as part of health "check-ups" and "executive screening programs" in Malaysia, many otherwise completely healthy patients are now detected to have raised alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. These liver enzyme levels are reflected in the LIVER FUNCTION section of the blood test report.

Your doctor would then refer you to the Radiologist for an ultrasound examination. This would involve scanning the upper part of your abdomen and normally in this ultrasound scan the whole of the involved system (called the hepatobiliary system) is examined. This refers to your liver, gallbladder and pancreas. The spleen is included as well.

In fatty liver, the radiologist finds that your liver shows a particularly “bright” pattern on ultrasound with no other abnormalities. Although this is not the only condition that gives a “bright” liver on ultrasound, the Radiologist may make this as an initial diagnosis depending on your symptoms and blood test results. Your doctor will be able to put all the information from the various tests together and may then refer you to a specialist in liver conditions depending on the severity of the abnormal liver function.

The rise in liver enzymes is usually mild and not exceeding 4 times the upper limit of normal. It is imperative in every case before such a "diagnosis" is accepted that we go through a checklist excluding diagnoses such as chronic hepatitis B and C infection, surreptitious alcohol intake and "drug induced" hepatitis associated with commonly used drugs such as the "statins" for high cholesterol, ticlodipine and non-steroidal anti-inflammatory drugs. Many patients in our local context also take traditional and herbal remedies, which may cause a rise in liver enzymes. In young adults, Wilson's disease must be considered as another possible diagnosis. Autoimmune hepatitis (condition where our immune system attacks our liver) may also present with raised liver enzymes with few symptoms.
 

Fatty liver is a general term that refers to all types of fatty deposition in the liver. In a western population, where alcohol intake is generally higher, fatty liver is often associated with alcoholic hepatitis. (Hepatitis is an inflammation of the liver and there are many causes of this inflammation).  

In 1980, Ludwig and colleagues from the Mayo clinic in 1980 coined the term nonalcoholic hepatitis (NASH) to describe the (appearance) pattern of liver injury in 20 patients seen over a 10 year period of time. Although the microscopic finding was similar to that seen in alcoholic hepatitis, yet, none of these patients had history of alcohol abuse. In all, there was steatosis (increased fat within the liver cells) on microscopic examination of the liver. No cause for liver disease could be found.  

Ludwig and colleagues noted that the majority of their patients in their study were obese, and 25% of them had high lipid levels in their blood and also adult-onset diabetes mellitus. 

NASH however, represents only a stage in the spectrum of non-alcoholic fatty liver disease (NAFLD). The spectrum of NAFLD is wide and ranges from simple accumulation of fat in liver cells (steatosis), to fat accumulation with necroinflammatory activity with or without fibrosis (steatohepatitis), to the development of advanced liver fibrosis or cirrhosis.  NASH should be differentiated from benign steatosis, which as the name states, offers little danger to the person.
 

Despite research into this condition, no one really knows exactly why this occurs. The frequent association of steatosis and NASH with obesity, type II diabetes mellitus and dyslipidemia suggests a potential role of tissue resistance to insulin as the cause of liver disease. Additionally, obesity and type II diabetes have been shown to be risk factors for the development of severe disease in NASH patients.  

High insulin levels may lead to fatty liver because it blocks fatty acid oxidation in the liver cells.Too much “fat” within the liver cell may be toxic to the cell resulting in inflammation and fibrosis.
 

CT scan showing the spleen to be brighter than the liver and the blood vessels of the liver also appear as if they have been enhanced with contrast media. In a normal patient, the spleen is not brighter than the liver and the blood vessels in the liver will appear “dark” against the background of the liver.

Statins is a common medicine as many today are suffering from high cholesterol levels and have heart disease. As one of the side effects of this drug is to raise the liver enzymes, your doctor may ask you to stop taking this medicine for a while and monitor the liver enzyme levels. This will exclude a drug induced raised liver enzymes.

Confirmation of a diagnosis of fatty liver (and NASH) strictly requires liver biopsy and histological (examining tissue under the microscope) examination. Many patients, who are otherwise well, are naturally reluctant for this procedure.

The opposite occurs in ultrasound examination where the fatty liver appears “bright” compared to the kidney and the walls of the blood vessels cannot be differentiated from the adjacent liver tissue. Ultrasound is a common initial (screening) examination as it is widely available, fast, uses sound waves (no radiation involved unlike CT Scan) and is cheaper. It also is a comfortable examination for the patient.

Tissue of the liver obtained from needle biopsy and examined under microscopy shows large fat vacuoles (round white sacs).

An enlarged liver may be found on physical examination in more than half the patients but there are few signs of chronic liver disease. Ultrasound findings of a "bright" liver are present when there is substantial fat accumulation but lesser amount of fat deposition may not be detected.

CT scan will show decreased density of the liver compared to the spleen. A liver biopsy while not absolutely necessary, nonetheless, allows us to assess the presence and severity of inflammation and fibrosis (steatohepatitis).

We do not need a liver biopsy when the liver enzymes are normal yet radiological imaging suggests fatty liver. Although severe and progressive disease may be present, the probability of this occurrence is very low and does not warrant a biopsy.
 

If our doctor finds that we have benign steatosis, there is no need to worry as it is a completely benign disease.  

The natural history (progression of the disease) of NASH (non-alcoholic steatohepatitis) however, is not entirely established. In the majority of people with NASH, it is still largely a benign disease. In some studies, 50% of those with NASH may have progression of the disease.  

However, progression of the disease may not necessarily be accompanied by clinical deterioration (your symptoms and signs) in most cases. In other words, evidence of inflammation of the liver (raised enzymes on testing your blood) and even on liver biopsy may not necessarily mean you will feel sick. You may still feel perfectly well.  Your doctor will then ensure that you go for regular checkups as well as follow up blood tests to monitor your progress.
 

Unfortunately, treatment options are limited for those with NASH. Benign steatosis does not require any treatment. 

Weight loss has been shown to result in normalization of liver enzymes in some studies and remains the most viable option for our patients with NASH who are obese.  

Medical treatment is largely unestablished.  Several drugs including the lipid lowering agents, gemfibrozil and clofibrate have been used without much success. Ursodeoxycholic acid has resulted in liver enzyme improvement but no change in the grade of inflammation or fibrosis. A few drugs are being studied currently and may prove to be useful in the future. These are those used to improve insulin resistance and thereby, reduce fat accumulation in the liver cells. There are many claims of “traditional” or totally natural herbal remedies but these have not been proven scientifically to be able to treat fatty liver (NASH type).

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Last Updated:
Thursday, 21 August, 2003