Fatty Liver (cont.)
In this Article
How are NAFLD and NASH diagnosed?
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.
Next: What are the difficulties in evaluating NAFLD and NASH? »
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