Fatty Liver (cont.)
In this Article
What are the diagnostic clues for severe NASH?
The early identification of
severe liver scarring, or cirrhosis, in NASH patients is of clinical importance
because of the prognostic (outcome) information it conveys. This fact has led to
several studies attempting to identify factors that predict severe liver
scarring in patients with NASH and/or obesity. These studies found that patients
at risk for severe scarring are most often age 50 or older, significantly obese
(BMI greater than 30 kg/m2), and have DM2. Also, they often show an increase in
liver enzymes (AST greater than ALT) despite the absence of alcohol use.
As
already mentioned, some iron deposits in the liver (iron overload) may be
associated with NAFLD or NASH. This appears to be more common at the stage of
severe, irreversible liver scarring (cirrhosis). Testing for serum iron markers,
however, turns out to be of little use in predicting any degree of liver
scarring (fibrosis). Moreover, the predictive role of genetic markers (HFE mutations) of
hemochromatosis (hereditary iron overload) appears questionable.
What can a liver biopsy show and when should it be done?
In order to diagnose
NASH with precision and characterize its severity, there is still no substitute
for performing a liver biopsy. To date, however, no consensus exists for a
precise microscopic (pathological) definition of NASH or for a system to grade
its severity.
The initial descriptions defined NASH, as its name would suggest, as the
association of a fatty liver and inflammation, regardless of the presence of
associated liver abnormalities. Such abnormalities can include destroyed liver
cells (hepatocellular necrosis), scarring in different areas of the liver
(sinusoidal or portal fibrosis), abnormal proteins (Mallory bodies) that deposit
inside the liver cells, presumably due to peroxidation, and complex sugars that
deposit in the nuclei of the liver cells (glycogenated nuclei, often seen in
diabetes).
So, the initial studies on NASH included patients with simple criteria (just
fatty liver and inflammation) for the diagnosis. Later, it was suggested that a
fatty liver with inflammation alone (steatohepatitis) was not specific and that
some degree of liver cell death (steatonecrosis) was required to diagnose NASH.
The idea was that only a fatty liver with accompanying inflammation along with
liver cell death represented significant disease, based on the biochemical
findings and the potential to form cirrhosis.
Given these uncertainties as to what is or is not NASH, specialists in the
field are now suggesting that a more descriptive approach be used. The trend is
now to use a simple criterion (fatty liver) to establish the diagnosis of NAFLD,
and then grade the severity of the disease according to inflammation,
destruction of liver cells, scarring, and abnormal liver proteins.
Still, specialists do not agree as to when a liver biopsy should be
performed. Since, as will be discussed below, no specific treatment is available
for NAFLD or NASH, the result of a biopsy would not impact the patient's
treatment. In other words, if an individual is obese and/or diabetic, he or she
will be encouraged to lose weight by diet and exercise, regardless of the biopsy
result.
On the other hand, it may be important to know whether an individual has
severe NASH, especially if she or he is young. Severe NASH would indicate that
the risk of developing cirrhosis later on is high. Therefore, a liver biopsy can
provide important information about outcome (prognosis). It also can exclude the
presence of other liver diseases. In research protocols, a liver biopsy may be
required to qualify a patient for an investigational drug. Otherwise, the
decision as to whether or not to biopsy the liver to diagnosis NASH in clinical
practice should be made on a case-by-case basis.
Next: How are NAFLD and NASH treated? »
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