Fatty Liver (cont.)
In this Article What is the future of NAFLD and NASH?
NAFLD is probably the single most
common liver abnormality in the United States. It appears to be linked directly
to the growing epidemic of obesity in adults as well as in children. Thus, in a
sense, NAFLD is a sell-inflicted liver disease, much like alcoholic liver
disease. But only a minority of patients who are obese or diabetic will develop
severe liver disease and this is most likely determined genetically. In
addition, increasing evidence suggests that obesity and diabetes can worsen
alcoholic liver disease and liver disease due to HCV.
For these reasons, basic science researchers, liver specialists
(hepatologists), nutritionists, and hormone specialists (endocrinologists) are
combining their efforts to better understand and contain this process that has
been recognized for only the past 30 years.
Research into the genetics of this process will reveal the pathways that lead
to severe disease and help to recognize those patients most at risk. Clinical
research will help us understand the natural clinical history of this process
and perhaps identify predictors of outcome. Basic science research will be aimed
at understanding how the disease comes about and the processes involved. This
knowledge then may lead to the development of specific treatments. Currently,
small trials are ongoing that involve insulin-sensitizing agents, such as
metformin (Glucophage), rosiglitazone (Avandia), and pioglitazone (Actos). Other
treatments with anti-oxidant effects may prove of value.
The bottom line, however, is that the single most effective treatment for
obese people with NASH is to simply lose weight through diet and exercise.
Unfortunately, this is no easy task in our present society, which is dominated
by a sedentary lifestyle and high-calorie, high-carbohydrate, high-fat diets.
With great effort, however, weight loss is achievable. Furthermore, in view of
the likely role of fatty infiltration in other liver diseases, weight loss might
be added on to the treatment of these other liver diseases, such as anti-viral
therapy for HCV. Ultimately, NASH can probably be largely prevented and
eliminated by promoting healthy eating habits and active lifestyles in children,
where it all begins.
- Accumulation of fat in the liver (fatty liver) is
common to all stages of nonalcoholic fatty liver disease (NAFLD). The initial
stage in the spectrum of NAFLD is simple fatty liver (steatosis).
- The basic cause of NAFLD is insulin resistance, which
is a biochemical state that diminishes the effects of insulin. The most
frequent risk factor for insulin resistance is obesity, especially abdominal
obesity.
- Simple fatty liver is in itself quite harmless,
disappears rapidly with weight loss, and only a minority of those affected
progress to NASH, which is the next stage of NAFLD,
- Along with the accumulation of liver fat, NASH
involves inflammation of the liver (hepatitis), destruction (necrosis) of
liver cells, and scarring (fibrosis) of the liver. It can progress to severe
liver disease, including cirrhosis, which is the last stage of NAFLD.
- The risk factors, the time-line, and the processes
(mechanisms) responsible for progression through the stages of NAFLD are still
unknown.
- Estimates of the number of cases of NAFLD among the
obese and patients with diabetes mellitus type 2 (DM2) suggest that 90% have
simple fatty liver, 20% have NASH, and 10% have cirrhosis. Among those with
cirrhosis, primary liver cancer develops at a rate of approximately 1% to 2%
per year.
- The presumptive diagnosis of NAFLD or NASH is made in
individuals who are insulin resistant, have mildly elevated liver enzymes
(transaminases) in the blood, and have signs of fatty liver on an ultrasound.
These patients will have no other known cause for these enzyme elevations or
for the fatty liver, particularly no significant alcohol use.
- If weight loss results in a decrease or normalization
of the liver enzymes, the diagnosis of NAFLD is practically assured. Only a
liver biopsy, however, can confirm the diagnosis of NAFLD and NASH and
determine the severity of the disease.
- Whether or not it is vital to perform a liver biopsy
in suspected NAFLD or NASH is still debated among liver specialists since no
specific treatments are available. A liver biopsy can exclude other liver
diseases and provide information about the outcome (prognosis) of the
condition.
- A liver biopsy may also provide an incentive for the patient to adopt a
healthy lifestyle (diet and exercise) with the aim of losing weight. Weight
loss, if overweight, and correcting elevated cholesterol, triglycerides, and
blood sugar should be beneficial in NAFLD.
Last Editorial Review: 8/29/2005
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