Obesity: Body Fat, the Silent Killer (cont.)
One common cause of liver failure (and thus a common
reason for transplantation of the liver) is cryptogenic cirrhosis (cryptogenic
meaning that the cause of the cirrhosis is unknown). Doctors now believe that a
large number of patients with cryptogenic cirrhosis are actually patients in the
late stages of nonalcoholic fatty liver disease. Doctors and public health
officials project that obesity related liver
diseases (cryptogenic cirrhosis and liver cancer) will become the leading cause
of liver failure and liver transplantation in the not too distant future.
How are nonalcoholic fatty liver disease and nonalcoholic
Losing excess weight is the
cornerstone of treatment of nonalcoholic fatty liver disease. One retrospective
study (that is, a study that looks back in time) found that among obese
individuals with elevated transaminases, weight gain led to a further increase
in the level of the liver enzymes. In contrast, a 10% loss of weight leads to a
significant decrease in the levels of the enzymes, and the enzymes even may
become normal. The decrease in enzymes occurred at the rate of 8% per 1% loss of
body weight. In studies of patients undergoing stomach (gastric) reduction
operations for morbid obesity, substantial weight loss is accompanied by a
marked reduction in transaminases and a regression (improvement) of non
alcoholic fatty liver disease.
Doctors also are using medications to treat nonalcoholic fatty liver disease. For example,
insulin-sensitizing agents, such as the thiazolidinediones, pioglitazone (Actos)
and rosiglitazone (Avandia), and metformin (Glucophage) not only help to control
blood glucose in patients with
diabetes, but they also improve enzyme levels in patients with Nonalcoholic
fatty liver disease. Medications in the statin class of drugs (for example,
decrease the bad LDL cholesterol
and, improve enzyme levels among patients with
atorvastatin. More studies are necessary to determine whether these medications also
reduce the amount of fat and inflammation in the liver.
Early uncontrolled studies (not the strongest type of studies) suggested
possible benefit of ursodiol (Actigall, Urso) and vitamin E in treating
but more recent studies showed no benefit of either of these medications in
The bottom line, however, is that the single most
effective treatment for obese people with Nonalcoholic steatohepatitis is to
simply lose weight through diet and exercise. Unfortunately, this is no easy
task in a society 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 possible detrimental effects of fat in
other liver diseases, weight loss might be added to the treatment of other liver
diseases that are not primarily due to fat, such as hepatitis C. Ultimately, non
alcoholic steatohepatitis probably can be largely prevented and eliminated by
promoting healthy eating habits and active lifestyles in children,
where it all begins.
For more, please read our
Fatty Liver article.
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
At A Glance
Last Editorial Review: 3/8/2007
- Accumulation of fat in the liver (fatty liver) is
common in all stages of nonalcoholic fatty liver disease (NAFLD). The initial
stage in the spectrum of nonalcoholic fatty liver disease is fatty liver
- The basic cause of nonalcoholic fatty liver disease
is insulin resistance, a condition in which the effects of insulin on cells
within the body are reduced. The most frequent risk factor for insulin
resistance is obesity, especially abdominal obesity.
- Fatty liver is itself quite harmless, disappears
rapidly with loss of weight, and infrequently progresses to Nonalcoholic
steatohepatitis, which is the next stage of nonalcoholic fatty liver disease.
- In Nonalcoholic steatohepatitis there is accumulation of fat in the liver, but there also is
inflammation (hepatitis), destruction (necrosis) of liver cells, and
scarring (fibrosis) of the liver. The scarring can progress to cirrhosis,
which is the last stage of nonalcoholic fatty liver disease.
- The risk factors, the time-line, and the processes
(mechanisms) responsible for progression through the stages of Nonalcoholic
fatty liver disease are still unclear.
- Estimates of the number of cases of nonalcoholic fatty liver disease among the obese and patients
with diabetes mellitus type 2 (DM2)
suggest that 90% have fatty liver, 20% have Nonalcoholic steatohepatitis, and
10% have cirrhosis. Among those with cirrhosis, liver cancer develops in
approximately 1% to 2% of patients per year.
- The presumptive diagnosis of Nonalcoholic fatty
liver disease or Nonalcoholic steatohepatitis is made in individuals who are
insulin resistant, have mildly elevated liver enzymes in the blood, and have
signs of fatty liver on an ultrasound. These patients must have no other cause
for the abnormal enzymes or for the fatty liver, particularly no excessive use
- If weight loss results in a decrease or normalization of the liver
enzymes, the diagnosis of nonalcoholic fatty liver disease is practically assured. Only a liver biopsy, however, can confirm the diagnosis of Nonalcoholic fatty liver
disease and Nonalcoholic steatohepatitis and determine the severity of the
- Whether or not it is vital to perform a liver biopsy
in individuals with suspected nonalcoholic fatty liver disease or non
alcoholic steatohepatitis is still debated among liver specialists since no
well-proven treatments are available. A liver biopsy can exclude other liver
diseases as the cause of the abnormal tests or fat and provide information
about the stage (and therefore the expected outcome) of Nonalcoholic fatty
liver disease. It also may provide an incentive for an individual 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 Nonalcoholic fatty