Body Fat, the Silent Killer

DOCTOR'S VIEW ARCHIVE

Obesity Can Lead to Fatty Liver...a Silent Killer

Medical Author: Dennis Lee, MD
Medical Editor: Jay W. Marks, MD

Obesity is a major health problem worldwide. In the United States, roughly 300,000 deaths per year are related to obesity. Obesity also increases the risk of developing several chronic diseases such as type II diabetes, insulin resistance, coronary heart disease (responsible for heart attacks), cerebrovascular disease (responsible for strokes), high blood pressure, gout, gallstones, colon cancer, sleep apnea, and a form of liver disease called nonalcoholic fatty liver disease (NAFLD).

Obesity is defined as an excess amount of body fat. The normal amount of body fat (expressed as a percentage of body weight) is between 25-30% in women and 18-23% in men. Women with over 30% body fat and men with over 25% body fat are considered obese. Another easier way of defining obesity is by calculating the body mass index (BMI). The BMI is a mathematical formula that takes into account both a person's weight and height in calculating the degree of obesity. In adults, normal weight is defined as a BMI between 20 and 25 BMI units, overweight from 25 to 30, obesity from 30 to 35, significant obesity from 35 to 40, morbid obesity from 40 to 45, super obesity from 45 to 50, and super-morbid obesity greater than 50. Eighty percent of deaths related to obesity occurs in obese individuals with a BMI greater than 30. To find out what your BMI is, please refer to the Body Mass Index (BMI) Table for Adults, and the Body Mass Index (BMI) Index Table for Teens.

What is nonalcoholic fatty liver disease (NAFLD)?

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver diseases ranging from the most common, fatty liver (accumulation of fat in the liver, also known as steatosis), to Nonalcoholic steatohepatitis (NASH, fat in the liver causing liver inflammation), to cirrhosis (irreversible, advanced scarring of the liver as a result of chronic inflammation of the liver). All of the stages of Nonalcoholic fatty liver disease are now believed to be due to insulin resistance, a condition closely associated with obesity. In fact, the BMI correlates with the degree of liver damage, that is, the greater the BMI the greater the liver damage.

The term Nonalcoholic is used because liver disease due to alcohol can show the same spectrum of liver disease as nonalcoholic fatty liver disease; however, patients with nonalcoholic fatty liver disease do not consume excessive amounts of alcohol.

Alarming statistics about nonalcoholic fatty liver disease

As expected, nonalcoholic fatty liver disease is observed principally in developed countries. In these societies, a sedentary lifestyle and high calorie, sugar, and fat intake lead to a high prevalence of obesity, insulin resistance, and diabetes.

Nonalcoholic fatty liver disease is currently the most common liver disease in the U.S. and worldwide, affecting estimated 10-24% of the world's population. In the U.S., the Centers for Disease Control reports that currently, approximately one half of the U.S. adult populationisoverweight (BMI>25) and one quarter of the U.S. adult population isobese(BMI>30). That means upwards of 29 million Americans have nonalcoholic fatty liver disease, while 6.4 million of these persons have nonalcoholic steatohepatitis (NASH). Even more alarming than these statistics, nonalcoholic fatty liver disease is occurring among children in the U.S.

In most patients nonalcoholic fatty liver disease causes no symptoms. Nonalcoholic fatty liver disease often is discovered when routine blood tests show slightly elevated levels of liver enzymes (ALT and AST) in the blood. Another way in which nonalcoholic fatty liver disease is discovered is when ultrasound examination of the abdomen is done for other purposes, say for looking for gallstones, and fat is found in the liver. In the late stages of non alcoholic fatty liver disease, the development of cirrhosis can lead to failure of the liver, swelling of the legs (edema), accumulation of fluid in the abdomen (ascites), bleeding from veins in the esophagus (varices), and mental confusion (hepatic encephalopathy). Patients with cirrhosis caused by Nonalcoholic fatty liver disease also may be at risk of developing liver cancer (hepatocellular carcinoma, HCC).

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 steatohepatitis treated?

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.

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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, atorvastatin/Lipitor) 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 atorvastatin, but more recent studies showed no benefit of either of these medications in treating atorvastatin.

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

• 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 (steatosis).
• 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 of alcohol.
• 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 disease.
• 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 liver disease.