Medical mystery: What's cause of fatigue, abdominal pain?

After several months of unusual fatigue and dull, sporadic upper-abdominal pain on the right side, Ms. L. came to my office looking for an answer.

A month before our appointment, she had her gallbladder removed by a surgeon who thought that was the problem. During the surgery, her doctor noticed her liver appeared to have nodules and referred her to my office for follow-up.

At 60, Ms. L. had struggled with obesity for years and also had type 2 diabetes and high levels of LDL cholesterol. Lab tests revealed abnormal liver enzymes, but additional analysis did not identify a viral or autoimmune cause.

Despite watching her diet and rarely drinking alcohol, she had gained a good deal of weight over the last six years.

During the physical exam, I could feel that her liver was enlarged, but she did not have any skin changes or other findings that would have made me suspect advanced liver disease.

Despite her gallbladder surgery, her abdominal pain and fatigue persisted.

Next, I ordered a liver ultrasound, which showed chronic damage to her liver. The next step was a liver biopsy.

The biopsy revealed Ms. L. had nonalcoholic fatty liver disease (NAFLD), complicated by liver inflammation (nonalcoholic steatohepatitis, or NASH), and early cirrhosis. She was surprised to learn liver disease was caused not only by alcohol, toxins, and viruses, but also could be the result of an unhealthy diet and dysregulation of the metabolism, such as insulin resistance.

Fatty liver is one of the most common reasons for abnormal liver blood tests. Normally, the liver is very active in handling fat. It takes lipoproteins (fats) from the blood, reworks them, and secretes them in a different form. However, when a person develops insulin resistance, her metabolic system is changed, and the liver can no longer process the fat in the same way.

Most people with NAFLD have no symptoms. If the liver is enlarged, there may be an ache or mild tenderness in the right upper abdomen. Liver ultrasound can detect excess liver fat and MR elastography or transient elastography (Fibroscan) can show whether the liver is denser than usual, signaling a buildup of scar tissue.

About 10 percent to 20 percent of NAFLD cases can develop into a more serious condition in which fat causes inflammation and fibrosis (scar tissue) in the liver. Of those who develop this advanced form of NAFLD, 15 percent TO 25 percent may progress to end-stage liver disease within a decade or two.

Because of the obesity and diabetes epidemics, it has been estimated that by 2020, NAFLD will be the leading reason for liver transplants in the United States.

With lifestyle changes, NAFLD, liver tissue inflammation, and even some liver fibrosis can be reversed.

Once the diagnosis was made, Ms. L. started an intensive lifestyle-modification program, including dietary changes and weight loss. Her liver test normalized, and she has lost 20 pounds. Her liver disease is monitored, and she may need to consider emerging treatment for fatty liver disease. These treatments are being developed at a fast pace to meet the increasing prevalence of NAFLD.