What the Heck is Fatty Liver Disease?

IN OUR 20s, my best childhood friend, Lizzie, told me she’d recently almost died from fatty liver disease, which neither of us had heard of and she could not explain.  Today, the aggressive form of fatty liver disease may soon become the number one reason for liver transplants.

The benign condition, non-alcoholic fatty liver disease (NAFLD), affects about one-third of Americans — more than 80 million, compared with 35 million for both types of diabetes combined, although the conditions are related. NAFLD occurs in 40 to 80 percent of people who have type 2 diabetes, as well as in 30 to 90 percent of people who are obese.

(Newly diagnosed cases of diabetes linked to severe Covid-19 may have arisen in conjunction with NAFLD: in these patients, levels in the blood of both sugar and ketones are extremely high.  Fatty deposits in the liver produce ketones to prevent starvation when insulin levels fall too low to metabolize sugar.)

Benign fatty liver disease can cause fatigue and abdominal pain but most often has no symptoms, and diagnosis usually arises only in the course of treating other conditions. Experts compare NAFLD to “pre-diabetes,” requiring attention only to prevent an advance to the more aggressive form of the disease.

Aggressive liver disease, called NASH (for nonalcoholic steatohepatitis), causes scarring, which leads to cirrhosis in about 5 to 10% of patients. Besides fatigue, symptoms of NASH include severe abdominal pain and swelling, weight loss and sometimes reddish palms and yellowing of the skin and eyes. Risk of developing NASH increases for patients who are obese and have poorly controlled diabetes.

Of about 30 million Americans with NASH, 90% are either overweight or obese—although about 7% with the disease are “lean.” Genes play a role, with the genetic variant linked to fatty liver disease, PNPLA3, present in about 18% of African Americans, 25% of European Caucasians, and 49% of Hispanics, who are “disproportionately affected by fatty liver disease,” according to Jay Horton, nutrition director at UT Southwestern Medical Center.  For people with this gene, obesity is like “a switch that turns the [fatty liver] disease on.”

The most common cause of death in NASH sufferers is cardiovascular disease, as it is with uncontrolled diabetes. High levels of glucose in the blood can damage blood vessels and the nerves that control both the blood vessels and the heart. People with diabetes tend to develop heart disease at a younger age and are nearly twice as likely to die from heart disease or stroke than those without diabetes.

“The connection between fatty liver and early signs of plaque in the coronary arteries is increasingly compelling,” says hepatologist Tracey Simon at Massachusetts General Hospital. And excess fat around the liver and other organs in the abdomen—known as abdominal obesity —seems to accelerate the progression of fatty liver to the more serious disease.

Early detection of fatty liver disease is currently not a priority because there are no drug treatments—although many pharmaceutical companies are working on drugs to reduce fat in the liver. Finding a cure for fatty liver disease is the “next big frontier” in medical advancements, according to Rohit Loomba, chairman of the American Liver Foundation’s National Medical Advisory Committee — because the number of deaths from chronic liver disease and cirrhosis has risen every year since 2007.

On the other hand, diet and exercise can reverse most damage: The liver is capable of regenerating to become healthy and whole even with as little as 25% intact.  Located in the upper abdomen just below the diaphragm on the right side extending toward the left, the liver is the largest and heaviest internal organ—in women averaging 3.25 pounds, compared to 2.71 pounds for the brain.

The liver metabolizes food to create energy by storing glucose, converting fat and breaking down proteins. The liver also clears the body of toxic substances including poisons, drugs, alcohol and waste products —which can accumulate in the body as the liver becomes impaired and in dire cases requires emergency treatment.

The best-known emergency condition is “acute fatty liver of pregnancy,” a rare complication that occurs most often in mothers with low body weight when the fetus is male. My friend Lizzie said her doctors had never seen an urgent case before in someone who wasn’t pregnant. Also, she was not overweight and drank no more than the rest of us, in our 20s in the 1970s.

After her near-death bout, Lizzie learned that she could “never drink again,” which sounded dire at that point in our lives. For most, though, fatty liver is not a disease —but, like pre-diabetes, just another reason to be vigilant about diet and exercise.