How what we eat is destroying our livers

The patient who walked into Joel Lavine’s office at the University of California, San Diego (UCSD), medical center one day in the mid-1990s didn’t know how sick he really was. He was morbidly obese. A brownish blemish known as acanthosis nigricans sprawled over the nape of his neck and into his armpit, signaling that he probably had developed insulin resistance, a condition in which cells don’t respond normally to the hormone that controls blood sugar.

A biopsy revealed striking damage to the patient’s liver: so much fat crammed into the cells that it squashed their nuclei and other contents. Cirrhosis, or severe liver injury, was beginning as scar tissue ousted healthy cells. The patient essentially had the liver of a middle-aged alcoholic. Yet he was only 8 years old.

To Lavine, a pediatric hepatologist, it was clear the boy was suffering from nonalcoholic steatohepatitis (NASH). A condition usually associated with obesity, NASH results from excess fat in the liver and, as the name indicates, doesn’t stem from the alcohol abuse that causes many cases of severe fatty liver disease. Because NASH can destroy the liver, patients can require a liver transplant or even die.

Although Lavine had come across a few kids with NASH earlier in the 1990s when he worked at Boston Children’s Hospital, he found “it was rampant” in San Diego among the large Hispanic population. A dozen children suspected of having the illness were coming to his office every week for diagnosis. “It was clear we had an epidemic of sorts,” says Lavine, who is now at Columbia University’s College of Physicians and Surgeons.

That epidemic has now spread throughout the country as our livers pay the price for our calorie-rich diets and sedentary lifestyles. About 20% to 30% of people in the United States who don’t abuse alcohol carry extra fat in their livers, a precursor to NASH. The condition is even turning up in unlikely places such as rural India. “It’s becoming an important problem everywhere,” says hepatologist Vlad Ratziu of the Pitié-Salpêtrière Hospital in Paris.

That’s worrying, doctors and researchers say, because although such liver fat accumulation is usually benign, NASH develops in about 30% of people with fat in the liver. It can lead to liver failure, liver cancer, and death, and no drug treatments exist yet. A new liver is the only option for many people. NASH is now the number two reason for liver transplants, and it will probably rise to number one by the end of the decade as a new generation of antiviral drugs controls hepatitis C, currently the largest cause of liver failure, says hepatologist Naga Chalasani of the Indiana University School of Medicine in Indianapolis.

At the same time, the paths by which NASH develops and worsens are becoming clearer, sparking a surge of interest by pharmaceutical companies, which have more than 20 potential drugs in some stage of development. Several have performed well in early clinical trials, and one, obeticholic acid, recently impressed researchers by reducing the amount of liver scarring, a serious consequence of NASH. “We are at a pivotal time” in the history of NASH, Lavine says. “In 5 years we will have at least one treatment approved,” Ratziu predicts.