Obesity, Liver Disease and Cancer: A Deadly Mix

As obesity rates rise, nonalcoholic fatty liver disease is driving a rise in liver cancers

an elder obese man with his hands on his belly

The “obesity epidemic” has unleashed a horde of ills on affluent nations worldwide: rising rates of heart disease, diabetes, and disability, to name a few.

Less known is the insidious effect of excessive weight gain on vital organs such as the liver.

Over time, obesity and the metabolic upset it causes can affect the liver in the form of nonalcoholic fatty liver disease (NAFLD) – a gradual deposition of fat within the organ. 

In fact, NAFLD is now the most common liver disorder in Western industrialized countries. The U.S. National Institute for Diabetes and Digestive and Kidney Diseases now estimates that between 30 and 40 percent of American adults have this often asymptomatic condition. 

In many cases, no substantial harm may result from NAFLD. However, about one-fifth of NAFLD cases progress to a more serious condition, called nonalcoholic steatohepatitis (NASH).

“Having NASH means that you actually have inflammation from the fat in the liver, and when you have long-term inflammation, you can develop scarring or fibrosis of the liver, as well, which can progress to cirrhosis,” explained

Dr. Sonal Kumar, assistant professor of medicine at Weill Cornell Medical College in New York City.

Silent Killer

surgeon making a puzzle of a liver using his equipment to pick the pieces

Both NAFLD and NASH have strong links to hepatocellular (liver) cancer, as well. It is estimated that there are about 40,000 new cases of liver cancer annually in the United States with close to 30,000 deaths. The majority of these are due to viral hepatitis and cirrhosis.

According to a recent review in the journal Liver International, about 2.5 percent of patients with NASH will go on to develop cirrhosis or liver cancer. Currently, almost 15 percent of liver cancer in the U.S. is due to this condition.

NASH, and the liver cancers associated with it, are often “silent killers,” showing no symptoms until they reach a comparatively late stage.

And Kumar said that as obesity rates rise, she’s seeing more cases of liver cancer linked to chronic NASH. 

Just how NASH directly causes liver cancer is still unclear. But both NAFLD and NASH can progress to liver cirrhosis, Kumar noted, “and cirrhosis is itself a risk factor for liver cancer.”

But recent research has found that cirrhosis was not present in up to 50 percent of cases where liver cancer was linked to NAFLD/NASH – suggesting that other factors may be at work.

“It is thought that inflammatory molecules seen with NASH may also increase the likelihood that tumors develop,” Kumar said.

Whatever the mechanisms, NAFLD and NASH are now on track to become a leading cause of liver cancer in wealthy nations.

“Especially as hepatitis C infection is being eradicated [through powerful new drugs], we’re estimating that NASH will shortly be the number one cause of liver transplant in the United States,” Kumar said.

Knowledge Gap

Unfortunately, there’s been little progress in terms of treating NAFLD/NASH in obese populations, Kumar added. “The only thing that’s been shown to work is weight loss,” she said. “There are a lot of drugs that are being studied, but nothing is FDA-approved.”

There’s also a knowledge gap among the public in this area. Millions of obese people in the United States and around the world may have no idea that their widening waistlines pose a risk to their livers, Kumar said.

“Patients don’t really ‘get it’ as a risk factor, they don’t completely understand what it means,” Kumar said.

The fact that NASH can show no symptoms doesn’t help, she added

“Patients think, ‘OK, I feel fine, so it must not be serious,” Kumar said. “So

I really have to educate my patients about what the disease is and its implications.”

NAFLD and NASH are serious conditions, however, affecting not only the liver but the cardiovascular system. So, fatty buildup in the liver can be a “double whammy” – raising risks for the two biggest killers, heart disease and cancer.

All of this means that better education – on obesity’s effect on the liver and how to prevent it – will be key to curbing rates of NASH-linked liver cancer.

“As America and the world gets more and more obese, NAFLD and NASH are just becoming more common,” Kumar said. “I feel that all this has a lot of implications – from a cancer standpoint, a liver transplant standpoint, for general morbidity and mortality. But people aren’t even aware that it exists.” 

Sonal Kumar

Sonal Kumar, MD, MPH
Director of Clinical Hepatology
Division of Gastroenterology and Hepatology
Weill Cornell Medical College
New York, NY