The emergence of nonalcoholic fatty liver disease (NAFLD) as the most common liver disorder in the U.S. and many other countries has set the stage for a potential increase in liver cancer.

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Stephen H. Caldwell, MD

While there isn’t a demonstrated cause-and-effect relationship between NAFLD and liver cancer, there is growing evidence of increased risk of liver cancer associated with NAFLD. The question is whether this association relates to underlying nonalcoholic hepatosteatosis (NASH), or if a fatty liver itself is a risk factor, said Stephen H. Caldwell, MD, professor and director of hepatology at the University of Virginia Health System, Charlottesville.

Dr. Caldwell and Hashem B. El-Serag, MD, MPH, chief of gastroenterology and hepatology at Baylor College of Medicine, Houston, TX, will co-moderate an AASLD Clinical Symposium on Monday titled Cancer and Nonalcoholic Fatty Liver Disease.

“We have several questions to explore, starting with whether liver cancer occurs in patients with fatty liver disease who do not have cirrhosis,” Dr. El-Serag said. “What are the risk factors for developing liver cancer among patients with obesity, diabetes or metabolic syndrome?”

Evidence suggests that obesity increases the risk for liver cancer, but there is no evidence that weight loss reduces the future risk of liver cancer, Dr. El-Serag said.

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Hashem B. El-Serag, MD, MPH

“We know that weight loss can reduce the progression from NAFLD to fibrosis and that advanced fibrosis increases the risk of liver cancer,” he explained. “By extrapolation, reducing progression to fibrosis might reduce the subsequent risk of liver cancer, but no one knows. Liver cancer is a rare event and it is difficult to show that short-term measures affect rare events.”

Analysis of liver transplantation lists shows that NAFLD-related, end-stage liver disease is moving to replace viral hepatitis-related cirrhosis as the most common indication for liver transplant, Dr. El-Serag said. Even so, liver cancer is still primarily related to viral hepatitis, especially hepatitis C, and not to NAFLD, he said.

“But it may take 30 or 40 years to develop liver cancer from NAFLD and we are still early in development of the NAFLD cohort,” he added. “It may take several years for advanced complications like liver cancer to be seen on a broad scale.”

Research links the increase in fatty liver disease to the same factors that are driving increases in obesity and diabetes in the overall population. Poor dietary habits and lack of exercise can lead to increased insulin resistance, and this pathogenic abnormality gives rise to NAFLD, type 2 diabetes, hyperlipidemia and other metabolic problems.

“Fatty liver is one of the most common liver diseases that most GIs see in the office,” Dr. Caldwell said. “This session will be helpful in counseling, educating and managing patients the day you get back to the office.”

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