SAN DIEGO—The American Gastroenterological Association recently updated its clinical practice guidelines to recommend screening for all patients with nonalcoholic fatty liver disease and cirrhosis.

NAFLD is now the most common liver disease in the U.S.—and among veterans. Because hepatocellular carcinoma, which is one of the most dangerous outcomes of the condition, might have no notable symptoms in people with NAFLD until it is quite advanced, screening is critically important.

“Nonalcoholic fatty liver disease is when fat stores increase in the liver of somebody who rarely drinks,” said Elizabeth Maguire, MSW, communications lead for the VA’s HIV, Hepatitis, and Related Conditions Program Office. “The fat deposits can cause liver damage.”

NAFLD affects 1 in 4 Americans and an even greater percentage of veterans are at risk. Obesity, diabetes and high cholesterol dramatically increase risk of NAFLD and are significantly more common among veterans who receive care through the VA.

These veterans are almost twice as likely to be obese, with nearly 80% of former servicemembers having a body mass index of 30 or higher, compared to 42.5% of the general population, according to the U.S. Centers for Disease Control and Prevention. Obesity increases the odds of developing NAFLD 7.59-fold compared to those with a BMI of less than 25.

Veterans also have more than double the prevalence of diabetes, with nearly one-quarter having high glucose compared to 10.5% of the U.S. general population. About 80% of patients with NAFLD also have diabetes or obesity.

“Most of us don’t realize that most of the patients with diabetes we have in our clinics also have nonalcoholic fatty liver disease. That’s because we don’t have an easy diagnostic tool or an easy treatment. It’s an unmet clinical need,” explained Christos Mantzoros, MD, DSc, PhD, professor of medicine at Harvard Medical School, chief of endocrinology at the Boston Veterans Affairs Healthcare System and director of the human nutrition unit at Beth Israel Deaconess Medical Center in Boston. Mantzoros provided that analysis in a presentation at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease.

Untreated, NAFLD can progress with devastating results.

“If inflammation develops to remove the fat, we call it [non-alcoholic steatohepatitis] NASH. If this progresses to decompensated reaction and fibrosis and cirrhosis, then we call it nonalcoholic steatohepatitis with fibrosis. That can lead to liver cirrhosis, hepatocellular carcinoma and liver failure,” Mantzoros said.

New Recommendations

The AGA sought to define the parameters for screening as hepatocellular carcinoma frequently remains undetected in patients with NAFLD until it develops beyond the point at which curative therapies are options.

“The incidence of NAFLD-related HCC is increasing in the United States. Despite this rise in the incidence, screening and surveillance for HCC among patients at risk of developing HCC is suboptimal in general and is disproportionately lower in patients with NAFLD-related HCC,” the authors of the update noted.1

Authors included Rohit Loomba, MD, MHSc, of the University of California at San Diego; Joseph Kim MD, of the Yale University School of Medicine in New Haven, CT; Heather Patton, MD, of the VA San Diego Healthcare System; and Hashem El-Serag, MD, MPH, of Baylor College of Medicine and the Michael E. DeBakey VAMC, both in Houston.

Physicians should offer screening for “patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately equal to or greater than 1.5% per year, as has been noted with NAFLD cirrhosis,” according to the clinical practice update. “[T]herefore, we recommend that best practice guidance is to consider and offer HCC screening to all patients with NAFLD cirrhosis.”

While individuals with NAFLD without cirrhosis can also develop hepatocellular carcinoma, the authors restricted the screening recommendation to those with compensated cirrhosis or decompensated cirrhosis listed for liver transplantation.

Patients with NAFLD with noninvasive markers that indicate advanced liver fibrosis or cirrhosis should also be screened. Proper staging in NAFLD can be challenging, however.

Liver biopsy may be helpful, but it would be overwhelming with the number of patients who have NAFLD and it poses significant risk to patients. “It would be impossible to do biopsies in the 80 million at-risk Americans, and, even if we did, it would result in tens of thousands of subjects suffering complications and about 16,000 deaths each year from complications,” Mantzoros said.

Imaging can rule in cirrhosis but cannot reliably indicate advanced fibrosis. The update authors acknowledged that ultrasound can accurately and cost-effectively detect HCC in some patients with cirrhosis, but in about 20% of patients, particularly those who are overweight or obese and more likely to have already progressed to NASH, ultrasound quality may be inadequate. In those instances, the authors advised documenting the quality issues and using magnetic resonance imaging or computed tomography scans every six months in the future. 

Currently, noninvasive tests include point-of-care tests, specialized blood tests and imaging-based tests. The update authors recommend using two different noninvasive testing modalities to assess presence of advanced fibrosis or cirrhosis. “These tests should also be interpreted in context of full clinical information, including physical examination, laboratory profile, and imaging findings,” the authors wrote. In addition, “a higher cut-point threshold is desirable to maximize specificity (90%).” They recommended 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

  1. Loomba R, Lim JK, Patton H. El-Serag HB. AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology. 2020 May;158(6):1822-1830. doi: 10.1053/j.gastro.2019.12.053. Epub 2020 Jan 30.