Courtesy Dr. Christos S. Mantzoros
Dr. Christos S. Mantzoros
Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.
This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.
“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.
“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
Dramatic prevalence rates in patients with T2D
Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.
One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .
The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.
Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”
“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.
Doug Brunk/Frontline Medical News
Dr. Kenneth Cusi
“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”
“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.
These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”