A multidisciplinary panel of U.S. experts released a “Call to Action” for improved screening, diagnosis, and treatment of patients with nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD) on July 26, an effort organized by the American Gastroenterology Association in collaboration with seven other U.S. medical organizations including several endocrinology groups.
The published statement, “Preparing for the NASH Epidemic: A Call to Action,” proposes several urgent steps for the U.S. clinical community to provide better-focused and better-coordinated care for patients at risk for developing or having NAFLD or NASH, particularly among “emerging” at-risk cohorts such as patients with diabetes and obesity. It appears in the journals Gastroenterology, Diabetes Care, Metabolism: Clinical and Experimental, and Obesity.
The statement’s central pitch is that improvements in care won’t be possible unless the several medical specialties that deal with affected or at-risk patients stop working “in separate silos,” and instead create “a collective action plan,” and also organize multidisciplinary teams that “integrate primary care, hepatology, obesity medicine, endocrinology, and diabetology via well-defined care pathways.”
“The overarching goal” is a “unified, international public health response to NAFLD and NASH,” said the statement, which stemmed from a conference held in July 2020 that included representatives from not only the lead gastroenterology group but also the American Diabetes Association, the American Association for the Study of Liver Diseases, the American Association of Clinical Endocrinologists, The Endocrine Society, The American Academy of Family Physicians, The Obesity Society, and the American College of Osteopathic Family Physicians.
The statement cites sobering prevalence numbers, with estimates that NAFLD exists in more than half the patients with type 2 diabetes, while NASH affects about a third, rates that translate into many millions of affected Americans, given recent estimates that the U.S. prevalence of type 2 diabetes exceeds 30 million people. And the numbers continue to rise along with increases in the prevalence of obesity and type 2 diabetes.
“It’s an enormously common disease, and there are not enough gastroenterologists, to say nothing of hepatologists, to care for every patient with NAFLD,” said Anna Mae Diehl, MD, a gastroenterologist and professor at Duke University in Durham, N.C., who was not involved with the conference nor in writing the statement.
Clinical Care Pathways Coming Soon
Another key part of this initiative is development of clinical care pathways that will have “careful explication of each step in screening, diagnosis, and treatment,” and will be designed to inform the practice of primary care physicians (PCPs) as well as clinicians from the various specialties that deal with these patients.
The clinical care pathways are on track to come out later in 2021, said Fasiha Kanwal, MD, a professor and chief of gastroenterology at Baylor College of Medicine in Houston, and lead author on the Call to Action document.
“The Pathways will include practical recommendations about whom to screen and when to refer, and the criteria primary care physicians can use for diagnosis and risk stratification,” Kanwal said in an interview. “Patients can benefit from a standardized approach.”
The new document also includes results from a recent survey about NAFLD and NASH management completed by 751 U.S. physicians, including 401 (53%) primary care physicians, 175 gastroenterologists, (23%) and 175 endocrinologists (23%; percentages total 99% because of rounding).
The results showed “significant gaps in knowledge about whom to screen and how to diagnose and treat patients at high risk for NASH,” concluded the statement’s authors. Barely more than a third of the respondents knew that almost all patients with severe obesity likely have NAFLD, and fewer than half the endocrinologists and the primary care physicians appreciated that NAFLD is very common among patients with type 2 diabetes.
‘ Understanding of NAFLD Is Not There ‘
“I applaud this effort that calls attention to an emerging public health problem. This paper and survey are great ideas. The findings are not surprising, but they’re important,” said Diehl said in an interview. “Much more needs to be done” including changes in social behavior and government policies.
“The public’s understanding of NAFLD is not there,” and many physicians also have an incomplete understanding of NAFLD and more serious stages of metabolic liver disease. “Physicians know that patients with obesity are at risk for heart disease, diabetes, and stroke, but they may not always be aware that these patients can also have cirrhosis,” noted Diehl, who published in 2019 a call to action for NAFLD of her own with some associates.
“My referrals are fueled by primary care physicians who recognize patients with significant liver disease. It would be great to outline recommended practice; I have no doubt that providers will embrace this,” as well as the broader concept of multidisciplinary teams, another focus of the statement. Diehl cited the “Cancer Center model,” where an oncologist takes primary responsibility for caring for a cancer patient while coordinating care with other specialists, an approach facilitated by EMRs that allow seamless data and chart sharing and something that many health systems have either already adopted or are moving toward.
She said the NASH Call to Action may help catalyze broader application of this model to many more patients with NAFLD or NASH, and noted that some U.S. centers already use this approach – including Diehl’s program at Duke – which brings together her gastroenterology colleagues with cardiologists, radiologists, endocrinologists, and bariatric surgeons. But she noted that for most patients with metabolic liver disease, the hub clinician needs to be a PCP, especially for patients with earlier-stage disease, because the number of affected patients is so huge.
“Key steps toward establishing such teams include establishing protocols for risk stratification and referral, definition of roles and responsibilities, and buy-in from institutions and payers. Clearly a lot of work needs to occur to get to these multidisciplinary teams,” said Kanwal.
Ralph A. DeFronzo, MD, professor and deputy director of the Texas Diabetes Institute at UT Health San Antonio, who was not involved with the conference or statement, had a different take on what the future of NASH and NAFLD care may look like.
“Endocrinologists, hepatologists, and obesity experts will work within their individual specialties to diagnose and manage NASH,” he said in an interview. But he acknowledged that “an integrated effort by specialists would be important” to help “primary care physicians who are less familiar with the disease.”
Controversy Over Pioglitazone?
DeFronzo endorsed development of clinical care pathways as “important,” but also as a potential source of “controversy, especially with respect to treatment.”
The Call to Action statement cites lifestyle-based therapies, such as an appropriate diet; regular, moderate exercise; and elimination when possible of obesogenic medications as cornerstone interventions for patients with NAFLD or early-stage NASH, interventions that can be prescribed by PCPs. For patients with NASH and stage 2 or worse fibrosis, the statement endorses liver-directed pharmacotherapy. While noting that no agents currently carry a Food and Drug Administration–approved indication for treating NASH, the statement cites evidence that 800 IU/day of vitamin E improves steatosis in patients with NASH but not type 2 diabetes.
For patients with type 2 diabetes, the statement notes that results from five randomized trials indicated that pioglitazone could reverse steatohepatitis, findings that led to its recommendation in guidelines from a modest circle of medical groups, including the American Association for the Study of Liver Diseases and the European Association for the Study of Diabetes. However, the 2021 Standards of Medical Care in Diabetes from the American Diabetes Association gives these agents limited endorsement, saying: “Pioglitazone, vitamin E treatment, and liraglutide treatment of biopsy-proven nonalcoholic steatohepatitis have each been shown to improve liver histology, but effects on longer-term clinical outcomes are not known.”
“The strongest evidence by far is for pioglitazone for treating NAFLD and NASH,” said DeFronzo, a vocal proponent of the drug for this indication. But he added that “hepatologists don’t feel comfortable with drugs from the thiazolidinedione class,” which includes pioglitazone.
“We don’t yet know how to optimally configure the health system for NAFLD and NASH to make it more efficient and helpful to patients, but models exist, and the approach is evolving,” said Diehl.
Diehl and Kanwal had no relevant disclosures. DeFronzo has been a speaker on behalf of AstraZeneca and Novo Nordisk, has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, and Janssen, and has received research funding from AstraZeneca, Janssen and Merck.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.