October 06, 2020
With high rates of fatty liver disease known to occur among people with type 2 diabetes, is it time to introduce routine liver screening into daily diabetes practice? The answer depends on whom you ask, and then there are still some important caveats.
From the hepatologist's perspective, there is no excuse not to consider liver surveillance now that noninvasive screening methods are available, suggested Michael Trauner, MD, of the Medical University of Vienna.
"From a practical standpoint, I think every type 2 diabetic over 50 years of age is at high risk," and consequently should be screened at diagnosis, Dr Trauner said during a debate at the virtual annual meeting of the European Association for the Study of Diabetes. "I would screen at diagnosis and then decide on recall depending on noninvasive fibrosis markers."
"It's a rising problem that we are facing these days," observed Michael Roden, MD, chair and professor of internal medicine, endocrinology and metabolic diseases at Heinrich-Heine University in Dusseldorf, Germany, and who cochaired the session. Not only do people with type 2 diabetes have an increased risk for developing liver diseases, but also there's a higher risk for those with fatty liver diseases developing type 2 diabetes.
A meta-analysis published in Gut in just last week illustrates just how big a problem this is - nonalcoholic fatty liver disease (NAFLD) "doubled the risk of type 2 diabetes," said Dr Rosen, who is also the director of the division of endocrinology and diabetology at University Clinics Dusseldorf. That analysis was based on more than 500,000 people, almost 28,000 of whom had incident diabetes over a 5-year period.
Screening Tools Scarce
This makes liver screening in type 2 diabetes patients "a formidable challenge," cautioned Gianluca Perseghin, MD, professor of endocrinology at the Monza (Italy) Polyclinic and the University of Milano-Bicocca in Milan.
"Hepatologists generally see only the most severe cases," Dr Perseghin said. Diabetologists and endocrinologists would be likely to see huge numbers of patients that could potentially be at risk for liver disease and following the recommendations set out in the joint European Association for the Study of the Liver/EASD/European Association for the Study of Obesity guidelines would result in a huge number of patients being identified and potentially needing referral, he argued.
"At this stage, we need to build friendly, reliable and cost-effective screening process to be applied in the health systems," Dr Perseghin suggested. He proposed that liver surveillance would need to be not only personalized on a patient level, but also at the infrastructure level. Measuring liver enzymes, for example, was going to be less accurate in picking up liver disease but blood tests were widely available, whereas imaging methods were not going to be something all diabetes clinics would have immediate access to.
"There are clearly a lot of provocative decisions still to be made," acknowledged Philip Newsome, PhD, FRCPE, an honorary consultant hepatologist at the University of Birmingham (England) and who cochaired the debate.
"We need to demonstrate that looking for the presence of liver disease in this cohort changes their outcomes in a way that is cost effective," Dr Newsome, who is also the secretary general of EASL.
"Tests are evolving, but more importantly, treatments are evolving. So, the decision around cost effectiveness will clearly change," he added.
NAFLD Therapies Unclear
"There are still a lot of questions," Dr Newsome said during a Novo-Nordisk–sponsored "Meet the Expert" session discussing EASL-EASD-EASO guidelines. "We don't have any licensed therapies at the moment. But there's been a huge amount of investment, looking at all sorts of different approaches."
Dr Newsome added: "We also don't know how to monitor these patients. Most of the noninvasive are very useful for staging patients, but we don't really understand how useful they are for monitoring changes in fibrosis."
Diabetologist Hannele Yki-Järvinen, MD, PhD, of the University of Helsinki, gave her thoughts on the topic during the same session.
"We should add FIB-4 [Fibrosis-4 index] to the annual exam and ask the lab to calculate FIB-4 automatically," Dr Yki-Järvinen said. FIB-4is calculated using the patients age and the results of readily available blood tests that measure the AST/ALT ratio and the platelet count.
Dr Trauner has received advisory fees and grant support from various companies with an interest in developing liver-directed therapies, and is also a coinventor of 24-norursodeoxycholic acid under development for cholestatic liver disease and potentially NAFLD. Dr Perseghin has received honoraria and grant support from various pharmaceutical companies with an interest in diabetes care. Dr Roden did not provide any disclosures. Dr Newsome has received research grants from Boehringer Ingelheim and Novo Nordisk and acted as a consultant to many pharmaceutical companies. Dr Yki-Järvinen disclosed receiving consultancy fees from Eli Lilly, MSD, and Novo Nordisk.