When Amreen Dinani, MD, conducted a novel study to assess the impact of screening for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, she made two notable discoveries. Seventy-eight percent of the patients she diagnosed with NAFLD using vibration controlled transient elastography (VCTE) presented with normal aminotransferase levels and thus would not have been referred for further workup. And only 20 percent of the patients she diagnosed using VCTE presented with imaging that documented fat in their livers.
“By definition, NAFLD means the liver cells contain at least 5 percent fat, but imaging technologies such as computed tomography scans and ultrasound only detect NAFLD when there is 20 percent fat in the cells, and that finding is incidental to imaging conducted for other reasons,” says Dr. Dinani, Assistant Professor of Medicine (Liver Diseases) at the Icahn School of Medicine at Mount Sinai. “That means that patients whose liver fat is in the 5 percent to 20 percent range would not have been captured and referred for screening.”
Screening patients with type 2 diabetes for NAFLD in an urban primary care clinic is one of three projects Dr. Dinani has undertaken to address the longstanding challenges involved in identifying, risk-stratifying, and treating NAFLD in patients with type 2 diabetes—a population considered at high risk for NAFLD, nonalcoholic steatohepatitis, and fibrosis. The primary endpoint was to determine the burden of disease in this population, which would have otherwise not been routinely screened for NAFLD or liver scarring (liver fibrosis) based on American Association for the Study of Liver Diseases (AASLD) guidelines, which say that NAFLD should be considered in persons presenting with elevated liver tests or imaging showing hepatic steatosis.
To answer this important question, Dr. Dinani approached patients with type 2 diabetes to be screened for NAFLD in a primary care clinic. She informed them of the association between type 2 diabetes and NAFLD, and asked if they would be willing to be screened for it. She recruited 60 participants and each underwent screening for NAFLD with VCTE—commonly known as Fibroscan—which detects the degree of fibrosis and hepatic steatosis using controlled attenuation parameter (CAP). The results showed that 41 participants (70 percent) had NAFLD, 15 of whom had a fibrosis score of ≥ F2 and 26 of whom had a score of < F2. Of these 41 patients, 80 percent would not have been identified based on the criteria of elevated liver tests. Furthermore, 80 percent had evidence of liver fat on imaging but none had NAFLD as a diagnosis or were referred to liver care. The findings were presented and published in abstract form at the AASLD meeting in 2019.
“These results make a strong case for screening high-risk populations such as type 2 diabetics for NAFLD, stratification, and connection to liver care,” Dr. Dinani says.
The second phase of this study was to risk-stratify those identified with NAFLD into < F2 fibrosis and > F2 fibrosis (significant fibrosis) cohorts. Given the evidence of increased morbidity and mortality associated with significant fibrosis due to NAFLD, the 15 patients identified with > F2 fibrosis were referred to hepatology care and continue to be followed to date. Dr. Dinani, who is following these patients, says, “The next phase is to conduct a two-armed study looking at the impact of multidisciplinary clinic care on metabolic and liver-related health outcomes in patients with NAFLD and > F2 fibrosis.”
The third project that has stemmed from her initial work in identifying high-risk populations with NAFLD and significant fibrosis is a one-year program looking at the impact of a modified diabetes prevention program (DPP) on NAFLD and metabolic outcomes. The DPP is an evidence-based lifestyle intervention program targeted to individuals with prediabetes to encourage weight loss and behavior change. Dr. Dinani says there is a close relationship between type 2 diabetes and NAFLD; she thus decided to adapt an existing, successful program for patients with NAFLD to assess the potential to have an impact on their disease, hepatic steatosis, and comorbidities.
Fourteen patients were recruited for the study, which consisted of two components: 16 weekly group sessions led by a lifestyle coach and physician, who shared nutrition, exercise, stress reduction, sleep, and self-motivation techniques; and 12 maintenance sessions, which were held every two to four weeks. Participants had a weight loss goal of 7 percent and weigh-ins were conducted at every session. On completion, there was a 79 percent retention rate (11 participants).
Participants who completed the program achieved statistically significant weight loss, with all of them meeting or exceeding the 7 percent target. Dr. Dinani also observed significant changes in liver fat CAP (354 to 303), HbA1c (6.3 to 6.0), triglycerides (171 to 138), and high-density lipoproteins (51 to 60). Interestingly, the low-density lipoproteins increased from a mean of 115 to 125 over the course of the study.
“That was the only metric where we were unable to meet our goal and we have not determined why this increase occurred,” Dr. Dinani says. “We will explore that further in the next phase of our studies, but this pilot demonstrates that strategic lifestyle intervention initiatives can be effective in helping patients manage and prevent progression of NAFLD in the absence of approved therapies.”
Amreen Dinani, MD
Assistant Professor of Medicine (Liver Diseases)