Diabetes drives increase in fatty liver, higher risk for fibrosis in the US
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Prevalence of fatty liver in the United States increased significantly between 1999 and 2016 with high- and moderate-risk groups also growing, according to a presentation at Digestive Diseases Week.
“This is an important study to inform policy makers what is it that we are going to deal with in fatty liver disease in the future, so we address treatment strategies and algorithms to identify these patients in the general population and connect and link them to appropriate care,” Zobair Younossi, MD, told Healio. “In 2016, about 38% of patients with fatty liver disease, which is approximately 30 to 35 million adults in the United States, have clinically significant fibrosis. About 2.5 million adults have really what we call advanced fibrosis as estimated by FIB4.”
Younossi and colleagues used data from the National Health and Nutrition Examination Survey (NHANES), looking at adults aged 20 years or older from 1999 to 2016, and NHANES III, which looked at adults from 1988 to 1994. They defined NAFLD by a US Fatty Liver Index (US-FLI) score of 30 or greater, excluding other causes of liver disease. They assessed fibrosis using Fibrosis-4 (FIB-4) score.
With data available for 11,532 participants in NHANES III, NAFLD prevalence by ultrasound was 19.4% (95% CI, 17.7-21.3). Of those with NAFLD, the researchers stratified by risk for hepatic fibrosis: 80% at low risk; 18.6% at moderate risk; and 1.4% at high risk.
Those patients with moderate or severe fibrosis also bore the highest rates of cardiovascular disease (50.8%), diabetes (33.5%), cancer history (32%), hypertension (26.3%) and hyperlipidemia (21.1%).
Using US-FLI, the researchers determined prevalence of NAFLD in this cohort to be 23.6% (95 CI, 21.7-25.5) with 77.5% at low risk for hepatic fibrosis, 20.8% at moderate risk and 1.65% at high risk.
In the latter NHANES group, there were 17,216 participants and the prevalence of NAFLD based on US-FLI increased from 29.5% (25.6-33.4) to 40.3% (36.6-44) for an annual percent change of 2% (P = .013).
“NAFLD is increasing over time and the highest increases in the NAFLD population are in this so-called high risk NAFLD with moderate risk NAFLD following,” Younossi said.
Moderate risk among NAFLD increased from 6.26% (1.1-14.17) to 14.17 (12.06-16.28) for an annual percent change of 5.59% (P =<.001). Severe risk increased from 0.49% (0.17-0.81) to 1.15% (0.45-1.85) for an annual percent change of 8.75% (P = .004). Low risk did not change.
These increases in prevalence and risk did not differ by sex, but Younossi said it predominately occurs in patients aged 40 or older, which is the group at highest risk for NASH, and more commonly seen in patients categorized as Mexican American or non-Hispanic white.
“When you run the multivariate analysis of what’s actually the driver of this increase, the most important driver was type 2 diabetes,” he said. “Type 2 diabetes was the most important predictor of increase in what I call high risk NAFLD or high risk for advanced fibrosis in these patients. ... When you look at patients with fatty liver disease and advanced fibrosis – primarily in the age group of 40 or older, which is considered at the prime of their productivity – the main driver behind the increase in this group is the high rate of diabetes.”
Perspective
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A couple of important points from this study are that Younossi estimated that 30 to 35 million adults with fatty liver disease have clinically significant fibrosis and, about 2.5 million individuals have advanced fibrosis. He derived these estimates by examining NHANES III (1988-1994) and NHANES (1999-2016) data defining NAFLD using a U.S. fatty liver index (US-FLI) score of 30 or greater and excluding other causes of liver disease.
The prevalence of NAFLD in the earlier NHANES-III cohort determined by US-FLI was 23.6% and those patients who had moderate or severe fibrosis also had the highest rates of cardiovascular disease and diabetes in addition to a cancer history and high blood pressure. In the latter NHANES cohort, the prevalence of NAFLD by US-FLI increased by an annual rate of 2% to 40.3% by 2016 with significant increases during this time in those with moderate or high risk for hepatic fibrosis. This shows us that NAFLD prevalence is increasing over time, and the highest increases in the NAFLD population are also in the high-risk NAFLD group.
His data suggest the most important driver of increase in NAFLD is type 2 diabetes, and type 2 diabetes was also associated with the highest risk for more significant fibrosis. In our own clinics, we're have to be more vigilant about using these data to try to identify the number of individuals with NAFLD who have the highest risks for fibrosis, we all see large numbers of NAFLD patients and we can use these data derived from NHANES to help tailor our efforts to identify people with the most significant risk for developing more advanced liver disease; these are the individuals who are most likely to benefit from therapies directed toward the treatment of both diabetes and NAFLD.
There will be more data emerging over the next few years, but this was an important study that is going to help us to identify those at highest risk for developing significant fibrosis, and ultimately cirrhosis. In addition, we mustn't lose sight of the fact that even if you don't have advanced liver disease, or advanced hepatic fibrosis with NAFLD, you're still at risk for cardiovascular events. The identification of this population with linkage to multi-disciplinary care is going to be a priority to reduce the morbidity and mortality associated with NAFLD.
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Younossi Z. Abstract 96. Presented at: Digestive Disease Week; May 21-24, 2021 (virtual meeting).
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