Noninvasive Markers of Liver Disease May Improve Referrals, Predict Complications in Diabetes

Fatty Degeneration Of Liver
Light micrograph of fatty degeneration of human hepatocyte,40x,hematoxylin and eosin staining
With the use of age-adjusted thresholds for noninvasive markers of liver steatosis and fibrosis, patients with type 2 diabetes may be referred more efficiently to specialists.

With the use of age-adjusted thresholds for noninvasive markers of liver steatosis and fibrosis, patients with type 2 diabetes (T2D) may be referred more efficiently to specialists, according to study results published in BMJ Open Diabetes Research & Care. Furthermore, the researchers found a consistent association between these markers and chronic complications of T2D.

Current guidelines for T2D care recommend routine screening for the presence of nonalcoholic fatty liver disease (NAFLD), as well as assessment of advanced liver fibrosis in high-risk patients, using ultrasound and serum biomarkers. Patients with T2D are at increased risk of progressing from NAFLD to steatohepatitis and liver-related mortality. The goal of the current study was to examine changes in specialist referrals after the use of suggested noninvasive biomarkers of steatosis and fibrosis in patients with T2D. In addition, the association between these biomarkers and cardiovascular and kidney morbidity was investigated.

The retrospective study included adults with T2D who were treated at the diabetes clinic at Policlinico di Monza in Monza, Italy, between 2013 and 2018.

Liver steatosis assessment was based on the Fatty Liver Index, Hepatic Steatosis Index, and NAFLD Ridge Score. Risk for advanced fibrosis was assessed by using the Fibrosis-4 (FIB-4) score, NAFLD Fibrosis Score, aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, and the AST to platelet ratio index.

Of 2770 patients with T2D included in the study, data on liver steatosis markers were available in 1519, 2076, and 1082 for Fatty Liver Index, Hepatic Steatosis Index, and NAFLD Ridge Score, respectively. Data needed to calculate liver fibrosis scores were available for 2096, 1429, 1421, and 370 patients for AST/ALT ratio, AST/platelet ratio index, FIB-4, and NAFLD Fibrosis Score, respectively.

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High probability of liver steatosis was evident in most patients based on each of the 3 steatosis scores (65%-88%). However, there was a wide variation in the high probability of advanced fibrosis according to different noninvasive markers, ranging from 1% with the use of the AST/platelet ratio index to 33% using the NAFLD Fibrosis Score. A significant number of patients were classified as having indeterminate risk, ranging from 23.1% using the AST/platelet ratio index to 55.8% using the AST/ALT ratio.

With a sequential combination of 2 noninvasive markers of steatosis (Fatty Liver Index) and fibrosis (FIB-4) with standard cutoffs, 28.3% of patients would require referrals to specialized hepatologists because of either intermediate (253 patients) or high risk (36 patients). With the use of age-adjusted cutoffs, this rate significantly decreased to 13.4% of the entire population (102 patients with intermediate risk, 35 with high risk).

Biomarkers of steatosis were significantly associated with risk for albuminuria. Among patients with Fatty Liver Index scores in the intermediate- or high-risk category, prevalence of microalbuminuria was significantly higher (odds ratio [OR], 3.49; 95% CI, 2.05-5.94).

Cardiovascular disease was more common in patients within the intermediate- (OR, 2.0; 95% CI, 1.6-2.5) and high-risk (OR, 2.6; 95% CI, 1.7-4.0) categories for FIB-4 score and within the intermediate (OR, 1.73; 95% CI, 1.4-2.1) and high (OR, 1.86; 95% CI, 1.4-2.5) categories of the AST/ALT ratio. For patients within the lower-risk category for fibrosis, risks for coronary heart disease and stroke were significantly lower.

The researchers acknowledged the results may be limited given that other etiologies of liver disease were not examined.

“While the use of different non-invasive fibrosis scores among patients with type 2 diabetes identify different proportion of patients with advanced fibrosis, the use of age-adjusted FIB-4 cut-offs leads to a drop in gray-zone results, making referrals to hepatologists more sustainable for the healthcare system,” the researchers wrote.

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Ciardullo S, Muraca E, Perra S, et al. Screening for non-alcoholic fatty liver disease in type 2 diabetes using non-invasive scores and association with diabetic complications. BMJ Open Diabetes Res Care. 2020;8:e000904.