Dual screening for liver fibrosis and retinopathy in type 2 diabetes

Combining retina scanning with liver stiffness assessment offers a promising, efficient approach to identify advanced fibrosis and MASLD in type 2 diabetes patients.

A recent Lancer Gastroenterology and Hepatology study hypothesizes that retina scanning and examination with vibration-controlled transient elastography (VCTE) could be implemented simultaneously with a high acceptance rate in type 2 diabetes (T2D) patients.

Diagnosing progressive liver fibrosis

Hepatic steatosis in the presence of a metabolic risk factor like T2D is referred to as metabolic dysfunction-associated steatotic liver disease (MASLD). Current estimates indicate that about 38% of the global population is affected by MASLD, which increases the risk of hepatocellular carcinoma and end-stage liver disease. T2D patients are particularly vulnerable to MASLD, with a prevalence rate of 65%.

The diagnostic accuracy of the commonly recommended non-invasive test fibrosis-4 (FIB-4) score for MASLD may be lower in T2D patients. Therefore, other methods are currently being used, some of which include VCTE, magnetic resonance elastography with two metabolic risk factors, and enhanced liver fibrosis (ELF) score.

In Sweden, T2D patients are referred from primary care centers to retina scanning facilities, where screening is performed through fundus photography at regular intervals. This approach has the potential to determine whether VCTE can also be implemented simultaneously with retina scanning to identify advanced fibrosis and MASLD.

About the study

In the current study, data were collected between November 6, 2020, and June 20, 2023, at Capio Eye Globen, which is one of the largest retina scanning facilities in Stockholm, Sweden. In addition to the retina scan, patients were offered examinations for liver stiffness and liver steatosis with VCTE.

T1D patients, pregnant individuals, individuals with known liver disease, those reporting heavy alcohol consumption, non-Swedish speakers, and individuals younger than 18 years of age were excluded. All study participants had T2D and underwent a minimum two-hour fasting period prior to the examination.

Increased liver stiffness was defined as at least eight kPa, according to VCTE measurements. VCTe measurements exceeding 12 kPa indicated possible advanced fibrosis.

A controlled attenuation parameter (CAP) value of 280 dB/m or higher was considered the threshold value for the presence of MASLD. The fraction of eligible people approached for screening who accepted served as the primary outcome.

Secondary outcomes included the proportion of high liver stiffness readings at the first visit that were not elevated in the secondary evaluation, the presence of metabolic dysfunction-associated steatotic liver disease, and the prevalence of elevated liver stiffness.

Study findings

Over 92% of the 1,655 T2D patients initially scheduled for regular retina scanning attended their appointments. A total of 1,301 patients satisfied the inclusion and exclusion criteria, 1,005 of whom accepted simultaneous liver screening. The median participant age was 67.3 years, 37.1% of whom were female.

A total of 331 participants were examined with the XL probe, whereas 644 were examined with the M probe. The median CAP was 283 dB/m, with 51.8% of the cohort having CAP values of 280 dB/m or higher, thus indicating steatotic liver disease.

The median VCTE measurement was 5.4 kPa, with about 82% of the study cohort having values less than eight kPa. Values of eight kPa or higher were reported among 154 participants, whereas 49 individuals had VCTE values exceeding 12 kPa.

Of the 1,005 participants included in the analysis, 16.4% with unreliable or elevated liver stiffness measurements were referred to the liver unit. About 9% of patients were not referred due to old age or severe comorbidities. A total of 124 patients had elevated liver stiffness measurements from the first visit, 56 of whom had values less than eight kPa upon assessment with a second VCTE.

The median time between the first and second visits was 39 days. About 10% of study participants with CAP values of 280 dB/m or higher at the second visit had phosphatidyl ethanol values higher than 210 ng/mL, thus indicating the presence of alcohol-related liver disease. Based on these observations, 99 patients were identified to have MASLD as the primary cause of their hepatic steatosis.

A weakly positive correlation was observed between liver stiffness measurements at the first and second VCTE assessments. High liver stiffness measurements at the first assessment was associated with certain predictors such as high CAP, body-mass index (BMI), and retinopathy grade values.

In an adjusted analysis, these factors were independently associated with elevated liver stiffness. Some of the predictors that were consistently associated with elevated liver stiffness measurements included high BMI, CAP, liver stiffness measurements, and fasting serum insulin levels.

Conclusions

Simultaneous retina scanning and examination with VCTE in T2D patients has the potential to be an effective screening approach for liver fibrosis. About 3% of patients in the current study had advanced liver fibrosis, with about 52% predicted to have MASLD. The presence of false positives should be considered if implementing this method into clinical routine.

Journal reference:

• Lindfors, A., Strandberg, R., & Hagstrom, H. (2024) Screening for advanced liver fibrosis due to metabolic dysfunction-associated steatotic liver disease alongside retina scanning in people with type 2 diabetes: a cross-sectional study. The Lancet Gastroenterology & Hepatology. doi:10.1016/S2468-1253(24)00313-3