One of the most important emerging complications associated with diabetes is the Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD). The liver fibrosis index-4 (FIB-4) is proposed, as a first approach, to screening for cirrhosis in these patients.
Patients and methodsAll unique patients attended by diabetes in the EDN department of our hospital from 1 January 2022 to 31 December 2022 were included. The FIB-4 value for each patient was obtained retrospectively from the laboratory programme of our hospital.
Results1259 unique patients with type 2 diabetes were attended, and the prevalence of advanced FIB-4 in these patients was 4.77% [95%CI: 3.66–6.09%]. 580 unique patients with type 1 diabetes were attended, and the prevalence of advanced FIB-4 in these patients was 1.72% [95%CI: 0.83–3.15%].
DiscussionOur study confirms the importance of FIB-4 in people with diabetes to identify patients at higher risk of advanced liver fibrosis. We must highlight that 10.9% of patients with type 2 diabetes and 9.5% of patients with type 1 diabetes had an indeterminate FIB-4 result.
Una de las complicaciones emergentes más importantes asociadas a la diabetes es la enfermedad hepática grasa asociada a disfunción metabólica. El cálculo del índice de fibrosis hepática-4 (FIB-4) constituye la primera aproximación para el cribado de cirrosis en estos pacientes.
Pacientes y métodosSe incluyeron todos los pacientes únicos atendidos por diabetes en el Servicio de Endocrinología, Diabetes y Nutrición de nuestro hospital desde el 1 de enero al 31 de diciembre de 2022. El cálculo del FIB-4 se realizó retrospectivamente a partir de los datos de laboratorio.
ResultadosSe atendieron 1.259 pacientes únicos por diabetes tipo 2. La prevalencia de FIB-4 positiva entre estos pacientes fue del 4,77% (IC 95%: 3,66-6,09%). Se atendieron 580 pacientes únicos con diabetes tipo1 con una prevalencia de FIB-4 positivo del 1,72% (IC 95%: 0,83-3,15%).
DiscusiónNuestros resultados confirman la importancia del cálculo del FIB-4 en los pacientes con diabetes para identificar el riesgo de fibrosis hepática. Resultó destacado que el 10,9% de los pacientes con diabetes tipo 2 y el 9,5% de los pacientes con diabetes tipo 1 presentaban un resultado de FIB-4 indeterminado.
Diabetes is one of the fastest growing diseases worldwide and is associated with classic acute and chronic complications as well as general and cardiovascular mortality.1 Beyond these classic complications, in recent years, new complications associated with diabetes have been described that have a great impact and that should be properly assessed in people with diabetes. One of the most important emerging complications associated with diabetes is the nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis.2
There are different terms related to fatty liver disease in people with diabetes, however, in the last years, the term MAFLD (Metabolic dysfunction-Associated Fatty Liver Disease) and MASLD (Metabolic dysfunction-Associated Steatotic Liver Diseases) started to be used more broadly as more inclusive concepts for people who are overweight or obese, with clinical features of metabolic syndrome, and with type 2 diabetes.3,4 MAFLD is currently the most common chronic liver disease and its incidence is expected to continue to increase in the coming years due to its close association with diabetes mellitus, metabolic syndrome and cardiovascular risk factors.5,6
The American Association of Clinical Endocrinologists (AACE), the American Association for the Study of Liver Diseases (AASLD) and the American Diabetes Association (ADA) recommend liver assessment in people with type 2 diabetes. This assessment is aimed at the prevention of cardiovascular disease and the prevention of liver cirrhosis.2,7
As a first approach to screening for cirrhosis, the liver fibrosis index-4 (FIB-4) is proposed. FIB-4 is a non-invasive, easily accessible and low-cost tool that takes into account the patient's age, plasma aminotransferase levels and platelet count for its calculation (supplementary appendix 1).8 A calculated FIB-4 value of less than 1.30 rules out the presence of advanced fibrosis (low), a value greater than 2.67 suggests the presence of advanced fibrosis and advises assessment by a Digestive specialist with expertise in liver disease (advanced). A FIB-4 value between 1.30 and 2.67 indicates that the patient is in an indeterminate risk (indeterminate), suggesting further evaluation with other complementary tests that may be more complex, costly and less accessible.5
In September 2024, the European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) included in their Clinical Practice Guidelines on the management of MASLD a low-risk cut-off value (low) of FIB-4 lower than 2 for people over 65 years of age.9
Lomonaco R et al. showed that 5% of patients with type 2 diabetes attending primary care or endocrinology outpatient clinics had a FIB-4 value≥2.67.10
The main aim of our study was to know the prevalence of positive FIB-4 values among people with type 2 and type 1 diabetes attended in Endocrinology, Diabetes and Nutrition (EDN) outpatient clinics.
Patients and methodsA single-centre, cross-sectional, retrospective and descriptive study was carried out. The protocol was approved by the Ethics Committee of the Albacete University Hospital Complex. All unique patients attended by diabetes in the EDN department of our hospital from 1 January 2022 to 31 December 2022 were included. The FIB-4 value for each patient was obtained retrospectively from the laboratory programme of our hospital, calculating the mean value from all analytical determinations that included the values necessary for the calculation from 1 January 2019 to the date of the study. Statistical analysis of the data was carried out with the IBM SPSS Statistics 28.0.0.0 programme (licensed by the Faculty of Medicine of Albacete). Qualitative variables shall be expressed as absolute number and relative frequency. Quantitative variables shall be expressed as mean and standard deviation (SD). Dependence between qualitative variables was assessed using the Chi-square test. Student's t-test was used for the comparison of means after assessment of equality of variances (Snedecor's F-test). Differences between results were considered statistically significant if the p-value was less than 0.05.
ResultsDuring the period described, a total of 1259 unique patients with type 2 diabetes were attended in our EDN outpatient clinics, 43.3% female, with a mean age of 62.88±11.98 years. During the three-year period analyzed, patients with type 2 diabetes had an average of 5.52 blood tests, which is an estimate of approximately 2 tests per year. 148 patients (11.8%) had only one test during this time period. 1062 patients attended for type 2 diabetes (84.35%) had a low FIB-4 result and 137 patients (10.88%) indeterminate. The prevalence of advanced FIB-4 in these patients was 4.77% [95%CI: 3.66–6.09%; p=0.7029 compared to the expected value of 5% showed by Lomonaco R et al.]. The prevalence of advanced FIB-4 was 6.16% in men and 2.94% in women (p<0.05). The mean age of patients with advanced FIB-4 (68.43±9.37) was higher than that of patients with low or indeterminate results (62.60±12.03) (p<0.05). Fig. 1 shows the distribution of FIB-4 results for each analytical determination by age in individuals with type 2 diabetes.
A total of 580 unique patients with type 1 diabetes were attended, 52.2% female, with a mean age of 43.00±16.54 years. Patients had an average of 3.54 blood tests, which is an estimated 1–2 tests per year. 163 patients (28.1%) had only one blood test during this time period. 515 patients attended for type 1 diabetes (88.79%) had a low FIB-4 result and 55 patients (9.48%) indeterminate. The prevalence of advanced FIB-4 in these patients was 1.72% [95%CI: 0.83–3.15%; p<0.05 compared to the value of 4.77% observed in type 2 patients]. The prevalence of advanced FIB-4 was 1.81% in men and 1.65% in women (p=0.8862). The mean age of patients with advanced FIB-4 (68.40±13.33) was higher than that of patients with low or indeterminate results (42.55±16.25) (p<0.05). Fig. 2 shows the distribution of FIB-4 results for each analytical determination by age in individuals with type 1 diabetes.
Discussion
Screening for fibrosis using the FIB-4 score is recommended in adults with type 2 diabetes or with prediabetes, particularly in those with obesity or other cardiometabolic risk factors or established cardiovascular disease. Therefore, in people with type 1 diabetes should only be considered in the presence of additional risk factors for MASLD, such as obesity, incidental hepatic steatosis on imaging, or elevated plasma aminotransferases. Our findings support this recommendation. Introduction of FIB-4 in patients with diabetes attended in the EDN outpatient clinics of our hospital has allowed us to detect 4.8% advanced results among patients with type 2 diabetes and 1.7% among patients with type 1 diabetes. These results confirm the importance of implementing this recommendation to identify patients at higher risk of advanced liver fibrosis.2
However, we must highlight that 10.9% of patients with type 2 diabetes and 9.5% of patients with type 1 diabetes had an indeterminate FIB-4 result. This result recommends continuing the evaluation by performing, as the test of choice, vibration-controlled transient elastography to assess liver stiffness. The second test recommended is shear wave elastography or, if unavailable, an enhanced liver fibrosis test.7
In any case, the evaluation of these patients should be adequately planned according to the resources available and should be followed by a process of evaluating results.
The main limitation of our work is inherent in the retrospective nature of its design.
FundingOur work has not received external funding.
Conflicts of interestThere are no conflicts of interest related to the preparation of this work.
Data confidentialityWe have followed our workplace protocols regarding the publication of patient data.
