Influence of Diabetic Control on the Degree of Liver Fibrosis Assessed by Non-invasive Scores in Patients Followed in Diabetology

Influence of Diabetic Control on the Degree of Liver Fibrosis Assessed by Non-invasive Scores in Patients Followed in Diabetology: a Retrospective Study

Metabolic steatopathy (nonalcoholic fatty liver disease or NAFLD) has seen its prevalence soar in recent years that it is now the leading cause of chronic liver disease in developed countries, surpassing viral and alcoholic etiologies and affecting approximately 25% of the world's population. This growth is explained by a change in eating habits, lifestyle, and the increase in the prevalence of obesity in the general population. This hepatopathy evolves in successive stages in a slow and insidious manner: from simple fatty overload in the liver (NALF, steatosis), to steatosis plus hepatic inflammation (NASH - "nonalcoholic steatohepatitis"), up to the stage of cirrhosis with all its own complications Isolated steatosis has a rather benign course, whereas the transition to NASH is associated with a high risk of general mortality and liver-related causes. NASH is the stage at which fibrogenesis accelerates with the risk of progression to cirrhosis and/or primary liver cancer. The degree of hepatic fibrosis has a major influence on the prognosis of patients with NAFLD. Specifically, the presence of fibrosis greater than or equal to 2 (F≥2) is associated with increased risk of liver events and liver-related mortality. The risk of cardiovascular events increases as early as fibrosis grade 1 (F≥1). In addition, the presence of advanced fibrosis or cirrhosis (F≥3) greatly increases the risk of developing hepatocellular carcinoma, and patients require biannual monitoring by liver ultrasound. Systematic screening of diabetic patients with advanced fibrosis is necessary to establish specific surveillance. Non-invasive scores have been developed to assess the degree of liver fibrosis in patients with NAFLD. Among these scores, FIB4 ("Score Fibrosis-4") has the advantage of being easy to use in routine practice with good diagnostic performance for liver fibrosis in patients with NAFLD. A FIB4 value ≤ 1.3 has a negative predictive value of 90% for the diagnosis of severe fibrosis (F≥3), whereas a FIB4 > 2.67 has a positive predictive value of 80% for severe fibrosis. Diagnostic performance is poorer for patients older than 65 years, and an FIB4 cutoff <2 is used in this case to identify those at very low risk of advanced fibrosis. This score is calculated from platelet count, patient age, and transaminases (ASAT: Aspartate-Amino-Transferase and ALAT: Alanine-Amino-Transferase) according to the following formula: (age x ASAT) / (platelets x √[ALAT]). It allows selection of patients with a higher risk of advanced fibrosis who will require further investigations and specialist advice. It also allows to avoid unnecessary explorations in patients with a low risk of advanced fibrosis (FIB4<1.3 if age<65 years or FIB4<2 if age>65 years). There is currently no pharmacological treatment with market authorization. The mainstay of treatment is a change in lifestyle and habits (dietary and behavioral, including increased physical activity) with the aim of "fat cleansing" the liver. There is a strong link between the presence of type 2 diabetes and the risk of developing NAFLD and/or NASH. NAFLD is present in 70% of patients with type 2 diabetes. Furthermore, the presence of diabetes is associated with an increased risk of developing advanced fibrosis, cirrhosis and hepatocellular carcinoma in patients with NAFLD. Glycation end products are substances that result from the reaction between a carbohydrate and protein residues, but can also result from lipid oxidation. These molecules have been associated with accelerated aging and increased risk of cardiovascular disease. The accumulation of glycation end products during periods of prolonged hyperglycemia seems to contribute to the progression of hepatic fibrosis. In this context, our study aims to evaluate the impact of type 2 diabetes control on the degree of liver fibrosis using non-invasive tests. The primary objective is to evaluate the association between diabetic disease control and the degree of liver fibrosis. The secondary objectives are: to evaluate the practices in terms of evaluation of hepatic fibrosis and management of diabetic patients at risk of advanced fibrosis in a tertiary diabetes service, to evaluate the association between the use of certain treatments and the degree of hepatic fibrosis, to evaluate the impact of the variation of the Body Mass Index (BMI) on hepatic fibrosis and to evaluate the percentage of patients at risk of severe fibrosis in a population of type 2 diabetic patients followed up in a tertiary diabetology service.

Inclusion Criteria:

• Patient with age ≥ 18 years
• Patient with a diagnosis of type 2 diabetes, identified by ICD-10 codes, among patients hospitalized between 01/03/2018 and 17/03/2020 in HDJ in the Diabetes Service of GHPSJ
• French-speaking patient

Exclusion Criteria:

• Absence of at least one HbA1c measurement per year available over a period of 5 years (This is obtained by different means: handwritten in the patient's file, performed in the HDJ, performed in town and integrated into the patient's file, reported orally by the patient during the follow-up consultation. Glycated hemoglobin data for the 5-year retrospective period available).
• Lack of sufficient data to calculate the non-invasive fibrosis score FIB4.
• Secondary diabetes (neoplasia, chronic calcifying pancreatitis, post pancreatectomy pancreatic insufficiency for various reasons: see figure 8 below)
• HDJ for pre-bariatric surgery evaluation
• Other declared causes of chronic liver disease according to the patient's medical record
• Patient under guardianship or curatorship
• Patient deprived of liberty
• Patient under court protection
• Patient objecting to the use of his/her data for this research