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

NCT05605821 | Unknown

• 1 other identifier: DIAFIB
• Study Type: observational
• Target: 520
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diabete Type 2

Outcome Measures

Primary Outcomes (1)

• Evaluation of the association between diabetic disease control and the degree of hepatic fibrosis

  This outcome corresponds to the level of association between long-term diabetes control estimated from the evolution of glycated hemoglobins (HbA1c) over the study period and the degree of liver fibrosis assessed by the FIB4 score (non-severe fibrosis: FIB4\<1.3 if age\<65 years or FIB4\<2 if age\>65 years; severe or undetermined fibrosis: FIB4\>1.3 if age\<65 years or FIB4\>2 if age\>65 years).

  Month1

Secondary Outcomes (4)

• Practices in terms of evaluation of hepatic fibrosis and management of patients

  Month 1

• Association between the use of certain treatments and the degree of hepatic fibrosis

  Month1

• Impact of Body Mass Index (BMI) variation on liver fibrosis

  Month1

• Percentage of patients at risk of severe fibrosis in a population of type 2 diabetics followed in a tertiary diabetes service.

  Month1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondation Hôpital Saint-Joseph: lead

Study Sites (2)

Hôpital Antoine Béclert

Clamart, France

Location

Groupe Hospitalier Paris Saint-Joseph

Paris, 75014, France

Location

Related Publications (4)

• Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, Srishord M. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011 Jun;9(6):524-530.e1; quiz e60. doi: 10.1016/j.cgh.2011.03.020. Epub 2011 Mar 25.

  PMID: 21440669 BACKGROUND

• Torres DM, Williams CD, Harrison SA. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012 Aug;10(8):837-58. doi: 10.1016/j.cgh.2012.03.011. Epub 2012 Mar 23.

  PMID: 22446927 BACKGROUND

• McPherson S, Hardy T, Dufour JF, Petta S, Romero-Gomez M, Allison M, Oliveira CP, Francque S, Van Gaal L, Schattenberg JM, Tiniakos D, Burt A, Bugianesi E, Ratziu V, Day CP, Anstee QM. Age as a Confounding Factor for the Accurate Non-Invasive Diagnosis of Advanced NAFLD Fibrosis. Am J Gastroenterol. 2017 May;112(5):740-751. doi: 10.1038/ajg.2016.453. Epub 2016 Oct 11.

  PMID: 27725647 BACKGROUND

• Hamaguchi E, Takamura T, Sakurai M, Mizukoshi E, Zen Y, Takeshita Y, Kurita S, Arai K, Yamashita T, Sasaki M, Nakanuma Y, Kaneko S. Histological course of nonalcoholic fatty liver disease in Japanese patients: tight glycemic control, rather than weight reduction, ameliorates liver fibrosis. Diabetes Care. 2010 Feb;33(2):284-6. doi: 10.2337/dc09-0148. Epub 2009 Oct 30.

  PMID: 19880582 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Adela VOICAN, MD

  Fondation Hôpital Saint-Joseph

  STUDY DIRECTOR

Central Study Contacts

Adela VOICAN, MD

CONTACT

144123395; avoican@ghpsj.fr

Helene BEAUSSIER, PharmD, PhD

CONTACT

144127883; crc@ghpsj.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2022
• First Posted: November 4, 2022
• Study Start: January 15, 2024
• Primary Completion: February 15, 2024
• Study Completion: December 30, 2024
• Last Updated: December 15, 2023

Record last verified: 2023-12

Locations

FR (2)