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

Diabete Type 2 Clinical Trial

— DIAFIB  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05605821
• Other study ID #: DIAFIB
• Status: Not yet recruiting
• Start date: January 15, 2024
• Est. completion date: December 30, 2024

Study information

• Verified date: December 2023
• Source: Fondation Hôpital Saint-Joseph
• Contact: Adela VOICAN, MD
• Phone: 144123395
• Email: avoican[@]ghpsj.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 520
• Est. completion date: December 30, 2024
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabete Type 2
• Diabetes Mellitus, Type 2
• Liver Cirrhosis

Locations

Country	Name	City	State
France	Hôpital Antoine Béclert	Clamart
France	Groupe Hospitalier Paris Saint-Joseph	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Fondation Hôpital Saint-Joseph

Country where clinical trial is conducted

France, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Practices in terms of evaluation of hepatic fibrosis and management of patients	This outcome corresponds to the percentage of patients at risk of advanced fibrosis who had additional investigations (pulse elastometry, liver biopsy) and were referred to hepatology.	Month 1
Secondary	Association between the use of certain treatments and the degree of hepatic fibrosis	This outcome corresponds to the association between the use of antidiabetic treatments and the degree of hepatic fibrosis.	Month1
Secondary	Impact of Body Mass Index (BMI) variation on liver fibrosis	This outcome corresponds to the BMI value at study entry and the degree of fibrosis according to the FIB4 score at entry and its evolution over time.	Month1
Secondary	Percentage of patients at risk of severe fibrosis in a population of type 2 diabetics followed in a tertiary diabetes service.	This outcome corresponds to the percentage of patients with severe fibrosis in a population of type 2 diabetics.	Month1

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