Non-Alcoholic Fatty Liver Disease
Conditions
Brief summary
This study aims to measure the effect of GLP-1 analogues on non-alcoholic fatty liver disease in patients with diabetes and/or obesity in a clinical context. Previous studies showed a positive effect of this medication, but these studies always took place in highly controlled settings. The question is to what extent liver values evolve in a non-controlled context. The real effect and thus the clinical utility of GLP-1 analogues will be measured.
Detailed description
This study aims to measure the effect of GLP-1 analogues on non-alcoholic fatty liver disease in patients with diabetes and/or obesity in a clinical context. Previous studies showed a positive effect of this medication, but these studies always took place in highly controlled settings. The question is to what extent liver values evolve in a non-controlled context. The real effect and thus the clinical utility of GLP-1 analogues will be measured. Patients in whom a GLP-1 analogue is started (as it would be outside the context of this study) may be recruited. Patients in whom a GLP-1 analogue was started 12 months earlier are also eligible. Once they were screened on the inclusion and exclusion criteria and they took into account and signed the informed consent, they can be definitively included. Participants will be followed for 12 months. There are 2 contact points, the first on the start day and the second after 12 months. During this period, serum markers of liver injury, type 2 diabetes and dyslipidaemia are monitored. With these, additional scores for hepatic steatosis (NAFLD liver fat score) and fibrosis (FIB-4 index) are calculated. A fibroscan (or elastography) is also performed to monitor the evolution of hepatic steatosis and fibrosis. The evolution of data is statistically analysed and hereby compared with the starting points.
Interventions
OTHERnon-interventional
non-interventional
Sponsors
Universitair Ziekenhuis Brussel
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The patient is older than 18 years old. * The patient has obesity, defined as a BMI of 30 or higher; and/or the patient suffers from T2DM, defined as a twice measured sfG of 125 mg/dl or higher, or a sfG of 100 to 125 mg/dl and a twice measured oral glucose tolerance test (OGTT) with a serum glucose (sG) of 200 mg/dl, or higher after 2 hours, or a random sG of 200 mg/dl or higher in symptomatic patients. * The patient suffers from NAFLD in any stage, except cirrhosis. This has to be objec-tively diagnosed by either a CAP fibroscan (cutoff: \> 238 dB/m); or by the calculated NAFLD liver fat score (cutoff: \> -0,64), at least one of which has to be positive. * The patient is starting a GLP-1 analogue as treatment for T2DM or obesity as would be prescribed outside of this study; or the patient has started a GLP-1 analogue as treatment for T2DM or obesity as would be prescribed outside of this study 12 months prior. * If the patient is part of the retro-prospective branch data collected 12 months prior include at least a (CAP) fibroscan, a blood sample (measuring AST, ALT, GGT, sfG, sfI, HbA1c, HDL, LDL, total cholesterol and platelets) and a physical examination (measuring blood pressure, waist circumference, weight and length).
Exclusion criteria
* The patient suffers from alcohol induced fatty liver disease. Macrocytic anemia; de-creased vitamin B12 and folic acid; increased GGT, bilirubin, ferritin, TG and AST/ALT ratio can be used as serum markers of alcohol abuse. Interpretation of these results will be the left to the patient's clinician and their clinical expertise. Alterna-tively a weekly alcohol consumption of 21 units for men and 14 units for women can be used as a cutoff. * The patient suffers from drug induced liver steatosis. Drugs warranting exclusion include glucocorticoids, amiodarone, tamoxifen, methotrexate, valproate, tetracycline and chemotherapeutic agents. * The patient suffers from any other chronic liver disease. These will be checked trough lab test results in the patients file. * The patient has liver cirrhosis, defined as a fibroscan score of 14 kPa or more; or a FIB-4 index of \> 2,67. Elastography * The patient is pregnant at time of enrolment or at any time during the study. * The patient refuses to agree to the informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Markers (sfG) to Follow the Evolution of Liver Damage | From time of infomed consent till 1 year after signing informed consent. | This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to follow the evolution of liver damage. |
| Fatty Liver Index (FLI) | From time of signing the ICF till 1 year after given informed consent | This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to calculate the Fatty Liver Index to evaluate steatosis. The Fatty Liver Index (FLI) (calculated using TG, GGT, abdominal waist circumference and BMI) was employed to monitor the risk for steatosis. FLI: \< 30 as low risk, 30 to \< 60 as intermediate risk, and ≥ 60 as high risk for liver steatosis. |
| FIB-4 Index | From time of signing the ICF till 1 year after given informed consent | This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to calculate the FIB-4 index to evaluate fibrosis. The FIB-4 index is a non-invasive tool used to assess the likelihood of advanced liver fibrosis in individuals, particularly those with conditions like non-alcoholic fatty liver disease (NAFLD) or type 2 diabetes. It combines age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count to generate a score that helps categorize patients into low, intermediate, or high risk for significant liver scarring. FIB-4 index: \< 1,3 for patients \< 64 years or \< 2 for those \> 64 years as low risk (F0-1 = mild fibrosis); 1,3 - 2,67 (\< 64 years) or 2 - 2,67 (\> 64 years) as intermediate risk (F2-3 = moderate fibrosis); and \> 2,67 as high risk for advanced fibrosis (F4 = severe fibrosis to cirrhosis). |
| Serum Markers (HbA1c) to Follow the Evolution of Liver Damage | From time of infomed consent till 1 year after signing informed consent. | This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to follow the evolution of liver damage. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Group Obese and/or diabetic patients with objectified NAFLD starting a GLP-1 analogue | 48 |
| Total | 48 |
Baseline characteristics
| Characteristic | Study Group | — |
|---|---|---|
| Age, Continuous | 58 years | — |
| Indication of GLP1a Obesity | 2 Participants | — |
| Indication of GLP1a T2DM | 46 Participants | — |
| prevalence prevalence of liver steatosis in patients participating | 48 participants | — |
| prevalence prevalence of obesity in patients participating | 48 participants | — |
| prevalence prevalence of T2DM in patients participating | 48 participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 19 Participants | — |
| Sex: Female, Male Male | 29 Participants | — |
| Use of statins at initiation of GLP1a patients not using statins | 10 Participants | — |
| Use of statins at initiation of GLP1a patients using statins | 38 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 48 |
| other Total, other adverse events | 0 / 48 |
| serious Total, serious adverse events | 0 / 48 |
Outcome results
Primary
Fatty Liver Index (FLI)
This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to calculate the Fatty Liver Index to evaluate steatosis. The Fatty Liver Index (FLI) (calculated using TG, GGT, abdominal waist circumference and BMI) was employed to monitor the risk for steatosis. FLI: \< 30 as low risk, 30 to \< 60 as intermediate risk, and ≥ 60 as high risk for liver steatosis.
Time frame: From time of signing the ICF till 1 year after given informed consent
Population: no FLI was available at month 12 for 11 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Fatty Liver Index (FLI) | FLI at month 0 | 88.92 units on a scale | Standard Deviation 10.31 |
| Study Group | Fatty Liver Index (FLI) | FLI at month 12 | 80.39 units on a scale | Standard Deviation 15.3 |
Primary
FIB-4 Index
This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to calculate the FIB-4 index to evaluate fibrosis. The FIB-4 index is a non-invasive tool used to assess the likelihood of advanced liver fibrosis in individuals, particularly those with conditions like non-alcoholic fatty liver disease (NAFLD) or type 2 diabetes. It combines age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count to generate a score that helps categorize patients into low, intermediate, or high risk for significant liver scarring. FIB-4 index: \< 1,3 for patients \< 64 years or \< 2 for those \> 64 years as low risk (F0-1 = mild fibrosis); 1,3 - 2,67 (\< 64 years) or 2 - 2,67 (\> 64 years) as intermediate risk (F2-3 = moderate fibrosis); and \> 2,67 as high risk for advanced fibrosis (F4 = severe fibrosis to cirrhosis).
Time frame: From time of signing the ICF till 1 year after given informed consent
Population: no FIB-4 score was available for 4 patients at month 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | FIB-4 Index | FIB-4 at month 0 | 1.17 units on a scale | Standard Deviation 0.54 |
| Study Group | FIB-4 Index | FIB-4 at month 12 | 1.09 units on a scale | Standard Deviation 0.56 |
Primary
Serum Markers (HbA1c) to Follow the Evolution of Liver Damage
This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to follow the evolution of liver damage.
Time frame: From time of infomed consent till 1 year after signing informed consent.
Population: no HbA1c was available for 3 patients at month 12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Serum Markers (HbA1c) to Follow the Evolution of Liver Damage | HbA1c at month 0 | 8.16 percentage | Standard Deviation 0.996 |
| Study Group | Serum Markers (HbA1c) to Follow the Evolution of Liver Damage | HbA1c at month 12 | 7.14 percentage | Standard Deviation 1.18 |
Primary
Serum Markers (sfG) to Follow the Evolution of Liver Damage
This study aims to measure the effect of GLP-1 analogues on liver steatosis and fibrosis in diabetic and obese patients in a real-life clinical setting. Serum markers will be used to follow the evolution of liver damage.
Time frame: From time of infomed consent till 1 year after signing informed consent.
Population: To better understand potential therapeutic effects in patients with more pronounced liver involvement, subjects presenting with liver enzymes levels above the ULN at baseline were analyzed separately also.~no AST under ULN was available at month 12 (m12) for 3 patients. no ALT under ULN was available at m12 for 1 patients. no GGT under ULN was available at m12 for 2 patients. no ALT above ULN was available at m12 for 2 patients. no GGT above ULN was available at m12 for 1 patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | AST under ULN at month 0 | 22.59 U/L | Standard Deviation 7.997 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | ALT under ULN at month 0 | 28.51 U/L | Standard Deviation 14.716 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | GGT under ULN at month 0 | 38.59 U/L | Standard Deviation 22.542 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | AST under ULN at month 12 | 21.34 U/L | Standard Deviation 8.515 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | ALT under ULN at month 12 | 27.58 U/L | Standard Deviation 15.448 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | GGT under ULN at month 12 | 36.68 U/L | Standard Deviation 22.534 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | AST above ULN at month 0 | 37.86 U/L | Standard Deviation 2.61 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | ALT above ULN at month 0 | 45.54 U/L | Standard Deviation 13.457 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | GGT above ULN at month 0 | 71 U/L | Standard Deviation 22.857 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | GGT above ULN at month 12 | 63 U/L | Standard Deviation 30.054 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | AST above ULN at month 12 | 29.43 U/L | Standard Deviation 13.501 |
| Study Group | Serum Markers (sfG) to Follow the Evolution of Liver Damage | ALT above ULN at month 12 | 38.45 U/L | Standard Deviation 17.218 |