Obesity is a significant public health issue, increasingly linked to liver fibrosis, a condition marked by the excessive accumulation of extracellular matrix proteins in the liver. This condition is primarily mediated by Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), which encompasses a spectrum of liver disorders, from simple steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH). MASH often progresses to liver fibrosis, highlighting the importance of early detection and intervention. The rising prevalence of liver fibrosis among individuals with obesity underscores the need for timely clinical management to avoid severe liver-related complications.
Obesity and Liver Fibrosis: Mechanisms and Risk Factors
Obesity contributes to liver fibrosis through various mechanisms, including adipose tissue dysfunction, altered lipid metabolism, and dysregulated adipokines. The excessive influx of free fatty acids into the liver leads to hepatic steatosis, which results from increased triglyceride synthesis and decreased fatty acid oxidation. This accumulation initiates inflammatory pathways, promoting MASH, characterized by lobular inflammation and hepatocyte ballooning. The presence of insulin resistance exacerbates these conditions, driving further liver damage and fibrosis progression. Consequently, patients with liver fibrosis face increased risks of cardiovascular diseases and liver-related morbidities.
MAFLD, introduced as a more inclusive term for fatty liver diseases, now refers to a range of liver conditions characterized by hepatic steatosis and associated metabolic dysfunction. This term better reflects the multifactorial nature of liver disease and its link to metabolic abnormalities, including insulin resistance, obesity, hypertension, and dyslipidemia. Diagnosing MAFLD requires the presence of hepatic steatosis and one of the following: Type 2 Diabetes (T2D), metabolic dysregulation, or obesity.
Prevalence and Risk Factors of MAFLD
The global prevalence of MAFLD is approximately 33%, with the highest rates in South America (44%) and the lowest in Sub-Saharan Africa (14%). The condition is particularly prevalent among individuals with higher Body Mass Index (BMI), as the risk of developing MAFLD increases by 5.5 times with each unit increase in BMI. Furthermore, T2D is a significant risk factor for MAFLD, accelerating disease progression. However, a considerable proportion of MAFLD patients may not be obese, highlighting the importance of metabolic health, independent of BMI.
Lifestyle factors, such as poor diet and inactivity, along with genetic predisposition, also contribute to MAFLD progression, even in individuals of normal weight. Consequently, lifestyle modifications, including dietary changes and physical activity, are essential in managing and reversing MAFLD.
Bariatric Surgery and its Effects on Liver Fibrosis
Given the increasing burden of MAFLD and its associated liver fibrosis, particularly among those with obesity and T2D, bariatric surgery has gained prominence as an effective treatment option. Clinical studies have demonstrated that bariatric procedures, such as gastric bypass and sleeve gastrectomy, yield superior outcomes compared to lifestyle modifications and medical therapies. These surgeries not only facilitate significant weight loss but also improve serum lipid profiles, blood glucose control, and reduce the reliance on medications for diabetes, hypertension, and dyslipidemia.
Such improvements reduce the risk of cardiovascular diseases, as evaluated using tools like the Framingham risk equation. However, the impact of bariatric surgery on liver fibrosis, specifically among individuals with T2D, remains underexplored. This study aimed to evaluate the changes in liver fibrosis indices following bariatric surgery in T2D patients over a two-year follow-up period.
Study Design and Methodology
This study involved 1,205 adults with obesity and T2D who underwent one of three bariatric surgery types: one anastomosis gastric bypass (OAGB/MGB), sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB). The study was conducted retrospectively at the Surgical Department of Hazrat-e Rasool Hospital, Tehran, Iran. The inclusion criteria followed the diagnostic standards for T2D established by the American Diabetes Association (ADA). The study was approved by the institution’s ethics committee, and informed consent was obtained from all participants.
The study collected various demographic and metabolic data, including comorbidities (e.g., dyslipidemia, hypertension), anthropometric measurements (e.g., BMI, weight), and biochemical parameters (e.g., fasting blood glucose, HbA1c, serum lipids). Liver fibrosis indices, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS), and Fibrosis-4 (FIB-4) index, were assessed preoperatively and during follow-up visits at 6, 12, and 24 months post-surgery.
Fibrosis Indices and Liver Health
The APRI, NFS, and FIB-4 indices are non-invasive tools used to assess liver fibrosis severity. These indices are calculated based on various clinical parameters such as liver enzymes, platelet count, and BMI. For instance:
- FIB-4: A combination of age, AST, ALT, and platelet count.
- NFS: Combines age, BMI, presence of diabetes, AST/ALT ratio, platelet count, and albumin.
- APRI: Based on AST levels and platelet count.
The trend of these indices was analyzed throughout the two-year follow-up to evaluate their performance in diagnosing liver fibrosis among T2D patients after bariatric surgery.
Statistical Analysis and Data Interpretation
Statistical analysis was performed using IBM SPSS version 24. The Kolmogorov-Smirnov test was used to assess data normality. Categorical variables were compared using the Chi-square test, and continuous variables were analyzed using one-way ANOVA. The results were presented as mean ± standard deviation (SD).
In addition, the FIB-4 index was divided into low-risk and indeterminate-risk groups for liver fibrosis based on the established cut-off of 1.3, and the trends of these groups were separately analyzed.
Ethical Considerations
This study was conducted in accordance with the principles of the Declaration of Helsinki and received ethical approval from the Tehran University of Medical Sciences (TUMS). Informed consent was obtained from all participants.
Conclusion
Bariatric surgery has been shown to effectively improve metabolic parameters, including weight, glucose control, and lipid profiles, among patients with T2D. This study will provide valuable insights into the impact of bariatric surgery on liver fibrosis indices and liver health in individuals with T2D, highlighting the potential for early intervention in preventing further liver damage and improving long-term outcomes for these patients.
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