Effects of Weight Loss on Non-Alcoholic Fatty Liver Disease (NAFLD) in a United Arab Emirates Based Population: A Comparative Analysis of Bariatric Surgery and Non-Surgical Interventions

doi:10.21203/rs.3.rs-5240706/v1

Introduction: Non-Alcoholic Fatty Liver Disease (NAFLD) is highly prevalent in the United Arab Emirates, but the comparative effects of bariatric surgery and medical weight loss on NAFLD in this population remain understudied. This study aimed to evaluate the impact of these interventions on NAFLD parameters in severely obese patients.

Methods: This prospective study compared 51 patients undergoing bariatric surgery (surgical cohort) with 35 patients undergoing supervised medical weight loss (medical cohort). Anthropometric measurements, comprehensive laboratory tests, and transient elastography (Fibroscan®) were performed at baseline and 12-month follow-up. Intraoperative liver biopsies were conducted for the surgical cohort.

Results: At 12-month follow-up, the surgical cohort showed significantly greater improvements in BMI (29.65 ± 5.39 vs 38.42 ± 6.39 kg/m², p<0.001), total weight loss (29.25% vs 1.34%, p<0.001), and liver function markers including ALT (16.55 vs 30.29 U/L, p<0.001). HbA1c levels were lower in the surgical group (5.07% vs 5.57%, p=0.014). Lipid profiles improved more in the surgical cohort. Fibroscan results demonstrated greater reductions in controlled attenuation parameter (321.26 to 234.08 vs 316.88 to 321.00 dB/m, p<0.001) and liver stiffness (5.74 to 4.56 vs 5.84 to 5.36 kPa, p=0.062) in the surgical group, indicating improved liver fat content and fibrosis.

Conclusion: Bariatric surgery resulted in superior outcomes for weight loss, metabolic parameters, and improvement in NAFLD markers compared to medical weight loss in this UAE-based population. This suggests its efficacy as an intervention for NAFLD in severely obese patients, though long-term studies are needed to confirm the sustainability of these improvements.

Severe obesity

NASH

NAFLD

fibroscan

bariatric surgery and medical treatment

Bariatric surgery led to significantly greater weight loss and improvement in liver function markers compared to medical weight loss.
Fibroscan results showed more substantial reductions in liver fat content and fibrosis in the surgical group.
The study provides evidence supporting bariatric surgery as an effective intervention for NAFLD in severely obese patients in the UAE.
Further research is needed to explore long-term outcomes and potential gender-specific effects of bariatric surgery on NAFLD.

Severe obesity in the Middle East has reached epidemic proportions, with the prevalence of obese and overweight adults in the gulf states ranging from 50 to 80%¹. In the United Arab Emirates (UAE), this trend is particularly concerning, with obesity rates among the highest in the region. The association of severe obesity with diseases such as type 2 diabetes (T2D) and cardiovascular diseases (CVD) has been well described, and the incidence of these obesity-related comorbidities has increased in parallel with the rise of obesity in the region^2,3. Treatment and management of these conditions have become a tremendous cost burden in Gulf Cooperation Council (GCC) countries, with the cost of CVD and TD2 exceeding $11 billion in 2013⁴.

Severe obesity has been strongly associated with an increased risk of Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD is now the most common cause of chronic liver diseases worldwide, and in the United Arab Emirates, its prevalence was estimated to be 25.0% in 2017, with predictions of a further increase to 30.2% by 2030^5–7. NAFLD encompasses a spectrum of liver conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma^5,8,9. Moreover, NAFLD has significant clinical implications beyond liver health, including a higher risk of insulin resistance and increased risk of CVD¹⁰.

The "gold standard" for diagnosing and characterizing the extent of NAFLD involves liver biopsy and histological analysis. However, this method is expensive, invasive, and carries risks of complications^11,12. In response to these limitations, non-invasive diagnostic modalities have gained prominence. Vibration-controlled transient elastography (TE) (Fibroscan®) is an ultrasound-based technique that can assess liver stiffness and elasticity¹³. TE offers several advantages over liver biopsy, including being non-invasive, less costly, and capable of evaluating both fibrosis and steatosis in NAFLD¹⁴. These characteristics make TE particularly valuable in the UAE context, where non-invasive and cost-effective diagnostic tools are crucial for managing the growing NAFLD epidemic.

Weight loss is recognized as the primary therapy for NAFLD, as it can improve liver steatosis, inflammation, and fibrosis². Lifestyle modifications, such as diet and exercise, are recommended as an initial treatment approach for NAFLD⁵. However, many patients find it challenging to implement and maintain these changes⁵. A recent prospective study involving 39 patients reported an improvement in liver fibrosis measured using TE and Alanine aminotransferase (ALT) levels after lifestyle modifications¹⁵.

For patients who struggle with lifestyle modifications alone, bariatric surgery has demonstrated as a powerful intervention. Bariatric surgery can achieve substantial and sustained weight loss, and has shown to be more effective than supervised medical weight loss alone in improving hepatic steatosis and inflammation, although its effect on fibrosis remains a subject of debate^5,7,16–18. A meta-analysis of 3751 patients undergoing bariatric surgery reported complete resolution of steatosis, ballooning degeneration, inflammation, and fibrosis in 56%, 49%, 45%, and 25% of patients, respectively⁵. Furthermore, a prospective study with 18 nondiabetic and severely obese patients undergoing Roux-en-Y gastric bypass (RYGB) suggests that NASH improves after bariatric surgery, with beneficial effects extending beyond weight loss alone¹⁹. This study also reported that hormonal changes due to surgery, especially in glucagon-like peptide 1 (GLP-1), modify insulin sensitivity and lipid metabolism, independently improving the histological features of NASH¹⁹.

Despite the growing scientific evidence supporting the efficacy of bariatric surgery in managing NAFLD, there is a notable gap in the literature comparing the effects of medical supervised weight loss and bariatric surgery on NAFLD, particularly in the UAE population. Additionally, there is limited data comparing the use of TE versus liver biopsy for the diagnosis of NAFLD in obese patients within this specific demographic. Given the rising prevalence of obesity and NAFLD in the UAE, understanding the relative effectiveness of these interventions is crucial for informing clinical practice and health policy in the region.

Therefore, the aim of this study was to evaluate the effect of surgical weight loss on NAFLD in severely obese patients undergoing primary bariatric surgery versus non-surgical control undergoing supervised medical weight loss in a United Arab Emirates (UAE) based population.

Study design and ethical approvals:

This was a prospective study conducted with the approval of the local research ethical committee (REC) under the internal number A-2019-020.

Population:

Patients undergoing primary bariatric surgery and medically supervised weight loss. Patients were divided into two cohorts: 1. Surgical Cohort (SC) – patients undergoing primary bariatric surgery including RYGB or Sleeve Gastrectomy (SG). 2 Medical Cohort (MC) – patients undergoing medically supervised weight loss.

Primary objective:

To evaluate the effect of surgical weight loss on NAFLD in severely obese patients undergoing primary bariatric surgery versus non-surgical control undergoing supervised medical weight loss.

Secondary objectives:

To compare the impact of weight loss on NAFLD, measured by TE, between the SC and MC after 12 months of follow-up. To assess the correlation between TE and liver biopsy in diagnosing NAFLD in patients undergoing bariatric surgery.

Eligibility criteria:

The inclusion and exclusion criteria for the study were distinctly outlined between the two arms, SC and MC. In the SC, participants had to be aged between 18 and 65, with a BMI exceeding 35. Eligible patients were those who had agreed to undergo primary bariatric surgery, either SG or RYGB, and were willing to have both a Fibroscan and a liver biopsy. Additionally, participants had to express their willingness to participate in the study. For the MC, the criteria were similar regarding age (18 to 65 years) and BMI (>35). These patients needed to be undergoing supervised medical weight loss, agree to a Fibroscan, and be willing to participate in the study. Exclusion criteria for the SC included the presence of co-existing liver disease, viral hepatitis, hepatocellular carcinoma, overt hepatic decompensation, or a history of prior bariatric or weight loss procedures. For the MC, patients with co-existing liver disease, viral hepatitis, hepatocellular carcinoma, overt hepatic decompensation, or those who had received weight loss medical treatment within the last 12 months before the enrollment date were excluded from the study.

Informed consent process:

Patients eligible for study participation were approached in the outpatient clinics by the investigators. Patients and investigators discussed the study's objectives, procedures, risks, and benefits. Patients were given time to review the study documents, ask questions, and clarify concerns. Their decision to participate was voluntary, and they could withdraw from the study at any time. Subjects who chose to participate in the study, they signed the consent form and ongoing communication was maintained throughout the trial to keep them informed. This process ensured that patients were well-informed and could make an informed decision about their participation while upholding ethical and regulatory guidelines.

Research procedures:

SC: Patients who underwent primary bariatric surgery including SG or RYGB underwent pre-operative investigations with TE and blood chemistry analysis including: Complete blood count (CBC), complete metabolic panel (CMP), Gamma-Glutamyl Transferase (GGT), High Sensitivity C- Reactive Protein (HSCRP), lipid profile and Hemoglobin A1c (HbA1C). For the SC, intraoperative liver biopsy was performed. Laboratory studies and TE were at 12 months post- operatively. Changes in liver fibrosis, steatosis and resolution of comorbidities were analyzed between cohorts.

MC: Patients who underwent medically supervised weight supervised weight loss underwent baseline investigations with TE and blood chemistry analysis as the SC. For the MC, intraoperative liver biopsy was not performed. Laboratory studies and TE were at 12 months post- operatively.

Data Collection and Statistical Analysis:

Data was collected from electronic medical records, including basic demographic data, preoperative laboratory test, preoperative clinical imaging, intraoperative procedures for the SC, follow up laboratory test and follow up clinical imaging. Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR) as appropriate, while categorical variables were presented as frequencies and percentages. Data preparation involved encoding binary variables as 0 or 1, removing administrative variables and those without data, replacing "<2.5" values with 2.5 for continuous variables, and calculating weight loss measures using baseline weight and BMI. Baseline comparisons between surgical and medical groups were conducted using the Mann-Whitney U test for continuous variables, Fisher's exact test for binary variables with low sample counts, and chi-squared test for categorical variables. Longitudinal analysis to assess changes from baseline to 12-month follow-up within each group employed the Wilcoxon signed-rank test for continuous variables and McNemar's test for binary variables, applied to liver outcomes, blood markers, and weight outcomes. The correlation between Fibroscan and biopsy scores at baseline for steatosis and fibrosis was evaluated using the phi coefficient. A two-tailed p-value < 0.05 was considered statistically significant for all analyses. All statistical analyses were performed using R (version 2.13 or higher, The R Foundation for Statistical Computing, Vienna, Austria).

Sample size calculation:

Sample size was calculated to detect a medium to large effect size (Cohen's d = 0.68) between the surgical and medical groups, with 80% power at a 5% significance level (two-tailed test). This effect size was deemed clinically meaningful based on previous studies reporting substantial improvements in NAFLD markers following bariatric surgery. A minimum of 35 participants per group was determined to be sufficient, allowing for the detection of clinically significant differences while considering feasibility and resource constraints. Assuming a 20% dropout rate, we aimed to recruit 44 participants per group to ensure at least 35 complete datasets at the end of the 12-month follow-up period.

Definitions:

NAFLD: NAFLD is defined by the presence of fatty tissue in the liver (hepatic steatosis) and is confirmed using imaging or liver histology. It excludes any secondary causes such as significant alcohol consumption, certain medications such as valproic acid, tetracycline and aspirin, and other medical conditions such as viral hepatitis^20,21.

NASH: NASH is a progressive form of NAFLD which involves additional factors such as insulin resistance and endothelial cell activation. NASH can lead to fibrosis or scarring of the liver, cirrhosis and hepatocellular carcinoma²². Consequently, the deterioration of the liver can potentially impact the structure and function of other organs and systems through extra-hepatic pathways²². NASH is associated with the development of chronic kidney disease, T2D and CVD.

MASLD: MASLD is defined as the presence of hepatic steatosis (fatty liver) in individuals with one or more metabolic risk factors, such as obesity, type 2 diabetes, dyslipidemia, or hypertension. It is diagnosed through imaging techniques or liver histology, in the absence of other causes of liver disease such as excessive alcohol consumption, viral hepatitis, or certain medications. MASLD comprises a spectrum of liver conditions, from simple steatosis to more severe forms that can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. This term has been proposed to replace NAFLD (Non-Alcoholic Fatty Liver Disease) to better reflect the underlying metabolic dysfunction and to avoid the stigma associated with alcohol-related terminology.²²

Transient elastography (TE) (Fibroscan®): TE (FibroScan) is a non-invasive method proposed for the assessment of hepatic fibrosis in patients with chronic liver disease by measuring liver stiffness. The most important parameters evaluated by the TE include the liver stiffness measurement (LSM), which is a radiological sign of liver fibrosis and the controlled attenuation parameter (CAP), which is a radiological sign of steatosis or fat accumulation in the liver.

Liver Biopsy: Liver Biopsy is a procedure in which a small needle is inserted into the liver to collect a very small sample, is often performed to determine how much damage the liver has sustained by assessing the stage of fibrosis. In this study, the liver biopsies were performed laparoscopically only in the SC during the bariatric surgical procedure.

Medically supervised weight loss: It is defined as a structured program of lifestyle modifications, including dietary changes and increased physical activity, that is overseen and guided by a healthcare team.

Demographics and baseline characteristics

A total of 86 patients were included in the study, with 51 in the SC and 35 in the MC. The baseline characteristics of both groups are presented in Table 1. The SC was significantly younger (32.94 ± 7.81 years vs 41.23 ± 11.18 years, p<0.001) and had a higher mean BMI (41.83 ± 6.95 kg/m² vs 38.86 ± 6.22 kg/m², p=0.002) compared to the MC. Both groups were predominantly female (68.6% in SC, 60.0% in medical) and of Arab ethnicity (98.0% in SC, 88.6% in MC).

Comorbidities were similarly distributed between the groups, with no significant differences in the prevalence of diabetes mellitus, hypertension, hyperlipidemia, or gastroesophageal reflux disease. However, the surgical group had a higher, though not statistically significant, proportion of current smokers (21.6% vs 5.7%, p=0.065).

Baseline laboratory tests showed comparable levels of HbA1c, ALT, total cholesterol, and triglycerides between the groups. However, the medical cohort had significantly higher HDL levels (1.26 ± 0.27 mmol/L vs 1.13 ± 0.27 mmol/L, p=0.017) and marginally higher AST levels (25.09 ± 12.51 U/L vs 22.14 ± 9.95 U/L, p=0.050). Baseline Fibroscan results were similar between the groups, with no significant differences in CAP, LSM, steatosis level, or fibrosis level. (Table 1)

Intraoperative findings and correlation between fibroscan and biopsy (SC)

In the SC (n=51), SG was the predominant procedure, performed in 33 patients (64.7%), while RYGB was performed in 18 patients (35.3%). Intraoperative liver biopsies revealed steatosis in 42 patients (82.4%) and fibrosis in 6 patients (11.8%).

The correlation between Fibroscan and biopsy results at baseline was assessed for both steatosis and fibrosis. For steatosis, there was essentially no correlation (phi coefficient = -0.05, p=0.96). Similarly, for fibrosis, there was only a weak, non-significant correlation (phi coefficient = 0.15, p=0.43). These results suggest limited agreement between Fibroscan and biopsy findings for both steatosis and fibrosis in this patient population. (Table 2)

Weight loss, blood tests, and fibroscan results at 12-Month Follow-up

At the 12-month follow-up, the SC demonstrated significantly greater improvements in weight loss and metabolic parameters compared to the MC (Table 3). The SC achieved a mean total weight loss (%TWL) of 29.25 ± 8.91% compared to only 1.34 ± 3.96% in the medical group (p<0.001). This translated to a significantly lower mean BMI in the surgical group at follow-up (29.65 ± 5.39 kg/m² vs 38.42 ± 6.39 kg/m², p<0.001).

Laboratory tests at 12 months showed significant improvements in the SC compared to the MC. HbA1c levels were lower in the SC (5.07 ± 0.48% vs 5.57 ± 1.14%, p=0.014), as were ALT levels (16.55 ± 7.51 U/L vs 30.29 ± 19.14 U/L, p<0.001). The SC also demonstrated a more favorable lipid profile, with lower triglycerides (0.91 ± 0.34 mmol/L vs 1.50 ± 0.81 mmol/L, p<0.001) and higher HDL (1.39 ± 0.32 mmol/L vs 1.21 ± 0.26 mmol/L, p=0.028). Furthermore, CRP levels were significantly lower in the SC (2.57 ± 2.13 mg/L vs 6.72 ± 5.56 mg/L, p<0.001), indicating a reduction in systemic inflammation. (Table 3)

Fibroscan results at baseline and 12-month follow-up

Fibroscan results at 12 months showed marked improvements in the SC compared to the medical cohort. The surgical group demonstrated a significant reduction in CAP, indicating decreased liver fat content (from 321.26 ± 48.17 dB/m to 234.08 ± 58.22 dB/m), while the medical group showed a slight increase (from 316.88 ± 56.59 dB/m to 321.00 ± 50.91 dB/m) (p<0.001 between groups).

Liver stiffness measurements (LSM) improved in both groups, with a more pronounced decrease in the SC (from 5.74 ± 2.59 kPa to 4.56 ± 2.14 kPa) compared to the MC (from 5.84 ± 3.44 kPa to 5.36 ± 2.96 kPa), although this difference did not reach statistical significance (p=0.062). Steatosis levels as measured by Fibroscan showed a significant improvement in the SC (from 2.44 ± 0.75 to 1.00 ± 0.82) compared to minimal change in the MC (from 2.56 ± 0.71 to 2.48 ± 0.72) (p<0.001). Similarly, fibrosis levels improved more markedly in the SC (from 0.41 ± 0.78 to 0.06 ± 0.24) than in the MC (from 0.46 ± 0.79 to 0.33 ± 0.69), with the difference approaching statistical significance (p=0.050). (Table 4)

The findings of this study demonstrated several differences between the surgical cohort (SC) and the medical cohort (MC). After 12 months follow-up, the SC showed a substantial decrease in median BMI, with a greater proportion of patients losing more than 10 kg/m² compared to the MC. Blood chemistry tests found that the SC had a greater improvement in ALT levels, indicating resolution of liver inflammation. Additionally, the SC reported a higher reduction of cholesterol, triglyceride, alkaline phosphatase, and LDL levels in comparison with the MC. Changes in liver stiffness and CAP were more favorable in the SC, with a greater improvement in fibrosis and steatosis scores. These results are comparable with previous literature reporting a reduction of BMI for both cohorts of treatments^{7,15,16,23–27}. Lee et al., in their meta-analysis of 3751 patients undergoing bariatric surgery reported a 24.98% total reduction in BMI after bariatric surgery within a median follow-up period of 15 months²⁵. In contrast, Paul et al. reported only a 6.9% decrease in mean BMI after 6 months of lifestyle modifications in NAFLD patients¹⁵. This demonstrates that while both interventions lead to BMI reduction, bariatric surgery proves more effective for weight loss, possibly due to targeted and drastic changes to metabolic processes^5,19.

The positive impact of bariatric surgery on hepatic function is well-established^16,25–27. Our findings of improved ALT levels in the SC align with those of Garg et al., who showed significant declines in ALT levels 12 months post-bariatric surgery^7,28. This improvement in liver function markers supports the "2-hit" hypothesis of NAFLD progression, where weight loss addresses both the accumulation of liver fat and the oxidative stress leading to necroinflammation^29–33. Our study also assessed the correlation between Fibroscan and liver biopsy results. We found essentially no correlation for steatosis assessment (phi coefficient − 0.05, p = 0.96) and a weak, non-significant correlation for fibrosis assessment (phi coefficient 0.15, p = 0.43). These findings suggest that Fibroscan may have limitations in accurately assessing NAFLD in our specific population of UAE-based bariatric surgery candidates. Factors such as high BMI, population-specific NAFLD prevalence, or unique ethnic characteristics might contribute to these discrepancies³⁴. Clinically, these results imply that while Fibroscan may be useful as a screening or monitoring tool, liver biopsy remains necessary for definitive NAFLD assessment in this population, especially for critical treatment decisions³⁵.

Our findings have significant implications not only for the UAE but also for the global management of NAFLD in severely obese patients. The superior outcomes of bariatric surgery in improving NAFLD markers, compared to lifestyle modifications alone, contribute to the growing body of evidence supporting surgical interventions for metabolic diseases³³. This is particularly relevant in regions with high obesity rates, such as the Middle East, North America, and parts of Europe and Asia^18–21. The discrepancies we observed between Fibroscan and liver biopsy results highlight a critical issue in NAFLD management worldwide. As healthcare systems globally seek cost-effective and non-invasive methods for diagnosing and monitoring NAFLD, our results underscore the need for population-specific validation of these tools. This finding could impact clinical practice guidelines not only in the UAE but in other countries with diverse ethnic populations.

Moreover, our study addresses a crucial gap in NAFLD research by directly comparing surgical and non-surgical interventions in a prospective design. This approach provides valuable data for health policymakers and clinicians worldwide who are grappling with the rising tide of obesity and its hepatic complications. The cost-effectiveness of bariatric surgery in improving NAFLD, as suggested by our results, could inform resource allocation decisions in various healthcare systems, particularly in countries with similar demographic and epidemiological profiles to the UAE. This study has several strengths. It is the first in the UAE and the Middle East to measure the effectiveness of bariatric surgery on NAFLD and the first to directly compare lifestyle modifications with primary bariatric surgery for NAFLD improvement. The prospective design, use of both invasive and non-invasive assessment methods, and the focus on a specific ethnic population contribute to its novelty and clinical relevance.

However, there are also limitations to consider. The study was conducted during the COVID-19 pandemic, which led to a loss of patients during follow-up from the initial enrollment number, potentially affecting our final sample size and results. This experience serves as a reminder of the challenges facing long-term clinical research globally and can inform future study designs, emphasizing the need for robust follow-up mechanisms that can withstand unforeseen global events. The predominantly female population in the surgical cohort, while consistent with previous studies^{16, 25,26}, may limit generalizability to male patients. We were unable to compare our results with other non-invasive tests like Fatty Liver Index (FLI) or Enhanced Liver Function (ELF) score due to their unavailability. Additionally, the use of fixed CAP score ranges for steatosis grades, rather than BMI-adjusted scores as suggested by Agarwal et al.¹⁶, may have influenced our steatosis assessments.

Future research should extend beyond regional boundaries, considering gender-specific effects and exploring more accurate non-invasive diagnostic tools across diverse populations. Multi-center, international collaborative studies with larger, more diverse sample sizes would enhance our understanding and optimize NAFLD management strategies globally. Such studies could investigate the long-term sustainability of improvements post-bariatric surgery and their impact on overall morbidity and mortality across different ethnic groups; the development and validation of population-specific Fibroscan cut-off values or alternative non-invasive assessment tools for NAFLD; the role of genetic and environmental factors in NAFLD progression and treatment response in diverse populations; the impact of different bariatric surgery techniques on NAFLD outcomes in various ethnic groups; and the cost-effectiveness of bariatric surgery for NAFLD management in different healthcare systems and economic contexts. Additionally, future steps should focus on translating these findings into clinical practice guidelines that can be adapted for different healthcare settings worldwide. This could include developing risk stratification tools for identifying patients most likely to benefit from bariatric surgery for NAFLD management

In conclusion, our study provides strong evidence that bariatric surgery is more effective than lifestyle modifications in improving NAFLD among severely obese patients in the UAE. We observed significant improvements in liver health markers, weight loss, and metabolic parameters in the surgical group compared to the medical management group. However, the weak correlation between Fibroscan and liver biopsy results highlights the need for cautious interpretation of non-invasive assessments in this population. While our research was conducted in the UAE, its implications extend globally, contributing to the wider dialogue on NAFLD management in diverse populations. As obesity and NAFLD rates continue to rise worldwide, this research provides crucial insights that can inform clinical practice, guide health policies, and ultimately improve patient outcomes on an international scale.

Author Contribution

J.S.B-G., M.S.I.K., and G.D.D.G. conceived and designed the study. J.S.B-G., M.S.I.K., G.D.D.G., and H.R. acquired the data. J.P.P., C.A., and C.M. analyzed and interpreted the data. J.R., F.K., and R.G. drafted the manuscript. M.C. and H.S. critically revised the manuscript for important intellectual content. R.C., J.R., and M.K. provided administrative, technical, and material support. J.S.B-G. and M.K. supervised the study.All authors made substantial contributions to the conception or design of the study; or the acquisition, analysis, or interpretation of data. All authors drafted the work or revised it critically for important intellectual content. All authors approved the final version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the study are appropriately investigated and resolved.

Acknowledgement

None

Conflict of Interest Statement:

• Author 1, MD: No conflict of interest

• Author 2, BSc: No conflict of interest

• Author 3, MD: No conflict of interest

• Author 4, MD: No conflict of interest

• Author 5, MD, PhD: No conflict of interest

• Author 6, MD: No conflict of interest

• Author 7, MD: No conflict of interest

• Author 8, MD: No conflict of interest

• Author 9, MD: No conflict of interest

• Author 10, MD: No conflict of interest

• Author 11, MD: No conflict of interest

• Author 12, MD: No conflict of interest

• Author 13, MD, PhD: No conflict of interest

• Author 14, MD: No conflict of interest

• Author 15, MD: No conflict of interest

Statement of Human and Animal Rights/Ethical Approval: This was a prospective study conducted with the approval of the local research ethical committee (REC) under the internal number A-2019-020.

Statement of Informed Consent: Informed consent was obtained from all individual participants included in the study.

Statement of Funding Declaration: This research was funded by a research grant from Mohammed Bin Rashid University (MBRU).

SD

Standard Deviation

%TWL

Percentage Total Weight Loss

%EBMIL

Percentage Excess BMI Loss

HbA1c

Glycated Hemoglobin

ALT

Alanine Aminotransferase

AST

Aspartate Aminotransferase

HDL

High-Density Lipoprotein

LDL

Low-Density Lipoprotein

CRP

C-Reactive Protein.

Musaiger AO. Overweight and obesity in Eastern Mediterranean Region: Prevalence and possible causes. J Obes. 2011;2011:407237.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84.
Ajlouni K, Khader YS, Batieha A, Ajlouni H, El-Khateeb M. An increase in prevalence of diabetes mellitus in Jordan over 10 years. J Diabetes Complications. 2008 Sep-Oct;22(5):317-24.
Alshaikh MK, Filippidis FT, Al-Omar HA, Rawaf S, Majeed A, Salmasi AM. The ticking time bomb in lifestyle-related diseases among women in the Gulf Cooperation Council countries; review of systematic reviews. BMC Public Health. 2017 Jun 15;17(1):536.
Zhou H, Hu L, Qin Y, Zhang X, Tang G. Bariatric Surgery Improves Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Obes Surg. 2022 Jun;32(6):1872-1883.
Alswat K, Aljumah AA, Sanai FM, Abaalkhail F, Alghamdi M, Al Hamoudi WK, et al. Nonalcoholic fatty liver disease burden - Saudi Arabia and United Arab Emirates, 2017-2030. Saudi J Gastroenterol. 2018 Jul-Aug;24(4):211-219.
Garg H, Aggarwal S, Shalimar, Yadav R, Datta Gupta S, Agarwal L, et al. Utility of transient elastography (fibroscan) and impact of bariatric surgery on nonalcoholic fatty liver disease (NAFLD) in morbidly obese patients. Surg Obes Relat Dis. 2018 Jan;14(1):81-91.
Rocha R, Cotrim HP, Carvalho FM, Siqueira AC, Braga H, Freitas LA. Body mass index and waist circumference in non-alcoholic fatty liver disease. J Hum Nutr Diet. 2005 Oct;18(5):365-70.
Loomba R, Sanyal AJ. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90.
Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology. 2010 Feb;51(2):679-89.
Straub BK, Schirmacher P. Pathology and biopsy assessment of non-alcoholic fatty liver disease. Dig Dis. 2010;28(1):197-202.
Thampanitchawong P, Piratvisuth T. Liver biopsy: complications and risk factors. World J Gastroenterol. 1999 Aug;5(4):301-304.
Gennisson JL, Deffieux T, Fink M, Tanter M. Ultrasound elastography: Principles and techniques. Diagn Interv Imaging. 2013 May;94(5):487-95.
Mikolasevic I, Orlic L, Franjic N, Hauser G, Stimac D, Milic S. Transient elastography (FibroScan®) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand? World J Gastroenterol. 2016 Aug 28;22(32):7236-51.
Paul J, Venugopal RV, Peter L, Hussain S, Shetty KNK, Shetti MP. Effects of lifestyle modification on liver enzyme and Fibroscan in Indian patients with non-alcoholic fatty liver disease. Gastroenterol Rep (Oxf). 2018 Feb;6(1):49-53.
Agarwal L, Sahu AK, Baksi A, Agarwal S, Goel S, Jaiswal G, et al. Bariatric Surgery in Nonalcoholic Fatty Liver Disease (NAFLD): Impact Assessment Using Paired Liver Biopsy and Fibroscan. Obes Surg. 2021 Feb;31(2):809-821.
Schiavon CA, Bersch-Ferreira AC, Santucci EV, Oliveira JD, Torreglosa CR, Bueno PT, et al. Effects of bariatric surgery in obese patients with hypertension the GATEWAY randomized trial (gastric bypass to treat obese patients with steady hypertension). Circulation. 2018 Mar 13;137(11):1132-1142.
Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, et al. Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 5-Year Outcomes. N Engl J Med. 2017 Feb 16;376(7):641-651.
Rinella ME, Sanyal AJ. Management of NAFLD: A stage-based approach. Nat Rev Gastroenterol Hepatol. 2016 Apr;13(4):196-205.
Puri P, Sanyal AJ. Nonalcoholic fatty liver disease: Definitions, risk factors, and workup. Clin Liver Dis (Hoboken). 2012 Aug 23;1(4):99-103.
Kolaric TO, Ninčević V, Smolič R, Smolič M, Wu GY. Drug-induced fatty liver disease: Pathogenesis and treatment. J Clin Transl Hepatol. 2021 Oct 28;9(5):746-754.
Targher G, Byrne CD. Non-alcoholic fatty liver disease: An emerging driving force in chronic kidney disease. Nat Rev Nephrol. 2017 May;13(5):297-310.
Angulo P, Hui JM, Marchesini G, Bugianesi E, George J, Farrell GC, et al. The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007 Apr;45(4):846-54.
Treeprasertsuk S, Björnsson E, Enders F, Suwanwalaikorn S, Lindor KD. NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol. 2013 Feb 28;19(8):1219-29.
Lee Y, Doumouras AG, Yu J, Brar K, Banfield L, Gmora S, et al. Complete Resolution of Nonalcoholic Fatty Liver Disease After Bariatric Surgery: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2019 May;17(6):1040-1060.e11.
Yang A, Nguyen M, Ju I, Brancatisano A, Ryan B, van der Poorten D. Utility of Fibroscan XL to assess the severity of non-alcoholic fatty liver disease in patients undergoing bariatric surgery. Sci Rep. 2021 Jul 8;11(1):14148.
Rezende REF, Duarte SMB, Stefano JT, Roschel H, Gualano B, De Sá Pinto AL, et al. Randomized clinical trial: Benefits of aerobic physical activity for 24 weeks in postmenopausal women with nonalcoholic fatty liver disease. Menopause. 2016 Aug;23(8):876-83.
Zimmerman HJ, West M. Serum enzyme levels in the diagnosis of hepatic disease. Am J Gastroenterol. 1963 Oct;40:387-404.
Shen HC, Zhao ZH, Hu YC, Chen YF, Tung TH. Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver disease in the elderly agricultural and fishing population of Taiwan. Clin Interv Aging. 2014 Mar 19;9:501-8.
Stratopoulos C, Papakonstantinou A, Terzis I, Spiliadi C, Dimitriades G, Komesidou V, et al. Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity. Obes Surg. 2005 Sep;15(8):1154-60.
Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009 Oct;50(4):1105-12.
Van Der Heijden GJ, Wang ZJ, Chu ZD, Sauer PJJ, Haymond MW, Rodriguez LM, et al. A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, hispanic adolescents. Obesity (Silver Spring). 2010 Feb;18(2):384-90.
Mathurin P, Hollebecque A, Arnalsteen L, Buob D, Leteurtre E, Caiazzo R, et al. Prospective Study of the Long-Term Effects of Bariatric Surgery on Liver Injury in Patients Without Advanced Disease. Gastroenterology. 2009 Aug;137(2):532-40.
De Lédinghen V, Wong GLH, Vergniol J, Chan HLY, Hiriart JB, Chan AWH, et al. Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: Comparison between M and XL probe of FibroScan®. J Hepatol. 2012 Apr;56(4):833-9.
Myers RP, Pomier-Layrargues G, Kirsch R, Pollett A, Duarte-Rojo A, Wong D, et al. Feasibility and diagnostic performance of the FibroScan XL probe for liver stiffness measurement in overweight and obese patients. Hepatology. 2012 Jan;55(1):199-208.

Table 1: Baseline characteristics of surgical and medical Cohorts

Characteristic	Surgical Cohort (n=51)	Medical Cohort (n=35)	P-value
Demographics
Age (years), mean ± SD	32.94 ± 7.81	41.23 ± 11.18	<0.001
Female, n (%)	35 (68.6%)	21 (60.0%)	0.492
Arab ethnicity, n (%)	50 (98.0%)	31 (88.6%)	0.243
Anthropometrics
Weight (kg), mean ± SD	113.45 ± 22.81	106.23 ± 20.41	0.176
BMI (kg/m²), mean ± SD	41.83 ± 6.95	38.86 ± 6.22	0.002
Comorbidities
Diabetes Mellitus, n (%)	14 (27.5%)	11 (31.4%)	0.810
Insulin use, n (%)	2 (3.9%)	4 (11.4%)	0.219
Hypertension, n (%)	9 (17.6%)	11 (31.4%)	0.194
Hyperlipidemia, n (%)	22 (43.1%)	16 (45.7%)	0.829
GERD, n (%)	11 (21.6%)	9 (25.7%)	0.796
OSA requiring CPAP/BiPAP, n (%)	7 (13.7%)	1 (2.9%)	0.134
Current Smoker, n (%)	11 (21.6%)	2 (5.7%)	0.065
Laboratory tests
HbA1c (%), mean ± SD	5.60 ± 1.08	5.91 ± 1.43	0.241
ALT (U/L), mean ± SD	33.06 ± 24.59	34.79 ± 23.42	0.166
AST (U/L), mean ± SD	22.14 ± 9.95	25.09 ± 12.51	0.050
Total Cholesterol (mmol/L), mean ± SD	4.44 ± 0.89	4.50 ± 1.05	0.611
Triglycerides (mmol/L), mean ± SD	1.61 ± 0.85	1.36 ± 0.69	0.894
HDL (mmol/L), mean ± SD	1.13 ± 0.27	1.26 ± 0.27	0.017
LDL (mmol/L), mean ± SD	3.07 ± 0.79	2.96 ± 0.92	0.787
CRP (mg/L), mean ± SD	9.71 ± 7.23	6.96 ± 5.20	0.090
Baseline Fibroscan
CAP (dB/m), mean ± SD	321.26 ± 48.17	316.88 ± 56.59	0.806
LSM (kPa), mean ± SD	5.74 ± 2.59	5.84 ± 3.44	0.990
Steatosis level, mean ± SD	2.44 ± 0.75	2.56 ± 0.71	0.475
Fibrosis level, mean ± SD	0.41 ± 0.78	0.46 ± 0.79	0.624

Abbreviations: SD: Standard Deviation; BMI: Body Mass Index; GERD: Gastroesophageal Reflux Disease; OSA: Obstructive Sleep Apnea; CPAP: Continuous Positive Airway Pressure; BiPAP: Bi-level Positive Airway Pressure; HbA1c: Glycated Hemoglobin; ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; HDL: High-Density Lipoprotein; LDL: Low-Density Lipoprotein; CRP: C-Reactive Protein; CAP: Controlled Attenuation Parameter; LSM: Liver Stiffness Measurement.

Table 2: Intraoperative findings and correlation between fibroscan and biopsy

Characteristic	Surgical Cohort (n=51)
Surgical Procedure
Sleeve Gastrectomy, n (%)	33 (64.7%)
Roux-en-Y Gastric Bypass, n (%)	18 (35.3%)
Liver Biopsy Results
Steatosis present, n (%)	42 (82.4%)
Fibrosis present, n (%)	6 (11.8%)
Correlation between Fibroscan and Biopsy (Baseline)
Steatosis
Phi coefficient	-0.05
Chi-Squared Statistic	0.0025
P-value	0.96
Fibroscan steatosis sum	64.0
Biopsy steatosis sum	42.0
Fibrosis
Phi coefficient	0.15
Chi-Squared Statistic	0.63
P-value	0.43
Fibroscan fibrosis sum	25.0
Biopsy fibrosis sum	6.0

Table 3: Weight loss, blood tests, and fibroscan results at 12-month follow

Characteristic	Surgical Cohort (n=51)	Medical Cohort (n=35)	P-value
Weight Loss Outcomes
Weight (kg), mean ± SD	80.41 ± 16.94	105.10 ± 20.95	<0.001
BMI (kg/m²), mean ± SD	29.65 ± 5.39	38.42 ± 6.39	<0.001
%TWL, mean ± SD	29.25 ± 8.91	1.34 ± 3.96	<0.001
%EBMIL, mean ± SD	76.84 ± 26.97	4.13 ± 12.44	<0.001
Laboratory Tests
HbA1c (%), mean ± SD	5.07 ± 0.48	5.57 ± 1.14	0.014
ALT (U/L), mean ± SD	16.55 ± 7.51	30.29 ± 19.14	<0.001
AST (U/L), mean ± SD	21.80 ± 15.71	22.64 ± 8.68	0.017
Cholesterol (mmol/L), mean ± SD	4.46 ± 0.95	4.87 ± 1.02	0.050
Triglycerides (mmol/L), mean ± SD	0.91 ± 0.34	1.50 ± 0.81	<0.001
HDL (mmol/L), mean ± SD	1.39 ± 0.32	1.21 ± 0.26	0.028
LDL (mmol/L), mean ± SD	2.92 ± 0.85	3.27 ± 0.90	0.076
CRP (mg/L), mean ± SD	2.57 ± 2.13	6.72 ± 5.56	<0.001

Abbreviations: SD: Standard Deviation; %TWL: Percentage Total Weight Loss; %EBMIL: Percentage Excess BMI Loss; HbA1c: Glycated Hemoglobin; ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; HDL: High-Density Lipoprotein; LDL: Low-Density Lipoprotein; CRP: C-Reactive Protein.

Table 4: Fibroscan results at baseline and 12-month follow-up

Characteristic	Surgical Cohort (n=51)		Medical Cohort (n=35)		P-value
	Baseline	12-Month Follow-up	Baseline	12-Month Follow-up
CAP (dB/m), mean ± SD	321.26 ± 48.17	234.08 ± 58.22	316.88 ± 56.59	321.00 ± 50.91	<0.001
LSM (kPa), mean ± SD	5.74 ± 2.59	4.56 ± 2.14	5.84 ± 3.44	5.36 ± 2.96	0.062
Steatosis level, mean ± SD	2.44 ± 0.75	1.00 ± 0.82	2.56 ± 0.71	2.48 ± 0.72	<0.001
Fibrosis level, mean ± SD	0.41 ± 0.78	0.06 ± 0.24	0.46 ± 0.79	0.33 ± 0.69	0.050

Abbreviations: SD: Standard Deviation; CAP: Controlled Attenuation Parameter; LSM: Liver Stiffness Measurement; dB/m: decibels per meter; kPa: kilopascals.

No competing interests reported.

Effects of Weight Loss on Non-Alcoholic Fatty Liver Disease (NAFLD) in a United Arab Emirates Based Population: A Comparative Analysis of Bariatric Surgery and Non-Surgical Interventions

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