Int J Gastrointest Interv 2023; 12(3): 123-129
Published online July 31, 2023 https://doi.org/10.18528/ijgii220061
Copyright © International Journal of Gastrointestinal Intervention.
1Laparoscopy Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2Department of Bariatric Surgery, Laparoscopy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3Department of Clinical Nutrition, Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
Correspondence to:*Department of Clinical Nutrition, Nutrition Research Center, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Razi Boulevard, Shiraz 7153675500, Iran.
E-mail address: firstname.lastname@example.org (S.J. Msoumi).
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Morbid obesity increases the risk of various diseases, including non-alcoholic fatty liver disease (NAFLD). Bariatric surgery is one of the most effective tools to achieve significant weight loss and reduce complications in morbidly obese people. The present study was conducted to assess the effects of bariatric surgery on NAFLD-related factors.
Methods: This quasi-experimental study was conducted among 40 patients with obesity who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between July and November 2020. Biochemical factors and liver steatosis were evaluated by ultrasonography.
Results: The results revealed a significant decrease in alanine aminotransferase, triglyceride, and low-density lipoprotein levels in both groups. After RYGB, a significant decline was observed in aspartate aminotransferase, alkaline phosphatase, and total cholesterol (TC) levels. In contrast, after SG, high-density lipoprotein levels were considerably elevated. Ultrasonography results showed a significant reduction in steatosis following RYGB, but not SG. However, no significant differences were observed between the two groups, except in TC levels.
Conclusion: This study demonstrated that SG and RYGB had significant and beneficial short-term (6-month) effects on biochemical factors such as lipid profiles, liver enzymes, and blood glucose levels. While RYGB showed a slight advantage over SG in some parameters, the only statistically significant difference between groups was in the TC level. Furthermore, ultrasound findings revealed no statistically significant differences between SG and RYGB, suggesting that both procedures are effective at improving steatosis.
Keywords: Bariatric surgery, Lipids, Liver, Non-alcoholic fatty liver disease, Obesity, morbid
With the constant increase in obesity worldwide,1 the rates of associated complications such as type 2 diabetes mellitus, gallbladder disease, hypertension, cardiovascular disease, obstructive sleep apnea, and some types of cancer have dramatically escalated.2,3 The obesity epidemic has also caused a rise in non-alcoholic fatty liver disease (NAFLD).4 In most studies, the prevalence of NAFLD has been estimated to range from 25% to 45%, and it has increased along with obesity and diabetes.5 NAFLD is characterized by a broad spectrum of liver damage including non-alcoholic fatty liver, non-alcoholic steatohepatitis, cirrhosis, and fibrosis, which may be accompanied by hepatocarcinoma and hepatic failure.6
Many factors have been hypothesized to cause NAFLD, but the exact cause is unknown. The two-hit hypothesis suggests that NAFLD results from the hepatocytic accumulation of triglycerides (TGs), which causes steatosis. Affected hepatocytes are more susceptible to the second hit caused by inflammatory cytokines, adipokines, mitochondrial dysfunction, and oxidative stress, which can lead to steatohepatitis and/or fibrosis. Nonetheless, it is essential to note that TGs do not directly cause liver damage; rather, they are assessed as a marker of exposure to potentially toxic free fatty acids.7 NAFLD is characterized by insulin resistance and dyslipidemia. Obesity and central obesity are related to excess free fatty acid supply to the liver and consequent insulin resistance.8 In people with obesity, chronic inflammation due to lipid accumulation also contributes to NAFLD development. B cells and other immune cells can release inflammatory cytokines and immunomodulatory mediators that can mediate hepatocyte necrosis, liver steatosis, and liver fibrosis in NAFLD.9 Weight loss is essential for the improvement of NAFLD, as the current guidelines indicate that weight loss can decrease steatosis.9,10
As most cases of obesity are refractory to lifestyle modification and few truly effective pharmaceutical agents exist for treating obesity, particularly morbid obesity, bariatric surgery is the best alternative to help people lose weight.11,12 Evidence has indicated that bariatric surgery can significantly improve or resolve comorbidities associated with obesity such as type 2 diabetes, hypertension, sleep apnea, and dyslipidemia.13 Moreover, some studies have reported improvements in steatosis and steatohepatitis following bariatric surgery in NAFLD.14–18 However, the efficacy of bariatric surgery in NAFLD has remained unclear. Therefore, the present study was designed to assess the effect of weight loss after bariatric surgical procedures on liver biochemical factors and sonography during a 6-month follow-up period.
This quasi-experimental study was conducted among patients referred to the obesity center of the Qadir Mother and Child specialized hospital in Shiraz, Iran between June and November 2020. The participants included 40 obese patients (33 females and 7 males) with NAFLD who were candidates for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and were selected through non-randomized sampling. The patients were evaluated for bariatric surgery by a multidisciplinary committee that included a psychologist, a nutritionist, surgeons, and sports physicians. The inclusion criteria of the study were body mass index (BMI) ≥ 40 kg/m2 or BMI ≥ 35 kg/m2 with comorbidities, diagnosis of NAFLD, and at least 18 years of age. The exclusion criteria were alcohol consumption ≥ 20 g/day for females and ≥ 30 g/day for males, lactation, chronic hepatitis B or C virus infection, and taking of medications known to cause hepatic steatosis or liver damage. Patients who had previously undergone bariatric surgery were also excluded. After being informed of study objectives and confidentiality, the participants were required to sign written informed consent forms. The study was approved by the institutional ethics committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1399.245).
The primary outcome of the study was the change in the grade of NAFLD 6 months after surgery. The secondary outcomes were the impacts of bariatric surgery on body weight and biochemical parameters such as blood glucose level, lipid profile levels, and liver enzyme levels.
At the beginning of the study, the patients’ demographic characteristics (age, marital status, education level, occupation, medical history, eating habits, medications and supplements, and history of smoking and alcohol consumption) were collected. In addition, physical activity was assessed using the International Physical Activity Questionnaire at the beginning and end of the study. Clinical data including BMI, percentage total weight loss (%TWL), percentage excess weight loss (%EWL), and presence of comorbidities (hypertension and hypothyroidism) were analyzed preoperatively and 6 months after surgery. BMI was calculated as weight (kilograms) divided by the square of height (meters). Hypertension was defined as systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or prior use of antihypertensive drugs. Biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), TG, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and fasting blood sugar levels were measured in the laboratory of Qadir Hospital before and 6 months after surgery. Standard laboratory methods were used for all measurements. Levels of each liver enzyme were considered elevated or abnormal based on at least one measurement of the following: ALT level > 45 U/L in male and > 34 U/L in female patients; AST level > 35 U/L in male and > 31 U/L in female patients; ALP level > 129 U/L in male and > 104 U/L in female patients. Normal serum lipid levels were defined according to the National Cholesterol Education Program Adult Treatment Program III guidelines as follows: TG, < 150 mg/dL; TC, < 200 mg/dL; LDL, < 130 mg/dL; and HDL, > 40 mg/dL.
The bariatric procedures performed were SG and RYGB. All bariatric surgery was laparoscopic and was carried out by the same surgical team according to standard techniques.
Under general anesthesia, a standard five-port laparoscopic approach was used for surgery. Following a longitudinal resection from approximately 6 cm proximal to the pylorus to the angle of His with a linear stapler, SG was performed. To calibrate the remaining stomach, a 32-F bougie was inserted along the lesser curvature and reinforced with an omental pouch. The steps for RYGB were gastric pouch creation, biliopancreatic limb creation, jejunojejunostomy creation, and gastrojejunostomy creation.
Those who met the criteria for surgery were referred to an obesity clinic where they were evaluated by psychologists, cardiologists, endocrinologists, nutritionists, dietitians, and anesthesiologists. A specialized team at the hospital took a complete history of each patient, including physical activity patterns, current eating habits, and details of all previous attempts to lose weight. In addition to explaining the surgical technique, advantages, disadvantages, and complications, the surgeon also inquired about patient preferences and expectations. Accordingly, the type of surgery was chosen for each patient.
NAFLD was assessed using a SonoAce R5 ultrasound device (Samsung) with a 3.5-MHz convex probe. One radiologist performed general abdominal ultrasonography at the same hospital. We diagnosed fatty liver with ultrasonography based on standard criteria, including liver and kidney echogenicity differences and the visibility of the intrahepatic vessel walls. Accordingly, fatty liver was classified as mild (grade I), moderate (grade II), or severe (grade III). Grade I was characterized by the smallest increase in liver echogenicity, with the liver appearing brighter than the kidney cortex and the intrahepatic vessel walls clearly visualizable. Hepatic echogenicity was moderately greater in grade II, and the echo line of the intrahepatic vessels was lost. Grade III involved a severe increase in the echogenicity of the liver and poor penetration of the posterior segment of the right lobe.19,20
The collected data were analyzed using IBM SPSS version 21 (IBM Corp.). The Kolmogorov-Smirnov test was used to determine the normality of the data. Then, the chi-square test was used to compare the demographic characteristics of the participants. Additionally, baseline data of the two groups were compared using the Mann-Whitney test. The Wilcoxon test was utilized to compare the mean changes in each group before and after surgery. Descriptive statistics were given as mean ± standard deviation, and
Among the 40 patients (33 females and 7 males), 30 underwent RYGB and 10 underwent SG. No patient was excluded during the study. The mean age of the patients was 39.15 ± 12.24 years. Hypertension and hypothyroidism were detected in 25.0% and 22.5% of patients, respectively. The results revealed no significant differences between the two groups regarding the demographic characteristics and comorbidities (Table 1).
Table 1 . Comparison of Baseline Patient Characteristics.
|Variable||Sleeve gastrectomy (||Roux-en-Y gastric bypass (|
|Age (yr)||37.90 ± 14.20||39.57 ± 11.75||0.827|
|Female||9 (90.0)||24 (80.0)||0.656|
|Male||1 (10.0)||6 (20.0)|
|Weight (kg)||116.05 ± 23.52||120.85 ± 19.11||0.281|
|BMI (kg/m2)||43.48 ± 5.34||44.59 ± 6.33||0.365|
|Hypertension||1 (10.0)||9 (30.0)||0.401|
|Hypothyroidism||1 (10.0)||8 (26.6)||0.404|
|Heartburn||4 (40.0)||4 (13.3)||0.089|
|Knee pain||5 (50.0)||10 (33.3)||0.457|
|Sleep apnea||1 (10.0)||1 (3.3)||0.442|
|Asthma||1 (10.0)||5 (16.6)||0.999|
|Type 2 diabetes||1 (10.0)||0 (0)||0.250|
|ALT (IU/L)||33.88 ± 21.58||34.40 ± 26.62||0.907|
|AST (IU/L)||25.00 ± 12.62||27.76 ± 14.46||0.377|
|ALP (IU/L)||168.70 ± 58.48||182.52 ± 55.07||0.465|
|TC (mg/dL)||183.44 ± 36.43||194.13 ± 29.51||0.677|
|TG (mg/dL)||195.11 ± 117.90||156.96 ± 60.94||0.680|
|LDL-C (mg/dL)||115.88 ± 31.69||121.93 ± 27.29||0.810|
|HDL-C (mg/dL)||39.66 ± 7.74||46.08 ± 11.72||0.144|
|FBS (mg/dL)||118.00 ± 64.74||97.25 ± 12.48||0.943|
|Physical activity (MET-min/week)||428.10 ± 259.4||453.17 ± 577.3||0.382|
|Fatty liver grading|
|Grade I||5 (50.0)||14 (46.7)||0.999|
|Grade II||4 (40.0)||14 (46.7)|
|Grade III||1 (10.0)||2 (6.7)|
The main obesity-related comorbidities in the present study were hypertension (found in 10 of the patients, or 25.0%), hypothyroidism (found in 9 patients [22.5%]), heartburn (8 patients [20.0%]), knee pain (15 patients [37.5%]), sleep apnea (2 patients [5.0%]), asthma (6 patients [15.0%]), and type 2 diabetes (1 patient [2.5%]) (Table 1).
The mean preoperative weight was 116.05 ± 23.52 kg in the SG group and 120.85 ± 19.11 kg in the RYGB group. The mean BMI had fallen from 43.48 ± 5.34 kg/m2 to 32.77 ± 5.46 kg/m2 (
Table 2 . Effects of SG and RYGB on Clinical and Biochemical Measurements.
|Weight (kg)||SG||116.05 ± 23.52||82.85 ± 13.86||0.005||0.435|
|RYGB||120.85 ± 19.11||88.43 ± 16.23||< 0.001|
|BMI (kg/m2)||SG||43.48 ± 5.34||32.77 ± 5.46||0.005||0.901|
|RYGB||44.59 ± 6.33||32.83 ± 5.88||< 0.001|
|%EWL||SG||-||50.03 ± 27.68||-||0.595|
|RYGB||54.11 ± 19.09|
|%TWL||SG||-||26.29 ± 17.48||-||0.435|
|RYGB||26.64 ± 8.62|
|ALT (IU/L)||SG||33.88 ± 21.58||19.73 ± 8.58||0.015||0.839|
|RYGB||34.40 ± 26.62||20.80 ± 9.92||0.001|
|AST (IU/L)||SG||25.00 ± 12.62||18.70 ± 4.69||0.313||0.876|
|RYGB||27.76 ± 14.46||20.46 ± 9.10||0.026|
|ALP (IU/L)||SG||168.70 ± 58.48||143.66 ± 57.46||0.109||0.546|
|RYGB||182.52 ± 55.07||170.72 ± 66.54||0.047|
|TC (mg/dL)||SG||183.44 ± 36.43||181.22 ± 44.37||0.262||0.049|
|RYGB||194.13 ± 29.51||153.20 ± 33.10||< 0.001|
|TG (mg/dL)||SG||195.11 ± 117.90||121.90 ± 80.01||0.008||0.542|
|RYGB||156.96 ± 60.94||102.26 ± 26.57||< 0.001|
|LDL-C (mg/dL)||SG||115.88 ± 31.69||101.24 ± 31.72||0.011||0.192|
|RYGB||121.93 ± 27.29||86.60 ± 18.91||< 0.001|
|HDL-C (mg/dL)||SG||39.66 ± 7.74||48.90 ± 6.91||0.008||0.987|
|RYGB||46.08 ± 11.72||49.41 ± 11.77||0.367|
|FBS (mg/dL)||SG||118.00 ± 64.74||88.45 ± 8.50||0.041||0.430|
|RYGB||97.25 ± 12.48||85.65 ± 8.14||0.001|
The results revealed a significant decline in ALT levels after both SG (
Six months after surgery, 60.0% of the patients who had undergone SG and 50.0% of those treated with RYGB showed no steatosis of any grade. Moreover, grade 3 stenosis had completely disappeared from both study groups. However, a significant reduction was observed in steatosis among only the RYGB patients (
Table 3 . Comparison of Liver Steatosis after RYGB and SG.
|Fatty liver grading||SG (||RYGB (|
|Grade 0||0||6 (60.0)||0.193||0||15 (50.0)||0.017||0.880|
|Grade I||5 (50.0)||3 (30.0)||14 (46.7)||11 (36.6)|
|Grade II||4 (40.0)||1 (10.0)||14 (46.7)||4 (13.3)|
|Grade III||1 (10.0)||0||2 (6.7)||0|
Obesity is one of the most critical risk factors for NAFLD. People with morbid obesity are particularly vulnerable to hepatic injury and progression to more dangerous stages of the disease, such as cirrhosis and liver failure. Due to the lack of definitive clinical treatment for this condition, weight loss has been considered the best way to deal with NAFLD in people with obesity.4,6 Clinical treatments are not practical for long-term sustained weight loss, as nearly 95% of patients regain the lost weight within two years.21 The most effective treatment for obesity and metabolic disorders is bariatric surgery, which can result in a weight loss of more than 55%.22 Currently, RYGB and SG are the two most common weight-loss procedures globally.23
Our previous study showed that among patients with morbid obesity, more severe NAFLD was associated with higher weight and BMI; higher ALT, AST, TG, and fasting blood sugar levels; and lower HDL levels.19 In the present study, as reported in other research, patients experienced significant reductions in %TWL, %EWL, and BMI after both SG and RYGB.15,16,24 Furthermore, no significant differences were observed between the two groups in weight loss after 6 months, which aligned with the results of studies with longer follow-up periods.25,26
Similar to the current findings, the results of multiple studies have shown that bariatric surgical procedures improve hepatic aminotransferase levels.15,18,27 However, the present study findings indicate that RYGB had advantages over SG in normalizing liver transaminases during the 6-month follow-up period. In contrast, Azulai et al28 reported that relative to bypass surgery, SG was associated with a significant reduction in liver enzyme levels as well as a lower incidence of postoperative increase in ALT level. In a separate study of 500 individuals conducted by Guan et al,27 the reduction of aminotransferase levels was significant in both SG and RYGB groups. Bariatric surgery has been found to reduce transaminase levels by reducing liver fat and inflammation as well as by improving insulin resistance following calorie restriction and appetite reduction.29 Bariatric surgery also provides considerable metabolic benefits to the liver by reducing glucose production, improving insulin sensitivity, decreasing the very-low-density lipoprotein/TG secretion rate, and dramatically reducing the fat content of the liver.30
According to the results of this and previous studies,16,31,32 the dyslipidemia status of patients improved after both SG and RYGB. However, RYGB was more effective than SG in lowering the TC level. In the same vein, Spivak et al33 found that reductions in TC and LDL levels were significantly greater after RYGB compared to SG at 12 ± 4 months after surgery. Similarly, a number of studies34–36 have demonstrated that SG improves the lipid profile mainly by reducing TGs and elevating HDL cholesterol, with little influence on LDL cholesterol. Additionally, Heffron et al37 conducted a meta-analysis based on 178 studies and found that RYGB improves lipid profile more than SG.
Several studies have demonstrated that increased LDL and decreased TC after RYGB may be due to factors other than weight (such as neurohormonal factors).33,38,39 Although the mechanisms contributing to the improvement of lipid profile after bariatric procedures remain unclear, some studies38,40 have suggested that significant weight loss is primarily responsible for the improvement in the lipid profile following RYGB. However, the RYGB approach also reduces the preference for a high-fat diet and increases the content of fecal fat.40
Losing weight leads to improved insulin sensitivity and glucose metabolism, which may affect lipid-lipoprotein metabolism.30 In line with previous findings, the current study showed an improvement in fasting blood glucose levels after bariatric surgery.32,41,42 The normalization of blood glucose and insulin levels within a few days after surgery has not been well understood medically. However, in addition to improved glucose utilization and decreased insulin resistance, many factors—including changes in bile acid metabolism and nutrient sensing in the gastrointestinal tract as well as changes in the intestinal microbiome—have been identified as contributors. Increased secretion of glucagon-like peptide-1 after bariatric surgery may also play a role.43
Froylich et al44 performed a cohort study of obese patients with NAFLD and found that both RYGB and SG effectively improved liver function and structure, but RYGB was more effective than SG in promoting NAFLD regression. A recent meta-analysis also indicated that bariatric surgery could resolve or halt the progress of liver fibrosis in 30% of patients, indicating that it was far more effective than any other treatment for non-alcoholic steatohepatitis. Those researchers also noted that RYGB had a greater effect than SG on the histological features of NAFLD.45 According to ultrasound findings in the present study, no statistically meaningful differences were present between the two procedures (
The strength of the present study was its comparison of two popular procedures and recognition of the differences between them, which may help surgeons determine the most appropriate procedure for obese patients with NAFLD. Nevertheless, the study had limitations, most notably the short follow-up period and the small number of patients in each group.
In conclusion, this study demonstrated the improvement of clinical and biochemical factors (lipid profiles, liver enzymes, and blood glucose levels) after both RYGB and SG. Improvement in these factors may indicate a protective role of bariatric surgery in chronic liver damage as well as the possible prevention of NAFLD progression to cirrhosis and fibrosis. Although RYGB showed a slight advantage over SG in some parameters, only the differences in TC level were statistically significant. However, further research with a larger sample size is needed to clarify the effects of these two types of surgery on NAFLD among patients with morbid obesity.
The data that support the findings of this study are available from the corresponding author upon reasonable request.
The authors would like to thank Ms. A. Keivanshekouh at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for her invaluable assistance in editing the manuscript.
No potential conflict of interest relevant to this article was reported.
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