Abstract
Aim:
This study aimed to compare the effect of the same volume of moderate- and high-intensity aerobic exercise on patients' liver steatosis and fibrosis.
Background:
Exercise is known strategy to deal with non-alcoholic fatty liver disease (NAFLD).
Methods:
This Randomized Control Trial was performed on 60 patients randomly assigned to three arms of the study (1:1:1). Fibrosis and steatosis of liver including Control Attenuated Parameter (CAP) determined using Transient Elastography (TE). The control group was advised to adjust their lifestyle, as a routine management. The intervention groups additionally, participated on supervised exercise programs with two different intensities but the same volume of 1000 KCal per week. The intensities of 50% and 70% of V02 reserve were considered for moderate-intensity and vigorous programs, respectively.
Results:
On six-month follow-up, none of outcomes were statistically significant among three arms of study. However, changes in some outcomes were reached to statistically significant difference in follow-up in comparison with baseline. The mean of CAP score changes was -19.43 (31.43) (P=0.03), 9.92 (26.81) (P=0.21), and 14.61 (18.03) (P=0.01) in control, moderate- and high-intensity groups, respectively. In the high-intensity group, in addition to steatosis, this difference was also observed in the rate of fibrosis. Besides, the level of serum aminotransferases in the group with moderate exercise after six months had a significant decrease compared to baseline. (P=0.01)
Conclusion:
Improvement in steatosis and fibrosis was more evident in high- intensity group. As the rate of drop out was high, caution is needed in interpretation of the results.
Key Words: Exercise, Non-alcoholic fatty liver disease, Fatty liver
Introduction
Non-alcoholic fatty liver disease (NAFLD) has been defined as the accumulation of fat in the liver in the absence of alcohol consumption or any other specific causes. It is known as the most common chronic liver disease worldwide (1). The global prevalence of NAFLD was estimated to be 24%. This number varied across continents and was 27% in Asia (2).
Fatty liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). In all cases the risk of cirrhosis is increased due to fibrosis (3). The increasing prevalence of NAFLD in adults, adolescents, and children appears to be a serious threat. (4) Obesity, insulin resistance, diabetes mellitus type 2, and hyperlipidemia are known risk factors of NAFLD (5). Therefore, its prevalence in obese and diabetic people reaches 70% and 90%, respectively (6).
Currently, worsening the obesity epidemic in the world has led to increase in the prevalence of NAFLD (7).
Early treatment is known as the most cost-effective approach in this regard. As the early diagnosis is mandatory for early treatment (8), the importance of diagnostic methods cannot be overstated.
Several methods have been used to diagnose hepatic steatosis. On the one hand, liver ultrasound is the easiest and most accessible of these methods but on the other hand (9), ultrasound cannot show steatosis less than 30%. Also ultrasound is a highly operator-dependent modality (6, 10). According to the American Association for the Study of Liver Disease (ASSLD), the gold standard for diagnosing NAFLD is biopsy (6). Due to the difficulty of performing a liver biopsy and its invasiveness and complications such as the risk of bleeding, the use of Transient Elastography (TE) as a non-invasive method is a practical solution in this regard (11, 12).
Use of indices is another non-invasive method for estimating liver fibrosis. These indexes are obtained through the introduced formulas using clinical and laboratory findings. FIB-4 is recognized as one of the best indices for estimating fibrosis in NAFLD patients (13).
Although there are significant limitations in pharmacological and surgical treatments in NAFLD, recent studies have shown that lifestyle intervention including activity could have a significant effect in this area (8).
Several studies have supported the benefits of aerobic training. It is thought aerobic exercise is responsible for reducing hepatic fat component within the range of 3-40% (9).
It is likely exercise induces fatty acid beta-oxidation, hepatic autophagy, PPAR-y pathway, as well as, insulin sensitivity, and reduces intrahepatic fat accumulation. Furthermore, increase in anti-inflammatory molecules, and anti-oxidant enzymes via exercise could lead to a reduction in ROS and OS generation during NAFLD progression (9).
Researchers declare that sedentary behavior among obese individuals increases the risk of developing NAFLD compared with active peers. These results support the theory of the positive effect of increasing the level of physical activity and exercise on NAFLD, and it seems that exercise is a good and inexpensive way to prevent and treat NAFLD (7).
One of the main challenges in this field is related to the proper amount of exercise (including intensity and volume) to effectively reduce liver fat content. However, what is certain is that aerobic and strength training, even in the absence of weight loss, can play a pivotal role in treating NAFLD (14).
This study aimed to evaluate the effect of the same volume of moderate- and high- intensity aerobic exercise on patients' liver steatosis and fibrosis.
Methods
This parallel RCT was performed on 60 patients with NAFLD randomly assigned to three groups of 20 people. Patients were followed for six months.
Adult patients with NAFLD who had been confirmed by clinical, laboratory, and imaging tests (TE) were selected on the basis of the following criteria; no other liver disease or any chronic disease that affects the function or histology of the liver, had not a previous history of regular exercise before the start of treatment.
All patients referred to the gastrointestinal clinic of Taleghani Hospital during the years 2018-2019, who were eligible, were offered to enter the study. Written informed consent was obtained from all included patients and then they were referred to the sports medicine ward of Taleghani hospital.
The protocol of this study is based on the principles of Helsinki and has been accepted in the ethics committee of Shahid Beheshti University of Medical Sciences under the number of IR.SBMU.MSP.REC.1395.252.
In the current study exclusion criteria were defined as follows; use of other treatments, refusal to continue study participation, refusal to perform paraclinical tests, the occurrence of any new disease that interferes with the patient's tests, consumption of alcohol or other drugs that affect the liver, and diabetes.
Outcomes measurement
All Outcomes measured in the baseline, and after six months of follow up.
Anthropometric findings
Anthropometric assessment including height, weight, Body Mass Index (BMI), Waist Hip Ratio (WHR) were performed by one person.
Percentage of Body Fat (PBF)
In this study we use of BioImpedance Analysis (BIA) to determine body composition. PBF, fat free mass including skeletal bones, muscle mass, and total body water, are components that measured by BIA (15).
Cardiopulmonary exercise test
Cardio Pulmonary Exercise Test (CPET) was performed with Bruce modification protocol, and VO2 Reserve (VO2R) was measured.
Blood biochemistry
Biochemistry investigation were performed after 12 hours of fasting in the laboratory of Taleghani Hospital. Serum aminotransferases including Alanine Transaminase (ALT) and Aspartate Transaminase (AST), Ferritin levels, Lipid profiles (including High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol, TriGlycerid (TG)), insulin resistance factors included Fasting Blood Sugar (FBS), fasting insulin level, HemoglobinA1c (HbA1c) were measured.
Liver steatosis and fibrosis
A liver TE was performed to determine fibrosis. To determine the degree of hepatic stiffness, the evaluation was performed by an experienced gastroenterologist using a standard protocol and a FibroScan device. In addition to estimating liver stiffness, liver TE can be used to quantify and approximate liver fat by measuring the Controlled Attenuation Parameter (CAP) score. It is measured based on ultrasound attenuation by intrahepatic fat at the central frequency of the TE probe (16). This score increases with increasing fat percentage and is known as an acceptable diagnostic method for steatosis detection.
FIB-4 index
It was introduced as a non-invasive fibrosis scoring method. According to the formula presented by Sterling et al. (17), this index was calculated by combining the routine serological factors such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet data, with age in the current study.
Randomization
Randomization was performed simply and individually. patients were grouped in groups of control, moderate-, and high-intensity groups, respectively.
Control group was only advised to adjust their lifestyle, including general recommendations for healthy eating, such as reducing dietary carbohydrate and fat intake and increasing physical activity. In intervention groups, in addition to nutritional recommendations similar to the control group, the exercise prescription was given according to the principles of FITT (Frequency, Intensity, Time, Type) (18). The FITT principles were introduced by American College of Sports Medicine (ACSM) order to provide a standard exercise prescription (19).
Exercise Prescription
In the current study, exercise prescription was determined as walking and walking on a treadmill with two different intensities but the same volume. The intended volume was 1000 kcal, and the average exercise intensity was 50% VO2R for -moderate intensity group, and 70% of VO2R for high intensity group. The frequency of exercise was considered five days a week, so that at least two days of it should be done under supervision in the sports medicine ward.
In people who were not physically fit at first, in the first one to two weeks, the exercise program started at a lower intensity and gradually increased to the desired level.
For home exercise sessions, the appropriate intensity was prescribed to the patient, according to the individual facilities and conditions of each patient, in the form of treadmill speed or the number of steps per minute based on the desired speed.
Statistical Analysis
Analysis of variance (one-way ANOVA test) was used to compare the baseline variables. To evaluate the comparison between groups and changes within groups, ANOVA and Paired-sample t-test were used, respectively. Analysis of covariance (one-way ANCOVA) were applied order to determine the baseline characteristics as covariates. For all analyzes, we used SPSS version 18 and defined the alpha error rate of 0.05.
Blinding
Due to the nature of the intervention, it was not possible to blind the participants. However, it was tried that the person who performs laboratory evaluations and TE examination, as well as statistical analyzer, to be unaware of the groups' assignment.
Results
Descriptive demographic variables are presented in Table 1.
Table 1.
Demographic and clinical characteristics of patients in the baseline
| Variable | Control (N=20) |
Moderate intensity (N=20) |
High intensity (N=20) |
P value |
|---|---|---|---|---|
| Age (y) | 49.85 (11.27) | 53.20 (9.60) | 47.55 (9.65) | .221 |
| Sex (male/female) | 11/9 | 11/9 | 11/9 | 1.000 |
| Height (cm) | 162.50 (7.74) | 163.50 (8.70) | 163.50 (9.85) | .918 |
| Weight (Kg) | 80.58 (11.98) | 83.89 (16.16) | 82.40 (17.45) | .793 |
| BMI (kg/m2) | 30.67 (5.30) | 31.31 (4.74) | 30.70 (5.34) | .905 |
| Waist circumference (cm) | 101.23 (8.11) | 105.65 (14.52) | 98.00 (10.02) | .171 |
| Hip circumference (cm) | 108.00 (8.62) | 112.12 (14.10) | 104.26 (6.69) | .118 |
| WHR | 0.79 (0.34) | .75 (.39) | .70 (.42) | .745 |
| PBF (%) | 32.83 (6.35) | 33.71 (6.72) | 31.91 (7.61) | 0.716 |
| Fibrosis | 6.39 (1.93) | 7.78 (2.42) | 7.78 (2.55) | .101 |
| Steatosis | 296.65 (44.29) | 303.15 (28.90) | 290.50 (45.79) | .625 |
| ALT (IU/L) | 43.00 (19.06) | 40.90 (21.16) | 45.65 (23.55) | .781 |
| AST (IU/L) | 29.75 (13.99) | 28.80 (10.19) | 33.55 (20.58) | .595 |
| Ferritin (ng/ml) | 122.43 (80.77) | 98.37 (80.41) | 164.64 (84.50) | .095 |
| FBS (mg.dl) | 104.76 (23.24) | 115.62 (25.87) | 96.28 (11.49) | .064 |
| A1c (%) | 5.96 (1.47) | 5.82 (1.15) | 5.36 (1.01) | .392 |
| Insulin (mIU/L) | 12.29 (3.74) | 17.14 (9.96) | 11.62 (5.11) | .058 |
| TC (mg/dl) | 163.35 (29.01) | 192.65 (49.99) | 179.85 (32.22) | .060 |
| TG (mg/dl) | 186.85 (68.05) | 162.10 (77.08) | 180.35 (98.11) | .616 |
| HDL (mg/dl) | 38.35 (8.19) | 44.73 (11.13) | 45.68 (10.98) | .056 |
| LDL (mg/dl) | 96.50 (19.35) | 120.84 (37.75) | 99.52 (25.38) | .020* |
| Vo2max (ml/kg.min-1) | 26.75 (4.76) | 26.26 (6.22) | 31.72 (7.50) | .022* |
| FIB-4 | 1.58 (0.68) | 1.57 (.58) | 1.52 (.63) | .971 |
Abbreviation
ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: Body Mass Index, FBS: Fasting Blood Sugar, HC: Hip Circumference, HDL: High Density Lipoprotein, LDL: Low Density Lipoprotein, PBF: Percent of Body Fat, TC: Total Cholesterol, TG: Triglyceride, WC: Waist Circumference, WHR: Waist Hip Ratio * statistical significant.
In this study, 33 women and 27 men were randomized in three groups of 20 people.
The Figure 1 shows the flowchart of participants through the study. As can be seen 6, 7, and 7 participants were withdrawn from the study in control, moderate-, and high-intensity groups, respectively.
Figure 1.
Flowchart of participants through the study
At baseline there was no significant difference between the groups in terms of gender, age, anthropometric findings (height, weight, BMI, WHR), and PBF (p-value > 0.05). Also as shown in Table 1, no differences in fibrosis, steatosis, and FIB-4 were observed between the study groups. The only differences between the groups in the baseline were their VO2 Max (p-value = 0.03), and Low Density Lipoprotein (LDL). Consequently, the groups were not homogeneous in this respect.
According to Table 2, a paired t-test showed a significant decrease in steatosis after six months of follow-up in control group as well as high-intensity group. Changes in primary outcomes including FIB-4 index, fibrosis, and steatosis between before and after intervention by treatment arm have been shown in the Figures 2, 3, and, 4 respectively. The mean of CAP scores changes were -19.43 (31.43) (P=0.03), 9.92 (26.81) (P=0.21), and 14.61 (18.03) (P=0.01) in control, moderate- and high-intensity groups, respectively. In the high-intensity group, in addition to steatosis, this difference was also observed in the rate of fibrosis. The means of fibrosis changes were 0.03 (0.72) (P=0.85), -0.56 (1.54) (P=0.21), and -0.68 (0.82) (0.01) in control, moderate- and high-intensity groups, respectively. Besides, the laboratory findings of ALT, AST, and HbA1c in the group with moderate exercise after six months had a significant decrease compared to baseline (P=0.01, P=0.01, P=0.03).
Table 2.
Comparison of variables within groups. SE: Standard Error, CI: Confidence Interval, WHR: Waist Hip Ratio, FBS: Fasting Blood Sugar,TG: Triglycerides, HDL: High Density Lipoprotein, LDL: Low Density Lipoprotein, *: statistical significant
| high intensity (N=13) | Moderate intensity (N=13) | Control (N=14) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P | Paired difference | P | Paired difference | P | Paired difference | ||||||||||
| CI 95% | SD | mean | CI 95% | SD | mean | CI 95% | SD | Mean | |||||||
| lower | upper | lower | upper | lower | upper | ||||||||||
| .04* | 0.09 | 2.96 | 2.25 | 1.53 | 0.01* | 0.67 | 3.98 | 2.74 | 2.32 | 0.06 | -0.12 | 3.65 | 3.27 | 1.76 | Weight (kg) |
| .03* | 0.09 | 1.14 | 0.83 | 0.62 | 0.01* | 0.26 | 1.47 | 1.00 | 0.86 | 0.07 | -0.06 | 1.25 | 1.14 | 0.60 | BMI (kg/m2) |
| 0.02* | 0.25 | 2.37 | 1.75 | 1.31 | 0.01* | 0.78 | 2.76 | 1.47 | 1.77 | 0.47 | -2.37 | 4.80 | 6.21 | 1.21 | WC (CM) |
| 0.79 | -1.05 | 1.36 | 1.99 | 0.15 | 0.02* | 0.21 | 1.61 | 1.04 | 0.91 | 0.36 | -1.65 | 4.22 | 5.09 | 1.28 | HC (CM) |
| 0.01* | 0.00 | 0.02 | 0.01 | 0.01 | 0.01* | 0.00 | 0.01 | 0.01 | 0.01 | 0.85 | -0.02 | 0.02 | 0.04 | 0.002 | WHR |
| 0.27 | -.59 | 1.94 | 2.09 | 0.68 | 0.95 | -1.59 | 1.68 | 2.71 | 0.05 | 0.39 | -0.42 | 1.01 | 1.24 | 0.29 | PBF (%) |
| 0.01* | 0.19 | 1.18 | 0.82 | 0.68 | 0.21 | -0.36 | 1.49 | 1.54 | 0.57 | 0.85 | -0.44 | 0.37 | 0.71 | -0.03 | Fibrosis |
| 0.01* | 3.72 | 25.51 | 18.03 | 14.62 | 0.21 | -6.28 | 26.13 | 26.81 | 9.92 | 0.03* | 1.28 | 37.57 | 31.42 | 19.42 | Steatosis |
| 0.92 | -9.91 | 8.99 | 15.64 | -0.46 | 0.01* | 2.15 | 14.31 | 10.07 | 8.23 | 0.18 | -1.36 | 6.51 | 6.82 | 2.57 | ALT (IU/L) |
| 0.85 | -3.89 | 3.27 | 5.92 | -0.31 | 0.01* | 1.60 | 9.01 | 6.13 | 5.31 | 1.00 | -2.94 | 2.94 | 5.09 | 0.00 | AST (IU/L) |
| 0.07 | -3.07 | 58.92 | 51.29 | 27.92 | 0.05 | -27.31 | 0.04 | 20.35 | -13.64 | 0.35 | -14.53 | 37.53 | 45.08 | 11.50 | Ferritin (ng/ml) |
| 0.78 | -4.03 | 3.11 | 5.91 | -0.46 | 0.11 | -3.89 | 34.43 | 28.52 | 15.27 | 0.47 | -6.74 | 3.32 | 8.72 | -1.71 | FBS (mg/dl) |
| 0.94 | -0.44 | 0.47 | 0.75 | 0.02 | 0.03* | 0.07 | 1.13 | 0.78 | 0.60 | 0.76 | -0.39 | 0.29 | 0.60 | -0.05 | HbA1C |
| 0.51 | -3.58 | 1.87 | 4.51 | -0.85 | 0.42 | -0.84 | 1.88 | 2.03 | 0.52 | 0.14 | -1.40 | 0.23 | 1.42 | -0.58 | Insulin (mIU/L) |
| 0.90 | -11.01 | 9.78 | 17.20 | -0.62 | 0.33 | -12.06 | 32.96 | 33.51 | 10.45 | 0.02* | -18.05 | -1.37 | 14.44 | -9.71 | TC (mg/dl) |
| 0.98 | -22.06 | 22.68 | 37.01 | 0.31 | 0.18 | -12.28 | 57.73 | 52.11 | 22.73 | 0.01* | -17.60 | -3.39 | 12.30 | -10.5 | TG (mg/dl) |
| 0.74 | -3.94 | 2.87 | 5.64 | -0.54 | 0.52 | -4.19 | 7.83 | 8.94 | 1.82 | 0.03* | -6.42 | -0.28 | 5.31 | -3.35 | HDL (mg/dl) |
| 0.06 | -14.12 | 0.27 | 11.91 | -6.92 | 0.25 | -4.93 | 16.75 | 16.14 | 5.91 | 0.20 | -13.66 | 3.23 | 14.63 | -5.21 | LDL (mg/dl) |
| 0.06 | -3.28 | 0.05 | 2.75 | -1.62 | 0.35 | -2.99 | 1.15 | 3.26 | -0.92 | 0.79 | -0.50 | 0.64 | 0.99 | 0.07 | VO2max (ml/kg.min-1) |
| 0.61 | -0.08 | 0.05 | 0.11 | -0.02 | 0.33 | -0.12 | 0.32 | 0.37 | 0.10 | 0.28 | -0.18 | 0.05 | 0.21 | -0.06 | FIB- 4 |
Abbreviation
ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: Body Mass Index, FBS: Fasting Blood Sugar, HC: Hip Circumference, HDL: High Density Lipoprotein, LDL: Low Density Lipoprotein, PBF: Percent of Body Fat, TC: Total Cholesterol, TG: Triglyceride, WC: Waist Circumference, WHR: Waist Hip Ratio * statistical significant.
Figure 2.
Changes in FIB-4 index between before and after intervention by treatment arm
Figure 3.
Changes in fibrosis between before and after intervention by treatment arm
Figure 4.
Changes in steatosis between before and after intervention by treatment arm
A closer look at the data indicates that in both intervention groups, a decrease in anthropometric variables were observed. However, the results show that the greatest change in these findings were seen in the group with moderate exercise.
Table 3 shows the findings of the ANOVA analysis, which compared the mean of variables after six months between groups. Steatosis, fibrosis, and other anthropometric, and laboratory findings do not show a significant difference. The only significant measure was in the amount of VO2 Max, which was seen in the baseline too. Considering baseline characteristics as covariates, ANCOVA test did not show any significant differences between groups.
Discussion
Introduction of physical activity into people's lives are valuable therapeutic interventions for NAFLD (6).
This study compared different intensities of aerobic exercise for the treatment of NAFLD. Although our results did not reach to statistical significant difference in the measured outcomes between the three arm of study, the before and after comparison revealed that moderate intensity exercise could have a beneficial role in reduction of serum aminotransferase. Also improvement in steatosis and fibrosis was observed in intervention group with high intensity aerobic exercise.
In this regard, Abdelbasset et al. (20) that compared the effect of High-Intensity Interval (HIIT) aerobic exercise with the moderate-intensity in diabetic patients with fatty liver, argue that the two exercise programs have similar effects on fatty liver.
Although there are significant changes in anthropometric and biochemistry outcomes in moderate intensity groups, the mean of steatosis and fibrosis did not reach to statistical significant difference. Similarly, a 2017 meta-analysis study conducted by Katsagoni et al, revealed that continuous high intensity exercise could be of more benefit to reduction the Intrahepatic TG (IHTG) than moderate and interval high intensity training (8).
The available evidence seems to point to reduction in the fat accumulation of the liver is independent of weight loss (21-28).
Table 3.
Comparison of variables between groups
| Control (N=14) | Moderate (N=13) | High (N=13) | P value | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | SD | Mean | SD | Mean | SD | ANOVA | Factorial ANCOVA | ||||
| Weight (kg) | 80.71 | 13.23 | 81.94 | 19.18 | 79.40 | 16.48 | .93 | .61 | |||
| BMI | 31.22 | 6.10 | 30.56 | 5.71 | 29.12 | 4.55 | 0.62 | 0.63 | |||
| WC (cm) | 100.93 | 11.05 | 103.91 | 16.54 | 97.08 | 10.39 | 0.42 | 0.38 | |||
| HC (cm) | 107.36 | 9.07 | 110.36 | 16.66 | 103.62 | 6.84 | 0.35 | 0.14 | |||
| WHR | 0.94 | 0.07 | 0.80 | 0.36 | 0.94 | 0.06 | 0.63 | 0.38 | |||
| PBF (%) | 32.39 | 6.66 | 32.69 | 7.58 | 28.20 | 6.01 | 0.18 | 0.94 | |||
| Fibrosis | 6.53 | 2.08 | 7.48 | 2.14 | 6.95 | 2.16 | 0.51 | 0.44 | |||
| Steatosis | 289.86 | 40.08 | 296.77 | 32.96 | 293.85 | 38.15 | 0.89 | 0.87 | |||
| ALT (IU/L) | 44.21 | 16.58 | 28.15 | 16.42 | 47.77 | 25.09 | 0.03* | 0.52 | |||
| AST (IU/L) | 31.57 | 13.17 | 21.62 | 8.13 | 33.69 | 21.06 | 0.10 | 0.64 | |||
| Ferritin (ng/ml) | 118.29 | 50.88 | 83.18 | 35.96 | 132.08 | 54.10 | 0.05 | 0.76 | |||
| FBS (mg/dl) | 104.50 | 17.81 | 103.00 | 10.44 | 96.54 | 10.65 | 0.30 | 0.32 | |||
| HbA1c | 6.00 | 1.14 | 5.50 | 0.85 | 5.28 | 0.76 | 0.14 | 0.17 | |||
| Insulin (mIU/L) | 13.09 | 4.36 | 15.63 | 10.39 | 12.85 | 6.24 | 0.59 | 0.29 | |||
| TC (mg/dl) | 172.07 | 34.61 | 175.64 | 51.39 | 171.08 | 20.53 | 0.95 | 0.61 | |||
| TG (mg/dl) | 212.00 | 69.55 | 156.91 | 80.03 | 210.38 | 103.70 | 0.22 | 0.54 | |||
| HDL (mg/dl) | 39.64 | 10.53 | 43.82 | 9.68 | 42.69 | 8.93 | 0.54 | 0.93 | |||
| LDL (mg/dl) | 104.21 | 21.90 | 108.00 | 43.52 | 98.46 | 13.16 | 0.70 | 0.74 | |||
| VO2max (ml/kg.min-1) | 26.71 | 5.00 | 25.92 | 5.90 | 34.15 | 6.64 | 0.002* | 0.17 | |||
| FIB- 4 | 1.64 | 0.65 | 1.47 | 0.41 | 1.54 | 0.66 | 0.75 | 0.32 | |||
Abbreviation
ALT: alanine aminotransferase, AST: aspartate aminotransferase, BMI: Body Mass Index, FBS: Fasting Blood Sugar, HC: Hip Circumference, HDL: High Density Lipoprotein, LDL: Low Density Lipoprotein, PBF: Percent of Body Fat, TC: Total Cholesterol, TG: Triglyceride, WC: Waist Circumference, WHR: Waist Hip Ratio * statistical significant.
The results of this study also showed that aerobic exercise with independent of weight loss can reduce the rate of steatosis. Improvements in insulin resistance, fatty acid metabolism in the liver, the mitochondrial function of the liver, and inflammatory cascade activity appear to be molecular mechanisms for this effect (7).
Saldiran et al., who compared aerobic exercise for 8 weeks with and without vibration, reported a decrease in liver enzymes in their study groups (29). In the current study only in the group with moderate aerobic exercise, statistical analysis showed a significant difference in the reduction of liver enzymes. However, the overall course of enzymes, especially ALT in all three groups was reduced. The relevant guidelines in this regard, despite the recommendation to study these enzymes for patients' follow-up, state that the reduction of liver fat content is not necessarily accompanied by a decrease in liver enzymes (29).
The present study showed that moderate-intensity aerobic exercise can effectively improve HBA1c levels in NAFLD patients, a finding not found in the group with high-intensity aerobic exercise. However, other insulin resistance factors, such as FBS and insulin levels, did not change significantly in any of the study groups. Along this line, previous studies mentioned that moderate-intensity exercise can play a more effective role in improving blood sugar levels than high-intensity exercise (30, 31).
Strength and Limitation
Since the follow-up period in this study was six months, it seems that this relatively long time has been able to show the changes caused by fibrosis in patients with fatty liver. However, this strength point leads to a relatively significant drop in participants. Although, the rate of loss was similar among participants in different study groups, high rate of drop out could lead to attrition bias.
Another strength point of this study was the supervision of intervention groups. Also the use of TE order to determine CAP score in this study could be a strong point.
In this study, we sought to determine the appropriate intensity of exercise therapy in NAFLD patients. Since, according to ethics, we could not exclude patients from exercise as an effective intervention for NAFLD, general recommendations for aerobic exercise were also given to the control group. Another limitation in this study was the non-withdrawal of NASH patients. It is likely that NASH is more prone to cirrhosis in comparison with simple steatosis (32). In light of these consideration, the therapeutic effect of exercise for NAFLD patients might underestimated in this study.
Conclusion
The present study suggests that both moderate and high intensity aerobic exercise can improve the course of disease in NAFLD patients. However, improvement in steatosis and fibrosis was more evident in high intensity training. Considering the high rate of drop out in the current study, caution is needed in interpretation of the results. Further large and well-designed RCTs are needed order to generalize the findings.
Conflict of interests
The authors declare that they have no competing interests.
Acknowledgment
Special thanks to our clients in Tabriz children's hospital for their patience and cooperation in this study.
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