Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
Non-alcoholic fatty liver disease
Brief summary
There is no effective therapy for non-alcoholic fatty liver disease (NAFLD), although intensive calorie restriction is typically recommended but dietary adherence is an issue. Currently, there are no studies had been focusing the effect of Modified Alternate Day Calorie Restriction in NAFLD patient focusing on changes in liver steatosis and fibrosis.
Detailed description
Disease activity and progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) and cirrhosis can be highly variable, where 2-3% will eventually progress to end-stage liver diseases. With the rising prevalence of metabolic syndrome and obesity, NAFLD has become the most frequent form of chronic liver disease in the West but also in Asia. There are good evidence that weight loss is effective in improving liver histology in NAFLD, for example, 31 obese patients with NASH was randomised into intensive lifestyle changes over 48 weeks versus structured basic education only, and the intensive lifestyle group showed significant improvements in steatosis, necrosis, and inflammation. Intense calorie restriction is the recommended form of dietary strategy for management of NAFLD. Even though such intense dietary strategy has proven to be effective, some patients find it difficult to adhere and maintain. On the other hand, intermittent fasting achieves more consistent weight loss by improving adherence, as intermittent fasting only requires calorie restriction every other day compared to conventional form of daily calorie restriction. Alternate day calorie restriction can be divided into two components, a 'feed day' and a 'fast day' where food is consumed ad libitum for 24 hours period alternating with either complete or partial (modified) calorie restriction for the next 24 hours. MACR, the dietary strategy employed in the investigator's study, restricts 70% of an individual's daily requirement of calorie per day. There are other forms of intermittent fasting, for example, 2-4 days of ad libitum feeding alternating with 2-4 days of calorie restriction. Currently, there are no approved pharmacological therapies for NAFLD, and many guidelines advocate recommendation with a focus on controlling risk factors and lifestyle interventions that include dietary and physical activities. No specific NAFLD trials have evaluated the effectiveness of modified form of intermittent fasting in the control of NAFLD activity.
Interventions
BEHAVIORALCalorie restriction (MACR)
This was a randomized, single-blind controlled trial with modified alternate-day calorie restriction (MACR) as the active intervention and normal habitual diet as control at Hospital University of Sains Malaysia.
Sponsors
Universiti Sains Malaysia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants were blinded after assignment to interventions or control group.
Intervention model description
Participants who fulfilled the selection criteria were randomly assigned to the modified alternate-day calorie restriction (MACR) group or the control group after a 2 week run-in period. During the 2 weeks, participants were required to keep their body weight stable by maintaining their usual eating habits and their daily activities. Randomization was performed using a random number generator with recruitment aimed for three MACR participants for every control participant by principal investigator.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Have elevated ALT or AST level (ALT \>41 or AST\>34 IU/L) * No evidence of other forms of liver diseases * For those with diabetes mellitus and dyslipidaemia, they must be on a stable therapy for at least 6 months prior to study enrolment
Exclusion criteria
* Significant alcohol consumption (\> 1 standard drink per day) * Pregnancy * Involvement in an active weight loss program or taking weight loss medications * Substance abuse and significant psychiatric problems.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of aspartate aminotransferase (AST) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in U/L. |
| Change from baseline shear wave elastography (SWE) at 8 weeks | Change from baseline at 8-week | Through the intercostal approach, SWE measurements were performed in the right liver lobe, at the supine position with the right arm in maximal abduction. The sonographer, assisted by an ultrasonic time-motion image, located a liver portion of at least 6 cm thick, free of large vascular structures. Once the measurement area had been located, the sonographer pressed the probe button to start an acquisition. Patients were asked to hold their breath for about five seconds, while the stiffness of the region of interest was measured and 10 measurements were made for each patient and the median average value of those measurements was recorded in kilopascals (kPa: metric). |
| Change from baseline liver steatosis at 8 weeks | Change from baseline at 8-week | Ultra-sonographic measurements including liver steatosis and shear wave elastography (SWE) were performed with the SuperSonic Imagine's Aixplorer® Ultrasound machine (Super Sonic Image, Aix-en Provence, France). All measurements were performed by a single sonographer where the inter-observer agreement level with another experienced sonographer was 85%. |
| Concentration of high-density lipoprotein (HDL) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected from participants at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L. |
| Concentration of low-density lipoprotein (LDL) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L. |
| Concentration of triglycerides (TG) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L. |
| Concentration of total cholesterol (TC) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L. |
| Concentration of fasting blood sugar (FBS) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in mmol/L. |
| Concentration of alanine aminotransferase (ALT) | Change from baseline at 8-week | Blood samples (8-10 hours of fasting blood samples) were collected at 8-10 am at baseline and 8-week post intervention for biochemical analysis. It was measured in U/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dietary plan adherence | At 8-week | Adherence data were assessed each week as percentage of adherence |
Outcome results
None listed