{'fraction_non_alphanumeric': 0.04945366248482396, 'fraction_numerical': 0.032780250910562525, 'mean_word_length': 5.062806673209028, 'pattern_counts': {'":': 0, '<': 7, '<?xml version=': 0, '>': 8, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Sustainability of diet-based moderate calorie restriction among obese patients with metabolic-associated fatty liver disease

Background and Aim: The long-term sustainability of weight loss continues to be a subject of investigation. This study was designed to examine the effects of weight loss and the long-term sustainability of lifestyle modifications among obese patients with metabolic-associated fatty liver disease (MAFLD). Materials and Methods: A total of 40 patients who were prescribed a hypocaloric diet (~500 calories reduction for each patient), and who were followed up for 12 weeks in 4 face-to-face interviews were enrolled in the study. The patients were contacted at the 36th month, and their current weight was recorded. Results: The mean weight at baseline of 87±13 kg decreased to 79±11 kg after 12 weeks of intervention (p<0.001). The mean weight at the 36th month did not significantly differ from that measured at the baseline (p=0.563). The mean controlled attenuation parameter decreased from 320±13 dB/m to 273±37 dB/m (p<0.001), while the median liver stiffness measurement decreased from 8.7 kPa (3.6–45.7 kPa) to 5.7 kPa (2.2–29.9 kPa) (p<0.001). Conclusion: Strict follow-up through nutritional consultation can help achieve weight loss in obese patients with MAFLD. However, for long-term results, the collaboration of nutritionists and gastroenterologists is essential to prevent weight regain.

therefore, international collaborative efforts have renamed this disease for the sake of competently reflecting the disease's pathophysiology. [2][3][4] Metabolic (dysfunction)-associated fatty liver disease (MAFLD), formerly called NAFLD, is a recently proposed nomenclature that is defined as evidence of hepatic steatosis in addition to being overweight, with T2DM or metabolic dysfunction criteria. [5] MAFLD has been estimated to affect approximately one-quarter of the world population. [6] As the problem of widespread obesity grows, MAFLD constitutes a major public health burden. [7,8] The growing prevalence notwithstanding, there is currently no approved pharmacotherapy to address this health concern. The most established treatment remains a recommendation for lifestyle modifications that are targeted at weight reduction. [9,10] A weight loss of >10% of body weight has been demonstrated to show improvement in hepatic steatosis, steatohepatitis, and fibrosis by at least one stage. Even a modest weight loss of >5% produces beneficial improvement in the disease. [11] The benefit of weight reduction has been proven; [12][13][14] however, it has been shown that only a minority of patients achieve the targeted sustained weight loss using standard lifestyle interventions. [15] Scragg et al. [16] demonstrated that an extremely low-calorie diet may help to achieve a targeted weight loss of >10% and maintain the loss with continued use in 9 months of follow-up. However, weight regain has been reported in long-term follow-up even when the targeted weight loss was achieved. [17] Nonetheless, Haufe et al. [18] observed that the effects of weight loss persisted in terms of insulin resistance and hepatic fat content, despite weight regain.
A few studies notwithstanding, [15][16][17][18] there is a paucity of studies that have investigated the sustainability of an effective diet in the long-term follow-up. Here, we have referred to this issue with respect to our obese MAFLD population using a calorie-restriction diet.

Introduction
An increased prevalence of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic fatty liver disease (NAFLD) reflects the close relationship between these disease etiologies. [1] Based on the available insights of the disease pathophysiology, it has been proposed that NAFLD may be an hepatic manifestation of systemic metabolic dysfunction; pressure ≥130/85 mmHg or undertaking a specific drug treatment; 3) TG ≥1.70 mmol/L or undertaking a specific drug treatment; 4) HDL cholesterol (HDL-C) <1.0 mmol/L in men and <1.3 mmol/L in women; 5) prediabetes (i.e., fasting glucose levels of 5.6-6.9 mmol/L, or 2-hour post-load glucose levels of 7.8-11.0 mmol/L, or HbA1c 5.7%-6.4%; 6) homeostasis model assessment-insulin resistance (HOMA-IR) score ≥2.5; and 7) a C-reactive protein level of >2 mg/L. [5] Diet prescription and follow-ups. A 12-week with a hypocaloric diet was prescribed by a dietician (B.E.T) after assessing the patients' individual requirements. The total caloric consumption was reduced by ~500 kcal for each patient. The macro-nutritional ingredients were 45%-60% carbohydrates, 10%-20% proteins, and 25%-35% fat. Complex carbohydrates and nutrition with a low glycemic index were recommended. During the visits, the patients were also educated about healthy cooking methods and nutrition. The study involved 4 face-toface interviews, conducted at initiation, 4, 8, and 12 weeks. The patients were interviewed again by phone after 36 months to assess adherence to lifestyle modifications and their current weight.
At baseline, the nutritional status of the patients was assessed based on a 3-day food consumption record using Nutritional Information System software (BeBİS; Ebispro for Windows, Stuttgart, Germany; Turkish version 8.1). The laboratory data included the values of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase, serum insulin, hemoglobin A1c, and fasting blood glucose. Elevated AST and ALT levels were defined as >37 U/L and >40 U/L, respectively. [20] Bioimpedance analysis was performed using a Tanita MC 780 P device (Tanita Corp., Tokyo, Japan) to estimate body composition data. A baseline FibroScan (Echosens SA, Paris, France) examination was also performed. Face-to-face interviews were conducted in the fourth and eighth weeks to evaluate patient compliance with the therapy. Anthropometric measurements, laboratory tests, and FibroScan results were reassessed in the twelfth week.

Transient Elastography
Transient elastography using the FibroScan device was performed by a single operator according to the manufacturer's instructions detailed elsewhere. [21] At least 10 valid measurements were performed during each examination and an interquartile range-to-median ratio of ≤0.3 was achieved. [22] Hepatic steatosis was defined as a controlled attenuation parameter cut-off of ≥238 dB/m. [23] A liver stiffness measurement of ≥8.95 kPa and ≥11 kPa indicated significant (F≥2) and advanced fibrosis (F ≥3), respectively. [24] Statistical Analysis All of the study analyses were performed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). The normality of distribution was analyzed using the Kolmogorov-Smirnov test. Normally and not-normally distributed data were expressed as mean±SD and median [minimum-maximum], respectively. Dependent continuous variables were compared using a paired t-test and the Wilcoxon signedrank test. Dependent categorical dependent data were compared using McNemar's test. The level of statistical significance was set at p<0.05.

Ethics
This study was conducted according to the Declaration of Helsinki and approved by the ethics committee of Bahcesehir University (date: 18.10.2017, number: 2017-16/01). Written informed consent was obtained from all of the patients.

Results
The study population comprised 40 patients with MAFLD (mean age: 56±10 years; 25 women [66%], 13 men [34%]). Initially, 25 patients (63%) were categorized as class I obesity, 8 (20%) as class II, and 5 (13%) as class III. The baseline anthropometric, laboratory, and Fi-broScan parameters are provided in Table 1, as well as the compar- ison to the values determined at the 12 th week of follow-up. All of the patients complied with their diet. A weight loss of 5% to 10% of the body weight was recorded for 27 patients (68%). The remaining patients achieved a weight loss of >10%. At the end of the 12 th week, regression in both hepatic steatosis and fibrosis was observed. The initial prevalence of significant and advanced fibrosis decreased from 47.4% (n=18) and 31.6% (n=12) to 15.8% (n=6) and 10.5% (n=4), respectively (p<0.001 and p=0.008, respectively). Elevated transaminase levels were recorded in 58% (n=23) of the patients at baseline and in only 25% (n=10) after the weight reduction. The change in hepatic fibrosis is depicted in Figure 1.
According to the patients' statements, the daily mean caloric consumption was 1480±373 kcal (range: 725-2701 kcal). At the 36 th month, 23 patients (61%) had abandoned their diet plan completely, while 15 patients (39%) still partially followed the diet. The change in the weight and BMI of these patients is illustrated in Figure 2.
The weight at baseline did not significantly differ from the final weight at the 36 th month (p=0.563); however, the BMI decreased significantly (p=0.046).

Discussion
Our results demonstrated successful improvement in the status of hepatic fibrosis and steatosis in obese patients with MAFLD following weight reduction and nutritional consultation; however, the long-term observation after termination of follow-up revealed weight regain and noncompliance with the recommended diet.
Successful and sustained weight loss has been previously defined as a loss of 10% of the body weight maintained for >12 months. [25] Franz et al. [26] reported in a systematic review of weight loss interventions that weight loss (5%-9%) plateaued at the 6 th month and stabilized at the 12 th month (4.8%-8%) in some patients. Most patients regained 30% of the lost weight in the first 12 months following the discontinuation of the intervention. As observed in our research, most patients with MAFLD report having regained the weight lost by dieting. [27][28][29] Therefore, it appears that the period after reaching the plateau at the 6 th month should be targeted with a change in the diet strategy and a focus on lifestyle and weight loss maintenance. [30] For MAFLD patients in particular, sustained lifestyle modifications that include improved eating and the inclusion of physical activity constitute the cornerstone of disease management. Amelioration of laboratory and histological parameters has consistently been reported following use of a hypocaloric diet. [31] Surgical interventions, such as sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and adjustable gastric banding, have offered an alternative means to achieve long-term weight loss in patients with MAFLD. All of these options have been associated with the improvement of MAFLD. [32][33][34] Unlike lifestyle modification, bariatric surgery is associated with sustained weight loss in 40% to 70% of patients.
In the systematic review of Hafeez et al., [35] for instance, complete regression of NAFLD was reported to be 60% to 83%, and fibrosis resolution occurred in 35% to 50% of the patients who underwent bariatric surgery. However, there were also some incidences of worsening fibrosis after RYGB, which may be associated with the surgical intervention or inadequate replacement of macro/micronutrients; [36][37][38] therefore, recent MAFLD guidelines suggest that bariatric surgery is most appropriate for patients with at least obesity class II and without liver cirrhosis. [10] The main strength of this study lies in the long-term observation of 36 months. In addition, we used FibroScan, a diagnostic tool that has been recognized as an accurate means to evaluate hepatic steatosis and fibrosis status. [39][40][41] Limitations of this study include the fact that, due to the ongoing coronavirus 2019 pandemic, we could not conduct face-to-face interviews in the 36 th month. The information about current weight was provided in a phone interview; we could not conduct FibroScan or laboratory examinations. Second, only 3 days of food consumption were recorded, which may have influenced the low caloric consumption data.
In conclusion, obese patients with MAFLD can benefit from weight reduction and strict follow-up with a nutritional consultation. For long-term success, it appears that a more flexible follow-up with a nutritional specialist may prevent weight regain. The collaboration of gastroenterologists and nutritional specialists plays a significant role in disease management.