Weight-Loss Plateau during Lifestyle Intervention Predicts Treatment Response in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of progressive hepatic damage and metabolic abnormalities, ranging from liver steatosis and inflammation injuries to liver fibrosis, along with various extents of metabolic comorbidities such as dysglycemia and dyslipidemia. It is highly prevalent, affecting approximately 30% of the general population and over 69% of individuals with overweight worldwide [1, 2]. Recent data from the Global Burden of Disease study alerted a rapid increase in global MASLD prevalence in the next decade due to the obesity epidemic [3, 4]. Lifestyle interventions using calorie-restricted diets and increased regular physical activity remain the first line and cornerstone of MASLD management, especially for individuals with obesity. However, these interventions may result in inadequate weight loss, difficulties in sustaining weight loss, and even fluctuations, which can pose a major obstacle to efficacy [5].

Previous research on obesity treatments has shown that various interventions, such as lifestyle changes, medications, and surgery, ultimately lead to a weight plateau despite ongoing treatment. The greatest weight loss typically occurs within 6–9 months of starting treatment, followed by a prolonged maintenance phase marked by a weight plateau and potential subsequent weight regain [6]. Multiple studies have indicated that the pattern of reaching a weight plateau during obesity treatment, including changes in weight or time points, can significantly affect both medium-term and long-term outcomes. A prospective cohort study of a 1-year behavioral weight-loss program in patients with obesity suggested that 6- and 12-week weight variability was closely linked to subsequent weight loss at 12 and 24 months [7]. Another study involving individuals with obesity found that the weight changes in the first 6–12 months after bariatric surgery could predict weight loss results 5 years post-surgery [8]. Furthermore, recent findings from the Michigan Bariatric Surgery Cohort revealed that preexisting MASLD might weaken the weight-loss response to bariatric surgery for obesity treatment [9]. However, there still needs to be more understanding of how MASLD could meaningfully impact weight plateaus during lifestyle modifications.

In the present study, we utilized a prospective cohort with or without MASLD to determine trajectories of weight changes and the key time point of attaining maximum weight loss and analyze its associations with later treatment response in hepatic steatosis, injury, and fibrosis. These findings may help in developing preventive programs aimed at overcoming the weight-loss plateau and improving long-term treatment efficacy.

This single-center, prospective case-control study was conducted at the Fatty Liver Center and Nutrition Clinic of the First Affiliated Hospital of Sun Yat-sen University from January 2015 to April 2023, with a 12-month follow-up survey until May 2024. Patients with MASLD and obesity (body mass index [BMI] ≥25.0 kg/m²) were diagnosed according to the 2024 joint EASL-EASD-EASO consensus statement, using magnetic resonance imaging-based proton density fat fraction with Dixon sequence (MRI-PDFF) for hepatic steatosis identification [10]. A control group of individuals without MASLD (non-MASLD) was randomly recruited from subjects requiring lifestyle interventions for obesity but with neither fatty liver detected via liver sonography nor elevated aminotransferase levels.

All participants were required to have obesity and be at least 18 years old, completing a 12-month treatment follow-up. Exclusion criteria included (i) incomplete data; (ii) decompensated cirrhosis or concurrent other causes of liver diseases, such as viral hepatitis, excessive alcohol consumption (>30/20 g daily for males/females), autoimmune liver disease, and secondary fatty liver disease; (iii) history of surgical weight-loss procedures; (iv) malignancy or major systemic diseases; (v) pregnancy and breastfeeding; and (vi) patients with diabetes were eligible if they exhibited at least moderately well-controlled (hemoglobin A1c <9.0%). The study protocol was approved by the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University (code: [2014]112), and informed consent was obtained from all participants.

Anthropometric measures, including body weight, height, waist circumference (WC), hip circumference, and blood pressure, were evaluated by trained physicians. The waist-to-hip ratio was determined by dividing WC by hip circumference. BMI (kg/m²) was calculated by dividing body weight (kg) by the square of height (m). Participants were classified into class I and class II or III obesity based on BMI thresholds of 25.0 and 30.0 kg/m², respectively [10]. Thresholds of 90 cm for males and 80 cm for females were utilized to identify increased WC [11]. Hypertension was defined as a blood pressure reading of 140/90 mm Hg or higher or the use of antihypertensive medications [12].

Venous blood samples were collected after an 8-h overnight fast and analyzed for lipid profiles, free fatty acids, fasting glucose (FBG) and insulin (FINS), uric acid, and liver biochemistry with the Abbott c8000 Automatic Biochemistry Analyzer (Abbott, Abbott Park, IL, USA). The homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated as FBG × FINS/22.5, with insulin resistance defined as HOMA-IR ≥2.5 [11]. The upper limit of normal for alanine aminotransferase (ALT) was set at 33 IU/L for males and 25 IU/L for females [10].

Prior to enrollment, all individuals with non-MASLD underwent abdominal ultrasound examination for confirmation. Hepatic steatosis was identified using ultrasonic diagnostic criteria, such as reduced contrast between the liver and kidney, with or without unclear visualization of intrahepatic tubular structure [13]. Patients with MASLD underwent upper abdomen MRI-PDFF to quantify liver fat content (LFC) using a 3.0-Tesla MRI scanner (Siemens 3.0 T Magnetom Verio; Siemens, Munich, Germany). The scanning protocol and imaging parameters were detailed in a previous publication, specifying TE1 of 2.5 ms, TE2 of 3.7 ms, repetition time of 5.47 ms, 5° flip angle, ±504.0 kHz per pixel receiver bandwidth, and 3.0 mm slice thickness [14]. The diagnostic threshold for identifying fatty liver was established at an average LFC of ≥5.0%. Fatty liver severity was classified as mild (5–10%), moderate (11–18%), or severe (16–23%) [10].

Two-dimensional shear wave elastography (2D-SWE) was conducted to assess liver stiffness measurement (LSM) values using a Supersonic Imagine system (Aix-en-Provence, France). A rectangular electronic region of interest measuring approximately 4 × 3 × 3 cm and positioned 1–2 cm under the liver capsule was chosen for each patient. Within this ROI, a circular ROI with a diameter of about 2 cm was defined for analysis. The mean LSM values were derived from five consecutive 2D-SWE images, and specific threshold values were used to determine the stage of hepatic fibrosis: F0: ≤6.3 kPa, F1: 6.4–7.5 kPa, F2: 7.6–8.8 kPa, F3: 8.9–9.8 kPa, and F4: ≥9.9 kPa [15].

During the initial face-to-face visit, all study participants completed comprehensive surveys covering demographic information, medical history, anthropometric measurements, and biochemical tests. Subsequently, personalized lifestyle guidance was provided by a professional nutritionist following the current MASLD guidelines. This guidance included an easy-to-carry booklet outlining calorie-restricted diets and recommendations for regular physical activity [10, 11, 13, 16]. The calorie restriction program aimed to reduce daily energy intake by at least 500 kcal, with a macronutrient distribution of 30% fat, 15% protein, and 55% carbohydrates, based on individual caloric requirements calculated using weight and physical activity levels [16]. Participants were instructed to consume 25 g/day of fiber and <250 mg/day of cholesterol. Moreover, they were encouraged to achieve a minimum of 10,000 steps daily and engage in various moderate to vigorous physical activities such as running, basketball, swimming, and carrying or lifting heavy loads. The exercise regimen comprised more than 150 min of moderate-intensity or over 75 min of vigorous-intensity physical activity per week. If needed, medication was prescribed by a multidisciplinary team specializing in fatty liver disease and metabolic disorders [17‒19]. This included lipid-lowering drugs such as statins and fenofibrate for hyperlipidemia, uric acid-lowering medications like febuxostat and benzbromarone for hyperuricemia and gout, as well as insulin or oral antihyperglycemic agents for individuals with diabetes.

During the 12-month follow-up period, participants were instructed to maintain their personalized dietary and physical activity routines. They were asked to record their daily food intake in a food diary, providing insights into how closely they met their caloric restriction goals. Additionally, participants engaged in self-monitoring of the duration of moderate to vigorous physical activity each week. Follow-up interviews were conducted by a professional nutritionist monthly for the first 6 months and then quarterly for the remaining 6 months. During these interviews, participants reported their weight and completed a brief self-report questionnaire assessing their compliance with the lifestyle modification regimen over the preceding month. This questionnaire specifically documented the number of days participants adhered to or deviated from calorie restrictions, as well as the number of weeks they followed or strayed from their exercise regimen. The proportion of participants who occasionally failed to adhere to the lifestyle modification regimen at each follow-up time point was calculated by dividing the number of individuals who did not consistently adhere to the calorie restrictions or exercise regimen during the previous month by the total number of participants. The total weight loss (%TWL) was calculated using the formula: %TWL = (weight at follow-up−initial weight)/initial weight × 100.

For patients with MASLD, biochemical tests, MRI-PDFF, and 2D-SWE assessments were scheduled at the initial and 12-month visits to assess changes in MASLD characteristics. The weight-loss goal was set at a minimum of 5.0% reduction from baseline [10]. In terms of hepatic steatosis, a response in MRI-PDFF was considered as a ≥30% relative decrease in LFC from baseline [20]. For hepatic injury, an ALT response was characterized by a ≥17 IU/L absolute decrease from baseline in individuals with MASLD and abnormal ALT levels [10, 13]. Regarding hepatic fibrosis, an LSM response was defined as a decline of ≥1 stage from baseline in patients with fibrosis ≥1 stage.

Propensity score matching was utilized to match the MASLD and non-MASLD groups using the nearest neighbor-matching approach with a 0.1 caliper width, without replacement, based on age, sex, BMI, and diabetes status. Continuous variables were described as mean ± SD or median (interquartile range [IQR]), while categorical variables were presented as frequencies (percentages). Statistical tests such as Student’s t test, Mann-Whitney U test, or chi-square test were employed to compare the clinical parameters between the MASLD and non-MASLD groups, depending on the variable distribution. A two-way (group × time) repeated-measure analysis of variance (ANOVA) was conducted to assess between-group differences. Subsequently, a one-way (time) repeated-measure ANOVA was used to compare %TWL changes over time within each group. Post hoc tests with Bonferroni adjustment were conducted for pairwise comparisons. Logistic regression analyses were carried out to explore the associations between the time point of maximum weight loss and the 12-month improvement in hepatic steatosis, injury, and fibrosis. Statistical analyses were performed using SPSS version 25.0 (IBM, Chicago, IL, USA) and R version 4.3.1 software. Additionally, the dynamic change in %TWL was visually depicted using nonlinear regression with a standard one-phase decay model in Prism version 10.1.2 (GraphPad Software Inc., San Diego, CA, USA). Results were considered statistically significant at a two-sided p value <0.05.

A total of 408 study participants were included in the final analysis, consisting of 305 patients with MASLD and 103 individuals with non-MASLD. The baseline characteristics of the sample are detailed in Table 1. Sex proportions, ages, BMIs, WCs, and prevalence of diabetes and hypertension were similar between the two groups (all p > 0.05). Patients with MASLD had a mean age of 42.3 ± 13.7 years, a mean BMI of 27.9 ± 2.8 kg/m², and 66.9% (n = 204) were male at baseline. The median LFC was 12.6% (IQR: 8.7%–20.2%), and the median LSM was 5.9 kPa (IQR: 5.1–7.1 kPa). Compared to individuals without MASLD, those with MASLD exhibited significantly higher baseline serum levels of triglycerides, FINS, HOMA-IR, uric acid, albumin, and liver enzymes (all p < 0.05). No significant differences in serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, free fatty acids, FBG, and total bilirubin levels were observed between the two groups (all p > 0.05).

There were no significant differences in the proportions of individuals who occasionally did not adhere to lifestyle modifications at 3, 6, 9, and 12 months within either the MASLD or non-MASLD groups (all p > 0.05, online suppl. Fig. S1; for all online suppl. material, see https://doi.org/10.1159/000543818). Specifically, a repeated-measure ANOVA using Greenhouse-Geisser values revealed no significant differences in the duration of non-adherence to caloric restriction or the exercise regimen assessed at 3, 6, 9, and 12 months for either group (all p > 0.05, online suppl. Table S1). After 12 months of lifestyle intervention, 127 out of 305 patients with MASLD (41.6%) showed a treatment response in hepatic steatosis. Among the 196 patients with elevated ALT levels at baseline, 93 (47.4%) achieved a treatment response in hepatic injury. Of the 119 patients with liver fibrosis at baseline, 55 (46.2%) experienced a reduction of ≥1 stage from their baseline condition (online suppl. Table S2).

When comparing the weight change trajectories between MASLD and non-MASLD groups, both showed a decrease in body weight and %TWL, whereas patients with MASLD exhibited less weight loss in response to lifestyle intervention (Fig. 1; online suppl. Table S3). Specifically, the results of a two-way repeated-measure ANOVA revealed significant main effects of group (F = 6.05, degrees of freedom [df] = 1, $ηp2$ = 0.02, p = 0.01), time (F = 153.28, df = 2.32, $ηp2$ = 0.27, p < 0.001), and interaction (group × time) (F = 38.62, df = 2.32, $ηp2$ = 0.09, p < 0.001) on body weight. The post hoc analysis showed no significant weight differences between groups in the first 2 months (all p > 0.05), but differences emerged from 3 to 12 months (all p < 0.05) (Fig. 1a). At the 12-month follow-up, patients with MASLD had a lower percentage of achieving weight-loss goals compared to individuals with non-MASLD (29.8% vs. 46.6%, p = 0.002). Similar trends were observed in both class I (26.4% vs. 41.0%, p = 0.01) and class II or III obesity (42.9% vs. 70.0%, p = 0.03) (Fig. 1b). Additionally, the two-way ANOVA analysis showed statistically significant main effects of group (F = 88.36, df = 1, $ηp2$ = 0.18, p < 0.001), time (F = 102.12, df = 2.32, $ηp2$ = 0.20, p < 0.001), and group-time interactions (F = 23.63, df = 2.32, $ηp2$ = 0.06, p < 0.001) on %TWL (Fig. 1c). The Bonferroni’s post hoc test indicated significant differences in %TWL between groups at all post-intervention visits (all p < 0.001, online suppl. Table S3).

Subgroup analyses within the MASLD group indicated a notable decrease in body weight following lifestyle intervention for individuals with more severe baseline conditions, such as class II or III obesity (P_subgroup = 0.01, online suppl. Fig. S2D), increased WC (P_subgroup = 0.04, online suppl. Fig. S2E), abnormal ALT levels (P_subgroup = 0.007, online suppl. Fig. S2G), moderate to severe steatosis (P_subgroup <0.001, online suppl. Fig. S2H), and fibrosis stage ≥1 (P_subgroup = 0.03, online suppl. Fig. S2I). However, no significant variations in weight-loss patterns were observed across subgroups when stratified by sex, age, presence of diabetes, and insulin resistance status (online suppl. Fig. S2). For individuals with non-MASLD, subgroup analysis demonstrated that those with class II or III obesity (P_subgroup = 0.003, online suppl. Fig. S3D) and increased WC (P_subgroup < 0.001, online suppl. Fig. S3E) experienced notably greater weight reduction. In contrast, there were no substantial differences in weight-loss trends among individuals with non-MASLD when subgrouped by sex, age, presence of diabetes, and insulin resistance status (online suppl. Fig. S3).

The maximum %TWL during the 12-month follow-up was attained at 6 months for both groups (Fig. 1c; online suppl. Table S3). The time of 6 months during the lifestyle intervention appeared to be a critical time point for the onset of a weight-loss plateau or weight regain. Subsequent one-way repeated-measure ANOVA with Bonferroni post hoc tests indicated that patients with MASLD began to lose weight compared to baseline between the 1st and 6th months. The average %TWL at 6 months was similar to that at 9 and 12 months, suggesting that patients with MASLD encountered a prolonged period of weight stability after the 6-month mark (all p > 0.05, online suppl. Table S3). Conversely, individuals with non-MASLD experienced more significant weight loss in the initial 6 months but started regaining weight by the 9th and 12th months, with the average %TWL being higher than that at 6 months (all p < 0.05, online suppl. Table S3). Subgroup analyses revealed that most patients with MASLD achieved their highest %TWL at 6 months, while female patients, individuals with class II or III obesity, increased WC, insulin resistance, normal ALT levels, and mild hepatic steatosis reached their peak %TWL at 9 months (online suppl. Table S4). With the exception of those with diabetes, the majority of subjects with non-MASLD also reached their maximum %TWL at 6 months (online suppl. Table S5).

To investigate the relationship between 6-month %TWL and 12-month treatment response in hepatic steatosis, injury, and fibrosis among patients with MASLD, individuals were categorized into tertiles based on their 6-month %TWL (Fig. 2). In the analysis of hepatic steatosis efficacy involving 305 patients with MASLD and obesity, the 6-month %TWL was divided into tertiles based on the 33rd (−4.40%) and 66th (−0.55%) percentiles, with tertile 1 representing the highest weight loss. The percentage of MRI-PDFF response at 12 months demonstrated an increase with greater weight loss at 6 months (p < 0.001, Fig. 2a, d). For the hepatic injury efficacy analysis, 196 patients with abnormal ALT at baseline were categorized into tertiles based on the 33rd (−4.71%) and 66th (−1.13%) percentiles of their 6-month %TWL. The results revealed that the proportion of 12-month ALT response increased with greater weight loss (p < 0.001, Fig. 2b, e). In the evaluation of hepatic fibrosis efficacy, 119 patients with baseline liver fibrosis ≥1 stage were grouped based on the 33rd (−4.91%) and 66th (−1.09%) percentiles of their 6-month %TWL. However, no significant difference was observed in the proportion of 12-month LSM response among the tertiles (p = 0.23, Fig. 2c, f).

In addition, 98 patients with MASLD underwent an unscheduled comprehensive assessment at 6 months, including liver biochemistry, MRI-PDFF, and 2D-SWE. Among these patients, 61 had elevated serum ALT levels, and 41 had liver fibrosis at baseline. When analyzing the treatment response for hepatic steatosis, injury and fibrosis, the 33rd percentile was −4.79%, −4.71%, and −5.68%, respectively, while the 66th percentile was −1.67%, −1.32%, and −1.25%, respectively. The results indicated that the proportion of 6-month treatment response in hepatic steatosis increased with weight loss (p = 0.03). Although patients with the most significant weight loss tended to observe greater enhancements in hepatic injury and fibrosis at 6 months, the results did not reach statistical significance (all p > 0.05) (online suppl. Fig. S4).

Further binary logistic regression analyses indicated a relationship between an increase in 6-month %TWL and the achievement of treatment response for hepatic steatosis (OR: 0.77, 95% CI: 0.72–0.83, p < 0.001) and hepatic injury (OR: 0.83, 95% CI: 0.77–0.90, p < 0.001) at 12 months (Fig. 3). Similar findings were observed in the subgroup of patients with MASLD categorized by various baseline characteristics, such as sex, age, presence of diabetes, anthropometric measures, and liver condition (all p < 0.05). Notably, weight loss at 6 months was a significant predictor of the 12-month treatment response to hepatic fibrosis merely in female patients (OR: 0.79, 95% CI: 0.64–0.97, p = 0.03), those aged ≤40 years (OR: 0.84, 95% CI: 0.70–0.995, p = 0.04), and those without diabetes (OR: 0.89, 95% CI: 0.79–0.997, p = 0.04) (Fig. 3).

After multivariable adjustment for sex, age, anthropometric measures, history of diabetes and liver condition, 6-month %TWL remained significantly linked to 12-month treatment response in hepatic steatosis (OR: 0.78, 95% CI: 0.72–0.84, p < 0.001) and injury (OR: 0.82, 95% CI: 0.76–0.90, p < 0.001), but not in fibrosis (OR: 0.92, 95% CI: 0.82–1.03, p = 0.13) (Table 2).

This study examined the characteristics of weight plateau in MASLD and observed that the highest weight loss occurred at the 6-month mark following a lifestyle intervention. Patients with MASLD initially showed less weight loss compared to individuals with non-MASLD, but they were able to maintain their weight for a longer period before experiencing weight regain. The amount of weight loss at 6 months was found to be associated with the subsequent response to treatment for hepatic steatosis and injury at 12 months among patients with MASLD. These findings suggest that the first 6 months of lifestyle intervention could be a critical time to identify and potentially intervene with patients with MASLD who are at a higher risk of not achieving significant treatment response.

The results of this study are consistent with previous research on obesity, indicating that individuals with a healthy liver experienced greater weight loss and metabolic improvements compared to those with MASLD [21]. Possible explanations for this discrepancy include genetic variations, lower metabolic rates in MASLD due to impaired liver function, and specific pathophysiological features of MASLD such as increased insulin resistance and inflammation levels and microbial dysregulation [22]. In line with previous research [23, 24], individuals with higher baseline BMI and WC, regardless of MASLD status, were more likely to experience substantial weight loss over time. This may be due to higher metabolic rates and energy expenditure in individuals with greater obesity or the baseline levels of these parameters, leading to more noticeable changes [25]. Therefore, further research, particularly focusing on genotypes and clinical phenotypes, is necessary to gain a better understanding of the factors influencing these outcomes.

According to the 2024 joint EASL-EASD-EASO consensus statement, a bodyweight reduction of ≥5% is necessary to reduce hepatic steatosis, 7–10% to improve inflammation, and ≥10% to improve liver fibrosis [10]. In our study, patients with MASLD achieved the highest weight loss at 6 months (−2.55%) and gradually weight regained to a net weight loss of about 2.26% at 12 months. This pattern was supported by previous studies conducted on patients with MASLD, revealing a maximal weight loss at 6 months, followed by a plateau in weight loss and potential weight regain [26, 27]. The plausible mechanism of weight-loss plateau was that periods of active weight loss, marked by a negative energy balance, may be associated with hypometabolism (energy expenditure below expected levels based on changes in body mass and composition) and hyperphagia (increased appetite compared to energy expenditure), ultimately contributing to weight regain [28‒30]. It is noteworthy that the weight reduction at 6 months observed in the MASLD cohort (−2.55%) was comparable to our previous research findings (approximately −1.4%) [31, 32], but lower than the results reported in randomized clinical trials by Wei et al. [26] and Marin-Alejandre et al. [27] (−10.6% and −9.7%, respectively). The discrepancies could be attributed to the differences in study design, methodologies, characteristics of the study populations, and sample size. In addition, our results indicated that only a limited proportion (29.8%) of patients with MASLD achieved a weight reduction of ≥5% at 12 months, which also aligns with another prospective “non-interventional” cohort study involving 293 patients with histologically proven MASLD (30.0%) [33].

A noteworthy discovery from our research was the ability to predict the 12-month treatment response in hepatic steatosis and injury based on the amount of weight loss achieved at 6 months following lifestyle modification. Previous studies have indicated that early weight loss can serve as an indicator of long-term outcomes [7, 24, 34]. For example, Du et al. [24] found that weight loss at 6 months could forecast successful weight loss after 5 years in Chinese individuals with obesity post-bariatric surgery. Similarly, a prospective cohort study involving 327 adults with obesity and diabetes revealed that weight loss at 2 months could help identify individuals unlikely to achieve significant 1-year weight loss despite undergoing intensive lifestyle intervention [34]. Our study, however, was the first to establish a correlation between weight loss in the initial months of treatment and the 1-year response in hepatic steatosis and injury among patients with MASLD. As patients with MASLD lose weight, there is a reduction in liver triglyceride accumulation, along with improvements in insulin resistance, inflammatory response, and oxidative stress in the liver, all of which are crucial factors in reversing liver steatosis and injury [35]. These findings offer valuable clinical insights on enhancing lifestyle interventions to overcome weight-loss plateaus at 6 months, as individuals who do not respond early on have a low probability of success at 12 months if they continue with the original intervention. Nevertheless, it remains to be seen if these results would hold true in longer follow-up studies or treatment programs integrating pharmacotherapy.

Liver fibrosis, a complex condition associated with various risk factors like obesity, steatohepatitis, insulin resistance, and lipotoxicity, was explored in the current study [36, 37]. The findings revealed that early weight loss within 6 months was not a reliable indicator of liver fibrosis reversal at 1 year. Importantly, the majority of our patients had already reached a weight-loss plateau by the 6-month mark. Those who had not achieved a weight loss of at least 10% by 6 months were less likely to reach a ≥10% weight loss by 12 months, underscoring the potential necessity for more intensive interventions or pharmaceutical treatments.

The strengths of the present study included its prospective follow-up at specific time points and comprehensive monitoring of changes in liver characteristics, anthropometric measurements, and metabolic responses to lifestyle modifications. However, limitations of the study included potential selection bias due to its single-center nature in tertiary care centers in China, which may restrict the generalizability of the findings to other populations. Participants did not receive daily in-person guidance on diet and exercise, impacting the assessment of compliance with lifestyle interventions. Although MRI-PDFF is a noninvasive and relatively accurate tool for measuring LFC [38], the 2D-SWE fibrosis staging system might not be sensitive enough to detect fibrosis reversal. Therefore, future studies with extended follow-up periods and more sensitive histological scales are needed to confirm the results of this study.

In summary, the study demonstrated that patients with MASLD initially experience moderate weight loss, followed by a period of weight plateau and eventual weight regain during lifestyle interventions, with the maximal weight loss typically occurring at 6 months. The weight loss within the first 6 months of lifestyle intervention can serve as a predictor for the 1-year treatment response. Therefore, timely identification of suboptimal weight loss in patients with MASLD can prompt the implementation of more intensive lifestyle interventions earlier on to enhance their long-term treatment outcomes (Fig. 4).

We are grateful to Prof. Aihua Lin from the School of Public Health, Sun Yat-sen University, for her assistance in statistical analysis of this study.

This study protocol was reviewed and approved by the Ethics Committee of Institutional Review Board of the First Affiliated Hospital, Sun Yat-sen University, Approval No. [2014]112. All individuals who agreed to participate in the research provided written informed consent.

The authors have no conflicts of interest to declare.

This work was supported by National Natural Science Foundation of China (82370587, 82100648) and Natural Science Foundation of Guangdong Province, China (2022A1515012369).

Bihui Zhong and Shuyu Zhuo supervised the project. Ling Luo and Junzhao Ye analyzed and interpreted the data and drafted the manuscript. Ling Luo and Ting Zhou collected clinical data. Shuyu Zhuo, Zhi Dong, Shiting Feng, and Wei Wang performed clinical evaluation. All authors revised the manuscript and read and approved the final manuscript.

Ling Luo and Junzhao Ye contributed equally to this work.

Due to ethical restrictions, the analyzed data in this study are not available to the public but can be requested from Prof. Bihui Zhong. For further inquiries, please contact Prof. Bihui Zhong.