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Saroglitazar and vitamin E vs. lifestyle interventions in metabolic dysfunction associated steatotic liver disease: A 3-arm randomised study
For correspondence: Dr Anurag Kumar Tiwari, Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, Uttar Pradesh, India e-mail: tiwarianuragk@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Tiwari AK, Singh G, Kumar V, Yadav DP, Shukla SK, Singh V, et al. Saroglitazar and vitamin E vs. lifestyle interventions in metabolic dysfunction associated steatotic liver disease: A 3-arm randomised study. Indian J Med Res. 2026;163:598-605. doi: 10.25259/IJMR_2511_2025
Abstract
Background and objectives
Lifestyle interventions are a vital component for the management of metabolic dysfunction-associated steatotic liver disease (MASLD). In the present study, we investigated the differential effect of saroglitazar or vitamin E vs. lifestyle interventions only.
Methods
A total 150 non-diabetic patients aged 19-55 yr were recruited to receive saroglitazar and vitamin E along with lifestyle interventions and lifestyle interventions alone (n=50 in each arm, A, B and C, respectively) for 24 weeks. Liver stiffness measurements and NAFLD fibrosis score were the primary outcomes. The study was registered under Trial registration (CTRI/2022/05/042462).
Results
Per-protocol analysis was performed in 136 patients (n=46, 47, and 43 in arms A, B and C, respectively). The changes from baseline were not-significant for NAFLD fibrosis score [0.05±0.52, 0.06±0.64 and -0.12±1.0, 95% confidence interval (CI), P =0.41] and liver stiffness measurement [-1.25 (-2.6, -0.2), -1.4 (-3.7, 0.4,) and -0.7 (-1.8, -0.2), P =0.22] in either arm. Changes in secondary outcomes were also not-significant except triglyceride [-13.95 (-61, -18), -4.3 (-28.8, 49) and -13 (-127, 3) P=0.035]. A considerable proportion of patients had at least ‘2 Kpa reduction’ in liver stiffness measurement in arm A (39%) compared to C (19%).
Interpretation and conclusions
Saroglitazar or vitamin E are similar to lifestyle interventions in improving different non-invasive parameters in MASLD at 24 weeks of intervention.
Keywords
Lifestyle interventions
Liver stiffness measurement
NAFLD fibrosis score
Saroglitazar
Vitamin E
Metabolic dysfunction associated steatotic liver disease (MASLD) is defined as steatosis of at least 5% of the hepatocytes and the presence of at least one of the five cardio-metabolic risk factors after excluding secondary causes of fat accumulation.1 The estimated prevalence of MASLD among adults is 32% across the globe, with a higher prevalence in males (40%) than females (26%).2 The prevalence of MASLD in Indian population is estimated between 9-53% in different studies and often associated with metabolic syndrome.3,4 Oxidative stress, environmental factors, and genetic polymorphisms (SNPs) have been implicated in its pathogenesis.5 MASLD includes simple steatosis, metabolic dysfunction associated steatohepatitis, cirrhosis, and hepatocellular carcinoma in its spectrum.3 Interventions in MASLD must be introduced before development of the cirrhosis and its complications to have a purposeful and lasting effect. The management of MASLD currently involves lifestyle interventions and a range of pharmacological agents targeting the underlying metabolic disturbances, inflammation, and associated fibrosis. Lifestyle interventions are a vital component of the management plan for MASLD; however, it is very difficult to reach at adequate lifestyle interventions in general population. Lifestyle interventions often include exercise and dietary modifications in various forms and usually are a part of different approaches targeting the MASLD/MASH with or without diabetes. Various methods applied to dietary restrictions include but not limited to, hypocaloric diet,6 mediterranean diet,7,8 and intermittent fasting.9
Until now, only resmetirom, a thyroid hormone receptor-β agonist is approved by US Food and Drug Administration (USFDA, March 2024) to treat MASLD/MASH.10 Pioglitazone, an insulin sensitiser, has been widely used to treat type 2 diabetes mellitus associated MASLD/MASH due to its ability to improve insulin sensitivity and has a positive impact to reduce hepatic steatosis and fibrosis. Vitamin E has been frequently used due to its antioxidant properties and thereby leading to a reduction in liver inflammation and improved liver histology in biopsy proven, non- diabetic MASH patients.11 Saroglitazar, a dual peroxisome proliferator activated receptor α/γ agonist, has been used to treat dyslipidaemia and can reduce hepatic fat content and inflammation.12-14 Due to the current lack of an effective therapeutic agent to manage MASLD, Saroglitazar, in addition to lifestyle intervention is endorsed by Indian National Association for Study of Liver (INASL) to manage MASLD in India.15 Various other agents have been proposed for treatment of MASLD with conflicting results. Given the complex and heterogeneous nature of MASLD, therapeutic strategies often require a multifaceted approach. The present trial aimed to investigate the effect of saroglitazar and vitamin E along with lifestyle interventions when compared to lifestyle interventions only, for reducing liver stiffness measurement in patients with MASLD.
Methods
The present study was an investigator-initiated, prospective, randomised, 3-arms, open label trial. This trial was performed at department of Gastroenterology, Institute of medical sciences, Banaras Hindu University, Varanasi, tertiary care hospital in the North India, between June 2022 to January 2024. The study was conducted according to the Declaration of Helsinki 1975, as revised in 2013. The study was approved by Institutional ethics committee of the institute. Trial was registered prospectively in Indian trial registry (No. CTRI/2022/05/042462/www.ctri.nic.in). All the participants provided written informed consent before inclusion in the study.
Sample size
There is scarcity of studies on comparison of saroglitazar or vitamin E with lifestyle interventions. We assumed that for a medium effect size (Cohen’s f=0.30), α-error 0.05 and power of 85%, for a 3-arm comparison of means using ANOVA, a sample size of 42 will be required in each arm. Accounting for maximum allowable dropout of approximately 20%, we included 50 patients in each arm (total=150). Sample size calculation was performed using G* power software version 3.1.9.7.
Study design
Allocation of treatment was done by sealed opaque envelopes containing computer generated random numbers. Randomisation was done in the block of 3 (1:1:1 in each arm). The study arms were saroglitazar plus lifestyle interventions (A), vitamin E plus lifestyle interventions (B), and lifestyle interventions only (C). Neither patients nor investigators were blinded.
Study patients and interventions
Patients aged 19-55 years, with a diagnosis of MASLD/MASH without diabetes mellitus (random plasma glucose <200 mg/dL, HbA1c < 6.5 and not on any glucose lowering agent) and having alanine aminotransferase (ALT) elevation of at least 1.5 times of upper limit were included. Patients with present or past (within 2 year of inclusion) alcohol use (>20g/day in males; >10g/day in females); history of liver disease (viral hepatitis B or C, cholestatic and metabolic liver diseases, autoimmune hepatitis); decompensated cirrhosis; thyroid disorders; pregnant and lactating females during study period; chronic kidney disease or any chronic systemic illness that in view of investigator would make patient unsuitable for study; and patients using alternative medicines or ursodeoxycholic acid, S-adenosylmethionine (SAM-e), betaine, or pentoxifylline in last 1 month from inclusion were excluded.
Eligible patients were randomised into arm A (Saroglitazar 4 mg/day plus lifestyle interventions), arm B (Vitamin E, 400 mg twice a day plus lifestyle interventions) and arm C (lifestyle interventions only) for 24 weeks. Lifestyle interventions included dietary restrictions and exercise. Although non-standardised, we aimed at restricting food items with high glycaemic index such as potato, rice, and sugar containing foods, which are major sources of daily carbohydrates in the study participant’s geographic area. A dietician was involved to advise regarding calorie compensation due to carbohydrate restriction in the diet. All participants were advised to perform brisk walk of 30-40 min/day (amounting to 4-5 km) throughout study duration. Reinforcement for lifestyle interventions compliance was done at least twice during intervention period of 24 weeks at follow up visits or by telephone. Baseline parameters were recorded prior to intervention and included age, sex, weight, height, thyroid function tests, random blood sugar, HbA1c, haemoglobin, total leucocyte count, platelets, liver function tests, renal function tests, triglyceride level, liver stiffness measurement, and controlled attenuation parameter. Liver stiffness measurement and controlled attenuation parameter measurements were performed by Echosens Fibroscan®. Other potential etiologies of deranged liver function were excluded with suitable testing whenever deemed necessary. A liver biopsy was not performed, except where alternate etiologies were suspected clinically and required biopsy figure (The CONSORT chart) depicts the processes of inclusion (and exclusion), randomisation, follow up, data collection and analysis.
Follow up
After randomisation, patients were given assigned interventions and followed for 24 weeks. At completion of 24 weeks, weight, complete blood counts (CBC) with platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride level, liver stiffness measurement, and controlled attenuation parameter were recorded. AST to platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4) and NAFLD fibrosis score were calculated at baseline and at completion of the study (24 wk). All patients were reinforced to follow lifestyle interventions as advised during follow up. Patients were monitored for any adverse event during follow up. A patient reported record was maintained for the compliance to lifestyle interventions during entire intervention period. Complete exclusion of potato, rice, and sugar containing foods along with 30-40 min of brisk walk/day were considered as ‘complete’ adherence to advised lifestyle interventions, while any adherence less than complete was considered as ‘partial’. Adherence was labelled as ‘none’ when patient denied any compliance to advised lifestyle interventions.
Outcome measures
Primary: (i) Change in NAFLD fibrosis score at 24 weeks; (ii) change in liver stiffness measurement at 24 weeks
Secondary: Changes at 24 weeks of intervention in-AST, ALT, triglycerides level, weight, FIB-4 score, and APRI score. Any adverse events.
Statistical analysis
Data normality was assessed by Shapiro-Wilk test. Parametric and non-parametric data were represented by mean±SD and median with interquartile range (IQR), respectively. Within group comparisons were performed by chi-square (χ2) test for categorical variables and paired t-test for continuous variables. For non-parametric data, Wilcoxon signed rank test was used. Between group comparisons were performed by oneway ANOVA and Kruskal-Wallis test for parametric and non-parametric data, respectively. All data were analysed per-protocol after exclusion of the patients lost to follow up. A P value of <0.05 was considered significant. Analysis of data was performed using SPSS version 17.0 (IBM, Chicago, USA).
Results
Baseline characteristics
Out of 327 participants evaluated, 150 patients with MASLD were randomised in 3 active arms (50 in each arm; A, B and C) to receive saroglitazar and vitamin E plus lifestyle interventions and lifestyle interventions only for 24 weeks, respectively. Fourteen patients were excluded from per-protocol analysis as they were lost to follow up ( Figure). Patients’ adherence to advised lifestyle interventions (during 24 weeks of intervention) was 85.3% (∼50% partial) and proportion was 83%, 85% and 86% in arms A, B and C, respectively. Fourteen percent patients did not follow the advised lifestyle interventions, even partially. Among 150 participants, 60% had liver stiffness measurement value of ≥ 6.5 Kpa and 86.67% had controlled attenuation parameter value of ≥ 250 at baseline. Baseline parameters were available for all 150 patients and were similar across 3 groups. Median age (in years) [33 interquartile range (IQR), 28-40; 35.5 (IQR, 27.75-42); and 34 (IQR, 30-41.25), respectively] and gender distribution (predominant males 86%, 90% and 86%, respectively) were similar across arms. Baseline demographic and biochemical parameters were similar in all the three arms ( Table I).
| Study arms | ||||
|---|---|---|---|---|
| Parameters | A (Saroglitazar arm); N=50 | B (Vitamin E arm); N=50 | C (Lifestyle intervention only); N=50 | P value |
| Age (yr) | 33 (28-40) | 35.5 (27.75-42) | 34 (30-41.25) | 0.64 |
| Gender, Male (%) | 86 | 90 | 86 | |
| Height (m)* | 1.68 ±0.10 | 1.68±0.06 | 1.65±0.08 | 0.14 |
| Weight (kg)# | 80.75 (70.75-87.25) | 75 (68.75-80) | 75.80 (67-85.25) | 0.10 |
| BMI (kg/m2)* | 27.79±3.33 | 26.86±3.34 | 27.46±3.69 | 0.36 |
| Haemoglobin* (13.0-17.0 g/dL) | 13.98±1.44 | 13.74±1.47 | 14±1.47 | 0.61 |
| Total leucocyte count* (4.0-10.0 thousands/µL) | 8150±1889 | 7214±2209 | 7683±2062 | 0.08 |
| Platelet count# (150-410 thousands/ µL) | 189.50 (168-228.75) | 177.50 (143.50-206.25) | 169 (150-199.25) | 0.07 |
| Serum AST# (<40 IU/L) | 53.90 (43.3-72.5) | 52.60 (42.5-73.4) | 56.20 (39.9-80.4) | 0.95 |
| Serum ALT# (<40 IU/L) | 89.55 (69.35-127.5) | 84.50 (72.4-116.15) | 75.20 (67-126.5) | 0.47 |
| TB# (<1.2 mg/dL) | 0.70 (0.50-0.98) | 0.70 (0.50-0.9) | 0.70 (0.60-0.93) | 0.56 |
| Total protein* (6.40-8.30 g/dL) | 7.95±0.59 | 7.80±0.42 | 7.90±0.62 | 0.59 |
| Serum albumin* (3.9-4.9 g/dL) | 4.58±0.37 | 4.58±0.28 | 4.59±0.41 | 0.99 |
| Serum alkaline phosphatase# (40-129 IU/L) | 138.95 (109.12-198.82) | 132.75 (99.35-173.37) | 143.80 (108.85-314.20) | 0.32 |
| Serum triglycerides# (<150 mg/dL) | 178.85 (144.05-226.00) | 179.15 (132.87-223.27) | 185.77 (135.97-284.40) | 0.59 |
| Liver stiffness measurement# (KPa) | 6.75 (5.52-8.22) | 7.20 (5.67-9.22) | 6.60 (5.25-7.91) | 0.24 |
| Controlled attenuation parameter # | 301.50 (273.50-327.25) | 297.00 (276.00-324.00) | 303.50 (268.50-340.00) | 0.96 |
| FIB-4# | 1.01 (0.72-1.39) | 1.18 (0.83-1.56) | 1.28 (0.80-1.80) | 0.06 |
| APRI# | 0.69 (0.54-1.01) | 0.77 (0.65-1.15) | 0.77 (0.60-1.15) | 0.47 |
| NAFLD fibrosis score* | -2.78±0.71 | -2.62±0.96 | -2.43±0.99 | 0.15 |
*Parametric data (oneway ANOVA; mean±SD)
#Non-parametric data (Kruskal-Wallis test; median, IQR)
BMI, body mass index; AST, aspartate amino transferase; ALT, alanine amino transferase; TB, total bilirubin; FIB-4, fibrosis index based on 4 factors; APRI, AST to platelet ratio index
Primary and secondary outcome measures
Changes from baseline were not significant for primary outcome measures, NAFLD fibrosis score and liver stiffness measurement between 3 treatment arms ( Table II). Most of the secondary outcome measures also did not result in notable change from baseline except triglyceride level ( Table II), which was significantly reduced in arm A and C compared to arm B. Within arm comparisons (pre-post analyses) were performed for primary and secondary outcome measures. No significant difference in NAFLD fibrosis score was observed in any of the arms after 24 weeks of intervention. Liver stiffness measurement improved significantly after 24 weeks of intervention in all 3 arms compared to baseline values ( Table III). Various secondary outcome measures including weight, body mass index, AST, ALT, controlled attenuation parameter and, APRI were significantly reduced from baseline across all 3 arms. Reductions in triglyceride levels were significant only in arm A and C; while arm B observed a slight increment in triglyceride level. Reductions in FIB-4 were significant only in arm B and C ( Table III). Magnitude of liver stiffness measurement reduction in arms A, B and C was 21%, 26 % and 10.8%, respectively. Magnitudes of AST and ALT reduction in arms A, B and C were 33.6 and 47.5 %, 22.2 and 34.1% and 31.8 and 27.1%, respectively. A significantly higher proportion of participants had at least 2 Kpa fall in liver stiffness measurement in arm A compared to arm C; however, these proportions were not significant between Arm A vs. B or B vs. C ( Table IV). Further, an analysis of the patients with baseline liver stiffness measurement ≥ 6.5 Kpa failed to demonstrate any significant change from baseline between 3 interventions for any of the primary or secondary outcome measures (Supplementary Table). None of the patients in any 3 arms reported any adverse or serious adverse events.
| Variables | A (Saroglitazar); N=46 | B (Vitamin E); N=47 | C (lifestyle intervention only); N=43 | P value |
|---|---|---|---|---|
| NAFLD fibrosis score* | 0.05±0.52 | 0.06±0.64 | -0.12±1.0 | 0.41 |
| Liver stiffness measurement# (KPa) | -1.25 (-2.6, -0.2) | -1.4 (-3.7, 0.4) | -0.7 (-1.8, -0.2) | 0.22 |
| Weight (kg)* | -2.5±3.6 | -1.31±2.6 | -1.72±2.6 | 0.17 |
| BMI (kg/m2)* | -0.84±1.2 | -0.46±0.9 | -0.62±0.96 | 0.23 |
| Serum AST# (<40 IU/L) | -15.1 (-36, -4) | -11.4 (-23.5, -3.4) | -11.2 (-31.4, -4) | 0.48 |
| Serum ALT# (<40 IU/L) | -38.7 (-71, -26.5) | -38 (-56.4, -11.0) | -35.5 (-57.8, -12.5) | 0.31 |
| Serum Triglycerides # (<150 g/dL) | -13.95 (-61, -18) | -4.3 (-28.8, 49) | -13 (-127, 3) | 0.035 |
| Controlled attenuation parameter* | -24.5±38.4 | -27.4±43 | -23.7±44.7 | 0.91 |
| FIB-4# | -0.007 (-0.28, 0.11) | -0.06 (-0.4, 0.09) | -1.0 (-0.34, 0.06) | 0.48 |
| APRI# | -0.17 (-0.55, - 0.05) | -0.21 (-0.5, -0.03) | -0.23 (-0.45, -0.04) | 0.96 |
*Parametric data (oneway ANOVA; mean±SD)
#Non-parametric data (Kruskal-Wallis test; median, IQR)
| Saroglitazar arm | Vitamin E arm | Lifestyle intervention only arm | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Variable | Pre (N=46) | Post (N=46) | P value | Pre (N=47) | Post (N=47) | P value | Pre (N=43) | Post (N=43) | P value |
| Weight (kg) | 79.99±12.20 | 77.55±12.19 | <0.001* | 75.00 (70-80) | 74.00 (70-79) | <0.001# | 76.36±12.01 | 74.65±11.86 | <0.001* |
| BMI (kg/m2)* | 27.79±3.33 | 26.95±3.55 | <0.0001 | 26.86±4.34 | 26.40±4.0 | <0.001 | 27.48±3.69 | 26.84±3.63 | <0.0001 |
| Serum AST (<40 IU/L) | 53.9 (42.89-72.50) | 35.75 (30.77-42.75) | <0.001# | 52.70 (41.00-73.30) | 41.00 (27.90-50.10) | <0.001# | 57.20 (40.00-80.20) | 39.00 (30.00-55.20) | <0.001# |
| Serum ALT (<40 IU/L) | 89.55 (69.35-127.47) | 47.00 (37.37-60.65) | <0.001# | 85.00 (73.00-114.20) | 56.00 (34.00-84.00) | <0.001# | 76.00 (61.10-132.80) | 55.40 (40.00-77.30) | <0.001# |
| Serum Triglycerides (<150 g/dL) | 178.85 (145.00-241.40) | 164.20 (117.60-214.50) | <0.028# | 180.00 (137.00-228.30) | 192.00 (132.41-230.30) | 0.90# | 203.30 (140.20-293.40) | 154.00 (125.30-211.00) | <0.001# |
| Liver stiffness measurement (KPa) | 6.70 (5.52-8.32) | 5.30 (4.9-6.45) | <0.001# | 7.30 (5.70-9.30) | 5.40 (4.50-6.90) | <0.001# | 6.5 (5.10-7.80) | 5.80 (4.90-6.70) | <0.001# |
| Controlled attenuation parameter | 304.02 ±36.29 | 279.47±43.61 | <0.001* | 299.00 (278.00-325.00) | 276.00 (244.00-300.00) | <0.001# | 300.46±50.63 | 276.72±45.93 | 0.001* |
| FIB-4 | 1.01 (0.75-1.40) | 0.93 (0.67-1.20) | 0.323# | 1.16 (0.81-1.56) | 1.08 (0.74-1.42) | 0.04# | 1.28 (0.80-1.81) | 0.98 (0.76-1.40) | 0.01# |
| APRI | 0.71 (0.54-1.05) | 0.49 (0.36-0.62) | 0.001# | 0.78 (0.67-1.13) | 0.60 (0.38-0.81) | <0.001# | 0.77 (0.61-1.14) | 0.55 (0.37-0.78) | <0.001# |
| NAFLD fibrosis score* | - 2.77±0.70 | -2.72±0.85 | 0.50* | -2.59±0.98 | -2.53±0.92 | 0.50* | -2.47±0.99 | -2.59±1.10 | 0.42* |
*Parametric data (Paired t-test; mean±SD)
#Non-parametric data (Wilcoxon-signed rank test; median, IQR)
| Arms | Proportions | Differences in proportions (95% Confidence interval) | P value |
|---|---|---|---|
| Arm A vs. B | 39% vs. 34% | 5.0 (-14, 23.76) | 0.61 |
| Arm A vs. C | 39% vs. 19% | 20.53 (1.53, 37.44) | 0.034 |
| Arm B vs. C | 34% vs. 19% | 15.44 (-2.93, 32.5) | 0.09 |
Discussion
Present study demonstrates that none of the primary outcome measures i.e. changes in NAFLD fibrosis score and liver stiffness measurement were different in either of the three treatment arms. Changes in secondary outcome measures were also statistically similar across 3 arms except significantly improved triglyceride levels in saroglitazar and lifestyle intervention only arms compared to vitamin E arm. To the best of our knowledge this is probably the first study to compare NAFLD fibrosis score, a non-invasive tool to assess fibrosis; after treatment with saroglitazar, vitamin E and lifestyle interventions in MASLD. Most of the secondary outcome measure changes were also similar across all 3 arms except triglyceride level. Present study demonstrates that all 3 interventions have ability to improve various non-invasive parameters assessed in MASLD with few exceptions.
Our results are consistent with the studies by Chaudhary et al16 and Goyal et al14 where saroglitazar significantly reduced liver stiffness measurement after 24 weeks of treatment (23% and 10.7%, respectively); however, lack of a control group in these studies poses a difficulty in interpretation. In our study, both vitamin E and Saroglitazar had better, but statistically non-significant reduction in liver stiffness measurement compared to ‘lifestyle interventions only’ at 24 weeks. In several studies, vitamin E 800 mg daily, given for varying duration of several weeks to several months has been associated with reduction in ALT and various inflammatory histology parameters. However, its effect on fibrosis is controversial. In a post-hoc analysis of PIVENS trial,17 at least 2 kg weight loss resulted in histological liver fibrosis improvement, both in vitamin E and placebo group.18 Similar weight loss was observed in the present study in 3 arms and explains significant within arm improvements in liver stiffness measurement. Findings in the present study are in line with a recent four arm trial where, neither saroglitazar nor vitamin E along with lifestyle interventions had a significant reduction in liver stiffness measurement after 24 weeks therapy when compared to lifestyle interventions alone.19 It is also emphasised here that a weight loss or inclusion of regular exercise is required to achieve fibrosis regression, as in previous studies.20,21 An interesting finding in the present study is that a higher proportion of participants had a marginal benefit of reduced liver stiffness measurement by at least 2 Kpa with saroglitazar (statistically significant) and vitamin E (statistically non-significant) vs. life style interventions only. Reductions in AST, ALT, triglyceride level and controlled attenuation parameter with 24 weeks of Saroglitazar treatment, in our study were similar to the studies by Goyal et al14 (58.4%, 58.5%, 48.4% and 23.6%, respectively) and Chaudhary et al16 (25%, 36.7%, 29.6% and 14.8%, respectively). Joshi22 reported a higher reduction in ALT (76.4%) and triglyceride (60%) after 24 weeks of Saroglitazar therapy. A subgroup analysis including patients with baseline liver stiffness measurement≥6.5 KPa also failed to find a significant difference between changes in NAFLD fibrosis score, liver stiffness measurement, weight, AST, ALT, FIB-4, triglyceride level, and controlled attenuation parameter between 3 arms. These findings suggest that within the arm differences in our study could have resulted primarily due to common intervention in all 3 arms i.e. lifestyle interventions.
An important strength of our study was inclusion of lifestyle interventions as an active arm with a patient reported adherence to it. Few limitations of our study can be highlighted as open label design, lack of objectivity to assess fibrosis (i.e. histological assessment for fibrosis), shorter duration of intervention, and lack of standardised lifestyle interventions and subjective assessment of patient reported compliance to it.
Based on these findings we conclude that adding saroglitazar or vitamin E to lifestyle interventions have similar effect compared to ‘lifestyle interventions only’ after 24 weeks of treatment in improving non-invasive parameters (including liver stiffness measurement) in patients with MASLD. Saroglitazar and vitamin E may have marginal benefit over lifestyle interventions in selected patients in reducing liver stiffness measurement, however, studies of prolonged duration are required to demonstrate additional benefit, if any.
Acknowledgment
Shri Anup Singh for data maintenance and follow up.
Author contributions
AKT: Conceived and designed the research, interpreted data, manuscript writing; GS: Conducted randomisation, collected data, manuscript writing; VK: Acquisition of data, manuscript writing; DPY: acquisition of data, manuscript writing; SKS: Methodology, monitoring of project progress; VS: data analysis, manuscript writing; GM: Randomisation; NKT: Interpreted data, statistical analysis; AA: Interpreted data, randomisation; DS: randomisation; DC: manuscript writing. All authors have read and approved the final printed version of the manuscript.
Financial support and sponsorship
The study received funding support from Intramural grant (No. 6031) from the Institution of Eminence, Banaras Hindu University, Varanasi, India.
Conflicts of Interest
None.
Use of Artificial Intelligence (AI)-Assisted Technology for manuscript preparation
The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.
References
- A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol.. 2023;79:1542-56.
- [CrossRef] [PubMed] [Google Scholar]
- Global incidence and prevalence of nonalcoholic fatty liver disease. Clin Mol Hepatol.. 2023;29:S32-4.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Nonalcoholic fatty liver disease: Indian perspective. Clin Liver Dis (Hoboken).. 2021;18:158-63.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A community-based study to determine the prevalence of nonalcoholic fatty liver disease (NAFLD) and its metabolic risk factors in urban and rural communities of North India. J Gastroenterol Hepatol.. 2019;34:310-10.
- [PubMed] [Google Scholar]
- The relationship between pathogenesis and possible treatments for the MASLD-cirrhosis spectrum. Int J Mol Sci.. 2024;25:4397.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Sustainability of diet-based moderate calorie restriction among obese patients with metabolic-associated fatty liver disease. Hepatol Forum.. 2021;2:97-101.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Adherence to mediterranean diet: Any association with NAFLD? Antioxidants (Basel). 2023;12:1318.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Mediterranean diet affects the metabolic outcome of metabolic dysfunction-associated fatty liver disease. Front Nutr.. 2023;10:1225946.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Effect of 5:2 intermittent fasting diet versus daily calorie restriction eating on metabolic-associated fatty liver disease-a randomized controlled trial. Front Nutr.. 2024;11:1439473.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Resmetirom: First approval. Drugs.. 2024;84:729-35.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Vitamin E as a treatment for nonalcoholic fatty liver disease: Reality or myth? Antioxidants (Basel) 2018. ;7:12.
- [Google Scholar]
- Effect of saroglitazar 2 mg and 4 mg on glycemic control, lipid profile and cardiovascular disease risk in patients with type 2 diabetes mellitus: A 56-week, randomized, double blind, phase 3 study (PRESS XII study) Cardiovasc Diabetol.. 2020;19:93.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- New dual peroxisome proliferator activated receptor agonist-Saroglitazar in diabetic dyslipidemia and non-alcoholic fatty liver disease: Integrated analysis of the real world evidence. Cardiovasc Diabetol.. 2019;18:80.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: A prospective, observational, real world study. Sci Rep.. 2020;10:21117.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Indian national association for study of the liver (INASL) guidance paper on nomenclature, diagnosis and treatment of nonalcoholic fatty liver disease (NAFLD) J Clin Exp Hepatol.. 2023;13:273-302.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Efficacy and safety of saroglitazar in real-world patients of non-alcoholic fatty liver disease with or without diabetes including compensated cirrhosis: A tertiary care center experience. JGH Open.. 2023;7:215-20.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Pioglitazone, vitamin e, or placebo for nonalcoholic steatohepatitis. N Engl J Med.. 2010;362:1675-85.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther.. 2013;38:134-43.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- A prospective randomised comparative four-arm intervention study of efficacy and safety of saroglitazar and vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-SVIN TRIAL. J Clin Exp Hepatol.. 2024;14:101398.
- [CrossRef] [PubMed] [PubMed Central] [Google Scholar]
- Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology.. 2015;149:367-78.
- [CrossRef] [PubMed] [Google Scholar]
- Total body weight loss of = 10% is associated with improved hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig Dis Sci.. 2015;60:1024-30.
- [CrossRef] [PubMed] [Google Scholar]
- Saroglitazar for the treatment of dyslipidemia in diabetic patients. Expert Opin Pharmacother.. 2015;16:597-606.
- [CrossRef] [PubMed] [Google Scholar]