Preliminary evidence of improved liver biomarkers in adolescents with obesity and suspected metabolic dysfunction‐associated steatotic liver disease treated with semaglutide: A case series

Abstract

Metabolic dysfunction‐associated steatotic liver disease (MASLD) affects 30%–40% of youth with obesity and lacks approved pharmacologic therapies. In this single‐center retrospective case series at a tertiary care safety‐net children's hospital, we evaluated five adolescents (mean age: 17.0 years; 100% Hispanic; 60% male; mean body mass index: 50.8 kg/m²) treated with semaglutide for ≥3 months. Baseline liver enzymes and fibrosis marker (mean ± standard deviation) included alanine aminotransferase (ALT): 107.4 ± 26.8 IU/L, aspartate aminotransferase (AST): 64.6 ± 16.2 IU/L, and AST to platelet ratio index (APRI): 0.41 ± 0.07. After treatment, values decreased to ALT: 69.0 ± 17.9 IU/L, AST: 43.6 ± 8.8 IU/L, and APRI: 0.28 ± 0.05. Reduction in ALT (p < 0.01), AST (p < 0.01) and APRI (p = 0.01) were all statistically significant. These findings suggest semaglutide may improve hepatic inflammation and fibrosis in adolescents with MASLD. Larger prospective studies are needed to confirm these early signals in high‐risk pediatric populations.

What is Known

• Metabolic dysfunction–associated steatotic liver disease (MASLD) is the primary cause of liver disease in the United States.

• Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have demonstrated efficacy in adults for obesity and MASLD.

What is New

• We found a statistically significant reduction in alanine aminotransferase (ALT) levels aspartate aminotransferase (AST) levels and AST to platelet ratio index (APRI) before and after treatment with a GLP‐1RA in adolescents with MASLD.

• GLP‐1RAs may reduce hepatic inflammation and fibrosis in adolescents with MASLD.

1. INTRODUCTION

Obesity affects over 14 million youth in the United States, with 30%–40% developing metabolic dysfunction–associated steatotic liver disease (MASLD). ¹ , ² , ³ MASLD is defined by ≥5% hepatic steatosis in the presence of at least one metabolic risk factor (e.g., obesity, insulin resistance, hypertension, or dyslipidemia), and is now the leading cause of pediatric liver disease. ¹ , ² , ³ , ⁴ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly used noninvasive indicators of hepatic inflammation. ¹ , ² , ³ , ⁴ Current first‐line treatment involves lifestyle modifications targeting diet and physical activity. However, evidence shows that these strategies alone result in limited MASLD resolution in youth. ¹ , ² , ³ , ⁴

Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), such as semaglutide and liraglutide, have demonstrated efficacy in adults for obesity and MASLD. These agents mimic endogenous GLP‐1, enhancing insulin secretion, suppressing glucagon, delaying gastric emptying, and reducing appetite. ¹ , ⁵ A randomized controlled trial of 1197 adults with metabolic dysfunction‐associated steatohepatitis (MASH) and liver fibrosis found semaglutide significantly improved histologic resolution of MASH versus placebo. ⁵ Similarly, liraglutide showed histologic improvement in a study of 52 adults with nonalcoholic steatohepatitis (NASH). ⁶ On August 15, 2025, the Federal Drug Administration (FDA) approved an additional indication for Wegovy® (semaglutide 2.4 mg once‑weekly injection) for the treatment of non‑cirrhotic MASH in adults with moderate to advanced fibrosis (stage F2–F3) in combination with diet and increased physical activity.

Despite the promising adult data, pediatric studies remain sparse. A retrospective analysis at Children's Healthcare of Atlanta (CHOA) found that GLP‐1RA therapy in youth with elevated alanine transaminase (ALT) reduced levels by an average of 98 IU/L. ⁷ A similar study at Children's Hospital of Philadelphia (CHOP) reported a 23 IU/L reduction in ALT after 6 months of treatment. ⁸ Given the growing off‐label use of GLP‐1RAs in adolescents and young adults with obesity and potential liver disease, we aimed to assess changes in liver inflammation and fibrosis in youth following semaglutide initiation using noninvasive laboratory markers (AST and ALT) and the AST to platelet ratio index (APRI).

2. METHODS

The objective of this study was to assess changes in liver inflammation (ALT and AST) and a fibrosis marker (APRI) in adolescents with obesity following treatment with the GLP‐1RA semaglutide.

2.1. Ethics statement

It was a single‐center, retrospective chart review conducted at the Children's Hospital Los Angeles (CHLA) and approved by the CHLA Institutional Review Board (IRB# [CHLA‐22‐00119]).

2.2. Patient identification and data collection

A query was performed using the electronic medical record to identify all patients seen in the Obesity Clinic between January 1, 2022, and January 1, 2024, who were prescribed semaglutide. The initial dataset included demographic data, medication orders, encounter notes, and laboratory values. Two independent reviewers (R.S. and K.F.) screened the records to determine eligibility and extract relevant clinical data. Discrepancies in abstraction were resolved by consensus or a third reviewer.

2.3. Inclusion criteria

Patients were eligible for inclusion if they were between the ages of 12 and 21 years at the time of semaglutide initiation and carried a clinical diagnosis of obesity, defined either by a body mass index at or above the 95th percentile for age and sex or a body mass index (BMI) of 30 kg per square meter or higher. Eligible participants must have been prescribed semaglutide and used it consistently for a minimum duration of 3 months, as confirmed through clinical documentation and pharmacy records. In addition, all patients were required to have undergone an abdominal ultrasound demonstrating hepatic steatosis prior to or around the time of semaglutide initiation. Laboratory data—specifically ALT, AST, and platelet counts—must have been available both prior to treatment (within 3 months of initiation) and after treatment, with post‐treatment labs drawn at least 12 weeks following the start of therapy.

2.4. Exclusion criteria

Patients were excluded if they had a diagnosis of type 1 or type 2 diabetes mellitus. Individuals with type 2 diabetes were excluded specifically to isolate the effects of semaglutide on liver biomarkers in the absence of concomitant glucose‐lowering medications or baseline hyperglycemia, both of which could confound the interpretation of liver‐related outcomes. Additional exclusion criteria included the presence of any underlying liver disease other than MASLD or MASH, such as autoimmune hepatitis, viral hepatitis, Wilson's disease, or alpha‐1 antitrypsin deficiency. Patients with genetic or syndromic forms of obesity, including those with Prader‐Willi syndrome or chromosomal abnormalities, were also excluded. Other exclusion criteria included endocrinopathies such as panhypopituitarism or growth hormone deficiency, a history of bariatric surgery, concurrent use of other pharmacologic weight‐loss treatments, or the presence of an active malignancy or chronic inflammatory disease.

2.5. Outcome measures

The primary outcome was change in liver inflammation, measured by ALT and AST levels. The secondary outcome was change in estimated liver fibrosis, assessed using APRI, calculated as:

APRI = (AST (IU/L)/AST ULN (IU/L)) × 100 ÷ Platelet count (10⁹/L) where ULN refers to the upper limit of normal for AST, standardized at 40 IU/L. APRI, although validated in adults, has shown moderate utility in pediatric MASLD (AUC ~ 0.65) and was selected due to its availability in routine labs. ⁹ We acknowledge its limited sensitivity for advanced fibrosis in youth and emphasize this in our discussion.

2.6. Statistical analysis

Descriptive statistics were used to summarize patient characteristics. Paired t‐tests were conducted to compare pre‐ and posttreatment values of ALT, AST, and APRI. A p‐value of <0.05 was considered statistically significant. All statistical analyses were performed using R Studio (Version 2022.12.0 + 353 [2022.12.0 + 353]).

3. RESULTS

A total of 517 patients were identified as having been prescribed semaglutide between January 2022 and January 2024. Following manual review and application of inclusion and exclusion criteria, five patients (1%) met eligibility requirements for the current study. Reasons for exclusion included type 1 or type 2 diabetes (n = 132), insufficient duration of semaglutide use (n = 186), missing relevant laboratory data (n = 121), use of other weight‐loss medications (n = 43), history of bariatric surgery (n = 16), and other exclusionary diagnoses such as genetic or endocrine disorders (n = 14).

3.1. Patient characteristics

The final analytic sample included five adolescents with obesity who received semaglutide for ≥3 months. The mean age at the time of semaglutide initiation was 17.0 years (range: 16–18), and the mean baseline body mass index (BMI) was 50.8 kg/m² (range: 41–68). All patients self‐identified as Latino, and three of the five participants (60%) were male.

3.2. Laboratory outcomes

Markers of liver inflammation and fibrosis were assessed using ALT, AST, and APRI. Baseline mean (±SD) ALT, AST, and APRI values were 107.4 ± 26.8 IU/L, 64.6 ± 16.2 IU/L, and 0.41 ± 0.07, respectively. Following semaglutide treatment, mean ALT decreased to 69.0 ± 17.9 IU/L, AST to 43.6 ± 8.8 IU/L, and APRI to 0.28 ± 0.05 (Table 1). Change in BMI from baseline to last measurement available are shown in Table 1. Paired t‐tests comparing pre‐ and posttreatment values demonstrated a statistically significant reduction in ALT levels (mean difference: −38.4 IU/L; p < 0.01), AST (mean difference: −21.0 IU/L; p < 0.01) and APRI (mean difference: −0.13; p = 0.01), suggesting potential clinical benefit. Individual changes in liver biomarkers are shown in Figure 1, illustrating consistent directional improvement across all participants.

Table 1.

Clinical and laboratory characteristics of adolescents treated with semaglutide.

Patient ID	Age (years)	Sex	Ethnicity	Race	Baseline BMI (kg/m²)	BMI at stop of GLP‐1	% BMI change	Semaglutide duration (weeks)	Baseline ultrasound	MRI elastography	Baseline ALT (IU/L)	Follow‐up ALT (IU/L)	Baseline AST (IU/L)	Follow‐up AST (IU/L)	Baseline APRI	Follow‐up APRI
001	17	Male	Hispanic	Mixed	68	62	8.8	14	Hepatic steatosis	Not available	72	44	43	32	0.39	0.35
002	16	Female	Hispanic	Mixed	44	43	2.3	12	Hepatic steatosis	Not available	98	62	59	40	0.36	0.25
003	18	Female	Hispanic	Mixed	49	42	14.2	16	Hepatic steatosis	Not available	146	92	88	55	0.52	0.30
004	17	Male	Hispanic	Mixed	41	36	12.2	18	Hepatic steatosis	Liver Fat Fraction: Mean 17% Liver Stiffness: Mean 1.92 kPa	114	78	66	49	0.43	0.27
005	17	Male	Hispanic	Mixed	52	48	7.7	15	Hepatic steatosis	Liver Fat Fraction: Mean 22.34% Liver Stiffness: Mean 1.72 kPa	107	69	67	42	0.34	0.23

Note: APRI calculated using the formula: ([AST/AST ULN]/Platelet count) × 100, where AST ULN = 40 IU/L.

Abbreviations: ALT, alanine aminotransferase; APRI, AST to platelet ratio index; AST, aspartate aminotransferase; BMI, body mass index; GLP‐1, glucagon‐like‐peptide‐1; MRI, magnetic resonance imaging.

Figure 1.

Change in ALT, AST, and APRI, levels before and after 3–7 months of GLP‐1RA treatment in adolescents with obesity. ALT, alanine aminotransferase; APRI, AST to platelet ratio index; AST, aspartate aminotransferase; GLP‐1RA, Glucagon‐like peptide‐1 receptor agonist.

3.3. Adverse events and treatment persistence

No serious adverse events were observed in our cohort, and all patients remained on therapy throughout the observation period (see Table 1 for exact timing of treatment course by youth). Minor side effects, primarily gastrointestinal in nature, were self‐limited and did not require dose reduction or discontinuation in any of the young people.

4. DISCUSSION

Our study builds on prior pediatric studies by presenting semaglutide‐specific liver outcome data—including APRI—for adolescents with obesity and MASLD. It is the first to detail individual patient characteristics and fibrosis markers in a homogenous, high‐risk Latino cohort. While our cohort was ethnically homogenous (100% Latino), this reflects a population disproportionately affected by MASLD and with limited representation in pediatric liver disease trials. ¹⁰ These findings align with emerging evidence suggesting that GLP‐1RAs may improve markers of liver inflammation and early fibrosis in youth, as has been more robustly demonstrated in adult populations. ⁴ , ⁵

The recent FDA approval of semaglutide (2.4 mg weekly) for the treatment of non‐cirrhotic MASH with moderate to advanced fibrosis (F2–F3) in adults with obesity underscores the therapeutic potential of GLP‐1RAs in managing liver disease associated with metabolic dysfunction. ¹¹ This approval, based on results from the phase 3 ESSENCE trial, demonstrated that semaglutide significantly improved liver histology, with 63% of participants achieving resolution of steatohepatitis without worsening of fibrosis, and 37% showing fibrosis improvement without worsening of steatohepatitis after 72 weeks of treatment. ⁵ While these findings support semaglutide's efficacy in adults, pediatric data remain scarce. In this retrospective case series, semaglutide use for ≥3 months was associated with clinically significant reductions in liver enzymes and APRI, a noninvasive marker of fibrosis. Specifically, mean ALT decreased by 38.4 IU/L (p < 0.01), mean AST decreased by 21.0 IU/L (p < 0.01), and mean APRI decreased by 0.128 (p = 0.01). Importantly, no serious adverse events were observed in our cohort, and all patients remained on therapy throughout the treatment period. Mild gastrointestinal symptoms were reported but were self‐limited and did not necessitate dose reduction or discontinuation. These observations are consistent with prior pediatric studies of semaglutide, in which nausea, vomiting, and abdominal discomfort have been the most commonly reported adverse effects, with low rates of discontinuation due to side effects. These early findings, though limited by small sample size, align directionally with adult data and suggest that semaglutide may hold promise for improving liver health in adolescents with obesity and metabolic liver disease. These patterns mirror findings from previous pediatric studies at CHOA and CHOP, which demonstrated reductions in ALT following GLP‐1RA therapy in youth with obesity, diabetes, or pre‐diabetes. ⁶ , ⁷ Further prospective pediatric studies are warranted to evaluate long‐term histologic outcomes, optimal treatment duration, and safety in this population. ³ , ¹⁰

This study is not without limitations. The small sample size, due to stringent eligibility criteria, limits the generalizability of our findings and precludes more sophisticated multivariate analysis. Additionally, the reliance on laboratory markers (ALT, AST, and APRI) rather than imaging or histologic data limits our ability to definitively assess liver fibrosis or steatohepatitis resolution. While APRI has shown moderate utility in pediatric MASLD with an AUC of 0.65 for predicting liver stiffness, ⁹ it is not a substitute for magnetic resonance elastography or liver biopsy, which remain the gold standards for evaluating fibrosis and histologic improvement. ³

Despite these limitations, our findings support the feasibility and potential effectiveness of semaglutide as a therapeutic option for adolescents with MASLD. As there are currently no FDA‐approved pharmacologic treatments for MASLD in the pediatric population, our results emphasize the urgent need for larger, prospective trials evaluating semaglutide and other GLP‐1RAs in this context. Future studies should include validated imaging modalities (e.g., elastography, magnetic resonance imaging proton density fat fraction) or liver biopsy endpoints to more accurately assess hepatic outcomes, as well as racially and ethnically diverse populations to enhance generalizability.

5. CONCLUSION

In conclusion, our preliminary findings suggest that semaglutide may reduce hepatic inflammation and fibrosis and potentially improve liver health in adolescents with MASLD. The use of semaglutide also appeared to be safe in our patient population as no significant adverse events were experienced. While additional research is required, GLP‐1RAs represent a promising therapeutic avenue in a field with limited treatment options and a rising burden of disease.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

Schenker R, Fomenko K, Mitsinikos FT, Vidmar AP. Preliminary evidence of improved liver biomarkers in adolescents with obesity and suspected metabolic dysfunction‐associated steatotic liver disease treated with semaglutide: a case series. JPGN Rep. 2026;7:349‐354. 10.1002/jpr3.70131

DATA AVAILABILITY STATEMENT

The datasets from this study will be available from the corresponding author on written request. The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author upon reasonable request.