Comparative efficacy of febuxostat and vitamin E in the management of MASLD: Insights from a randomized parallel clinical study.

2025-08
European journal of pharmacology 1000
- Hadier El-Sheikh
- Sahar El-Haggar
- Rehab Badawi
- Eslam Habba

PubMed: 40383220
DOI: 10.1016/j.ejphar.2025.177735

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 32
Population: 64 MASLD patients
Methods: divided into two groups: 32 patients received 80 mg of febuxostat daily, while the other 32 patients received 400 mg of vitamin E twice daily for 24 weeks
Blinding: Open-label
Duration: 24 weeks
Funding: Unclear

Aim

We aimed to determine whether inhibiting xanthine oxidase (XO) activity and NLRP-3 activation in the liver with febuxostat could influence the progression of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

Sixty-four MASLD patients were divided into two groups: 32 patients received 80 mg of febuxostat daily, while the other 32 patients received 400 mg of vitamin E twice daily for 24 weeks. A gastroenterologist assessed the degree of steatosis using Fibroscan and controlled attenuation parameter (CAP) measurements at baseline and after six months. Additionally, hepatic steatosis index (HSI), HAIR-score, and levels of NLRP-3, TIM-3, HOMA-IR, MDA, uric acid, lipid profile, and liver function tests were measured before and after treatment.

Results

Improvement in steatosis was observed in 50 % of febuxostat group and 46.9 % of vitamin E group. Both groups showed a significant reduction in CAP scores, with more pronounced decrease in vitamin E group (p < 0.001) compared to febuxostat group (p = 0.001). Febuxostat group exhibited significantly lower levels of NLRP-3, MDA, TIM-3, and uric acid compared to vitamin E group. HSI, HAIR score, and liver functions improved similarly in both groups.

Conclusion

Febuxostat appears to be effective in reducing steatosis in MASLD patients, suggesting its potential as a treatment option for non-cirrhotic MASLD.

Clinicaltrials

gov identifier is NCT05574036, Registered October 6, 2022 - Retrospectively.

Research Insights

Vitamin E→Improved Hair Score
HSI, HAIR score, and liver functions improved similarly in both groups.
Effect
Beneficial
Effect size
Small
Dose
400 mg twice daily
Vitamin E→Improved Hepatic Steatosis Index
HSI, HAIR score, and liver functions improved similarly in both groups.
Effect
Beneficial
Effect size
Small
Dose
400 mg twice daily
Vitamin E→Improved Liver Function
HSI, HAIR score, and liver functions improved similarly in both groups.
Effect
Beneficial
Effect size
Small
Dose
400 mg twice daily
Vitamin E→Reduced Controlled Attenuation Parameter Score
Both groups showed a significant reduction in CAP scores, with more pronounced decrease in vitamin E group (p < 0.001) compared to febuxostat group (p = 0.001).
Effect
Beneficial
Effect size
Large
Dose
400 mg twice daily
Vitamin E→Reduced Malondialdehyde Level
Febuxostat group exhibited significantly lower levels of NLRP-3, MDA, TIM-3, and uric acid compared to vitamin E group.
Effect
Neutral
Effect size
Small
Dose
400 mg twice daily
Vitamin E→Reduced NLRP-3 Level
Febuxostat group exhibited significantly lower levels of NLRP-3, MDA, TIM-3, and uric acid compared to vitamin E group.
Effect
Neutral
Effect size
Small
Dose
400 mg twice daily
Vitamin E→Reduced Steatosis
Improvement in steatosis was observed in ... 46.9 % of vitamin E group.
Effect
Beneficial
Effect size
Moderate
Dose
400 mg twice daily
Vitamin E→Reduced TIM-3 Level
Febuxostat group exhibited significantly lower levels of NLRP-3, MDA, TIM-3, and uric acid compared to vitamin E group.
Effect
Neutral
Effect size
Small
Dose
400 mg twice daily
Vitamin E→Reduced Uric Acid Levels
Febuxostat group exhibited significantly lower levels of NLRP-3, MDA, TIM-3, and uric acid compared to vitamin E group.
Effect
Neutral
Effect size
Small
Dose
400 mg twice daily