Publication Name	World Journal of Hepatology
Manuscript ID	124519
DOI	10.4254/wjh.124519
Country	Russia

Category	Gastroenterology & Hepatology
Manuscript Type	Review
Article Title	Hyperammonemia as a potential contributor to fatigue in metabolic dysfunction-associated steatotic liver disease: A mechanistic review
Manuscript Source	Invited Manuscript
All Author List	Anna F Sheptulina, Julia A Golubeva, Diana L Valeeva, Anton R Kiselev and Oksana M Drapkina
Funding Agency and Grant Number	Funding Agency Grant Number Scientific Work of National Medical Research Center for Therapy and Preventive Medicine According to the State Assignment of the Ministry of Health of the Russian Federation 126020116173-4 (2026-2028)
Corresponding Author	Anton R Kiselev, Head, Professor, Coordinating Center for Fundamental Research, National Medical Research Center for Therapy and Preventive Medicine, Petroverigsky per., 10, str. 3, Moscow 101990, Moskva, Russia. antonkis@list.ru
Key Words	Metabolic dysfunction-associated steatotic liver disease; Hyperammonemia; Fatigue; Urea cycle; Sarcopenia; Mediterranean diet; Physical activity
Core Tip	Hyperammonemia may develop in precirrhotic metabolic dysfunction-associated steatotic liver disease (MASLD) as a consequence of impaired ureagenesis associated with reduced expression and activity of urea cycle enzymes, together with alterations in glutamine metabolism. Current evidence suggests that ammonia may contribute to both central and peripheral fatigue through interconnected mechanisms involving neuroinflammation, impaired neurotransmission, mitochondrial dysfunction, oxidative stress, and skeletal muscle impairment. However, most available evidence originates from experimental studies, whereas direct clinical evidence in patients with MASLD remains limited. Although dietary factors, skeletal muscle status, and physical activity may influence ammonia homeostasis, their specific role in hyperammonemia in MASLD remains uncertain and should be regarded as hypothesis-generating. A better understanding of ammonia metabolism may facilitate the development of targeted strategies for fatigue management in MASLD.
Citation	Sheptulina AF, Golubeva JA, Valeeva DL, Kiselev AR, Drapkina OM. Hyperammonemia as a potential contributor to fatigue in metabolic dysfunction-associated steatotic liver disease: A mechanistic review. World J Hepatol 2026; In press DOI: https://doi.org/10.4254/wjh.124519
PDF	124519-in-press.pdf

Received	2026-06-17 02:17
Peer-Review Started	2026-06-17 02:18
First Decision by Editorial Office Director
Return for Revision	2026-07-20 06:40
Revised	2026-07-29 19:12
Publication Fee Transferred
Second Decision by Editor	2026-09-10 02:43
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-09-10 10:05
Articles in Press	2026-09-10 10:05
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5182 (online)
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