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Page 6 of 8 Li et al. Metab Target Organ Damage. 2025;5:19 https://dx.doi.org/10.20517/mtod.2025.05

Moving forward, robust, multicenter collaborations will be pivotal for generating consensus on clinical
endpoints, bridging methodological discrepancies, and establishing universally accepted treatment
algorithms. Integration of big data analytics, coupled with machine learning techniques, may further refine
patient stratification and illuminate novel, sex-specific targets amenable to OCM-based interventions.
Ultimately, these interdisciplinary efforts stand to elevate MASLD management, opening new avenues not
only for preventing advanced disease but also for mitigating the oncogenic potential associated with
MASLD over the long term.

BEYOND THE SCALPEL: METABOLIC AND PRECISION MEDICINE INSIGHTS
In recent years, PLC has come to be recognized as a systemic metabolic disease rather than a strictly
localized malignancy. From an anatomical perspective, the liver functions as the central hub of whole-body
metabolism, and recurrence or metastasis - rather than merely the primary tumor load - remains a leading
[25]
cause of mortality in PLC . Concurrently, tumorigenesis in PLC is fundamentally driven by metabolic
reprogramming , signifying that no extent of local surgical excision can wholly resolve this global
[26]
metabolic disorder. Given that MASLD is an established risk factor for PLC, and in light of the promising
implications of the OCM-Hcy-MASLD axis, there is a need for a comprehensive treatment paradigm that
addresses the metabolic underpinnings of disease. However, it is important to note that the current evidence
on the role of OCM in hepatocarcinogenesis is still limited, and further research is needed to fully
understand its impact on PLC development and progression.

Revisiting oncological priorities in MASLD-related PLC
MASLD-associated hepatic dysfunction presents unique surgical challenges, particularly regarding
compromised hepatic reserve and altered regenerative capacity. Current evidence suggests R0 resection
should be balanced with functional preservation , especially given the increased perioperative risks in
[27]
metabolically compromised patients. Emerging data indicate that preoperative metabolic optimization may
improve surgical tolerance, though specific protocols require further validation.

Incorporating the OCM-Hcy pathway into full-cycle intervention
The OCM-Hcy axis represents one of several metabolic pathways implicated in MASLD progression. While
Suzuki et al.’s modeling provides theoretical support for cofactor supplementation, clinical translation
[2]
requires rigorous validation . Current evidence supports considering metabolic status during surgical
planning rather than implementing specific OCM-targeted protocols.

Refining perioperative management in metabolically at-risk patients
Recent studies have emphasized the need for comprehensive metabolic assessment in patients with MASLD
undergoing hepatectomy, and the study by Lopez-Pascual et al. has created a new way to develop
perioperative management strategies for patients with MASLD from the perspective of nanomaterials .
[28]
Sex-specific metabolic changes merit consideration but should not override established perioperative
protocols.

Anticipating future directions for MASLD-related PLC management
Therapeutic interventions targeting metabolic pathways, such as the OCM-Hcy-MASLD axis, may reduce
perioperative risks. For patients with MASLD-related PLC, leveraging this axis through targeted
pharmacotherapy - e.g., Hcy-lowering agents and metabolic regulators - could disrupt tumor-promoting
processes while simultaneously improving hepatic reserve. Moreover, integrating these regimens with
minimally invasive surgical approaches has the potential to minimize postoperative morbidity, especially in
individuals burdened by obesity or other metabolic derangements.