Malnutrition in MASLD-related hepatocellular carcinoma: assessment limitations, multidimensional mechanisms, and microbiome-based interventions

Abstract

With the rapid rise in hepatocellular carcinoma (HCC) incidence associated with metabolic dysfunction-associated steatotic liver disease (MASLD), malnutrition has emerged as a critical comorbidity that affects treatment tolerance and survival outcomes. This review systematically examines the challenges of assessing malnutrition in metabolic dysfunction-associated steatotic liver disease-related hepatocellular carcinoma (MASLD-HCC), its multidimensional pathological mechanisms, and emerging intervention strategies. In current clinical practice, the absence of specialized assessment tools limits the effectiveness of existing evaluation systems in addressing distinct phenotypes, such as obesity and ascites. The underlying mechanisms are complex; disruptions of the “gut-liver-muscle axis”, centered on intestinal dysbiosis, form a key network driving metabolic reprogramming, chronic inflammation, and muscle wasting. Regarding interventions, microbiome-targeted therapies - including fecal microbiota transplantation and probiotics/synbiotics - have shown promise in preclinical studies for modulating immunometabolism and improving nutritional status. However, their translation into routine clinical practice remains constrained by major bottlenecks, including insufficient large-scale randomized controlled trial evidence, uncertainty regarding long-term safety, and inadequate standardization. Future efforts should urgently focus on establishing precise assessment systems and conducting high-quality clinical validation.

Keywords

Hepatocellular carcinoma / MASLD-HCC / malnutrition assessment / gut-liver-muscle axis / microbiome-targeted therapy

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