The Sponge Hypothesis of Sarcopenia: Functional Hyponatremia and the Liver-Muscle-Fluid Axis in Chronic Liver Disease

Background & AimsDilutional hyponatremia and sarcopenia (SP) are prognostic factors linked to portal hypertension (PHT) in chronic liver disease (CLD). Because skeletal muscle functions as the bodys largest intracellular water reservoir, early Na decline may reflect impaired muscular buffering rather than renal Na loss. This MRIbased study investigated the relationship between serum Na, SP, and PHT. MethodsWe retrospectively analyzed 880 CLD patients who underwent MR elastography. SP was defined as low muscle mass by MRI. Patients were categorized into five Na strata (<135, 135-136, 137-138, 139-140, [&ge;]141 mEq/L). Individuals with Na <139 mEq/L were further stratified by ALBI score and SP to construct the liver-muscle phenotype (LMP) classification. ResultsSP prevalence was 28% and increased stepwise with decreasing Na levels. In non-HCC patients, Na <139 mEq/L optimally identified both SP and PHT. Liver stiffness increased progressively across SP, Na <139, and PHT (3.3[-&gt;]4.6 kPa, all P<0.01). Decision-tree analysis identified ALBI score (cutoff -2.16) and SP as major determinants of Na <139, producing four LMP types with graded Na decline (P<0.01). Among advanced CLD patients without ascites, worsening LMP predicted higher incidence of new-onset ascites (P<0.01). In Cox models, LMP4 (ALBI [&ge;]-2.16 with SP) independently predicted poor prognosis (HR 3.87, P<0.01). ConclusionsFunctional hyponatremia (Na <139) reflects early hemodynamic stress associated with asymptomatic PHT. Given its central role in systemic water handling, distinct from the hepato-renal axis, SP may represent a modifiable target for early intervention before overt decompensation. Key PointsO_ST_ABSSignificant findings of the studyC_ST_ABSO_LIFunctional hyponatremia (Na <139 mEq/L) and sarcopenia emerge at nearly identical liver stiffness thresholds, preceding classical portal hypertension. C_LIO_LIThe novel Liver-Muscle Phenotype (LMP) classification identifies a high-risk group (LMP4) for fluid retention that is often underestimated by conventional MELD scores. C_LI What this study addsO_LIEarly sodium dilution and muscle loss reflect impaired buffering by skeletal muscle--the bodys largest intracellular water reservoir--within the liver-muscle-fluid axis. C_LIO_LISarcopenia defines a reversible therapeutic window in which targeted nutrition and rehabilitation may restore fluid balance before overt retention develops. C_LI