Periarterial nerves along the human hepatic artery: anatomical determinants for cardiometabolic neuromodulation

Preclinical and early clinical studies suggest that catheter-based hepatic artery denervation is a neuromodulation strategy with potential relevance for blood pressure and cardiometabolic regulation, but high-resolution human data on nerves along the hepatic arterial course remain limited. This study aimed to characterize periarterial nerves along the human hepatic artery and to identify anatomically favorable target regions for catheter-based denervation. Hepatic arteries with surrounding tissue were excised from 10 human donors. Immunofluorescence staining was used to assess periarterial nerve density and diameter. A total of 13,165 nerves were analyzed. Median nerve diameter decreased from 93 µm [IQR 54-165] at 1 cm to 72 µm [IQR 48-120] at 7 cm distal to the coeliac trunk (p < 0.001). The largest nerves were predominantly located in the posterior and inferior quadrants, with median diameters of 85 µm [IQR 48-176] and 85 µm [IQR 48-158], respectively. Mean nerve density was significantly higher in proximal (1-3 cm) than distal (4-7 cm) segments (233 ± 124 vs. 159 ± 76 nerves/cm², p < 0.001). Lumen-nerve distance was significantly shorter in proximal than distal segments (2.03 mm [IQR 1.23-3.58] vs. 2.57 mm [IQR 1.26-4.67], p < 0.001) and was shortest in the anterior quadrant (1.75 mm [IQR 1.10-3.23], p < 0.001). Thus, proximal hepatic artery segments are characterized by larger nerve diameters, higher nerve density, and shorter lumen-nerve distances than distal segments. These anatomical findings identify a potentially favorable target zone and may help guide the safe and effective application of hepatic denervation in humans. Size and distribution of periarterial hepatic artery nerves across segments. Plots show the proportion of nerves located within <2, <4, <6, <8, and <10 mm from the arterial lumen, and the distribution of nerve diameters across predefined size categories (<50 µm, 50-69 µm, 70-89 µm, 90-110 µm, and >110 µm). Colors indicate the corresponding nerve size categories, and quadrants are indicated.