Gray matter alterations and neurotransmitter system associations in hepatitis B virus-related cirrhosis: insights into neuropathogenesis and therapeutic targets.

Introduction: The associations between gray matter (GM) change and neurotransmitter systems in hepatitis B virus-related cirrhosis (HBV-RC) are still poorly understood.

Methods: We recruited 60 HBV-RC patients and 60 healthy controls (HCs). Difference of GM volume between HBV-RC and HC groups was evaluated at global and voxel levels. The potential relationship between GM morphology and prognostic models of liver function was evaluated at voxel level in HBV-RC patients. The spatial correspondence between regional GM alteration and the distribution of multiple neurotransmitter systems in HBV-RC compared to healthy controls was assessed by the JuSpace toolbox covering various neurotransmitter maps.

Results: Total GM volume in HBV-RC group was smaller than in HC group (p < 0.05), and the pattern of GM volume alterations showed significantly increased volume in bilateral thalamus and ventral diencephalon and decreased volume in bilateral basal ganglia and cerebellum (p < 0.05, FWE corrected). In HBV-RC group, the volume of left superior frontal gyrus medial segment and right middle frontal gyrus was positively correlated with serum albumin level and negatively correlated with ALBI score, and serum bilirubin level was negatively correlated with right hippocampus and caudate (p < 0.05, FWE corrected). GM alterations in HBV-RC patients relative to HCs were significantly associated with the intrinsic distribution of various neurotransmitter pathways, including GABAergic, cholinergic, serotonergic, and dopaminergic (p < 0.05).

Conclusion: The pattern of GM alteration correlated with liver function and specific neurotransmitter deficits in HBV-RC patients. These findings provide new insight into the complex neuropathogenesis of HBV-RC and the possible therapeutic targets based on neurotransmitter modulation.