Sympathetic and Vagal Distribution in Hepatic Alveolar Echinococcosis and Its Clinical Correlation

Acta Parasitologica (2026) 71:102 https://doi.org/10.1007/s11686-026-01261-w RESEARCH Sympathetic and Vagal Distribution in Hepatic Alveolar Echinococcosis and Its Clinical Correlation Rongdong He1,2 · Zongding Wang1,3,4 · Zhihao Song1,2 · Lijiao Li5 · Li Sun1 · Hao Wen1,2 Received: 31 October 2025 / Accepted: 24 February 2026 © The Author(s) 2026 Abstract Introduction To explore the distribution characteristics of sympathetic and vagal nerves in hepatic alveolar echinococcosis (AE). By analyzing pathological specimens from patients, we focused on the differential distribution of nerves in lesions, perilesional zones, and normal liver tissues and revealed their correlation with clinical local staging, hepatic fibrosis and regenerative processes. Methods Pathological specimens from 74 patients diagnosed with hepatic AE were analyzed. The differential distribution of sympathetic and vagal nerves was examined in three distinct tissue regions: the central lesion, the perilesional zone, and distal normal liver tissue. The correlation between the percentage of sympathetic nerve positivity and clinical local stage, fibrosis, and cell proliferation was statistically analyzed. Results The analysis revealed a marked hyperplasia of sympathetic nerves specifically within the lesion and the perilesional zone, whereas no significant changes were observed in the normal liver tissues. The distribution of vagal nerves showed no significant variation across all regions. The density of sympathetic nerves demonstrated a positive correlation with the clinical local staging of the disease. Histopathological examination confirmed multiple round lesions with fibrous encapsulation and prominent inflammatory cell infiltration in the perilesional zone. Furthermore, sympathetic nerve hyperplasia was significantly correlated with the degree of fibrosis in both the lesion and perilesional zone. The density of sympathetic nerves in the perilesional zone was also positively associated with local inflammatory cell proliferation. Conclusion Sympathetic nerves, but not vagal nerves, exhibit significant hyperplasia within and around hepatic AE lesions. The density of these sympathetic nerves is strongly correlated with disease progression, the extent of fibrosis, and local cellular proliferation. These findings suggest that sympathetic nerves may play a key role in the pathological remodeling and progression of hepatic AE. Keywords Hepatic alveolar echinococcosis · Sympathetic nerves · Vagus nerve · Clinical local staging · Hepatic fibrosis · Cell proliferation Rongdong He and Zongding Wang contributed equally to this work. 2 Li Sun Department of Hepatobiliary & Hydatid Disease, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China 3 Hao Wen Department of Hepatobiliary Surgery, Fengjie County People’s Hospital of Chongqing, Fengjie 404600, China 4 State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, 137 Liyushan South Road, Urumqi 830054, Xinjiang, China Department of Hepatobiliary Surgery, Fengjie Hospital, The Second Affiliated Hospital of Chongqing Medical University, Fengjie 404600, China 5 Department of Nephrology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China Rongdong He 1 13 102 Page 2 of 11 Acta Parasitologica Abbreviations AE Alveolar echinococcosis CE Cystic echinococcosis HE Hematoxylin–eosin TH Tyrosine hydroxylase PGP9.5 Protein gene product 9.5 GAP43 Growth associated protein 43 VAChT Vesicular acetylcholine transporter PCNA Proliferating cell nuclear antigen α-SMA Alpha-smooth muscle actin PET-CT Positron emission tomography-computed tomography Introduction Echinococcosis is a severe zoonotic parasitic disease caused by infections with Echinococcus granulosus and Echinococcus multilocularis, leading to cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively [1, 2]. This disease is primarily prevalent in livestock-intensive regions such as Western China, Central Asia and South Asia. It is mainly transmitted through the fecal–oral route, poses a significant threat to human health, and remains a major public health issue [3–5]. After completing its life cycle in the intestines of the definitive host, Echinococcus multilocularis gravid proglottids continuously release infective eggs into the environment through feces. When an intermediate host inadvertently ingests contaminated eggs, the oncospheres hatch in the duodenum and penetrate the intestinal mucosal barrier, preferentially localizing to the liver parenchyma via the portal venous system. Some larvae can disseminate through the Table 1 Clinical data of study subjects Characteristics Male Female Age(years) 0–20 20–40 40–60 > 60 Stage(P) P1 P2 P3 P4 History of hepatectomy First Second History of viral hepatitis B No Yes 13 Cases(%) 37(50%) 37(50%) 11(14.9%) 35(47.3%) 21(28.4%) 7(9.5%) 7(9.5%) 22(29.7%) 25(33.8%) 20(27%) 57(77%) 17(23%) 69(93.2%) 5(6.8%) (2026) 71:102 bloodstream, affecting extrahepatic organs such as the brain, lungs, and skeletal system [6–8]. The liver is the primary target organ in AE and is characterized by the accumulation of vesicles of varying sizes, with a hard texture, significant fibrosis, and aggressive growth that poorly delineates the boundary with surrounding tissues [9]. AE often metastasizes distantly via the lymphatic or vascular routes, and its growth pattern resembles that of malignant tumors, earning it the term “worm cancer” [10]. The liver is an organ with rich neural innervation [11], and hepatic malignancies are often associated with sympathetic nerve proliferation in both the tumor and surrounding tissues [12, 13]. AE lesions exhibit local invasiveness and distant metastasis similar to malignant tumors; however, there is currently no research on the distribution characteristics of vagal and sympathetic nerve fibers in liver AE lesions. Therefore, this study systematically investigates the distribution patterns of autonomic nerves in surgically resected liver AE specimens diagnosed pathologically, and explores the correlation between these patterns and local staging, fibrosis, and liver regeneration through histological analysis. Materials and Methods Ethical Statement The study design adhereds to the principles outlined in the Declaration of Helsinki [14]. This retrospective observational study was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (No. 20200116-04), and written informed consent was obtained from all participants or their guardians. Inclusion and Exclusion Criteria A total of 74 AE patients at different stages were selected from the First Affiliated Hospital of Xinjiang Medical University. These patients were diagnosed and staged based on preoperative clinical diagnosis and surgical pathology. Basic info (...truncated)