The onset of AE is insidious and often lacks typical clinical manifestations, making clinical diagnosis challenging. When multiple organ lesions occur, it further increases the difficulty of diagnosis and treatment. Understanding the presence or absence of extrahepatic metastasis, as well as the location and extent of metastasis, is of great significance for selecting a reasonable treatment plan 8. Brain involvement resulting from AE is rare (1%) and usually manifests as focal neurological deficits and increased intracranial pressure 9. The mortality and recurrence rate of CAE are high, and the treatment results for CAE are not ideal 6. Therefore, identifying factors that affect HAE brain metastasis is crucial to reduce the difficulty of treatment and improve the prognosis of patients. This study analyzed the clinical indicators of HAE and CT imaging signs, revealing that the presence of inferior vena cava invasion, hepatic artery invasion, and metastasis to other organs are independent risk factors for predicting brain metastasis of HAE. A logistic regression model was constructed based on these risk factors and displayed in the form of a nomogram. The aim is to identify potential risk factors for brain metastasis early, quantitatively, visually, and non-invasively, and to provide a basis for formulating reasonable treatment plans and assessing the prognosis for HAE patients.
3.1. Correlation between imaging characteristics and clinical indicators of HAE and brain metastasis
In recent years, some scholars have studied the correlation between extrahepatic invasion and metastasis of HAE and imaging characteristics of the primary lesion 4,10, but there have been no reports on the study of predicting HAE brain metastasis alone. This study found, through univariate analysis, that the diameter of the lesion, whether it is enhanced, and the treatment method are related to HAE brain metastasis. This may be because patients with larger lesions tend to be in the late stage, and brain involvement is usually considered to have developed to the late stage of the disease 6. The larger the HAE lesion, the more likely it is to undergo extrahepatic metastasis, which is consistent with the study by Tilmann G et al. 11. During the enhanced scan, it was found that the edge zone of the lesion was significantly enhanced, indicating that HAE is in the active phase at this time and has a strong invasive ability. Radical liver resection is the gold standard for the treatment of HAE and the only possible method to achieve a final cure. For severely ill patients whose lesions exceed the resectable level or patients with decompensated liver function caused by HAE, liver transplantation is the only possible way to achieve survival and cure 12,13. However, conservative treatment cannot completely remove the active part of the lesion, which may continue to invade outwards and cause metastasis. Therefore, reasonable HAE treatment methods are very important. However, the differences in these influencing factors were not statistically significant in multivariate analysis, which may be related to the small sample size of this study.
While HAE erodes the liver parenchyma, it can also affect the vascular system of the liver. Studies have shown that angiogenesis occurs at the edge of HAE lesions 14. The walls of new capillaries are weak, lack a muscle layer, and the basement membrane is often incomplete, making it easier for alveolar echinococcosis to invade new blood vessels and metastasize. Studies by some scholars have shown that more than one-third of HAE patients will experience vascular stenosis or invasion 15, and veins are more susceptible to invasion, mainly because the vein walls are thin and the venous lumen is larger than the arterial lumen 16.The specific location of HAE invasion of the inferior vena cava varies. The posterior hepatic segment of the inferior vena cava between the left atrium and the right renal vein is the main affected site 17. Imaging can accurately evaluate the invasion of liver blood vessels 18. It is reported that inferior vena cava angiography shows that the collateral vessels of the vertebral venous plexus are mainly intraspinal veins that ascend along the spinal canal. This pathway is crucial for communication between the superior and inferior vena cava, as well as intracranial and extracranial connections. Due to its lack of venous valves and extensive communication branches with other venous plexuses (intracranial venous sinuses, thoracic, abdominal, and pelvic venous plexuses), it holds important physiological and clinical significance for the spread of infection, tumor metastasis, and the formation of collateral circulation 19-21. In the study by Jiang TM et al. 17, it was pointed out that HAE invades the inferior vena cava, causing it to form collateral vessels, which may be a neglected pathway for HAE to transfer to the brain. Our study found that invasion of the inferior vena cava is an independent risk factor for predicting brain metastasis in HAE, consistent with previous studies. In addition to invading veins, HAE can also invade arteries. The study by Yang XF et al. 22 indicated that the incidence of arterial involvement in HAE lesions is 26.87%. Due to the larger size of arteries compared to veins, with more smooth muscle and elastic fibers in the vascular wall, arteries are less susceptible to invasion compared to veins. Our study found that invasion of the hepatic artery is an independent risk factor for HAE brain metastasis. We speculate that this may be because the wall of the hepatic artery is thicker, and the lumen is narrower. When invaded, the lesions often progress to an advanced stage, and brain metastasis is relatively more likely to occur in the late stage. This further illustrates that hepatic artery invasion is an indirect sign of brain metastasis.
HAE reproduces through exophytic budding, growing into the surrounding liver parenchyma to form new vesicle structures. The vesicles contain cyst fluid, which continuously extravasates into the surrounding tissues through the incomplete cyst wall, and infiltrates outward continuously. The exogenous vesicle structure of HAE budding can invade blood vessels and lymphatic vessels, and then metastasize to distant sites 23,24. Distant metastasis of HAE mainly spreads through the blood circulation, and some adjacent organs can be affected by direct invasion 25,26. The proliferative buds of the cystic coccoides fall off and spread through the blood. They can be transferred to any part of the body to parasitize and form granulomas. The most common metastasis is to the lungs, followed by the brain 8,27. Our study found that patients with metastasis to other organs are often accompanied by brain metastasis and are the strongest independent predictors of brain metastasis. This may be because when HAE enters the bloodstream through the liver blood vessels, it can reach various organs throughout the body through the blood circulation, leading to the possibility of lesions appearing in multiple organs simultaneously.
3.2 Clinical application value of HAE brain metastasis nomogram prediction model
The nomogram is a visual tool used to optimize statistical models. It provides patients with personalized and accurate risk assessment, integrates multiple predictive factors to improve the readability of research results, and has been widely used in clinical practice 28-30. This study analyzed the imaging characteristics of primary HAE lesions and incorporated clinical indicators into the construction of the model to improve the efficiency of the prediction model. Through multivariate logistic regression analysis, three main independent risk factors for HAE brain metastasis were identified: the presence of inferior vena cava invasion, hepatic artery invasion, and metastasis to other organs. Based on these independent risk factors, a prediction model for HAE brain metastasis was constructed and presented in the form of a nomogram. Drawing the ROC curve revealed that the AUC value of the nomogram in the training set was 0.922, indicating high prediction performance. Further evaluation and analysis through the calibration curve showed that the predicted values were highly consistent with the measured values, indicating that the nomogram achieved the goal of better predicting HAE brain metastasis. These results were further confirmed in the validation set. The clinical application value of the nomogram was verified through decision curve analysis. The results showed that within a certain range, using the nomogram to predict HAE brain metastasis will yield more benefits, proving that this nomogram has good clinical application value. It enables the clinical non-invasive identification of potential risk factors for brain metastasis of HAE, thereby allowing the formulation of individualized treatment plans to maximize patient benefit.
3.3 limitation
Our study has certain limitations. Firstly, this study is a retrospective, single-center study, and there is a certain sample selection bias. Secondly, the sample size included in this study is not large enough, and more studies need to be conducted in a larger population. Clinical studies will be undertaken to verify the results. Additionally, radiologists may manually interpret the films to obtain image features, introducing some potential subjective errors. In subsequent studies, radiomics and other data will be incorporated to strive for unearthing more valuable information.
In summary, the nomogram prediction model of HAE brain metastasis constructed in this study, based on imaging characteristics and clinical indicators, can effectively assist clinicians in predicting the risk of HAE brain metastasis. It is expected to help clinicians formulate reasonable treatment plans and assess patient prognosis, contributing to the realization of individualized and precise medical decisions.