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Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 116-121

Hepatic parasitic diseases − state of the art: Imaging study

Department of Radiology, Guangxi Medical University, Nanning, China

Date of Submission09-Apr-2021
Date of Acceptance04-Sep-2021
Date of Web Publication5-Apr-2022

Correspondence Address:
Dr. Jinyuan Liao
The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/RID.RID_27_21

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Parasites are an important cause of human diseases. With the increase in global population migration, the decline of population immunity, and changes in living habits, parasitic diseases have been increasing year by year. Because the liver has a unique blood supply system and a biliary system that communicates with the intestinal tract, it is relatively more vulnerable to a variety of parasitic infections. Imaging examinations play an important role in the early detection, characterization, evaluation, and treatment of hepatic parasitic diseases. Various imaging methods can not only detect hepatic parasitic diseases accurately but also evaluate liver injury, liver fibrosis, abnormal blood perfusion, metabolic changes, and malignant tumors caused by parasitic infection. Familiarity with the imaging features of hepatic parasitic diseases is helpful for the early diagnosis and treatment. This article reviews the progress in imaging research on common hepatic parasitic diseases.

Keywords: Imaging, liver, parasitic disease

How to cite this article:
Xiang Y, Li N, Liao J. Hepatic parasitic diseases − state of the art: Imaging study. Radiol Infect Dis 2021;8:116-21

How to cite this URL:
Xiang Y, Li N, Liao J. Hepatic parasitic diseases − state of the art: Imaging study. Radiol Infect Dis [serial online] 2021 [cited 2022 Sep 25];8:116-21. Available from: http://www.ridiseases.org/text.asp?2021/8/3/116/342621

  Pathological Basis of Common Hepatic Parasitic Diseases Top

Many kinds of parasitic liver diseases exist, and different parasitic diseases have specific epidemic areas and life histories. Their invasion routes, parasitic sites, and biological behaviors lead to liver lesions with different characteristics.

The liver has a dual blood supply. Echinococcosis, malaria, schistosomiasis, and amoebiasis are pathogens that flow into the liver through the portal vein, whereas clonorchiasis involves a parasite that invades the bile duct through the digestive tract. Fascioliasis is also an infection involving a parasite that penetrates into the abdominal cavity through the digestive tract, with the parasite penetrating the liver capsule into the liver parenchyma and bile duct.

After the parasite Echinococcus echinococcosis invades the liver, tissue destruction can lead to the formation of giant vesicles (hepatic cystic echinococcosis, [HCE]), and can also result in the formation of numerous small vesicles with a diameter of 0.1–1 cm, which proliferate by budding or infiltrating. Hepatic alveolar echinococcosis (HAE) can not only directly invade the adjacent tissue structure but can also have biological behavior similar to that of tumor. It can also be transferred to retroperitoneal and distant organs such as the brain and lungs through lymphatics and blood vessels.[1]

The liver damage caused by malaria parasites is mainly through damage to hepatocytes and erythrocytes, with red blood cells blocking liver capillaries and causing tissue ischemia and hypoxia, and immune responses mediated by cytotoxic T-cells and involving inflammatory cytokines, especially tumor necrosis factor α. The increase of free heme caused by intravascular hemolysis damages hepatocytes. The main pathological change to the liver caused by malaria is hepatocyte necrosis, with either focal or massive necrosis.[2],[3]

The eggs of schistosomiasis are deposited in the portal area and portal vein branches of the liver, resulting in granuloma formation and presinus hypertension and can cause liver cell compression, atrophy, and pathological changes to the portal area, resulting in hepatic fibrosis and portal hypertension, and eventually calcification.[4]

The liver damage caused by amoeba trophozoites involves liver necrosis caused by the dissolution of leukocytes and macrophages, and the release of toxic cytokines caused by the amoeba, resulting in a typical “chocolate abscess.”[5]

After Clonorchis sinensis enters the bile duct, various physical, chemical, and immune processes lead to bile duct epithelial adenomatoid hyperplasia, bile duct metaplasia, bile duct dilatation, inflammation and fibrosis around the bile duct, and atypical hyperplasia of bile duct and epithelial cells. Long-term infection can eventually lead to the occurrence of cholangiocarcinoma.[6]

After entering the liver parenchyma, the metacercariae of Fasciola hepatica wander randomly in the liver parenchyma and can cause inflammation, abscess formation, bleeding, necrosis, granulation tissue, and fibrosis.[7] After invading the bile duct, they can grow and lay eggs within it, which can cause bile duct obstruction and bile duct wall thickening.

  Imaging Study of Hepatic Parasitic Diseases Top


Ultrasound is considered to be the first choice for the diagnosis and screening of parasitic liver diseases because of its relatively low costs and noninvasive characteristics. Hepatic echinococcosis and amoebic liver abscess often show cystic or cystic and solid masses of the liver, with a well-defined round anechoic area. The manifestations of hepatic echinococcosis are various, with HCE having high specificity with the “blizzard sign,” “spoke wheel sign,” “water lily sign,” and “wool ball sign.” Most HAE lesions show as irregular and hyperechoic solid lesions on ultrasound, and irregular liquefaction, necrosis, and calcification may also be apparent. There is no capsule in the periphery of HAE, and it is therefore easy to confuse it with hepatic hemangioma and hepatocellular carcinoma on ultrasonography. Contrast-enhanced ultrasound (CEUS) can be used to differentiate HAE from intrahepatic cholangiocarcinoma. On CEUS, there is no contrast medium perfusion in HAE foci, and the lesions show signs of a “lack of blood supply.”[8]

On ultrasound, malaria-induced liver injury can manifest as enlargement of the liver, decreased echo, widening of the inner diameter of the portal vein, and increased blood flow (BF) velocity.[9]

Hepatic schistosomiasis shows a high echo pattern and tortoise shell-like features on ultrasound. Other signs include left hepatic lobe hypertrophy, right hepatic lobe atrophy, gall bladder wall thickening, granuloma, and splenic nodule formation. Color Doppler ultrasound can detect hepatic schistosomiasis, portal vein diameter widening, BF slow down, reverse, umbilical vein reopening, and esophagogastric varices.[10],[11]

Periportal fibrosis is a typical change caused by schistosomiasis, in which the thickened hyperechoic fibrous bands along the portal vein and its branches can be seen on ultrasound, and the concentric annulus around the portal vein can show “cow eye”-like changes on cross-sectional observation. This kind of peri-portal fibrosis can be qualitatively evaluated by image classification[12] or quantitatively measured according to the diameter of the tertiary portal vein.[13]

Clonorchiasis and fascioliasis can cause intrahepatic bile duct dilatation. Clonorchiasis is mainly characterized by “cystic and pestle” dilatation of Grade II and III bile ducts under the hepatic capsule, and it can also damage hepatic parenchyma. Tunnel-like changes in the liver parenchyma have certain characteristics.

Long-term infection with Schistosoma japonicum and C. sinensis can lead to liver fibrosis. Ultrasound elastography can be used to evaluate liver fibrosis noninvasively. Veiga[14] used transient elastography (TE) to evaluate liver and spleen hardness in patients with schistosomiasis and liver cirrhosis. The study found that liver hardness may be a useful tool to diagnose portal hypertension and hepatic schistosomiasis associated with liver cirrhosis. Gao[15] used TE to evaluate liver hardness in patients with clonorchiasis and suggested that liver hardness is high in patients with clonorchiasis, and therefore, TE can provide quantitative analysis of liver damage in patients with hepatic parasitic diseases, and can be used to evaluate the degree of liver fibrosis.

Computerized tomography

The computerized tomography (CT) findings of hepatic parasitic diseases are similar to those of ultrasound, but they are obtained with fast CT acquisition speed and high-density resolution. CT can comprehensively evaluate lesions and surrounding tissues, organs, and blood vessels and is more sensitive to calcification than ultrasound and magnetic resonance imaging (MRI). It can better identify and evaluate calcified foci caused by hepatic echinococcosis and hepatic schistosomiasis, and bile duct stones caused by clonorchiasis. Cystic hepatic echinococcosis may show partial or total calcification of the cyst wall, but partial calcification of the cyst does not indicate cyst death, although calcification of the cyst wall and central contents often does.[16] Computed tomography angiography can be used to evaluate the degree of compression of hepatic echinococcosis on adjacent organs, and the vessels invaded.

Amoeba trophozoites migrate from the intestinal tract to the liver through the portal vein circulation, which can cause venous thrombosis disrupting the blood supply to the liver, leading to ischemia or infarction. When amoeboid liver abscess is complicated by portal vein and hepatic vein thrombosis, it is often characterized by insufficient segmental portal vein perfusion. CT findings of venous thrombosis may indicate that the condition is serious and requires active treatment and percutaneous drainage.[17]

CT perfusion techniques can detect the microcirculation of HAE foci, and some studies have found strong correlations between BF, blood volume (BV), and microvessel density (MVD) in the area of the lesion.[18]

CT perfusion techniques can also be used to quantitatively evaluate HAE, and the CT perfusion parameters of the focus (BF, BV, artery liver perfusion, and portal liver perfusion) are typically lower than those of the background liver.[19] Liver perfusion parameters can also reflect the BF in the marginal zone of HAE, which is of importance for operative evaluation and prognostication in patients with echinococcosis.[20]

Jibo et al.,[21] found that with aggravation of the morphological grade of schistosomiasis cirrhosis, the liver perfusion values of BV and BF gradually decreased, while the values of mean transit time, hepatic artery flow, and hepatic artery perfusion gradually increased, indicating that CT perfusion imaging can be used as an important reference for evaluating the degree of schistosomiasis-related cirrhosis and liver reserve function.

Unlike traditional CT imaging, which can only show the shape and density of lesions, energy spectrum CT is a new functional imaging method that can display and quantitatively analyze specific substances.[22]

Energy spectrum CT can more safely show changes in blood supply by quantitatively measuring iodine parameters (Kev value, attenuation curve, and iodine concentration) of HAE foci. It has shown a strong correlation between the iodine concentration in the marginal area of HAE lesions measured by dual-energy CT and MVD in the enhanced CT portal venous phase. The iodine concentration in the marginal zone of HAE lesions is significantly higher than that of solid and cystic components, which indicates that the quantitative dual-energy CT iodine method can be used to evaluate the blood supply distribution of HAE lesions.[23]

Magnetic resonance imaging

MRI has the characteristics of high soft-tissue resolution and multi-functional sequences and is therefore widely used in liver diseases. The MRI findings of hepatic parasitic diseases are similar to those of ultrasound and CT. MRI has obvious advantages in display of the marginal infiltration zone, vesicles, and bile duct system of hepatic echinococcosis. It is the best imaging method to show cysts, matrix, echinococcosis (composed of free scolex fragments), and daughter cysts.[24]

Magnetic resonance cholangiopancreatography (MRCP) can show the relationship between the lesion and bile duct and the changes in the bile duct. It is sensitive to bile duct dilatation caused by C. sinensis and F. hepatica. MRCP can also show parasites located in distal bile duct or gallbladder, and fuzzy slender low-signal filling defects. Contrast-enhanced MRCP (CE-MRCP) is used to evaluate the biliary tract because of the high bile excretion rate of the hepatobiliary-specific contrast agent disodium gadolinium (Gd-EOB-DTPA).[25] Kulali et al.[26] evaluated the value of CE-MRCP and T2-HASTE sequences in the diagnosis of biliary communication in hydatid cysts. Their study found that disodium gadolinate leakage in hepatic hydatid cysts indicates biliary communication.

Diffusion-weighted MRI (DWI) can qualitatively and quantitatively evaluate the diffusion coefficient of protons in tissue water by the apparent diffusion coefficient (ADC). The marginal infiltration zone of HAE was poorly displayed on T1-weighted imaging, but it showed a continuous or discontinuous high-signal ring on T2-weighted imaging, and most of the upper marginal zone showed a continuous or discontinuous high-signal ring on DWI. Display of the marginal zone on DWI was clearer, more complete, and wider than on T2-weighted imaging. Some studies have found that the ADC value of HAE lesions is lower than that of other cystic liver lesions, which is helpful for their differential diagnosis, especially the exclusion of simple bile duct cysts and malignant lesions.[27]

Sade et al.,[28] compared the ADC values of HAE, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma and found that the average ADC value of the solid component of HAE was significantly higher than that of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which indicated that the ADC value was helpful for distinguishing between them.

MRI is very useful for differentiating alcoholic or virus-induced cirrhosis from chronic schistosomiasis, with the presence of peripheral periportal fibrosis, heterogeneity of hepatic parenchyma, splenic siderotic nodules, and the splenic index and caudate lobe-right lobe ratio being useful features.[29]

Some studies[27],[28],[30] have reported the value of intro voxel incoherent motion DWI (IVIM) and T1 mapping in the diagnosis of HAE. Their results showed that IVIM-derived parameters may be more suitable for evaluating the characteristics of HAE than T1 mapping, and that the f-value derived from IVIM may be a valuable index of HAE features.

Magnetic sensitivity-weighted imaging (SWI) is an MRI technique that can help to identify calcification or hemosiderin deposition. Mueller et al.[31] found that SWI was highly sensitive to calcification in hepatic echinococcosis. It can provide valuable information in the diagnosis of hepatic echinococcosis and avoid the requirement for additional CT scanning.

MR spectroscopy (MRS) is a noninvasive technique for detecting chemical changes in living tissues, and is also the only technique that can qualitatively and quantitatively evaluate metabolism in vivo.[32]

Pershina et al.[33] used in vivo MRI and MRS to identify and evaluate liver abnormalities caused by C. sinensis in an experimental animal model. They found a correlation between MRI results and histological and biochemical data of liver tissue. Analysis using 1H and 31P MRS combined with biochemical data showed that C. sinensis infection disturbed the metabolism of the host liver and resulted in cholesterol deposition. Therefore, MRS can noninvasively evaluate metabolic changes in the liver caused by C. sinensis infection.

Superparamagnetic iron oxide nanoparticles (SPIO-Eh) can be used to label parasites. Ernst[34] infected mice with SPIO-Eh-labeled Entamoeba histolytica and performed MRI examinations to qualitatively and quantitatively evaluate the distribution of SPIO-Eh in mouse liver. This study demonstrated the feasibility of effective magnetic labeling and noninvasive MR tracking of amoeboid histolytica in a living mouse model. Thus, SPIO-Eh can provide a noninvasive imaging tool for the study of parasites and host-specific pathological mechanisms in the future.

Nuclear medicine

Fluorodeoxyglucose positron emission tomography (FDG-PET) is currently considered to be the only noninvasive tool for detecting metabolic activity.[35] FDG-PET can directly display the boundary of HAE foci, analyze the radioactive uptake and concentration of HAE foci, and evaluate the efficacy of drugs in the treatment of HAE foci.[36] One study found that FDG-PET was better than CT on the assessment of disease activity in alveolar echinococcosis.[37] Some studies[36],[38] found a significant negative correlation between the ADC value of DWI and the PET-measured maximum standardized uptake value of HAE lesions. This finding suggests that DWI, like PET-CT, may provide information for the evaluation of metabolic activity in patients with HAE. PET-MRI can provide similar metabolic activity diagnostic information for the treatment of HAE. Compared with PET/CT, the reduced radiation exposure may be particularly important for children and young patients who are not suitable for therapeutic surgery and need to undergo dual-imaging modalities for the long-term follow-up. Further research is needed to prospectively evaluate the potential of PET/MRI in HAE.[39]

Applications of artificial intelligence in liver parasitic diseases

Convolution neural networks are widely used in computer vision tasks because of their strong feature extraction ability and have achieved remarkable success in classification, detection, and segmentation tasks.[40],[41],[42]

The classification of hepatic echinococcosis depends mainly on the subjective judgment of imaging doctors, and the process is time-consuming and misjudgment can easily occur. Xin et al.[43] proposed an automatic segmentation and classification network for echinococcosis based on CT images, which included lesion localization and lesion segmentation modules. The network can help doctors accurately locate hepatic echinococcosis, determine its size and boundary, and determine the type of hepatic echinococcosis. Finally, the accuracy of diagnosis and the chance of successful treatment were improved.

The prediction of malaria-potential genes by a network-based clustering method can be used to identify disease phenotypes and treatment options for malaria, to reduce malaria-related mortality.[44],[45] Machine learning techniques can be successfully used to rapidly diagnose and predict malaria using patient information.[46] A back-propagation neural network (BPNN) was used to further classify cellular granuloma, fibrous cell granuloma, and fibrous granuloma of chronic hepatic schistosomiasis. The results showed that the accuracy of a BPNN was as high as 98.3%, and that it provided valuable results for the early prediction of schistosomiasis and liver fibrosis.[47]

All of these studies show that artificial intelligence has high potential and application value in the diagnosis, classification, and prognosis of parasitic diseases of the liver.

  Summary Top

Imaging plays an important role in the discovery, diagnosis, treatment, and prognosis of hepatic parasitic diseases. Functional imaging techniques, such as ultrasonic elastography, CT perfusion imaging, and energy spectrum CT bring more information for showing the morphology of hepatic parasitic diseases, hemodynamic changes, liver hardness, and substance content. Although CT presents a risk from ionizing radiation, it is superior to other imaging methods in showing hepatic parasitosis calcification, which is common in parasitic diseases and is related to the progression and prognosis of the disease. MRI has the advantages of multi-parameter imaging, no ionizing radiation, perfusion weighted imaging, DWI, MRS, and SWI sequences, and the use of new contrast agents to obtain more pathophysiological information. PET-CT/MRI has unique advantages for observing tissue metabolism. The comprehensive application of a variety of imaging techniques is of great help in the diagnosis, curative-effect evaluation, and prognosis of parasitic diseases of the liver, from gross morphology to the molecular level. In addition, the rise of artificial intelligence and imaging science is expected to provide more auxiliary diagnosis and decision support for parasitic diseases of the liver.

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Conflicts of interest

There are no conflicts of interest.

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