Intrahepatic manifestation and distant extrahepatic disease in alveolar echinococcosis: a multicenter cohort study

Abstract

Background

The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE.

Purpose

To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China.

Material and Methods

Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama’s classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion.

Results

Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher’s exact test: P=0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ² = 11.92; P = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P<0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations.

Conclusion

Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Keywords

Alveolar echinococcosis Echinococcus multilocularis Kodama classification magnetic resonance imaging vascular/biliary involvement extrahepatic manifestation

Introduction

Human alveolar echinococcosis (AE) is a rare malignant parasitic disease resulting from infection with the larval stage of Echinococcus multilocularis (1). Because of frequent exogenous tumor-like proliferation and destructive growth, AE resembles a malignant tumor in behavior and appearance, and can lead to infiltration of affected organs and to severe disease and even death (2). AE has become a serious global problem, occurring in moderate to cold climate zones in the northern hemispheres (3).

Imaging tools such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and 18F fluorodeoxyglucose (FDG)-positron emission tomography (PET) are used to diagnose AE lesions, combined with results of immunodiagnosis (specific serology), histology and epidemiological findings (4 –8). CT scans can reveal shape, number, size, and location of lesions more accurately than ultrasound and also demonstrates the typical calcifications most clearly (9). MRI best captures the structural alveolar characteristics. In 2003, Kodama et al. (6) classified the image morphological characteristics of AE lesions for MRI by describing small and large cysts and solid components (Table 1). Combined with CT or MRI, FDG-PET can be used to evaluate local inflammatory activity of the lesion. Absence of metabolic activity, however, does not necessarily mean that the parasite is non-viable and may indicate suppressed immune defenses (10). The diagnosis of AE remains challenging. Delayed diagnosis significantly limits treatment options (11).

Table 1.

Description of Kodama’s classification by MRI of AE (6).

Kodama type	Description
I	Multiple small round cysts without a solid component
II	Multiple small round cysts with a solid component
III	A solid component surrounding large and/or irregular cysts with multiple small round cysts
IV	A solid component without cysts
V	A large cyst without a solid component

AE, alveolar echinococcosis.

The liver usually is the first organ affected by larval infestation. A manifestation outside the liver without liver involvement is rare (12). HAE can affect intrahepatic blood vessels and bile ducts. With involvement of such structures in the hilum, a radical resection is difficult or impossible. In the literature, hepatobiliary complications in AE are reported with an incidence of 10%–30% (13 –17). Vascular complications include Budd–Chiari and vena cava syndromes (18 –21). Hepatobiliary infiltrations can lead to serious complications and therefore can have a lasting effect on the further course of the disease (11,13).

This multicenter study was based in two Chinese and two European (German and French) university clinics, which are international leaders in research and treatment of AE. These centers, located in AE-endemic areas, carried out the Xining-Urumqi-Ulm-Besançon (XUUB) imaging project.

The aim of the present study was to assess the vascular/biliary involvement and the distant extrahepatic disease manifestations of the different cases in a collective of 200 German, French, and Chinese patients with HAE on the basis of MRI Kodama’s classification concerning the AE liver lesions. The present study is the first to compare cases from four different centers located in three countries and in an intercontinental context with regard to the present questions.

Material and Methods

Ethics statement

For German patients, the study was approved by the local ethics committee and conducted in accordance with the Declaration of Helsinki (ref. no. 409/15). Because of its retrospective design and pseudonymized evaluation of imaging, no ethics approval was necessary for France and China. All data were analyzed anonymously.

Inclusion and exclusion criteria

The following inclusion criteria were defined. Retrospectively, we included the 50 most recent abdominal gadolinium contrast-enhanced MRI examinations at each of the four centers (n=200), performed because of hepatic AE from 27 September 2004 to 5 April 2018. The number of cases was estimated after consultation with the respective countries involved and the number of MRI examinations in recent months. The previous clinical and imaging morphological findings had to have been classified as confirmed AE according to Brunetti et al.’s case definition (2). Antibody status, possible subsequent therapeutic strategies, and socioeconomic factors were not considered in the inclusion criteria.

Examination and classification

Kodama’s classification provides a scheme for classifying the very different morphological appearances of HAE lesions on the basis of T2-weighted (T2W) MRI sequences (6). The classification of all HAE cases according to Kodama’s classification was carried out by the first reader during 9–14 April 2018. The first reader was the most experienced colleague in the study group who had previously worked the most with Kodama’s classification in a clinical and scientific context. A T2 sequence was used to classify the lesions. The largest lesion within a liver was used to determine the morphological type after Kodama et al., and all further evaluations in the present study reference these. The lesion size was measured during the first joint evaluation in consensus with all readers involved in T1-weighted (T1W) contrast-enhanced sequence, transverse sections. A local experienced radiologist at each of the four centers became the second reader for their own 50 cases and independently reclassified the local cases. Criteria concerning the classification of the lesions, as well as further technical and disease-related information, were collected on a detailed report form. In addition to the essential patient data (sex and age), technical information included the basic technical modality of the MRI scan. The following MRI scanners were used in the different centers: 3.0 T Achieva, Philips Healthcare, Amsterdam, the Netherlands (Xining); 1.5 T Avanto, Siemens Healthcare, Erlangen, Germany (Urumqi); 3.0 T Skyra and 1.5 T Avanto, Siemens Healthcare, Erlangen, Germany (Ulm); and 3.0 T Signa HDx, GE Healthcare, Chicago, USA (Besançon)

Disease-related information included the affected hepatic lobes and a detailed listing of the liver segments involved, as well as the number of lesions, any vascular/biliary involvement, and the overall dimension of the biggest lesion. The evaluation regarding vascular/biliary involvement of the liver lesions was based on a detailed joint case discussion and the consensus of all five readers, all experienced radiologists. The involvement of large central or medium-sized peripheral portal venous, venous, or arterial vessel sections and a central or peripheral cholestasis (peripheral bile ducts >2 mm) caused by lesions was evaluated using a gadolinium contrast-enhanced T1 sequence. Vascular infiltration was defined as a morphologically recognizable vascular lumen infiltration, vascular occlusion followed by an uncontrasted vessel, or an associated thrombosis. From an anatomical point of view, this association points to an involvement of the jointly running portal biliary and vascular structures. The criteria for vascular and biliary involvement were therefore considered to be common criteria.

Whether a distant extrahepatic disease manifestation was present was determined retrospectively based on respective whole-body staging examinations. Whole-body examinations were carried out as part of the initial staging, before the start of therapy. The different centers occasionally handled these differently, depending on local conditions and practices. In Ulm and Besançon, whole-body imaging was performed during a PET-CT examination. In the two Chinese centers, where no PET-CT examinations were performed, the chest was examined using CT and the cranium was examined using complementary MRI, assessing the corresponding clinical symptoms. All distant extrahepatic manifestations were histologically confirmed as AE.

Solely accentuated but well-circumscribed lymph nodes without infiltrating aspects were not evaluated as extrahepatic manifestations. Furthermore, the direct infiltration of organs adjacent to the liver or an infiltration of parahepatic connective tissue or diaphragm, respectively, through the liver lesion was also not evaluated as a separate (metastasis-like) extrahepatic manifestation. For further calculations concerning extrahepatic disease manifestations, these cases were not included unless distant extrahepatic manifestations were simultaneously recorded, but they were documented separately. These features had the following distribution: lymph nodes (n = 2, 4.00%); diaphragm (n = 3, 6.00%); retroperitoneum close to the liver (n = 5, 10.00%); right adrenal gland (n = 4, 8.00%); and mediastinum/pericardium/right atrium (n = 2, 4.00%). Within those cases, simultaneous distant extrahepatic manifestations were recorded for both cases with accentuated lymph nodes, for one case with mediastinal and another case with retroperitoneal infiltration, and for one of the four cases with infiltration of the right adrenal gland.

The presence of vascular/biliary involvement by the AE liver lesion as well as of distant extrahepatic disease manifestations was finally associated with the presented Kodama classification and size of liver lesion.

Statistical analysis

We performed statistical analyses using SAS Version 9.4 (SAS Institute Inc., Cary, NC, USA). Descriptive analysis of the data was performed to obtain absolute and relative frequencies, as well as measures of central tendency and dispersion. Pearson’s χ² and Fisher’s exact test were used to determine possible relationships and differences in the frequency distribution between dichotomous variables. Differences in mean values were determined with the single factor analysis of variance (ANOVA). Inter-rater reliability between reader 1 and reader 2 was determined by kappa coefficients. The level of significance was set at α = 0.05, and a P value < 0.05 was considered to be statistically significant with a 5% probability of error.

Results

Sex proportion, age, inter-rater reliability, and distribution of Kodama types

In the overall collective (n = 200), 52% were women (mean age = 47.08 ± 18.63 years, age range = 11–89 years). The Fleiss kappa inter-rater reliability for reporting the findings using Kodama’s classification was 0.96 (95% confidence interval [CI] = 0.93–0.99). The distribution of the Kodama types of the different centers is shown in Table 2. If, in view of the different intercontinental distribution pattern, the frequencies of types I–II and III–V are dichotomized, a significant difference between Europe and China is noticeable 42/100 vs. 17/100 (χ² = 15.03, P = 0.0001).

Table 2.

Types of liver lesions classified according to Kodama’s classification.

Kodama type	XUUB total (n = 200)	Xining (n = 50)	Urumqi (n = 50)	Ulm (n = 50)	Besançon (n = 50)	Europe (n = 100)	China (n = 100)
I	7 (3.50)	0 (0.00)	2 (4.00)	5 (10.00)	0 (0,00)	5 (5.00)	2 (2.00)
II	52 (26.00)	9 (18.00)	6 (12.00)	22 (44.00)	15 (30.00)	37 (37.00)	15 (15.00)
III	117 (58.50)	31 (62.00)	37 (74.00)	22 (44.00)	27 (54.00)	49 (49.00)	68 (68.00)
IV	14 (7.00%)	8 (16.00)	1 (2.00)	1 (2.00)	4 (8.00)	5 (5.00)	9 (9.00)
V	10 (5.00)	2 (4.00)	4 (8.00)	0 (0.00)	4 (8.00)	4 (4.00)	6 (6.00)

Values are given as n (%).

XUUB, Xining-Urumqi-Ulm-Besançon.

Localization and size of the liver infestation

Involvement of the right hepatic lobe was present in 79%, which is also reflected in similar values in the intercontinental comparison of 71% for Europe and 87% for China. For the total collective, segment VIII, which is centrally located on the right hepatic side, was most frequently involved, occurring in 54.50%. The mean lesion size of the largest liver lesion was 95.49 ± 50.94 mm (median = 88 mm, range = 10–258 mm).

Distribution of extrahepatic manifestations

Distant extrahepatic manifestations were rather rare in the total collective, occurring in 15/200 (7.50%) patients. Table 3 provides an overview of the localization of the respective distant extrahepatic manifestations. However, Europe and China differed significantly in rates of these features, with 3/100 (3%) cases in Europe compared to 12/100 (12%) in China (Fisher’s exact test: P=0.0286) (Table 4). In the Chinese group, the presence of a distant extrahepatic manifestation was approximately balanced, with 5 (10.00%) cases in Urumqi and 7 (14.00%) cases in Xining. The three cases (6.00%) in Europe were all from the German data, with no cases recorded in the French collective.

Table 3.

Patients with distant extrahepatic disease manifestation from AE (n = 15).

Patient	Sex	Age (years)	Center	Kodama type (liver)	Involved organs (distant extrahepatic)
1	M	36	Ulm	II	Lumbal spine with infiltration of M. psoas
2	M	70	Ulm	III	Lung
3	F	59	Ulm	III	Lung
4	M	55	Urumqi	III	Lung
5	M	49	Urumqi	III	Lung
6	M	52	Urumqi	III	Retroperitoneal (distant from liver)
7	M	30	Urumqi	III	Lung
8	F	44	Urumqi	III	Lung
9	F	32	Xining	IV	Lung
10	F	51	Xining	III	Lung
11	F	30	Xining	V	Brain, lung
12	M	17	Xining	III	Lung
13	M	29	Xining	III	Brain, lung
14	M	50	Xining	III	Brain, lung
15	M	49	Xining	III	Lung

AE, alveolar echinococcosis; M, male; F, female.

Table 4.

Vascular and biliary involvement and extrahepatic manifestations in Europe and China.

	Extrahepatic manifestation	No extrahepatic manifestation	P
Europe (n = 100)	3 (3)	97 (97)	0.0286
China (n = 100)	12 (12)	88 (88)	0.0286

	Vascular and biliary involvement	No vascular and biliary involvement
Europe (n = 100)	65 (65)	35 (35)	0.0006
China (n = 100)	86 (86)	14 (14)	0.0006

Values are given as n (%).

Association of extrahepatic manifestations with lesion sizes and Kodama types

We identified a significant difference between the presence and absence of distant extrahepatic disease and the size of the liver lesion, for the total dataset (132.53 ± 48.65 vs. 92.49 ± 50.06, P = 0.0030). Overall, distant extrahepatic manifestations were significantly more common in larger lesions of the liver (Fig. 1).

Fig. 1.

Measure of dispersion for liver lesion sizes stratified according to extrahepatic manifestation in China vs. Europe. P < 0.05 was evaluated as statistically significant.

With respect to the Kodama types of liver lesions, type I was not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types II–V were found to varying degrees, with a maximum of 12/117 (10.26%) for type III. In contrast, types II (1/52, 1.92%), IV (1/14, 7.14%), and V (1/10, 10.00%) were represented with only one case of extrahepatic involvement each. Figure 2 shows two cases of hepatic AE, each with an associated extrahepatic manifestation.

Fig. 2.

Two cases of hepatic AE, each with an associated extrahepatic manifestation. (a, b) Case 1: (a) MRI, T2W. Hepatic AE lesion (Kodama type II); (b) MRI, T1W, contrast-enhanced. Extrahepatic AE manifestation of lumbal spine and infiltration of right psoas muscle. The white arrows demonstrate the respective lesion boundaries. (c, d) Case 2: (c) MRI, T2W. Hepatic AE lesion (Kodama type III); (d) CT scan of the lung. Extrahepatic AE manifestation with multiple pulmonary nodules. The white arrows demonstrate the respective lesions. In the case of the lung with multiple small lesions, only some representative lesions were indicated. AE, alveolar echinococcosis, CT, computed tomography; MRI, magnetic resonance imaging; T1W/T2W, T1-weighted/T2-weighted.

Distribution of vascular/biliary involvement

Vascular/biliary involvement of the largest liver lesion was found in 151/200 (75.50%) cases. In the Chinese data, 86/100 (86%) showed this involvement, which was significantly higher than in the European data, with 65/100 (65%) cases (χ² = 11.92, P = 0.0006; Table 4).

Association of vascular/biliary involvement with lesion sizes and Kodama types

The presence of vascular/biliary involvement highly significantly correlated with liver lesion size for the total group (111.10 ± 47.44 vs. 47.36 ± 24.36, P < 0.0001) as well as for the European (89.73 ± 40.00 vs. 39.81 ± 19.91; P < 0.0001) and Chinese datasets separately (127.25 ± 46.41 vs. 66.28 ± 24.81, P < 0.0001).

Among the 200 cases, vascular/biliary involvement as a function of lesion morphology according to Kodama ranged from a minimum of 1/7 (14.29%) type I liver lesions to a maximum of 9/10 (90.00%) type V lesions. Other Kodama types were associated with roughly high rates of vascular/biliary involvement: 29/52 (55.77%) for type II; 103/117 (88.03%) for type III; and 9/14 (64.29%) for type IV.

Discussion

In the present study, an international collective of German, French, and Chinese patients with HAE was evaluated after prior classification of the liver lesions based on Kodama’s classification by MRI (6). The evaluation comprised findings of vascular/biliary involvement of the liver lesions and distant extrahepatic disease. The aim was to obtain information about the different manifestations of this parasitosis at the respective sites.

AE lesions appear almost exclusively in the liver. In addition to lesion size, its infiltration into vascular and biliary structures is clinically important (11,13 –17). Extrahepatic localizations of primary AE lesions are rare, but there may be invasion into neighboring organs or distant disease manifestations (1,12). The exact prognostic relevance of distant extrahepatic manifestations in AE as well as the mechanism driving these so-called “distant metastases” of AE are debated (22 –26). Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease manifestations can lead to further complications and may increase morbidity in patients with AE.

Here, with regard to intrahepatic disease, the involvement of the right hepatic lobe was most common, occurring in 79% of the total cases. The same held for comparisons among regions (Europe vs. China). The fact that segment VIII was most frequently involved for all four centers is certainly because of its central location and size, taking up a larger volume compared to the left lobe. Azizi et al. (7) and Becce et al. (27) also described a predominately right hepatic distribution of AE lesions.

In the present study, if only a continuous infiltration of the liver lesion was present locoregionally with some extrahepatic tendency, these cases were not adjudicated as extrahepatic disease. Similarly, solely accentuated, well-circumscribed lymph nodes were not evaluated as extrahepatic manifestations. These nodes can exhibit so-called “small particles of Echinococcus multilocularis,” which can lead to corresponding inflammatory reactivity without representing a confirmed parasitic disease manifestation (28).

True distant extrahepatic manifestations, which were quite rare overall, showed a significant difference in comparison between the European and Chinese centers, with more identified in the Chinese data. This finding could be viewed as an indication of more advanced cases in China at the time of diagnosis. It is also consistent with this assumption that there is a significant difference in the frequency distribution of the presumably earlier types I–II and the probably more advanced types III–V in an intercontinental comparison. Distant extrahepatic manifestations in the lung were most common in the overall group, followed by lesions in the brain. Distant extrahepatic AE manifestations are also described more frequently in these two organs in other studies (29 –31).

In addition, in the context of cystic echinococcosis, which is more frequent worldwide than AE, cerebral involvement can occur and then can be classified according to the WHO classification depending on the stage of disease (32,33). For AE, however, no stage-adapted classification exists so far. In the present study, Kodama type I was not associated with any cases of distant extrahepatic disease, and type III was most frequently associated with it (10.26%). This result may indicate different stages of development through the lesion types, with incrementally different degrees of progression of the overall disease.

We found a significant relationship between the presence of distant extrahepatic disease and the size of the liver lesion in the overall group, with significantly more frequent extrahepatic involvement in cases with larger lesions of the liver. These findings imply that the detection of distant extrahepatic manifestations is related to disease progression.

The vast majority (75.5%) of cases in the overall dataset showed vascular/biliary involvement of the largest liver lesion, and the patient population in China had significantly more frequent involvement compared to the European patients. Involvement of vascular and biliary structures also significantly correlated with lesion size. A 2018 MRI study, which was not based on Kodama’s classification, showed that the invasion of liver vessels by an AE lesion depends on the progression of the disease stages (34). Our observations add further support to earlier evidence that Chinese cases of AE are more advanced at detection, based on lesion size and of the distribution of the various morphological appearances of liver lesions (35).

As Kodama type I had the least vascular/biliary involvement at 14.29%, this seems to be an early stage of the disease, whereas the other types with a maximum of up to 90% for type V presumably indicate more advanced stages. This would also be supported by the results of Azizi et al. (7), considering the fact that microcysts are no longer found in type V lesions which is pointing to a liquid necrotized late stage lesion that had already achieved maximum infiltration.

The present study has some limitations. One limitation is the assessment of vascular/biliary involvement of HAE lesions, which was based purely on image morphological criteria, although all experienced reviewers agreed on the conclusions. The different age of the MRI scans as well as the use of different 1.5-T and 3.0-T MRI scanners may be mentioned as a further limitation. However, the T2W and contrast-enhanced T1W sequences, used for the evaluations in the present study, are well-established and stable protocols. Due to the retrospective nature of the study, no uniform settings could be selected. In future prospective studies, correspondingly uniform investigation protocols should be applied. The study design precluded a histopathological evaluation of these criteria. Furthermore, the presence of distant extrahepatic disease was determined retrospectively based on whole-body staging examinations. As described above, these exams were occasionally handled differently for the different centers, depending on local conditions and practices.

In conclusion, the current findings show the differences between Chinese and European cases of AE in terms of vascular/biliary involvement, distant extrahepatic disease manifestations, and Kodama types of liver lesions associated with these features. Distant extrahepatic AE manifestations are significantly more frequent in China than in Europe. The various Kodama types also differ between centers, as does their association with distant extrahepatic manifestations. Unlike types II–V, type I showed no association with extrahepatic disease manifestation in these data. Type III was most frequently associated with extrahepatic manifestation. We found a significant relationship between distant extrahepatic disease and the size of the liver lesion in the complete dataset. Vascular/biliary structures were significantly more frequently involved in cases from China than from Europe. A significant correlation also was identified between involvement of vascular/biliary structures and hepatic lesion size. Different Kodama types were associated with varying frequencies of vascular/biliary involvement, with a minimum for type I lesions and a maximum for type V cases. The study design does not allow direct conclusions as to why the extent of the disease differed between China and Europe. The results may provide information about the potential behavior of this disease and may suggest cases of varying degrees of progress in an intercontinental comparison. Since the observation of untreated AE cases would not be justifiable prospectively, such initial suspicions of disease development as raised in the present work must of course be pursued further with other study approaches.

Members of the Consortium

Members are listed by center and alphabetically.

Besançon, France: Anne-Pauline Bellanger, Oleg Blagosklonov, Solange Bresson-Hadni, Eleonore Brumpt, Eric Delabrousse, Florent Demonmerot, Frederic Grenouillet, Bruno Heyd, Jenny Knapp, Stephane Koch, Laurence Millon, Damien Montange, Josephine Moreau, Carine Richou, Celia Turco, Claire Vanlemmens, Dominique A Vuitton, Lucine Vuitton; Ulm, Germany: Thomas FE Barth, Sven Baumann, Ambros J Beer, Meinrad Beer, Hartmut Döhner, Iris Fischer, Tilmann Graeter, Hans-Jürgen Groß, Beate Gruener, Doris Henne-Bruns, Andreas Hillenbrand, Silke Kapp-Schwörer, Katharina Klein, Wolfgang Kratzer, Patrycja Schlingeloff, Julian Schmidberger, Rong Shi, Steffen Stenger, Frauke Theis; Urumqi, China: Yi Jiang, Renyong Lin, Wenya Liu, Yingmei Shao, Aji Tuerganaili, Jian Wang, Hao Wen, Wenbao Zhang; Xining, China: Yanling Bai, Haihua Bao, Jiayuan Cao, Haining Fan, Yingli Kang, Weixia Li, Ren Li, Haijiu Wang, Xiaoping Wang, Shengbao Wen, Yousen Wu, Guixiu Yin, Wang Zhixin.

Footnotes

Acknowledgements

The authors thank the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE), especially Dominique A Vuitton, for initiating the XUUB cooperation.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received the following financial support for the research, authorship, and/or publication of this article: The study was supported by a German Research Foundation (DFG)-funded project called “Establishment of a national database for alveolar echinococcosis” (ref. no. KA 4356/3-1) and “Implementation of interfaces for the standardization of national database systems for alveolar echinococcosis and its transformation processes” (ref. no. KR 5204/1-2); the Natural Science Foundation of China (NSFC) (81260232, Multiple imaging study of the Hepatic Alveolar Echinococcosis after albendazole treatment); and the Qinghai Science & Technology Department (ref. no. 2017-SF-158).

ORCID iD

Wolfgang Kratzer

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