Follow-up in Hepatic Alveolar Echinococcosis under Benzimidazole Therapy Using Computed Tomography
Alveolar echinococcosis (AE), caused by the parasite Echinococcus multilocularis, is one of the most severe parasitic zoonoses in the temperate regions of the northern hemisphere, particularly in Central Europe and parts of North and Central Asia. Without treatment, AE has a very high mortality rate. The liver is the most commonly affected organ, often presenting with complex, infiltrative lesions. When surgical resection is not feasible, long-term pharmacotherapy with benzimidazoles, such as albendazole or mebendazole, is the standard treatment to inhibit disease progression. This study investigates the morphological changes in hepatic AE lesions under benzimidazole therapy using computed tomography (CT) scans, based on the E. multilocularis Ulm classification for CT (EMUC-CT).
The EMUC-CT classification system provides a standardized framework for describing hepatic AE lesions, facilitating diagnostic accuracy and enabling comprehensive comparisons of CT findings. Previous studies have shown that neither individual parameters nor the duration of benzimidazole therapy alone can reliably indicate parasitic activity or viability. Therefore, this study aimed to explore the influence of parasitostatic therapy on lesion morphology by analyzing CT scans at two different time points in patients undergoing continuous benzimidazole treatment.
The study retrospectively analyzed 72 patients with hepatic AE from the national German AE database at the University Hospital Ulm. These patients had not undergone liver surgery for AE and were receiving continuous benzimidazole therapy at standard doses: albendazole (10–15 mg/kg body weight per day, divided into two doses) or mebendazole (40–50 mg/kg body weight per day, divided into three doses). Patients were classified into confirmed (n = 32) and probable (n = 40) cases based on World Health Organization criteria. The cohort included 38 women (52.8%) and 34 men (47.2%), with a mean age of 65.8 years and a mean body mass index of 24.3 kg/m².
CT datasets from the venous phase of contrast-enhanced positron emission tomography-CT scans were used to assess AE liver lesions. Evaluations were based on the initial imaging and the most recent follow-up imaging, with a mean interval of 39.8 months between scans. The size of the largest lesion in the liver was measured in the transverse plane during baseline CT, and the same lesion was re-evaluated in the follow-up CT. Two independent readers classified the lesion morphology according to EMUC-CT, achieving an inter-rater reliability of 0.8268. Additionally, the degree of calcification in the largest lesion was assessed using a four-stage scale, and the total number of AE lesions in the liver was recorded.
The EMUC-CT classification identified type I “diffuse infiltrating” as the most common primary morphological type (n = 33, 45.8%), followed by type II “primarily circumscribed tumor-like” (n = 15, 20.8%), type IIIa/b “primarily cystoid” (n = 13, 18.0%), type IV “small cystoid/metastasis-like” (n = 10, 14.0%), and type V “mainly calcified” (n = 1, 1.4%). Over the course of treatment, the primary morphological type changed in only one patient (1.4%), from type IIIa to type V. Similarly, changes in EMUC-CT sub-criteria were observed in only one patient (loss of “cystoid portion” in type II). These findings indicate a high degree of morphological consistency under benzimidazole therapy, consistent with the parasitostatic effect of these drugs.
Calcification is a hallmark of AE. In this study, the EMUC-CT calcification pattern changed in 12 cases (16.7%) between baseline and follow-up CTs, with all changes reflecting a shift from a more discreet to a more dominant pattern (e.g., from “feathery calcification” to “diffuse calcification”). The overall degree of calcification increased significantly over time: baseline classifications were “none” (n = 5, 6.9%), “slight” (n = 29, 40.3%), “moderate” (n = 24, 33.3%), and “considerable” (n = 14, 19.4%), while follow-up classifications were “none” (n = 2, 2.8%), “slight” (n = 14, 19.4%), “moderate” (n = 30, 41.7%), and “considerable” (n = 26, 36.1%). This increase in calcification aligns with previous studies suggesting that calcification may be associated with reduced parasitic activity in AE.
The mean size of the largest lesion decreased significantly from baseline to follow-up (86.2 mm vs. 80.9 mm). Lesion size varied among EMUC-CT types, with type IIIb lesions being the largest, followed by type II, type I, type IIIa, type IV, and type V. Significant reductions in lesion size were observed for type I (80.6 mm vs. 75.3 mm), type II (110.9 mm vs. 105.4 mm), and type IIIa/b (113.4 mm vs. 104.2 mm). Type IV lesions did not show significant size changes, while type V lesions could not be evaluated due to their small number. Type V lesions, which are completely or almost completely calcified, likely represent an inactive stage or residual form of other types. These findings support the potential of benzimidazoles to reduce the size of AE lesions, as previously reported, but with the added insight of differentiation by morphological type.
The total number of lesions remained relatively stable from baseline to follow-up, consistent with the known persistence of lesions or their residues under parasitostatic therapy. Interestingly, there was a moderate to strong relationship between the mean number of lesions and the mean lesion size across different morphological types: the more lesions present in the liver, the smaller their individual size. This observation raises questions about the growth behavior of lesions within the same liver.
The study has some limitations, including the relatively small sample size when stratified by primary morphological types, sub-criteria, and calcification patterns. Additionally, the subjective assessment of calcification degree may introduce bias. Further multicenter studies with larger case numbers are needed to confirm these findings.
In conclusion, long-term benzimidazole therapy preserves the primary morphology of AE lesions while increasing calcification. Significant reductions in lesion size occur in types I, II, and III, potentially improving operability in cases where surgery was initially not feasible. These findings highlight the importance of continuous monitoring and morphological classification in managing hepatic AE under benzimidazole therapy.
doi.org/10.1097/CM9.0000000000000874
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