|Year : 2016 | Volume
| Issue : 1 | Page : 56-68
Hepatic visceral larva migrans, a resilient entity on imaging: Experience from a tertiary liver center
Shalini Thapar Laroia1, Archana Rastogi2, Chhagan Bihari2, Ajeet Singh Bhadoria3, Shiv Kumar Sarin4
1 Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
2 Department of Hepato Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
3 Department of Community Medicine and Public Health, Institute of Liver and Biliary Sciences, New Delhi, India
4 Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
|Date of Acceptance||28-Oct-2015|
|Date of Web Publication||28-Jan-2016|
Shalini Thapar Laroia
Department of Radiology, Institute of Liver and Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi - 110 070
| Abstract|| |
Introduction: Hepatic visceral larva migrans (VLM) is an uncommon parasitic manifestation seen in the liver. It presents as coalescing, conglomerated, or solitary abscess cavities in the liver on imaging. We conducted a retrospective clinico-radiological analysis of 24 patients with biopsy proven VLM who were reviewed and followed up at our tertiary liver institute over a period of 4 years. Materials and Methods: The study was performed to correlate the radiological features and imaging response to therapy for hepatic VLM. The disease course, imaging findings, progressive, absolute eosinophil counts (AEC), hydatid serology, and the extent of radiological regression of the liver lesions, on follow-up were analyzed. Results: Imaging showed a diagnostic accuracy of 42%. Hydatid serology was positive in 46% patients before starting treatment. The median pretreatment AEC of 507 showed a significant posttreatment AEC decline to median value of 117. The Wilcoxon signed ranks test showed significant decline in the AEC (P < 0.001). Radiological regression was present in all lesions. However, patients showed residual abscesses on imaging, up to 2 years on follow-up. Conclusion: This study reveals that AEC has a significant predictive value in diagnosis and as a marker for disease regression. Complete radiological resolution of hepatic lesions does not correlate with total clinical remission. This finding warrants the need for further studies to look into the role of prolonged medical therapy or surgery as an alternate to current therapy module in cases of hepatic visceral larva abscesses.
Keywords: Absolute eosinophil count, antihelminthic therapy, hepatic, imaging, visceral larva migrans
|How to cite this article:|
Laroia ST, Rastogi A, Bihari C, Bhadoria AS, Sarin SK. Hepatic visceral larva migrans, a resilient entity on imaging: Experience from a tertiary liver center. Trop Parasitol 2016;6:56-68
|How to cite this URL:|
Laroia ST, Rastogi A, Bihari C, Bhadoria AS, Sarin SK. Hepatic visceral larva migrans, a resilient entity on imaging: Experience from a tertiary liver center. Trop Parasitol [serial online] 2016 [cited 2019 Dec 10];6:56-68. Available from: http://www.tropicalparasitology.org/text.asp?2016/6/1/56/175100
| Introduction|| |
Visceral larva migrans (VLM) is used to describe the migratory larva stage of nematodes in human beings. Dogs and cats are the most common primary hosts for the disease causing nematodes Toxocara canis and Toxocara cati respectively. Lesser known and uncommonly found parasites such as Capillaria hepatica, Ascaris suum, Baylisascaris procyonis as well as Ancylostoma species also infect human beings and cause similar disease pattern, particularly, in the liver. ,, Human beings acquire the infection through accidental ingestion of embryonated eggs present in the soil or the arrested second-stage larvae of nematodes from the animal host tissues which are consumed as meat. This route is similar to parasitic infestation of primary animal hosts such as dogs and cats. Since humans are not primary hosts of these organisms, the ingested eggs or larvae can only evolve into migrating larvae, which are released into the small bowel. From there, they enter the portal venous system through the intestinal walls and migrate systemically to infest the liver, lungs, brain, heart, and eyes. , This process of migration and subsequent clinical symptoms has earned this larva, the name of VLM.
VLM manifest in the liver as eosinophilic granulomas. This pathological entity is a lesser known presentation of parasitic liver abscesses. Eosinophilic abscesses or granulomas are necrotizing lesions seen in the liver. They appear as ill-defined, conglomerating, and sometimes discrete focal lesions, with imaging features resembling nonspecific abscesses or mimicking cystic/liquefied mass lesions. These lesions may sometimes gradually change shape and positions on successive imaging, which is consistent with the presentation of migratory larva disease.  Sonographic appearance of these lesions usually shows multiple rounded or oval hypoechoic lesions. Lesion size may vary from a single sub-centimeter focal area to a confluent mass, large enough to involve an entire lobe of the liver.
Imaging features of these lesions on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) include ill-defined enhancing walls of liquefied conglomerating lesions which may be oval, rounded, or asymmetrical seen predominantly in the venous and equilibrium phases.  A unique characteristic feature of these abscesses on noncontrast MRI study is the presence of a hyperintense rim on T1-weighted sequences, with corresponding diffusion restriction on echo planar imaging. 
The imaging features of VLM, on CT and MRI, are suggestive, but not characteristic and need correlation with laboratory parameters such as antigen serology and eosinophilic counts. ,, Gold standard of diagnosis is cytology or biopsy from the lesions. , VLM has a worldwide prevalence, although it is more common in developing countries.  There have been case series and case reports on VLM describing the radiological findings on sonography, CT, and MRI. ,,, To our knowledge, existing literature did not reveal studies with long-term follow-up on imaging to assess the therapeutic response of hepatic VLM. Existing studies were found lacking in correlation of clinical resolution of this entity with imaging findings after antihelminthic treatment. We conducted this study using systematic retrospective analysis to compare and follow-up the pre- and post-treatment resolution pattern of radiology findings in cytopathologically proven hepatic eosinophilic abscesses caused by VLM. We also correlated these imaging features on subsequent follow-up studies with the AEC.
| Subjects and Methods|| |
The study, which was retrospective in design, was approved by the institutional review board of our hospital and informed consent from the patient study group was waived off. During the time period January 2010-January 2014, only those patients (n = 456) who were referred to the Radiology Department at our institute with suspected hepatic abscesses or infective granulomatous lesions were included in the study group. They underwent imaging tests in the form of sonography, dynamic CT, or MRI for evaluation. Clinically, these patients had symptoms ranging from vague right hypochondrial abdominal pain at one end to fever with chills and pyrexia of unknown origin at the other end. Within this group, 24 patients (15 men, 9 women; age range, 7-62 years, mean age, 33.8 ± 17.4 years) had indeterminate hepatic focal lesions on imaging, which could not be diagnosed as classical abscesses or suspected granulomatous lesions. These patients underwent further clinical, laboratory, imaging, and histopathological evaluation. The diagnosis of hepatic eosinophilic abscesses consistent with hepatic VLM granulomas was established by cytology and histopathology.
Interestingly, at the time of referral, a specific or differential diagnosis of parasitic liver disease was not suspected in any of these patients and was suggested for the first time on imaging studies. No history of ingestion of uncooked meat or animal liver was elicited from these patients.
Among the 24 patients, 11 patients underwent sonography, eight underwent CT, three had an MR cholangiopancreatography (MRCP), and two underwent an MRI upper abdomen study. All patients (100%) underwent a first follow-up within 6 months to 1 year and 20 patients (83.3%) had an additional second follow-up within the next 1 year. CT was used as follow-up modality in 12 patients, sonography in 10 patients, and MRI in 2 patients.
The study group was investigated for peripheral blood eosinophilia using AEC and serology test for hydatid disease. These investigations were performed within a span of 5 days after the radiology investigations, but prior to the cytopathology and histopathology. The pretreatment AEC was compared with the AEC on posttreatment follow-up. The posttherapeutic AEC was done on the same day as the follow-up imaging study.
Fine needle aspiration cytology (FNAC) and biopsy procedures for all the patients were performed under sonographic guidance. These were uneventful and no postprocedure complications were reported.
None of the patients had a known history of primary/secondary malignancy or diffuse liver disease. All the 24 patients were found to have discrete, solitary rounded-ovoid or multiple conglomerated, and coalescing lesions in the liver on imaging (using sonography, CT, or MRI) without presence of underlying liver disease or any other incidental finding on imaging.
At our hepatology clinics, the policy for therapy is to treat all patients positive for hepatic parasitic abscesses on cytology and histopathology, with antihelminthic therapy, using oral albendazole at 400 mg/day for 6-8 weeks in a cyclical manner.
The clinical course and therapeutic response were mapped for 6 months to 2 years (mean period of 13.5 months) after the prescribed antihelminthic therapy. Follow-up imaging of the hepatic lesions was compared with clinical response to treatment. Pre- and post-treatment analysis of the imaging findings was done with the consensus of two radiologists (VK, STL, with experience of 4 and 9 years, respectively, specifically in abdominal radiology). The analysis included a qualitative and quantitative assessment of the lesions in the liver, before and after treatment.
Imaging techniques used
Routine trans-abdominal B mode sonographic examination of the upper abdomen in the right oblique and supine position was performed using 3.5-5.0 MHz convex transducers. All examinations were performed on commercially available sonography machine IU 22 (Philips, The Netherlands). The method was standardized for all abdominal sonography scans carried out in the department. Different radiologists with experience of 3-5 years in abdominal imaging with sonography performed these scans. The reports were finalized by the consensus of two radiologists with 4 and 9 years' experience in abdominal sonography.
Standardized protocols for a dynamic three phase study are routinely used for suspected focal lesion under evaluation in the liver at our department. All the patients underwent a dynamic triple phase study on helical MDCT (Discovery 750 HD, GE Healthcare, USA). Unenhanced scans were obtained with 1 mm reconstruction interval and slice thickness. Contrast-enhanced scans were obtained in the hepatic arterial, portal venous, and equilibrium phases with the help of bolus tracking technique for triggering of the contrast at maximum iodine density of 100HU in the descending thoracic aorta. 80-100 ml contrast (Iomeron 400 mg/dl iodine, Bracco) was injected at 3-4 ml/h through the ante-cubital vein. The hepatic arterial, portal venous, and equilibrium phases were obtained at 30, 70, and 180 s, respectively. Multiplanar reformations and projections were used whenever required and all cases were viewed and analyzed on the ADW 4.4 digital viewer and workstation (GE healthcare, USA).
Magnetic resonance imaging
All examinations were performed in the 3 Tesla magnetic system (Somatom, GE Healthcare, USA) at our institute using standard protocols employed to scan upper abdomen and cholangiopancreatography. Patients were made to lie supine in the scanner with the body coil and asked to follow breath holding instructions as and when required. The scanning protocol included the following sequences for MR upper abdomen: Axial T1-weighted spoiled gradient-echo (TR/TE, 155/4.6; flip angle, 80°) followed by axial T2-weighted turbo spin-echo (1600/80; 90° flip angle), fat suppressed T1- and T2-weighted sequences as well as echo planar imaging. After acquiring routine upper abdominal sequences, 0.1 mmol/kg of MR contrast material; Gadobenate Dimeglumine BOPTA (MultiHance; Bracco) was injected intravenous and was flushed by 10 ml of normal saline. The dynamic images were obtained at 30-35 s (hepatic arterial phase), 70-90 s portal venous phase (PVP), and 3-5 min (delayed phase) after contrast injection. A delayed hepatobiliary phase series was obtained after 60 min postinjection of contrast. Field of view was maintained at 350 mm; and matrix, 256 × 256-512 × 512. Dynamic axial T1-weighted images fat spectral saturated MR images were obtained with echo-fast three-dimensional gradient-echo (7-9/2-3; 15° flip angle).
All sonography, CT, and MRI images were reviewed by two certified practicing radiologists (with experience in abdominal imaging in the respective modalities ranging from 4 to 9 years). Final consensus on follow-up imaging findings was also made by the same radiologists. The lesions were evaluated retrospectively for location, number, size, pattern, enhancement characteristics, and internal contents as well as associated complications. Follow-up images were also compared on the same guidelines. All the above findings were divided, posttherapy, into two conclusive categories of regressive or nonregressive pattern of disease.
Absolute eosinophils count was measured with the formula:
AEC = % eosinophils × total leukocyte count/100
ELISA (hydatid serology)
The RIDASCREEN ® Echinococcus IgG (r-biopharm, Germany) test is an enzyme immuno-assay for the qualitative determination of IgG antibodies against Echinococcus granulosus and Echinococcus multilocularis in human serum. The test is used for confirmation when there is a suspected case of infection with Echinococcus or for assessing the immune status. Purified antigens are bound to a microwell plate. Antibodies which are present in the patient samples attach themselves to the antigens and are determined during the second phase of the test by enzyme-labelled antihuman antibodies (the conjugate). The enzyme converts the colorless substrate (urea peroxide/TMB) to a blue end product. The enzyme reaction is stopped by adding sulfuric acid. The color of the mixture then switches from blue to yellow. A final measurement is carried out in a photometer at 450 nm using a reference wavelength ≥620 nm. Result interpretation is based on the sample index; <0.9 - nonreactive, 0.9-1.1 - indeterminate, >1.1 - reactive.
Cytology and histopathology technique
Sonographically guided FNAC or percutaneous biopsy was performed in all the patients in the study group using an 18 gauge biopsy needle.
Air dried and alcohol fixed smears were prepared. Air dried smears were stained for Giemsa and alcohol fixed smears were stained with hematoxylin and eosin (H and E) staining.
Percutaneous biopsy tissue was fixed in 10% buffered formalin. Tissues were processed, embedded, and cut as per the standard protocol in histopathology practice. H and E staining was performed on each biopsy section.
| Results|| |
Majority (n = 22) of the twenty-four patients who underwent diagnostic imaging tests were found to have multiple rounded to ovoid lesions showing conglomerated appearance with fine enhancing walls and central liquefied appearance [Figure 1]. Two patients had separate solitary lesions in the right and left lobes [Figure 2]a and b. Twenty-two patients had multiple lesions. Both lobes of the liver were involved in 2 patients [Figure 3]. Restriction of lesions to single lobe was seen in 22 patients.
|Figure 1: The appearance of focal lesions of hepatic visceral larva migrans in the liver on different modalities. (a) Sonography in a patient with hepatic visceral larva migrans, shows ill-defined confluent appearing, liquefied hypoechoic (*) lesions in the liver. (b) Contrast-enhanced computed tomography examination shows conglomerating and discrete hypoattenuating, fluid density lesions in the right sub-capsular lobe of liver (black arrow). (c) Axial T2-weighted magnetic resonance sequence in a case of visceral larva migrans in the liver shows well defined oval-rounded hyperintense fluid intensity lesions appearing clustered together (white bold arrow)|
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|Figure 2: (a) Hepatic visceral larva migrans presenting as a solitary focal lesion in the right lobe of liver showing intra-lesional honeycombing and septations with internal liquefied contents (white arrow) on the hepatic arterial phase (2ai), portal venous phase (2aii), and equilibrium phases (2aiii). (b) Hepatic visceral larva migrans presenting as a solitary focal lesion (white arrow) in the left lobe of liver with septations and hypoattenuating contents on the hepatic arterial phase (2bi), portal venous phase (2bii), and equilibrium phases (2biii)|
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|Figure 3: Sonographic appearance of hepatic visceral larva migrans involving both lobes of liver with scattered heteroechoic lesions showing clusters and discrete areas (white arrow with black margin showing right lobe lesion and white bold arrow showing left lobe lesion)|
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Associated complications in the form of portal vein thrombosis were seen in three patients [Figure 4]. Mild enhancement of the thrombus with perfusion abnormality in one of the patients was suspected to be due to its pseudotumor appearance and this patient was later taken up for lobectomy [Figure 5]a. Left lobe intra-hepatic biliary dilatation around the lesion was suspected to be due to biliary communication with the lesion [Figure 5]b.
|Figure 4: Portal vein thrombosis in different patients on contrast-enhanced computed tomography (portal venous phase) involving right portal vein posterior division (white arrow) and left portal vein (black arrow) which are not visualized|
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|Figure 5: (a) Dynamic contrast-enhanced computed tomography performed in a 35-year-old lady for pain in abdomen and fever showed a pseudotumor appearance of the visceral larva migrans lesion in the left lobe of liver. Perfusion abnormality (*) with left portal vein thrombosis (arrow) and pseudotumor appearance of hepatic visceral larva migrans in a 35-year-old lady who underwent contrast-enhanced computed tomography triple phase of the liver (b) Biliary dilatation (arrow) of the left lobe radicals in the 35-year-old lady seen on contrast-enhanced computed tomography of liver with associated liver lesion in the left lobe|
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Attenuated portal vein segmental division on the right side was identified on sonography in one patient only.
Hepatic vein thrombosis involving the middle hepatic vein was present in one patient [Figure 6]. Partial rupture and associated perihepatic collections were noted in only two patients in the entire series [Figure 7]a and b. Enlarged abdominal, periportal, and peripancreatic lymph nodes in the upper abdomen with a mean short axis diameter of approximately 20 mm were found associated with these lesions in four patients [Figure 8].
|Figure 6: Contrast-enhanced computed tomography of the abdomen in a 21-year-old male patient shows partially occluding hypodense thrombus in the middle hepatic vein (arrow). Multiple hypoattenuating lesions of visceral larva migrans are seen in the sub capsular right lobe and segment IV of the liver (*)|
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|Figure 7: (a) Contrast-enhanced computed tomography of the abdomen in a 8-year-old female child shows partial rupture of the lesion into the right sub-diaphragmatic location (*) with reactive right pleural fluid (black open arrow) and basal atelectasis (bold white arrow) (b) Contrast-enhanced computed tomography abdomen of 25-year-old female patient who had partial intra-peritoneal rupture of the visceral larva migrans lesions in the right lobe of liver, extending into hepato-duodenal ligament (*) and the sub hepatic (white arrow) and perihepatic region (black open arrow)|
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|Figure 8: Contrast-enhanced computed tomography of the abdomen shows enlarged nodes (*) in upper abdomen, periportal, and peripancreatic locations|
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Incidental findings on the imaging tests were seen in two patients. Both patients had gall bladder fundal focal wall thickening which was likely to represent adenomyomatosis [Figure 9]. Perfusion abnormality in the PVP along the lesion contours was found in two patients [Figure 10].
|Figure 9: Contrast-enhanced computed tomography shows incidental focal fundal gall bladder mural thickening (bold arrow) in a 45-year-old male patient with multiple hepatic visceral larva migrans lesions (open arrow)|
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|Figure 10: Contrast-enhanced computed tomography in a 25-year-old male patient with hepatic visceral larva migrans shows perfusion abnormality (arrow) in the portal venous phase along the lesion (*) contours|
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In all patients where dynamic contrast studies were performed, lesions were best identified and most conspicuous on the portal venous and equilibrium phases of the dynamic MR and CT studies [Figure 11] and [Figure 12]. On sonography, all lesions were heteroechoic, predominantly hypoechoic with conglomerating, and few discrete lesions spread within the liver parenchyma [Figure 13]. However, on follow-up, they showed heterogeneous echogenicity with echogenic areas seen [Figure 14]. Out of the 24 patients confirmed to have hepatic VLM on fine needle cytology and histopathology, an imaging differential diagnosis of eosinophilic parasitic abscesses was suggested in ten patients (diagnostic accuracy of 42%). One patient underwent a left hepatectomy for extensive eosinophilic abscesses confined to the left lobe with a preoperative suspicion of malignancy. This patient was found to have an enhancing intra-luminal left portal vein thrombus and possibility of biliary communication with dilated isolated left lobar intra-hepatic biliary radicles. Twenty-three patients were given oral antihelminthic therapy for a mean duration of 6-8 weeks. Follow-up scans were performed for the entire study patient population. Twenty-four patients underwent follow-up within 6 months to 1 year of therapy. Four patients underwent two successive follow-ups (between 1 and 2 years posttherapy).
|Figure 11: Dynamic contrast-enhanced magnetic resonance imaging (performed with hepatocyte specific contrast Gadobenate Dimeglumine) in 42-year-old male patient with hepatic visceral larva migrans lesions. (a) Arterial phase of the dynamic contrast-enhanced magnetic resonance imaging, T1-weighted fat suppressed axial section of the liver shows ill-defined hypointense - isointense conglomerating lesions (arrow) in the right lobe of liver. (b) The portal venous phase of the dynamic contrast-enhanced magnetic resonance imaging, T1-weighted fat suppressed axial section of the liver shows well defined rounded hypointense confluent and few discrete lesions (arrow) in the right lobe of liver. (c) The equilibrium phase of the contrast-enhanced magnetic resonance imaging, T1-weighted fat suppressed axial section of the liver shows well defined rounded hypointense confluent and few discrete lesions (arrow) in the right lobe of liver. (d) The 1 h delayed hepatocyte-specific contrast-enhanced magnetic resonance imaging, T1-weighted fat suppressed axial section of the liver shows well defined rounded hypointense confluent and few discrete lesions (arrow) in the right lobe of liver|
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|Figure 12: Dynamic triple phase contrast-enhanced computed tomography scan of a 35-year-old female patient with hepatic eosinophilic visceral larva migrans lesions in the liver. (a) Noncontrast computed tomography images of the axial section of the liver shows ill-defined mildly hypoattenuating lesions (arrow) in the right lobe of liver. (b) Arterial phase of the contrast-enhanced computed tomography, axial section of the liver shows ill-defined hypoattenuating conglomerating lesions (arrow) in the right lobe of liver. (c) The portal venous phase of contrast-enhanced computed tomography, axial section of the liver shows well defined hypoattenuating conglomerating lesions (arrow) in the right lobe of liver. (d) The equilibrium phase of the contrast-enhanced computed tomography, axial section of the liver shows hypoattenuating lesions (arrow) in the right lobe of liver|
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|Figure 13: Sonography of the liver of a 26-year-old male patient with multiple heteroechoic lesions in the liver proven histopathologically to be visceral larva migrans lesions. (a-d) Multiple ill-defined heteroechoic conglomerating lesions (arrows) in the liver with fuzzy walls and variable echoes within the lesions|
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|Figure 14: (a-d) The 2 years follow-up lesions (arrows) of the same patient show significant regression in size, with minimal Doppler vascularity and predominantly hypoechoic appearance with well-defined outlines|
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Mode of follow-up was variable during posttreatment phase. CT was used as a modality for imaging the disease regression in 12 cases. Sonography was used as a means of follow-up for 10 patients. MRI was used for follow-up in 2 patients in the study group. Sonography was the preferred modality due to its easy accessibility and radiation free scanning.
Hydatid serology was positive in 46% patients before initiating treatment.
The median pretreatment AEC was 507 (inter-quartile range [IQR] 305-1016) and posttreatment AEC showed a median value of 117 (IQR 69-130). The Wilcoxon signed rank test showed a significant decline in the absolute eosinophil counts (P < 0.001).
Radiological regression of lesions was seen in 23 patients at the first follow-up imaging within 6 months to 1 year of therapy [Figure 15], [Figure 16], [Figure 17] and [Figure 18].
|Figure 15: Sonography images of an 8-year-old male child diagnosed with hepatic visceral larva migrans before initiation of therapy. (a) Hepatic visceral larva migrans lesions (white bold arrow) showing poor echoes within and multiple lesions clustered around it in the right lobe of liver. (b) Hepatic visceral larva migrans cystic lesion (upward pointing arrow) with associated heterogeneous, ill-defined hypoechoic lesions clustered around this lesion (downward pointing arrow). (c) Hepatic visceral larva migrans lesions seen as an ovoid well defined focal area with multiple internal echoes (solid black arrow with white outline)|
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|Figure 16: The follow-up sonogram of the 8 years of male child after therapy at 6 months. (a) The lesion seen on previous scan corresponding to Figure 15a is regressed, but well visualized on the current study (white bold arrow). (b) The lesions (upward and downward pointing arrows) correspond to the previously seen lesions on Figure 15b and appear to have regressed, but not resolved. (c) The lesion corresponds to Figure 15c (bold black arrow with white outline) and is regressed in size; however, no definite resolution is seen. Instead, (d) shows new migratory lesions (*) in the right lobe|
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|Figure 17: A 36-year-old lady presented with hepatic visceral larva migrans and underwent a contrast-enhanced magnetic resonance imaging pretherapy which was followed by a contrast-enhanced computed tomography for comparison after 6 months. (a) Axial section of the liver in portal venous phase of contrast-enhanced magnetic resonance imaging for upper abdomen reveals sub capsular conglomerated hypointense, ring enhancing lesions in the right lobe of liver with documented size (bold black arrow outlined with white). (b) Similar lesions in the axial section of liver in the portal venous phase of contrast-enhanced magnetic resonance imaging in segment V of right lobe of liver (bold white arrow). (c) Lesions (bold black arrow) in segment V extending to segment VI of right lobe liver appearing hypointense and conglomerating|
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|Figure 18: Contrast-enhanced computed tomography performed for the patient described in Figure 17 after 6 months postantihelminthic therapy, in a known case of visceral larva migrans. (a) The lesions (bold black arrow outlined with white) show decrease in the size as documented, compared to Figure 17a, but are still well visualized. (b) The lesions are smaller (bold black arrow) in segment V compared to those in Figure 17b. (c) The lesions are present even after therapy in segment V and VI (bold black arrow) as compared to Figure 17c, but are smaller in size and distribution|
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Further regression at second follow-up (within 1-2 years) was present in all 4 patients who underwent imaging at this stage [Figure 19], [Figure 20] and [Figure 21].
|Figure 19: A 39-year-old lady presented with hepatic visceral larva migrans and underwent a contrast-enhanced magnetic resonance imaging pretherapy which was followed by a contrast-enhanced magnetic resonance for comparison after 2 years posttherapy. (a) Axial section of the liver in portal venous phase of contrast-enhanced magnetic resonance imaging for upper abdomen reveals multiple conglomerated hypointense, ring enhancing lesions in the right lobe of liver, segments VI and VII (bold black arrow outlined with white). (b) Similar lesions in the coronal section of liver in the portal venous phase of contrast-enhanced magnetic resonance imaging are seen in the right lobe of liver (bold white arrow). (c) Lesions (bold black arrow) in posterior segments of the right lobe liver appearing hypointense and conglomerating. (d) Lesions (bold black arrow with white outline) in posterior segments of the right lobe liver appearing hypointense and conglomerating|
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|Figure 20: Contrast-enhanced magnetic resonance performed for the patient, a known case of visceral larva migrans, described in Figure 19 after 2 years postantihelminthic therapy. (a) The lesions (bold black arrow outlined with white) show decrease in the size as compared to Figure 19a, but are still well visualized. (b) The lesions are smaller (bold white arrow) as compared to those in Figure 19b. (c) The lesions are present after antihelminthic therapy in the posterior and inferior segments (bold black arrow) as compared to Figure 19c, but are smaller in size and distribution. (d) Lesions are significantly regressed (bold black arrow with white outline) as compared to Figure 19d|
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|Figure 21: Contrast-enhanced magnetic resonance performed for the patient, a known case of visceral larva migrans, with a repeat follow-up sonogram after 2 years. (a) Coronal section of the liver in portal venous phase of contrast-enhanced magnetic resonance imaging for upper abdomen performed before initiation of antihelminthic drugs reveals a conglomerated hypointense, ring enhancing lesion in the right lobe of liver, segments VI and VII (bold white arrow outlined with black). (b) Axial section of the liver in portal venous phase of contrast-enhanced magnetic resonance imaging for upper abdomen performed before initiation of antihelminthic drugs reveals a conglomerated hypointense, ring enhancing lesion in the right lobe of liver, segments VI and VII (bold white arrow outlined with black). (c) The lesions are visualized after therapy in the posterior segment (bold white arrow) as compared to Figure 21a and b and appear smaller in size|
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However, the noteworthy observation remained that none of these patients, who underwent exclusive oral antihelminthic therapy, were free of residual lesions. Imaging showed regression of the lesions, but absolute resolution of lesions was not present in any of these cases except the single patient who underwent partial hepatectomy.
Statistical analysis was done using IBM SPSS Statistics for Windows, Version 22.0. (Armonk, NY: IBM Corp). Descriptive statistics was presented as proportion, mean ± standard deviation, and median with IQR. Pre- and post-treatment comparative analysis was performed by utilizing Wilcoxon signed rank test. The results of the statistical analysis are described comprehensively in [Table 1].
|Table 1: Descriptive statistics of cases of Visceral larva migrans (n=24)|
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| Discussion|| |
VLM is the name coined for the migratory larvae of toxocara. , Some rarer parasites have also been known to manifest as migrating larvae. Even though this disease is thought to be predominantly seen in the tropical countries, it has been found to be endemic worldwide.  Humans are not the natural hosts of these parasites and get infected by these parasites, accidentally through uncooked bovine meat or oro-fecal contamination. The eggs in the meat or soil hatch into the larva stage and migrate within human tissues, causing symptomatic disease at the site of embedding larva. Clinical features of abdominal manifestation of the disease are pain abdomen, fever, malaise, and other nonspecific features due to abscess and granulomas formation. ,, Imaging is an important step in the diagnostic algorithm of hepatic VLM. The findings on CT, sonography, and MRI are representative of the disease process and its manifestation in the liver. The lesions on imaging may be focal, discrete or conglomerating, coalescing abscesses, and granulomas. The extent of lesions, their number, lobar involvement, and possible complications such as partial rupture, vascular thrombosis, and associated features of abdominal lymphadenopathy can only be assessed by radiological investigations. Underlying liver abnormality and incidental abdominal pathologies are also visualized on scans before treatment is initiated. Imaging differential diagnosis includes other parasitic, pyogenic as well as amoebic abscesses, which may be difficult to distinguish without laboratory and pathological correlation. 
Clinical and imaging criteria are, however, insufficient to make a definitive diagnosis, and serological markers, absolute eosinophil counts, erythrocyte sedimentation rates, and hypergammaglobulinemia are essential for leading the clinician toward this diagnosis. The final gold standard remains aspiration cytology and histopathology, which can be attempted with the help of sonographic guidance. 
The incidence of VLM, like other parasitic diseases, is higher in young adults and children.  In our study group, three out of 24 patients were children and the mean age of presentation was 33.87 years, which corroborated with the worldwide age prevalence. This is probably because of higher rates of travel, activity, and meat eating propensity in younger population. The clinical manifestations of the disease are nonspecific and hence imaging can play a very important role in the management of this disease. The clinical symptoms of VLM in our patient population were not characteristic and were seen ranging from fever to abdominal pain, as has been described by other investigators in previous studies. ,
All three modalities including sonography, CT, MRI, and MRCP were used for the detection of this pathology in our study group and the detection rate was unaffected by the modality used. The overall detection rate of the diagnosis of VLM by the radiologist, where it was reported as a primary or differential diagnostic possibility was 42%. The imaging findings of VLM have been described and corroborated by various investigators and authors. ,,, On sonography, the lesions have been described usually as multiple, hypoechoic, coalescing, or conglomerating, with variable internal echoes. VLM lesions are usually difficult to distinguish from other evolving or residual liver abscesses. Doppler does not help in differentiation from similar focal lesions due to lack of adequate vascularity of these abscesses. However, it may be able to define associated vascular involvement in the form of thrombosis of portal and hepatic veins, occasionally. CT and MRI have been used for characterization of internal contents of hepatic parasitic lesions. Lesions have been found predominantly hypodense and liquefied on contrast-enhanced CT. Similar findings were seen in our patient study group who underwent CT. On noncontrast MRI, VLM abscesses have been described as T2 hyperintense/T1 hypointense with associated restriction on diffusion weighted sequences. Diffusion restriction was present in all patients who underwent MRI in our group [Figure 22].
|Figure 22: Diffusion-weighted sequence performed in a patient with visceral larva migrans. (a and b) Lesions are seen as hyperintense (bold white arrow with black outline) on diffusion sequence with B values = 1000. (c) The ADC map of the same lesions shows restriction of the signal within them (bold white arrow with black outline)|
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All the patients in our study group showed peripheral rim enhancement (seen better on the portal and equilibrium phases) on the contrast-enhanced dynamic studies. Multiple lesions were seen in 22 out of 24 patients (91.6%). Solitary lesions were found in two patients. Both lobes of the liver were involved in 2 patients (8.3%) Single lobe involvement was present in 22 patients (91.6%). VLM abscesses have been predominantly known to present as multiple focal lesions with migration within the liver on repeated imaging.  In addition, our experience suggests that coalesced appearance of multiple lesions may sometimes mimic a honeycomb and give a solitary pseudotumor-like appearance. This needs to be kept in mind when forming a differential diagnosis of such a presentation in the liver. ,
Few of our patients showed disease-related complications on imaging. In n = 1 patient, biliary communication was suggested due to the presence of peri-lesional associated dilated intra-hepatic bile ducts. The abutting left portal vein showed an associated enhancing intra-luminal thrombus. A possibility of a tumor was considered and subsequently, the patient underwent left lobectomy. Other complications in the study group included vascular (portal and hepatic veins) thrombosis (n = 4) [Figure 5] and [Figure 6] and partial rupture of the abscess into the peritoneal cavity (n = 1) [Figure 7]. Such complications have not been described by previous investigators. It would be prudent to suggest that, since these lesions behave like abscesses, these complications can be expected under similar clinical situations and are not specific to the above, however further long-term studies would be required to validate the same. Associated systemic complications specific to VLM such as pulmonary infiltrates, ocular and neurological complications have been reported in literature.  None of the patients in our study group showed any clinical signs of systemic disease progression or involvement by VLM.
It has been well documented by various groups that peripheral eosinophilia is associated with parasitic infections, especially involving the liver. ,
In our study group, we used estimation of AEC for monitoring treatment effectiveness along with imaging and found that the decline in AEC pre- and post-treatment with antihelminthic drugs was significant (P < 0.001). This validates the significance of monitoring the role of anti-parasitic drug therapy in hepatic VLM.
Biopsy and histopathology are the gold standard of diagnosis  [Figure 23]. The demonstration of eosinophilic abscesses with Charcot-Leyden crystals and small granulomas is important to make a diagnosis before commencement of therapy and to distinguish these lesions from other metastatic and neoplastic liver nodules which may present in a similar fashion. In the presence of underlying liver disease or concomitant malignancy, it may be virtually impossible to differentiate a secondary deposit or primary hepatic cancer from migrating parasitic abscesses on imaging.  In our study, underlying hepatosteatosis was found in n = 2 patients. No evidence of chronic liver disease was found on imaging or histopathology in these patients. Incidental smooth focal fundal thickening due to gall bladder adenomyomatosis was noted in two patients on CT.
|Figure 23: Hematoxylin and Eosin stained smear showing Charcot-Leyden crystals (white bold arrows with black outline) and eosinophils in the background of degenerated cells in a patient with hepatic visceral larva migrans in our study population|
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An important observation made among our study group was the presence of enlarged abdominal lymph nodes, predominantly in the peri-portal, peri-pancreatic, and upper abdomen mesentery. These nodes were labeled as enlarged when the short axis diameter was found to be >15 mm. Enlarged reactive lymph nodes were likely due to the underlying infective process and systemic spread of the larvae from the intestine to the liver.
Therapy for VLM has been advocated for all its systemic manifestations in the form of antihelminthic oral treatment using albendazole. It has been demonstrated that albendazole in the dose of 400 mg/day in three repeated cycles (initial two cycles for 14 days and third cycle for a week) for hepatic VLM is effective as treatment.  The laboratory markers used for monitoring the treatment efficacy included white blood cell, eosinophil counts, as well as liver transaminase enzymes.  They added a fourth course of praziquantel at a dose of 120 mg/kg for a short period of 3 days for the final normalization of the laboratory markers. The role of high dose albendazole therapy has also been described by some authors.  Use of steroids for ocular, neurological, and cardiac involvement by VLM has been demonstrated by a few investigators. ,,,, The above studies have indicated the need for prolonged therapy and intensive monitoring of the entire disease process.
The efficacy and ability of combined therapy using albendazole and prednisolone has been well documented. There are no definite guidelines as to the recommendations regarding the use of prednisolone for toxocariasis and VLM and the above investigators have used it in combination with albendazole for rare manifestations including myocarditis and oculo-neurological spread.
Usage of prednisolone therapy for hepatic VLM has been reported in few odd cases in literature and has shown beneficial results in these isolated studies.  However, random clinical drug trials are required for confirming clinical benefits of add-on steroids in hepatic VLM. In our study, repeated cyclical courses of high dose antihelminthic therapy using albendazole, without steroids were given for all patients. The average time duration over which therapy was given, ranged from 6 months to 1 year interval and a single therapeutic cycle varied from 2 to 4 weeks. Daily dose recommended was 400 mg/day, per orally. All the patients showed 100% compliance and tolerated the therapy well. All (n = 23 patients) reported improvement in clinical symptoms within 4-8 weeks of therapy and were asymptomatic within 6 months of initiation of therapy. Repeated laboratory and imaging follow-up was done to look for complete disease resolution.
Our study revealed that imaging resolution lagged behind the clinical resolution of the disease. This has been suggested, but not validated on long-term follow-up in few earlier studies. ,,
Our study had a few limitations. The diagnosis and follow-up of the patients was done on different modalities and at different time intervals. A prospective study with a consistent imaging modality and similar time period of monitoring may be utilized in further trials for further uniformity. The number of patients who underwent surgery was limited and hence the true efficacy of surgery as an optional mode of treatment could not be assessed.
In summary, this is the first report and interpretation of a series of patients on imaging where patients with histopathologically proven hepatic VLM were evaluated. Long-term follow-up on imaging was compared with laboratory markers, eosinophil counts, and clinical symptoms of the disease. Imaging was able to diagnose almost 40% of the patients with unsuspected hepatic focal lesions under evaluation. Imaging assisted in the final diagnosis and follow-up of the liver lesions and was found to be an effective means of depicting residual disease after the eosinophil counts, liver enzymes, and clinical symptoms resolved completely. This study raises the need for understanding the kind of medical antiparasitic therapy, treatment length, need for adjunctive drugs, and the role of surgery in nonresolving cases on follow-up scans.
| Conclusions|| |
This study reveals that hepatic VLM can be diagnosed on imaging with a diagnostic accuracy of almost 42%. Imaging characteristics are not specific, however indicative of this unique entity. The absolute eosinophil counts have a definite predictive value in diagnosis of this disease. Radiological resolution of the disease may not correlate with complete clinical remission and parasitic residual abscesses may be seen up to 2 years posttherapy. This warrants a need for further long-term studies and clinical trials to explore the requirement for prolonged medical therapy or surgery as an adjunct to the existing treatment options.
The authors thank Rita Gulabani for assistance in manuscript preparation, Abhishek for his technical assistance, and Vivek Kasana for his data collection and supervision.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16], [Figure 17], [Figure 18], [Figure 19], [Figure 20], [Figure 21], [Figure 22], [Figure 23]