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1
Department of Radiology, University of California—San Francisco, 505
Parnassus AVe. (M-372), San Francisco, CA 94143.
2
Present address: Department of Radiology, Children's Hospital Oakland, 747
Fifty-Second St., Oakland, CA 94609.
3
Department of Pediatrics, University of California San Francisco, San
Francisco, CA 94143.
Received December 14, 2000;
accepted after revision May 10, 2001.
Address correspondence to B. F. Kammen.
Abstract
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MATERIALS AND METHODS. We retrospectively analyzed 305 consecutive contrast-enhanced abdominal CT examinations of 218 children and young adults with no known liver disease, performed during 2 years at our institution, to identify focal fatty infiltration of the liver. The imaging criterion for focal fatty infiltration of the liver on helical CT was a geometric or ovoid low-attenuation area adjacent to the falciform ligament, gallbladder fossa, or porta hepatis. If a patient's findings met the CT criterion for focal fatty infiltration of the liver, all previous abdominal CT and MR imaging examinations performed for that patient were reviewed to assess the evolution of focal fatty infiltration of the liver.
RESULTS. Of 218 children and young adults, 20 (9.2%) met the CT criterion for focal fatty infiltration of the liver. In our population, focal fatty infiltration of the liver was identified only adjacent to the falciform ligament. The prevalence of focal fatty infiltration of the liver increased significantly with advancing age: 0% for ages 1 month—4 years; 7.3% for 5-9 years; 10.2% for 10-14 years, and 25.6% for 15-19 years (p < 0.0001).
CONCLUSION. Focal fatty infiltration of the liver was identified in 9.2% of patients in our population, and occurrence of this lesion in children increases significantly with advancing age. However, focal fatty infiltration of the liver is uncommon in infants and young children and should be a diagnosis of exclusion.
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When focal fatty infiltration of the liver has the appearance of a small nodule, it can be confused with a more serious hepatic abnormality [6,7,8,9]. Because a high percentage of CT examinations in children are performed to evaluate tumor progression, knowledge of the CT appearance of focal fatty infiltration of the liver is critical for accurate interpretation. Therefore we undertook this study to analyze the prevalence and spectrum of CT imaging findings of focal fatty infiltration of the liver in the pediatric population and in young adults.
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In patients with no known liver disease, CT was performed to evaluate for extrahepatic malignant tumor, abdominal pain, infection, or trauma. We excluded from our study patients with known liver disease, including those with history of a liver transplant, cirrhosis, congenital liver or biliary anomaly, liver abscess, or hepatic neoplasm.
After lesions that met the imaging criterion for focal fatty infiltration of the liver were identified on contrast-enhanced CT examination, each patient's radiology records were reviewed to determine if other CT or MR imaging examinations had been performed. When available, these additional studies were also evaluated for the presence of focal fatty infiltration of the liver. In patients with radiographic evidence of focal fatty infiltration of the liver, medical records were reviewed to exclude patients with symptoms referable to the liver and abnormal liver function tests.
CT Imaging
Imaging was performed with a helical CT unit (HiSpeed Advantage; General
Electric Medical Systems, Milwaukee, WI). All patients underwent
contrast-enhanced helical CT of the abdomen and pelvis with images obtained
during the portal venous phase of enhancement (scan delay, 70 sec).
Collimation ranged from 5 to 10 mm and pitch varied between 1:1 and 2:1.
Nonionic IV contrast medium (iohexol [Omnipaque 240; Nycomed, New York, NY]) at a dose of 2 mL/kg was injected via a uniphasic power injector (MCT Plus; Madrid, Pittsburgh, PA) at a rate of 1-2 mL/sec, depending on the gauge of the peripheral IV catheter and according to the manufacturer's guidelines. If the patient had a central venous catheter or a peripheral percutaneous catheter, a hand injection was performed.
MR Imaging
MR imaging examinations were performed on a 1.5-T magnet (Signa 1.5,
software version 4.8; General Electric Medical Systems) using a phased array
torso coil. A routine liver protocol (coronal T1 localizer, axial T1-weighted
and T2-weighted MR images) was used. Imaging techniques and parameters used
varied. The T1-weighted images were acquired using one or more sequences:
Axial, in-phase, fast multiplanar spoiled gradient-recalled imaging (FMPSPGR)
(TR range/TE, 90-150/4.2; flip angle, 70°); axial, out-of-phase, FMPSPGR
(TR range/TE range, 90-150/1.9-2.1; flip angle, 70°); and optional axial,
spin-echo (300-400/10-15). T2-weighted sequences were obtained with axial,
fast spin-echo (TR range/effective TE, 4000-5000/100; echo train length, 8)
and coronal single-shot fast spin-echo (TR/TE, infinite/100). The imaging
matrix was 256 x 128-192 pixels for spin-echo and gradient-echo
sequences and 256 x 256 for fast spin-echo sequences. The sampling
bandwidth was 16 kHz for FMPSPGR, fast spin-echo, and spin-echo, and 62.5 kHz
for single-shot fast spin-echo sequences. The section thickness was 5-8 mm
with a section gap of 1 mm. In patients requiring contrast enhancement,
multiphasic dynamic FMPSPGR images (TR range/TE, 90-150/4.2; flip angle,
70°) were obtained before and after the administration of gadopentetate
dimeglumine (Magnevist; Berlex, Wayne, NJ).
After unenhanced images were acquired, contrast material (0.1 mmol/kg of body weight) was injected IV as a rapid bolus, followed by a normal saline flush of 10 mL. Contrast-enhanced imaging was initiated immediately after completion of the saline injection (20 sec) and was repeated at 70 sec, 2 min, and 3 min to obtain multiphasic images (arterial, portal, and equilibrium phases). Delayed-phase contrast-enhanced gradient-echo images with fat suppression were acquired 5 min after injection of contrast material.
Image Interpretation
All 305 CT examinations were retrospectively analyzed by three pediatric
radiologists experienced in abdominal imaging; decisions were reached by
consensus. On CT, the imaging criterion for focal fatty infiltration of the
liver was a geometric or ovoid low-attenuation area adjacent to the falciform
ligament, gallbladder, or porta hepatis
(Fig. 1A).
To obtain an unbiased evaluation of the lesions of focal fatty infiltration of the liver selected by consensus review, three abdominal radiologists (different from the three pediatric radiologists who reviewed the studies in consensus) did a blinded review of 40 studies (the 20 with focal fatty infiltration of the liver and 20 negative controls). Each reviewer had to assess the liver for presence or absence of focal fatty infiltration of the liver and, if present, characterize the shape, size, and location.
When available, MR imaging examinations were considered accepted proof for the presence of focal fatty infiltration of the liver. On MR imaging, the criterion for focal fatty infiltration of the liver was a geometric or ovoid region adjacent to the falciform ligament, gall bladder fossa, or porta hepatis with loss of signal on out-of-phase images when compared with in-phase images (Figs. 1B and 1C). If an MR imaging examination was not available, the results from the initial consensus review were considered the standard of reference.
Statistical Analysis
Descriptive analysis was performed using proportions, means, standard
deviations, and ranges. The reviewer agreement among the three abdominal
radiologists who were unaware of the consensus results was evaluated using
kappa statistics [11]. To
further understand the effect of patient age and lesion size on the agreement
in the blinded review, we arranged the studies in two groups. The
"agreed" group included patients for whom all three radiologists
had consensus as positive or negative findings for focal fatty infiltration of
the liver; the "disagreed" group included patients for whom no
consensus readings were achieved by three radiologists in their independent
evaluations. We compared differences in patient age and lesion size between
the two groups for positives and negatives using Wilcoxon's rank sum test. The
effect of age on prevalence of focal fatty infiltration of the liver was
evaluated using a logistic regression analysis with 95% confidence interval
(CI) of odds ratios. Statistical calculation was derived using JMP 4.0 (SAS
Institute, Cary, NC). A significance level of 0.05 was considered as
statistically significant.
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The incidence of focal fatty infiltration of the liver increased with advancing age: for ages 1 month-4 years it was 0%; for ages 5-9, 7.3%; for ages 10-14, 10.2%; and for ages 15-19, 25.6%. Logistic regression analysis revealed a significant elevated risk of focal fatty infiltration of the liver with increase in age. The odds ratio per year was 1.24 with 95% CI (1.12, 1.39). Except for children in the 1 month—4 years group, in each age cohort the mean age was similar in patients with and without focal fatty infiltration of the liver, which confirms that the statistical significance was not likely due to selection bias of the study cohorts.
In the blinded review of 40 studies (the 20 patients with focal fatty infiltration of the liver and 20 negative controls), initial disagreement requiring some concession by one of the parties occurred in seven instances (five patients with focal fatty infiltration of the liver and two without). Kappa statistics of agreement for the 40 studies was 77% with 95% CI (55%, 94%), which was considered a good agreement. The size of the five lesions disagreed upon ranged from 2 mm to 8 mm (mean size ± SD, 5 mm ± 2.6 mm). Wilcoxon's rank sum test yielded p values of 0.449 for patient age and 0.001 for lesion size. Overall, for negative cases the percentage of consistent reading among three reviewers was 90% (18/20) with 95% CI (77%, 100%). For the positive cases, it was 75% (15/20) with 95% CI (56%, 94%).
Four patients with focal fatty infiltration of the liver underwent a total of 10 additional contrast-enhanced CT examinations, performed within 1 week to 17 months of the initially reviewed study. Nine of the 10 studies showed stability of the lesions. On one examination, the lesion was not identified. This examination was obtained between two examinations in which focal fatty infiltration of the liver was identified. One patient had an examination that included delayed imaging in which a low-attenuation lesion adjacent to the falciform ligament that was identified during the portovenous phase of enhancement persisted on the delayed images (Fig. 2A,2B). Three patients with focal fatty infiltration of the liver underwent both unenhanced and enhanced CT; in two of the three, unenhanced CT showed a geometric low-density region corresponding to the defect on the enhanced images (Fig. 3A). Two patients with CT evidence of focal fatty infiltration of the liver also had MR imaging that showed decreased signal on T1-weighted out-of-phase sequences when compared with in-phase images of the same region as shown by CT (Figs. 1A,1B,1C and 3A,3B,3C).
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The CT appearance of focal fatty infiltration of the liver was usually a low-attenuation geometric defect in the medial segment of the left lobe of the liver abutting the falciform ligament (Figs. 1A,1B,1C,2A,2B,3A,3B,3C) (Table 1). Less commonly, lesions were ovoid (Fig. 2A,2B) or identified on both sides of the falciform ligament (Fig. 4) (Table 1). In our study population, focal fatty infiltration of the liver was not identified adjacent to the gall bladder fossa or in the porta hepatis. Overall, the mean diameter of all lesions was 1.3 cm (range 0.4 - 2.2 cm).
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When the lesions were independently reviewed, the radiologists had overall good agreement. Agreement regarding large lesions was much greater than for small lesions. However, when the missed lesions were reviewed in consensus by the radiologists who had participated in the blinded review, agreement was then reached that focal fatty infiltration of the liver was indeed present. Patient age did not appear to affect agreement for positive cases. Regarding the disagreement on the two cases that were negative controls, the two lesions initially interpreted by one observer as being consistent with focal fat were later agreed upon by all three observers to be caused by streak artifact from the stomach.
Our study is limited by the fact that histologic proof was not obtained and biopsy would have been difficult to justify. In two of the 20 patients with focal fatty infiltration of the liver on CT, MR out-of-phase T1-weighted imaging showed loss of signal in the lesion related to the presence of microscopic fat that can be used as definitive proof for focal fatty infiltration of the liver (Figs. 1A,1B,1C and 3A,3B,3C). For the purpose of our study, in patients undergoing CT for abnormality not related to the liver, the characteristic CT appearance of a spherical or geometric low-attenuation defect that is penetrated by vessels not displaying mass effect was considered sufficient evidence of focal fatty infiltration of the liver. As seen in two patients, focal fatty infiltration of the liver sometimes can be detected on unenhanced scans depending on the size and amount of lipid content in the lesion. Defects from these lesions can also persist on delayed scans.
Follow-up studies in four patients showed no change in the appearance of the lesion, which is frequently the case with focal fat in the liver. However, focal fatty infiltration of the liver can be transient in nature and may not consistently be seen on examinations; the case of one patient in our study corroborated this. In adults, it has been shown that fat deposition and reversal can be quite rapid, on the order of three weeks [10].
Differential diagnostic possibilities for a focal low-attenuation lesion in the liver include a flow-related pseudolesion. This entity has been described in the characteristic locations for focal fatty infiltration of the liver and can occur during the hepatic arterial phase of helical scanning related to vascular variations in the dual blood supply to portions of the liver [12]. All livers reviewed in this study were imaged during the portal venous phase of enhancement, which makes flow phenomena an unlikely cause of the lesions identified.
The major challenge can be the differentiation of nodular focal fatty infiltration of the liver from a malignant neoplastic lesion. The characteristic location and lack of mass effect in children and young adults who had no evidence of liver disease support the diagnosis of focal fatty infiltration of the liver. When there is doubt of the diagnosis, MR imaging can confirm the presence of microscopic lipid infiltration [4, 5]. Some have advocated using a combination of CT and liver scintigraphy to confirm the presence of focal fat, because fat deposition should not produce a defect on colloid scans [2, 7, 8]. Xenon-133 scanning may also prove useful because the 133Xe is taken up by lipid [13].
In conclusion, focal fatty infiltration of the liver was identified in 9.2% of patients evaluated in our study. In patients older than 5 years, the incidence of focal fatty infiltration of the liver increases with advancing age and should be taken into consideration when evaluating the liver for possible disease. In children younger than 5 years, focal fatty infiltration of the liver is extremely uncommon and should be a diagnosis of exclusion. Liver lesions with findings suggestive of disease should be further investigated to exclude a more serious abnormality. However, if the diagnosis of focal fatty infiltration of the liver is suggested, a lipid-sensitive sequence on MR imaging can reliably establish the diagnosis.
Acknowledgments
We thank Wendy Neale for assistance with manuscript preparation.
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