Introduction

Lobular dissecting hepatitis (LDH) is a specific form of chronic hepatitis. The hallmark histopathologic findings for LDH is the disruption of normal lobular architecture. The lobular parenchyma is divided by fine collagen and reticulin fibers into single hepatocytes and small groups of cells.¹ The division of hepatocytes is sometimes accompanied by inflammatory cellular infiltrates comprised of neutrophils, macrophages, lymphocytes, and plasma cells.² The etiology of LDH is unknown. Despite being classified as a chronic hepatitis, once the diagnosis is made, there is a relatively rapid progression of the clinical signs with a poor long-term prognosis. In recent review of canine hepatitis, LDH was confirmed in 7 dogs of a case series of 101 dogs over a 4 yr period (∼7%), with LDH having the shortest survival time.³ In a collection of 21 cases of LDH, the average age at first presentation was 11 mo, with over 54% of the cases presenting before 7 mo of age.⁴

Case Report

A 9 mo old female intact golden retriever presented to Ohio State University’s Veterinary Medical Center for evaluation of chronic lethargy and decreased appetite. The dog weighed 20.8 kg with a body condition score of 4/9. The owners reported the dog was smaller than her littermates with less activity. The dog had a subjectively dull mentation on the physical examination. The rest of the physical examination was unremarkable. The serum biochemistry profile at presentation revealed the following increased liver enzymes: alanine aminotransferase 183 IU/L (normal range 10–55 IU/L), aspartate aminotransferase 104 IU/L (12–40 IU/L), alkaline phosphatase 308 IU/L (15–120 IU/L), and gamma-glutamyltransferase 18 IU/L (<3–6 IU/L), consistent with a mixed hepatocellular and cholestatic pattern. The blood urea nitrogen and albumin were both at the low end of the normal range with a blood urea nitrogen of 5 mg/dL (5–20 mg/dL) and albumin of 3.1 g/dL (2.9–4.2 mg/dL). Plasma ammonia was normal at 13 µmol/L (0–29 μmol/L). The pre- and postbile acids were both elevated at 26.4 and 88 µmol/L (25 µmol/L is high end of normal), respectively. Cholesterol was normal at 157 mg/dL (80–315 mg/dL), glucose was normal at 108 mg/dL (77–126 mg/dL), and total bilirubin was normal at 0.2 mg/dL (0.1–0.4 mg/dL). A coagulation panel revealed a normal prothrombin time of 12.9 s (9.0–21.0 s) and a slightly elevated partial thromboplastin time at 9.0 s (6.0–7.5 s). A computed tomographic angiography (CTA) of the abdomen was requested to evaluate for a portosystemic shunt.

A multiphase CTA was performed of the abdomen. A precontrast series was acquired in a helical fashion from the caudal aspect of the heart to include the full abdomen extending to the acetabula. The CTA scan was performed using an 8-detector helical computed tomography (CT) scanner^a with the settings 120 kVp, 150 mA, 0.6 s tube rotation time, 1.25 mm slice thickness, and 1.35 pitch. Images were acquired in the transverse plane with a standard soft tissue filter algorithm using window level of 40 and window width of 400 display settings and bone filter algorithm using window level of 250 and window width of 2500 display settings. Images were reconstructed into the dorsal and sagittal planes during postprocessing. A timing bolus technique was used to plan for an arterial phase, venous phase, and a delayed venous phase. An image that contained the aorta, caudal vena cava, and portal vein was selected for evaluation of bolus timing. Images were obtained at a 0.625 mm slice thickness every 2 s for a total acquisition time of 40 s using a power injector at a rate of 3 mL/s via a left cephalic venous catheter. The timing bolus was performed using Iohexol (240 mgI/mL)^b with a dose of 240 mgI/kg. The arterial phase was timed at 12 s, portal phase at 15 s, venous phase at 24 s, and the delayed phase occurred at 120 s. The multiphase CTA was then performed using an Iohexol dose of 480 mgI/kg administered using a power injector at a rate of 3 mL/s via a left cephalic venous catheter.

Numerous well-defined, hyperattenuating, minimally contrast-enhancing nodules/masses of various sizes were identified throughout all liver lobes. Multiple nodules caused bulging of the hepatic capsule. The largest mass measured ∼3.6 × 3.4 × 3.1 cm in diameter for length × width × height, respectively. The cross-sectional diameter sizes ranged from 0.43 to 3.6 cm. Most of the nodules were <3 cm. Circular regions of interest for nodules and masses were drawn on transverse images with the largest cross-sectional diameter to measure Hounsfield units (HU). The region of interest included as much of the nodule possible without extending beyond the borders of the nodule or including discrete blood vessels. Three nodules/masses were chosen to measure on the precontrast images as well as during each phase. The nodules were hyperattenuating compared with hepatic parenchyma on the precontrast series of images (Figures 1A, B). Precontrast HU of the nodules were ∼75 HU (standard deviation [SD] 11.4), while the hepatic parenchyma was approximately 50 HU (SD 8.9). Vasculature was identified within and around the hyperattenuating nodules on both the arterial and venous phases (Figure 1C). The vasculature within the nodules during the arterial phase was irregular and tortuous. The nodules remained hyperattenuating to hepatic parenchyma on the arterial phase, whereas the nodules were iso-to-mildly hyperattenuating on the portal, venous, and delayed phases; the nodules were ∼85 HU (SD 15.8) on arterial phase, 129 HU (10.5) on the portal phase, 116 HU (SD 11.3) on venous phase, and 109 HU (SD 10.7) on the delayed phase. The circular regions of interest for background parenchyma were drawn on the same transverse images as the masses/nodules. The region of interest included hepatic parenchyma without a portion of the nodule and did not include discrete blood vessels. Surrounding the hepatic parenchyma was ∼65 HU (SD 9.7) on the arterial phase, 103 HU (11.4) on the portal phase, ∼111 HU (SD 12.1) on the venous phase (Figure 1D), and ∼105 HU (SD 13.9) on the delayed phase. No extrahepatic or intrahepatic portosystemic shunting vessel was identified. Other findings included a splenic venous thrombus near the confluence of the splenic vein and left gastric vein that extended to the portal vein.

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Prior to obtaining a needle biopsy, fine-needle aspiration using ultrasound guidance was performed. On ultrasound, there were numerous hyperechoic hepatic nodules with no portal markings surrounded by ultrasonographically normal hepatic parenchyma. Fine-needle aspiration of a representative nodule within the left liver was performed. Twenty-five and 22 gauge needles were used with a sewing-needle technique with and without negative-pressure suction. The cytology was consistent with hepatocellular hyperplasia with mild vacuolation, presumed to be glycogen accumulation. There was no infectious or neoplastic process. A needle biopsy using a 16 gauge needle^c was performed using ultrasound guidance of two nodules within the left liver (one from the left lateral liver lobe and one from the left medial liver lobe). Three total core biopsies were acquired and submitted for histopathologic evaluation; a left lateral nodule was large and most safely accessible, so it was sampled twice. The general hepatic parenchyma was not sampled, and only discrete nodules were sampled.

Histopathology showed that the lobular architecture of the liver was lost because of the presence of significant diffuse fibrosis composed of fine septa of collagenous fibers that dissect through the lobule, isolating individual or small clusters of hepatocytes (Figure 2). Variably sized nodules were apparent. Portal tracts generally retained normal portal vein profiles, but they were small in ∼10% of the tracts. The fine septa were associated with a light-mixed inflammatory infiltrate composed of lymphocytes, macrophages, and smaller numbers of neutrophils (Figure 2A). Hepatocytes were variably vacuolated and in other areas modestly pleomorphic with variously sized nuclei. Sirius red staining was used to highlight the fine fibrous septa (Figure 2B). Copper stain revealed a moderate amount of copper retention with a distribution that spared the periportal regions. Iron was limited to isolated macrophages most commonly within the septa. Lipofuscin was distributed in a pattern similar to that of the copper granules. The histopathologic diagnosis was LDH.

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The dog was discharged with treatment for medical management of presumed hepatic encephalopathy while the biopsy results were pending. The patient was prescribed lactulose (5 mL of 0.25 mL/mg by mouth every 12 hr), amoxicillin (250 mg by mouth every 12 hr), and omeprazole (20 mg by mouth every 24 hr). It was recommended that she eat a lower protein, hydrolyzed soy diet^d to reduce the risk of hepatic encephalopathy.⁵ Approximately 3 mo later, the owner reported that the dog was clinically normal. She was still eating the hydrolyzed soy diet, and all medications had been discontinued. No follow-up laboratory values were available for review.

Discussion

Multifocal, multilobar, and hyperattenuating hepatic nodules on noncontrast CT are an abnormal finding. Reports and descriptions of precontrast hyperattenuating nodular hepatic disease are lacking in veterinary medicine, and therefore, the differential list of potential etiologies is not only vague, but unknown. The working differential diagnosis list prior to sampling included granulomatous disease with fungal and/or bacterial abscesses, multifocal fibrotic disease, or neoplasia. CT descriptions of hepatic masses of both malignant and nonmalignant origins describe variations of arterial, venous, and equilibrium enhancement patterns; however, the precontrast characterization of hepatic nodules is primarily hypoattenuating to isoattenuating relative to the surrounding parenchyma.^6–10 The postcontrast (arterial, portal, venous, and delayed phases) characteristics of the nodules were similar to the enhancement HU values reported for nodular hyperplasia or hepatocellular carcinoma; however, the timing technique used differed.¹⁰ This is the first report of a rare form of hepatitis described on both noncontrast-enhanced CT, as well as multiphase CTA. The significance of the splenic venous thrombus is unknown as the coagulation panel was unremarkable, and there were no infarctions of the splenic parenchyma or peritoneal effusion.

Increased liver enzymes are nonspecific in dogs with a heterogeneous array of differential diagnoses that may arise from primary or secondary causes of hepatic pathology. Canine hepatopathies, both acute and chronic, may be caused by metabolic disease, infectious organisms (e.g., viral, parasitic, bacterial, fungal), excess copper accumulation, toxic substances, or neoplasia.¹¹ A recent review article focused on inflammatory hepatopathies found that idiopathic hepatitis was the most common diagnosis for both acute and chronic hepatitis in a population of dogs in the Netherlands.³ A specific inciting etiology for hepatopathy can be difficult to determine, and the use of diagnostic imaging varies for the workup of hepatic disease based on clinician preference and available tools/techniques. Advanced modalities may include one or a combination of ultrasonography, nuclear medicine, CT, or MRI depending on availability and clinical questions of the attending clinician. Ultrasound-guided needle biopsies of the focal liver lesions were chosen because of the increased accuracy of histopathologic diagnosis. Needle core biopsies provide a larger collection of portal triads compared with fine-needle aspirations, which are vital for the evaluation of inflammatory hepatopathy compared with neoplasia.^12–14 Surgical-wedge biopsy or necropsy would provide larger samples to increase the diagnostic certainty; however, these options were not available in this patient.

The cause for the hyperattenuating appearance of the nodules relative to the liver is unknown. The collection of dense collagen fibers between hepatocytes is hypothesized as a contributing cause for the hyperattenuating appearance, although this is not supported in veterinary or human literature. Tissue density and the atomic elemental numbers that comprise the tissue are the major factors causing attenuation of the computed tomographic photons.¹⁵ The authors propose that the density of the fibers is more of a contribution to the change in the attenuation values rather than the elemental composite of the tissue. There is mixed information regarding the role of copper in causing hyperattenuating nodules in a noncontrast-enhanced CT. Copper accumulation within the liver of humans has not shown to change the CT attenuation values.¹⁶ However, patients with Wilson’s disease, a hereditary disorder resulting in an accumulation of copper in the liver, have demonstrated hyperattenuating nodules in noncontrast CT.¹⁷ It is not known what concentration of copper is needed to increase the attenuation factor of the liver, if it does indeed impact the attenuation values.

In a retrospective study of primary hepatitis in dogs, LDH had the lowest mean survival time when compared with copper-associated or idiopathic types for both acute and chronic hepatopathies.³ The mean survival time for LDH was 2.9 mo with cases that ranged 0.1–11.0 mo; in comparison, the mean survival times were 8.1 and 4.1 mo for copper-associated and idiopathic chronic hepatopathies (ranging up to 36.8 and 30.6 mo), respectively. Acute hepatopathy mean survival time was 9.2 mo with survival times up to 35 mo.³ The long-term management of this patient with a lower protein, hydrolyzed diet, and the duration of survival is unknown as the patient was lost to follow-up.

Conclusion

This is the first case report using CT to describe the rare condition of LDH. The imaging characteristics are relatively unique with multiple hyperattenuating nodules throughout the liver of a young dog on noncontrast-enhanced images. A larger sample of cases is needed to confirm this as a consistent finding. Increasing the number of cases is needed to better understand what tissue characteristics contribute to the hyperattenuating appearance of the nodules.