Hepatic artery pseudoaneurysms and hepatic ischaemic injury: a rare complication of polyarteritis nodosa

Abstract

A woman in her 70s presented with months of intermittent fevers, severe fatigue, headaches, abdominal pain and haematuria. She developed acute onset left-sided weakness and was found to have radiographic evidence of right frontal and left parietal intraparenchymal haemorrhages with subarachnoid haemorrhage. She also had markedly elevated liver transaminases with subsequent abdominal MRI that revealed hepatic artery pseudoaneurysms (HAP) requiring embolisation. The case required a multidisciplinary approach consisting of hepatology, interventional radiology and rheumatology. Ultimately, the aetiology was attributed to polyarteritis nodosa (PAN). Through this case report, we highlight HAP as an extremely rare complication of PAN. Although it is a challenging diagnosis to make, it has a favourable response to immunosuppression with high-dose corticosteroids.

Background

Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis preferentially targeting medium-sized arteries resulting in aneurysms. It typically involves nerves and skin, however, it can affect the gastrointestinal tract, kidneys, heart and central nervous system (CNS).¹ The estimated annual incidence of PAN in adults is 2–9 cases per million, with an average onset of disease between 25 and 50 years of age.² Although there is an association with hepatitis B and C infection, PAN remains largely idiopathic.³ A French retrospective study concluded that factors including age >65 years, hypertension and gastrointestinal manifestations requiring surgery are independent predictors of death.⁴ Another retrospective analysis demonstrated worse outcomes in late-onset PAN (age >65 years) with increased treatment-associated morbidity.⁵

Cases of hepatic artery pseudoaneurysm (HAP)⁶ are typically encountered secondary to trauma or iatrogenic causes.^6–11 However, HAP can be a life-threatening and rare manifestation of the inflammatory vasculitides such as PAN. There is high morbidity and mortality if the diagnosis is delayed and treatment is not initiated promptly.^12–17 Complications of HAP include spontaneous rupture, gastrointestinal bleeding, haemoperitoneum, haemorrhagic shock and death.¹⁸ We present a case of HAP complicated by hepatic ischaemic injury secondary to vasculitis. Prompt initiation of steroids and immunomodulator therapy was conducive to a good patient outcome.

Case presentation

The patient is a woman in her 70s with a history of hypertension, hypothyroidism, meningioma status postresection, nephrolithiasis with recent lithotripsy, and seizure disorder on antiepileptics. She presented with acute onset left-sided weakness, abdominal pain and haematuria in a background of months of intermittent fevers, fatigue, headaches and abdominal pain. On admission to a nearby community hospital, her vitals were temperature of 36.5°C, blood pressure 110/70, heart rate 78 and oxygen saturation at 100% on room air. On examination, she was noted to have left-sided weakness and right-sided gaze preference concerning for an acute stroke. Basic laboratory investigations included a basic metabolic profile notable for a potassium of 2.5 mMol/L but otherwise within normal limits. Liver chemistry demonstrated elevated aminotransferases with AST 310 U/L (8–33 U/L), ALT 592 U/L (4–36 U/L) and a normal ALP of 47 U/L (44–147 U/L). Complete blood count was significant for an elevated white blood count of 12.4×10⁹ cells/L and haemoglobin of 96 g/L (baseline normal at >130 gm/L) with a normal platelet count. Her coagulation studies showed a mildly elevated INR of 1.5, PT of 18.3 s and PTT 34.6 s. Her urinalysis demonstrated large proteinuria and haematuria. Emergent CT head revealed multicompartmental haemorrhage most predominant along the superior aspects of the parietal lobes bilaterally, with only localised mass effect and no evidence of midline shift (figure 1). CT Head angiogram showed beaded irregularity of the cervical internal carotid arteries compatible with fibromuscular dysplasia without dissection, vessel occlusion or stenosis (figure 2). Brain MRI redemonstrated bilateral parietal intraparenchymal haemorrhages, as well as subjacent subarachnoid haemorrhage along the bilateral frontal and parietal sulci and left occipital sulci (figure 3). Given these findings, the patient was started on a nicardipine drip to keep her systolic blood pressures below 140 mm Hg and she was transferred to our tertiary academic centre for further workup and monitoring in our neurological ICU.

Figure 1.

Axial CT images demonstrating multicompartmental haemorrhage most predominant along the superior aspects of the parietal lobes bilaterally with only localised mass effect. No evidence of midline shift. Redemonstration of a left temporal craniectomy with cranioplasty. Reconstruction for prior meningioma resection with suspected residual meningioma measuring 1.8×1.2x1.3 cm. Note residual contrast as this was done after an abdominal CT with contrast.

Figure 2.

CT head angiogram coronal and sagittal slices showing beaded irregularity of the cervical internal carotid arteries (red arrows) compatible with fibromuscular dysplasia, without dissection, vessel occlusion or stenosis.

Figure 3.

Susceptibility-weighted axial MR sequences demonstrate the bilateral parietal lobe intraparenchymal haemorrhages (I, II) and bilateral subdural haematomas (III). Images from the vertex through the parietal lobes.

She was maintained on continuous EEG monitoring which displayed no seizures. Repeat stability head CT scans were without progression of her intracranial bleed. She underwent a transthoracic echocardiogram which was normal. Neurosurgery was consulted and recommended no surgical intervention. CT with contrast of the chest, abdomen and pelvis was obtained to rule out malignancy. Her chest and pelvis were unremarkable, however, abdomen revealed a 7×5 cm wedge-shaped hypoattenuation in the right posterior hepatic lobe predominantly involving segment 6, with an enhancing nodule of up to 1.5 cm along the innermost aspect (figure 4). Subsequent abdominal MRI showed a hypervascular focus within segment 5 on the arterial phase measuring 1.4×1.1 cm which was compatible with a right hepatic artery branch pseudoaneurysm—all major hepatic vessels were patent and there was no evidence of cirrhosis or steatosis (figure 5).

Figure 4.

CT abdomen with geographic hypoattenuation in the right posterior hepatic lobe predominantly involving segment six extending to the capsule measures up to 7×5 cm with an enhancing nodule measuring up to 1.5 cm along the inner most aspect.

Figure 5.

Delayed venous phase Mr abdomen with hypervascular focus is shown on the arterial phase measuring 1.4×1.1 cm, which follows blood pool on later phases, compatible with a right hepatic artery branch pseudoaneurysm. Also redemonstrated is wedge-shaped hypoenhancement extending to the periphery within segment 6.

The abrupt elevation of aminotransferases, wedge-shaped hypoattenuation and HAP were concerning for ischaemic injury. Notably, the patient had undergone recent lithotripsy for kidney stones and so it was originally thought this could be a precipitating cause. Given the high risk for bleeding from the pseudoaneurysm, interventional radiology was consulted for vascular embolisation. Hepatic artery angiography revealed multiple bilobar intrahepatic aneurysms with a dominant one in the right posterior location showing contained extravasation—findings were concerning for hepatic artery vasculitis.(figure 6). Interrogation of other arterial beds showed beading, stenosis, and a pseudoaneurysm in the renal artery (figure 7). She underwent successful glue embolisation (figure 8), her haemoglobin remained stable, and her liver enzymes continued to downtrend.

Figure 6.

Coeliacarteriogram demonstrating multiple irregular aneurysms of various size throughout both lobes of the liver. The largest of these is in the right lower lobe and shows evidence of contained extravasation. The common hepatic artery is also markedly irregular in appearance. Delayed phase image shows the contained pooling of contrast within the pseudoaneurysm.

Figure 7.

Renal angiogram with beading appearance concerning for fibromuscular dysplasia.

Figure 8.

Post n-BCA: Lipiodol embolisation of the large pseudoaneurysm shows the glue cast and exclusion of the PA. n-BCA, N-butyl cyanoacrylate.

Further investigations

The patient underwent further rheumatological workup which included an elevated sedimentation rate of 66 mm/hour (1–20 mm/hour), elevated C reactive protein 10.7 mg/dL (< 10 mg/L), high complement C3 of 181 mg/dL (80–178 mg/dL) and normal complement C4 of 36 mg/dL (12–42 mg/dL). Urine albumin, immunoglobulins (including IgA), antineutrophil cytoplasmic antibodies, antinuclear antibody, interferon-gamma release assay and cryoglobulin levels were unremarkable. Lyme screening was positive, however, confirmatory Western Blot returned negative. Hepatitis B and C testing were negative. Carotid artery abnormalities raised concern for fibromuscular dysplasia and cerebral angiography was considered but ultimately deferred as there would have been a high risk of precipitating dissection.

Differential diagnosis

N/A.

Treatment

Treatment was started with steroids at 1 mg/kg daily for presumed PAN given multisystemic involvement of CNS (intraparenchymal haemorrhage, beading of cervical internal carotid arteries), liver (multiple hepatic pseudoaneurysms) and kidney (proteinuria, haematuria, vascular beading and pseudoaneurysms).

Outcome and follow-up

She was transitioned to an extended steroid taper and received cyclophosphamide 500 mg with intravenous Mesna prior to discharge with a planned total course of 6 doses every 2–3 weeks. Thiopurine methyltransferase level was low and thus azathioprine as maintenance therapy was deferred. She was started on trimethoprim-sulfamethoxazole for pneumocystis jirovecii pneumonia prophylaxis, proton pump inhibitor for gastric protection and calcium-vitamin D supplements. She responded well clinically and was without significant myelosuppression on outpatient follow-up. She is now back home with 24/7 supervision after completing 1 month of inpatient rehabilitation.

Discussion

HAP refers to a collection of blood or ‘haematoma’ into surrounding tissue following hepatic vessel injury that remains in persistent communication between the originating vessel and the adjacent cavity. HAP is a rare phenomenon typically associated with trauma or iatrogenic complications of abdominal procedures including laparoscopic cholecystectomy, percutaneous procedures or liver transplants. More unusual causes include infection,⁶ acute pancreatitis¹⁹ and inflammatory disorders such as vasculitis.¹⁶ HAP may be an incidental imaging finding or present, as our patient did, with abdominal pain and abnormal liver enzymes, or worse with rupture, haemodynamic instability and catastrophic haemorrhage.²⁰

Angiography is the diagnostic test of choice for HAP with a sensitivity of 96%,²¹ with digital subtraction angiography considered to be the gold standard. However, non-invasive imaging methods including CT angiography and MR angiography as used in our patient, have been gaining favour due to obtaining a quicker diagnosis and being less invasive however sensitivity and specificity varies.^{22 23}

Embolisation is the gold standard treatment for hepatic pseudoaneurysms and is usually an endovascular approach involving coils, thrombin or N-butyl cyanoacrylate or ‘glue’. Our patient underwent endovascular embolisation using glue technique which has a high viscosity and short polymerisation time. Our patient had active extravasation from a likely inflammatory aneurysm in a right posterior division branch artery. Her bleeding hepatic vessel was very small in calibre (1 mm) and tortuous in configuration. In addition, the cause of this patient’s vasculitis was not known at time of her procedure, and arteries in certain vasculitides can be quite friable and prone to injury. Distal catheterisation to achieve proximal/distal microcoil embolisation was not feasible in this patient, nor would it definitively occlude the actively bleeding aneurysm as intrahepatic collaterals can be robust. The n-BCA embolisation, as performed, was the safest and most effective way to treat this patient. This embolic can be pushed to thrombose the bleeding vessel and aneurysm neck permanently and quickly despite small vessels and vascular tortuosity. The n-BCA/Lipiodol ratio can also be customised to affect speed of thrombosis based on vessels size and perfusion. In this case, a 1:1.5 concentration was used and there was immediate cessation of bleeding with preservation of distal perfusion. Complications from glue therapy include nontarget vascular occlusion, premature polymerisation and catheter retention, and delayed polymerisation with migration of glue.²⁴ A few case reports^25–27 have described percutaneous approaches to embolisation of HAP, which offered advantages of being less invasive, no need for general anaesthesia and lower risk of organ damage. Disadvantages included requiring skilled personnel to perform the procedure and inadvertent nontarget catheterisation. Another treatment option is the placement of an angiographic stent which can preserve visceral perfusion when sacrificing the artery is not tolerable and has been trialled as a safe and effective method.²⁸ Lastly, surgical ligation or surgical resection are other options when previous methods are unavailable, have failed or pseudoaneurysm recurs.²⁵

In our case study, our patient was an elderly female with HAP in the setting of newly diagnosed PAN. Interestingly, she presented immediately after lithotripsy for nephrolithiasis, thus corresponding to an iatrogenic complication in an individual predisposed by inflammation and aneurysmatic changes in the hepatic arterial vasculature. There are only a few case reports in the literature describing this rare clinical presentation. Most patients presented with life-threatening intraabdominal haemorrhage. This emphasises the importance of having a high degree of suspicion for vasculitis in elderly patients who present with unexplainable visceral aneurysms. The risk of rupture, as high as 76%,²¹ correlates with the size of the pseudoaneurysm and some studies advocate for prophylactic treatment.²⁹ Overall, PAN is a treatable disease in which glucocorticoids and cyclophosphamide represent the cornerstone of therapy. Cyclophosphamide is used as induction therapy while azathioprine is often used for remission maintenance for a total duration of treatment of 18 months. For persons with this disease receiving treatment, the 5-year survival approaches 85%.³⁰

Learning points

• Hepatic artery pseudoaneurysms (HAP) usually occur secondary to trauma or iatrogenic intervention, however, it can be an exceedingly rare and potentially life-threatening manifestation of inflammatory vasculitides such as polyarteritis nodosa (PAN).

• HAP may present in various ways such as an incidental finding on imaging, as a manifestation of hypoxic liver injury with elevated liver transaminases, or clinically with abdominal pain and catastrophic bleeding.

• Management options for HAP include endovascular embolisation (gold standard), percutaneous embolisation, placement of an angiographic stent, surgical ligation or surgical resection as a last resort.

• It is crucial to consider inflammatory vasculitides in elderly patients who present with unexplainable visceral aneurysms.

• Glucocorticoids plus cyclophosphamide are the first-line treatment for PAN.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).