Spontaneous hepatic rupture due to primary amyloidosis

Abstract

Spontaneous hepatic rupture is an uncommon cause of haemorrhagic shock and very rarely happens due to amyloidosis. This report describes one such case in which a middle-aged man presented in extremis. He was managed initially with massive transfusion, interventional radiology embolisation and decompressive laparotomy for abdominal compartment syndrome. Subsequent coagulopathy was treated with activated factor VII due to deficient native activity. Serum protein electrophoresis and liver biopsy during his hospital course yielded a diagnosis of amyloidosis, which was treated palliatively with steroids and bortezomib. Despite supportive care, he died 10 days after presentation. This case illustrates the importance of considering an uncommon pathology when a patient presents with a condition in an uncommon way.

Background

Bleeding from liver capsular rupture is a rare presentation of amyloidosis.¹ Its management can be difficult due to the low index of suspicion and the condition in which the patient may present. This case is one such example and serves as a reminder to consider the unexpected when patients present in uncommon ways.

Case presentation

A 60-year-old man presented to the emergency department with 2 days of worsening diffuse abdominal pain and distension. He had no prior surgical history and did not report any nausea, vomiting, changes to bowel habits or rectal bleeding. He also denied any recent trauma, even mild. He was diagnosed with factor X deficiency 1 year earlier during an episode of rectal bleeding, but did not complete his planned workup with haematology afterwards. Physical examination was notable for hypotension, with mean arterial pressures between 40 and 50 mm Hg, and abdominal examination showing gross distension and diffuse tenderness consistent with peritonitis.

Investigations

Initial investigations included basic laboratory tests (complete blood count, coagulation profile, arterial blood gas and serum lactate), all of which indicated severe haemorrhagic shock and developing liver dysfunction (haemoglobin 51 g/L, platelets 117×10⁹ cells/L, international normalised ratio 3.57, partial thromboplastin time 65 s, arterial pH 6.88, base deficit 23 mmol/L and lactate 18 mmol/L (reference range <2.1 mmol/L). At this early juncture, it was unclear whether the liver dysfunction was due to impaired perfusion or underlying hepatic pathology. Urinalysis on presentation was notable for large proteinuria (100 mg/dL). CT arteriography showed multiple punctate areas of extravasation (figure 1). A multidisciplinary decision was made for assessment by interventional radiology, which found on angiography the same punctate areas of extravasation in the right hepatic arterial distribution (figure 2) and performed embolisation successfully.

Figure 1.

CT angiography of the abdomen at presentation demonstrating one of many areas of extravasation within the liver.

Figure 2.

Conventional angiography of the right hepatic artery demonstrating multiple areas of punctate extravasation.

Further investigation followed in the next few days after the patient failed to respond to blood products meant to reverse his coagulopathy. Factor activity assays showed low factor VII activity of 27% (reference range 50%–150%) and normal factor IX (78%) and factor X (59%) activity. Of note, his previous factor X level a year prior was 19% (factor V level at the time was 74%; no other factors were tested at any time). The coagulopathy was partially reversed with anti-inhibitor coagulant complex (FEIBA, Takeda Pharmaceutical Company, Lexington, Massachusetts, USA). Exploratory laparotomy showed abnormal appearance of the liver and spleen, and surgical biopsy revealed hepatic amyloidosis, with Congo red staining highlighting amyloid depositions. Serum immunoglobulin (Ig) assays showed low/normal IgG of 646 mg/dL (reference range 700–1600 mg/dL), IgA of 119 mg/dL (reference range 70–400 mg/dL) and IgM of 56 mg/dL (reference range 40–230 mg/dL). Serum protein electrophoresis was notable for highly elevated lambda light chains of 1514 mg/L (reference range 5.7–26.3 mg/L), along with normal kappa light chains of 14.7 mg/L (reference range 3.3–19.4 mg/L), and decreased free light chain ratio of 0.01 (reference range 0.26–1.65). Other results of protein electrophoresis were as follows: alpha 1 globulin of 0.30 g/dL (reference range 0.13–0.45 g/dL), alpha 2 globulin of 0.43 g/dL (reference range 0.37–0.93 g/dL), beta globulin of 0.50 g/dL (reference range 0.69–1.29 g/dL), gamma globulin of 0.57 g/dL (reference range 0.58–1.50 g/dL) and total protein of 4.4 g/dL (reference range 6.58–8.51 g/dL). Transthoracic echocardiogram showed no evidence of cardiac amyloidosis with a preserved left ventricular ejection fraction of 63% and no anatomic abnormalities.

Differential diagnosis

The differential diagnosis evolved throughout the patient’s clinical course. At initial presentation, our first thought was visceral artery pseudoaneurysm or aneurysm rupture based on the limited history available and the initial laboratory and imaging findings. However, after successful embolisation of extravasating vessels, the patient’s persistent coagulopathy and bleeding needed another explanation. Based on the appearance of his liver and spleen during exploratory laparotomies, lymphoma and systemic amyloidosis entered the differential diagnosis. The fragility of his liver capsule was notable, as even light touch caused persistent large bleeding. Results of the surgical biopsy confirmed amyloidosis of the liver. The final step was to determine which type of amyloidosis, and his elevated lambda light chains and IgG was suspicious for multiple myeloma. However, due to lack of bone marrow biopsy and his condition, workup was unable to be definitively completed, and his working diagnosis at the time of death was primary amyloidosis.

Treatment

Initial treatment focused on blood product balanced resuscitation and haemorrhage control. Two approaches were considered—interventional radiology or exploratory laparotomy. Due to the findings of multiple punctate areas of haemorrhage, multidisciplinary team consults decided that interventional radiology may be more successful at selective embolisation, especially as some of these areas appeared deep in liver parenchyma on imaging. Interventional radiology successfully embolised these areas. However, his development of abdominal compartment syndrome required exploratory laparotomy. After decompression, attempts at haemostasis for persistent liver parenchymal oozing in this setting were only marginally successful, as tissues were friable and the liver capsule very delicate. Cautery and adjuncts were minimally effective; and the bleeding seemed coagulopathic in nature.

Treating his coagulopathy was the next major issue, and traditional blood products were unsuccessful. Factor assays proved valuable in this setting, as a finding of low factor VII activity prompted use of FEIBA, which contains inactivated factors II, IX, and X and activated factor VII. This produced some degree of coagulopathy reversal, although this effect was the only transient due to the short-lived activity of the factors and his hepatic failure.

After diagnosis of lambda light chain multiple myeloma, treatment included steroids and bortezomib, a proteasome inhibitor designed to incite B-cell apoptosis and reduce lambda light chain burden. This approach, however, was the only palliative in nature as the damage to our patient’s liver was irreversible.

Outcome and follow-up

Despite ongoing active resuscitation and investigations, his health continued to decline, with worsening encephalopathy, coagulopathy and multiple organ failure. Ten days after admission, he developed an arrhythmia, which progressed to pulseless electrical activity, and multiple rounds of cardiopulmonary resuscitation were performed without success. An autopsy was deferred by his family.

Discussion

Amyloidosis is typically a systemic disease process with multiple potential aetiologies. Although rare, amyloidosis must be considered when other causes for presentation similar to our patient are ruled out. A number of cases have been reported describing liver/splenic rupture from amyloidosis with mostly poor clinical outcomes.^1–7

Our patient presented in haemorrhagic shock from hepatic bleeding. The first decision point was whether to pursue endovascular or open surgical intervention. For patients with hepatic or splenic rupture from tumours, trauma or HELLP (haemolysis, elevated liver enzyme, low platelets syndrome, a combination of interventional radiology and surgical therapy is usually performed, with the choice tailored to each individual situation.^{8 9} In our case, our interventional radiology colleagues were available and able to quickly diagnose and address the issue. Our decision was confirmed to be correct when we later performed decompressive laparotomy for abdominal compartment syndrome and found the diffuse oozing difficult to control with multiple different haemostatic techniques and topical agents.

Review of previous cases of amyloidosis resulting in organ perforation yielded a variety of cases throughout the body. Patients with solid organ, namely hepatic and splenic ruptures have been mentioned previously. Gastrointestinal tract perforations have also been noted, with an inciting event infrequently identified.^10–13 Patients with these issues generally had favourable short-term outcomes, with reversal of the acute issue often enough to return them to their previous state of health, although one patient died from postoperative complications.^{10 11} Other cases have been reported of pneumatosis intestinalis as the presenting symptom of amyloidosis. These patients also did well, usually with conservative management.^{12 13} It is important to note that none of these patients had mention of severe liver dysfunction at the time of diagnosis, or throughout their hospital stays. One patient who did have advanced systemic amyloidosis presented with bladder perforation and passed away postoperatively after exploratory laparotomy and repair of the bladder defect.¹⁴ Even corneal rupture has been noted in several patients due to amyloidosis, further evidence that the disease is extensive and can cause widespread systemic damage.¹⁵

The next decision of note was how to treat his coagulopathy. As noted in the investigations, with the help of our haematology/oncology colleagues, we were able to diagnose our patient’s lambda light chain amyloidosis. Factor activity assays showed decreased factor VII activity and normal factor X activity, a change from studies 1 year earlier that only showed decreased factor X activity. FEIBA has mostly been studied for use in haemophilia,¹⁶ but was appropriate to use in this situation, and it did work to some degree. However, effects were transient, and addressing the underlying cause of the coagulopathy would be needed for any lasting effect. As discussed previously, multiorgan, particularly hepatic, dysfunction from primary amyloidosis makes postoperative recovery much more difficult, and this was the case for our patient.

This led to our final decision on how to reverse his disease process. Unfortunately, there is no proven way to reverse organ damage from amyloidosis. Treatment of steroids and bortezomib has been employed in prior cases,¹⁷ but patients usually have poor outcomes as the organ damage has been done. A specific case citing reversibility of kidney damage has been reported,¹⁸ but no cases of reversible hepatic damage were found in the literature. If diagnosed early, perhaps these treatment modalities could prolong the disease course, but routine screening for a rare disease process such as our case is not currently recommended.

Learning points.

• Amyloidosis should be suspected in patients presenting with spontaneous liver rupture and the appropriate workup should be initiated with urine and serum protein electrophoresis and liver biopsy.

• Treatment of hepatic rupture should be with resuscitation and urgent interventional radiological or open surgical intervention based on the location of bleeding. Open intervention may be difficult in the setting of amyloidosis due to the engorged liver capsule and underlying hepatic dysfunction causing coagulopathy.

• Coagulopathy should prompt investigations for abnormal clotting factor function, with treatment focused on the specific deficits encountered.

• If hepatic amyloidosis is discovered in the setting of hepatic rupture and is thought to be the driving force of liver failure, the disease process is likely at an advanced stage.

• Palliative steroids and/or bortezomib may be offered, but patients and families should be counselled that the prognosis may still remain poor.