Spontaneous hepatic haemorrhage secondary to ruptured hepatocellular adenoma in a young male patient

Abstract

A 27-year-old man presented with acute right upper quadrant abdominal pain and vomiting. He was clinically in hypovolaemic shock. Investigations revealed normocytic anaemia with a normal bilirubin and moderate liver function test abnormalities. CT abdomen and pelvis demonstrated haemoperitoneum and a large solitary hepatic mass in segments V and VI, suspicious for a ruptured hepatic tumour. Massive transfusion protocol was commenced and angioembolisation of the inferior branch of the right hepatic artery was undertaken. Despite this, his haemorrhagic shock was resistant to resuscitation. Thus, he underwent emergent exploratory laparotomy, which resulted in segments V and VI liver resection and packing. Re-look laparotomy 2 days following initial exploration was performed where haemostasis was confirmed. Histopathology revealed a ruptured well-differentiated hepatocellular adenoma. The patient made a good recovery following a 2-week admission.

Background

Hepatocellular adenoma (HA) is a benign hepatic tumour predominantly identified in women exposed to excess oestrogen with a female:male ratio up to 11:1.^{1 2} Incidence in men is low (1%) and usually confined to men with anabolic steroid use or glycogen storage disorders.¹ HA can be complicated by haemorrhage, rupture and malignant change.³ Rupture of HA can cause life-threatening haemorrhage, carrying a 5%–10% mortality rate and occurring in up to 27% of tumours.⁴

We present the case of ruptured HA in a young male requiring operative management due to uncontrolled haemorrhage despite resuscitation and angioembolisation. The case demonstrates challenges in distinguishing between well-differentiated hepatocellular carcinoma (HCC) and HA in the presence of a large solitary hepatic tumour. Our case also evidences the value and safety of step-up approach in managing ruptured HA that involves multidisciplinary team involvement.

Case presentation

We present a 27-year-old man who presented to a district hospital emergency department with sudden onset of right upper quadrant pain radiating to the right flank and back. This was associated with nausea and vomiting. He had no other bowel, urinary nor systemic symptoms. Background history included tonsillectomy and obesity with a body mass index of 34 kg/m². He had no regular medications, no prior anabolic steroid usage and was a non-smoker. He had no drinking history nor significant family history.

On examination, he had a respiratory rate of 28/min, oxygen saturation of 92% on room air, heart rate of 117 beats/min, blood pressure of 83/38 mm Hg and temperature of 37.7°C. He had cold and clammy peripheries and exhibited localised right-sided peritonism.

Investigations

On presentation, the patient had mild lactic acidosis (lactate 4.2 mmol/L (≤2.0 mmol/L)) with initial haemoglobin of 121 g/L (130-180 g/L). He had associated leucocytosis to 17.2×10⁹/ L (3.7–9.5×10⁹/ L), raised alanine transaminase (198 U/L (10–50 U/L)), aspartate transaminase (301 U/L (10–35 U/L)), γ-glutamyl transferase (181 U/L (≤50 U/L)) and alkaline phosphatase (408 U/L (30–110 U/L)). Bilirubin (6 μmol/L (≤19 μmol/L)), international normalised ratio (1.0) and lipase (42 U/L (≤60 U/L)) levels were normal.

CT abdomen and pelvis (figure 1) revealed haemoperitoneum likely resulting from a haemorrhagic source within a parenchymal lesion (120×95×130 mm) arising from the right lobe of the liver (predominantly segments V and VI). Heterogeneous areas of hyperdensity within the tumour were observed with ill-defined punctate areas of vascular enhancement which was suspicious for active haemorrhage or pseudoaneurysm. The remainder of the hepatic parenchyma was diffusely hypodense. The subsequent hepatitis screen was negative for hepatitis B, C and Wilson’s disease and the α-fetoprotein level was normal (1 IU/mL (≤8 IU/mL)).

Figure 1.

CT image (coronal view) demonstrating a right sided hepatic tumour with haemoperitoneum (arrow: vascular enhancement).

Differential diagnosis

The mass was suspicious for a large HA but well-differentiated HCC was not able to be excluded. In the absence of risk factors for liver disease, HA was a more feasible diagnosis.

Treatment

The patient was transferred to our tertiary hospital for urgent angioembolisation with the interventional radiology team after initial resuscitation with massive transfusion protocol. In our institution, this is a transfusion of packed red blood cells, fresh frozen plasma and cryoprecipitate in a 1:1:1 ratio, with targeted adjustments according to thromboelastography. There was no contrast extravasation identified on angiogram but gel foam was applied to the inferior branch of the right hepatic artery empirically given the patient’s haemodynamic instability (figure 2). Despite angioembolisation, the patient continued to clinically and biochemically deteriorate. He remained tachycardic (>130 beats/min) and febrile up to 38.5°C. Notwithstanding ongoing blood product resuscitation, his haemoglobin declined to 69 g/L.

Figure 2.

Gel foam angioembolisation to the inferior branch of the right hepatic artery (left: before, right: after).

Therefore, the decision was made to undertake operative management with the hepatobiliary surgical team. Resection was performed as a damage control measure, taking into consideration the possible diagnosis of well-differentiated HCC as this was a previously undiagnosed liver lesion. Thus, resection of liver segments V and VI was deemed to be the best approach for both haemorrhage control and achieving a curative oncological outcome (figure 3). This operation was technically difficult due to fluid overload, obesity and the size of the hepatic mass, now more swollen with haematoma. A Pringle manoeuvre was required to facilitate transection. The remnant liver was packed while further resuscitation was undertaken by the intensive care team. Re-look laparotomy and cholecystectomy were performed 2 days later and haemostasis was confirmed. Bile leak was tested intraoperatively through the cystic duct remnant.

Figure 3.

Macroscopic photograph of resected partial hepatectomy specimen with evidence of liver capsular rupture.

Outcome and follow-up

The patient recovered well but required a further percutaneous haematoma drainage on postoperative day 10. He was subsequently discharged and at 1 month follow-up he had returned to all daily activities.

Histopathology of the operative specimen revealed a 150×110×85 mm well-differentiated hepatocellular neoplasm with haemorrhage and extensive necrosis, as well as prominent steatohepatitis changes in surrounding liver parenchyma. There were no convincing malignant features; hence the appearance was consistent with HA. There was extensive amyloid A immunohistochemical staining which suggested an inflammatory subtype. The extensive diffuse pattern of glutamine synthetase staining also suggested β-catenin activation (figure 4).

Figure 4.

Histopathological photography demonstrating: (A) H&E stained representative slide demonstrating well-differentiated hepatocellular neoplastic cells on a background of acute inflammation and a region of necrosis in the top right corner (acquired with 10× objective). (B) Glutamine synthetase immunohistochemistry stained representative slide demonstrating a diffuse heterogeneous pattern throughout the tumour present in the top left of the slide (acquired with 4× objective). (C) Reticulin stained representative slide demonstrating preserved reticulin throughout the specimen (acquired with 10× objective). (D) H&E stained representative slide on the non-neoplastic liver demonstrating preserved architecture with portal tracts containing mild inflammatory cellular infiltrates and moderate macrovesicular steatosis (acquired with 20× objective).

Discussion

HA is a relatively uncommon benign tumour that has been historically reported almost exclusively in women of childbearing age exposed to oral contraceptive pills (OCP). Chang et al challenged this in their 2013 review showing a shift in epidemiological trends of HA with increases in men and in the absence of OCP use, and an increase in patients with multiple HAs. They postulate the trend as a result of newer OCP formulations and the increasing prevalence of obesity and metabolic syndrome.⁵ Our case embodies this trend and highlights the importance to consider the diagnosis of HA in men who present with a large hepatic mass and no risk factors for liver disease, especially if they are obese.

HA are hypervascular lesions with an exclusive arterial supply and can be complicated by life-threatening rupture with haemorrhage. There is an increased risk in tumours with increased diameters, exophytic growth pattern and in the sonic hedgehog and inflammatory subtypes.³

The mechanism of spontaneous rupture of HA is not clear but may be inferred from hypotheses regarding spontaneous HCC rupture. These include rapid growth of the tumour and necrosis leading to splitting of the overlying liver parenchyma or erosion of a vessel, and direct compression of hepatic veins due to the tumour. Other theories include vascular dysfunction due to degeneration of elastin and collagen, rendering the blood vessels susceptible to rupture from hypertension or minor trauma.⁶

Another important factor emphasised by this case relates to the difficulty in confirming accurate diagnoses acutely. This is crucial as implications of their diagnosis can be vastly distinct and lead to different management. A large HA and well-differentiated HCC can be difficult to differentiate morphologically and biopsy specimens can even be difficult to distinguish on histopathology.^{7 8} Rupture can occur in 3%–15% of HCC and does not distinguish between the two pathologies.⁶

Non-ruptured HAs in men are recommended for a resection irrespective of size due to a significantly higher incidence of malignant transformation,^{9 10} although recent evidence suggests there is a potential role for definitive selective angioembolisation.¹¹ However, for the management of ruptured HA, it is difficult to make a direct comparison between resection, angioembolisation and active observation. The European Association on the Study of Liver guidelines recommend that ruptured HA with haemodynamic instability should preferentially undergo urgent angioembolisation with delayed resection of the residual viable lesion on subsequent follow-up.⁹ Angioembolisation leads to a decrease in tumour size and resorption of the haematoma, making elective resection easier with a lower risk of transfusion.¹² Selective angioembolisation of the hepatic artery has shown to be safe and efficacious in avoiding emergency surgery without significant long-term complications.¹³ As our patient failed to respond to angioembolisation, management of life-threatening haemorrhage had to be prioritised with resection even if it may impact on oncological outcome. Strikingly, a recent case series of 52 patients who underwent resection for HA revealed that the presence of haemorrhage did not impact on overall short-term outcomes nor mortality.¹⁴ This contributes to the evidence confirming the safety of resection in HA with spontaneous rupture.^{15 16} Rosales et al report in their single-centre case series of 26 patients that there was no difference in short term outcome including the length of hospital stay between patients managed supportively, with angioembolisation or resection following spontaneous hepatic haemorrhage, although 50% of their cohort who initially underwent angioembolisation rebled requiring re-embolisation.¹⁶

Rupture and haemorrhage of HA benefit from a multidisciplinary approach encompassing critical care, surgical and interventional radiology teams. Although observation and angioembolisation have proven to be safe options in certain clinical situations, operative resection may still be required when haemorrhage remains uncontrolled despite these measures.

Learning points.

• Hepatocellular adenoma is a benign liver lesion that may be increasing in incidence in male patients due to increased prevalence of obesity and metabolic syndrome.

• Hepatocellular adenoma and well-differentiated hepatocellular carcinoma can be difficult to differentiate radiologically.

• A multidisciplinary approach, including interventional radiological and operative management, can be pursued to manage ruptured hepatocellular adenomas.