Pictorial review of ischaemic hepatitis and its mimics

INTRODUCTION

Ischaemic hepatitis is a diffuse liver injury that most commonly occurs as a result of acute hypoperfusion.[1] Also often referred to as shock liver, this condition occurs in up to 10% of patients admitted to an intensive care unit.[2] For patients admitted to an intensive care unit with upper gastrointestinal variceal haemorrhage, the incidence of ischaemic hepatitis has been reported to be close to 10%.[3] Although the treatment is mostly supportive, ischaemic hepatitis carries a much poorer prognosis than other causes of hepatitis, especially in critically ill patients, where the mortality rate increases to 25%.[4]

PATHOPHYSIOLOGY

The liver has a dual blood supply. The arterial system accounts for approximately one-third of the hepatic blood supply, and the portal system accounts for the remaining two-thirds. In addition, an extensive collateral pathway between the intrahepatic arterial and portal venous supply protects the liver from ischaemia. A further rich network of intrahepatic and extrahepatic accessory and collateral arteries creates a complex system of compensation in the event of reduced or absent blood flow.[5]

Ischaemic hepatitis occurs in the setting of a systemic decrease in perfusion or oxygenation, which compromises both hepatic arterial and portal venous blood supply concurrently. An isolated occlusion of either has not been reported to result in ischaemic hepatitis in the literature. This is in contrast to hepatic infarction, which can occur from focal interruption of a single intrahepatic branch of the hepatic artery.[6]

The liver is divided histologically into lobules [Figure 1]. The central vein lies within the centre of the lobule and the portal triads lies at the periphery. Functionally, the liver can be divided into three zones based on oxygen supply. Zone 1 (periportal zone) encircles the portal tracts where the oxygenated blood from hepatic arteries enters. Zone 3 (centrilobular zone) is located around the central veins where oxygenation is poor. Zone 2 (intermediary zone) is located in between Zones 1 and 3. The pathological hallmark of ischaemic hepatitis is hepatocellular necrosis in the centrilobular zone, known as hepatic centrilobular necrosis, where necrosis is confined predominantly to Zone 3.[7] This pattern of involvement differs from hepatic infarction, which involves all three zones of the hepatic acinus.[8]

Figure 1.

Diagram of a liver lobule. The central vein lies at the centre of the lobule and the portal triads lie at the periphery. Functionally, the liver can be divided into three zones based on oxygen supply. Zone 1 (in purple) is closest to the portal triad, receives the most oxygenated blood and is least susceptible to ischaemic injury. Conversely, zone 3 (in yellow), which is closest to the central vein, receives the least oxygenated blood and is therefore, most susceptible to ischaemia.

DIAGNOSIS

Three criteria are currently accepted for the diagnosis of ischaemic hepatitis:[9] (a) appropriate clinical setting resulting in systemic hypoperfusion, such as severe heart failure, respiratory failure and septic shock; (b) characteristic transient but significant rise in serum aminotransferase levels, with a minimum of ten times sudden increase in serum aspartate aminotransferase (AST) levels being the accepted cut-off point; [10] and (c) exclusion of other causes of hepatocellular necrosis, especially viral hepatitis or drug-induced hepatopathy. In ischaemic hepatitis, the sudden rise in AST and alanine aminotransferase (ALT), particularly AST, is due to anoxic–hypoxic injury to the liver centrilobular hepatocytes. Another characteristic is the significant elevation of serum lactate dehydrogenase (LDH) level. On the contrary, elevation of serum alkaline phosphatase and bilirubin levels is typically mild to modest. Increase in serum creatinine level is a common accompanying finding.[11]

DISCUSSION

Although ischaemic hepatitis is a well-recognised clinical entity, its imaging appearances are not well described in the literature. In this article, we present the imaging appearances of four cases of ischaemic hepatitis. The patient demographics and key biochemical findings are summarised in Table 1.

Table 1.

Patient demographics and biochemical findings.

No.	Age (yr); gender	Peak level (U/L)
		ALT (IRR 10–70)	AST (IRR 10–50)	ALP (IRR 40–130)	LDH (IRR 250–580)
1	60; M	348	1204	156	6509
2	3; M	3852	9648	619	>30,000
3	47; F	3716	>10,000	1005	>30,000
4	50; F	1338	2233	197	5973

F: female, IRR: institutional reference intervals, M: male

Case 1

A 60-year-old man with a history of Child–Pugh B alcoholic liver cirrhosis presented with massive haematemesis. He was hypotensive and tachycardic on presentation. The abdomen was nondistended and nontender. Initial biochemical tests demonstrated an acute drop in haemoglobin level. He was intubated in the emergency department. Emergency oesophago-gastroduodenoscopy was performed, but attempts to achieve endoscopic haemostasis were futile and a Sengstaken–Blakemore tube was inserted. He was planned for a transjugular intrahepatic portosystemic shunt (TIPS) procedure, and multiphasic computed tomography (CT) of the liver was performed [Figure 2].

Figure 2.

Case 1: Axial contrast-enhanced CT images in the (a) portovenous phase and (b) delayed phase show persistent heterogeneous hypoenhancement of the liver, with a branching pattern along the central veins. (c) Coronal and (d) axial CT images in the arterial phase show abrupt non-opacification of the hepatic artery (arrows), in keeping with thrombosis. The arrowhead in 2d shows the portal vein.

As previously discussed, the hepatic artery provides approximately one-third of the hepatic blood supply, and occlusion, even in the main branch, is unlikely to result in significant hypoperfusion of the entire liver. We presume this was an ancillary finding rather than a major cause of ischaemic hepatitis. The linear pattern of hepatic hypoenhancement [Figure 2a & b] may have been contributed by a compromised arterial blood supply. Hepatic artery occlusion was a contraindication for TIPS, thereby precluding this treatment option. A relook oesophago-gastroduodenoscopy revealed extensive blood clots in the upper gastrointestinal tract, but no active bleeding was seen in the oesophagus or stomach. A decision was made for comfort care, and the patient passed away a few hours after the scan.

Case 2

A 3-year-old boy suffered haemorrhagic shock as a result of liver and splenic lacerations after a fall from height, as well as long bone fractures. After the initial CT scan showed active haemorrhage [Figure 3a & b], the patient underwent a conventional angiogram, confirming the presence of active arterial bleeding from the inferior sectoral branch of the right hepatic artery. This was successfully embolised. A CT done the next day showed new hypoenhancing regions in both the central hepatic lobes, which were separate from the initial site of injury [Figure 3c]. The hypodense areas in both the hepatic lobes were noted to be more extensive on a subsequent CT scan performed a few days later [Figure 3d]. These changes coincided with a rapid rise in hepatic enzymes, consistent with ischaemic change. This was an unsurprising finding, given the presence of haemorrhagic shock on presentation. Computed tomography also revealed a biloma secondary to a posttraumatic bile leak [Figure 3c], which was confirmed on subsequent magnetic resonance cholangiopancreatography and hepatobiliary iminodiacetic acid (HIDA) studies. Exploratory laparotomy revealed a large amount of hemobilous fluid. Large-bore abdominal drains were inserted. The output from the abdominal drains continued to rise in the subsequent days. Eventually, the patient developed cardiovascular collapse. Aggressive resuscitative efforts were futile, and the patient eventually passed away.

Figure 3.

Case 2: (a & b) Initial axial CT images show ill-defined and branching hypodensities in the right hepatic lobe, extending to the posterior capsular surface, compatible with lacerations. Arterial phase blush was present in the right hepatic lobe (arrow in a) with pooling in the portovenous phase (arrow in b), associated with haemoperitoneum. (c) CT performed the next day due to increasing abdominal distension shows new areas of hypoenhancement in both the central hepatic lobes with relative sparing of the periphery, which were separate from the initial site of laceration. The linear hypodensity in the right hepatic lobe (arrow) was shown to be a dilated bile duct that resulted in posttraumatic bile leak and biloma formation (*). (d) Repeat CT shows a significant increase in the volume of haemoperitoneum and further progression of hypoattenuation in both the hepatic lobes.

This case illustrates a central geographical pattern of hepatic hypoattenuation in ischaemic hepatitis. The hypodense areas also progressed on subsequent CT, corresponding to rising hepatic enzymes. More extensive changes on CT may therefore indicate more severe hepatocellular injury.

Case 3

A 47-year-old woman was admitted for type I respiratory failure secondary to pneumonia. She deteriorated in the intensive care unit despite inotropic and ventilatory support, with worsening metabolic acidosis, hyperlactaemia and multiorgan failure.

In addition to changes in the liver on the initial CT [Figure 4a & b], there was also hyperenhancement of the left adrenal gland and collapse of the inferior vena cava in keeping with a hypoperfusion complex. Computed tomography performed 2 days later showed worsening hypoenhancement in the liver [Figure 4c & d]. There were also new findings of small and large bowel mural hypoenhancement in keeping with ischaemic bowel, as well as wedge-shaped hypodensities in both kidneys, compatible with infarcts. In view of the very high morbidity and mortality of surgery, the decision was made for conservative management. The patient passed away 2 days after the final CT scan was performed.

Figure 4.

Case 3: (a) Axial unenhanced and (b) contrast-enhanced CT images in the portovenous phase show a subtle area of hypoenhancement near the gallbladder fossa (arrow in b). CT was performed 2 days later. Axial CT images show (c) a larger and more prominent area of wedge-shaped hypoenhancement adjacent to the gallbladder fossa (arrow) and (d) new areas of patchy and geographical hypoenhancement in the rest of both the hepatic lobes (arrows).

Initial CT findings may be subtle, involving only a small area of the liver. In the appropriate clinical context, even mild changes should allude to ischaemic changes, especially when other features of a CT hypoperfusion complex are present.

Case 4

A 50-year-old woman presented with large bowel obstruction secondary to a sigmoid tumour. She underwent subtotal colectomy on the second day of admission. Intraoperatively, an obstructive sigmoid colonic tumour was found with dusky appearances of the caecum and some ileal loops, suggestive of bowel ischaemia. On postoperative day 4, she developed septic shock with raised lactate level and severe metabolic acidosis. The patient underwent several CT scans due to concerns of surgical complications [Figure 5]. The patient was discharged well after the episode, but eventually passed away 6 months later due to gradual deterioration.

Figure 5.

Case 4: A series of CT performed after surgery. Axial CT images on (a) postoperative day (POD) 4 shows normal hepatic attenuation, which was similar to that of the spleen, (b) POD 6 shows diffuse hypoattenuation of the liver relative to the spleen, and (c) POD 9 shows more discrete, wedge-shaped areas of hypoenhancement in the subcapsular right hepatic lobe (arrows). (d) Axial CT image shows resolution in the areas a week later, concurrent with normalisation of hepatic enzymes. While the imaging appearances would be more suggestive of established infarcts, interval resolution would suggest that they were instead a result of ischaemia.

This case illustrates a diffuse pattern of hepatic hypoattenuation in ischaemic hepatitis, which can be easily mistaken for fatty infiltration if the change from the recent CT is not noticed [Figure 5a & b]. These hypodense areas became more wedge shaped and discrete on subsequent CT [Figure 5c], with imaging appearances more suggestive of infarcts. However, the fact that these areas eventually resolved with normalisation of hepatic enzymes [Figure 5d] suggests that they were likely related to ischaemia rather than infarction.

OUTCOMES

All four patients were diagnosed with ischaemic hepatitis clinically, showing expected biochemical derangement of hepatic enzymes. In particular, a rapid rise in serum AST levels was observed, associated with an early massive rise in LDH levels. Peak AST levels in thousands were reached within 1–3 days of the haemodynamic insult. The first three patients passed away shortly after the diagnosis of ischaemic hepatitis. In the last patient, there was a rapid fall in transaminases within days of supportive treatment, as is expected in the recovery of ischaemic hepatitis.[12]

IMAGING MIMICS AND PITFALLS

The radiological appearance of hepatic infarction is well documented. The most common appearances are wedge-shaped areas of hypoenhancement at the periphery of the liver, rounded or oval hypodense lesions or irregularly shaped low-attenuation lesions paralleling bile ducts,[13] as compared to a diffuse and less-marginated pattern in ischaemic hepatitis.

Diffuse fatty infiltration of the liver is a common entity, which may mimic diffuse parenchymal hypoenhancement of the liver on single-phase, contrast-enhanced CT [Figure 6]. Fat infiltration or sparing may demonstrate a geographical, patchy or perivascular distribution [Figure 7].[13] All these patterns may overlap with the imaging features of ischaemic hepatitis, as illustrated in our cases. Other diffuse hepatic parenchymal pathologies, such as storage, vascular or inflammatory conditions, may show nonspecific appearances of hypoattenuation [Figures 8 & 9].[14] Infiltrative neoplasms such as cholangiocarcinoma, lymphoproliferative disease and infiltrative metastases can result in a diffuse pattern of abnormal hepatic attenuation, especially around the portal tracts [Figure 10].[15]

Figure 6.

(a) Axial noncontrast CT image of the liver shows diffusely reduced hepatic parenchymal attenuation, suggestive of fatty infiltration. The degree of steatosis is sufficiently severe that the hepatic veins (arrows) appear hyperattenuating as compared to the liver. (b) Coronal contrast-enhanced CT in the portovenous phase shows reduced hepatic parenchymal attenuation as compared to the spleen (arrow), suggestive of fatty infiltration.

Figure 7.

(a) Axial and (b) coronal contrast-enhanced CT of the liver in the portovenous phase show an area of increased attenuation adjacent to the gallbladder fossa with relatively linear margins (arrows). The location and appearance are typical of an area of focal fatty sparing.

Figure 8.

(a) Axial contrast-enhanced CT of the liver in the portovenous phase shows diffuse mottling of the hepatic parenchyma in a patient with Budd–Chiari syndrome, classically described as nutmeg liver. (b) Another CT image in the same study, which is slightly more superior to (a), shows nonopacification of the hepatic veins, either due to collapse or diminished flow.

Figure 9.

A patient with congestive hepatopathy. (a) Axial contrast-enhanced CT of the liver in the portovenous phase shows diffuse mottling of the liver parenchyma. There is also dilatation of the inferior vena cava (*). (b) Axial CT in the arterial phase reveals that the hepatic veins are also dilated (arrows). (c) Axial CT through the lower chest shows the presence of cardiomegaly and bilateral pleural effusions, which further explain the appearances of the liver in (a).

Figure 10.

A patient with metastatic breast cancer. Axial contrast-enhanced CT of the liver in the portovenous phase shows extensive hepatic parenchymal involvement; some of the metastatic deposits are more discrete, while many others appear as confluent, ill-defined, hypodense areas. Mass effect is still appreciated in the latter, as evidenced by effacement of some of the intrahepatic vessels (arrow) and the inferior vena cava (curved arrow).

The pattern of hepatic hypoenhancement in ischaemic hepatitis can be variable. On CT, it may be seen as patchy or geographical areas of hypoenhancement. It may also be seen as diffuse hypoenhancement of the hepatic parenchyma. The morphological changes on CT may evolve or resolve upon normalisation of hepatic enzymes. The appearance of hepatic hypoenhancement on a contrast-enhanced CT should be read in conjunction with an unenhanced phase or a recent previous CT study to help differentiate it from other infiltrative causes of hepatic parenchymal hypoattenuation. Table 2 shows a summary of the common CT findings for the various conditions.

Table 2.

Computed tomography (CT) findings in ischaemic hepatitis and imaging mimics.

Condition	Common CT findings
Ischaemic hepatitis	• Variable patterns of reduced hepatic parenchymal enhancement (ranging from focal to diffuse), which may worsen or resolve in time with normalisation of hepatic enzyme levels
	• Absence of mass effect on vessels and other liver structures
Hepatic infarction	• Peripheral wedge-shaped areas of low attenuation (on noncontrast CT) or reduced enhancement (on contrast-enhanced CT), which extend to the capsular surface
	• Enhancement of the infarcted area may be heterogeneous due to the presence of viable tissue
	• Typical geographical or segmental distribution, which may demonstrate straight margins
	• Absence of mass effect on vessels and other liver structures
	• Bile lakes may form as a late complication of infarction, due to ischaemic necrosis
Budd–Chiari syndrome/hepatic venous outflow obstruction	Acute • Diffuse hypoattenuation and enlargement of the liver
	• Narrowing of the IVC and hepatic veins Chronic
	• Dysmorphic liver with caudate lobe hypertrophy
	• IVC and hepatic veins usually not visible due to collapse or diminished flow rate
	• Heterogeneous parenchymal enhancemen
	• Development of large regenerative nodules as a result of decreased hepatic perfusion
	• Development of systemic, portal and intrahepatic collaterals
Passive hepatic congestion	• Dilated IVC and hepatic veins, with early enhancement in the arterial phase
	• Heterogeneous, mosaic hepatic parenchymal enhancement pattern
	• Hepatomegaly and extrahepatic manifestations such as ascites, cardiomegaly and evidence of congestive cardiac failure in the imaged lungs may be present
Hepatic steatosis	Diffuse deposition
	• Most frequently encountered CT pattern
	• Homogeneous hypoattenuation of at least 10 HU less than the spleen or if hepatic attenuation is less than 40 HU on noncontrast CT
	• Intrahepatic vessels may appear hyperattenuating compared to the fat-containing liver on noncontrast CT Focal deposition or focal sparing
	• Tends to occur in characteristic areas, e.g., adjacent to the falciform ligament or gallbladder fossa
	• Absence of mass effect on vessels and other liver structures
	• Geographical configuration
	• Isoenhancing to hypoenhancing compared to the rest of the normal liver on contrast-enhanced CT
Primary hepatic malignancies or metastases	• Tend to exert mass effect
	• Infiltrative tumours may be more difficult to distinguish on CT, although diagnosis can usually be clinched with MRI

IVC: inferior vena cava, MRI: magnetic resonance imaging

CONCLUSION

There is little emphasis placed on the imaging appearances of ischaemic hepatitis, despite remarkable changes on CT as illustrated in this article. In the appropriate clinical context, alterations in hepatic parenchymal enhancement should raise the possibility of ischaemic hepatitis. The pattern of hypoenhancement may be heterogeneous or homogeneous but will diffusely involve the liver in contrast to hepatic infarction, which is observed as a focal area of hypoenhancement. Parenchymal abnormalities may be subtle in the early stages; therefore, the radiologist must scrutinise the images for such findings in a patient with relevant risk factors. These findings should be discussed early with the clinical team, and this may help to reinforce a prospective diagnosis of ischaemic hepatitis. Furthermore, CT findings may help to determine the cause of rising lactate levels in the unwell patient. We have observed that morphological changes on CT may be seen before the rapid rise in hepatic enzymes, thereby allowing a pre-emptive and timely diagnosis.

Conflicts of interest

There are no conflicts of interest.

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 14 February 2025

Question: Answer True or False
1. Regarding blood supply to the liver:
(a) The arterial and portal venous systems each account for about 50% of hepatic blood supply.
(b) Both the arterial and portal venous supply to the liver are usually compromised in ischaemic hepatitis.
(c) Reduction in blood supply to the liver typically occurs as a result of a systemic decrease in perfusion or oxygenation.
(d) There exists a collateral network of arteries to the liver that can compensate in the event of reduced blood flow.
2. Regarding the pathophysiology of ischaemic hepatitis:
(a) It is a diffuse liver injury.
(b) It occurs as a result of anoxic injury to the liver centrilobular hepatocytes.
(c) The pathologic hallmark of ischaemic hepatitis is hepatocellular necrosis in Zone 1 of the liver hepatocytes.
(d) The centrilobular zone has poor oxygenation.
3. Regarding the management of ischaemic hepatitis:
(a) It is not necessary to exclude other causes of hepatitis before a diagnosis of ischaemic hepatitis is made.
(b) Ischaemic hepatitis can occur in up to 10% of patients admitted to intensive care.
(c) Treatment of ischaemic hepatitis is mainly surgical.
(d) Ischaemic hepatitis carries a better prognosis than other causes of hepatitis.
4. Regarding imaging findings of ischaemic hepatitis:
(a) Initial imaging findings of ischaemic hepatitis on CT may be subtle.
(b) Initial imaging findings of ischaemic hepatitis on CT may regress and resolve with time.
(c) Imaging findings of ischaemic hepatitis on CT would take precedence over laboratory results when making a diagnosis.
(d) Findings of ischaemic hepatitis on CT may either be diffuse or focal.
5. Regarding potential imaging mimics of ischaemic hepatitis:
(a) Fatty liver can appear as diffuse hepatic hypoenhancement or parenchymal attenuation on CT.
(b) Fatty liver can appear as geographic or patchy areas of altered hepatic attenuation or enhancement on CT.
(c) Diffuse hepatic malignancies may mimic imaging appearances of ischaemic hepatitis on CT.
(d) Inflammatory and vascular disorders may result in imaging appearances that overlap with ischaemic hepatitis.

Funding Statement

Nil.