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Liver: Liver Transplantation: Preoperative CT Evaluation

Harpreet K. Pannu, M.D.(1) Warren R. Maley, M.D.(2) Elliot K. Fishman, M.D.(1)

Abstract

Liver transplantation is a successful therapeutic option for chronic liver disease and liver failure with a one-year survival of greater than 80%. Orthotopic transplantation is usually performed from a cadaveric or living adult donor. Evaluation of recipients and donors is necessary prior to transplantation and this is successfully done by CT. The purpose of this review is to illustrate the utility of computed tomography (CT) in liver transplantation. Clinically relevant information for recipients includes size of the caudate lobe, exclusion of advanced hepatoma as well as other malignancy, patency of the venous system, presence of perihepatic varices, patency of the celiac artery, exclusion of splenic artery aneurysm and position of iatrogenic venous shunts. For living donors, clinically relevant information includes variant hepatic arterial anatomy, source of the artery to segment IV, intraparenchymal anatomy of the hepatic veins and accessory hepatic veins, trifurcation of the portal vein or hepatic duct, liver volume and fatty change of the parenchyma. Surgical approaches and the imaging findings that influence management will be reviewed.

Introduction

Orthotopic liver transplantation is the mainstay of therapy for multiple irreversible acute and chronic liver diseases. Survival after transplantation has been improved due to advances in immunosuppressive therapy and surgical techniques allowing many patients to live many years after transplantation. The five-year survival is between 65 and 78%(1). Approximately 4000 liver transplants are performed each year with the majority of livers coming from cadaveric donors(2). As the number of transplant candidates is greater than the availability of cadaveric livers, techniques such as split-liver donation and living donor transplantation have been developed(3). Split-liver donation involves dividing the cadaveric liver so that the lateral segment of the left lobe may be transplanted into a pediatric patient and the remainder of the liver may be transplanted into an adult. In living donor transplantation, the donor undergoes partial hepatectomy for donation to a recipient. If the recipient is a child, the left lateral segment is used for donation. If the recipient is an adult, the right lobe of the liver is usually donated although occasionally the left lobe is sufficient.

Successful transplantation requires thorough evaluation of the recipient and living donor. Noninvasive imaging with computed tomography (CT) has a role in the evaluation of both the transplant candidate and the potential living donor. In this article we present the utility of CT in preoperative assessment of liver transplantation and donation. Specific questions that can be answered by CT and their influence on the management of recipients and living donors will be reviewed. As surgical technique varies slightly between cadaveric and living donation, the surgical method for each will first be briefly reviewed. CT protocols for single and multidetector scanners are also presented.

SURGICAL TECHNIQUE: An overview

Hepatectomy

A total hepatectomy is performed in the recipient(4). The hepatic artery, portal vein and common duct are ligated close to the liver. The intrahepatic inferior vena cava (IVC) is resected or is left intact for cadaveric transplants. The IVC is preserved for living donor transplantation. The diseased liver is removed. A partial hepatectomy is performed in living donors. The hepatic artery, portal and hepatic veins and bile duct of the graft lobe are isolated. The hepatic parenchyma is then dissected to isolate the graft lobe and it is removed.

Implantation of the graft in the recipient

The donor and recipient IVC and portal vein are anastomosed for cadaveric transplants. The donor hepatic vein is anastomosed to the recipient IVC for living donor transplantation. The donor hepatic artery is anastomosed to the recipient hepatic artery. A duct to duct anastomosis is performed or a hepaticojejunostomy is constructed.

Computed tomography protocol

Single detector spiral CT

A helical scan is performed through the liver after the ingestion of 750 cc water as a negative oral contrast agent and intravenous (IV) injection of 150 cc of nonionic contrast at 3 cc/second. A delay of 25 seconds is used for the arterial phase and a delay of 55 seconds is used for the venous phase. The scan collimation is 3 mm, table speed is 6 mm/second and reconstruction interval is 1-2 mm for the arterial and the venous phase.

Multidetector spiral CT

The injection parameters and scan delay are for a single detector scanner except for a decrease in contrast volume to 120 cc. The slice collimation is 1.0 mm, table feed is 6 mm/rotation and reconstructed slice width is 1.25 mm for the arterial and the venous phase, with the scan reconstructed every 1 mm.

Evaluation of recipients

Assessment of the recipients on CT includes evaluation of the liver parenchyma and vasculature. Exclusion of intrahepatic and extrahepatic malignancy, venous thrombosis, extensive perihepatic varices, celiac stenosis, splenic artery aneurysm and incorrect location of a transjugular portosystemic shunt is clinically helpful(1). The gallbladder is removed in all cases, therefore, identification of abnormalities usually does not alter the surgical plan.

Evaluation of liver parenchyma

The liver can appear normal in 25% of patients with cirrhosis(5). However, the liver contour is usually nodular and there is atrophy of the right lobe and hypertrophy of the lateral segment and caudate lobes . The caudate can enlarge and surround the inferior vena cava. Exposure and removal of the liver off the retrohepatic inferior vena cava in these recipients is difficult (6). This becomes relevant in cases of living donor transplantation where the cava is preserved.

Presence and extent of hepatocellular carcinoma

60-90% of hepatomas in this country are associated with cirrhosis(1). The frequency of the tumor is 5-15% in areas where hepatitis B is uncommon(1). Transplantation is feasible in patients with stage I and II disease as it can be curative(1,2). If one mass less than 5 cm, or up to three masses, each less than 3 cm, are present in the liver without evidence of extrahepatic metastases, transplantation can be performed(2). Extrahepatic metastases are an absolute contraindication for transplantation. Enlarged nodes are common in patients with cirrhosis and are usually due to benign hyperplasia(7). Nodal size is not a reliable criterion for malignancy(8). As adenopathy in this patient population may be secondary to chronic liver disease or tumor spread, it does not preclude an attempt at liver transplantation. Staging is performed by surgical nodal biopsy prior to transplantation.

80% of hepatomas larger than 2 cm are detected on multiphase CT(9). The presence of fibrosis, fatty infiltration, necrosis and regenerative nodules can make the detection of tumors in cirrhotic livers difficult(10). The density of tumors is variable on enhanced and non-enhanced scan(11). On noncontrast images, the tumors are usually hypodense(12). Isodense tumors may have a low attenuation tumor capsule(12). Hepatomas are hyperdense or are of mixed attenuation in the majority of patients on arterial phase images(13). Small tumors tend to be homogeneously hyperdense(11). Over 90% of tumors detected at CT are seen on the arterial phase, 10% of which are only seen during this phase(12,13). Hepatomas are hypodense or isodense compared to liver parenchyma on portal venous phase images (12). This pattern is due to supply of the tumor by the hepatic artery. Other findings are nodules of mixed attenuation and delayed capsular enhancement(12). On noncontrast scans, hypodense and hyperdense areas in the tumor are due to fat and blood, respectively. Calcification occurs in 5-10% of cases and poorly differentiated tumors tend to be infiltrating(14).

Signs of vascular invasion of hepatoma are filling defects in vessels and expansion of the vessel lumen. With arterioportal shunting, there is early or prolonged enhancement of the portal vein and transient hyper-attenuation peripheral to the tumor(12). Extrahepatic metastases most commonly occur to lung, abdominal nodes and bone and are seen with advanced hepatic tumors(8). Nodal metastases usually occur to periceliac and porta hepatis nodes, which may enhance with contrast(8). Patients with bony metastases frequently have lytic lesions and concomitant spread to nonosseous tissues(8).

Presence of cholangiocarcinoma and other malignancies

Known cholangiocarcinoma, especially a hilar tumor, is an absolute contraindication to transplantation due to a high recurrence rate of 44%(1,15). Tumors tend to recur early and the five year survival ranges from 7-17%(15). Although a strong association does not exist between cirrhosis and cholangiocarcinoma, patients with conditions such as sclerosing cholangitis are at increased risk for developing this malignancy(12). Detection of a primary tumor outside the liver, with or without hepatic metastases, is also an absolute contraindication to transplantation. Hepatic metastases have a recurrence rate of almost 60% after transplantation(15).

Intrahepatic cholangiocarcinoma represents 10% of primary cholangiocarcinomas(16). Based on its macroscopic appearance, tumors are classified into three types * mass forming, periductal-infiltrating and intraductal(17). The mass forming tumor is the most common type and is usually hypodense on noncontrast scans(12,17). Although it enhances with contrast, the amount of enhancement is less than the adjacent parenchyma on arterial and portal venous phase images (18). With the injection of contrast, most commonly there is early peripheral enhancement with progressive filling of the lesion(16,19). Delayed enhancement of the center is due to diffusion of contrast into the extravascular space of fibrous tissue in the tumor(16,19). A peripheral low attenuation halo can give a bull’s eye appearance(18). If images are obtained more than 10 minutes after contrast injection, the tumor is often hyperdense to normal parenchyma secondary to this delayed enhancement(1,20,21). Filling of the lesion with contrast may not be seen if the center of the tumor is necrotic(19).

Hilar tumors are infiltrating or exophytic(22). Hilar tumors of the infiltrating stenotic variety can be hyperdense on arterial phase images(22). Intraductal tumors appear as hypodense masses in dilated ducts on enhanced scans(17). Masses greater than 1 cm can be seen and the ductal dilatation is segmental or lobar(17). In some cases, the dilated ducts can appear hyperdense due to tumor casts(17).

Other features of cholangiocarcinomas are: 1) focal dilatation of intrahepatic bile ducts peripheral to the mass seen in almost one-half of cases, 2) a wedge-like area of increased enhancement peripheral to the tumor, 3) retraction of the liver capsule in 20% of tumors and 4) satellite nodules in advanced tumors(16,19). Hepatic vessels are encased by tumor in almost half the patients but, unlike hepatoma, the tumor is usually not intravascular(12,19,23).

Patency of the portal vein and superior mesenteric vein

Portal vein thrombosis is seen in 15% of patients with chronic liver disease(24). Thrombosis is due to increased resistance in the liver and resultant slow venous flow(25). Although thrombosis of the portal vein was initially considered an absolute contraindication to transplantation, a variety of surgical techniques are now used in cases of portal vein abnormalities(1,24). If acute portal thrombus is present, manual thrombectomy is performed at surgery(24). If chronic portal venous thrombosis is present or the portal vein diameter is less than 4 mm, the donor portal vein is anastomosed to the splenomesenteric confluence, the superior mesenteric vein or to a splenic varix(24,26,27). If the graft portal vein is not long enough to reach the confluence, an iliac vein graft is obtained from the donor(26). Higher recipient morbidity due to uncontrolled bleeding has been described if phlebitis is present with thrombosis(24). Diffuse thrombosis of the portal and superior mesenteric veins remains a contraindication to liver transplantation.

 

On unenhanced CT images, the density of acute thrombus is approximately 60-70 HU(28). On CT with IV contrast, the acute thrombus is a hypodense filling defect in the portal vein with partial or complete occlusion(25,29). Enhancement of the vasa vasorum in the vessel wall and lumen expansion may be present(25,29,30). Inflammatory stranding of the perivenous fat may be seen with phlebitis(24). There are secondary changes in the liver supplied by the thrombosed portal vein. On noncontrast scans the liver is hypodense because of depletion of glycogen content(25,29). On arterial phase images, compensatory increase in arterial flow causes the liver to transiently appear hyperdense(29). With time the thrombosed portal vein retracts and collateral veins dilate to give the changes of cavernous transformation (25).

Location of varices

Perihepatic and pericaval varices can cause increased bleeding when the native liver is excised. Collateral vessels adjacent to the liver and inferior vena cava are ligated as they are encountered during surgery(1). Varices in other parts of the abdomen do not affect the surgical procedure and decrease in size spontaneously after transplantation. On CT with IV contrast, varices are serpiginous structures that enhance on the portal venous phase images (29). These collateral vessels can be retroperitoneal, gastroesophageal, splenorenal or paraumbilical in location and develop due to portal hypertension(29).

 

Celiac stenosis

Celiac stenosis occurs with atherosclerotic disease and from compression by the median arcuate ligament. Atherosclerosis tends to occur in the proximal or mid-proximal artery(31). Compared to other sites such as the iliac arteries, significant disease of the visceral arteries is less common, affecting 2.6% of patients in a series of 13,827(31). The median arcuate ligament is a variable structure that is a condensation of the crura of the diaphragm(32). The ligament can compress the celiac artery and other visceral arteries as they arise from the aorta. Recipients with celiac artery stenosis are at risk for compromised blood flow to the transplant(33). The stenosis is therefore corrected at surgery. If the narrowing is due to arcuate ligament compression, the ligament is divided(33). If the stenosis is due to atherosclerosis, an alternative inflow tract is created(33). This is usually done by placing an interposition conduit from a cadaveric donor between the recipient infrarenal aorta or right common iliac artery and the donor hepatic artery(1,34).

CT angiography is an established technique for evaluating arterial anatomy, aneurysmal dilatation and stenosis. For example in the renal artery, sensitivity and specificity of CT angiography of >94% for significant stenoses have been reported(35). In a study of visceral vessels using a dual-slice CT scanner, all stenoses of the celiac trunk visualized on catheter angiography were depicted on CT(36). Severe celiac stenosis can be demonstrated on CT in liver transplant candidates(37). Both axial and 3D images are helpful for evaluation of arterial caliber. The origin of the celiac artery can usually be assessed on axial images as it is in the axial plane. However, the proximal artery follows an oblique course and the lumen cannot be adequately assessed on axial images. With volume rendering 3D technique, visualization of stenoses is not as dependent on vessel orientation(35). The entire length of the celiac artery can be displayed and narrowing or patency of the lumen demonstrated . Atherosclerotic calcification is well seen on maximum intensity projection (MIP) images. Other findings include mural thrombus and post-stenotic dilatation. In cases of median arcuate ligament compression, compression of the artery by the diaphragm is visible(32).

Splenic artery aneurysm

Splenic artery aneurysms result from increased flow in the splenic artery in patients with cirrhosis and portal hypertension(37). The incidence is estimated to be approximately 7-10% of patients and is higher in autopsy series(37). Consideration can be given to ligation of the aneurysms as they may rupture after transplantation. Since this area is not routinely explored at surgery, preoperative diagnosis is important(37). An aneurysm of the splenic artery is recognized as focal dilatation of the vessel on axial and 3D images.

Superior and inferior extent of the transjugular portosystemic (TIPS) shunt

Some transplant candidates will have a transjugular portosystemic shunt placed prior to transplantation. In these patients, the superior tip of the shunt is normally in the right hepatic vein and the inferior tip is in the right portal vein . Migration of the shunt and shunt-related stenosis are among the complications that can affect transplantation in 22-34% of patients(15,38). If the TIPS shunt extends into the inferior vena cava, inflammatory change can occur in the vessel wall and can lead to scarring and narrowing of the cava(38). The scarred vein wall is resected at transplantation and may necessitate supradiaphragmatic dissection. Occasionally, the shunt tip can be in the right atrium, which further complicates removal of the native liver(39). Narrowing of the cava may also preclude living donor transplantation where the recipients' inferior vena cava is normally left intact.

If the TIPS shunt extends into the extrahepatic main portal vein, that portion of the vein has to be resected due to scarring of the endothelium(39). This results in decreased length of the portal vein that is available for anastomosis to the donor liver. This may preclude living donor transplantation or require a vein graft for extension. Surgical complications are also increased due to peripancreatic dissection that occurs with isolating the spleno-mesenteric confluence. Another complication that has been noted with extrahepatic TIPS shunts is pseudoaneurysm of the portal vein(38). Use of shorter stents and pretransplant evaluation of their location have been suggested in transplant candidate's(39).

The location of the superior and inferior tips of the shunt can easily be determined on axial and 3D CT images(40). The metallic stent walls are seen as curvilinear densities. With superior migration, the tip can lie in the intrahepatic or suprahepatic inferior vena cava . In cases of low inferior shunt tips, the stent is seen in the extrahepatic portal vein . The relationship of the stent tip to the spleno-mesenteric confluence can be demonstrated on 3D images.

Evaluation of LIVING DONORS

 

Hepatic arterial anatomy to the graft lobe

Up to one-third of potential donors may be ineligible for transplantation because of unsuitable hepatic arterial anatomy(33). Adequate hepatic arterial flow is necessary for successful graft function and to avoid necrosis of biliary structures. In recipients with thrombosis of the hepatic artery, urgent retransplantation is necessary in most cases to avoid a fatal outcome(41). Since extrahepatic collateral routes that are present in the native liver are no longer available once it is removed from the donor, all vessels supplying the liver need to be identified prior to its removal(41). Only 55% of individuals have classic arterial anatomy with the right and left hepatic arteries arising from the proper hepatic artery(33). In the remainder, the arterial anatomy is variable. The right hepatic artery is replaced and arises from the superior mesenteric artery in 14% and the left hepatic artery is replaced and arises from the left gastric artery in 10% of subjects (42). Accessory right or left hepatic arteries are each present in approximately 8% of subjects .

The presence of accessory vessels to a lobe requires at least two arterial anastomoses and small caliber arteries, which are more likely to be present in donors with multiple vessels supplying a single lobe(43). If the size of these vessels is less than 2-3 mm, they are at increased risk of thrombosis after transplantation (43,44). To decrease this risk, surgeons use microsurgical techniques for performing the arterial anastomosis(43). In some cases, the presence of multiple small vessels precludes donation . Resection of the right lobe or left lateral segment is also aided by knowing the origin of the segment IV artery which can arise from the right or left hepatic artery . Atherosclerotic celiac artery disease in a donor precludes donation .

CT angiography is accurate in displaying hepatic arterial anatomy(44). In a series of 115 patients, CT angiography was demonstrated to be as accurate as catheter angiography for evaluation of hepatic arterial anatomy in liver transplant candidates(33). CT angiography is also a less invasive and shorter examination. In addition, both the liver parenchyma and vasculature can be assessed by a single study. The data can be displayed in a fashion similar to catheter angiography using 3D volume rendering techniques. With the availability of multidetector spiral scanners, 1 mm slices can be routinely obtained without sacrificing the volume of coverage. Preliminary observations have shown that the major branches of the superior mesenteric and celiac arteries can be routinely identified(45). The origin of the artery to segment IV has also been shown using multidetector CT(46). This detail will likely help in identifying small accessory hepatic arteries.

Venous and biliary anatomy

The three main branches of the hepatic vein, the right, left and middle veins drain into the inferior vena cava . A variable number of inconstant branches can also drain part of the posterior segment of the right lobe of the liver directly into the inferior vena cava (47). An accessory hepatic vein can cause increased bleeding if not recognized preoperatively and may also be necessary venous drainage for the transplanted right lobe. If there are multiple veins, venoplasty is performed or each vein is anastomosed separately to the inferior vena cava(48).

The portal vein usually bifurcates into right and left portal veins. The right portal vein is usually regarded as a continuation of the main portal vein(47). The main portal vein can also "trifurcate" with an early branching pattern in the right lobe . If there are two branches to the right lobe, two anastomoses are required when it is transplanted into an adult recipient.

Similar CT techniques are used for evaluation of venous anatomy as described for arterial anatomy. Volume rendered 3D images confirm the number of vessels seen on axial scans and better display the branching pattern. The images obtained with a 60 second delay after contrast injection are used to demonstrate the veins.

Single right and left hepatic bile ducts join to form the common hepatic duct. In some patients, segmental ducts from the right or left lobes can join the common hepatic duct separately(47). As non-dilated ducts are difficult to appreciate on CT without biliary contrast, MR or CT cholangiography is necessary. The latter can be performed by giving patients oral iopanoic acid and imaging after a 6-10 hour delay(49). In a pilot study of normal volunteers and patients, biliary anatomy was better demonstrated in the volunteer's(49).

Liver volumes

Donor liver volumes obtained by CT are matched with the volume needed by the recipient as calculated according to body surface area. The region of interest in the liver is outlined by hand on a workstation and automated software is used to compute the liver volume. The volume of the segment or lobe to be donated and remnant liver are calculated. A minimum of 40% of the normal liver volume is needed by the recipient(46). If the donor liver is too large, closure of the abdomen can be difficult and respiratory status may be compromised (1). The donor volume is also used to ensure that a minimum of 35% of the liver is left in the donor(46).

Liver parenchyma

Fatty change in the liver is not uncommon in the general population and has multiple etiologies such as diabetes, hyperlipidemia and steroid use(50). Histologic diagnosis of moderate to severe fatty change in a potential donor generally precludes donation due to lowering of the corrected graft mass(3). The presence of fatty change can be suggested on noncontrast CT scans performed with single-energy and dual-energy technique(46).

On noncontrast scans there is an inverse linear relationship between the CT attenuation of the liver and degree of fatty infiltration(51). With single-energy technique, attenuation of the liver lower than the spleen by more than 12 H on precontrast scans is indicative of fatty change(52). In the study by Mendler et al., the sensitivity of single-energy CT was greater for diagnosing fatty change in livers without iron overload than in those with iron overload(52). The sensitivity decreases in livers with iron-overload as iron and fat have opposing effects on density(52,53). For dual-energy CT, the principle that the attenuation of a fatty liver increases with increase in the energy of the applied beam is used(54). If the liver is scanned with a beam at 80 kVp and then 140 kVp, the change (increase) in Hounsfield units is greater for fatty livers than for normal parenchyma. A change of greater than 10 H is indicative of fatty change(54). The sensitivity has been reported as only 20% for livers without iron overload(52). As for single-energy scans, this technique is not reliable if fatty change is accompanied by iron overload in the liver(52,54). On scans obtained with IV contrast, the density of the liver and spleen depend on the injection rate and timing of the scan(51). There is overlap of the differential liver-spleen densities between normal and fatty livers limiting the diagnosis of fatty change on contrast enhanced scans(51,55). However, in cases of significant fatty infiltration, the density of the liver is lower than paraspinal muscle(53).

Summary

Liver transplantation is a successful therapeutic option for chronic liver disease and liver failure. Evaluation of recipients and donors is successfully done by CT. In recipients, assessment of the liver parenchyma for malignancy, patency of the portal vein and celiac artery and location of venous shunts is performed. In living donors, the liver parenchyma is evaluated for fatty change and liver volume is calculated. Arterial and venous anatomy is also mapped for surgical planning.

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this article is based om an article published in RadioGraphics 2001

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