Diagnosis of Complications: Role of Imaging Modalities
Systematic Follow-up
Ultrasonography with Doppler (US Doppler) is the best imaging modality for systematic follow-up of the liver allograft and for the detection and diagnosis of complications.
Grayscale mode allows for the analysis of graft parenchyma, vessels, and bile ducts and the detection of fluid collections ( Fig. 29.1 ). Color and pulsed Doppler modes allow the precise analysis of blood flow in the vessels and facilitate the diagnosis of bile duct dilation by showing tubular structures that are not color-encoded in contrast with the vessels ( Fig. 29.2 ).
There is no consensus in the literature concerning optimal systematic US screening during and after pediatric liver transplantation (LT). It is usually accepted that intraoperative US Doppler evaluation is helpful to detect very early vascular complication, thereby warranting immediate surgical repair. Routine follow-up varies among teams; some centers will recommend one US Doppler study every 12 hours, and others opt for every 24 hours, at least for the first few days after LT. After this period, weekly examinations are common and are then eventually limited to scheduled anniversary visits. The recommended systematic analysis with US Doppler is described in Tables 29.1 and 29.2 .
| Gray-scale imaging |
|
| Doppler study |
|
| Elastography (If available) |
|
| Normal | In case of stenosis | |
|---|---|---|
| Hepatic artery | Hepatopetal flow Velocity > 20 cm/s, no significant acceleration at the anastomosis RI > 0,50 | Velocity < 20 cm/s; prolonged acceleration time (> 80 ms) = Tardus parvus wave RI < 0,50 Stenotic velocity elevated > 200 cm/s |
| Portal vein | Hepatopetal flow Velocity > 15 cm/s no significant acceleration at the anastomosis | Slow velocity in intrahepatic branches < 10 cm/s Increased velocity at stenosis Intermittent or hepatofugal flow in the liver and upstream the portal anastomosis Presence of hepatopetal cavernoma, signs of portal hypertension Elevated spleen elasticity |
| Hepatic vein | Hepatofugal flow Velocity > 20 cm/s No significant acceleration at the anastomosis mono-, bi- or tri-phasic waveform | Decreased velocity of hepatic veins < 10 cm/s Increased velocity at stenosis > 200 cm/s Decreased velocity or even reversed flow in portal vein Signs of portal hypertension Elevated liver and spleen elasticity |
The healthy graft has a homogeneous echostructure. Note that the cut surface may be heterogeneous in smaller grafts. The normal Doppler patterns for graft vessels are summarized in Table 29.1 and illustrated in Fig. 29.1 .
Computed tomography (CT) scans and magnetic resonance imaging (MRI) scans are not necessary in routine follow-up.
Biliary Complications
Biliary complications are frequent after LT and may be challenging to diagnose. Two types of complications exist—leaks and strictures. (See Chapter 21 for a more detailed discussion of biliary complications.)
Leaks occur less than 30 days following transplantation and are mainly due to anastomotic disorders or the failure to anastomose an accessory bile duct at the time of transplantation. They usually appear on imaging as well-defined fluid collections, mainly anechoic. A rapid increase in size with time is very useful and may help differentiate bile leaks from a hematoma or ascites. In difficult cases, mainly for small leaks, magnetic resonance cholangiopancreatography (MRCP) with liver-specific contrast agent injection or hepatobiliary scintigraphy (HBS) can help identify the site of bile leakage.
Biliary strictures are more challenging to diagnose. In typical cases, the patients will have clinical and biological signs of cholestasis, and US will show dilated bile ducts (see Fig. 29.2 ). When there is an isolated biliary anastomotic stricture, bile ducts are dilated in all segments to the level of the anastomosis. If intrahepatic strictures exist, US may show suspended dilations of the bile ducts. US allows the depiction of thickened and/or irregular bile ducts walls and abnormal content, such as stones and sludge. Analysis of the entire biliary tree and the depiction of the exact site of obstruction are not always possible on US, however, and MRCP can be helpful for the exact mapping of the biliary tract (see Fig. 29.2 ).
Bile duct dilations may be absent on US in patients with biliary obstruction. Another important fact is that bile duct dilation is not well correlated with the severity of biliary strictures on percutaneous transhepatic cholangiography (PTC). In several studies, the sensitivity and specificity of US were between 79% and 93%, respectively. HBS has a better sensitivity (94%) and specificity (93%) but does not provide anatomical analysis of the bile ducts and anastomotic site. MRCP has the best diagnostic performance, with 100% sensitivity and 92% specificity. Moreover, it can show all the bile ducts and site of obstruction(s) precisely. However, in young children, MRCP is more challenging and may require sedation. Contrast-enhanced CT may show dilated bile ducts, but it is less effective than MRCP and exposes young patients to ionizing radiation. In daily practice, US is the best examination; MRCP or HBS is recommended for evaluating patients with possible biliary obstruction, regardless of findings on US.
Vascular Complications
Hepatic Artery
Hepatic artery (HA) complications are the most frequent vascular complications after LT, occurring in 1% to 26% of cases in published series. (See Chapter 20 for a more detailed discussion of arterial complications.)
Stenosis and thrombosis may occur any time after transplantation, but early thrombosis, within the first month after LT, is the most frequent and threatening complication. HA thrombosis (HAT) can lead to graft necrosis, deterioration of liver function, and/or biliary complications that are frequently delayed and appear after a few weeks. The mortality rate has been reported to be as high as 55.6% in cases of early occlusion, compared with 15% to 22.6% with late occlusion. The site of stenosis or thrombosis is usually the arterial anastomosis.
Early diagnosis is mandatory for emergent treatment to limit complications. HAS diagnosis relies on a Doppler US examination. CT angiography (angio-CT) or MR angiography (angio-MR) can confirm the diagnosis. HAS has a characteristic appearance on Doppler US. The intrahepatic arterial Doppler signal distal to the stenosis may show a tardus parvus pattern, with a decreased resistivity index (< 0.50) and a prolonged acceleration time (> 80 ms). At the site of narrowing, there is a focally accelerated velocity greater than 200 cm/s ( Fig. 29.3 ; see Table 29.1 ).
Of note, a decreased resistivity index can be a normal finding in patients with tachycardia. During the early phase of HAT, Doppler US will typically show the absence of arterial flow in the liver. However, within 2 weeks of the thrombotic event, collateral arteries develop, which may mimic normal arterial flow. They typically have a low resistive index and low peak systolic velocity, but a normal Doppler spectrum may be present.
Portal Vein
Portal vein complications include portal vein stenosis and thrombosis. They are explained in detail in Chapter 21 on vascular complications. Diagnosis relies mainly on Doppler US. Angio-CT or angio-MR is useful to confirm diagnosis.
Portal vein stenosis occurs at the anastomosis in the vast majority of the cases. The diagnosis may be quite difficult in some cases because of caliber mismatch between donor and recipient portal veins, something expected especially in very young children. This common finding is frequently associated with turbulence and even acceleration of the portal flow immediately downstream of the anastomosis, and it should not be mistaken as a stenosis. In case of portal stenosis, there is at least a 50% reduction of the diameter of the vessel lumen compared with the diameter of the prestenotic vessel using grayscale US. Cutoffs for the diameter of the anastomosis have been proposed ranging from less than 4 to 2.5 mm at the site of the narrowing.
Color Doppler US shows focal color aliasing at the site of the stenosis. A pulsed Doppler study shows a marked acceleration of the portal flow at the site of the narrowing. A cutoff value of 125 cm/s allows a 95% specificity with a 73% sensitivity. The comparison of pre-stenotic and post-stenotic portal flow velocity may also help; a ratio of 2 to 4 or a difference of 30 cm/s may reflect stenosis. The post-stenotic jet is usually fast and could explain the increased width of the portal vein. It has been suggested that portal vein stenosis is associated with a Rex recessus diameter >1.5cm (sensitivity 88%, specificity 83%). Portal flow velocity in the liver is slow. Slow portal flow in pre-stenotic portal vessels (portal, mesenteric, and splenic veins) argues in favor of a significant stenosis. Reverse flow upstream from the stenosis may be observed in severe cases. The presence of a venous cavernoma may also be helpful for the diagnosis of significant portal stenosis or thrombosis. Signs of portal hypertension, including splenomegaly and the presence of portosystemic shunts, are synonymous with venous congestion and, as such, may both facilitate diagnosis and follow-up after an intervention ( Fig. 29.4 ).
Angio-MR and angio-CT are useful to confirm diagnosis, study the portal vein in detail, and assess for signs of portal hypertension. Calcifications of the portal vein walls are better depicted on CT.
Acute portal vein thrombosis may be difficult to depict on a grayscale study because the thrombus is frequently anechoic. The absence of detectable flow in the portal vein is confirmatory. The intrahepatic portal flow will be either hepatopetal or reversed. Progressive narrowing or the portal lumen in the liver can be observed in two conditions: when the hepatopetal cavernoma is not efficient or if thrombosis has extended to the intrahepatic portal branches.
Hepatic Vein and Inferior Vena Cava
Stenosis or thrombosis of the hepatic veins or inferior vena cava (IVC) is another vascular complication that can arise after LT. (See Chapter 20 for a more detailed discussion of the complications of hepatic outflow obstruction.)
Hepatic outflow obstruction can be very difficult to diagnose on imaging. A venogram remains the gold standard for both diagnosis and treatment.
As in all vessels, hepatic veins or IVC stenosis will appear on grayscale US as a reduction of vessel diameter. Typically, the vessel upstream of the stenosis will display an increased diameter or the presence of a thrombus. Liver parenchyma may appear hyperechoic around the obstructed hepatic vein.
Stenosis of the IVC upstream of the hepatic vein or IVC anastomosis may be associated with clinical and histological signs of hepatic outflow obstruction. Significant stenosis leads to a very slow (< 10 cm/s) and even reversed flow in the hepatic veins or the IVC. Increased velocity at the site of the anastomosis may be present (> 100 cm/s) but is not specific. The association of increased peak anastomotic velocity and decreased intrahepatic venous velocity correlates strongly with significant outflow stenosis. The absence of the triphasic pattern of the hepatic veins on pulsed Doppler is not specific and may be observed in the absence of stenosis. On the other hand, the presence of a triphasic intrahepatic waveform offers a good negative predictive value for significant hepatic vein stenosis ( Fig. 29.5 ; see Table 29.1 ).
When outflow obstruction is significant, portal flow velocity may be decreased (< 10 cm/s), and signs of portal hypertension, especially ascites and pleural effusion, may be present. Recent reports have suggested that hepatic and splenic elastography are increased in case of venous congestion, which may be a useful parameter for the diagnosis and follow-up of hepatic outflow obstruction.
Angio-MR or angio-CT can be useful, but understanding the hepatic or caval anastomosis can be challenging. The classic signs of parenchymal heterogeneity associated with outflow obstruction in a native liver are not always present in liver grafts after contrast enhancement. Beyond the first week after LT, venography remains the gold standard for the diagnosis and management of hepatic or caval stenosis.
Steatosis
Liver graft steatosis commonly develops early after transplantation but rarely persists, with the exception of pre-disposing factors such as cystic fibrosis. It appears as a hyperechoic liver compared with the echogenicity of the renal cortex. There is no report in the literature concerning the evaluation and quantification of steatosis in LT using imaging modalities, especially MRI.
Tumors
Tumors may arise de novo following LT (e.g., post-transplantation lymphoproliferative disease). They may also result from recurrence of a primary disease, such as hepatoblastoma, hepatocarcinoma, or angiosarcoma. Imaging features of recurrent tumors are similar to those of the primary lesion and will not be covered further here.
Post-transplantation lymphoproliferative disorders may present as solid lesions in the spleen and/or lymph nodes, in the kidney and/or bowel, and on occasion in the liver graft. Thoracic, cervical, and cerebral involvements are also possible. CT or MRI with contrast injection will provide detailed evaluation of the extension of the disease. 18 F-Fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) is useful for staging, guiding biopsies, and following response to treatment.
Interventional Radiology for Diagnosis, Treatment, and Outcome
Image-Guided Biopsies (Percutaneous and Transjugular)
Liver biopsy is important in the management of patients following LT. In some centers, all biopsies are performed by the interventional radiology (IR) team, whereas in others, IR assistance is sought on a case-by-case basis. Two examples indicating biopsies in IR include significant hemostatic disorders or the presence of perihepatic ascites.
US guidance is essential, regardless of whether the percutaneous or transjugular route is favored. In the absence of any contraindication, percutaneous biopsy will be performed after selection of the biopsy tract with US. If necessary, the biopsy can be completely monitored with US guidance. When coagulation is abnormal, but does not preclude percutaneous biopsy, the biopsy tract can be embolized using gel foam to reduce the risk of hemorrhage.
When percutaneous liver biopsy is contraindicated because of coagulation abnormalities or the presence of ascites, a transjugular liver biopsy can be performed using continuous US guidance. Transjugular liver biopsies have been reported as soon as 6 days after LT. A standard percutaneous transjugular biopsy technique is used according to previous reports. US guidance is useful for internal jugular vein access and to avoid capsular perforation. Using this cautious approach, procedures can be performed safely, including in the very young infant.
Percutaneous Treatment of Biliary Complications
Biliary Leaks
In pediatric patients, because of the vast majority of left hepatic lobe grafts, bile leaks occur mostly in the right upper quadrant of the abdomen, along the cut surface. When the collection is large enough, percutaneous drainage is usually feasible, allowing confirmation of the diagnosis and allowing for fluid analysis and culture. Whenever possible, a drain will be left in place until resolution of the leak. The course after biliary drainage can vary from spontaneous resolution, with no further complications, to resolution followed by bile duct stenosis and biliary tract dilation, to the persistence of the leak, ultimately warranting surgery. In some cases, biliary drainage with the placement of a biliary stent or catheter, either with retrograde or percutaneous access, may allow resolution of the leak.
Biliary Strictures
There is no consensus in the literature about the treatment of biliary strictures after LT. Treatment options and prognosis vary according to the type of biliary anastomosis (bilioenteric vs. end-to-end choledochal) and the type of strictures (anastomotic and/or intrahepatic). Schematically, bilioenteric anastomoses are not treatable using endoscopy, and intrahepatic stenosis can only be treated by interventional radiology. Most pediatric patients have bilioenteric anastomosis that cannot be treated by endoscopy; PTC is then the only alternative to surgery.
The indication for PTC varies according to center. Some centers perform PTC even in patients with no bile ducts dilation if the suspicion of a biliary stricture is high. Other centers wait to have visible bile ducts that can be punctured under US guidance. Potential complications include sepsis and bleeding and are not life threatening in most cases, but it is nevertheless quite a safe procedure.
The PTC procedure consists of the following steps. First, the site of the stricture is determined using a fine-needle puncture of the bile ducts to access the ducts and perform a PTC. Second, an angioplasty balloon is placed over a guidewire across the stenosis and inflated to high pressure to relieve the stricture. Consensus may be lacking regarding the number and duration of balloon dilations and the type and duration of the drainage—external versus internal or external ( Figs. 29.6 and 29.7 ). In most published series, internal or external drainage is placed for several weeks or months. However, in addition to reducing the quality of life, long-term catheterization carries the risk of infection and obstruction, which may cause stones and progressing graft fibrosis.
Related posts:
What Is Different Between Pediatric and Adult Liver Transplantation?
Living Donor Liver Transplantation in Children
Recurrence of Disease After Liver Transplantation
Post-Operative Care After Liver Transplantation
Liver Transplantation for Acute Liver Failure in Children
Pediatric Liver Transplantation in South America: Incidence and Indications
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