Imaging diagnosis and staging of hepatocellular carcinoma

Authors


  • Potential conflict of interest: Nothing to report.

Despite the incremental technological advances in cross-sectional imaging techniques [ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI)], there is still some concern that the imaging technology available today is inadequate for appropriate prioritization for liver transplantation (LT) because it cannot provide a sufficiently accurate diagnosis of hepatocellular carcinoma (HCC) on a per-nodule basis or sufficiently accurate disease staging on a per-patient basis. In a recent study, a retrospective analysis of data from the United Network for Organ Sharing (which oversees solid organ transplantation in the United States) compared preoperative findings by cross-sectional imaging with postoperative explant pathology findings; in comparison with the pathological stages of the explanted livers, imaging was found to have underestimated or overestimated the tumor burden in approximately one-fourth of the cases.1 One might speculate that this finding not only is due to the inherent shortcomings of the cross-sectional imaging techniques that are generally available for the liver but also reflects significant differences in the technical specifications of scanner hardware and software, imaging protocols, and interpretive expertise, the lack of standardization of the language used in imaging reports, and the absence of widely accepted diagnostic criteria.

Here we discuss possible pathways to consensus positions on the following issues:

  • 1The minimal technical requirements for US, CT, and MRI.
  • 2The minimal requirements for operator expertise.
  • 3The standardization of imaging reports.
  • 4The classification of nodules on the imaging workup.
  • 5The staging of HCC.
  • 6The standardization of the evaluation of the results of locoregional therapy (LRT).
  • 7The standardization of surveillance for an early HCC diagnosis in patients listed for LT.
Abbreviations:

3D, three-dimensional; [18F]FDG, [18F]fludeoxyglucose; FAT SAT, fat saturated; CT, computed tomography; FNB, fine needle biopsy; HCC, hepatocellular carcinoma; LRT, locoregional therapy; LT, liver transplantation; MDCT, multidetector computed tomography; mRECIST, modified Response Evaluation Criteria in Solid Tumors; MRI, magnetic resonance imaging; PET, positron emission tomography; RECIST, Response Evaluation Criteria in Solid Tumors; TACE, transarterial chemoembolization; US, ultrasound.

MATERIALS AND METHODS

We performed a systematic review of the relevant literature and synthesized the available evidence with peer group appraisals and expert reviews. The consensus statements consist of recommendations and scientific comments that are based on a comprehensive review of the literature for each topic. The quality of the existing evidence and the strength of the recommendations have been ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford evidence-based approach to developing consensus statements.2

RESULTS

Minimal Technical Requirements for US, CT, and MRI

HCC can be diagnosed noninvasively (ie, on the basis of radiological findings) without biopsy if conclusive imaging features are present.3-8 These noninvasive diagnostic criteria require a contrast-enhanced study (dynamic CT, MRI, or both). This is reflected in the 2010 practice guideline recommendations of the American Association for the Study of Liver Diseases.9 The arterial enhancement of a nodule and the presence of washout on portal venous or delayed imaging are considered to be conclusive imaging features of HCC.6, 7, 10 For the diagnosis of HCC, a multiphasic contrast-enhanced imaging study, which includes optional unenhanced imaging followed by arterial, portal venous, and delayed phases, is required.8, 11, 12 Although several studies have demonstrated that contrast-enhanced US is very sensitive to the arterial vascularity of HCC,10, 13 US contrast agents unfortunately are not widely available in many countries, including the United States. Furthermore, US is operator-dependent; the limited field of view does not permit single-contrast phase imaging of the whole organ; and the body habitus of obese patients may interfere with high-quality imaging. US can be used for the diagnosis of HCC mainly because the contrast enhancement pattern of a previously noted liver lesion can be observed in high fidelity when the US examination is focused on that lesion before, during, and after the injection of the contrast agent. Although some reports have suggested CT or MRI screening as an alternative surveillance strategy for HCC because of the difficulties with US in obese individuals with fatty liver disease and advanced cirrhosis,14-16 most practices in the United States use US as a screening or surveillance tool for detecting HCC in cirrhotic livers, and once there is a positive focal finding, they use either CT or MRI for the characterization and follow-up.17-21 CT scanning is not recommended for surveillance because of the high false-positive rate and the risks associated with cumulative radiation exposure from repeated scans22; CT scanning is also not cost-effective.21 Therefore, although contrast-enhanced US plays a role in characterizing nodules in cirrhotic livers in some countries, contrast-enhanced CT and MRI are the most important and widely used techniques for the noninvasive diagnosis of HCC.23

Although conventional extracellular gadolinium chelates and iodinated contrast agents are the most commonly used contrast agents for dynamic MRI and CT, respectively, there have been several reports of promising single-center experiences with new paramagnetic, hepatocyte-specific contrast media: gadoxetate disodium (Primovist) and gadobenate dimeglumine (MultiHance). These contrast media combine the properties of conventional extracellular contrast agents and hepatobiliary agents and thus enable both dynamic multiphasic imaging and the depiction of hepatocyte uptake by the contrast agent and subsequent biliary excretion. Several previous studies have demonstrated that this kind of comprehensive vascular and functional evaluation of a nodule would improve the sensitivity and specificity of MRI for the diagnosis of HCC (particularly for nodules < 2 cm)24-26 and lead to a better diagnostic performance in comparison with multidetector computed tomography (MDCT).24, 27, 28 However, further studies are needed to assess (1) the real diagnostic value of additional hepatobiliary information for establishing a noninvasive diagnosis of HCC and (2) the positive predictive value for establishing the malignancy of nodules identified in cirrhotic livers when they are seen only on hepatobiliary phase images. In addition, recent studies have demonstrated that the addition of diffusion-weighted imaging to conventional T2-weighted imaging and dynamic imaging can improve the characterization of HCC and dysplastic nodules in cirrhotic livers and the detection of HCC.29, 30 Even though diffusion-weighted imaging is routinely included in MRI examinations of the liver at many centers, several issues regarding the role of diffusion-weighted imaging in the diagnosis of HCC in cirrhotic livers remain unresolved. These include the wide variations in the quality of the diffusion-weighted images generated by the different commercially available imaging platforms, the lack of standardization of protocols and sequences, and the significant overlap of benign and malignant liver lesions with respect to the qualitative appearance of the images and the quantitative values of the apparent diffusion coefficients.31, 32

Because the imaging diagnosis of HCC plays an important role in the clinical care and decision making of affected patients, it is crucial that imaging tests be performed with meticulous attention paid to the technical details. For example, several previous studies of the timing of arterial phase imaging with CT and MRI have demonstrated that the optimal detection of hypervascular HCC by CT or MRI requires the acquisition of images to be carefully timed to take place during the late arterial phase of contrast enhancement. Early arterial images are characterized by strong enhancement of the hepatic artery, but they do not allow enough time for contrast washin, so the enhancement of the tumors versus the background liver is insufficient.33-35 Early arterial phase imaging is, therefore, not recommended for HCC detection. Studies should be conducted with proven multiphasic contrast-enhanced imaging protocols. Suitable high-quality scanners should be used, and the studies should define the amount and injection rate of the contrast agent, the precise individualized timing of the image acquisition with respect to the injection of the contrast agent, and the suitable minimum slice thickness for the reconstruction of images (Tables 1–3).

Table 1. Minimum Technical Specifications for Liver US
FeatureSpecificationComment
Probe typeElectronic 
Frequency range3-5 MHzThe broadband technique is preferable.
Penetration/image uniformityProper receiver gain and time gain controls allow the echo texture to be visible in the deep region.The ability to image the entire liver uniformly without any artifacts (eg, streaks or dropouts) is necessary.
Accuracy of vertical and horizontal distance measurementsThe error is less than 5 mm. 
Doppler technique At least color Doppler imaging should be available.
Harmonic imaging The contrast-specific harmonic imaging technique is preferable.
Table 2. Minimum Technical Specifications for Dynamic Contrast-Enhanced MRI of the Liver
FeatureSpecificationComment
  1. NOTE: Reprinted with permission from Liver Transplantation.36 Copyright 2010, American Association for the Study of Liver Diseases.

Scanner type1.5-T or greater main magnetic field strengthLow-field magnets not suitable
Coil typePhased array multichannel torso coilUnless patient-related factors precludes use (eg, body habitus)
Gradient typeCurrent-generation high-speed gradients (providing sufficient coverage) 
InjectorDual-chamber power injector recommendedBolus tracking desirable
Contrast injection rate2-3 mL/second of gadolinium chelatePreferably resulting in vendor-recommended total dose
Minimum sequencesPrecontrast and dynamic post gadolinium T1-weighted gradient echo sequence (3D preferable), T2 (with and without FAT SAT), and T1w in- and out-of-phase imaging 
Mandatory dynamic phases on contrast-enhanced MRI (comments describe typical hallmark image features)1. Late arterial phase1. Artery fully enhanced, beginning contrast enhancement of portal vein
2. Portal venous phase2. Portal vein enhanced, peak liver parenchymal enhancement, beginning contrast enhancement of hepatic veins
3. Delayed phase3. Variable appearance, >120 seconds after the initial injection of contrast
Dynamic phases (timing)The use of a bolus tracking method for timing contrast arrival for late arterial phase imaging is preferable: portal venous phase (35-55 seconds after the initiation of a late arterial phase scan) and delayed phase (120-180 seconds after the initial contrast injection). 
Slice thickness5 mm or less for dynamic series, 8 mm or less for other imaging 
Breath holdingMaximum length of series requiring breath hold should be about 20 seconds with a minimum matrix of 128 × 256.Compliance with breath hold instructions is very important; technologists need to understand the importance of patient instruction before and during the scan.
Table 3. Minimum Technical Specifications for Dynamic Contrast-Enhanced Computerized Tomography of the Liver
FeatureSpecificationComment
  1. NOTE: Reprinted with permission from Liver Transplantation.36 Copyright 2010, American Association for the Study of Liver Diseases.

Scanner typeMultidetector row scanner 
Detector typeMinimum of 8 detector rowsNeed to be able to image the entire liver during the brief late arterial phase time window
Reconstructed slice thicknessMinimum reconstructed slice thickness of 5 mmThinner slices are preferable, especially if multiplanar reconstructions are performed.
InjectorPower injector, preferably a dual-chamber injector with a saline flushBolus tracking desirable
Contrast injection rateNo less than 3 mL/sec of contrast, 4-6 mL/sec better with at least 300 mg I/mL or a higher concentration for a dose of 1.5 mL/kg of body weight 
Mandatory dynamic phases on contrast-enhanced MDCT (comments describe typical hallmark image features)1. Late arterial phase1. Artery fully enhanced, beginning contrast enhancement of portal vein
2. Portal venous phase2. Portal vein enhanced, peak liver parenchymal enhancement, beginning contrast enhancement of hepatic veins
3. Delayed phase3. Variable appearance, >120 seconds after the initial injection of contrast
Dynamic phases (timing)Bolus tracking or timing bolus recommended for accurate timing 

Minimum Requirements for Operator Expertise

US

This cross-sectional imaging technique is highly operator-dependent, has a limited field of view, does not permit easy documentation of the whole organ, and is greatly influenced by a patient's phenotype (eg, abdominal fat, bowel gas, ascites, and chest wall deformities) as well as a patient's compliance with breathing commands during the acquisition of images. Moreover, because the cirrhotic liver typically is diffusely echogenic, the through-transmission of sound to the more remote portions of the organ is poor; this makes it fairly difficult to detect and characterize focal liver lesions.37 These limitations may explain the unsatisfactory pooled sensitivity (63%) of US as a surveillance test for revealing nonadvanced HCC (ie, HCC meeting the Milan criteria) in patients with cirrhosis; this sensitivity further decreases to 33% in studies using CT concurrently.38

Moreover, there are no particular training and licensure requirements for performing US in many countries. This procedure is performed worldwide by a very heterogeneous group of professionals, who include radiologists, hepatologists, gastroenterologists, internists, US technicians, and other physician extenders working on behalf of physicians. Notably, in the United States, examinations are frequently performed by technicians, who during the examinations select images to be archived for subsequent interpretation by radiologists. The interpreting physician often does not have easy access to the patient, so he cannot personally reevaluate areas of interest. Furthermore, this approach limits the evaluation of images to those identified by the US operator as worthy of documentation.

To optimize the use of US, the procedure may need to be performed by a physician with specific training in the performance of liver US [regardless of the physician's formal training credentials (medical or other)]. The use of US by unskilled sonographers or physicians should be considered inappropriate in this particular clinical context.39 Two separate and pertinent practice guidelines for US are promulgated by the American College of Radiology,40 and they outline the following minimum training and competency standards:

  • 1The performance and interpretation of diagnostic US examinations (revised in 2006).
  • 2The performance of US examinations of the abdomen and/or retroperitoneum.

Although these practice guidelines are valid only in the United States, they constitute a widely publicized and accepted framework for quality imaging examinations with this modality.

CT and MRI

A consensus conference panel of the United Network for Organ Sharing debated at length whether any accepted competency criteria were available for describing the particular competence of radiologists who interpret liver imaging.36 Although formal training in abdominal imaging could certainly be considered an advantage in this respect, it was agreed that an ongoing practice in an accredited, high-volume LT center is probably the best surrogate for professional competence; peer pressure and peer reviews in the typical interdisciplinary context found at such centers may over time result in the assurance that the imagers are practicing according to the highest possible standards. It was also recognized that testing a person's competence in any medical specialty is very difficult, and there are very few accepted and proven methods for ascertaining such competence. Certainly, the panel was not aware of any widely accepted methodology for testing or ascertaining competence in liver imaging and diagnosing HCC.

Standardization of Imaging Reports

The imaging report should always comment on the quality of the study (adequate or inadequate). If the study is inadequate or nondiagnostic, a repeat study should be performed before final decisions are made about the presence or absence of significant diseases such as HCC.41 For each detected focal liver lesion, the report should describe the following:

  • The location of the segment or segments.

  • The maximum diameter.

  • The lesion definition (well defined, moderately well defined, or poorly defined).

  • The echogenicity, attenuation, and signal intensity of the lesion during the various imaging phases versus the internal standards for the surrounding liver parenchyma.

  • The presence of a capsule or pseudocapsule.

  • Vascular thrombosis (benign versus malignant according to the contrast enhancement characteristics of the thrombus).

  • The involvement of the bile duct or a tumor thrombus of the bile duct.

  • The characteristics of the precontrast and postcontrast dynamic imaging phases (late arterial, portal venous, and delayed) and the hepatocyte imaging phase (for the hepatospecific MRI contrast agents).

Classification of Nodules on the Imaging Workup

For de novo 1- to 2-cm nodules in a cirrhotic liver, the specificity and positive predictive power of the typical radiological pattern of HCC, which is characterized by increased contrast enhancement (washin) during the late arterial phase and then by washout during the portal venous or delayed phase with a single dynamic technique (US, CT, or MRI), have been found to be high in single-center studies, although the negative predictive values have been only 42% to 50%.10, 42, 43 Therefore, any new nodule that is greater than 1 cm and shows this combination of imaging findings can be considered HCC when it is observed in a cirrhotic liver because metastatic disease, which can have a similar appearance, is exceedingly rare in cirrhotic livers (a conclusive diagnosis). The sensitivity of this single-technique policy to the malignancy of tiny lesions is 65%, whereas the sensitivity of the 2-technique policy (suggested by the 2005 guidelines from the American Association for the Study of Liver Diseases44) is only 35%; thus, the adoption of the single-technique policy could eliminate the use of fine needle biopsy (FNB) for a final diagnosis in one-third of patients43 (Fig. 1).

Figure 1.

Diagnostic algorithm for a newly detected nodule in a cirrhotic liver. Ø, nodule.

For hypervascular nodules without washout that are greater than 1 cm, the chance of being HCC is as high as 66%.42 Hence, this radiological pattern can be considered worrisome for the diagnosis of HCC. In these cases, an additional imaging technique for detecting washout is advisable so that the malignancy can be confirmed without FNB.

Additional imaging observations that are more commonly found in association with HCC include the following: high perfusion values for volume perfusion imaging with CT; hyperintensity on T2-weighted images; no uptake of hepatocyte-specific contrast agents during the hepatobiliary phase with MRI; hyperintensity on diffusion-weighted MRI sequences with high b values; peripheral rim enhancement during the delayed phase, intralesional fat (which is best assessed with in-phase and opposed-phase T1-weighted MRI sequences), an internal mosaic pattern, and vascular invasion on any dynamic postcontrast imaging; and the presence of a tumor capsule and interval growth (maximum diameter increase) of 50% or more on serial MRI or CT images obtained less than 6 months apart.30, 36, 45-47 The presence of one or several of these features may increase the confidence of the radiological diagnosis of HCC.

Hypovascular or isovascular HCC cannot be diagnosed with the aforementioned radiological criteria. Therefore, image-guided FNB or follow-up imaging needs to be considered for nodules that do not meet the qualitative criteria for HCC but raise concerns about HCC (eg, there is documented interval growth).

Staging of HCC Before LT

Liver

A liver containing at least 1 HCC must be staged with a suitable imaging technique that provides complete anatomic coverage of the liver.48-50 Dynamic contrast-enhanced CT and MRI are the only acceptable imaging techniques for this purpose.51-56 The faster imaging acquisition and the typically wider bore of the gantry of the machine may make CT preferable for patients who are unable to adequately hold their breath or are claustrophobic. US is inadequate because of its inability to reliably acquire images of the entire organ during a particular contrast phase.56 Several reports have shown that dynamic MRI seems to be more sensitive than CT for detecting small lesions (<2 cm).6, 26, 52, 57, 58 In addition, a systematic review of the accuracy of US, spiral CT, and MRI in diagnosing HCC in patients with chronic liver disease revealed the following pooled estimates: 60% specificity and 97% specificity for US (14 studies), 68% sensitivity and 93% specificity for CT (10 studies), and 81% sensitivity and 85% specificity for MRI (9 studies).59 The operative characteristics of CT are comparable, whereas MRI is more sensitive.52 However, a large-scale, systematic, prospective study is needed to determine which imaging modality is best for diagnosing HCC.

Extrahepatic Staging

For LT candidates, patient staging should routinely include CT scans of the chest, abdomen, and pelvis.60 Bone scintigraphy can be used for evaluating bone metastases.61 MRI can be an alternative for the abdominal cavity.44, 62

There are insufficient data for proposing [18F]fludeoxyglucose ([18F]FDG) positron emission tomography (PET) for HCC staging before LT. PET scans can reveal extrahepatic metastases that are not found with CT, but PET has a low sensitivity for tiny and/or well-differentiated HCCs when they are located within the liver because of the high background liver uptake of fludeoxyglucose; the specificity of PET is also very low.63 The use of dual-isotope PET ([18F]FDG and [11C]acetate) may increase the sensitivity for HCC because well-differentiated tumors have a high avidity for acetate rather than glucose.64, 65 However, the use of dual-isotope PET increases costs and a patient's exposure to radiation, and it is not widely available.

Notably, there is growing evidence that [18F]FDG PET before LT has a strong and independent prognostic power. In comparison with their counterparts, PET-positive tumors more frequently display unfavorable histological features (eg, high cellular dedifferentiation and microvascular invasion) heralding poorer recurrence-free survival after LT.66, 67 New studies should be aimed at assessing the potential role of PET in refining the priority criteria for patients listed for LT and in expanding the Milan criteria.

Standardization of the Evaluation of the Results of LRT

The goal of LRT is the complete removal of a tumor with hepatic resection or the complete necrosis of a tumor with locoregional ablative therapy [percutaneous thermal ablation, transarterial chemoembolization (TACE), or radioembolization]. Incomplete ablation has been reported to be a risk factor for post-LT tumor recurrence.68 LRT may need to be repeated to achieve complete necrosis. The need for additional interventions is typically assessed by imaging; specifically, an expert interprets images to determine whether a residual tumor exists.

Complete tumor ablation may be indicated by a complete absence of contrast-enhancing nodular tissue associated with the ablated lesion (any enhancement is evaluated in comparison with the background hepatic parenchyma). However, even if no residual enhancing tissue is perceptible, a viable tumor may remain in the treated areas, particularly when the lesions have a diameter greater than 3 cm before the treatment.69, 70 If there are areas of nodular or crescentic, extrazonal or intrazonal, enhancing nodular tissue in close association with the ablated lesion, residual or recurrent HCC may be suspected.71

Initially, the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines were proposed for measuring the treatment response according to tumor shrinkage, and they have been widely accepted as a valuable tool for measuring the antitumor activity of cytotoxic drugs. However, the conventional RECIST method, which takes into account only the overall diameter of a nodule, can be misleading when it is applied to HCC treated with either LRT or a systemic therapy such as sorafenib because treatment-induced changes in tissue viability often do not result in corresponding changes in the overall lesion size.72 More recently, a modified Response Evaluation Criteria in Solid Tumors (mRECIST) concept has been suggested for the evaluation of the treatment response in patients with HCC.72 Further studies are needed to confirm the validity of this concept.

Only well-delineated, arterially enhancing lesions can be selected as target lesions for mRECIST. The mRECIST concept for HCC includes the following amendments to the RECIST guidelines for the determination of the tumor response for target lesions72:

  • Complete response: the disappearance of any intratumoral arterial enhancement in all target lesions.

  • Partial response: at least a 30% decrease in the sum of the diameters of the viable target lesions (contrast enhancement in the arterial phase). The baseline sum of the diameters of the target lesions is used as the reference.

  • Progressive disease: at least a 20% increase in the sum of the diameters of the viable (enhancing) target lesions. The smallest sum of the diameters of the viable (enhancing) target lesions recorded since the initiation of the treatment is used as the reference.

  • Stable disease: any cases not qualifying for a partial response or progressive disease. Persistent fat after radiofrequency ablation in HCCs that contained fat before the treatment does not necessarily mean incomplete ablation.

Follow-up imaging with dynamic contrast-enhanced CT and MRI should be performed 1 to 3 months after LRT to establish the need for further treatment. Although 1-month follow-up CT or MRI after LRT is widely practiced at many centers, there are some difficulties in assessing the early tumor response, especially before or at 1 month because of arteriovenous shunts.73, 74 When lipiodol is used in conjunction with TACE, follow-up imaging with MRI may be preferable because the deposition of the extremely radiodense substance lipiodol may interfere with the CT evaluation of a marginal enhancement of the recurrent tumor after TACE. Lipiodol can, therefore, mask hypervascularity on CT imaging. Subtraction imaging may be helpful in these cases. The intense and complete capture of lipiodol by the tumor tissue is associated with extensive necrosis and is, therefore, considered by some to be a good prognostic factor. In any case, the interpretation of post-LRT images is made difficult by local alterations of the vasculature and the perifocal inflammatory response incited by the therapeutic procedures. Special expertise and experience with the interpretation of such images are, therefore, critical.

For the best possible comparability of images, serial posttreatment imaging follow-up is ideally performed with the same modality used to assess the presence of the tumor before or immediately after LRT.

Sorafenib, a multikinase inhibitor, was shown to significantly increase overall survival in a randomized, placebo-controlled, phase 3 trial of patients with HCC (the Sorafenib HCC Assessment Randomized Protocol), and this was also confirmed in another prospective trial from the Asia-Pacific region.75-77 Sorafenib is currently being tested in a randomized clinical trial as an adjuvant therapy for early and intermediate HCCs treated with surgical resection or LRT. If these trials provide positive results, sorafenib may become more widely used as an adjuvant therapy for patients with HCC who are listed for LT and are undergoing LRT.78 This combined therapy could increase the risk of an imaging misdiagnosis of a residual, locally treated tumor and prevent the imaging characterization of new lesions.78 We can expect the sensitivity of dynamic imaging techniques for HCC detection to be reduced in patients treated with the new antiangiogenic drugs because of their devascularizing effects on tumors, which can blunt or even suppress the arterial hypervascularity of HCC.79 Further studies for testing the ability of [18F]FDG PET/CT, perfusion CT, and diffusion-weighted MRI to improve the accuracy of the radiological diagnosis and staging of HCC in patients undergoing antiangiogenic treatments would be worthwhile.80

Standardization of Surveillance for an Early HCC Diagnosis in Patients Listed for LT

The early detection of HCC is of paramount importance for making optimal treatment decisions, including LT prioritization and the selection of the most suitable LRT, for affected patients. As previously mentioned, the diagnostic performance of US as a surveillance test is rather poor because of limitations due to both unfavorable patient characteristics and the nodular echo pattern of advanced cirrhosis in the liver. The drawbacks of US interfere with its ability to survey the selected population of patients waiting for LT.58, 81 The limited period of surveillance, the relatively low number of cases, and the high prognostic benefit offered by LT make it advisable to survey non-HCC patients who are listed for LT with CT or, preferably, MRI at 6-month intervals.57 It should be remembered that all the imaging techniques have a relatively poor sensitivity for minute nodules, and as many as 36% of synchronous HCC nodules that are detected during the pathological examination of the explant can be missed during the pre-LT imaging workup.82 Even when state-of-the-art MDCT technology and carefully timed multiphase image acquisition are used, as many as 11% of HCCs are missed, and the sensitivity of CT falls to 43% if the typical radiological pattern is required for the diagnosis of HCC.42 Similarly, for tumors whose size is less than 2 cm, the MRI sensitivity falls to 85%, and conclusive results are achieved in only 62% of cases.10 It is apparent that the diagnostic accuracy of all cross-sectional imaging modalities for detecting HCC is poor in patients with end-stage liver cirrhosis53, 58, 83; furthermore, surveillance recommendations for patients with end-stage liver cirrhosis are very different from country to country.44, 84, 85 A consensus on this topic could not be reached by the panelists. Therefore, further data are needed; in particular, proof is required for which imaging modality is ideal for HCC surveillance in patients who are listed for LT because of severe liver dysfunction.

SUMMARY AND RECOMMENDATIONS

Dynamic and multiphasic contrast-enhanced CT or MRI is recommended as a first-line diagnostic tool for HCC when an imaging assessment for the presence of HCC is indicated by screening or surveillance tests (level Ib, grade A).

For a given nodule in a cirrhotic liver, the presence of hyperenhancement in the late arterial phase and the subsequent washout of the contrast agent in the portal venous phase, delayed phase, or both are considered diagnostic for HCC (level II, grade B).

HCC can be diagnosed by imaging if the nodule is greater than 1 cm in diameter and these qualitative imaging criteria are met (level II, grade B).

Patients who have nodules with an atypical pattern of imaging findings (eg, an isovascular or hypovascular appearance in the arterial phase or arterial hypervascularity alone without portal venous washout) should undergo image-guided FNB or follow-up imaging (level III, grade C).

Imagers should employ carefully timed multiphasic contrast-enhanced imaging protocols on suitable high-quality scanners, and they should use a sufficient dose of the contrast agent, a sufficient injection rate, and a suitable minimum slice thickness for the reconstructed images (level III, grade C).

A liver containing at least 1 HCC must be staged with an imaging technique that affords complete anatomic coverage of the liver. Dynamic and multiphasic contrast-enhanced CT and MRI are the only acceptable imaging techniques for this purpose. Extrahepatic staging should routinely include CT scans of the chest, abdomen, and pelvis. MRI can be an alternative for the abdominal cavity (level III, grade C).

Complete tumor ablation after LRT for HCC may be indicated by a complete absence of contrast-enhancing nodular tissue associated with the ablated lesion (any enhancement is evaluated in comparison with the background hepatic parenchyma) on contrast-enhanced US, CT, or MRI images (level III, grade C).

Patients listed for LT without HCC should undergo serial imaging with CT or, preferably, MRI at 6-month intervals to ensure that the tumor remains absent or the tumor stage remains compatible with the transplant indication (level III, grade C).

Ancillary