Diagnostic Imaging Pathways - Hepatocellular Cancer (Suspected)
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This pathway provides guidance on the imaging investigation of adult patients with a focal liver lesion and risk factors for hepatocellular carcinoma.
Date reviewed: August 2015
Date of next review: August 2017
Published: February 2016
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| SYMBOL | RRL | EFFECTIVE DOSE RANGE |
 | None | 0 |
 | Minimal | < 1 millisieverts |
 | Low | 1-5 mSv |
 | Medium | 5-10 mSv |
 | High | >10 mSv |
Images
Image GalleryNote: These images open in a new page | ||
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| 1 |  |
Hepatic Haemangioma
Image 1 (Computed Tomography): Post-contrast images demonstrating initial peripheral enhancement, followed by delayed filling of the lesion with contrast. These features are typical of a haemangioma. |
| 2a |  |
Hepatic Haemangioma
Image 2a, 2b and 2c (Triphasic Computed Tomography): Non-contrast scan (Image 2a) demonstrates a subtle low attenuation lesion in segment 6 of the liver (arrow). There is globular peripheral enhancement of the lesion in the post contrast arterial phase scan (Image 2b) with delayed filling in of the lesion in the portal venous phase (Image 2c). |
| 2b |  |
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| 2c |  |
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| 2d |  |
Image 2d (Ultrasound): Ultrasound scan demonstrating the liver lesion in same patient. |
| 3 |  |
Hepatic Haemangioma
Image 3 (H&E, x2.5): Histological section of a hepatic haemangioma showing variously sized, dilated and congested blood vessels set in a fibrous stroma with residual islands of liver parenchyma. |
| 4a |  |
Hepatic Adenoma
Image 4a and 4b (Computed Tomography): Coronal and axial views demonstrating several enhancing liver lesions. |
| 4b |  |
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| 4c |  |
Image 4c (Ultrasound): Ultrasound scan demonstrating the liver lesions in same patient. |
| 5a |  |
Hepatic Focal Nodular Hyperplasia
Image 5a and 5b (Triphasic Computed Tomography): The arterial phase scan (Image 5a) shows a hyperattenuating nodular lesion (narrow arrow) with the typical central scar (broad arrow) in segment 4 of the liver. On the delayed portal venous phase (Image 5b), the lesion becomes isoattenuating (arrow). |
| 5b |  |
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| 6a |  |
Hepatic Focal Nodular Hyperplasia
Image 6a, 6b, 6c and 6d (Magnetic Resonance Imaging): Gadolinium-enhanced T1-weighted MRI (Image 6a) demonstrates an ill-defined low-signal intensity mass in segment 4 of the liver with intense enhancement in the arterial phase (Image 6b). Minor enhancement persists in the portal venous phase (Image 6c) and the lesion becomes isointense with enhancement of the central scar (arrow) on the delayed image (Image 6d). |
| 6b |  |
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| 6c |  |
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| 6d |  |
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| 7a |  |
Hepatic Focal Nodular Hyperplasia
Image 7a : Resection specimen showing the circumscribed, light brown to yellow nodular appearance withthe central stellate scar (arrow) characteristic of focal nodular hyperplasia. |
| 7b |  |
Image 7b (H&E, x10): Histological section showing hepatic nodules separated by fibrous septa with peripheral proliferation of bile ducts (arrow) associated with lymphocytic infiltration. The features are typical of focal nodular hyperplasia. |
| 8 |  |
Simple Hepatic Cyst
Image 8 (Ultrasound): Simple-appearing cyst in the left lobe of liver. |
| 9a |  |
Hepatocellular Carcinoma
Image 9a and 9b (Ultrasound): Within segment 6 of the liver, there is an approximately 2cm subcapsular hypoechoic lesion (arrow) which does not demonstrate any increased vascularity. |
| 9b | |
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| 9c |  |
Image 9c, 9d, 9e and 9f (Triphasic Computed Tomography): CT of the same patient shows a cirrhotic liver with patent hepatic and portal veins as well as ascites. Within segment 6, there is a nodular area which demonstrates slight enhancement corresponding to the lesion identified on ultrasound (arrow). This lesion could represent either a dysplastic cirrhotic nodule or an early hepatocellular carcinoma. |
| 9d |  |
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| 9e |  |
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| 9f |  |
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| 9g |  |
Image 9g, 9h, 9i and 9j (Magnetic Resonance Imaging): MRI of the same patient demonstrates a lesion measuring approximately 2.5 cm in diameter on the inferomedial aspect of segment 5 in a subcapsular location. This is bulging the capsule of the liver at the level of the upper pole of the right kidney. The lesion is essentially isointense to the rest of the liver on T1 weighted imaging (out of phase) but is slightly hyperintense on in-phase imaging suggesting that the rest of the liver has some fatty infiltration. The lesion is slightly hyperintense on first echo T2 but is not clearly visible on more heavily weighted T2 imaging. The lesion shows arterial enhancement but washes out in the portal venous phase, with the rim of the lesion remaining enhanced. The appearances are consistent with a hepatocellular carcinoma. |
| 9h |  |
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| 9i |  |
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| 9j |  |
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| 10a |  |
Hepatocellular Carcinoma
Image 10a and 10b : Hepatectomy specimens showing a multifocal hepatocellular carcinoma with areas of necrosis and haemorrhage arising in a cirrhotic liver. |
| 10b |  |
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| 10c |  |
Image 10c (H&E, x2.5) and 10d (H&E, x10): Histological sections of a hepatocellular carcinoma arising on a background of cirrhosis. The usual lobular architecture is replaced by irregular and thickened trabeculae of malignant hepatocytes. There is mild nuclear pleomorphism. |
| 10d |  |
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Teaching Points
Teaching Points
- In patients at risk of HCC
- Liver lesions <1cm are usually subject to follow-up imaging
- Lesions >1cm should undergo further imaging, preferably with MRI with a liver-specific contrast agent
- Lesions in patients at high risk for HCC showing typical features of HCC on imaging (arterial enhancement and then wash-out) can be treated as HCC without biopsy
- Biopsy should be reserved for lesions with non-diagnostic appearances on imaging
HS1
Hepatocellular Cancer (Suspected)
Risk factors for hepatocellular carcinoma
- Cirrhotic patients (AASLD)
- Non-cirrhotic patients with active chronic hepatitis B infection
- From Asian background
- 40-50 years of age (AASLD)
- Non-cirrhotic patients with chronic hepatitis C and advanced liver fibrosis [EASL 3 - lesser grade of recommendation]
- Cirrhotic patients due to hepatitis B or C [APASL, 4 JSH, 5]
- Patients with active chronic hepatitis B or C [JSH, 5]
- Patients with a family history of HCC
- Non-viral aetiology of liver cirrhosis [JSH, 5]
- e.g. alcoholic cirrhosis
- Haemachromatosis
- Primary biliary cirrhosis
- Auto-immune hepatitis
- Alpha-1 antitrypsin deficiency
- Non-alcoholic steatohepatitis
- Evidence for surveillance in patients with the above conditions without cirrhosis is scanty 5
Current existing international guidelines
- Internationally, there are several consensus-based guidelines for the investigation of suspected HCC, including the American Association for the Study of Liver Disease (AASLD), 1 the European Association for the Study of the Liver (EASL), 2 the Asian Pacific Association for the Study of the Liver (APASL), 3 the Japan Society of Hepatology, 4 and the Italian Association for the Study of the Liver. 5 While differences exist among these, it is possible to discern many similarities. The AASLD and Italian guidelines, divide detected lesions into <1cm and >1cm, whereas the EASL utilizes <1cm, 1-2cm and >2cm
- As the difference in recommendations between the latter two groups of the EASL guidelines is minor, this document has used the simpler categories of <1cm and >1cm
HS2
Typical Features of Hepatocellular Cancer (HCC)
Typical vascular pattern of HCC
- Most HCCs are hypervascular compared to the surrounding liver reflecting the predominant vascular supply to these lesions from branches of the hepatic artery, rather than the predominant portal venous supply of ‘normal’ liver
- Arterial enhancement followed by washout is considered the typical vascular pattern of HCC. This can be demonstrated on either 4-phase multi-detector CT or dynamic contrast-enhanced MRI or CEUS 1,6
- During the arterial phase, HCC enhances more intensely than the surrounding liver while during the venous phase HCC enhances less than the surrounding liver (known as 'wash-out')
- During the delayed phase, the 'wash-out' persists; sometimes the 'wash out' is only present during the delayed phase
- A recent systematic review indicated that for the evaluation of focal liver lesions, CT, MRI and CEUS had similar sensitivities for HCC 7
- In a further recent meta-analysis, comparing CT and MRI, MR imaging showed higher per-lesion sensitivity than multi-detector CT and was therefore recommended to be the preferred imaging modality for the diagnosis of HCCs in patients with chronic liver disease 8
HS3
Contrast-Enhanced Ultrasound (CEUS)
- Ultrasound contrast agents (‘microbubbles’) comprise an albumen or phospholipid shell containing a stable perfluorocarbon or sulfur hexafluoride gas. They are predominantly blood-pool agents, the encapsulated microbubbles being small enough to pass through pulmonary and systemic circulations after IV injection and durable enough to re-circulate for several minutes
- Ultrasound contrast agents are mainly based on the dynamic assessment of macro- and micro-vasculature of organs and their pathologies. They are, in principle, comparable to the use of contrast agents for CT and MRI with the added advantage of the capability for imaging continuously during the passage of the contrast agent, thereby obtaining what is effectively a dynamic real-time ultrasound angiogram with greater temporal resolution than contrast-enhanced CT or MRI. In addition, quantitative assessment of contrast uptake can be measured by generating Time-Intensity Curves
- CEUS was endorsed by AASLD in its 2005 guidelines 9 but removed from the list of diagnostic techniques in 2011, 1 partly due to lack of availability of ultrasound contrast in the USA and partly due to false-positive diagnoses in patients with intrahepatic cholangiocarcinoma (ICC). ICC’s may show peripheral ring enhancement, difficult to distinguish from small HCCs. In addition, washout of ICCs may mimic HCC washout; some small HCCs may fail to show washout. Nevertheless, controversy persists, since CEUS typical for HCC has a PPV of >95% 10 and it is suggested that the CEUS pattern is enough to establish whether malignancy is present. 11-14 Only 1-3% of newly developed tumours in cirrhosis are ICCs 15
- CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound 16 and, if available, can be recommended as the first diagnostic step when liver lesions are detected on ultrasound surveillance, 17 especially as the procedure can be performed immediately without the need for further attendance or preparation and may therefore avoid further and more expensive examinations 18
HS4
Magnetic Resonance Imaging (MRI) or Multiphase Computed Tomography (CT)
- CT and MRI are performed before and after intravenous contrast agents in multiple phases of enhancement. It is usual practice to acquire images in the arterial, portal venous and delayed post-contrast phases. In recent years agents have become available for MRI that exhibit a delayed hepatobiliary phase 19
- Two recent systematic reviews and meta-analyses have been published examining the performance of available modaliites for diagnosis of HCC 7,8 with the following findings from these studies and others
- For the evaluation of focal liver lesions, the sensitivites of CT, MR and CEUS are similar 7
- The sensitivity on a per lesion basis was higher for MRI than CT 8
- Specificity of CT and MRI ranged from 84-94% 7,8
- MRI using a gadolinium contrast agent that has a delayed hepatobiliary agent (a liver-specific agent) is very useful for the diagnosis of HCC 20,21 superior to MRI using a gadolinium contrast agent with only an extracellular phase 7,8,22 and is superior to CT 23
- MRI should be the preferred imaging modality for the diagnosis of HCC in patients with chronic liver disease 8, preferably with a liver-specific contrast agent
- Diffusion Weighted MRI
HS5
Image Guided Biopsy
- In the appropriate clinical context (patient at high risk of HCC) the typical radiological appearances of HCC (arterial enhancement and delayed wash-out) have very high specificity (almost 100%) , and therefore biopsy in this situation is rarely necessary 13,28
- Biopsy is required when the radiological appearances are non-diagnostic
- The accuracy for early HCC is approximately 90% 29
- Immediate complications include post-procedural pain and haemorrhage. The risk of major complications is 0.05% with a mortality of 0.01% 30
- A delayed complication is needle track seeding with tumour. A meta-analysis found the incidence to be 2.7% overall with a median time to seeding of 17 months 31
References
References
Date of literature search: August 2015
The search methodology is available on request. Email
References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document
- Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020-2. (Review article). View the reference
- European Association for the Study of the Liver, European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908-43. (Guidelines). View the reference
- Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439-74. (Guidelines). View the reference
- Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, et al. Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29(3):339-64. (Guidelines). View the reference
- Giannini EG, Cucchetti A, Erroi V, Garuti F, Odaldi F, Trevisani F. Surveillance for early diagnosis of hepatocellular carcinoma: how best to do it? World J Gastroenterol. 2013;19(47):8808-21. (Guidelines). View the reference
- Ronot M, Vilgrain V. Hepatocellular carcinoma: diagnostic criteria by imaging techniques. Best Pract Res Clin Gastroenterol. 2014;28(5):795-812. (Review article). View the reference
- Chou R, Cuevas C, Fu R, Devine B, Wasson N, Ginsburg A, et al. Imaging techniques for the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis. Ann Intern Med. 2015;162(10):697-711. (Level I evidence). View the reference
- Lee YJ, Lee JM, Lee JS, Lee HY, Park BH, Kim YH, et al. Hepatocellular carcinoma: diagnostic performance of multidetector CT and MR imaging-a systematic review and meta-analysis. Radiology. 2015;275(1):97-109. (Level I/II evidence). View the reference
- Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208-36. (Guidelines). View the reference
- Bolondi L, Cillo U, Colombo M, Craxi A, Farinati F, Giannini EG, et al. Position paper of the Italian Association for the Study of the Liver (AISF): the multidisciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis. 2013;45(9):712-23. (Guidelines). View the reference
- Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsoe CP, et al. Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS. Ultrasound Med Biol. 2013;39(2):187-210. (Guidelines). View the reference
- Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. J Hepatol. 2012;57(4):930-2. (Level IV/V evidence). View the reference
- Sangiovanni A, Manini MA, Iavarone M, Romeo R, Forzenigo LV, Fraquelli M, et al. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut. 2010;59(5):638-44. (Level III evidence). View the reference
- Numata K, Fukuda H, Nihonmatsu H, Kondo M, Nozaki A, Chuma M, et al. Use of vessel patterns on contrast-enhanced ultrasonography using a perflubutane-based contrast agent for the differential diagnosis of regenerative nodules from early hepatocellular carcinoma or high-grade dysplastic nodules in patients with chronic liver disease. Abdom Imaging. 2015. [Epub ahead of print]. (Level III evidence). View the reference
- Serste T, Barrau V, Ozenne V, Vullierme MP, Bedossa P, Farges O, et al. Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: role of biopsy. Hepatology. 2012;55(3):800-6. (Level III evidence). View the reference
- Xu HX, Lu MD, Liu LN, Zhang YF, Guo LH, Xu JM, et al. Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound. Br J Radiol. 2012;85(1018):1376-84. (Level III evidence). View the reference
- Dumitrescu CI, Gheonea IA, Sandulescu L, Surlin V, Saftoiu A, Dumitrescu D. Contrast enhanced ultrasound and magnetic resonance imaging in hepatocellular carcinoma diagnosis. Med Ultrason. 2013;15(4):261-7. (Level IV evidence). View the reference
- D'Onofrio M, Crosara S, De Robertis R, Canestrini S, Mucelli RP. Contrast-enhanced ultrasound of focal liver lesions. AJR Am J Roentgenol. 2015;205(1):W56-66. (Review article). View the reference
- Sirlin CB, Hussain HK, Jonas E, Kanematsu M, Min Lee J, Merkle EM, et al. Consensus report from the 6th International forum for liver MRI using gadoxetic acid. J Magn Reson Imaging. 2014;40(3):516-29. (Guidelines). View the reference
- Junqiang L, Yinzhong W, Li Z, Shunlin G, Xiaohui W, Yanan Z, et al. Gadoxetic acid disodium (Gd-EOBDTPA)-enhanced magnetic resonance imaging for the detection of hepatocellular carcinoma: a meta-analysis. J Magn Reson Imaging. 2014;39(5):1079-87. (Level I/II evidence). View the reference
- Zech CJ, Bartolozzi C, Bioulac-Sage P, Chow PK, Forner A, Grazioli L, et al. Consensus report of the Fifth International Forum for Liver MRI. AJR Am J Roentgenol. 2013;201(1):97-107. (Guidelines). View the reference
- Kwon HJ, Byun JH, Kim JY, Hong GS, Won HJ, Shin YM, et al. Differentiation of small (≤2 cm) hepatocellular carcinomas from small benign nodules in cirrhotic liver on gadoxetic acid-enhanced and diffusion-weighted magnetic resonance images. Abdom Imaging. 2015;40(1):64-75. (Level III evidence). View the reference
- Tsurusaki M, Sofue K, Isoda H, Okada M, Kitajima K, Murakami T. Comparison of gadoxetic acid-enhanced magnetic resonance imaging and contrast-enhanced computed tomography with histopathological examinations for the identification of hepatocellular carcinoma: a multicenter phase III study. J Gastroenterol. 2015. [Epub ahead of print]. (Level II/III evidence). View the reference
- Inchingolo R, De Gaetano AM, Curione D, Ciresa M, Miele L, Pompili M, et al. Role of diffusion-weighted imaging, apparent diffusion coefficient and correlation with hepatobiliary phase findings in the differentiation of hepatocellular carcinoma from dysplastic nodules in cirrhotic liver. Eur Radiol. 2015;25(4):1087-96. (Level III evidence). View the reference
- Sutherland T, Steele E, van Tonder F, Yap K. Solid focal liver lesion characterisation with apparent diffusion coefficient ratios. J Med Imaging Radiat Oncol. 2014;58(1):32-7. (Level III evidence). View the reference
- Wu LM, Xu JR, Lu Q, Hua J, Chen J, Hu J. A pooled analysis of diffusion-weighted imaging in the diagnosis of hepatocellular carcinoma in chronic liver diseases. J Gastroenterol Hepatol. 2013;28(2):227-34. (Level II/III evidence). View the reference
- Li Y, Chen Z, Wang J. Differential diagnosis between malignant and benign hepatic tumors using apparent diffusion coefficient on 1.5-T MR imaging: a meta analysis. Eur J Radiol. 2012;81(3):484-90. (Level II evidence). View the reference
- Sherman M, Bruix J. Biopsy for liver cancer: how to balance research needs with evidence-based clinical practice. Hepatology. 2015;61(2):433-6. (Level IV/V evidence). View the reference
- Caturelli E, Solmi L, Anti M, Fusilli S, Roselli P, Andriulli A, et al. Ultrasound guided fine needle biopsy of early hepatocellular carcinoma complicating liver cirrhosis: a multicentre study.Gut. 2004;53(9):1356-62. (Level II evidence). View the reference
- Chhieng DC. Fine needle aspiration biopsy of liver - an update. World J Surg Oncol. 2004;2:5. (Review article). View the reference
- Silva MA, Hegab B, Hyde C, Guo B, Buckels JA, Mirza DF. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut. 2008;57(11):1592-6. (Level II/III evidence). View the reference
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