New Insights in the Management of Hepatocellular Adenoma

Anne J. Klompenhouwer; Robert A. de Man; Marco Dioguardi Burgio; Valerie Vilgrain; Jessica Zucman-Rossi; Jan N. M. Ijzermans


Liver International. 2020;40(7):1529-1537. 

In This Article


As suggested by the 2016 EASL guidelines on the management of benign liver tumours, contrast enhanced MRI is the recommended imaging modality to analyse patients with suspected HCA allowing to determine the subtype in up to 80%.[11] Additionally, MRI is useful to differentiate HCA from focal nodular hyperplasia (FNH) using the combination of classical diagnostic criteria for FNH and lesion behaviour on hepatobiliary phase MRI using liver-specific contrast agents.[27] Contrast-enhanced CT also allows the visualization of lesion enhancement patterns and dilatation of intratumoral sinusoids, without any additional information over MRI. Contrast-enhanced ultrasound can be performed in addition to MRI to differentiate small (<3 cm) HCA from FNH in doubtful cases, although it has a limited value in differentiating among different HCA subtypes.[11,28,29]

HNF1A Inactivated HCA

Most of H-HCA is characterized microscopically by the presence of fat. The resulting diffuse and homogeneous drop of signal on opposed-phase T1-weighted MR images (Figure 2) has a very high specificity (89%-100%) and high sensitivity (87%-91%) for the diagnosis of H-HCA.[30,31] Other imaging features characterizing H-HCA include mild hyper-enhancement on hepatic arterial phase, followed by washout on later phases (Figure 2) and hypointensity on the hepatobiliary phase.

Figure 2.

H-HCA in a 23-year-old woman. MR images show a large lesion in the right liver lobe. The MR shows the presence of diffuse fat deposition within the lesion (drop of the signal on opposed-phase T1-weighted image B—if compared to in phase image—A). The lesion slightly enhances on hepatic arterial phase (C) and shows washout on portal venous phase (D)

Inflammatory HCA

I-HCA is characterized on MRI by strong hyperintensity on T2 images (diffuse or peripheral, "atoll sign"), and persistent enhancement on portal and delayed phases using extracellular MR contrast agents. Combination of these signs has a high specificity (88%-100%) for classifying inflammatory HCA[30–32] (Figure 3).

Figure 3.

I-HCA in a 26-year-old woman. The lesion is bright on T2-weighted image (A), is slightly hyperintense on fat-suppressed T1-weighted image (B), shows intense and heterogeneous enhancement on arterial phase (C), with persistent enhancement on portal venous phase after gadobenate dimeglumine injection (D). The lesion is hypointense on hepatobiliary phase (E–120 minutes)

Use of gadoxetic acid as liver-specific MRI contrast agent may modify the typical persistent enhancement. During transitional phase (3–5 minutes) vascular structures including dilated sinusoids within the tumour appear hypointense due to the rapid clearance of the gadoxetic acid from the vascular pool.[33] A study from Ba-Ssalamah et al showed that while 95% of inflammatory HCA presented with persistent enhancement on the portal phase after gadoxetic acid injection, only 48% showed persistent enhancement during the transitional phase.[34] Hence persistent enhancement should be only evaluated on portal venous phase when gadoxetic acid is used as contrast agent for MRI, while lesion hypointensity during transitional phase should not exclude the diagnosis of I-HCA.

In the hepatobiliary phase, most I-HCA are hypointense (Figure 3). Nevertheless, around one third of them show an iso- or hyperintense signal relative to the liver.[34–36] As I-HCA frequently develop in a steatotic liver and show spontaneous T1 hyperintensity, the reduced intensity of the background parenchyma (due to steatosis) on fat saturated sequences combined with their spontaneous hyperintensity on T1 can explain the lesion iso-hyperintensity in the hepatobiliary phase.[37] Therefore, a quantitative approach based on liver-to-lesion contrast enhancement ratio (LLCER), helps identify the real contrast uptake in the hepatobiliary phase.[35] Interestingly, in a recent study, 100% of I-HCA had a negative (<0%) LLCER whereas 86% of beta-catenin activated HCA (β-HCA) had a positive (>0%) LLCER.[37] The latter may be explained by the conserved expression of OATP (organic-anion-transporting polypeptide) in the b-HCA.

Beta-catenin Activated HCA—Sonic Hedgehog Activated HCA—Unclassified HCA

At present, it is not possible to accurately differentiate b-HCA, sh-HCA and U-HCA subtypes with imaging. Differently from I-HCA, b-HCA develop mostly in non steatotic livers.[37] b-HCA have initially been reported to be heterogeneous on all MR sequences,[30] sometimes with necrotic portions but without fat components, typically hypervascular with variable washout appearance.[30,34] These features are not sufficiently accurate. Practically, the diagnosis of b-HCA should be considered when a lesion that does not meet imaging criteria of focal nodular hyperplasia shows iso- to hyperintensity on the hepatobiliary phase or a positive LLCER between unenhanced and hepatobiliary phase (Figure 4), a heterogeneous appearance on T1-weighted images and a vague defined scar or heterogeneous appearance on T2-weighted images.[34,36–39] A recent study also suggested the potential added value of low ADC value for the diagnosis of b-HCA.[40] These preliminary data need to be validated in larger cohorts. Moreover an evident limitation of these studies is the absence of distinction between exon 3 and exon 7,8 b-HCA subtypes.

Figure 4.

bex3HCA in a 22-year-old woman. The lesion of the segment IV of the liver (arrows) is hyperintense with a heterogeneous appearance on T2-weighted image (A). The lesion is slightly hypointense on fat-suppressed T1-weighted image (B), slightly and heterogeneously hyperenhanced on arterial phase (C) and heterogeneously isointense on portal venous phase (D) after gadobenate dimeglumine injection. The lesion is visually hypointense on hepatobiliary phase (E—120 minutes) if compared to the background liver. A quantitative approach using LLCER helps point out the contrast uptake on hepatobiliary phase (LLCER measured at 18.6%). Diagnosis of bex3HCA activated hepatocellular adenoma was confirmed after resection

The combined form of I-HCA and exon 3 or exon 7,8 b-HCA (bex3IHCA or bex7,8IHCA), are likely to show the same imaging appearance as I-HCA.[30,41] Therefore, differentiating between a pure I-HCA and a b-IHCA is a new diagnostic challenge in imaging.

Finally, sh-HCA and U-HCA do not show specific imaging features and are often not distinguishable from hepatocellular carcinoma. Sh-HCA could be expected to present with haemorrhagic components at imaging,[21] but this still needs to be explored further.