Potentially misleading hypointensity on hepatobiliary phase MRI with hepatocyte-specific contrast medium

Clinical History

Middle-aged female patient with hepatitis C virus (HCV)-related cirrhosis, currently in good performance status and well-compensated with calculated Model For End-Stage Liver Disease (MELD) score 10. No significantly abnormal findings at physical examination.
Serum alpha-fetoprotein (AFP) at the upper normal limit (6 ng/ml).

Imaging Findings

Considering the patient's age and limited yield of previous ultrasound, the hepatologist requested periodic MRI follow-up. Initially, MRI (Figs. 1, 2) using hepatocyte-specific contrast agent (gadoxetic acid), detected a sizeable, moderately T2-hyperintense lesion centered in the 7th liver segment, with straight margins, wedge-shaped configuration, absent mass effect, bulging or retraction of liver contour. The lesion had unrestricted diffusion and appeared T1-hypointense before contrast, hypervascularised with progressive enhancement in portal and venous phases. In the delayed hepatobiliary acquisition it was hypointense compared to the surrounding, moderately enhanced parenchyma indicating lack of functioning hepatocytes. No other abnormalities were seen in the upper abdomen.
Ultrasound-guided fine-needle aspiration did not detect tumour cells.
Four months later repeated MRI (Figs. 3, 4) with nonspecific extracellular gadolinium contrast (gadobutrol) confirmed unchanged shape, size and unenhanced signal features of the lesion, progressive persistent enhancement during the dynamic vascular phases. Despite absent capsular retraction, the stable lesion was consistent with mass-like confluent fibrosis.

Discussion

Detection and characterisation of focal liver lesions are crucial for correct therapeutic choice and planning, and are increasingly performed using hepatocyte-specific MR contrast agents (HSMRCAs) [1-3]. Among these, gadoxetic acid (Gd-EOB-DTPA, PrimoVist, Schering, Germany) combines the properties of nonspecific extracellular gadolinium-based contrast, which allow for conventional dynamic enhanced liver study, with functional information provided by delayed T1-weighted hepatobiliary phase (HBP) imaging. In patients with normal liver function 50% of Gd-EOB-DTPA is actively transported into hepatocytes and excreted via hepatobiliary system, resulting in uniformly bright liver parenchyma from Gd-EOB-DTP accumulation in the HBP acquisition. Since intensity of enhancement depends on liver function, cirrhosis results in a delayed, diminished and heterogeneous HBP [2, 4-7].
In HBP, lesions without functioning hepatocytes and bile canaliculi such as metastases appear as focal hypointense defects. In chronic liver disease, hepatocellular carcinoma (HCC) represents the key concern and generally appears hypointense compared to background signal, albeit a minority (2-8%) of well-differentiated HCCs retains sufficient membrane transporters necessary for Gd-EOB-DTPA uptake. Since iso- or hyperintensity on HBP represents an indicator of benignity with 90% accuracy, use of HSMRCAs is appealing for differentiating benign from malignant liver lesions [2, 4-7].
However, as this case exemplifies, a potential pitfall of Gd-EOB-DTPA-enhanced HBP imaging is represented by mass-like confluent fibrosis (MCF), which results from parenchymal collapse and replacement with fibrosis, and is not unusually encountered in cross-sectional surveillance of cirrhosis, particularly alcohol-related. MCF most commonly occurs at the anterior and medial right lobe, and generally appears as a focal, often wedge-shaped lesion pointing towards the hepatic hilum and widest at the capsular surface which may be either flattened or retracted. Using HSMRCAs, MCF may be misinterpreted as HCC since it is hypointense on precontrast T1-weighted, faintly T2-hyperintense, and devoid of enhancement on HBP imaging due to scarce functioning hepatocytes. However, HBP findings should always be interpreted together with morphologic criteria, unenhanced signal features, diffusion-weighted and apparent diffusion coefficient (ADC) information, and dynamic enhancement patterns. Differently from HCC, MCF generally does not show lobulated margins, bulging contours, satellite nodules, mass effect, arterial-phase hypervascularity, portal venous phase contrast washout, and markedly reduced ADC values. Furthermore, as hereby demonstrated, compared to HBP hypointensity MCF characteristically shows a reversed appearance on delayed (equilibrium) phase imaging acquired with conventional (non-hepatocyte-specific) gadolinium contrast, with hyperintensity reflecting the progressive retention of extracellular contrast within fibrotic tissue, similarly to intrahepatic cholangiocarcinoma [4-11].

Differential Diagnosis List

Final Diagnosis

Focal confluent fibrosis in liver cirrhosis.

URL:	https://www.eurorad.org/case/13706
DOI:	10.1594/EURORAD/CASE.13706
ISSN:	1563-4086