Skip to main content
Top
Published in: European Radiology 8/2022

28-02-2022 | Liver Cirrhosis | Gastrointestinal

Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid–enhanced MRI: long-term follow-up in a surveillance cohort

Authors: Hyo Jung Park, Tae Young Lee, So Yeon Kim, Min-Ju Kim, Amit G. Singal, So Jung Lee, Hyung Jin Won, Jae Ho Byun, Young-Suk Lim

Published in: European Radiology | Issue 8/2022

Login to get access

Abstract

Objectives

With the increasing use of gadoxetic acid–enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data.

Methods

This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1–3 rounds of bi-annual surveillance gadoxetic acid–enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation.

Results

A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21–9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively.

Conclusions

About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules.

Key Points

The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC.
Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up.
Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249PubMed Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249PubMed
2.
go back to reference Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68:723–750CrossRef Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68:723–750CrossRef
3.
go back to reference European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236 European Association for the Study of the Liver (2018) EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69:182–236
4.
go back to reference Tzartzeva K, Obi J, Rich NE et al (2018) Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 154(1706-1718):e1701 Tzartzeva K, Obi J, Rich NE et al (2018) Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 154(1706-1718):e1701
5.
go back to reference Kim SY, An J, Lim YS et al (2017) MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol 3:456–463CrossRef Kim SY, An J, Lim YS et al (2017) MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol 3:456–463CrossRef
6.
go back to reference Yoon JH, Lee JM, Lee DH et al (2020) A comparison of biannual two-phase low-dose liver CT and US for HCC surveillance in a group at high risk of HCC development. Liver Cancer 9:503–517CrossRef Yoon JH, Lee JM, Lee DH et al (2020) A comparison of biannual two-phase low-dose liver CT and US for HCC surveillance in a group at high risk of HCC development. Liver Cancer 9:503–517CrossRef
7.
go back to reference Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) (2019) 2018 Korean Liver Cancer Association–National Cancer Center Korea practice guidelines for the management of hepatocellular carcinoma. Korean J Radiol 20:1042–1113CrossRef Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) (2019) 2018 Korean Liver Cancer Association–National Cancer Center Korea practice guidelines for the management of hepatocellular carcinoma. Korean J Radiol 20:1042–1113CrossRef
8.
go back to reference Besa C, Lewis S, Pandharipande PV et al (2017) Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid. Abdom Radiol (NY) 42:179–190CrossRef Besa C, Lewis S, Pandharipande PV et al (2017) Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid. Abdom Radiol (NY) 42:179–190CrossRef
9.
go back to reference Marks RM, Ryan A, Heba ER et al (2015) Diagnostic per-patient accuracy of an abbreviated hepatobiliary phase gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance. AJR Am J Roentgenol 204:527–535CrossRef Marks RM, Ryan A, Heba ER et al (2015) Diagnostic per-patient accuracy of an abbreviated hepatobiliary phase gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance. AJR Am J Roentgenol 204:527–535CrossRef
10.
go back to reference Tillman BG, Gorman JD, Hru JM et al (2018) Diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI protocol for hepatocellular carcinoma screening. Clin Radiol 73:485–493CrossRef Tillman BG, Gorman JD, Hru JM et al (2018) Diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI protocol for hepatocellular carcinoma screening. Clin Radiol 73:485–493CrossRef
12.
go back to reference Kudo M (2009) Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol 44(Suppl 19):112–118CrossRef Kudo M (2009) Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol 44(Suppl 19):112–118CrossRef
13.
go back to reference Joo I, Kim SY, Kang TW et al (2020) Radiologic-pathologic correlation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid–enhanced MRI: a multicenter study. Radiology 296:335–345CrossRef Joo I, Kim SY, Kang TW et al (2020) Radiologic-pathologic correlation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement at gadoxetic acid–enhanced MRI: a multicenter study. Radiology 296:335–345CrossRef
14.
go back to reference Kumada T, Toyoda H, Tada T et al (2011) Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium-enhanced MRI. AJR Am J Roentgenol 197:58–63CrossRef Kumada T, Toyoda H, Tada T et al (2011) Evolution of hypointense hepatocellular nodules observed only in the hepatobiliary phase of gadoxetate disodium-enhanced MRI. AJR Am J Roentgenol 197:58–63CrossRef
15.
go back to reference Motosugi U, Ichikawa T, Sano K et al (2011) Outcome of hypovascular hepatic nodules revealing no gadoxetic acid uptake in patients with chronic liver disease. J Magn Reson Imaging 34:88–94CrossRef Motosugi U, Ichikawa T, Sano K et al (2011) Outcome of hypovascular hepatic nodules revealing no gadoxetic acid uptake in patients with chronic liver disease. J Magn Reson Imaging 34:88–94CrossRef
16.
go back to reference Kim YK, Lee WJ, Park MJ, Kim SH, Rhim H, Choi D (2012) Hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with cirrhosis: potential of DW imaging in predicting progression to hypervascular HCC. Radiology 265:104–114CrossRef Kim YK, Lee WJ, Park MJ, Kim SH, Rhim H, Choi D (2012) Hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with cirrhosis: potential of DW imaging in predicting progression to hypervascular HCC. Radiology 265:104–114CrossRef
17.
go back to reference Hyodo T, Murakami T, Imai Y et al (2013) Hypovascular nodules in patients with chronic liver disease: risk factors for development of hypervascular hepatocellular carcinoma. Radiology 266:480–490CrossRef Hyodo T, Murakami T, Imai Y et al (2013) Hypovascular nodules in patients with chronic liver disease: risk factors for development of hypervascular hepatocellular carcinoma. Radiology 266:480–490CrossRef
18.
go back to reference Inoue T, Hyodo T, Murakami T et al (2013) Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma: a nationwide retrospective study on their natural course and risk factors. Dig Dis 31:472–479CrossRef Inoue T, Hyodo T, Murakami T et al (2013) Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma: a nationwide retrospective study on their natural course and risk factors. Dig Dis 31:472–479CrossRef
19.
go back to reference Joishi D, Ueno A, Tanimoto A et al (2013) Natural course of hypovascular nodules detected on gadoxetic acid-enhanced MR imaging: presence of fat is a risk factor for hypervascularization. Magn Reson Med Sci 12:281–287CrossRef Joishi D, Ueno A, Tanimoto A et al (2013) Natural course of hypovascular nodules detected on gadoxetic acid-enhanced MR imaging: presence of fat is a risk factor for hypervascularization. Magn Reson Med Sci 12:281–287CrossRef
20.
go back to reference Yoon JH, Lee JM, Yang HK et al (2014) Non-hypervascular hypointense nodules >/=1 cm on the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging in cirrhotic livers. Dig Dis 32:678–689CrossRef Yoon JH, Lee JM, Yang HK et al (2014) Non-hypervascular hypointense nodules >/=1 cm on the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging in cirrhotic livers. Dig Dis 32:678–689CrossRef
21.
go back to reference Kim YS, Song JS, Lee HK, Han YM (2016) Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long-term outcomes and risk factors for hypervascular transformation. Eur Radiol 26:3728–3736CrossRef Kim YS, Song JS, Lee HK, Han YM (2016) Hypovascular hypointense nodules on hepatobiliary phase without T2 hyperintensity on gadoxetic acid-enhanced MR images in patients with chronic liver disease: long-term outcomes and risk factors for hypervascular transformation. Eur Radiol 26:3728–3736CrossRef
22.
go back to reference Cho YK, Kim JW, Kim MY, Cho HJ (2018) Non-hypervascular hypointense nodules on hepatocyte phase gadoxetic acid-enhanced MR images: transformation of MR hepatobiliary hypointense nodules into hypervascular hepatocellular carcinomas. Gut Liver 12:79–85CrossRef Cho YK, Kim JW, Kim MY, Cho HJ (2018) Non-hypervascular hypointense nodules on hepatocyte phase gadoxetic acid-enhanced MR images: transformation of MR hepatobiliary hypointense nodules into hypervascular hepatocellular carcinomas. Gut Liver 12:79–85CrossRef
23.
go back to reference Briani C, Di Pietropaolo M, Marignani M et al (2018) Non-hypervascular hypointense nodules at gadoxetic acid MRI: hepatocellular carcinoma risk assessment with emphasis on the role of diffusion-weighted imaging. J Gastrointest Cancer 49:302–310CrossRef Briani C, Di Pietropaolo M, Marignani M et al (2018) Non-hypervascular hypointense nodules at gadoxetic acid MRI: hepatocellular carcinoma risk assessment with emphasis on the role of diffusion-weighted imaging. J Gastrointest Cancer 49:302–310CrossRef
24.
go back to reference Takeishi K, Yoshizumi T, Itoh S et al (2020) Surgical indications for hepatocellular carcinoma with non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI. Ann Surg Oncol 27:3344–3353CrossRef Takeishi K, Yoshizumi T, Itoh S et al (2020) Surgical indications for hepatocellular carcinoma with non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI. Ann Surg Oncol 27:3344–3353CrossRef
25.
go back to reference Velazquez RF, Rodriguez M, Navascues CA et al (2003) Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 37:520–527CrossRef Velazquez RF, Rodriguez M, Navascues CA et al (2003) Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 37:520–527CrossRef
28.
go back to reference Motosugi U, Murakami T, Lee JM et al (2018) Recommendation for terminology: nodules without arterial phase hyperenhancement and with hepatobiliary phase hypointensity in chronic liver disease. J Magn Reson Imaging 48:1169–1171CrossRef Motosugi U, Murakami T, Lee JM et al (2018) Recommendation for terminology: nodules without arterial phase hyperenhancement and with hepatobiliary phase hypointensity in chronic liver disease. J Magn Reson Imaging 48:1169–1171CrossRef
29.
go back to reference Toyoda H, Kumada T, Tada T et al (2013) Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy. J Hepatol 58:1174–1180CrossRef Toyoda H, Kumada T, Tada T et al (2013) Non-hypervascular hypointense nodules detected by Gd-EOB-DTPA-enhanced MRI are a risk factor for recurrence of HCC after hepatectomy. J Hepatol 58:1174–1180CrossRef
30.
go back to reference Lee DH, Lee JM, Lee JY et al (2015) Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: risk of HCC recurrence after radiofrequency ablation. J Hepatol 62:1122–1130CrossRef Lee DH, Lee JM, Lee JY et al (2015) Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MRI: risk of HCC recurrence after radiofrequency ablation. J Hepatol 62:1122–1130CrossRef
31.
go back to reference Akai H, Matsuda I, Kiryu S et al (2012) Fate of hypointense lesions on Gd-EOB-DTPA-enhanced magnetic resonance imaging. Eur J Radiol 81:2973–2977CrossRef Akai H, Matsuda I, Kiryu S et al (2012) Fate of hypointense lesions on Gd-EOB-DTPA-enhanced magnetic resonance imaging. Eur J Radiol 81:2973–2977CrossRef
32.
go back to reference Inoue M, Ogasawara S, Chiba T et al (2017) Presence of non-hypervascular hypointense nodules on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 32:908–915CrossRef Inoue M, Ogasawara S, Chiba T et al (2017) Presence of non-hypervascular hypointense nodules on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 32:908–915CrossRef
33.
go back to reference Lee DH, Lee JM, Yu MH et al (2019) Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MR can help determine the treatment method for HCC. Eur Radiol 29:3122–3131CrossRef Lee DH, Lee JM, Yu MH et al (2019) Non-hypervascular hepatobiliary phase hypointense nodules on gadoxetic acid-enhanced MR can help determine the treatment method for HCC. Eur Radiol 29:3122–3131CrossRef
34.
go back to reference Toyoda H, Tada T, Yasuda S et al (2019) The emergence of non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI in patients with chronic hepatitis C. Aliment Pharmacol Ther 50:1232–1238CrossRef Toyoda H, Tada T, Yasuda S et al (2019) The emergence of non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI in patients with chronic hepatitis C. Aliment Pharmacol Ther 50:1232–1238CrossRef
35.
go back to reference Goossens N, Singal AG, King LY et al (2017) Cost-effectiveness of risk score-stratified hepatocellular carcinoma screening in patients with cirrhosis. Clin Transl Gastroenterol 8:e101CrossRef Goossens N, Singal AG, King LY et al (2017) Cost-effectiveness of risk score-stratified hepatocellular carcinoma screening in patients with cirrhosis. Clin Transl Gastroenterol 8:e101CrossRef
36.
go back to reference Kim HL, An J, Park JA, Park SH, Lim YS, Lee EK (2019) Magnetic resonance imaging is cost-effective for hepatocellular carcinoma surveillance in high-risk patients with cirrhosis. Hepatology 69:1599–1613CrossRef Kim HL, An J, Park JA, Park SH, Lim YS, Lee EK (2019) Magnetic resonance imaging is cost-effective for hepatocellular carcinoma surveillance in high-risk patients with cirrhosis. Hepatology 69:1599–1613CrossRef
37.
go back to reference An JY, Pena MA, Cunha GM et al (2020) Abbreviated MRI for hepatocellular carcinoma screening and surveillance. Radiographics 40:1916–1931CrossRef An JY, Pena MA, Cunha GM et al (2020) Abbreviated MRI for hepatocellular carcinoma screening and surveillance. Radiographics 40:1916–1931CrossRef
38.
go back to reference Brunsing RL, Chen DH, Schlein A et al (2019) Gadoxetate-enhanced abbreviated MRI for hepatocellular carcinoma surveillance: preliminary experience. Radiol Imaging Cancer 1:e190010CrossRef Brunsing RL, Chen DH, Schlein A et al (2019) Gadoxetate-enhanced abbreviated MRI for hepatocellular carcinoma surveillance: preliminary experience. Radiol Imaging Cancer 1:e190010CrossRef
39.
go back to reference Nathani P, Gopal P, Rich N et al (2021) Hepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis. Gut 70:401–407PubMed Nathani P, Gopal P, Rich N et al (2021) Hepatocellular carcinoma tumour volume doubling time: a systematic review and meta-analysis. Gut 70:401–407PubMed
Metadata
Title
Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid–enhanced MRI: long-term follow-up in a surveillance cohort
Authors
Hyo Jung Park
Tae Young Lee
So Yeon Kim
Min-Ju Kim
Amit G. Singal
So Jung Lee
Hyung Jin Won
Jae Ho Byun
Young-Suk Lim
Publication date
28-02-2022
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 8/2022
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-022-08623-8

Other articles of this Issue 8/2022

European Radiology 8/2022 Go to the issue