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Published in: Hepatology International 2/2022

01-04-2022 | Hepatocellular Carcinoma | Original Article

Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma

Authors: Rex Wan-Hin Hui, Albert Chi-Yan Chan, Gladys Lo, Regina Lo, Cura Chan, Clarence Nicholas Kotewall, Lung-Yi Mak, Wong-Hoi She, Kin-Pan Au, Victor Ai, James Fung, Man-Fung Yuen, Wai-Kay Seto

Published in: Hepatology International | Issue 2/2022

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Abstract

Background

Magnetic resonance (MR) elastography and proton density fat fraction (PDFF) are emerging techniques for non-invasive assessment of liver stiffness and steatosis, respectively. We investigated the role of MR metrics in pre-treatment prognostication of hepatocellular carcinoma (HCC).

Methods

Patients with newly diagnosed HCC were prospectively recruited. Pre-treatment MR elastography and PDFF were performed on tumor and non-tumor regions. HCC treatment was categorized as potentially curative (resection/ablation) or non-curative (locoregional/systemic therapy). HCC recurrence, liver-related complications (ascites/ variceal bleeding/ hepatic encephalopathy) and mortality were monitored.

Results

Of the 158 recruited patients (mean age 62.9 years, 84.2% male, 82.9% viral hepatitis), 58.2% (n = 92) and 41.8% (n = 66) received potentially curative and non-curative therapy, respectively. Pre-treatment non-tumor liver stiffness independently predicted liver-related complications, regardless of treatment type (HR 1.384, 95% CI 1.067–1.796, p = 0.014). In the potentially curative therapy group, non-tumor stiffness and non-tumor PDFF were independently associated with HCC recurrence (HR 1.308, 95% CI 1.022–1.673 & HR 1.080, 95% CI 1.009–1.156 respectively, both p < 0.05); and non-tumor PDFF predicted mortality (HR 1.160, 95% CI 1.038–1.296, p = 0.009). In the non-curative group, tumor stiffness independently predicted liver-related complications (HR 1.299, 95% CI 1.023–1.651, p = 0.032), and a combination of tumor stiffness ≥ 5.7 kPa plus non-tumor stiffness ≥ 3.7 kPa was associated with a two-fold risk of liver-related complications (86.7% vs 40.0%, p < 0.001).

Conclusion

Pre-treatment MR elastography and PDFF over tumor and non-tumor regions demonstrated prognosticating roles in HCC. Simultaneous measurements of both metrics during conventional MR liver should be considered in the diagnostic workup of HCC.
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Literature
1.
go back to reference Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249CrossRefPubMed Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249CrossRefPubMed
2.
3.
go back to reference Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–338CrossRefPubMed Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–338CrossRefPubMed
4.
go back to reference Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–750CrossRefPubMed Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723–750CrossRefPubMed
5.
go back to reference Chernyak V, Fowler KJ, Kamaya A, et al. Liver imaging reporting and data system (LI-RADS) version 2018: imaging of hepatocellular carcinoma in at-risk patients. Radiology. 2018;289:816–830CrossRefPubMed Chernyak V, Fowler KJ, Kamaya A, et al. Liver imaging reporting and data system (LI-RADS) version 2018: imaging of hepatocellular carcinoma in at-risk patients. Radiology. 2018;289:816–830CrossRefPubMed
6.
go back to reference Omata M, Cheng A-L, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hep Int. 2017;11:317–370CrossRef Omata M, Cheng A-L, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hep Int. 2017;11:317–370CrossRef
7.
go back to reference Lee DH, Lee JM, Chang W, et al. Prognostic role of liver stiffness measurements using magnetic resonance elastography in patients with compensated chronic liver disease. Eur Radiol. 2018;28:3513–3521CrossRefPubMed Lee DH, Lee JM, Chang W, et al. Prognostic role of liver stiffness measurements using magnetic resonance elastography in patients with compensated chronic liver disease. Eur Radiol. 2018;28:3513–3521CrossRefPubMed
8.
go back to reference Thomaides-Brears HB, Lepe R, Banerjee R, et al. Multiparametric MR mapping in clinical decision-making for diffuse liver disease. Abdom Radiol (NY). 2020;45:3507–3522CrossRef Thomaides-Brears HB, Lepe R, Banerjee R, et al. Multiparametric MR mapping in clinical decision-making for diffuse liver disease. Abdom Radiol (NY). 2020;45:3507–3522CrossRef
9.
go back to reference Cho HJ, Kim B, Kim HJ, et al. Liver stiffness measured by MR elastography is a predictor of early HCC recurrence after treatment. Eur Radiol. 2020;30:4182–4192CrossRefPubMed Cho HJ, Kim B, Kim HJ, et al. Liver stiffness measured by MR elastography is a predictor of early HCC recurrence after treatment. Eur Radiol. 2020;30:4182–4192CrossRefPubMed
10.
go back to reference Siripongsakun S, Lee JK, Raman SS, et al. MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis. AJR Am J Roentgenol. 2012;199:1018–1025CrossRefPubMed Siripongsakun S, Lee JK, Raman SS, et al. MRI detection of intratumoral fat in hepatocellular carcinoma: potential biomarker for a more favorable prognosis. AJR Am J Roentgenol. 2012;199:1018–1025CrossRefPubMed
12.
go back to reference Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91–96CrossRefPubMed Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91–96CrossRefPubMed
13.
go back to reference Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85PubMed Child CG, Turcotte JG. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85PubMed
14.
go back to reference Chan A, Zhang WY, Chok K, et al. ALPPS versus portal vein embolization for hepatitis-related hepatocellular carcinoma: a changing paradigm in modulation of future liver remnant before major hepatectomy. Ann Surg. 2021;273:957–965CrossRefPubMed Chan A, Zhang WY, Chok K, et al. ALPPS versus portal vein embolization for hepatitis-related hepatocellular carcinoma: a changing paradigm in modulation of future liver remnant before major hepatectomy. Ann Surg. 2021;273:957–965CrossRefPubMed
15.
go back to reference Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699CrossRefPubMed Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699CrossRefPubMed
16.
go back to reference Ohki T, Tateishi R, Shiina S, et al. Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH. Gut. 2009;58:839–844CrossRefPubMed Ohki T, Tateishi R, Shiina S, et al. Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH. Gut. 2009;58:839–844CrossRefPubMed
17.
go back to reference Shinkawa H, Tanaka S, Takemura S, et al. Obesity and recurrence-free survival in patients with hepatocellular carcinoma after achieving sustained virological response to interferon therapy for chronic hepatitis C. Ann Gastroenterol Surg. 2018;2:319–326CrossRefPubMedPubMedCentral Shinkawa H, Tanaka S, Takemura S, et al. Obesity and recurrence-free survival in patients with hepatocellular carcinoma after achieving sustained virological response to interferon therapy for chronic hepatitis C. Ann Gastroenterol Surg. 2018;2:319–326CrossRefPubMedPubMedCentral
18.
go back to reference Mak LY, Hui RW, Fung J, et al. Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B. J Hepatol. 2020;73:800–806CrossRefPubMed Mak LY, Hui RW, Fung J, et al. Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B. J Hepatol. 2020;73:800–806CrossRefPubMed
19.
go back to reference Hui RWH, Seto WK, Cheung KS, et al. Inverse relationship between hepatic steatosis and hepatitis B viremia: results of a large case-control study. J Viral Hepatitis. 2018;25:97–104CrossRef Hui RWH, Seto WK, Cheung KS, et al. Inverse relationship between hepatic steatosis and hepatitis B viremia: results of a large case-control study. J Viral Hepatitis. 2018;25:97–104CrossRef
20.
go back to reference Lallukka S, Sädevirta S, Kallio MT, et al. Predictors of liver fat and stiffness in non-alcoholic fatty liver disease (NAFLD)—an 11-year prospective study. Sci Rep. 2017;7:14561CrossRefPubMedPubMedCentral Lallukka S, Sädevirta S, Kallio MT, et al. Predictors of liver fat and stiffness in non-alcoholic fatty liver disease (NAFLD)—an 11-year prospective study. Sci Rep. 2017;7:14561CrossRefPubMedPubMedCentral
21.
go back to reference Mathurin P, Beuzin F, Louvet A, et al. Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features. Aliment Pharmacol Ther. 2007;25:1047–1054CrossRefPubMed Mathurin P, Beuzin F, Louvet A, et al. Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features. Aliment Pharmacol Ther. 2007;25:1047–1054CrossRefPubMed
22.
go back to reference Vos B, Moreno C, Nagy N, et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease. Acta Gastro-Enterol Belg. 2011;74:389–394 Vos B, Moreno C, Nagy N, et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD): a major cause of cryptogenic liver disease. Acta Gastro-Enterol Belg. 2011;74:389–394
24.
go back to reference Bae JS, Lee DH, Yi NJ, et al. Magnetic resonance elastography versus transient elastography in the prediction of complications after resection for hepatocellular carcinoma. Ann Surg. 2020 Bae JS, Lee DH, Yi NJ, et al. Magnetic resonance elastography versus transient elastography in the prediction of complications after resection for hepatocellular carcinoma. Ann Surg. 2020
25.
go back to reference Singh S, Fujii LL, Murad MH et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11:1573–1584.e1571–1572 (quiz e1588–1579) Singh S, Fujii LL, Murad MH et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11:1573–1584.e1571–1572 (quiz e1588–1579)
26.
go back to reference Geethanath S, Vaughan JT Jr. Accessible magnetic resonance imaging: a review. J Magnet Resonance Imaging (JMRI). 2019;49:e65–e77CrossRef Geethanath S, Vaughan JT Jr. Accessible magnetic resonance imaging: a review. J Magnet Resonance Imaging (JMRI). 2019;49:e65–e77CrossRef
27.
go back to reference Ling W, Lu Q, Lu C, et al. Effects of vascularity and differentiation of hepatocellular carcinoma on tumor and liver stiffness: in vivo and in vitro studies. Ultrasound Med Biol. 2014;40:739–746CrossRefPubMed Ling W, Lu Q, Lu C, et al. Effects of vascularity and differentiation of hepatocellular carcinoma on tumor and liver stiffness: in vivo and in vitro studies. Ultrasound Med Biol. 2014;40:739–746CrossRefPubMed
28.
go back to reference Chan AWH, Zhong J, Berhane S, et al. Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol. 2018;69:1284–1293CrossRefPubMed Chan AWH, Zhong J, Berhane S, et al. Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol. 2018;69:1284–1293CrossRefPubMed
Metadata
Title
Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma
Authors
Rex Wan-Hin Hui
Albert Chi-Yan Chan
Gladys Lo
Regina Lo
Cura Chan
Clarence Nicholas Kotewall
Lung-Yi Mak
Wong-Hoi She
Kin-Pan Au
Victor Ai
James Fung
Man-Fung Yuen
Wai-Kay Seto
Publication date
01-04-2022
Publisher
Springer India
Published in
Hepatology International / Issue 2/2022
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-022-10305-y

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