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  • 1. Aims and Scope

    Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE

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    Yong Chan Lee Professor of Medicine
    Director, Gastrointestinal Research Laboratory
    Veterans Affairs Medical Center, Univ. California San Francisco
    San Francisco, USA

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    Jong Pil Im Seoul National University College of Medicine, Seoul, Korea
    Robert S. Bresalier University of Texas M. D. Anderson Cancer Center, Houston, USA
    Steven H. Itzkowitz Mount Sinai Medical Center, NY, USA
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    All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
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Non-Contrast Abbreviated Magnetic Resonance Imaging: A Cost-Effective Rookie in Hepatocellular Carcinoma Surveillance for Cirrhotic Patients

Subin Heo1 , Won-Mook Choi2

1Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Won-Mook Choi
ORCID https://orcid.org/0000-0002-9158-1765
E-mail dr.choi85@gmail.com

See “Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis” by Pakanat Decharatanachart et al. on page 135, Vol. 18, No. 1, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gut Liver 2024;18(1):7-9. https://doi.org/10.5009/gnl230537

Published online January 15, 2024, Published date January 15, 2024

Copyright © Gut and Liver.

Surveillance programs for early hepatocellular carcinoma (HCC) detection are imperative to enable potential curative treatments like local ablation or surgical resection. While current guidelines advocate for bi-annual ultrasound (US) with or without serum alpha-fetoprotein (AFP) for surveillance, the limited sensitivity of US in detecting early-stage HCC (reported within a range of 27.9% to 62%) may impede timely intervention.1-3 Consequently, there is a growing interest in exploring alternative imaging tools such as computed tomography or magnetic resonance imaging (MRI) for surveillance. In a surveillance setting requiring repeated examinations, MRI emerges as the preferred choice over computed tomography due to concerns about cumulative radiation hazards associated with the latter. While MRI utilizing hepatocyte-specific contrast agents demonstrates impressive diagnostic performance, concerns related to prolonged examination times and costs have prompted researchers to investigate abbreviated MRI (AMRI), a protocol incorporating only a few essential sequences. Three major AMRI protocols exist: gadoxetic acid-enhanced AMRI with hepatobiliary phase imaging, dynamic contrast-enhanced AMRI, and non-contrast AMRI. Non-contrast AMRI, encompassing T2-weighted imaging, diffusion-weighted imaging, and/or T1-weighted in/opposed imaging, holds distinct advantages over the other two types of AMRI using contrast agents: it poses no risk of gadolinium retention, boasts the lowest cost, and requires the shortest scan time. Moreover, non-contrast AMRI has shown acceptable sensitivity for HCC detection, ranging from 61.5% to 86.4% in four retrospective simulated studies.4-7 Two prospective clinical trials on non-contrast AMRI are on their way to be published (MAGNUS-HCC, NCT02551250; MIRACLE-HCC, NCT02514434).

In a previous study that evaluated the cost-effectiveness of MRI with liver-specific contrast compared to US in patients with cirrhosis, MRI surveillance was found to be a cost-effective option as the incidence of HCC increases.8 Specifically, in the United States, the incremental cost-effectiveness ratio for MRI surveillance fell below the cost-effectiveness threshold when the annual HCC incidence rate exceeded 1.81%. Furthermore, another study utilizing data from four French multicenter prospective cohorts also concluded that MRI is cost-effective for patients with an annual HCC risk greater than 3%, representing about one-third of cirrhotic patients in the context of hepatitis C virus eradication and hepatitis B virus control.9 These findings support the notion that contrast-enhanced MRI offers benefits over US in high-risk cirrhotic patients. In this regard, it would not be surprising to infer that non-contrast AMRI could be cost-effective compared to US in patients with cirrhosis; however, to date, this issue has not yet been thoroughly investigated.

In this study, Decharatanachart et al.10 investigated the cost-effectiveness of non-contrast AMRI for HCC surveillance in cirrhotic patients, compared with the current standard of US combined with AFP testing. Utilizing a Markov model, they analyzed data from both Thailand and the United States. In both countries, the surveillance protocol using non-contrast AMRI proved to be cost-effective according to the respective national cost-effectiveness thresholds, outperforming US with AFP in almost all analyses. In the probabilistic sensitivity analysis, non-contrast AMRI offered a probability of 0.98 for being the optimal surveillance strategy in the United States and 0.77 in Thailand. Consistent with these findings, it has been confirmed that in the United States, non-contrast AMRI is cost-effective in all scenarios where the incidence is 1% or higher. This holds true except in the unlikely real-world scenario where the sensitivity of US with AFP exceeds 0.781. These results indicate that in the United States, virtually all patients with cirrhosis, irrespective of their etiology, are likely to benefit more from non-contrast AMRI than from US with AFP. Due to differing economic conditions and healthcare environments, in Thailand, it was found that non-contrast AMRI is cost-effective compared to US with AFP in cases where the estimated incidence rate exceeds 2.5%, which appears to cover a significant number of cirrhotic patients.

Nonetheless, careful consideration is necessary when interpreting the results on this research topic due to certain limitations. In the absence of a prospective study on the surveillance performance of non-contrast AMRI, most evaluations of surveillance performance have relied on the results of retrospective simulation studies, presenting limitations in designing cost-effective study models. Moreover, aside from the cost-effectiveness of non-contrast AMRI, the intrinsic limitations of non-contrast AMRI should also be noted, especially when compared with dynamic contrast-enhanced AMRI, which is emerging as a rising star in HCC surveillance for cirrhotic patients. Firstly, its sensitivity, though higher than that of US, may be lower compared to AMRI using a contrast agent. In a retrospective simulated study by Vietti Violi et al.,4 the non-contrast AMRI showed significantly lower sensitivity than simulated AMRI with hepatobiliary phase imaging (61.5% vs 80.8%). Secondly, lesion detection in non-contrast AMRI heavily relies on diffusion-weighted imaging, a sequence easily affected by artifacts like susceptibility or motion artifacts. An image significantly hindered by artifacts may necessitate additional surveillance examination, potentially leading to unnecessary physical harm associated with surveillance. Thirdly, when non-contrast AMRI yields a positive result, an additional imaging exam using a contrast agent is always required for a definitive diagnosis.

In summary, despite the limitations previously mentioned, the strengths of non-contrast AMRI, combined with the research findings on its cost-effectiveness presented in this study, suggest that non-contrast AMRI could serve as a “cost-effective rookie” for HCC surveillance in cirrhotic patients. However, before its clinical application in cirrhotic patients for HCC surveillance, further studies, including the results of ongoing prospective clinical trials, are needed to determine whether non-contrast AMRI can demonstrate acceptable performance.

No potential conflict of interest relevant to this article was reported.

  1. Tzartzeva K, Obi J, Rich NE, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 2018;154:1706-1718.
    Pubmed KoreaMed CrossRef
  2. Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009;30:37-47.
    Pubmed KoreaMed CrossRef
  3. Kim SY, An J, Lim YS, et al. MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol 2017;3:456-463.
    Pubmed KoreaMed CrossRef
  4. Vietti Violi N, Lewis S, Liao J, et al. Gadoxetate-enhanced abbreviated MRI is highly accurate for hepatocellular carcinoma screening. Eur Radiol 2020;30:6003-6013.
    Pubmed CrossRef
  5. Park HJ, Jang HY, Kim SY, et al. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: comparison with ultrasound. J Hepatol 2020;72:718-724.
    Pubmed CrossRef
  6. Chan MV, McDonald SJ, Ong YY, et al. HCC screening: assessment of an abbreviated non-contrast MRI protocol. Eur Radiol Exp 2019;3:49.
    Pubmed KoreaMed CrossRef
  7. Whang S, Choi MH, Choi JI, Youn SY, Kim DH, Rha SE. Comparison of diagnostic performance of non-contrast MRI and abbreviated MRI using gadoxetic acid in initially diagnosed hepatocellular carcinoma patients: a simulation study of surveillance for hepatocellular carcinomas. Eur Radiol 2020;30:4150-4163.
    Pubmed CrossRef
  8. Kim HL, An J, Park JA, Park SH, Lim YS, Lee EK. Magnetic resonance imaging is cost-effective for hepatocellular carcinoma surveillance in high-risk patients with cirrhosis. Hepatology 2019;69:1599-1613.
    Pubmed CrossRef
  9. Nahon P, Najean M, Layese R, et al. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis. JHEP Rep 2021;4:100390.
    Pubmed KoreaMed CrossRef
  10. Decharatanachart P, Pan-Ngum W, Peeraphatdit T, et al. Cost-utility analysis of non-contrast abbreviated magnetic resonance imaging for hepatocellular carcinoma surveillance in cirrhosis. Gut Liver 2024;18:135-146.
    Pubmed CrossRef

Article

Editorial

Gut and Liver 2024; 18(1): 7-9

Published online January 15, 2024 https://doi.org/10.5009/gnl230537

Copyright © Gut and Liver.

Non-Contrast Abbreviated Magnetic Resonance Imaging: A Cost-Effective Rookie in Hepatocellular Carcinoma Surveillance for Cirrhotic Patients

Subin Heo1 , Won-Mook Choi2

1Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to:Won-Mook Choi
ORCID https://orcid.org/0000-0002-9158-1765
E-mail dr.choi85@gmail.com

See “Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis” by Pakanat Decharatanachart et al. on page 135, Vol. 18, No. 1, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Body

Surveillance programs for early hepatocellular carcinoma (HCC) detection are imperative to enable potential curative treatments like local ablation or surgical resection. While current guidelines advocate for bi-annual ultrasound (US) with or without serum alpha-fetoprotein (AFP) for surveillance, the limited sensitivity of US in detecting early-stage HCC (reported within a range of 27.9% to 62%) may impede timely intervention.1-3 Consequently, there is a growing interest in exploring alternative imaging tools such as computed tomography or magnetic resonance imaging (MRI) for surveillance. In a surveillance setting requiring repeated examinations, MRI emerges as the preferred choice over computed tomography due to concerns about cumulative radiation hazards associated with the latter. While MRI utilizing hepatocyte-specific contrast agents demonstrates impressive diagnostic performance, concerns related to prolonged examination times and costs have prompted researchers to investigate abbreviated MRI (AMRI), a protocol incorporating only a few essential sequences. Three major AMRI protocols exist: gadoxetic acid-enhanced AMRI with hepatobiliary phase imaging, dynamic contrast-enhanced AMRI, and non-contrast AMRI. Non-contrast AMRI, encompassing T2-weighted imaging, diffusion-weighted imaging, and/or T1-weighted in/opposed imaging, holds distinct advantages over the other two types of AMRI using contrast agents: it poses no risk of gadolinium retention, boasts the lowest cost, and requires the shortest scan time. Moreover, non-contrast AMRI has shown acceptable sensitivity for HCC detection, ranging from 61.5% to 86.4% in four retrospective simulated studies.4-7 Two prospective clinical trials on non-contrast AMRI are on their way to be published (MAGNUS-HCC, NCT02551250; MIRACLE-HCC, NCT02514434).

In a previous study that evaluated the cost-effectiveness of MRI with liver-specific contrast compared to US in patients with cirrhosis, MRI surveillance was found to be a cost-effective option as the incidence of HCC increases.8 Specifically, in the United States, the incremental cost-effectiveness ratio for MRI surveillance fell below the cost-effectiveness threshold when the annual HCC incidence rate exceeded 1.81%. Furthermore, another study utilizing data from four French multicenter prospective cohorts also concluded that MRI is cost-effective for patients with an annual HCC risk greater than 3%, representing about one-third of cirrhotic patients in the context of hepatitis C virus eradication and hepatitis B virus control.9 These findings support the notion that contrast-enhanced MRI offers benefits over US in high-risk cirrhotic patients. In this regard, it would not be surprising to infer that non-contrast AMRI could be cost-effective compared to US in patients with cirrhosis; however, to date, this issue has not yet been thoroughly investigated.

In this study, Decharatanachart et al.10 investigated the cost-effectiveness of non-contrast AMRI for HCC surveillance in cirrhotic patients, compared with the current standard of US combined with AFP testing. Utilizing a Markov model, they analyzed data from both Thailand and the United States. In both countries, the surveillance protocol using non-contrast AMRI proved to be cost-effective according to the respective national cost-effectiveness thresholds, outperforming US with AFP in almost all analyses. In the probabilistic sensitivity analysis, non-contrast AMRI offered a probability of 0.98 for being the optimal surveillance strategy in the United States and 0.77 in Thailand. Consistent with these findings, it has been confirmed that in the United States, non-contrast AMRI is cost-effective in all scenarios where the incidence is 1% or higher. This holds true except in the unlikely real-world scenario where the sensitivity of US with AFP exceeds 0.781. These results indicate that in the United States, virtually all patients with cirrhosis, irrespective of their etiology, are likely to benefit more from non-contrast AMRI than from US with AFP. Due to differing economic conditions and healthcare environments, in Thailand, it was found that non-contrast AMRI is cost-effective compared to US with AFP in cases where the estimated incidence rate exceeds 2.5%, which appears to cover a significant number of cirrhotic patients.

Nonetheless, careful consideration is necessary when interpreting the results on this research topic due to certain limitations. In the absence of a prospective study on the surveillance performance of non-contrast AMRI, most evaluations of surveillance performance have relied on the results of retrospective simulation studies, presenting limitations in designing cost-effective study models. Moreover, aside from the cost-effectiveness of non-contrast AMRI, the intrinsic limitations of non-contrast AMRI should also be noted, especially when compared with dynamic contrast-enhanced AMRI, which is emerging as a rising star in HCC surveillance for cirrhotic patients. Firstly, its sensitivity, though higher than that of US, may be lower compared to AMRI using a contrast agent. In a retrospective simulated study by Vietti Violi et al.,4 the non-contrast AMRI showed significantly lower sensitivity than simulated AMRI with hepatobiliary phase imaging (61.5% vs 80.8%). Secondly, lesion detection in non-contrast AMRI heavily relies on diffusion-weighted imaging, a sequence easily affected by artifacts like susceptibility or motion artifacts. An image significantly hindered by artifacts may necessitate additional surveillance examination, potentially leading to unnecessary physical harm associated with surveillance. Thirdly, when non-contrast AMRI yields a positive result, an additional imaging exam using a contrast agent is always required for a definitive diagnosis.

In summary, despite the limitations previously mentioned, the strengths of non-contrast AMRI, combined with the research findings on its cost-effectiveness presented in this study, suggest that non-contrast AMRI could serve as a “cost-effective rookie” for HCC surveillance in cirrhotic patients. However, before its clinical application in cirrhotic patients for HCC surveillance, further studies, including the results of ongoing prospective clinical trials, are needed to determine whether non-contrast AMRI can demonstrate acceptable performance.

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

References

  1. Tzartzeva K, Obi J, Rich NE, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology 2018;154:1706-1718.
    Pubmed KoreaMed CrossRef
  2. Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009;30:37-47.
    Pubmed KoreaMed CrossRef
  3. Kim SY, An J, Lim YS, et al. MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncol 2017;3:456-463.
    Pubmed KoreaMed CrossRef
  4. Vietti Violi N, Lewis S, Liao J, et al. Gadoxetate-enhanced abbreviated MRI is highly accurate for hepatocellular carcinoma screening. Eur Radiol 2020;30:6003-6013.
    Pubmed CrossRef
  5. Park HJ, Jang HY, Kim SY, et al. Non-enhanced magnetic resonance imaging as a surveillance tool for hepatocellular carcinoma: comparison with ultrasound. J Hepatol 2020;72:718-724.
    Pubmed CrossRef
  6. Chan MV, McDonald SJ, Ong YY, et al. HCC screening: assessment of an abbreviated non-contrast MRI protocol. Eur Radiol Exp 2019;3:49.
    Pubmed KoreaMed CrossRef
  7. Whang S, Choi MH, Choi JI, Youn SY, Kim DH, Rha SE. Comparison of diagnostic performance of non-contrast MRI and abbreviated MRI using gadoxetic acid in initially diagnosed hepatocellular carcinoma patients: a simulation study of surveillance for hepatocellular carcinomas. Eur Radiol 2020;30:4150-4163.
    Pubmed CrossRef
  8. Kim HL, An J, Park JA, Park SH, Lim YS, Lee EK. Magnetic resonance imaging is cost-effective for hepatocellular carcinoma surveillance in high-risk patients with cirrhosis. Hepatology 2019;69:1599-1613.
    Pubmed CrossRef
  9. Nahon P, Najean M, Layese R, et al. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis. JHEP Rep 2021;4:100390.
    Pubmed KoreaMed CrossRef
  10. Decharatanachart P, Pan-Ngum W, Peeraphatdit T, et al. Cost-utility analysis of non-contrast abbreviated magnetic resonance imaging for hepatocellular carcinoma surveillance in cirrhosis. Gut Liver 2024;18:135-146.
    Pubmed CrossRef
Gut and Liver

Vol.18 No.1
January, 2024

pISSN 1976-2283
eISSN 2005-1212

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