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Gd-EOB-DTPA-enhanced MRI—a noninvasive and short-term assessment method for liver necroinflammation after direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C

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Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

To assess liver necroinflammation in HCV patients undergone antiviral therapy by Gd-EOB-DTPA-enhanced MRI with histopathologic analyses as reference.

Methods

HCV patients were enrolled in this prospective study before antiviral treatment between 09–2016 and 07–2017. Unenhanced MR, Gd-EOB-DTPA-enhanced MR, and liver biopsy were performed before and 24 weeks after treatment of daclatasvir with asunaprevir (DAA). DWI was obtained using a breath-hold single-shot echo planar spin-echo sequence. Twenty minutes after administration of Gd-EOB-DTPA, the relative enhancement (RE) and the contrast enhancement index (CEI) were recorded. Liver necroinflammatory activity grades (G0–18) were categorized on the Ishak Scoring systems. CEI, RE, and DWI of baseline and 24 weeks after treatment were compared by paired t test. Relationship between MR parameters and histologic scores was evaluated by Pearson’s correlation. Receiver operating characteristic analysis evaluated the measurements’ diagnostic performance. MRI variability between two readers was assessed using the intraclass correlation coefficient.Results

Results

A decrease of liver necroinflammatory activity grade (p < 0.0001) was detected in final cohort (n = 21; mean age 44 years; 23 to 67 years; 11 F, 10 M). Statistical results of 42 person-times in 21 patients at baseline and follow-up showed CEI and ADC were significantly different (p = 0.006 and 0.036) across histologic grades of liver necroinflammation. Significant increase of CEI, RE, and ADC (p = 0.0004, 0.0032, 0.0110) 24 weeks after DAA treatment was seen. Additionally, CEI was correlated to necroinflammatory grade (r =  − 0.596, p = 0.006). AUROC for CEI, ADC, and CEI combined with ADC to differentiate patients with none and mild (G0–6) from patients with moderate and severe necroinflammation (G7–18) was 0.834 (95% CI 0.712–0.956, 0.724(95% CI 0.565–0.884) and 0.837(95% CI 0.717–0.956).

Conclusion

Gd-EOB-DTPA-enhanced MRI by CEI could be used as a noninvasive imaging biomarker to distinguish grades of necroinflammatory activity in patients with HCV after DAAs therapy at early stage and CEI combined with ADC could get a better diagnostic accuracy.

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References

  1. Celli R, Saffo S, Kamili S, Wiese N, Hayden T, Taddei T, Jain D (2021) Liver Pathologic Changes After Direct-Acting Antiviral Agent Therapy and Sustained Virologic Response in the Setting of Chronic Hepatitis C Virus Infection. Arch Pathol Lab Med 145:419-427

    Article  CAS  Google Scholar 

  2. Gurcan NI, Sakci Z, Akhan S, Altunok ES, Aynioglu A, Gurbuz Y, Sarisoy HT, Akansel G (2016) Liver Apparent Diffusion Coefficient Changes during Telaprevir-Based Therapy for Chronic Hepatitis C. Balkan Med J 33:602-606

    Article  Google Scholar 

  3. Wang Y, Rao H, Chi X, Li B, Liu H, Wu L, Zhang H, Liu S, Zhou G, Li N, Niu J, Wei L, Zhao J (2019) Detection of residual HCV-RNA in patients who have achieved sustained virological response is associated with persistent histological abnormality. EBioMedicine 46:227-235

    Article  Google Scholar 

  4. Shimamoto D, Nishie A, Asayama Y, Ushijima Y, Takayama Y, Fujita N, Shirabe K, Hida T, Kubo Y, Honda H (2015) MR Prediction of Liver Function and Pathology Using Gd-EOB-DTPA: Effect of Liver Volume Consideration. Biomed Res Int 2015:141853

  5. Xie S, Sun Y, Wang L, Yang Z, Luo J, Wang W (2015) Assessment of liver function and liver fibrosis with dynamic Gd-EOB-DTPA-enhanced MRI. Acad Radiol 22:460-466

    Article  Google Scholar 

  6. Goshima S, Kanematsu M, Watanabe H, Kondo H, Kawada H, Moriyama N, Bae KT (2012) Gd-EOB-DTPA-enhanced MR imaging: prediction of hepatic fibrosis stages using liver contrast enhancement index and liver-to-spleen volumetric ratio. J Magn Reson Imaging 36:1148-1153

    Article  Google Scholar 

  7. Watanabe H, Kanematsu M, Goshima S, Kondo H, Onozuka M, Moriyama N, Bae KT (2011) Staging hepatic fibrosis: comparison of gadoxetate disodium-enhanced and diffusion-weighted MR imaging--preliminary observations. Radiology 259:142-150

    Article  Google Scholar 

  8. Jang YJ, Cho SH, Bae JH, Kim GC, Ryeom H, Kim HJ, Shin KM, Lee HJ (2013) Noninvasive assessment of hepatic fibrosis using gadoxetate-disodium-enhanced 3T MRI. Ann Hepatol 12:926-934

    Article  CAS  Google Scholar 

  9. Verloh N, Utpatel K, Haimerl M, Zeman F, Fellner C, Fichtner-Feigl S, Teufel A, Stroszczynski C, Evert M, Wiggermann P (2015) Liver fibrosis and Gd-EOB-DTPA-enhanced MRI: A histopathologic correlation. Sci Rep 5:15408

    Article  CAS  Google Scholar 

  10. Wu Z, Matsui O, Kitao A, Kozaka K, Koda W, Kobayashi S, Ryu Y, Minami T, Sanada J, Gabata T (2013) Usefulness of Gd-EOB-DTPA-enhanced MR imaging in the evaluation of simple steatosis and nonalcoholic steatohepatitis. J Magn Reson Imaging 37:1137-1143

    Article  Google Scholar 

  11. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN, et al (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22:696-699

    Article  CAS  Google Scholar 

  12. Lok AS, McMahon BJ (2007) Chronic hepatitis B. Hepatology 45:507-539

    Article  CAS  Google Scholar 

  13. Leonhardt M, Keiser M, Oswald S, Kuhn J, Jia J, Grube M, Kroemer HK, Siegmund W, Weitschies W (2010) Hepatic uptake of the magnetic resonance imaging contrast agent Gd-EOB-DTPA: role of human organic anion transporters. Drug Metab Dispos 38:1024-1028

    Article  Google Scholar 

  14. Nassif A, Jia J, Keiser M, Oswald S, Modess C, Nagel S, Weitschies W, Hosten N, Siegmund W, Kuhn JP (2012) Visualization of hepatic uptake transporter function in healthy subjects by using gadoxetic acid-enhanced MR imaging. Radiology 264:741-750

    Article  Google Scholar 

  15. Fisher CD, Lickteig AJ, Augustine LM, Oude Elferink RP, Besselsen DG, Erickson RP, Cherrington NJ (2009) Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats. Eur J Pharmacol 613:119-127

    Article  CAS  Google Scholar 

  16. Kitao A, Zen Y, Matsui O, Gabata T, Kobayashi S, Koda W, Kozaka K, Yoneda N, Yamashita T, Kaneko S, Nakanuma Y (2010) Hepatocellular carcinoma: signal intensity at gadoxetic acid-enhanced MR Imaging--correlation with molecular transporters and histopathologic features. Radiology 256:817-826

    Article  Google Scholar 

  17. Yamada T, Obata A, Kashiwagi Y, Rokugawa T, Matsushima S, Hamada T, Watabe H, Abe K (2016) Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice. Magn Reson Imaging 34:724-729

    Article  Google Scholar 

  18. Czaja AJ (2014) Hepatic inflammation and progressive liver fibrosis in chronic liver disease. World J Gastroenterol 20:2515-2532

    Article  CAS  Google Scholar 

  19. Verloh N, Probst U, Utpatel K, Zeman F, Brennfleck F, Werner JM, Fellner C, Stroszczynski C, Evert M, Wiggermann P, Haimerl M (2019) Influence of hepatic fibrosis and inflammation: Correlation between histopathological changes and Gd-EOB-DTPA-enhanced MR imaging. PLoS One 14:e0215752

  20. Jang YJ, Cho SH, Bae JH, Kim GC, Ryeom H, Kim HJ, Shin KM, Lee HJ (2013) Noninvasive assessment of hepatic fibrosis using gadoxetate-disodium-enhanced 3T MRI. Ann Hepatol 12:926–934]

  21. Trivedi HD, Lin SC, D TYL (2017) Noninvasive Assessment of Fibrosis Regression in Hepatitis C Virus Sustained Virologic Responders. Gastroenterol Hepatol (N Y) 13:587-595

    Google Scholar 

  22. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, Kuroki T, Nishiguchi S, Sata M, Yamada G, Fujiyama S, Yoshida H, Omata M (2000) Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 132:517-524

    Article  CAS  Google Scholar 

  23. Sporea I, Lupusoru R, Mare R, Popescu A, Gheorghe L, Iacob S, Sirli R (2017) Dynamics of liver stiffness values by means of transient elastography in patients with HCV liver cirrhosis undergoing interferon free treatment. J Gastrointestin Liver Dis 26:145-150

    Article  Google Scholar 

  24. Yamada T, Obata A, Kashiwagi Y, Rokugawa T, Matsushima S, Hamada T, Watabe H, Abe K (2016) Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice. Magnetic Resonance Imaging 34:724-729

    Article  Google Scholar 

  25. Tsuda N, Okada M, Murakami T (2007) Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Invest Radiol 42:242-247

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Peking University People’s Hospital Research and Development Funds (RD-2016-10).

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Authors and Affiliations

  1. Department of Radiology, Peking University People’s Hospital, 11 Xizhimen South St, Beijing, 100044, China

    Anqi Li, Jing Wu, Jin Cheng, Caizhen Feng, Wei Liu, Yi Li, Nan Hong & Yi Wang

  2. Department of Hepatology, Peking University People’s Hospital, 11 Xizhimen South St, Beijing, 100044, China

    Huiying Rao & Rui Huang

  3. Department of Pathology, The Third People’s Hospital of Shenzhen, 29 Bulan Road, Longgang District, Shenzhen, 518100, China

    Guangde Zhou

Authors
  1. Anqi Li
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  2. Jing Wu
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  3. Jin Cheng
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  5. Wei Liu
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  6. Yi Li
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  10. Nan Hong
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  11. Yi Wang
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Contributions

AL participated in the investigation, methodology, and writing and preparation of the original draft; JW participated in the methodology and funding acquisition; JC participated in the writing, reviewing, and editing of the manuscript; CF participated in the investigation; HR and RH performed patient recruitment and liver biopsy operation; GZ performed pathologic analysis; NH participated in the supervision; YW participated in the conceptualization and writing, reviewing, and editing of the manuscript.

Corresponding author

Correspondence to Yi Wang.

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The authors declare no conflict of interest.

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This retrospective study was approved by our local institutional review boards, which waived the requirement for obtaining informed consent.

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Li, A., Wu, J., Cheng, J. et al. Gd-EOB-DTPA-enhanced MRI—a noninvasive and short-term assessment method for liver necroinflammation after direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C. Abdom Radiol 47, 174–183 (2022). https://doi.org/10.1007/s00261-021-03316-0

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  • DOI: https://doi.org/10.1007/s00261-021-03316-0

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