Comparison of guidelines for diagnosis of hepatocellular carcinoma using gadoxetic acid–enhanced MRI in transplantation candidates
Authors: Sun Kyung Jeon, Jeong Min Lee, Ijin Joo, Jeongin Yoo & Jin-young Park.
Journal: European Radiology. 2020 Apr 25. doi:
https://doi.org/10.1007/s00330-020-06881-y.
Domenico Salvatore Gagliano (radiology resident, University of Palermo, Palermo/IT) and Roberto Cannella (radiologist and PhD student, University of Palermo, Palermo/IT).
Liver cancers occupy the fourth place in the world as cancer-related mortality and the seventh place in terms of incidence according to WHO data [1]. Hepatocellular carcinoma (HCC) represents one of the few cancers that can be diagnosed by imaging without histopathological examination. Currently, four different guidelines – American Association for the Study of Liver Disease (AASLD), which integrated the Liver Imaging Reporting and Data System (LI-RADS) [2]; European Association for the Study of the Liver (EASL) [3]; Asian Pacific Association for the Study of the Liver (APASL) [4]; and Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) [5] – are used worldwide for the diagnosis of HCC. These guidelines have been updated between the years 2017 and 2018. Furthermore, through the Milan criteria, imaging is fundamental in the assessment of patients who can take advantage of the liver transplant, which in practice represents the only definitive therapy (removes HCC and liver disease).
Recently, Jeon et al. [6] retrospectively compared the diagnostic performances of these four guidelines in patients undergoing gadoxetic acid-enhanced MR imaging within three months of liver transplantation, in the absence of previous treatments for HCC. The reference standard was based on histopathological examination of explanted livers. The pre-transplant MR images of 81 patients were independently examined by three board-certified abdominal radiologists. A total of 154 nodules were assesses, including 116 HCCs, 24 dysplastic nodules, 6 FNH-like nodules, 5 combined hepatocellular-cholangiocarcinomas, and 3 hemangiomas.
The study results revealed that the per-lesion specificity for the diagnosis of HCC of AASLD/LI-RADS (97.4%) was the highest compared to EASL (92.1%), KLCA-NCC (92.1%) and APASL (78.9%). Particularly, APASL demonstrated significantly lower specificity compared to AASLD/LI-RADS. However, the sensitivity of APASL (75.9%) and KLCA-NCC (65.6%) was significantly higher than EASL (38.8%) and AASLD/LI-RADS (34.5%). KLCA-NCC resulted in significantly greater accuracy than EASL in classifying patients unsuitable for transplantation (68.4% vs. 31.8% respectively). Based on the Milan criteria for patients’ allocation, APASL (80.2%) and KLCA-NCC (75.3%) provided better accuracy than AASLD/LI-RADS (64.2%) and EASL (64.2%);
These data suggest that KLCA-NCC an APASL guidelines focus more on sensitivity and therefore on early diagnosis of HCC since the most common approach is to treat the tumor with locoregional therapies, while the AASLD/LI-RADS and EASL guidelines prioritize high specificity in order to reduce false positives as much as possible. The difference between these two different approaches is mainly reflected in the washout appearance definition, which in the AASLD/LI-RADS is limited to portal venous phase only when using gadoxetic acid, while KLCA-NCC guidelines also includes the transitional and hepatobiliary phases, thus achieving greater sensitivity. However, the diagnosis of HCC is excluded if there is hyperintensity on T2-weighted imaging, which may suggest cavernous hemangioma.
The difference in terms of specificity between APASL and KLCA-NCC, on the other hand, is likely due to excluded diagnosis of HCC not only after exclusion of hemangioma, but also in presence of targetoid appearance on diffusion-weighted images or contrast-enhanced sequences, which is an imaging feature of intrahepatic cholangiocarcinoma and other non-HCC hepatic malignancies [5]. The definition of targetoid appearance in KLCA-NCC, shared with the AASLD/LI-RADS, allows to increase the accuracy in the diagnosis of non-HCC malignancies.
Moreover, it is important to note that APASL is the only guideline that allows the definitive diagnosis of HCC, regardless for nodule size, while other guidelines can diagnose HCC only for nodules greater than 10 mm in diameter [7].
The combination of high sensitivity and specificity of the KLCA-NCC guideline allows better accuracy in patient allocation for liver transplant and in particular in classifying unsuitable for transplantation (with non-HCC malignancies or HCCs beyond the Milan criteria) compared to European guidelines.
In conclusion, when using gadoxetic acid-enhanced MR imaging in transplant candidates, the specificity of the AASLD/LI-RADS (97.4%), EASL (92.1%), and KLCA-NCC (92.1%) guidelines was higher than that of APASL (78.9%) and the KLCA-NCC guideline is more accurate in the selection of unsuitable liver transplant candidates.
REFERENCES
- International Agency for Research on Cancer, World Health Organization. Cancer today (https://gco.iarc.fr/today/home).
- 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;68:723-750. doi:10.1002/hep.29913.
- EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182-236. doi:10.1016/j.jhep.2018.03.019.
- Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-370. doi:10.1007/s12072-017-9799-9.
- Korean Liver Cancer Association (KLCA), National Cancer Center (NCC), Goyang, Korea. 2018 Korean Liver Cancer Association–National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol. 2019;20:1042-1113. doi.org/10.3348/kjr.2019.0140.
- Jeon, S.K., Lee, J.M., Joo, I. et al. Comparison of guidelines for diagnosis of hepatocellular carcinoma using gadoxetic acid–enhanced MRI in transplantation candidates. Eur Radiol. 2020. doi.org/10.1007/s00330-020-06881-y.
- Kim TH, Kim SY, Tang A, Lee JM. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update. Clin Mol Hepatol. 2019;25:245-263. doi:10.3350/cmh.2018.0090.
Dr. Domenico Salvatore Gagliano is a second-year young radiology resident at the University of Palermo (Italy) and an ESGAR member. Dr. Gagliano graduated at the University of Palermo in July 2017 with a thesis on MR imaging with gadoxetic acid. He recently won the Invest in the Youth application with the EPOS titled “Hyperintense liver lesions on hepatobiliary phase MR imaging in different clinical settings” presented during the 2020 European Congress of Radiology online. He is also involved in scientific researches regarding MR imaging of focal liver lesions.
Comments may be sent to domenicosalvatore.gagliano@gmail.com