Korean J Transplant.  2023 Mar;37(1):69-75. 10.4285/kjt.22.0054.

Posttransplant sequential adrenal and spine metastasis of hepatocellular carcinoma responsive to combined regorafenib and radiotherapy: a case report

• Kim JY
• Yi NJ
• Kim YJ
• Chie EK
• Kim J
• Choi HH
• Lee J
• Lee S
• Hong SY
• Lee JM
• Hong SK
• Choi Y
• Lee KW
• Suh KS

• KMID: 2541315
• DOI: http://doi.org/10.4285/kjt.22.0054

Abstract

Adrenal and spinal metastases of hepatocellular carcinoma (HCC) are rare entities with significant morbidity and mortality, particularly after liver transplantation (LT). We report a case of a 49-year-old man who underwent LT for hepatitis B-related end-stage liver disease and HCC (single 4.5 cm lesion [T1N0], without vascular invasion) in 2016. Eighteen months later, adrenal metastasis and hepatitis B seropositive conversion were developed with normal serum tumor. Adrenal metastasis was treated with radiation therapy (RT) and hepatitis B showed spontaneous seronegative conversion. However, 35 months later, spinal metastasis occurred with elevation of the protein induced by vitamin K absence or antagonist-II (PIVKA-II) level (197 mAU/mL), along with hepatitis B seropositive conversion. After sorafenib, sequential regorafenib with RT led to partial response of the spinal lesions, along with hepatitis B seronegative conversion and normal PIVKA-II levels. After 9 months of regorafenib combined with RT, two recurrent lesions were found, as well as hepatitis B seropositive conversion and lesions were treated with transarterial chemoembolization. The patient survived for more than 71 months after LT and 53 months after recurrence under various combinations of therapy. Combined systemic and locoregional therapies can be a treatment option for HCC recurrence, even in LT patients.

Keyword

Regorafenib; Radiotherapy; Sorafenib; Mortality; Case reports

Figure

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  Fig. 1 Computed tomography of the abdomen revealing hepatocellular carcinoma (approximately 4.7 cm). (A) Atrial phase (arrow), and (B) subtle washout in the delayed phase (arrow).

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  Fig. 2 Time flow of treatment after liver transplantation and hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) recurrence. DDLT, deceased donor liver transplantation; ES w II/m II, Edmonson-Steiner nuclear grade worst II/major II; PIVKA-II, protein induced by vitamin K absence or antagonist-II; AFP, alpha-fetoprotein; TACE, transarterial chemoembolization; RT, radiotherapy; IS, immunosuppressant; mTORi, mammalian target of rapamycin inhibitor; HBIG, HB immunoglobulin. a)Regorafenib 160 mg/day to 120 mg/day to 80 mg/day; b)Lipiodol 2 mL, adriamycin 10 mg.

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  Fig. 3 Hepatocellular carcinoma (HCC) recurrence in the right adrenal gland 18 months after transplantation. (A) Computed tomography (CT) scan of the abdomen revealing right adrenal metastasis of HCC (arrow). (B) Mild uptake in the right adrenal gland on positron emission tomography CT scans (arrow). CT scans with (C) arterial phase and (D) portal phase revealed recurrence in the right adrenal gland (arrow), 12 months after the first treatment for metastasis and 41 months after transplantation.

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  Fig. 4 Bone metastasis at the fourth lumbar pedicle 17 months later after the second recurrence (A) computed tomography (CT) revealed bone metastasis at the fourth lumbar pedicle (arrow). (B) On magnetic resonance imaging (MRI), bone metastasis at the lumbar pedicle progressed on sorafenib treatment (arrow). (C) On CT, adrenal lesions were stable 14 months after bone recurrence (arrow). (D) On MRI, the lumbar lesion was stable for 14 months after bone recurrence (arrow).

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  Fig. 5 Hepatocellular carcinoma metastasis in the liver 17 months after the third recurrence. Computed tomography revealed hepatic recurrence (A) at S7 (segment 7; arrow) and (B) at S3 (arrow). Magnetic resonance imaging scans revealed hepatic recurrence (C) at S7 (arrow) and (D) at S7 (arrow), (E) two lesions at S4 and S3 (arrows), and (F) one more at S3 (arrow).

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  Fig. 6 Hepatocellular carcinoma (HCC) recurrence and treatment, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels and hepatitis B surface antigen (HBsAg) titers. HCC and hepatitis B recurrences showed similar trends. LT, liver transplantation; DDLT, deceased donor LT; RT, radiotherapy; mTORi, mammalian target of rapamycin inhibitor; HBIG, HB immunoglobulin.

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