J Liver Cancer.  2021 Sep;21(2):169-176. 10.17998/jlc.2021.08.26.

Infiltrative hepatocellular carcinoma with multiple lung metastasis completely cured using nivolumab: a case report

  • 1Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea


The current Food and Drug Administration-approved systemic treatments for advanced hepatocellular carcinoma (HCC) include multikinase inhibitors (tyrosine kinase inhibitor [TKI]) and immune checkpoint inhibitors (ICIs). Among ICIs, nivolumab is used as secondline therapy for advanced HCC after sorafenib failure or patient intolerance. In this case, a patient with infiltrative HCC and portal vein tumor thrombosis was treated with hepatic arterial infusion chemotherapy (HAIC) and radiation therapy. New lung metastasis developed after HAICs; thus, lenvatinib treatment was initiated. However, the disease progressed. Thereafter, sorafenib treatment was initiated but he developed intolerance, with grade 3 sorafenib-related diarrhea. Subsequently, nivolumab was administered as rescue therapy. He demonstrated a partial response to nivolumab after the third treatment and viable HCCs in the lungs and liver completely disappeared after the 24th treatment. These findings suggest that nivolumab could be used as an effective rescue therapy for advanced HCC progression after TKI treatment.


Nivolumab; Immune checkpoint inhibitor; Advanced hepatocellular carcinoma; Case report


  • Figure 1 Hepatocellular carcinoma at initial diagnosis in order of abdomen, chest computed tomography (CT) and liver magnetic resonance imaging (MRI). Abdominal CT showing a single mass (arrows) on segment 6 with enhancement in the arterial phase (A) and wash-out on the delayed phase (B). Chest CT (C) showing no lung metastasis on initial diagnosis. Liver MRI showing a single mass (arrow) with an expansile tumor thrombus partially extending from the right portal vein to the main portal vein in the delayed arterial phase (D) of T1-weighted images. Transitional phase (E). T2-weighted image (F). Hepatobiliary phase (G). Diffusion-weighted image (b=800) (H).

  • Figure 2 A change in the portal vein tumor thrombus, newly developed hepatocellular carcinoma (HCC), and lung metastasis in liver dynamic computed tomography after HAIC with radiation therapy (RT). (A, B) Shrinkage of viable tumor and portal vein tumor thrombus (red arrow) after hepatic artery infusion chemotherapy (HAIC) with RT. (C, D) Multiple lung metastases (yellow arrow) after HAIC with RT. (E) New primary HCC (yellow arrow) in segment 8 after HAIC with RT.

  • Figure 3 Progression of hepatocellular carcinoma (HCC), portal vein tumor thrombus (PVTT), and lung metastases in liver dynamic computed tomography (CT) after lenvatinib therapy. Follow-up liver dynamic CT showing increase in the arterial enhancing portion of the existing primary HCC (red arrow) and PVTT (B) compared to before lenvatinib therapy (A). Additionally, new HCCs (yellow arrows) are visible in several hepatic segments (C–E) and multiple lung metastases show progression (yellow arrows) (F, G).

  • Figure 4 Changes in α-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-II) levels as well as liver function during nivolumab therapy. Serum AFP and PIVKA-II levels decreased continuously from the first administration of nivolumab. (A–D) Preserved liver function during nivolumab therapy.

  • Figure 5 Complete disappearance of multiple lung metastases (arrows) on chest computed tomography after the 18th nivolumab treatment. Multiple pulmonary nodules disappeared after the 18th administration of nivolumab (B, D) compared to before nivolumab therapy (A, C).

  • Figure 6 Liver magnetic resonance imaging after the 24th nivolumab treatment, showing no evidence of viable tumors exhibiting arterial enhancement in the liver and contracted expansile portal vein tumor thrombus. (A) T1-weighted image, hepatic arterial phase. (B) Portal venous phase. (C) Delayed phase. (D) T2-weighted image. (E) Hepatobiliary phase. (F) Diffusion-weighted image (b=800).



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