A clinical case of prolonged response to therapy for advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer mortality in the world, especially in regions with a high prevalence of viral hepatitis and cirrhosis of the liver. Systemic treatments remain the standard of treatment for common HCC. The most significant breakthrough was the appearance of a combination of the PD-L1 inhibitor Atezolizumab and the antiangiogenic drug Bevacizumab, which showed superiority over the tyrosine kinase inhibitor Sorafenib in key studies. A clinical case of treatment of a 61-year-old patient with advanced HCC on the background of cirrhosis of the liver of viral etiology, thrombosis of the portal vein and inferior vena cava with extrahepatic foci is presented. At the first stage, Atezolizumab and Bevacizumab were treated according to the first-line treatment protocol. Despite the development of immune-mediated toxic hepatitis and clinically significant bleeding, which required temporary discontinuation of treatment, repeated administration of the drugs led to a long-term stabilization of the process, confirmed by data from subsequent X-ray control studies. The case illustrates the effectiveness of a combination of immunotargeting therapy, including in patients with severe concomitant pathology, as well as the importance of a multidisciplinary approach and flexibility in correcting emerging complications.

1. Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019;380(15): 1450–1462. https://doi.org/10.1056/NEJMra1713263.

2. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127): 1301–1314. https://doi.org/10.1016/S0140-6736(18)30010-2.

3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82(2):315–374. https://doi.org/10.1016/j.jhep.2024.08.028.

4. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–390. https://doi.org/10.1056/NEJMoa0708857.

5. Petitprez F, Meylan M, De Reyniès A, Sautès-Fridman C, Fridman WH. The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies. Front Immunol. 2020;11:784. https://doi.org/10.3389/fimmu.2020.00784.

6. Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018;15(5):325–340. https://doi.org/10.1038/nrclinonc.2018.29.

7. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894–1905. https://doi.org/10.1056/NEJMoa1915745.

8. Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862–873. https://doi.org/10.1016/j.jhep.2021.11.030.

9. Chen CT, Feng YH, Yen CJ, Chen SC, Hsu CH, Shao YY. Long-term survival outcomes of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2025;43(4 Suppl):600. https://doi.org/10.1200/JCO.2025.43.4_suppl.600

10. Dzhanyan IA, Khagazheeva MN, Breder VV, Yudin DI, Pogrebnyakov IV, Kuzminov AE et al. Atezolizumab and bevacizumab in the treatment of advanced hepatocellular cancer with adverse factors and tumor thrombosis. Meditsinskiy Sovet. 2023;17(11):10–16. (In Russ.) https://doi.org/10.5009/gnl240085.

11. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, Garcia-Criado Á et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022;76(3):681–693. https://doi.org/10.1016/j.jhep.2021.11.018.

12. Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(7):991–1001. https://doi.org/10.1016/S1470-2045(21)00151-0.

13. Celsa C, Cabibbo G, Fulgenzi CAM, Scheiner B, D’Alessio A, Manfredi GF et al. Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours. J Hepatol. 2024;80(3):431–442. https://doi.org/10.1016/j.jhep.2023.10.040.

14. Balogh J, Victor D, Asham EH, Burroughs G, Boktour M, Saharia A et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2016;3:41–53. https://doi.org/10.2147/JHC.S61146.

15. Tümen D, Heumann P, Gülow K, Demirci CN, Cosma LS, Müller M, Kandulski A. Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma. Biomedicines. 2022;10(12):3202. https://doi.org/10.3390/ biomedicines10123202.

16. Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–1362. https://doi.org/10.1016/ S0140-6736(22)01200-4.