The dramatic improvement in disease burden described in these two cases raises the possibility that DAA treatment activating CD8+ T cells to respond to the HCV also induces a T-cell mediated response and increased immunosurveillance to the virus-induced aggressive HCC tumor. Ongoing large prospective cohorts of HCV patients treated with DAA are collecting longitudinal data that will ideally provide more clarity on how the interplay between viral elimination and immune surveillance effect HCC growth and identify cases similar to the two reported here.22 As per our institutional standard, the University of North Carolina Institutional Review Board and Office of Human Research Ethics has reviewed this project. This case series does not constitute human subjects’ research as defined under federal regulations; therefore, written consent from subjects is not required and IRB approval is not deemed necessary.


Continue Reading

The authors report no conflicts of interest in this work.

Anna S. Griffith,1 Paul H. Hayashi,1 Lauren M. B. Burke,2Autumn J. McRee1
1Department of Medicine, 2Department of Radiology, University of North Carolina at Chapel Hill Hospital, Chapel Hill, NC, USA 


1. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology. 2004;127(5):1372–1380.

2. Bandiera S, Billie Bian C, Hoshida Y, Baumert TF, Zeisel MB. Chronic hepatitis C virus infection and pathogenesis of hepatocellular carcinoma. Curr Opin Virol. 2016;20:99–105.

3. Li DK, Ren Y, Fierer DS, et al. The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: an ERCHIVES study. Hepatology. Epub 2017 Dec 2.

4. Ozturk M. Genetic aspects of hepatocellular carcinogensis. Semin Liver Dis. 1999;19(3):325–342.

5. Moradpour D, Blum HE. Pathogenesis of hepatocellular carcinoma. Eur J Gastroenterol Hepatol. 2005;17(5):477–483.

6. Yamaguchi R, Yano H, Iemura A, Ogasawara S, Haramaki M, Kojiro M. Expression of vascular endothelial growth factor in human hepatocellular carcinoma. Hepatology. 1998;28(1):68–77.

7. Moriya K, Fujie H, Shintani Y, et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med. 1998;4(9):1065–1067.

8. Sakamuro D, Furukawa T, Takegami T. Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. J Virol. 1995;69(6):3893–3896.

9. Gale M Jr, Kwieciszewski B, Dossett M, Nakao H, Katze MG. Antiapoptotic and oncogenic potentials of hepatitis C virus are linked to interferon resistance by viral repression of the PKR protein kinase. J Virol. 1999;73(8):6506–6516.

10. Nault JC, Colombo M. Hepatocellular carcinoma and direct-acting antiviral treatments: controversy after the revolution. J Hepatol. 2016;65(4):663–665.

11. ANRS Collaborative Study Group on Hepatocellular Carcinoma (ANRS CO22 HEPATHER, CO12 CirVir and CO23 CUPILT Cohorts). Lack of evidence of an effect of direct-acting antivirals on the recurrence of hepatocellular carcinoma: data from three ANRS cohorts. J Hepatol. 2016;65(4):734–740.

12. Conti F, Buonfiglioli F, Scuteri A, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related Cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727–733.

13. Reig M, Marino Z, Perelló C, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65(4):719–726.

14. Alberi A, Piovesan S. Increased incidence of liver cancer after successful DAA treatment of chronic hepatitis C: fact or fiction? Liver Int. 2017;37(6):802–808.

15. Cammà C, Cabibbo G, Craxì A. Direct antiviral agents and risk for HCC early recurrence: much ado about nothing. J Hepatol. 2016;65(4):861–862.

16. Romano A, Capra F, Piovesan S, et al. Incidence and pattern of “de novo” hepatocellular carcinoma in HCV patients treated with oral DAAs. Hepatology. 2016;64(S1):10A.

17. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–148.

18. Knolle PA, Thimme R. Hepatic immune regulation and its involvement in viral hepatitis infection. Gastroenterology. 2014;146(5):1193–1207.

19. Serti E, Chepa-Lotrea X, Kim YJ, et al. Successful Interferon-free therapy of chronic hepatitis C virus infection normalizes natural killer cell function. Gastroenterology. 2015;149(1):190–200.

20. Martin B, Hennecke N, Lohmann V, et al. Restoration of HCV-specific CD8+ T cell function by interferon-free therapy. J Hepatol. 2014;61(3):538–543.

21. Gabrielson A, Wu Y, Wang H, et al. Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC. Cancer Immunol Res. 2016;4(5):41930.

22. Terrault NA, Zeuzem S, DiBisceglie AM, et al; HCV-TARGET Study Group. Effectiveness of ledipasvir-sofosbuvir combination in patients with hepatitis C virus infection and factors associated with sustained virologic response. Gastroenterology. 2016;151(6):1131–1140.

Source: Journal of Hepatocellualr Carcinoma
Originally published May 31, 2018