Hepatocellular Carcinoma Recurrence in HCV Patients Treated with Direct Antiviral Agents

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2019 May 5

PMID 31052463

Citations 5

Authors

Marco Sanduzzi-Zamparelli

Loreto Boix

Cassia Leal

Maria Reig

Affiliations

Soon will be listed here.

Abstract

The risk of hepatocellular carcinoma recurrence is universal regardless of the treatment modality applied, and secondary prevention is still an unmet issue even though the elimination of hepatitis C (HCV) with direct antiviral agents (DAAs) was expected to be one of the new options. Unfortunately, the impact of DAAs on hepatocellular carcinoma (HCC) development (de novo and recurrence) is still controversial. Since the first publication on the subject in 2016, almost all groups worldwide have carried out research in this field with hundreds of publications now available. This revision is focused on the impact of DAAs on HCC recurrence and aims to discuss the potential underlying mechanisms and host factors pointing out the time association phenomenon between DAA treatment and HCC recurrence. Moreover, we comment on the methodological issues that could affect the different interpretations of the published results. In conclusion, this is an area of research with potential in the understanding of the impact of factors not previously considered, and may also help change hepatocarcinogenesis tenets, such as the belief that the elimination of HCV should be used as a second prevention treatment.

Citing Articles

Incidence and Risk Factors of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Treated with Direct-Acting Antivirals.

Leal C, Strogoff-de-Matos J, Theodoro C, Teixeira R, Perez R, Guarana T Viruses. 2023; 15(1).

PMID: 36680260 PMC: 9863874. DOI: 10.3390/v15010221.

Liver Disease Outcomes after Sustained Virological Response in Patients with Chronic Hepatitis C Infection Treated with Generic Direct-Acting Antivirals.

Abd El-Wahab E, Elgawad W, Abdelaziz M, Mikheal A, Shatat H Am J Trop Med Hyg. 2022; .

PMID: 35226870 PMC: 9128674. DOI: 10.4269/ajtmh.21-0918.

Genetic Determinants in a Critical Domain of NS5A Correlate with Hepatocellular Carcinoma in Cirrhotic Patients Infected with HCV Genotype 1b.

Alkhatib M, Di Maio V, De Murtas V, Polilli E, Milana M, Teti E Viruses. 2021; 13(5).

PMID: 33922732 PMC: 8146897. DOI: 10.3390/v13050743.

HCV Glycoprotein Structure and Implications for B-Cell Vaccine Development.

Stroh L, Krey T Int J Mol Sci. 2020; 21(18).

PMID: 32947858 PMC: 7555785. DOI: 10.3390/ijms21186781.

Addressing the Challenges of Hepatitis C Cure and Persistent Risk of Hepatocellular Carcinoma.

Baumert T, Hoshida Y Viruses. 2019; 11(5).

PMID: 31096600 PMC: 6563310. DOI: 10.3390/v11050441.

References

Allaire M, Rekik S, Layese R, Mumana A, Guyot E, Nkontchou G . Virologic control and severity of liver disease determine survival after radiofrequency ablation of hepatocellular carcinoma on cirrhosis. Dig Liver Dis. 2018; 51(1):86-94. DOI: 10.1016/j.dld.2018.07.014. View

Gitto S, Cicero A, Loggi E, Giovannini M, Conti F, Grandini E . Worsening of Serum Lipid Profile after Direct Acting Antiviral Treatment. Ann Hepatol. 2018; 17(1):64-75. DOI: 10.5604/01.3001.0010.7536. View

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

Rehermann B . Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med. 2013; 19(7):859-68. PMC: 4482132. DOI: 10.1038/nm.3251. View

Baumert T, Juhling F, Ono A, Hoshida Y . Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals. BMC Med. 2017; 15(1):52. PMC: 5348895. DOI: 10.1186/s12916-017-0815-7. View

El Kassas M, Funk A, Salaheldin M, Shimakawa Y, Eltabbakh M, Jean K . Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: A comparative analysis. J Viral Hepat. 2017; 25(6):623-630. DOI: 10.1111/jvh.12854. View

Sugiura A, Joshita S, Umemura T, Yamazaki T, Fujimori N, Kimura T . Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct-acting antivirals. J Viral Hepat. 2018; 25(12):1462-1471. DOI: 10.1111/jvh.12973. View

Teng M, Swann J, Koebel C, Schreiber R, Smyth M . Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol. 2008; 84(4):988-93. DOI: 10.1189/jlb.1107774. View

Saraiya N, Yopp A, Rich N, Odewole M, Parikh N, Singal A . Systematic review with meta-analysis: recurrence of hepatocellular carcinoma following direct-acting antiviral therapy. Aliment Pharmacol Ther. 2018; 48(2):127-137. PMC: 6019180. DOI: 10.1111/apt.14823. View

10.

Ono A, Goossens N, Finn R, Schmidt W, Thung S, Im G . Persisting risk of hepatocellular carcinoma after hepatitis C virus cure monitored by a liver transcriptome signature. Hepatology. 2017; 66(4):1344-1346. PMC: 5605396. DOI: 10.1002/hep.29203. View

11.

Tripodi A, DAmbrosio R, Padovan L, Tosetti G, Aghemo A, Primignani M . Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis. Liver Int. 2017; 37(9):1295-1303. DOI: 10.1111/liv.13374. View

12.

Beste L, Green P, Berry K, Kogut M, Allison S, Ioannou G . Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J Hepatol. 2017; 67(1):32-39. PMC: 6590903. DOI: 10.1016/j.jhep.2017.02.027. View

13.

Saberi B, Dadabhai A, Durand C, Philosophe B, Cameron A, Sulkowski M . Challenges in treatment of hepatitis C among patients with hepatocellular carcinoma. Hepatology. 2017; 66(2):661-663. DOI: 10.1002/hep.29126. View

14.

. 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. DOI: 10.1016/j.jhep.2016.05.045. View

15.

Cabibbo G, Petta S, Barbara M, Missale G, Virdone R, Caturelli E . A meta-analysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma. Liver Int. 2017; 37(8):1157-1166. DOI: 10.1111/liv.13357. View

16.

. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol. 2017; 2(3):161-176. DOI: 10.1016/S2468-1253(16)30181-9. View

17.

Weckermann D, Polzer B, Ragg T, Blana A, Schlimok G, Arnholdt H . Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer. J Clin Oncol. 2009; 27(10):1549-56. DOI: 10.1200/JCO.2008.17.0563. View

18.

Burchill M, Golden-Mason L, Wind-Rotolo M, Rosen H . Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals. J Viral Hepat. 2015; 22(12):983-91. DOI: 10.1111/jvh.12465. View

19.

Guarino M, Vigano L, Ponziani F, Giannini E, Lai Q, Morisco F . Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis. Dig Liver Dis. 2018; 50(11):1105-1114. DOI: 10.1016/j.dld.2018.08.001. View

20.

Halley-Stott R, Gurdon J . Epigenetic memory in the context of nuclear reprogramming and cancer. Brief Funct Genomics. 2013; 12(3):164-73. PMC: 3662891. DOI: 10.1093/bfgp/elt011. View