Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With Direct-acting Antiviral Therapy
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Purpose of review
The approval of direct-acting antiviral (DAA) therapy has revolutionized hepatitis C virus (HCV) treatment. However, the publication of a study from Barcelona in 2016 raised concern for an increased risk of recurrence of hepatocellular carcinoma (HCC) after potentially curative therapy in patients receiving DAAs. This article reviews the current literature on the interaction between HCC and hepatitis C eradication with DAAs.
Following publication of the initial observation in 2016, a number of studies have looked at the impact of active HCC on the success of antiviral therapy, as well as that of treatment with DAAs on both the occurrence and recurrence of HCC. The presence of active HCC decreases sustained virologic response (SVR) rates with DAAs. However, SVR rates improve in patients who have achieved complete radiological response or are treated post transplantation. With respect to occurrence of HCC after DAAs, many small single-center studies without a control group have documented high incidence. The rates are also higher when compared to those of historical controls treated with interferon, but these patients are not comparable because DAA-treated population is more likely to have advanced fibrosis or decompensation. In large studies that have included a control group (patients treated concurrently who did not achieve SVR), a decrease in the occurrence of HCC has been demonstrated. With regard to recurrence of HCC, while smaller single-center studies have shown an increase, larger studies with control group have not replicated those findings. However, methodological limitations in the published studies limit our ability to make a firm conclusion on both the occurrence and recurrence of HCC after DAA therapy.
The presence of active HCC decreases treatment success rates with DAAs. Therefore, it is recommended that treatment of HCV in patients with HCC be deferred till there is complete radiological response. Though there are major limitations with the currently published studies, the data does not support an increase in the occurrence or recurrence of HCC after DAA therapy.
KeywordsHepatocellular carcinoma Direct-acting antiviral Hepatitis C virus Liver cancer HCV treatment
Compliance with Ethical Standards
Conflict of Interest
Venkata Rajesh Konjeti declares that he has no conflict of interest.
Binu John declares that he has no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, version 1.0. International Agency for Research on Cancer Base no. 5. Lyon: IARC Press; 2001.Google Scholar
- 2.Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat database: incidence—SEER 9 Regs research data, Nov 2009 Sub (1973-2007). Bethesda, MD: National Cancer Institute, April 2010.Google Scholar
- 8.• Reig M, Mariño 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):719–26. This is the first study that raised concern about a potential increase in recurrence of HCC after potentially curative treatment after exposure to DAAs.PubMedCrossRefGoogle Scholar
- 9.• Prenner SB, VanWagner LB, Flamm SL, Salem R, Lewandowski RJ, Kulik L. Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals. J Hepatol. 2017;66(6):1173–81. https://doi.org/10.1016/j.jhep.2017.01.020. This is the first paper that described decreased SVR rates in patients with HCV and HCC. However, many patients were treated with an inadequate regimen, so it was unclear if the low SVR was secondary to the regimen used or due to HCC itself.PubMedCrossRefGoogle Scholar
- 10.• Beste LA, Green PK, Berry K, Kogut MJ, Allison SK, Ioannou GN. Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma. J Hepatol. 2017;67(1):32–9. https://doi.org/10.1016/j.jhep.2017.02.027. This is a large VA database study that looked at SVR rates with DAAs in veterans with HCC and documented decreased SVR in patients with HCC compared to HCV patients without HCC.PubMedCrossRefGoogle Scholar
- 12.Ravi S, Axley P, Jones D, Kodali S, Simpson H, McGuire BM. Singal AK unusually high rates of hepatocellular carcinoma after treatment with direct-acting antiviral therapy for hepatitis C related cirrhosis. Gastroenterology. 2017;152(4):911–2. https://doi.org/10.1053/j.gastro.2016.12.021.PubMedCrossRefGoogle Scholar
- 13.Cardoso H, Vale AM, Rodrigues S, Gonçalves R, Albuquerque A, Pereira P, et al. High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol. 2016;65(5):1070–1. https://doi.org/10.1016/j.jhep.2016.07.027.PubMedCrossRefGoogle Scholar
- 14.• Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, El-Serag HB. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology. 2017;153(4):996–1005.e1. https://doi.org/10.1053/j.gastro.2017.06.012. First large study based on VA database looking at the incidence of HCC in patients treated with DAAs. The study showed that patients who achieved SVR had a lower incidence of HCC compared to non-SVR controls.PubMedCrossRefGoogle Scholar
- 16.Ogata F, Kobayashi M, Akuta N, Osawa M, Fujiyama S, Kawamura Y, et al. Outcome of all-oral direct-acting antiviral regimens on the rate of development of hepatocellular carcinoma in patients with hepatitis C virus genotype 1-related chronic liver disease. Oncology. 2017;93:92–8.PubMedCrossRefGoogle Scholar
- 18.Ioannou GN, Green PK, BerryK. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2017.Google Scholar
- 20.El Kassas M, Funk AL, Salaheldin M, Shimakawa Y, Eltabbakh M, Jean K, et al. Increased recurrence rates of hepatocellular carcinoma after DAA therapy in a hepatitis C-infected Egyptian cohort: a comparative analysis. J Viral Hepat. 2017; https://doi.org/10.1111/jvh.12854.
- 21.Zavaglia C, Okolicsanyi S, Cesarini L, Mazzarelli C, Pontecorvi V, Ciaccio A, et al. Is the risk of neoplastic recurrence increased after prescribing direct-acting antivirals for HCV patients whose HCC was previously cured? J Hepatol. 2017;66(1):236–7. https://doi.org/10.1016/j.jhep.2016.08.016.PubMedCrossRefGoogle Scholar
- 22.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. https://doi.org/10.1016/j.jhep.2016.05.045
- 23.• Singal AG, Hoteit M, John BV, et al. Direct acting antiviral therapy is associated with shorter time to HCC recurrence but not increased risk of recurrence. In: Proceedings from the 2017 International Liver Cancer Association Annual Conference; September 15–17, 2017; Seoul, South Korea. Abstract 0–021. This is preliminary results from a multicenter US consortium that looked at patients with HCC who underwent complete radiological response and recurrence rates in SVR and non-SVR patients. The study showed no difference in incidence of recurrent HCC but a shorter time to recurrence in patients who received DAAs.Google Scholar