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Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With Direct-acting Antiviral Therapy

  • Liver (J Bajaj, Section Editor)
  • Published:
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Abstract

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.

Recent findings

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.

Summary

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.

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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.

  3. Kanwal F, Hoang T, Kramer JR, Asch SM, Goetz MB, Zeringue A, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011;140(4):1182–1188.e1.

    Article  PubMed  Google Scholar 

  4. Sangiovanni A, Del Ninno E, Fasani P, et al. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology. 2004;126:1005–14.

    Article  PubMed  Google Scholar 

  5. Bruix J, Sherman M, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Feld JJ, Jacobson IM, Hezode C, Asselah T, Ruane PJ, Gruener N, et al. Sofosbuvir and Velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infections. N Engl J Med. 2015;373:2599–607.

    Article  CAS  PubMed  Google Scholar 

  7. Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370:1879–88.

    Article  PubMed  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.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  11. Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727–33.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  CAS  PubMed  Google Scholar 

  15. Kozbial K, Moser S, Schwarzer R, Laferl H, Al-Zoairy R, Stauber R, et al. Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon free direct-acting antiviral treatment. J Hepatol. 2016;65:856–8.

    Article  PubMed  Google 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.

    Article  CAS  PubMed  Google Scholar 

  17. Cheung MC, Walker AJ, Hudson BE, Verma S, McLauchlan J, Mutimer DJ, et al. Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis. J Hepatol. 2016;65(4):741–7.

    Article  CAS  PubMed  Google Scholar 

  18. Ioannou GN, Green PK, BerryK. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2017.

  19. Roccaro GA, Goldberg DS. Early detection of hepatocellular carcinoma after treatment with direct-acting antivirals: selection bias or biologically plausible? Gastroenterology. 2017;152(8):2072–5. https://doi.org/10.1053/j.gastro.2017.04.041.

    Article  PubMed  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.

    Article  PubMed  Google 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.

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Authors and Affiliations

  1. Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA

    Venkata Rajesh Konjeti MD

  2. Department of Gastroenterology, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Blvd, Richmond, VA, 23249, USA

    Binu V. John MD, MPH

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  1. Venkata Rajesh Konjeti MD
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  2. Binu V. John MD, MPH
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Correspondence to Binu V. John MD, MPH.

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Venkata Rajesh Konjeti declares that he has no conflict of interest.

Binu John declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Liver

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Konjeti, V.R., John, B.V. Interaction Between Hepatocellular Carcinoma and Hepatitis C Eradication With Direct-acting Antiviral Therapy. Curr Treat Options Gastro 16, 203–214 (2018). https://doi.org/10.1007/s11938-018-0178-y

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  • DOI: https://doi.org/10.1007/s11938-018-0178-y

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