Active hepatocellular carcinoma is an independent risk factor of direct-acting antiviral treatment failure: A retrospective study with prospectively collected data

Autoři: Yi-Hao Yen aff001;  Chien-Hung Chen aff001;  Chao-Hung Hung aff001;  Jing-Houng Wang aff001;  Sheng-Nan Lu aff001;  Kwong-Ming Kee aff001;  Tsung-Hui Hu aff001
Působiště autorů: Department of Internal Medicine, Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article


Background & aims

Previous studies from western countries have reported that active hepatocellular carcinoma (HCC) was associated with direct-acting antiviral (DAA) treatment failure. We sought to examine this issue in an Asian cohort.


A retrospective cohort study was conducted on hepatitis C virus (HCV)-infected patients with advanced fibrosis who were treated with DAAs at our hospital between January 2017 and June 2018.


We treated 1021 HCV-infected patients during this period. A total of 976 of those patients were enrolled in a per-protocol analysis, including 556 (57.2%) who had genotype 1b infections, and 314 (32.3%) who had genotype 2 infections. The mean age of all 976 patients was 65.5 years, and 44.5% were male. 781 of the patients had no HCC, 172 had inactive HCC, and 23 had active HCC. Non-sustained virologic response (SVR) was noted in 10 (1.3%) patients without HCC, 5 (2.9%) patients with inactive HCC, and 4 (13.0%) patients with active HCC. After adjustment for confounders, active HCC (versus inactive HCC and non-HCC) was associated with non-SVR (adjusted odds ratio [AOR] = 24.5 (95% confidence interval [CI] = 4.4–136.9), P<0.001). Next, we excluded the 23 patients with active HCC from the multivariate analysis. After adjustment for confounders, inactive HCC (versus non-HCC) was not associated with non-SVR (AOR = 3.1 (95% CI = 0.94–9.95), P = 0.06).


Active HCC was associated with non-SVR, while inactive HCC was not. We thus suggest the deferral of DAA treatment until after the complete radiological response of HCCs to treatment.

Klíčová slova:

Cancer treatment – Cirrhosis – Fibrosis – Hepatitis C virus – Hepatocellular carcinoma – Liver transplantation – Variant genotypes – Nausea


1. Ji F, Yeo YH, Wei MT, Ogawa E, Enomoto M, Lee DH, et al. Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis. J Hepatol. 2019

2. Cabibbo G, Celsa C, Cammà C, Craxì A. Should we cure hepatitis C virus in patients with hepatocellular carcinoma while treating cancer? Liver Int. 2018;38:2108–2116. doi: 10.1111/liv.13918 29935096

3. Wang JH, Changchien CS, Hung CH, Eng HL, Tung WC, Kee KM,et al. FibroScan and ultrasonography in the prediction of hepatic fibrosis in patients with chronic viral hepatitis. J Gastroenterol. 2009;44:439–46. doi: 10.1007/s00535-009-0017-y 19308312

4. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, et. al. Development of a simple noninvasive index to predict significant fibrosis patients with HIV/HCV co-infection. Hepatology 2006;43:1317–1325. doi: 10.1002/hep.21178 16729309

5. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996; 24: 289–293. doi: 10.1002/hep.510240201 8690394

6. Karino Y, Toyota J, Ikeda K, Suzuki F, Chayama K, Kawakami Y, et al. Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir. J Hepatol. 2013;58:646–654. doi: 10.1016/j.jhep.2012.11.012 23178977

7. EASL recommendations on treatment of chronic hepatitis C 2016. J Hepatol 2017;66:153e94.

8. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67: 358–80. doi: 10.1002/hep.29086 28130846

9. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 2017;11:317–70. doi: 10.1007/s12072-017-9799-9 28620797

10. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236. doi: 10.1016/j.jhep.2018.03.019 29628281

11. Kudo M, Matsui O, Izumi N, Iijima H, Kadoya M, Imai Y; Liver Cancer Study Group of Japan. Surveillance and diagnostic algorithm for hepatocellular carcinoma proposed by the Liver Cancer Study Group of Japan: 2014 update. Oncology. 2014;87 Suppl 1:7–21.

12. European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018;69:461–511 doi: 10.1016/j.jhep.2018.03.026 29650333

13. Afdhal NH, Bacon BR, Patel K, Lawitz EJ, Gordon SC, Nelson DR, et al. Accuracy of fibroscan, compared with histology, in analysis of liver fibrosis in patients with hepatitis B or C: a United States multicenter study. Clin Gastroenterol Hepatol 2015;13:772–779, e771–e773. doi: 10.1016/j.cgh.2014.12.014 25528010

14. Degos F, Perez P, Roche B, Mahmoudi A, Asselineau J, Voitot H, et al. Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (the FIBROSTIC study). J Hepatol 2010;53:1013–1021. doi: 10.1016/j.jhep.2010.05.035 20850886

15. Zarski JP, Sturm N, Desmorat H, Melin P, Raabe JJ, Bonny C, et al. Noninvasive assessment of liver fibrosis progression in hepatitis C patients retreated for 96 weeks with antiviral therapy: a randomized study. Liver Int 2010;30:1049–1058. doi: 10.1111/j.1478-3231.2010.02265.x 20492512

16. Majumdar A, Kitson MT, Roberts SK. Systematic review: current concepts and challenges for the direct-acting antiviral era in hepatitis C cirrhosis. Aliment Pharmacol Ther. 2016;43:1276–1292 doi: 10.1111/apt.13633 27087015

17. Karino Y, Toyota J, Ikeda K, Suzuki F, Chayama K, Kawakami Y, et al. Characterization of virologic escape in hepatitis C virus genotype 1b patients treated with the direct-acting antivirals daclatasvir and asunaprevir. J Hepatol. 2013;58:646–654. doi: 10.1016/j.jhep.2012.11.012 23178977

18. Schneider MD, Sarrazin C. Antiviral therapy of hepatitis C in 2014: do we need resistance testing? Antiviral Res. 2014;105:64–71. doi: 10.1016/j.antiviral.2014.02.011 24583028

19. Pawlotsky JM. Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology. 2011;53:1742–1751. doi: 10.1002/hep.24262 21374691

20. Perez AB, Chueca N, Garcia F. Resistance testing for the treatment of chronic hepatitis C with direct acting antivirals: when and for how long? Germs. 2017;7:40. doi: 10.18683/germs.2017.1107 28331841

21. Pawlotsky JM. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology. 2016;151:70–86. doi: 10.1053/j.gastro.2016.04.003 27080301

22. 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;66:1173–1181. doi: 10.1016/j.jhep.2017.01.020 28161470

23. Bruix J, ShermanM. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53:1020–1022 doi: 10.1002/hep.24199 21374666

24. Kushner T, Dieterich D, Saberi B. Direct-acting antiviral treatment for patients with hepatocellular carcinoma. Curr Opin Gastroenterol 2018;34:132–139. doi: 10.1097/MOG.0000000000000431 29517502

25. Chtioui H. OATP1B1 and DAA treatment for hepatitis C in patients with hepatocellular carcinoma. Hepatology 2017;66:2091

26. Sugiura A, Joshita S, Umemura T, Yamazaki T, Fujimori N, Kimura T, et al. 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;25:1462–1471. doi: 10.1111/jvh.12973 30044517

27. Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology. 2017;65:310–335. doi: 10.1002/hep.28906 27786365

28. Liu CH, Su TH, Liu CJ, Hong CM, Yang HC, Tseng TC,et al. Sofosbuvir-based direct acting antiviral therapies for patients with hepatitis C virus genotype 2 infection. J Gastroenterol Hepatol. 2019 Jan 29. doi: 10.1111/jgh.14615 30693965

29. Cheng PN, Chiu YC, Chien SC, Chiu HC. Real-world effectiveness and safety of sofosbuvir plus daclatasvir with or without ribavirin for genotype 2 chronic hepatitis C in Taiwan. J Formos Med Assoc. 2019;118:907–913. doi: 10.1016/j.jfma.2018.09.016 30316677

30. 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;67:32–39. doi: 10.1016/j.jhep.2017.02.027 28267622

31. Cabibbo G, Petta S, Barbara M, Attardo S, Bucci L, Farinati F, et al. Italian Liver Cancer (ITA.LI.CA) group. Hepatic decompensation is the major driver of death in HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma. J Hepatol. 2017;67:65–71. doi: 10.1016/j.jhep.2017.01.033 28192185

32. Hu X, Qiu L, Liu D, Qian L. Acoustic Radiation Force Impulse (ARFI) elastography for noninvasive evaluation of hepatic fibrosis in chronic hepatitis B and C patients: a systematic review and meta-analysis. Med Ultrason 2017;19:23–31. doi: 10.11152/mu-942 28180193

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2019 Číslo 10
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