The Risks of Hepatocellular Carcinoma Development After HCV Eradication Are Similar Between Patients Treated with Peg-interferon Plus Ribavirin and Direct-acting Antiviral Therapy

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Aug 11

PMID 28797106

Citations 23

Authors

Yuko Nagaoki

Michio Imamura

Hiroshi Aikata

Kana Daijo

Yuji Teraoka

Fumi Honda

Yuki Nakamura

Masahiro Hatooka

Reona Morio

Kei Morio

Hiromi Kan

Hatsue Fujino

Tomoki Kobayashi

Keiichi Masaki

Atsushi Ono

Takashi Nakahara

Tomokazu Kawaoka

Masataka Tsuge

Akira Hiramatsu

Yoshiiku Kawakami

C Nelson Hayes

Daiki Miki

Hidenori Ochi

Kazuaki Chayama

Affiliations

Soon will be listed here.

Abstract

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10-196) and 23 (range 4-78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

Citing Articles

Impact of viral eradication by direct-acting antivirals on clinical outcomes after curative treatment for hepatitis C virus-associated hepatocellular carcinoma.

Nagaoki Y, Yamaoka K, Fujii Y, Uchikawa S, Fujino H, Ono A Therap Adv Gastroenterol. 2025; 18:17562848251324094.

PMID: 40078327 PMC: 11898033. DOI: 10.1177/17562848251324094.

Risk of hepatocellular carcinoma occurrence after antiviral therapy for patients with chronic hepatitis C Infection: a systematic review and meta-analysis.

Lv G, Ji D, Yu L, Chen H, Chen J, He M Hepatol Int. 2024; 18(5):1459-1471.

PMID: 38965190 DOI: 10.1007/s12072-024-10700-7.

Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies.

Yamagiwa Y, Tanaka K, Matsuo K, Wada K, Lin Y, Sugawara Y Sci Rep. 2023; 13(1):3445.

PMID: 36859564 PMC: 9977913. DOI: 10.1038/s41598-023-30467-5.

Prospective Comparison of Hepatocellular Carcinoma Behavior and Survival of Patients who Did or Did not Receive HCV Direct-Acting Antivirals.

El-Kassas M, Sayed H, Omran D, Eldahrouty A, Elbaz T, Kamal E Asian Pac J Cancer Prev. 2023; 24(2):597-605.

PMID: 36853310 PMC: 10162632. DOI: 10.31557/APJCP.2023.24.2.597.

Hepatocellular carcinoma, decompensation, and mortality based on hepatitis C treatment: A prospective cohort study.

Choi G, Jang E, Kim Y, Lee Y, Kim I, Bum Cho S World J Gastroenterol. 2022; 28(30):4182-4200.

PMID: 36157119 PMC: 9403421. DOI: 10.3748/wjg.v28.i30.4182.

References

DAgostino Jr R . Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998; 17(19):2265-81. DOI: 10.1002/(sici)1097-0258(19981015)17:19<2265::aid-sim918>3.0.co;2-b. View

Poynard T, Moussalli J, Ratziu V, Regimbeau C, Opolon P . Effect of interferon therapy on the natural history of hepatitis C virus-related cirrhosis and hepatocellular carcinoma. Clin Liver Dis. 2001; 3(4):869-81. DOI: 10.1016/s1089-3261(05)70244-0. View

Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K . A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology. 1993; 18(1):47-53. View

Ochi H, Miki D, Hayes C, Abe H, Hayashida Y, Kubo M . IFNL4/IL-28B haplotype structure and its impact on susceptibility to hepatitis C virus and treatment response in the Japanese population. J Gen Virol. 2014; 95(Pt 6):1297-1306. DOI: 10.1099/vir.0.060103-0. View

Niederau C, Lange S, Heintges T, Erhardt A, Buschkamp M, HURTER D . Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 1998; 28(6):1687-95. DOI: 10.1002/hep.510280632. View

Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, Mochizuki H . Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis. 2015; 15(6):645-53. DOI: 10.1016/S1473-3099(15)70099-X. View

Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P . Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016; 65(4):727-733. DOI: 10.1016/j.jhep.2016.06.015. View

Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M . Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999; 29(4):1124-30. DOI: 10.1002/hep.510290439. View

Kobayashi S, Takeda T, Enomoto M, Tamori A, Kawada N, Habu D . Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients. Liver Int. 2007; 27(2):186-91. DOI: 10.1111/j.1478-3231.2006.01406.x. View

10.

Layer P, Zinsmeister A, DiMagno E . Effects of decreasing intraluminal amylase activity on starch digestion and postprandial gastrointestinal function in humans. Gastroenterology. 1986; 91(1):41-8. DOI: 10.1016/0016-5085(86)90436-1. View

11.

Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S . Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology. 1998; 27(5):1394-402. DOI: 10.1002/hep.510270529. View

12.

Kobayashi M, Suzuki F, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T . Sustained virologic response by direct antiviral agents reduces the incidence of hepatocellular carcinoma in patients with HCV infection. J Med Virol. 2016; 89(3):476-483. DOI: 10.1002/jmv.24663. View

13.

Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Kubo M . ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy--a genome-wide study of Japanese HCV virus patients. Gastroenterology. 2010; 139(4):1190-7. DOI: 10.1053/j.gastro.2010.06.071. View

14.

Morio R, Imamura M, Kawakami Y, Morio K, Kobayashi T, Yokoyama S . Safety and efficacy of dual therapy with daclatasvir and asunaprevir for older patients with chronic hepatitis C. J Gastroenterol. 2016; 52(4):504-511. DOI: 10.1007/s00535-016-1255-4. View

15.

Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y . Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990; 12(4 Pt 1):671-5. DOI: 10.1002/hep.1840120409. View

16.

Reig M, Marino Z, Perello C, Inarrairaegui M, Ribeiro A, Lens S . Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016; 65(4):719-726. DOI: 10.1016/j.jhep.2016.04.008. View

17.

Sterling R, Lissen E, Clumeck N, Sola R, Correa M, Montaner J . Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006; 43(6):1317-25. DOI: 10.1002/hep.21178. View

18.

Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N . Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009; 41(10):1105-9. DOI: 10.1038/ng.449. View

19.

Chayama K, Notsumata K, Kurosaki M, Sato K, Rodrigues Jr L, Setze C . Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients. Hepatology. 2015; 61(5):1523-32. PMC: 5763364. DOI: 10.1002/hep.27705. View

20.

Rubin D . Estimating causal effects from large data sets using propensity scores. Ann Intern Med. 1998; 127(8 Pt 2):757-63. DOI: 10.7326/0003-4819-127-8_part_2-199710151-00064. View