Interferon Is Superior to Direct Acting Antiviral Therapy in Tertiary Prevention of Early Recurrence of Hepatocellular Carcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Dec 22

PMID 31861706

Citations 6

Authors

Wei Teng

Wen-Juei Jeng

Hwai-I Yang

Wei-Ting Chen

Yi-Chung Hsieh

Chien-Hao Huang

Chen-Chun Lin

Chun-Yen Lin

Shi-Ming Lin

I-Shyan Sheen

Affiliations

Soon will be listed here.

Abstract

The elimination of chronic hepatitis C infection (CHC) by pegylated interferon plus ribavirin (Peg-IFN/RBV) decreases hepatocellular carcinoma (HCC) recurrence rate. However, the tertiary prevention of HCC recurrence by direct acting antiviral agents (DAA) remains controversial. This study aims to compare the tertiary prevention effect between DAA and Peg-IFN/RBV in CHC-HCC patients. Three hundred and one patients who received curative HCC treatment were retrospectively recruited. The recurrence incidence rate (IR) was compared among patients either receiving Peg-IFN/RBV or DAA regimen or untreated by three timeframes (I: from HCC treatment to antiviral therapy; II: during antiviral therapy; III: after antiviral therapy). The prevention effect between Peg-IFN/RBV and DAA were compared in frame II and III after propensity score matching (PSM) with age, tumor staging, HCC treatment modality, and cirrhotic status. Before PSM, the recurrence IRs in three arms were comparable in frame I, while being lower in the Peg-IFN/RBV and DAA arm compared to the untreated arm in frame II. In frame III, the tertiary prevention effect lasted in the Peg-IFN/RBV arm ( < 0.001), but diminished in the DAA arm ( = 0.135) compared to untreated patients. After PSM, the HCC recurrence IR was higher in the DAA arm than the Peg-IFN/RBV arm in frame II (2724 vs. 666 per 10 person-years, log-rank = 0.042) and III (5259 vs. 3278 per 10 person-years, log-rank = 0.048). Preantiviral ALBI grade therapy is the only predictor for postantiviral therapy HCC recurrence. In conclusion, the tertiary prevention effect of HCC recurrence was not durable in DAA-treated patients, but persisted in Peg-IFN/RBV treatment patients.

Citing Articles

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References

Minami T, Tateishi R, Nakagomi R, Fujiwara N, Sato M, Enooku K . The impact of direct-acting antivirals on early tumor recurrence after radiofrequency ablation in hepatitis C-related hepatocellular carcinoma. J Hepatol. 2016; 65(6):1272-1273. DOI: 10.1016/j.jhep.2016.07.043. View

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

Warzyszynska K, Jonas M, Wasiak D, Kosieradzki M, Malkowski P . Accelerated hepatocellular carcinoma recurrence rate after postoperative direct-acting antivirals treatment - preliminary report. Clin Exp Hepatol. 2017; 3(4):194-197. PMC: 5731431. DOI: 10.5114/ceh.2017.71483. View

Singal A, Rich N, Mehta N, Branch A, Pillai A, Hoteit M . Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study. Gastroenterology. 2019; 156(6):1683-1692.e1. PMC: 6598433. DOI: 10.1053/j.gastro.2019.01.027. View

. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69(1):182-236. DOI: 10.1016/j.jhep.2018.03.019. View

Kinoshita M, Minami T, Tateishi R, Wake T, Nakagomi R, Fujiwara N . Impact of direct-acting antivirals on early recurrence of HCV-related HCC: Comparison with interferon-based therapy. J Hepatol. 2018; 70(1):78-86. DOI: 10.1016/j.jhep.2018.09.029. 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

Nagaoki Y, Imamura M, Nishida Y, Daijo K, Teraoka Y, Honda F . The impact of interferon-free direct-acting antivirals on clinical outcome after curative treatment for hepatitis C virus-associated hepatocellular carcinoma: Comparison with interferon-based therapy. J Med Virol. 2018; 91(4):650-658. DOI: 10.1002/jmv.25352. View

Kao W, Su C, Chiou Y, Chiu N, Liu C, Fang K . Hepatocellular Carcinoma: Nomograms Based on the Albumin-Bilirubin Grade to Assess the Outcomes of Radiofrequency Ablation. Radiology. 2017; 285(2):670-680. DOI: 10.1148/radiol.2017162382. View

10.

Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu M, Allen C . The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015. JAMA Oncol. 2017; 3(12):1683-1691. PMC: 5824275. DOI: 10.1001/jamaoncol.2017.3055. View

11.

Hiraoka A, Kumada T, Kudo M, Hirooka M, Tsuji K, Itobayashi E . Albumin-Bilirubin (ALBI) Grade as Part of the Evidence-Based Clinical Practice Guideline for HCC of the Japan Society of Hepatology: A Comparison with the Liver Damage and Child-Pugh Classifications. Liver Cancer. 2017; 6(3):204-215. PMC: 5473065. DOI: 10.1159/000452846. View

12.

. 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

13.

Kanogawa N, Ogasawara S, Chiba T, Saito T, Motoyama T, Suzuki E . Sustained virologic response achieved after curative treatment of hepatitis C virus-related hepatocellular carcinoma as an independent prognostic factor. J Gastroenterol Hepatol. 2015; 30(7):1197-204. DOI: 10.1111/jgh.12925. View

14.

Waziry R, Hajarizadeh B, Grebely J, Amin J, Law M, Danta M . Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression. J Hepatol. 2017; 67(6):1204-1212. DOI: 10.1016/j.jhep.2017.07.025. View

15.

. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol. 2018; 69(2):461-511. DOI: 10.1016/j.jhep.2018.03.026. View

16.

Jeong S, Aikata H, Katamura Y, Azakami T, Kawaoka T, Saneto H . Low-dose intermittent interferon-alpha therapy for HCV-related liver cirrhosis after curative treatment of hepatocellular carcinoma. World J Gastroenterol. 2007; 13(39):5188-95. PMC: 4171300. DOI: 10.3748/wjg.v13.i39.5188. View

17.

Nahon P, Layese R, Bourcier V, Cagnot C, Marcellin P, Guyader D . Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs. Gastroenterology. 2018; 155(5):1436-1450.e6. DOI: 10.1053/j.gastro.2018.07.015. View

18.

Huang A, Mehta N, Dodge J, Yao F, Terrault N . Direct-acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local-regional therapy or liver transplant waitlist dropout. Hepatology. 2018; 68(2):449-461. PMC: 6097892. DOI: 10.1002/hep.29855. View

19.

Cabibbo G, Celsa C, Calvaruso V, Petta S, Cacciola I, Cannavo M . Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients. J Hepatol. 2019; 71(2):265-273. DOI: 10.1016/j.jhep.2019.03.027. View

20.

Morgan R, Baack B, Smith B, Yartel A, Pitasi M, Falck-Ytter Y . Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013; 158(5 Pt 1):329-37. DOI: 10.7326/0003-4819-158-5-201303050-00005. View