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Rutledge et al. Hepatoma Res 2019;5:31 Hepatoma Research
DOI: 10.20517/2394-5079.2019.19

Meta-Analysis Open Access

No evidence for higher rates of hepatocellular
carcinoma after direct-acting antiviral treatment: a

meta-analysis

Stephanie M. Rutledge , Hui Zheng , Darrick K. Li , Raymond T. Chung 1,2
1,2
1,2
2
1 Department of Medicine, Massachusetts General Hospital, Gastroenterology Unit/Warren 10, Boston, MA02114, USA.
2 Liver Center, Gastrointestinal Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School,
Boston, MA 02114, USA.

Correspondence to: Dr. Raymond T. Chung, Department of Medicine, Massachusetts General Hospital, Gastroenterology Unit/
Warren 10, 55 Fruit Street, Boston, MA 02114, USA. E-mail: Chung.Raymond@mgh.harvard.edu
How to cite this article: Rutledge SM, Zheng H, Li DK, Chung RT. No evidence for higher rates of hepatocellular carcinoma after
direct-acting antiviral treatment: a meta-analysis. Hepatoma Res 2019;5:31. http://dx.doi.org/10.20517/2394-5079.2019.19

Received: 12 Jun 2019 First Decision: 1 Jul 2019 Revised: 6 Jul 2019 Accepted: 8 Jul 2019 Published: 7 Aug 2019
Science Editor: Ming-Lung Yu Copy Editor: Jia-Jia Meng Production Editor: Jing Yu

Received: First Decision: Revised: Accepted: Published: Abstract

Science Editor: Copy Editor: Production Editor: Jing Yu Aim: Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC) in the United States. Achieving
sustained viral response with interferon (IFN) treatment reduces the risk from 3%-5% to 0.5%-1% annually. Several
studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals (DAAs). The aim of
our study was to compare HCC rates in DAA-, IFN-treated and untreated populations.

Methods: A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through
January 2019. Studies were included if they measured rates of de novo or recurrent HCC (following curative
treatment) in HCV-infected persons. We included 138 studies (n = 177,512). Simple pooling of data and meta-
analysis were performed, using the random effects method.

Results: Mean age was higher in the DAA-treated vs. IFN-treated group (58.4 years vs. 52.6 years; P = 0.0073),
as were diabetes prevalence (34.5% vs. 11.7%; P ≤ 0.001) and incident cirrhosis (47.8% vs. 34.2%, P = 0.0017).
The incidence rate of de novo HCC was 2.01/100 person-years (py) (95%CI: 1.38, 2.67) in the DAA group and
1.45/100py (95%CI: 0.98, 1.94) in the IFN-treated group. HCC recurred at 16.76/100py (95%CI: 10.75, 22.91) in
the DAA-treated group vs. 20.04/100py (95%CI: 2.58, 45.21) after IFN. After adjusting for factors such as age and
cirrhosis, the hazard ratio was 0.58 (95%CI: 0.20, 1.07) for HCC occurrence and 0.59 (95%CI: 0.24, 1.03) for HCC
recurrence after DAA treatment compared to IFN-based treatment.

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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