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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
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