Research ArticleHCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma
Graphical abstract
Introduction
Eradication of HCV might be expected to reduce the risk of hepatocellular carcinoma (HCC) by preventing the future development of cirrhosis or by reversing early cirrhosis, a major risk factor for HCC. In addition, HCV might itself promote carcinogenesis,1 such that its eradication directly decreases HCC risk. Indeed, a meta-analysis of 18 studies of interferon (IFN)-based antiviral treatments for HCV suggested that sustained virologic response (SVR) was associated with reduced risk of HCC (relative risk 0.24; 95% CI 0.18–0.31).2 IFN-based treatments have now been replaced by direct-acting antiviral agents (DAAs). It is unclear whether the impact of SVR on HCC risk is different depending on whether SVR is achieved with either IFN-based regimens or DAAs. Surprisingly, recent studies suggested little or no impact of DAA-based antiviral treatment on HCC risk and even reported that DAAs might increase the risk of HCC recurrence.[3], [4], [5], [6], [7], [8] However, these studies were grossly underpowered, had limited follow-up time, mostly studied HCC recurrence rather than incidence, and did not compare those who achieved SVR because of DAAs to those who did not with respect to HCC risk.
In the current study, our aim was to determine the extent to which eradication of HCV with DAA-based treatments was associated with reduction in the risk of HCC, and whether this association was different for SVRs achieved by DAA vs. IFN-based regimens. We also aimed to determine whether receipt of DAA-based treatment compared with IFN-based treatment was associated with HCC risk.
Section snippets
Data source
The Veterans Affairs (VA) healthcare system is the largest integrated healthcare provider of HCV antiviral treatment in the USA. In 2014, 5,857,690 veterans received care in 154 medical centres and 875 ambulatory care and community-based outpatient clinics that comprise the VA healthcare system nationally,9 including 174,302 patients with known HCV infection (i.e. positive serum HCV viral load test).10
The VA uses a single, nationwide, comprehensive electronic healthcare information network
Characteristics of study population
Among the 62,354 patients who initiated their first antiviral regimen from 1 January 1999 to 31 December 2015, 34,660 (55.6%) achieved SVR. The antiviral treatments included 35,871 (58%) IFN-only regimens, 4,535 (7.3%) DAA + IFN regimens, and 21,948 (35%) DAA-only regimens. The distribution of different DAA regimens is shown (Table 1).
SVR rates were highest in the DAA-only regimens (90.7%), followed by the DAA + IFN regimens (60.9%), and lowest in the IFN-only regimens (33.4%). Patients were
Discussion
Most patients with HCV in the USA will undergo DAA-based antiviral treatment in the next few years and the majority of them will achieve SVR. Our results suggest that DAA-induced SVR is associated with a 71% reduction in HCC risk (AHR 0.29; 95% CI 0.23–0.37) compared with treatment failure. The reduction in HCC risk associated with SVR was similar irrespective of whether SVR was achieved by DAA-only, DAA + IFN, or IFN-only regimens. This suggests that eradication of HCV reduces HCC risk
Financial support
The study was funded by a NIH/NCI grant R01CA196692 and VA CSR&D grant I01CX001156 to GNI. The funding source had no role in study design, collection, analysis or interpretation of data.
Conflict of interest
The authors declare that they have no conflict of interest related to this manuscript.
Please refer to the accompanying ICMJE disclosure forms for further details.
Authors’ contributions
All authors approved the final version of the manuscript. G.I. is the guarantor of this paper and was responsible for the study concept and design; acquisition of data; statistical analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript; and obtaining funding; PG was responsible for the acquisition and analysis of data, and study design; and KB was responsible for the study design, analysis of data, and critical revision of the manuscript.
Disclaimer
The contents of this manuscript do not represent the views of the US Department of Veterans Affairs or the US Government.
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