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Page 2 of 9 Dai et al. Hepatoma Res 2020;6:16 I http://dx.doi.org/10.20517/2394-5079.2019.40

patients experienced HCC recurrence before DAAs. Among the 23 patients with viable HCC at the time of DAA
treatment, 10 patients had received curative therapy for HCC whereas the remaining 13 patients had HCC that
was never cured. The SVR12 rates were also similar among the four subpopulations, being 98.8% (83/84), 100%
(17/17), 90% (9/10) and 100% (13/13) respectively.

Conclusion: CHC patients with HCC who were adherent to potent DAAs achieved similar SVR12 rate compared to
those without HCC and could be effectively treated.

Keywords: Directly acting antiviral, chronic hepatitis C, hepatitis C virus, hepatocellular carcinoma, sustained
virological response

INTRODUCTION
[1]
Hepatocellular carcinoma (HCC) is one of the most common malignancies , which attributes to the second
[2]
cause of cancer-related death worldwide . Hepatitis C virus (HCV) infection is one of the leading etiologies
[3]
of HCC, which may account for one third of HCC patients . On the other hand, the risk of HCC decreases
[4]
drastically after successful antiviral therapy . Interferon-free all oral directly acting antivirals (DAAs) have
become a standard of care since 2014, providing ultimately high HCV cure rate and satisfactory safety
[5,6]
profiles . Emerging evidence has also shown the benefit of DAAs in reducing the development of HCV-
[7]
related HCC .
Recently, the issue concerning whether pre-existing HCC would compromise the sustained virological
response (SVR) rate in chronic hepatitis C (CHC) patients with DAAs has been raised, although discordant
[8]
results might in part be attributed to different treatment regimens and patient characteristics . In patients
with pre-existing HCC, a recent meta-analysis has shown that different treatment responses might exist
[9]
between patients with or without viable HCC at the time of initiating DAAs . Some of the earlier studies
[10]
used suboptimal treatment regimens that could not truly reflect the real world situation nowadays . By
using current DAAs, an SVR rate of > 95% could be accomplished across populations [11,12] . It is therefore
crucial to revisit the issue by using potent DAAs in daily practice. In addition, HCC patients might have
[5]
more safety concerns and are more likely to have experienced treatment discontinuation . Unequal
tolerability might further compromise efficacy evaluation in these patients. Herein, we aimed to explore the
issue by recruiting a well-characterized patient group in terms of HCC status who were adherent to novel
DAA regimens.

METHODS
Patients receiving DAAs were consecutively enrolled from Aug 2015 to Mar 2019. The treatment strategies
[13]
were based on regional guidelines and regulations of the Ministry of Health and Welfare of Taiwan.
Daclatasvir (DCV)/Asunaprevir (ASV) for HCV genotype 1 (HCV-1) and Sofosbuvir (SOF)/ribavirin for
HCV-2 have been reimbursed in Taiwan since 2017. Due to the previous relatively suboptimal treatment
responses, patients who used these regimens were excluded in the current study.

The diagnosis of HCC was ascertained by pathology or clinical judgments based on the guidelines of the
[14]
Asian Pacific Association for the Study of the Liver and the American Association for the Study of Liver
[2]
Diseases . HCC was defined as curative if the initial presentation could be managed by surgical resection,
local ablation or liver transplantation. The inactive HCC indicated that patients who had non-viable HCC
were defined as if there were no image evidence of recurrence within 6 months before initiating DAA
treatment. Other patients were defined with active HCC. The Review Board of the Kaohsiung Medical
University Hospital approved the protocols that followed the guidelines of the International Conference on
Harmonization for Good Clinical Practice. All patients provided written informed consent.