Highlights
- •Crude risk of HCC higher for IFN-free recipients than IFN-containing recipients.
- •IFN-free and IFN-containing recipients differ with respect to confounding factors.
- •Association between IFN-free therapy and HCC disappears after adjusting for baseline confounders.
- •At HCC diagnosis, no differences in nodule size or nodule number were apparent by regimen.
Background & Aims
Previous studies have reported a high frequency of hepatocellular carcinoma (HCC)
occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free
therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account
for this phenomenon using data from the Scottish HCV clinical database.
Methods
We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral
therapy in Scotland from 1997–2016 resulting in a sustained virologic response. Patients
were followed-up from their treatment start date to the earliest of: date of death,
date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the
risk of HCC occurrence according to treatment regimen after adjusting for relevant
co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health
behaviours, virology, and previous treatment experience). HCC occurrence was ascertained
through both the HCV clinical database and medical chart review. For our main analysis,
treatment regimen was defined as IFN-free vs. IFN-containing.
Results
A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free
regimen. Individuals receiving IFN-free therapy were more likely to be: older; of
white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced.
HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis,
IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48;
p = 0.021). However, after multivariate adjustment for baseline factors, no significant
risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744).
Conclusion
These findings suggest that the higher incidence of HCC following sustained virologic
response with IFN-free therapy relates to baseline risk factors/patient selection,
and not the use of IFN-free therapy per se.
Lay summary
We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who
received hepatitis C antiviral therapy and achieved a cure. We compared the risk of
first-time liver cancer in patients treated with the newest interferon-free regimens,
to patients treated with interferon. After accounting for the different characteristics
of these two treatment groups, we found no evidence that interferon-free therapy is
associated with a higher risk of liver cancer.
Graphical abstract
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Hepatitis C virus therapeutic development: in pursuit of “perfectovir”.Clin Infect Dis. 2015; 60: 1829-1836
- Safety and efficacy of elbasvir/gazoprevir in patients with hepatitis C virus infection and compensated cirrhosis: an integrated analysis.Gastroenterology. 2017; 152: 1372-1382
- Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.JAMA. 2012; 308: 2548-2593
- The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings.Ann Intern Med. 2012; 156: 263-270
- Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy.J Hepatol. 2016; 65: 719-726
- Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals.J Hepatol. 2016; 65: 719-726
- High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis.J Hepatol. 2016; 65: 1070-1071
- Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment.J Hepatol. 2016; 65: 856-868
- Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial.Lancet Oncol. 2015; 16: 1344-1354
- Risk of cirrhosis-related complications in patients with advanced fibrosis following hepatitis C virus eradication.J Hepatol. 2017; 66: 485-493
- Risk of hepatocellular carcinoma after sustained viral response in veterans with hepatitis C virus infection.. 2016; 64: 130-137
- Changes in patient background may increase the incidence of HCC after SVR in the era of IFN-free therapy for HCV.Hepatology. 2016; 64: 1818-1819
- Attendance at specialist hepatitis linics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland’s hepatitis C action plan.J Viral Hepat. 2014; 21: 366-376
- Toward a more complete understanding of the association between a hepatitis C sustained viral response and cause-specific outcomes.Hepatology. 2015; 62: 355-364
- EASL recommendations on treatment of hepatitis C 2014.J Hepatol. 2014; 61: 373-395
- Concordance of sustained virological response 4,12 and 24 weeks post-treatment with sofosbuvir-containing regimens for Hepatitis C.Hepatology. 2015; 61: 41-45
- EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943
- Shift in disparities in hepatitis C treatment from interferon to DAA era: a population-based cohort study.J Viral Hepat. 2017; 24: 624-630
- Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis.J Hepatol. 2016; 65: 741-747
- Utilisation of surveillance for hepatocellular carcinoma among hepatitis C virus-infected veterans in the United States.Ann Intern Med. 2011; 154: 85-93
- Lack of evidence of direct-acting antivirals on the recurrence of hepatocellular carcinoma: data from three ANRS cohorts.J Hepatol. 2016; 65: 734-740
- Effectiveness of hepatitis C antiviral treatment in a USA cohort of veteran patients with hepatocellular carcinoma.J Hepatol. 2017; 67: 32-39
Article info
Publication history
Published online: November 15, 2017
Accepted:
October 30,
2017
Received in revised form:
October 18,
2017
Received:
May 15,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
