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Systematic review
Oral direct-acting antivirals and the incidence or recurrence of hepatocellular carcinoma: a systematic review and meta-analysis
  1. Sonal Singh1,2,
  2. Amit Nautiyal3,
  3. Yoon K Loke4
  1. 1 Department of Family Medicine and Community Health, University of Massachusetts School of Medicine, Worcester, Massachusetts, USA
  2. 2 Meyers Primary Care Institute, University of Massachusetts School of Medicine, Worcester, MA, USA
  3. 3 Department of Medicine, Pulmonary and Critical Care Medicine, Albany Medical College, Albany, New York, USA
  4. 4 Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK
  1. Correspondence to Dr Sonal Singh, Department of Family Medicine and Community Health, University of Massachusetts School of Medicine, Worcester, MA 01655, USA; Sonal.Singh{at}


Background The influence of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus on the risk of hepatocellular carcinoma (HCC) is conflicting.

Methods We conducted a systematic review and meta-analysis to determine the incidence or recurrence of HCC associated with oral DAA therapy. We searched PubMed, Scopus, Embase from inception to August 2017 to identify observational studies reporting on HCC among patients treated with DAAs. Two independent reviewers extracted data and assessed the risk of bias. Data were pooled by random-effects model. The primary outcome was the proportion of participants with incidence or recurrence of HCC (PROSPERO number CRD42017057040).

Results After reviewing 2080 citations, we included 8 controlled studies and 36 uncontrolled studies. The pooled proportion for incident HCC was 1.5 % (95% CI 1.0% to 2.1%; I2=90.1%; n= 542/39 145) from 18 uncontrolled studies and 3.3% (95% CI 1.2% to 9%; I2 =96%; n=109/6909) from 5 controlled studies, respectively. The pooled proportion for recurrent HCC was 16.7% (95% CI 10.2% to 26%; I2=84.8%; n=136/867) from 12 uncontrolled studies and 20.1% (95% CI 5.5% to 52.1%; I2=87.5%; n=36/225) from 3 controlled studies, respectively. There was no statistically significant effect on the risk of recurrent HCC (OR 0.50, 95%CI 0.16 to 1.59; I2 =73.4%) in a meta-analysis of three studies.

Conclusions Our findings show low proportion of incident HCC, but high proportion of recurrent HCC on treatment with DAAs. Continued active surveillance for HCC after treatment with DAAs remains prudent.

  • hepatocellular carcinoma
  • antiviral therapy
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  • Contributors SS, AN and YKL contributed to the manuscript by planning the study and reviewing the literature. All the authors collected the data. SS did the meta-analysis. All authors contributed to the assessment and interpretation of data. All authors read, revised and approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval We did not obtain ethical approval since the study was a systematic review of summary data.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All the data are provided as Supplementary Appendix.

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