To Örebro University

Background and Aims: Direct acting antivirals (DAA) against hepatitis C virus (HCV) have been shown to have an immune modulatory effect, with a possibly decreased tumour specific CD8 T cell response. Reports indicative of a high risk for hepatocellular carcinoma or advanced tumours early after DAA treatment, have raised concerns about whether the risk for non-liver cancer could be increased. Therefore, our aim was to study the early incidence of non-liver cancer after initiation of DAA or interferon (IFN-based) therapy in a national HCV cohort.

Method: All diagnosed HCV-infected persons in Sweden, their antiviral treatments, non-liver cancer or death/emigration were identified retrospectively, using the national HCV-surveillance register and other national registers. Cox regression was used to compare persons treated with DAAs (n = 1,920), IFN-based therapy(n = 2,586) or no HCV therapy (n = 13,872) between 2009 and 2015. Persons with a previous cancer diagnosis (5.7%) were studied separately. Age was used as the time-scale, and the analyses were stratified by sex and adjusted for the Charlson comorbidity index.

Results: In total 492 non-liver cancers were diagnosed, with 222 among persons with no previous cancer and 270 new cancer diagnoses among those with previous cancer. Among persons with no previous cancer, 21, 24 and 177 developed non-liver cancer following DAA, IFN-based and no treatment, respectively. The corresponding numbers for those with previous cancer were 25, 20 and 225, respectively. The hazard ratios (and 95% confidence intervals) for non-liver cancer in the no previous cancer group are 1.35 (0.66–2.76; p = 0.41) for men and 1.75 (0.59–5.18; p = 0.31) for women with DAA treatment, compared with IFN treatment. For those with previous cancer, the corresponding hazard ratios are 1.03 (0.41–2.57; p = 0.95) for men and 0.86 (0.35–2.13; p = 0.75) for women with DAA treatment.

Conclusion: This study did not demonstrate any significantly increased risk for non-liver cancer early after DAA therapy initiation. The hazard ratio was slightly increased among those with outprevious cancer, but the cancers were few and the results were not statistically significant. Further studies with higher numbers of DAA treated patients and longer follow-up are needed to fully explore thisissue.