The risk of non-liver cancer is lower in people treated with direct-acting antivirals (DAAs) than in those treated with interferon and is probably an effect of the improved cure rate of hepatitis C on these drugs, according to an analysis of US patients treated for HCV presented last month at the 2018 International Liver Congress in Paris.
Several non-hepatic cancers occur more frequently in people with chronic hepatitis C infection, especially non-Hodgkin lymphoma. Successful interferon-based treatment for hepatitis C has been shown to reduce the risk of non-hepatic cancers but part of this effect may be a consequence of a direct anti-tumour effect of interferon. Any reduction in cancer incidence in people treated with DAAs might represent an effect of hepatitis C cure on cancer risk as DAAs have no known anti-tumour effects.
To investigate whether curing hepatitis C with DAAs reduces the risk of non-liver cancers compared to interferon-based treatment, researchers from pharmaceutical company Gilead Sciences looked at 367,156 adults with hepatitis C identified from US health insurance claims databases. Insurance claims data were used to identify treatment for both hepatitis C and for any form of cancer.
The researchers compared people treated for hepatitis C in two periods: between January 2006 and May 2011, when people would have been exposed to interferon or pegylated interferon only, and from December 2013 to March 2017, when people would have been exposed to DAA treatment (and excluding the first generation of DAAs that were used in combination with interferon).
The study identified 10,989 people treated with interferon and 22,894 people treated with DAAs. People treated with interferon were younger than those treated with DAAs (a median of 51 years compared to 57 years of age) and tended to have a lower prevalence of co-morbidities, risk factors for cancer such as smoking and obesity, and less advanced liver disease.
Interferon-treated individuals were treated for a median of 2.6 years and DAA-treated individuals for a median of one year.
Analysis of the relative risk of cancer showed that whereas the risk of cancers strongly associated with hepatitis C – non-Hodgkin lymphoma and bile duct cancer – was no lower in people treated with DAAs, the risk of several major cancers was reduced in people treated with DAAs. Prostate cancer, lung cancer, leukaemia and bladder cancer occurred less frequently in people treated with DAAs.
The reduction in the risk of a major cancer ranged from a 29% reduction in the risk of prostate cancer (adjusted hazard ratio 0.71, 95% CI 0.52-0.97), the most common major cancer in the study population (three cases per thousand people during each year of follow-up), to a 62% reduction in the risk of leukaemia (aHR 0.38, 95% CI 0.24-0.60), which occurred in less than one in a thousand people during each year of follow-up.
The study found no significant reduction in the risk of colorectal, breast, oesophageal or pancreatic cancers in people treated with DAAs.
The overall risk of any major cancer was reduced by 14% in those treated with DAAs when compared to those treated with interferon (aHR 0.86, 95% CI 0.80-0.93).
The investigators concluded that although the mechanisms for the differences in risk by tumour site are unclear, the overall reduction in the risk of major cancers may reflect the difference in cure rates between people treated with interferon-based regimens and people treated with much more effective DAA regimens.
By Keith Alcorn
Chokkalingam A et al. Risk of total non-hepatic cancer following treatment for HCV infection with direct-acting antiviral agents. The International Liver Congress, Paris, abstract PS-155, 2018. Journal of Hepatology 68: S86, 2018.