Enzyme Deficiency Protects from Ribavirin-Related Anaemia

Some 200 million people worldwide are estimated to be infected with the hepatitis C virus (HCV) which can eventually lead to cirrhosis, liver cancer, and in some cases, death. The current standard-of-care treatment for persistent infection – a combination of pegylated interferon-α and ribavirin – is able to clear the infection in around 50% of patients. In some patients, however, treatment is associated with haemolytic anaemia which may be severe enough to need dosage reduction or even discontinuation of treatment.

A team led by scientists at Duke University’s Institute for Genome Sciences & Policy (IGSP) have now discovered that loss of function mutations in the gene ITPA, which encodes the enzyme inosine triphosphatase, protect against the development of anaemia. Previous studies had identified the genetic variants with enzyme deficiency and, through a genome-wide association study, the Duke team were able to show that they were also protective against anaemia caused by ribavirin. The finding may offer new treatment opportunities for HCV patients with coronary artery disease or kidney disease who are often not treated with ribavirin because of fears that anaemia could exacerbate their condition.

Inosine triphosphatase deficiency was first recognised over 30 years ago and is not thought to be clinically important. A diagnostic test that could predict deficiency, and hence reduced susceptibility to ribavirin-associated anaemia, would allow broader treatment options for HCV patients.

The study is published in the journal Nature.