A new research paper published by the BC-CfE laboratory’s scientists will help healthcare providers improve treatments for people living with the hepatitis C virus (HCV). The study, led by Dr. Hope Lapointe, describes a new test that physicians can use to help “personalize” their patients’ HCV treatment.
HCV infection is a major public health concern in Canada and around the world. The World Health Organization estimates 71 million people globally live with chronic HCV infection and nearly 400,000 people die from the virus each year, largely due to liver cirrhosis and hepatocellular carcinoma. Here in BC, it’s estimated there are nearly 30,000 people living with untreated HCV. In Vancouver’s Downtown Eastside, home to about 18,000 people, the prevalence of HCV within the community is thought to be as high as 90%.
HCV infection is usually curable with oral treatments lasting several months. The therapeutic approach towards HCV chronic infection has vastly improved over the past decade, with the introduction of oral direct-acting antiviral (DAA) agents. This novel class of medications enables the specific targeting of HCV and has demonstrated treatment success rates above 90-95%. This success is further highlighted by the ability of some DAA regimens to target all genetically-distinct groups of HCV, known as HCV genotypes.
Despite the successes of DAA treatment, there are cases of DAA treatment failure associated with the emergence of drug resistance mutations known as resistance-associated substitutions (RAS). The presence of these mutations in the HCV genome can impair the ability of certain DAA agents to suppress the virus, thereby compromising treatment success. Identifying RAS can enable clinicians to personalize DAA treatment for a given patient, thereby enhancing the likelihood of treatment success.
To better guide clinical decision-making for HCV patients, the BC-CfE laboratory research team developed and validated a new laboratory test for HCV drug resistance. This test is novel as it uses “next-generation” sequencing to interrogate the entire HCV genome and works on all HCV genotypes. Previous assays were typically limited to analyzing HCV infections of a single genotype and/or could only identify mutations within a limited section of the genome. This new assay can identify resistance mutations regardless of HCV genotype and captures the entire HCV genome. This assay can therefore provide accurate and reproducible HCV drug resistance profiles for all currently available HCV therapeutic agents, regardless of HCV genotype. In practice, such an assay will be most useful in cases of DAA-treatment failure or in cases where a client has yet to initiate HCV care, in order to personalize HCV therapy.
In addition to the laboratory workflow, the article outlines the data processing workflow to analyze HCV whole-genome data. This bioinformatic pipeline, “MiCall”, written by Don Kirkby, the lead software developer with the BC-CfE Laboratory program and Art Poon, a former BC-CfE Research Scientist, is an open-source tool that produces drug resistance reports from both HCV and HIV sequence data.
This study highlights the performance of a freely available laboratory and bioinformatic approach for reliable HCV genotyping and drug resistance detection regardless of HCV genotype. These tools can feasibly be adopted by other laboratories globally to implement HCV drug resistance testing, with an end-to-end, sample-to-report workflow.
Although this manuscript was only published recently, this test has been in use at the BC-CfE Lab for several years. Physicians across Canada have used these results to help guide treatment for hundreds of Canadians with HCV. Very few groups have openly validated assays as thoroughly as this, and even fewer released have the entire wet-lab and bioninformatic workflows freely for public use. We hope this can help other labs to implement HCV drug resistance testing, or even HCV sequencing for research purposes, when they might otherwise have been unable to do this.
– Dr. Chanson Brumme, Assistant Director of the BC-CfE’s Research Laboratories and the study’s senior author