Genetic Variation: The Key to Ending the Silent Epidemic?

By Rukan Saif, Copy Editor


Graphic by Alex Jeon

Hepatitis C, caused by the hepatitis C virus (HCV), is the most common blood-borne infection in the U.S. In addition to the 3 million people living with chronic HCV, 170,000 new cases develop each year, many of which go unreported. It is for this reason that HCV can be so fatal; the virus is known as a “silent killer,” as it “has no symptoms and can go decades without detection,” according to the American Pharmacists Association. Unfortunately, the complications that can arise from hepatitis C, including cirrhosis and hepatocellular carcinoma (a type of liver cancer), claim over 400,000 lives globally each year.


According to the Centers for Disease Control and Prevention, though, about half of the people who test anti-HCV positive — meaning that antibodies targeting the hepatitis C virus are present in the blood — do not currently have a chronic infection. This implies that those people may have spontaneously cleared the virus. An array of epidemiological and host factors have been linked to spontaneous HCV clearance. For example, having jaundice, elevated ALT (alanine aminotransferase) levels, and hepatitis B virus surface antigen (HBsAg) positivity; being younger and/or female; and being infected with HCV genotype 1 have all been associated with such a phenomenon.


Most fascinating of all is the role that genetic polymorphisms play in spontaneous HCV clearance. In a 2009 study, a group of renowned scientists from the U.S. and U.K. examined the effect of genetic variation in a single nucleotide polymorphism (SNP), rs12979860, on viral clearance. This SNP is located 3 kilobases (kb) upstream of the IL28B gene, which encodes the type III interferon IFN-λ3. For background, interferons are signaling proteins made and released by host cells after viral detection.


Previously, it was known that IL28B had positive effects on HCV treatment response. However, this study sought to explain the most considerable genetic effect correlated to spontaneous clearance of HCV: the effect of the C/C genotype. This also further implicates the significant role IL28B plays. Using a genome-wide association study, an observational study of genetic variants aimed to conclude whether any variant is associated with a trait. Individuals with chronic HCV participated in a clinical treatment trial with pegylated interferon alpha and ribavirin, a viral therapy that has previously yielded consistent eradication in approximately 40% of cases. Conclusively, the C/C genotype produced a significantly greater rate of sustained virological response compared to the T/T genotype, proffering the idea that the C allele may favor the ability to clear the virus.


Though it may seem as if this study fulfilled its goal in answering questions about HCV clearance by effectively gauging the impact the rs12979860 polymorphism has on spontaneous clearance, it also created new questions about natural selection and survival rates throughout history. From here, it is essential that steps be taken to discern which mechanisms in the IL28B gene promote viral defense and the range of affected viruses. Hepatitis C continues to ravage the world today, causing issues like liver, blood, joint, skin, and nerve pain. Using genetics and genomics to discover the intricacies behind host and viral make-up may very well be the key to a vaccine — and the end of this silent epidemic.


References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172006/

https://www.webmd.com/hepatitis/hepatitis-c-no-treatment

https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

https://www.pharmacist.com/hepatitis-c-%E2%80%9Csilent-killer%E2%80%9D#:~:text=Hepatitis%20C%20has%20been%20called,C%20are%20on%20the%20rise.

https://www.hhs.gov/opa/reproductive-health/fact-sheets/sexually-transmitted-diseases/hepatitis-c/index.html#:~:text=More%20than%203%20million%20people,many%20of%20which%20go%20unreported.


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