Biological Individuality: The Microbiome as a Dynamic in HCV Liver Disease Progression

07/14/2017

Vivian Cheng​

Volume 2
Fall 2016 / Winter 2017

The precision medicine initiative was established to optimize patient outcomes through studying variations between individuals as a “one-size-fits-all” approach is seldom useful in disease treatment. The microbiome has been found to be specific to each individual, and differing microbial compositions play a large role in influencing human health. The microbiome tightly interacts with the immune system and host metabolism, rendering it a key player in determining an individual’s response to infectious disease. Chronic infection by the hepatitis C virus (HCV) can lead to severe liver conditions, specifically cirrhosis and hepatocellular carcinoma (HCC). Examining changes in the microbiome before and after HCV infection has the potential to provide insight into aspects of liver disease progression. For example, an unexplained discrepancy in HCV-associated disease severity exists; certain individuals are capable of clearing infection while others progress to chronic hepatitis C (CHC). What’s more, the existing microbiome of a hepatitis C patient receiving a liver transplant may have an effect on the rate of re-infection, and microbiome changes due to HCV infection may impact the likelihood of developing HCC even after clearing the infection. A potential longitudinal study design could involve following the microbiome changes of individuals throughout HCV infection, disease progression, and treatment. Specifically, the target population would be intravenous drug-users in downtown Vancouver, BC, who are at high risk of HCV infection. The microbiomes of individuals can be studied using next-generation sequencing methods and metagenomic analyses. Such a study would allow us to determine if particular microbial compositions or taxa are a driving force contributing to HCV-induced liver disease progression. The microbiome will then have demonstrated potential as a diagnostic and therapeutic target for personalized treatment. However, the dynamic and heterogeneous nature of the microbiome is as useful as it is challenging. Concerns may be raised regarding sample collection, proper data analysis, and bioethical considerations. Despite these challenges, the potential for investigation of the microbiome in the context of HCV infection to offer a wealth of information to improve hepatitis C patient outcomes renders it an important area of exploration, and such an investigation could be used as a model system to address other viral infectious diseases in the future.