TIGP (BIO)—Unveiling Clinical Outcomes in Liver Diseases: Exploring Virus-Related Factors and Host Genetic Variants

Abstract

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related fatalities worldwide. Well-documented risk factors for HCC and liver cirrhosis include infections with hepatitis B and C viruses (HBV and HCV). This presentation embarks on a journey through my research, initially centered around hepatitis C virus (HCV), and subsequently branching out into related studies influenced by insights gained from HCV investigations. Approximately 15 years ago, curative antiviral agents for chronic hepatitis C were still nonexistent, and crucial epidemiological data were lacking to inform risk stratification for hepatitis C patients. Our findings indicated an elevated risk of hepatic and extrahepatic diseases among chronic hepatitis C patients. Furthermore, viral factors such as viral load and genotypes played a pivotal role in HCC development. We integrated these predictors into risk prediction models to forecast long-term HCC risks, while also considering genetic variants. In our earlier genome-wide association study (GWAS), we identified variants near the human leukocyte antigen (HLA) region that were associated with HCC among HCV-infected patients. Notably, HLA DQB1*0301 and *0602 exhibited significant associations with the long-term risk of HCC occurrence. Subsequently, we established HLA imputation references specific to the Taiwanese population. By utilizing these population-specific references, imputation accuracy improved, reaching at least 98%, depending on the HLA locus. Building upon these references, we uncovered variants near HLA associated with HBV chronicity. More recently, we explored variants linked to HCC among individuals without HBV or HCV infections. Additional biomarkers hold promise for monitoring patients who have successfully undergone antiviral treatment with the newly advanced antivirals boasting high response rates. Genetic heterogeneity underscores the complexity of HCC. However, these genetic profiles can serve as candidate biomarkers, refining HCC screening and management by enabling individualized risk-based approaches and stratifications. A deeper understanding of the genetic mechanisms contributing to individual predisposition to HCC holds the potential to enhance prevention, early diagnosis, and the development of effective treatment strategies for this challenging malignancy.

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