Hepatocellular Carcinoma Prevention in the Era of Hepatitis C Elimination

Abstract

The hepatitis C virus (HCV), a single-stranded RNA virus belonging to the Flaviviridae family, is a major cause of hepatocellular carcinoma (HCC) worldwide. Tumors caused by HCC have an increased mortality rate globally, which is more accentuated in Western countries. The carcinogenic potential of this virus is mediated through a wide range of mechanisms, spanning from the induction of chronic inflammation to oxidative stress and deregulation of cellular pathways by viral proteins. As the number of new infections continues unabated, HCC-related mortality should be prioritized through early detection, continued prevention of HCV transmission, and treatment of HCV with safe and efficacious direct antiviral agents (DAAs). People who inject drugs (PWID) are a significant reservoir of new HCV infections globally, and in order to eliminate hepatitis C as a global health threat, as set out by the World Health Organization, an integrated approach based on the optimization of care delivery and increased access to harm reduction and treatment for PWID is needed. Thanks to the development of safe and effective antiviral agents, eradication of the infection is now possible in almost all treated patients, leading to a significant reduction but not the elimination of the risk for HCC in cured patients. This is particularly relevant among aged populations who have cofactors of morbidity known to accelerate HCC progression, such as diabetes, obesity, and excessive alcohol consumption. Given the restless accumulation of individuals with cured HCV infection, the implementation of risk-stratified surveillance programs becomes impellent from a cost-effectiveness perspective, whereas the availability of a performant biomarker to predict HCC in cured patients remains an unmet clinical need.

Inequities in primary liver cancer in Europe: The state of play

“…In patients with chronic HCV infection, a 70% reduction in the liver cancer incidence risk was reported after a sustained virologic response by the DAA therapy [48]. The significant reduction but not the elimination of the risk for HCC in HCV cured patients is particularly J o u r n a l P r e -p r o o f relevant among aged populations who have cofactors of morbidity known to accelerate HCC progression, such as diabetes, obesity, and excessive alcohol consumption [49].…”

“…Insufficient health infrastructure, harm reduction programs, and low awareness about HCV infection hamper HCV screening, diagnosis, and treatment in PWID in almost all European countries. An integrated approach based on the optimization of care delivery and increased access to harm reduction and treatment for PWID is needed [34, 49,50,52,53].…”

Insights into the Management of Chronic Hepatitis in Children—From Oxidative Stress to Antioxidant Therapy

“…HCV, which belongs to the Flaviviridae family, is the etiologic agent of worldwide viral hepatitis, causing hepatocyte inflammation, fibrosis, cancer, and, ultimately, liver failure [15]. Since this condition is typically asymptomatic, enhanced screening procedures such as ELISA and the more accurate HCV-RNA PCR have been used for early diagnosis [16].…”

A Comprehensive Review of the Vascular Consequences of Diabetes in the Lower Extremities: Current Approaches to Management and Evaluation of Clinical Outcomes

“…Research should focus on non-invasive, cost-effective methods to identify complications at their onset. This could involve advanced imaging techniques, such as ultrasound MRI, or even developing innovative wearable devices that monitor vascular health in real-time [78].…”