Early diagnosis of serious liver pathologies after hepatitis C cure

New combinations of antiviral drugs against the hepatitis C virus (HCV) have revolutionised therapy against chronic hepatitis C, with the eradication of the virus in almost all treated patients. However, the impact that elimination of the infection has on the incidence of development of hepatocellular carcinoma (the most common type of liver cancer) in these patients is unknown, a process that does not appear to be fully reversible despite the cure of HCV infection.

A study led by researchers from the Spanish National Research Council (CSIC) has identified a small number of genes that continue to be abnormally expressed in cells free of infection. These alterations are compatible with those observed in liver biopsies of patients cured of virology and show the value of infection models used to search for markers of liver status in patients after elimination of the infection, something that could facilitate the monitoring of these patients.

In the work, led by CSIC researcher at the National Biotechnology Centre (CNB) Pablo Gastaminza, they used two models of persistent infection in cell cultures to analyse and compare the differences in gene expression after the complete elimination of the viral infection. Gastaminza highlights that, in the new study, “we describe a generalised reversal of the expression of genes related to the infection after its resolution, and how, however, a small number of genes continue to be expressed abnormally in cells that are now free of infection.”

Victoria Castro, a researcher at the CNB (affiliated to the CSIC) and first author of the study, explains the novelty of the work: “The comparison of the results obtained in two types of cell culture models suggests that permanent transcriptional alterations may be established either by phenomena of selection of cell subpopulations with greater competitive capacity, in the case of proliferative cultures, or by a direct impact of viral replication on the regulation of cellular gene expression. In addition, some of the alterations observed in both models are compatible with those observed in liver biopsies of patients who have recovered from chronic infection.”

Furthermore, the researcher continues, “these infection models could provide relevant information for finding markers of post-healing liver status, which could facilitate the follow-up of these patients, who are not exempt from the risk of developing hepatocellular carcinoma. On the other hand, these data provide a new perspective on the direct contribution of viral replication in the development of hepatocellular carcinoma.”

Cell lines infected with the hepatitis C virus marked in green (left), and after the infection has been cured (right). (Photos: CNB)

This work is the result of collaboration between researchers from the Biomedical Research Network Center for Liver and Digestive Diseases (CIBEREHD) Pablo Gastaminza at the CNB and Sofía Pérez-del-Pulgar at IDIBAPS in Barcelona, ​​together with the Bioinformatics Unit for Genomics and Proteomics of the CNB.

The study is titled “Hepatitis C Virus-induced Differential Transcriptional Traits in Host Cells After Persistent Infection Elimination by Direct-Acting Antivirals in Cell Culture.” It has been published in the academic journal Journal of Medical Virology. (Source: CSIC)