EVALUATION OF THE HEPATIC MICROENVIRONMENT BEFORE AND AFTER ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C

Hepatitis C virus (HCV) infection remains a substantial global health burden, affecting millions annually despite recent therapeutic advances. Direct-acting antiviral (DAA) therapies have transformed clinical management, achieving cure rates exceeding 90% and significantly reducing complications such as hepatocellular carcinoma and mortality. However, challenges persist, including the absence of a vaccine and increasing infection rates associated with intravenous drug use. This study investigated gene and protein expression changes in the hepatic microenvironment of HCV patients before and after DAA treatment. Liver biopsies were analyzed using NanoString nCounter and multispectral imaging to determine gene expression and immune cells phenotypes. Then, the findings were correlated and analyzed with clinical outcomes. Patients achieved sustained virologic response (SVR) post-treatment, with significant reductions in inflammatory activity and liver enzymes, while no change was observed in the fibrosis stage. Gene expression analysis revealed distinct clusters before and after treatment, with upregulation of inflammatory and antiviral pathways pre-treatment and return to levels observed in healthy controls post-treatment. Patients with higher baseline gene expression (pre-hot) showed worse post-treatment outcomes, including cirrhosis and cancer progression, despite SVR. Spatial analyses highlighted shifts in macrophage and T cell populations post-DAA. Comprehending these immune dynamics and histological shifts following DAA therapy is critical yet hindered by the scarcity of post-therapy liver biopsies. Advanced imaging and cellular analysis techniques offer glimpses into alterations within the hepatic microenvironment, but comprehensive studies focusing on DAA-treated, HCV-free livers remain sparse. Addressing these knowledge gaps is essential for optimizing post-treatment care and improving long-term outcomes among individuals with HCV infection.

Name thesis:degree_name

Human Pathophysiology and Translational Medicine (Doctoral)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2024

Author dc:creator

• Millian, Daniel Enrique 1984-

Advisors dc:contributor.advisor

• Saldarriaga, Omar A (omsaldar@utmb.edu)
• Stevenson, Heather L (hlsteven@utmb.edu)

Committee members dc:contributor.committeemember

• Walker, David (dwalker@utmb.edu)
• Kueht, Michael (mlkueht@utmb.edu)
• Yi, Minkyung (miyi@UTMB.EDU)
• Burks,Jared K (jburks@mdanderson.org)

Language dc:language.iso

English

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12812

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12812