Novel insights in the management and immunopathology of Chronic Hepatitis B infections

Datum: 22 oktober 2020

Locatie: Online - - - - -

Tijdstip: 17.30 - 19.30 uur

Promovendus: Stijn Van Hees

Promotor: Prof. T. Vanwolleghem, prof. S. Francque & prof. K. Laukens

Korte beschrijving: PhD defence Stijn Van Hees - Faculty of Medicine and Health Sciences



Abstract

Chronic Hepatitis B is a chronic infection of the liver caused by the non-cytopathic Hepatitis B Virus. Currently, oral treatment consists of Nucleos(t)ide Analogues which efficiently suppress, though fail to eradicate the virus. As a consequence, life-long treatment is often indicated.

In a first part of this thesis, we evaluated the consequences of treatment cessation in a subpopulation of chronic hepatitis B patients after long-term medication-induced viral suppression. The first study of this part focused on viral rebound and clinical outcomes of patients who stopped treatment before they achieved functional cure. We found clinically significant viral rebound rates in two-thirds of the patients 6 years after treatment cessation. Additionally, two liver-related deaths were reported among the patients who stopped treatment.  In a second study of part 1 we investigated functional cure rates in patients who stopped treatment. Importantly, we found that all patients with functional cure after treatment cessation showed a sustained suppression of the virus after treatment cessation. These data thus suggest a predominant non-cytolytic clearance of the Hepatitis B Virus.  In a third chapter of part 1 we compared functional cure rates in patients who stopped treatment versus patients who continued treatment. We found Caucasian ethnicity, but not treatment cessation, to be associated with functional cure.

The data presented in the first three chapters of this thesis favor treatment continuation until functional cure is achieved. At the beginning of this PhD the durability of functional cure had, however, not been well investigated. Therefore, in the fourth study of the first part, we investigated the durability of functional cure. We did not observe any clinically significant relapses, indicating that functional cure is a good endpoint.

The long-term outcome of a chronic hepatitis B (CHB) infection largely depends on the clinical phenotype, but little is known on the underlying immunological mechanisms. Therefore, in part 2 of this thesis, we studied B cells during the natural history of a Chronic Hepatitis infection. B cell transcriptomes associated with the clinical phenotype of a CHB infection. In addition, we highlight important differences between peripheral and intrahepatic B cells.

In part 3 of this thesis we focused on Hepatocellular Carcinoma, a common long-term complication of Chronic Hepatitis infections. We first give an overview on circulating diagnostic and predictive biomarkers for Hepatitis B-associated Hepatocellular Carcinoma and then describe the challenges associated with the initiation of a Hepatocellular Carcinoma surveillance program in Uganda.



Link: http://www.uantwerpen.be/en/about-uantwerp/faculties/faculty-medicine-health-sciences/