Universität Tübingen
Hepatitis E virus superinfection and human SOCS3 and ISG15 in hepatitis B virus-related liver diseases
Abstract
Although the introduction of the Hepatitis B virus (HBV) vaccine has significantly reduced mortality and morbidity in many parts of the world, few pockets of high endemicity still remains in South-East Asia and in Sub-Saharan Africa. Despite, Vietnam initiated universal immunization for hepatitis B for infants in 2003, the rates of chronically infected patients with hepatitis B remains high with an estimated prevalence of >10%. The clinical course of HBV infection is influenced by both host and viral factors. In this thesis, I utilized a cohort of patients well characterized for clinical HBV infections, including acute and chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma. In chapter one of my thesis, I investigated 1318 Vietnamese HBV patients to elucidate if superinfection by other hepatitis viruses exists in this study population. In particular, I studied the HEV seroprevalences in patients with HBV and characterized specific HEV isolates at the molecular level to understand the consequences of HEV superinfections on the clinical course of HBV infections. This study showed that HEV may aggravate the clinical outcome of HBV infection. In chapter two of my thesis, I studied the contribution of negative regulator suppressor of cytokine signaling-3 (SOCS3) promoter variants in HBV disease. I genotyped 878 HBV patients and 272 healthy controls for SOCS3 promoter variants. SOCS3 promoter hyper methylation in HBV tumor tissues was examined by bisulfite sequencing and mRNA expression was quantified in tumor and non-tumor tissues. The results revealed that SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development. Additionally in chapter 2, investigations were carried out to associate Interferonstimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels, and relative mRNA expression with HBV-related liver diseases. ISG15 exon2 variant rs1921 was associated with HBV susceptibility. ISG15 serum levels were higher among HBV patients and were positively correlated with HBV-DNA loads. ISG15 mRNA expression was increased in HBV patients. The results reveal that ISG15 appears to be a proviral factor involved in HBV replication and triggers the progression of HBVrelated liver diseases. Taken together, this dissertation serves as a basis to understand the association of host and viral factors with HBV susceptibility and subsequent clinical outcomes of HBV related liver diseases.
Author and committee
dc:creator, dc:contributor.*- Author
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- Nghiem, Xuan Hoan
Identifiers
dc:identifier.*- Identifier
- hdl:10900/79498