File Download
Supplementary
-
Citations:
- Appears in Collections:
postgraduate thesis: Non-invasive assessment of liver outcomes in chronic hepatitis B infection
Title | Non-invasive assessment of liver outcomes in chronic hepatitis B infection |
---|---|
Authors | |
Issue Date | 2021 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Mak, L. L. Y. [麥龍兒]. (2021). Non-invasive assessment of liver outcomes in chronic hepatitis B infection. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Liver fibrosis is one of the most important predictors of outcome in patients
with chronic liver diseases. However, the “gold” standard of liver biopsy is invasive
and not widely accepted by patients, highlighting the need for non-invasive methods.
In this thesis, a series of studies were performed to demonstrate how non-invasive
fibrosis- and viral transcription- markers could be utilized in risk stratification in
patients with chronic hepatitis B infection (CHB), focusing on 3 important aspects.
These include liver fibrosis, antiviral therapy, and the development of hepatocellular
carcinoma (HCC).
In the first few chapters, serum fibrosis markers, such as Mac-2 binding protein
glycosylation isomer (M2BPGi), was shown to correlate well with liver fibrosis using
histological stage as the comparison. The correlation between serum fibrosis markers
and ultrasound-based fibrosis assessment (i.e. transient elastography) was
demonstrated and the strategy of combination non-invasive assessments of liver
fibrosis was explored. Liver fibrosis was shown to change dynamically with time. Risk
factors for fibrosis progression or lack of fibrosis regression in CHB patients were
identified, including hepatic steatosis, central obesity and metabolic syndrome, whereas
hepatitis B surface antigen (HBsAg) seroclearance and antiviral therapy were favorable
factors for fibrosis regression. The interaction between hepatic steatosis and liver
fibrosis was further evaluated. While hepatic steatosis, as assessed by controlled
attenuation parameter (CAP) via transient elastography, was associated with higher
chance of HBsAg seroclearance, severe steatosis was a risk factor for advanced fibrosis,
and insulin resistance and adipokines likely play a role in causing hepatic fibrosis in
patients with concomitant CHB and non-alcoholic fatty liver disease.
In the next few chapters, the effect and outcome of antiviral therapy on novel
HBV-related serum biomarkers, including hepatitis B core-related antigen (HBcrAg)
and HBV RNA, were elucidated. Both HBcrAg and HBV RNA are surrogate markers
for viral transcriptional activity. The kinetics of serum HBcrAg and HBV RNA during
nucleos(t)ide analogue (NA) therapy was described. There were no differences in
potencies of individual NA in reduction of serum HBcrAg. As HBV RNA was
persistently detected despite potent NA, the role of HBV RNA in predicting successful
NA cessation was explored and confirmed that treatment should not be discontinued in
patients with any detectable serum HBV RNA.
Finally, the role of different non-invasive fibrosis markers and viral
transcriptional markers in prediction of hepatocellular carcinoma (HCC) in CHB
patients was explored. Serum M2BPGi and HBcrAg were shown to be independently
associated with HCC development in CHB patients, and specific cut-off levels were
derived. Residual detectable viral nucleic acids in the serum were shown to be
associated with higher risk of HCC. The protective effect of hepatic steatosis on HCC
development was interrogated in the final chapter.
This series of studies demonstrate how non-invasive liver fibrosis- and viral
transcription- markers could be utilized in risk stratification in CHB patients for
outcome prediction and assessment in the natural history, those on antiviral therapy,
and also for HCC development.
|
Degree | Doctor of Medicine |
Subject | Hepatitis B - Diagnosis Diagnosis, Noninvasive |
Dept/Program | Medicine |
Persistent Identifier | http://hdl.handle.net/10722/309683 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mak, Loey Lung Yi | - |
dc.contributor.author | 麥龍兒 | - |
dc.date.accessioned | 2022-01-05T14:57:22Z | - |
dc.date.available | 2022-01-05T14:57:22Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Mak, L. L. Y. [麥龍兒]. (2021). Non-invasive assessment of liver outcomes in chronic hepatitis B infection. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/309683 | - |
dc.description.abstract | Liver fibrosis is one of the most important predictors of outcome in patients with chronic liver diseases. However, the “gold” standard of liver biopsy is invasive and not widely accepted by patients, highlighting the need for non-invasive methods. In this thesis, a series of studies were performed to demonstrate how non-invasive fibrosis- and viral transcription- markers could be utilized in risk stratification in patients with chronic hepatitis B infection (CHB), focusing on 3 important aspects. These include liver fibrosis, antiviral therapy, and the development of hepatocellular carcinoma (HCC). In the first few chapters, serum fibrosis markers, such as Mac-2 binding protein glycosylation isomer (M2BPGi), was shown to correlate well with liver fibrosis using histological stage as the comparison. The correlation between serum fibrosis markers and ultrasound-based fibrosis assessment (i.e. transient elastography) was demonstrated and the strategy of combination non-invasive assessments of liver fibrosis was explored. Liver fibrosis was shown to change dynamically with time. Risk factors for fibrosis progression or lack of fibrosis regression in CHB patients were identified, including hepatic steatosis, central obesity and metabolic syndrome, whereas hepatitis B surface antigen (HBsAg) seroclearance and antiviral therapy were favorable factors for fibrosis regression. The interaction between hepatic steatosis and liver fibrosis was further evaluated. While hepatic steatosis, as assessed by controlled attenuation parameter (CAP) via transient elastography, was associated with higher chance of HBsAg seroclearance, severe steatosis was a risk factor for advanced fibrosis, and insulin resistance and adipokines likely play a role in causing hepatic fibrosis in patients with concomitant CHB and non-alcoholic fatty liver disease. In the next few chapters, the effect and outcome of antiviral therapy on novel HBV-related serum biomarkers, including hepatitis B core-related antigen (HBcrAg) and HBV RNA, were elucidated. Both HBcrAg and HBV RNA are surrogate markers for viral transcriptional activity. The kinetics of serum HBcrAg and HBV RNA during nucleos(t)ide analogue (NA) therapy was described. There were no differences in potencies of individual NA in reduction of serum HBcrAg. As HBV RNA was persistently detected despite potent NA, the role of HBV RNA in predicting successful NA cessation was explored and confirmed that treatment should not be discontinued in patients with any detectable serum HBV RNA. Finally, the role of different non-invasive fibrosis markers and viral transcriptional markers in prediction of hepatocellular carcinoma (HCC) in CHB patients was explored. Serum M2BPGi and HBcrAg were shown to be independently associated with HCC development in CHB patients, and specific cut-off levels were derived. Residual detectable viral nucleic acids in the serum were shown to be associated with higher risk of HCC. The protective effect of hepatic steatosis on HCC development was interrogated in the final chapter. This series of studies demonstrate how non-invasive liver fibrosis- and viral transcription- markers could be utilized in risk stratification in CHB patients for outcome prediction and assessment in the natural history, those on antiviral therapy, and also for HCC development. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Hepatitis B - Diagnosis | - |
dc.subject.lcsh | Diagnosis, Noninvasive | - |
dc.title | Non-invasive assessment of liver outcomes in chronic hepatitis B infection | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Doctor of Medicine | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Medicine | - |
dc.description.nature | published_or_final_version | - |
dc.date.hkucongregation | 2021 | - |
dc.identifier.mmsid | 991044446453103414 | - |