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| Project Details |
| Funding Scheme : | General Research Fund | ||||||||||||||||
| Project Number : | 17125916 | ||||||||||||||||
| Project Title(English) : | Metabolic determinants of fibrosis reversal in advanced chronic hepatitis B during long-term nucleoside analogue therapy | ||||||||||||||||
| Project Title(Chinese) : | 慢性乙肝服藥期間肝纖維化逆轉率及相關代謝因素 | ||||||||||||||||
| Principal Investigator(English) : | Prof Seto, Wai Kay Walter | ||||||||||||||||
| Principal Investigator(Chinese) : | |||||||||||||||||
| Department : | Department of Medicine | ||||||||||||||||
| Institution : | The University of Hong Kong | ||||||||||||||||
| E-mail Address : | wkseto@hku.hk | ||||||||||||||||
| Tel : | |||||||||||||||||
| Co - Investigator(s) : |
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| Panel : | Biology & Medicine | ||||||||||||||||
| Subject Area : | Medicine, Dentistry & Health | ||||||||||||||||
| Exercise Year : | 2016 / 17 | ||||||||||||||||
| Fund Approved : | 768,228 | ||||||||||||||||
| Project Status : | Completed | ||||||||||||||||
| Completion Date : | 30-9-2019 | ||||||||||||||||
| Project Objectives : |
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| Abstract as per original application (English/Chinese): |
肝硬化現在是已發展國家中第二常見的消化系統疾病相關死亡原因。肝硬化及它的前身肝纖維化會增加門靜脈高壓相關的並發症和肝癌風險。在香港和亞太地區，慢性乙型肝炎是引致嚴重肝病的首要原因。 抗乙肝病毒藥是可以成功有效控制病毒複製,但並非每個乙肝病人會有肝纖維化逆轉.有初步臨床證據顯示肥胖及其他代謝因素會影響纖維化逆轉，但這在亞太乙肝病群中未經證實。 我們提出了一個前瞻性觀察研究，調查代謝因素如何影響乙肝服藥期間肝纖維化逆轉。利用無創肝纖維化檢查(一種非侵入性超聲技術)，我們會調查乙肝服藥期間肝纖維化逆轉率，也會評估不同代謝因素對肝纖維化逆轉的影響。這些代謝因素包括臨床因素，如體重指數, 代謝綜合徵, 及反映脂肪肝嚴重性的控制衰減參數。也包括實驗室的標誌物，如胰島素抵抗（HOMA-IR）及不同血清脂肪因子。透過3年期的前瞻性跟進，我們將確定代謝因素是否影響肝纖維化逆轉率。 這研究將提供寶貴的臨床數據及可以透過代謝因素的控制優化慢性乙肝的治療，減少肝硬化相關的並發症和肝癌。 |
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| Realisation of objectives: | As from our published article Mak LY et al. Liver International 2019, we were able to achieve the primary objectives. We determined the association of different metabolic parameters with persistent fibrosis or lack of fibrosis reversal, including body mass index, diabetes mellitus, and also a high serum adipocyte fatty acid-binding protein (AFABP) and low serum fibroblast growth factor 21 (FGF21). Hepatic steatosis as determined by controlled attenuation parameter (CAP) measurements via transient elastography was not a significant factor. Via multivariate analysis, we determined the odds ratio and 95% confidence intervals of body mass index, diabetes mellitus, serum AFABP and serum FGF21, demonstrating the relatives strengths of association. We also determined a synergistic effect of different factors: With a high body mass index, presence of diabetes and a high AFABP, the odds ratio of persistent fibrosis (lack of fibrosis reversal) was 3.712 (95%CI 1.36-38.1). From our cohort of 415 patients, after a median nucleoside analogue treatment duration of 6.2 years, 264 (63.6%) no longer had severe fibrosis / cirrhosis, while persistent severe fibrosis / cirrhosis was still noted in 151 (36.4%) of patients. We have hence achieved the various study objectives of this project. | ||||||||||||||||
| Summary of objectives addressed: |
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| Research Outcome | |||||||||||||||||
| Major findings and research outcome: | Concerning major findings, a total of 415 patients [mean age 59.6 years, 71.6% male, median treatment duration 6.2 years] were recruited. Patients with F3/F4 (N = 151) had lower FGF‐21 (11.7 vs 13.6 pg/mL, P = 0.055), higher AFABP (126.8 vs 84.1 pg/mL, P < 0.001) and HOMA‐IR (7.1 vs 5.1, P = 0.004) levels compared to those without F3/F4 (N = 264). Multivariate analysis showed that FGF‐21 level was associated with hepatic steatosis (OR 1.005, 95% CI 1.001‐1.009) and F3/F4 (OR 0.993, 95% CI 0.989‐0.998), while AFABP level (OR 1.001, 95% CI 1‐1.002), body mass index (BMI) (OR 1.107, 95% CI 1.037‐1.182) and presence of diabetes mellitus (OR 2.059, 95% CI 1.206‐3.516) were associated with F3/F4. With the combined presence of BMI ≥ 25 kg/m2, diabetes and AFABP > 105.9 pg/mL, the odds ratio for F3/F4 was 3.712 (95% CI 1.364‐10.105, P = 0.010). To conclude, a low FGF‐21 and high AFABP levels were associated with advanced fibrosis/ cirrhosis in CHB patients on antiviral treatment. Plasma AFABP, together with other metabolic risk factors, may aid identification of patients lacking fibrosis improvement during nucleoside analogue therapy. | ||||||||||||||||
| Potential for further development of the research and the proposed course of action: |
Serum AFABP elevation can be secondary to incrased hepatic production of AFABP by Kupffer cells, leading to a heightened inflammatory response and fibrosis in the liver. Low FGF21 can be secondary to reduce synthetic function of the liver in advanced fibrosis and cirrhosis. These hypothesis will need confirmation in mechanistic studies involving models combining HBV infection with non-alcoholic fatty liver disease. | ||||||||||||||||
| Layman's Summary of Completion Report: | Blood markers reflective of the body's metabolism play a role in the treatment response of chronic hepatitis B. The study demonstrates that it is not only virus-related factors that determine treatment response; host-related metabolic factors can also influence treatment outcomes. | ||||||||||||||||
| Research Output | |||||||||||||||||
| Peer-reviewed journal publication(s) arising directly from this research project : (* denotes the corresponding author) |
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| Recognized international conference(s) in which paper(s) related to this research project was/were delivered : |
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| Other impact (e.g. award of patents or prizes, collaboration with other research institutions, technology transfer, etc.): |
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| SCREEN ID: SCRRM00542 |