分析B型肝炎帶原者體內代謝小分子與肥胖相關肝臟疾病間關係：前瞻研究

Abstract

背景：非酒精性脂肪肝病是指在沒有過度飲酒的情況下，肝臟內過多脂肪囤積的ㄧ種現象。近十年間，非酒精性脂肪肝病廣泛且快速的影響到全球人類。其中造成非酒精性脂肪肝病的主要危險因子包括糖尿病與肥胖。本研究的目的是透過代謝體學去探討人體內代謝小分子在B型肝炎帶原者身上，在與肥胖相關肝癌發展中所扮演的角色為何。 材料方法：本研究針對711名過重和肥胖的B型肝炎帶原者，研究在進入世代研究時人體內代謝小分子與肥胖相關肝癌發展中及肝生化指標之間的相關性。 結果：使用PLS-DA模型，從22個辨識出來的代謝小分子中，找出區分有無非酒精性脂肪肝病及肝生化指標之重要因子，並且挑出12個區分三酸甘油脂是否異常增加的重要代謝小分子，評估三酸甘油脂異常增加、脂肪肝與肝硬化之風險。控制年齡、吸菸與喝酒習慣與追蹤之肝生化指標後，有4個個高度表現代謝小分子，包括丙酮、低密度脂蛋白與極低密度脂蛋白和不飽和脂肪，與脂肪肝達統計上顯著正相關，但卻與肝硬化呈現顯著負相關；而低度表現的8個代謝小分子，包括檸檬酸、肌酸、beta葡萄糖、麩醯胺酸、甲醇、脯氨酸、酪氨酸和纈氨酸，與脂肪肝達統計上顯著負相關，但卻與肝硬化呈現顯著正相關。而這12個代謝小分子與肝癌都沒有達統計上顯著相關。 結論：本研究初步的結果顯示代謝小分子和三酸甘油脂異常增加與肥胖相關肝臟疾病之間的關聯。但是這些代謝小分子和肥胖相關肝臟疾病之間的關係並不一致。

Background: Nonalcoholic fatty liver disease (NAFLD) occurs due to excessive fat accumulation in the liver cells, which is becoming an increasingly common cause of hepatic disease. Obesity and related metabolic syndrome increase the risk of NAFLD. The purpose of this study was to understand the mechanisms underlying the relationship between abnormal metabolism and obesity-related liver diseases in hepatitis B, with the use of metabolomics approach. Materials and methods: Study subjects included a total of 711 overweight or obese men with hepatitis B, who were recruited from a cohort study of civil servants. Information on demographics, lifestyle habits, and medical history was obtained from a structured questionnaire. Metabolomics profiles of baseline serum samples were deter-mined using 1H nuclear magnetic resonance (NMR)-based metabolomics assay. Partial least squares discriminant analysis (PLS-DA) was applied to analyze the profiling data to identify the distinguishing metabolites of dyslipidemia and liver biochemical and ultrasonographic abnormalities as well as hepatocellular carcinoma. Results: A total of 22 metabolites was identified, 12 of which were important for classification of triglycerides (TG) abnormality, including 4 that were up-regulated and 8 that were down-regulated in participants with TG abnormality. The up-regulation of 4 metabolites, including acetone, VLDL/LDL (CH3-(CH2)n), VLDL/LDL (CH3-(CH2)n) and unsaturated lipid, tend to be positively associated with fatty liver but were significantly, inversely associated with liver cirrhosis. The down-regulation of 8 metabolites, including citrate, creatine, beta-glucose, glutamine, methanol, proline, tyrosine and valine, tend to be inversely associated with fatty liver but significantly, positively associated with liver cirrhosis. On the other hand, none of these 12 metabolites were significantly associated with hepatocellular carcinoma. Conclusion: Our preliminary results showed an association between elevated TG and an altered metabolite signature. The altered metabolites in relation to TG abnormality revealed no consistent patterns in any type of liver abnormalities.