血液
adiponectin 值可以當作肥胖者合併非酒精性脂肪性肝炎嚴重
程度及預後的指標
The Plasma Adiponectin Levels as a Marker of the Severity
and
Prognosis for the Obese Patients with Non-alcoholic
Steatohepatitis
中文摘要
肥胖是造成非酒精性脂肪性肝炎 (NASH, nonalcoholic steatohepatitis) 的
主要原因之一 。非酒精性脂肪性肝炎的臨床症狀，可由無症狀到嚴重的肝硬化
都有；目前肝臟切片是評估肝臟的發炎及纖維化程度的主要方法。
Adiponectin
是由脂肪細胞分泌的細胞激素，血液中
adiponectin 值和體內的脂肪含量多寡
成反比的情形，並且影響肝細胞內脂肪的含量和葡萄糖糖質新生的功能。
Tumor
necrosis factor-α(TNF-α) 和其基因表現在脂肪肝和 NASH 的病理機轉中佔
有重要的角色，TNF-α對肝細胞造成程度不一的發炎，可導致脂肪肝或是
NASH；如果 TNF-α的基因表現出現 polymorphism 也會引發肝細胞發炎。
本研究的目的在分析血液
adiponectin 值與肥胖者合併非酒精性脂肪性肝炎的
嚴重度之關係，以及是否可以作為非酒精性脂肪性肝炎的預後評估指標；另外也
分析台灣脂肪肝和
NASH 病人是否也有 TNF-α polymorphism 的情形以及是
否也會影響疾病的病理生理的變化。研究設計乃收集北部某醫學中心之減重門診
的成年病人，分析其血液
adiponectin 值與（1）血液 alanine
aminotransferase 和 aspartate aminotransferase 值，（2）肝臟超音波的
變化，
（3）肝臟切片的病理分級的相關性。另外也收集 22 名的病人血液，以聚
合?連鎖反應 (Polymerase Chain Reaction, PCR) 和 sequence 來偵測病
人的
TNF-α polymorphism 表現，以及與臨床症狀和血液 adiponectin 值的
比較。
研究顯示在肥胖合併脂肪肝和 NASH 的病人中，（1）血液 adiponectin
值與病人的
BMI 和體脂肪呈現負相關的關係，（2）血液 adiponectin 值與
alanine aminotransferase，aspartate aminotransferase 值無顯著之關
係，但和
alanine aminotransferase 與 aspartate aminotransferase 之比
值有關，
（3）血液 adiponectin 值和肝臟超音波的變化有相關性，（4）台灣的
脂肪肝和
NASH 的病人也有 α polymorphism 的情形；並且出現
TNF-α polymorphism 的病人，其肝細胞損傷較嚴重，血液 adiponectin 值較低。
本研究的結果得知：在評估肥胖合併脂肪肝和
NASH 的病人的肝炎的嚴重度以
及預後，血液
adiponectin
值可以當做獨立的指標。在基因的變異因子中，TNF-α polymorphism 則與病人的肝炎嚴重度的指標有關。我們的研究確認了
adiponectin 與 TNF-α polymorphism 是影響肥胖合併脂肪肝和 NASH 病人
其疾病病程的因素，但是在肝細胞中
adiponectin 與 TNF-α和 TNF-α
polymorphism 之間的相互關係，仍需進一步之細胞、動物及大型的臨床實驗
來證明。
英文摘要
Obesity is one of major causes of nonalcoholic steatohepatitis (NASH). NASH may progress to cirrhosis without marked clinical symptoms or signs. Liver histology is the important method to evaluate the degree of hepatic steatosis and fibrosis. Adiponectin is a cytokine which is secreted from adipocytes, plasma adiponectin concentration is negatively correlated with body fat mass. Adiponectin has the effect on the hepatic fat volume and hepatic gluconeogenesis. Tumor necrosis factor-α(TNF-α) and its gene expression play an important role in the pathogenesis of steatosis and NASH. TNF-α may induce varied degree of steatosis and NASH. The occurrence of gene expression of TNF-α polymorphism may also induce steatosis and NASH. The aim of the study is to investigate the role of plasma adiponectin concentration on the severity of NASH in obese subjects, the prognosis predictor in NASH; the role of TNF-α polymorphism of steatosis and NASH in Taiwan, and the effects of TNF-α polymorphism expression on the pathogenesis of the disease. We have examined obese adults in a medical center in north Taiwan, measured and evaluated the relationship between fasting plasma adiponectin concentrations, fasting plasma alanine aminotransferase and aspastate aminotransferase concentration, the change of abdominal sonography and the degree of liver histology. We studied the clinical features, plasma adiponectin concentrations and TNF-α polymorphism in 22 subjects. The TNF-α polymorphism was studied using a PCR method and a sequence. The results have shown : (1) plasma adiponectin concentration is negatively correlated with body mass index (BMI) and body fat mass, (2) the relationship between plasma adiponectin concentration and alanine aminotransferase and aspartate aminotransferase was not significant, but
significantly related to the ratio of alanine aminotransferase and aspartate
aminotransferase, (3) plasma adiponectin concentration is related to the degree of fatty change by sonography, (4) TNF-α polymorphism is found in patients having steatosis and NASH in Taiwan. The gene expression of TNF-α polymorphisms is found in those with severe hepatic damage and lower plasma adiponectin
concentration. We have concluded: plasma adiponectin concentration may be one independent predictor for evaluation of the severity and prognosis of steatosis and NASH in obese patients. In gene expression, TNF-α polymorphism is related to the predictor of severity of the disease. Our limited results have confirmed adiponectin and TNF-α polymorphism may play a role in the progression of NASH in obese patients, but the relationship need further studies.
