概述非酒精性脂肪肝病與肝癌之關聯

Brief Elucidation for the Relationship between Non Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma

張育霖(Yu-Lin Chang) ； 曹書儀(Shu-Yi Tsao)

《內科學誌》 27卷4期 (2016/08) Pp. 195-201

https://doi.org/10.6314/JIMT.2016.27(4).06

摘要

肝癌是全球性健康議題！經多年慢性B型及C型肝炎防治，肝癌仍為台灣癌症發生率及死因排名第二位，除施行疫苗接種防止B型肝炎、以干擾素或直接抗病毒藥物治療C型肝炎外，也須留意其他致病原因並防治它。近年來有許多文獻闡述非酒精性脂肪肝病(Nonalcoholic fatty liver disease, NAFLD)與肝癌的關聯。全球包括亞州及台灣，非酒精性脂肪肝病隨飲食西方化、缺乏運動而愈來愈普遍，而其相關併發症風險也將提升。非酒精性脂肪肝病包括較輕微的非酒精性脂肪肝及較嚴重，肝有發炎及壞死的非酒精性脂肪肝炎。非酒精性脂肪肝炎在3至7年中有約3至5成風險發展至肝硬化，非酒精性脂肪肝炎併肝硬化者的肝癌發生率為4至27%，但非酒精性脂肪肝病也可能未經肝硬化即發生肝癌。非酒精性脂肪肝病導致肝癌的可能病理機轉包括：一、胰島素抗性使肝內積聚大量脂肪，增加氧化壓力及發炎反應；二、脂肪細胞激素失調使瘦體素增加，脂聯素減少，助長發炎及血管新生；三、類胰島素生長因子-1增加原致癌基因活性；四、腸道菌叢失衡，1.去氧膽酸增加，破壞肝臟星狀細胞的去氧核糖核酸，誘發老化關聯分泌顯型，導致發炎；2.升高腸壁通透性，致內毒素如脂多糖等進入循環，活化肝臟星狀細胞及巨噬細胞的類鐸受體，刺激肝腫瘤成長；五、遺傳因子如PNPLA3基因上的變異與非酒精性脂肪肝病脂質代謝及肝癌發展有關。因應慢性B型肝炎及C型肝炎已見控制曙光而非酒精性脂肪肝病為世界性日趨嚴重課題的時代，我們須重視對非酒精性脂肪肝病的追蹤與控制！

關鍵字

非酒精性脂肪肝病(Non alcoholic fatty liver disease, NAFLD) ； 非酒精性脂肪肝(Non alcoholic fatty liver, NAFL) ； 非酒精性脂肪肝炎(Non alcoholic steatohepatitis, NASH) ； 肝癌(Hepatocellular carcinoma, HCC) ； 代謝症候群(Metabolic syndrome)

並列摘要

Hepatocellular carcinoma(HCC) is a worldwide health issue. Despite control of hepatitis B and hepatitis C for years, HCC is still the second cancer of greatest frequency and the second leading cause of cancer related deaths in Taiwan. Besides vaccination for hepatitis B virus, treating hepatitis C with interferon or direct antiviral agent, we should explore the other cause to induce HCC and to control it. Many literatures elucidate the relationship of nonalcoholic fatty liver disease (NAFLD) and HCC. With more western diet and lack of exercise, NAFLD and its complications become common worldwide include in Asia and in Taiwan. NAFLD ranges from simple nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), a more aggressive form with inflammation and necrosis. About one third to one half of NASH patients exhibited progressive liver fibrosis over 3-7 years. About 4-27% of NASH-related cirrhosis patients progress to HCC over time. Patients with NASH may develop HCC without stage of liver cirrhosis. The potential pathways linking NAFLD to induce HCC include: (1) Insulin resistance induces accumulation of much fat in liver that induces oxygen stress and inflammation reaction. (2) Adipokine imbalance increases leptin and decreases adiponectin that enhances inflammation and angiogenesis. (3) IGF-1 activate proto-oncogens. (4) Dysbiosis in gut: (i) increases deoxycholic acid that damages the DNA of HSC that promotes a senescence-associated secretory phenotype that induces inflammation; (ii) changes gut permeability leading to the influx of LPS which activates TLR of HSC and macrophages, stimulates tumor development. (5) Inherited factors such as the variant of the PNPLA3 gene influencing hepatic lipid metabolism and affected the progress to cancer. At the era hepatitis B and hepatitis C get strategies to control but NAFLD becomes a worse health issue globally, we must pay much attention to the management of NAFLD.