脂肪肝治疗专业医学知识宣讲讲义.ppt

脂肪肝治疗专业医学知识宣讲,Wang Bing Yuan(,王炳元,),Department of Geriatric Gastroenterology,The First Hospital of China Medical University,Shenyang,CHINA,（,中国医科大学附属第一医院老年消化科,沈阳，中国,）,wangby,脂肪肝诊治进展,什么是脂肪肝？,肝细胞内脂质积聚超过,肝湿重,的,5%,称之脂肪肝。,正常人肝脏内脂质含量占肝湿重的,2%,4%,，其中,2/3,为磷脂，此外尚有胆固醇、中性脂肪，主要是构成细胞膜及其他细胞器的膜。,大多数脂肪肝属于三酰甘油含量异常增高，根据脂肪含量，可将脂肪肝分为轻型,(,含脂肪,5%,10%),，中型,(,含脂肪,10%,25%),，重型,(,含脂肪,25%,50%,或,30%),三型。,病理切片,：,每个视野下脂肪变的细胞,33%,称为脂肪肝,33%-67%,中度脂肪肝；,67%,重度脂肪肝,中国脂肪肝有何特点？,Prevalence of non-alcoholic fatty liver disease in various high-risk groups compared with the general adult population.,Digestive and Liver Disease 47(2015)9971006,导致脂肪肝的原因和危害因素？,脂肪肝分几大类？,非酒精性脂肪性肝病,（即脂肪肝）是如何发生的？,Figure 1:Overlap in Pathogenesis in NAFLD and ALD,Hepatology.2017 Jan 18.,Multiple hit,In the first hit,there is an accumulation of triglyceride as lipid droplets within the cytoplasm of hepatocytes(steatosis)in more than 5%of hepatocytes.Insulin resistance contributes to this hepatic steatosis.,This phase of benign hepatic steatosis is reversible and can be self-limited but makes the liver susceptible to the second hit which advances the liver to a necroinflammatory stage,i.e.,NASH.,Multiple hit,The second hit includes oxidative stress(free radical formation due to excessive fatty acid oxidation),cardiolipin(present on inner mitochondrial membrane)peroxidation leading to mitochondrial dysfunction and more reactive oxygen species formation,pro-inflammatory cytokine formation,apoptosis and gut-derived bacterial endotoxinemia.,Multiple hit,The third hit includes palatine-like phospholipase 3(PNPLA3)gene involvement,and impaired hepatocyte regeneration.,Certain single nucleotide polymorphisms(SNPs)have been found to be associated with higher frequency,severe histologic changes and more progression of NAFLD.,Variant SNPs in PZP and PNPLA3 genes were found to be independent risk factors for the development of NAFLD.,Hence genetics play an important role along with metabolic factors in the development of NAFLD.,A total of 7 observational studies met criteria for inclusion(one for cardiovascular endpoints and 6 forliverendpoints).,There was a positive association between moderate alcohol use and decreased NASH and fibrosis,however heavy episodic drinking may accelerate fibrosis progression and in patients with advanced fibrosis moderate alcohol use may increase the risk of hepatocellular carcinoma.,Hepatology.2017 Jan 18.,酒精对脂肪肝的影响,脂肪肝的结局,Progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)with or without fibrosis,cirrhosis,and hepatocellular carcinoma.,J.Hepatol.2015;62:11481155.Hepatol.2015;13:643654.,脂肪肝的必要检查,人体学,血压、脉搏、呼吸、身高、体重、腰围、臀围,病史：年龄性别、文化程度、职业；饮酒史、肥胖史、疾病史、用药史；饮食结构、运动方式,和程度,化验检查：肝功能、血脂、血常规、尿常规、尿酸、病毒学、胰岛功能、血糖（,0,和,120min,）、肾功能,Simple steatosis NASH cirrhosis.NASH classification:,type 1:Simple steatosis;,type 2:steatosis+inflammation(lobular and portal)NASH;type 3:steatosis+ballooned hepatocytes NASH;,type 4:steatosis+fibrosis NASH.,CT,MRI,MRS,DSA,B,超,HRPRIORITIES,安全、准确、,标准量化、无创？,影像检查,影像检查,脂肪肝的对策,2.,药物治疗策略,抗炎,保肝药物的分类,分类,作用机制,抗炎类,抗炎：抗抑制炎症因子、免疫性因子；免疫调节：刺激单核,-,巨噬细胞系统、诱生,-,干扰素，增强,NK,细胞活性；可抗过敏、抑制钙离子内流,代表药物异甘草酸镁注射液（天晴甘美）、天晴甘平、其它甘草制剂、双环醇,修复肝细胞膜类,与肝细胞膜及细胞器膜相结合，增加膜的完整性、稳定性和流动性，使受损肝功能和酶活性恢复正常，调节肝脏的能量代谢，促进肝细胞再生,代表药物多烯磷脂酰胆碱,解毒类,参与体内三羧酸循环及糖代谢，激活多种酶，促进糖、脂肪及蛋白质代谢，减轻组织损伤，促进修复,代表药物为,GSH,（还原型谷胱甘肽）、硫普罗宁,抗氧化类,抗脂质过氧化，增强肝细胞膜对多种损伤因素的抵抗力,代表药物为水飞蓟素类,利胆类,促进胆汁酸转运，达到退黄，降酶的作用,代表药物为,熊去氧胆酸（,UDCA,）,、,S-,腺苷蛋氨酸,.,王宇明,.,抗炎保肝药物的作用机制及地位,.,中华肝脏病杂志,2011,19(1):76-77.,继续巩固治疗,6-12,个月,药物,治疗,的,疗程,总结,脂肪肝已经成为我国第一大肝病,必须了解和重视脂肪肝的危害,要认真进行脂肪肝的检查,充分利用脂肪肝无创检查的手段,加强患者的健康指导和彻底治疗,Thank You!,脂肪肝诊治进展,王炳元 中国医科大学附属第一医院老年消化科,wangby,