终末期肝病的预后模式

几十年来,人们已建立了许多预后模式用于评估肝硬化和各类不同的慢性肝炎。其中,CTP(Child-Turcotte-Pugh)分级与终未期肝病的预后模式(model for end-stage liver disease,MELD)积分最为著名。终末期肝病预后的评估,对选择一些特殊治疗如肝移植等尤为重要。     

终末期肝病病情预测评分系统介绍

随着近年来肝移植和介入手术等治疗方法的不断出现,真实、准确、客观地评价终末期肝病患者病情或肝脏储备功能为临床医生选择适合不同个体的治疗方案提供了有力的帮助。应用40余年的Child—Turcotte—Pugh（CTP）分级在对终末期肝病患者病情判断方面已显示出其局限性。终末期肝病模型（model for end—stage liver disease,MELD）分级是近年来新创立的判断晚期肝病患者肝脏储备功能或病情的方法,其在临床上的应用,     

MELD:判断终末期肝病病情的新方法

MELD (modleforend -stageliverdisease)是美国MayoClinic的Malinchoc和Kamath于 2 0 0 0年创立的一个判断终末期肝病病情的新的分级方式 ,2 0 0 2年 2月被美国全国器官分配联合网络 (UNOS)正式规定为筛选肝移植的标准。MELD能不能替代目前最常用的Child -Turcotte -Pugh(CTP)分级 ,仍存在着较多争论。本文就MELD的产生、特点、临床应用和目前存在的问题作一综合叙述。1　MELD的产生美国MayoClinic的Malinchoc和Kamath等人[1] 利用Cox比例风险回归的统计学方式 ,确定了四个实验室和临床指标 :血清肌酐、胆红素、凝血酶原时间 …     

终末期肝病模型评分的临床应用

终末期肝病模型(MELD)是由美国著名肝病中心Mayo Clinic的Malinchoc等[1]在2000年提出的.为了寻找比CTP分级更能准确评估TIPS术后患者生存期的方法,他们选择为治疗肝硬化腹水和预防门静脉高压出血进行TIPS术的患者,用Cox比例风险回归的统计学模型确定了能较好判断患者3个月生存期的4项实验室和临床指标,包括血清肌酐、胆红素、凝血酶原时间的国际标准化比值(INR)和病因,由这四个指标的回归系数组成死亡风险预测公式:R=0.957×loge(肌酐mg/d1) 0.378×loge(胆红素mg/d1) 1.12×loge(INR) 0.643(病因:胆汁淤积性和酒精性肝硬化为0,其他原因为1).此后Kamath又进行了改良,将公式的各系数均乘以10,即R=9.6×loge(肌酐mg/d1) 3.8×loge(胆红素mg/d1) 11.2×loge(INR) 6.4(病因),结果取整数.随后选取4组独立的肝硬化患者资料进行分析验证,发现该公式能较好地预测各组患者的3个月生存期,故将此公式命名为"终末期肝病模型",即MELD[2].通过两年时间的验证,发现MELD某些方面优于传统CTP分级,该模型逐渐推广到肝移植和晚期肝病患者预后的判断,并最终于2002年起由美国器官分配联合网络(UNOS)采纳为成人肝移植的新标准.     

终末期肝病模型及Child-Pugh分级对肝硬化患者的短期预后分析

评价终末期肝病模型(MELD)评分、Child-Pugh(CTP)及包含血肌酐值的CTP(CrCTP)分级对肝硬化患者的短期预后的意义.分别计算104例肝硬化患者的MELD、CTP及CrCTP分值,运用ROC曲线及曲线下面积(AUC)比较MELD评分、CTP及CrCTP分级判断肝硬化患者3个月生存率的准确性.在判断患者3个月生存率的ROC曲线AUC比较中,MELD评分＞CrCTP分级＞CTP分级(P＜0.05).提示在CTP中引入血肌酐值可以提高CTP分级对肝硬化患者短期预后的判断准确性;MELD评分在判断肝硬化患者的短期预后方面优于CTP及CrCTP.     

终末期肝病模型判断肝硬化患者预后的价值

目的终末期肝病模型(MELD)是2000年由美国的Malinchoc等建立的一个判断终末期肝硬化患者新的预后模型,本研究旨在验证MELD判断我国肝硬化患者预后方面的价值。方法选择具有完整记录资料和随访结果的315例肝硬化患者进行分析,根据MELD公式计算每例患者的MELD值及Child-Turcotte-Pugh(CTP)评分和分级。运用受试者工作曲线(ROC曲线)及其曲线下面积(AUC)比较MELD、CTP评分和分级判断肝硬化患者生存3个月、1年、2年等不同时间的准确性。运用Kaplan-Meier生存分析,比较不同MELD值时患者的生存率变化。结果MELD在判断患者3个月、1年、2年等生存时间的ROC曲线AUC均大于0.8,并且均大于CTP分级或评分的面积;除与CTP分级在判断6个月、1年、3年和4年时的AUC差异有统计学意义外,在其余时间内两者之间的AUC差异无统计学意义。MELD和CTP评分在两者之间的AUC差异均无统计学意义。将患者依据MELD值分成4组后,不同分级内的生存率均存在明显差异(P<0.001)。结论MELD在判断肝硬化患者预后方面是一个很好的指标,但与CTP分级或评分相比,三者判断能力无明显差异。     

MELD和MELD-Na评分系统评估失代偿期肝硬化患者预后的研究

目的比较Child-Pugh(CTP)分级、终末期肝病模型(Model for End-stage Liver Disease,MELD)评分系统及MELD联合血清钠(MELD-Na)对失代偿期肝硬化患者3、6、12个月死亡危险的预测价值。方法入选151例肝硬化失代偿期患者,根据随访3、6、12个月的存活情况,分别观察CTP分级、MELD评分及MELD-Na对肝硬化失代偿期患者死亡率的预测情况。结果151例入选病例中,随访至3个月时,不论是CTP、MELD还是MELD-Na随着各相应分值的增高,生存率均显著降低(P0.01),提示CTP、MELD及MELD-Na均能较好地预测患者短期生存率。随访至6个月及12个月时患者生存率的变化仍可见到这种趋势。本研究应用C-统计学分析,通过CTP、MELD及MELD-Na对比发现,随访至3个月时,CTP、MELD、MELD-Na的AUC分别为0.819、0.835、0.842;随访至6个月时AUC值为0.820、0.818、0.832;随访至12个月时AUC分别为0.795、0.795、0.814。MELD-Na的数值均高于CTP及MELD,但统计学无显著差异。结论CTP、MELD和MELD-Na均可以对终末期肝病患者预后做出较准确的判断。MELD-Na在预测肝硬化失代偿期患者短期生存率方面有一定优势。     

终末期肝病模型的近期研究进展

自2000年美国Mayo Clinica的Malinchoc等[1]最初创立终末期肝病模型(MELD)评分以来,随后的研究证实其为不同的终末期肝病生存率准确的预测指标.2002年美国器官分配网络(UNOS)正式将MELD评分作为确定肝移植器官分配优先权的标准.     

判断终末期肝病病情：从CTP到MELD

从40年前Child和Turcotte开始创立Child—Turcotte分级到Pugh予以完善并形成CTP分级，肝病专家始终没有放弃寻找一个真实、客观反映终末期肝病病情的方法。MELD分级是美国Mayo Clinic的Malinchoc和Kamath于2000年创立的一个判断晚期肝病病情的新分级方式。此文就MELD分级的产生、特点、临床应用和目前存在的问题作一综述。     

判断终末期肝病病情:从CTP到MELD

从40年前Child和Turcotte开始创立Child Turcotte分级到Pugh予以完善并形成CTP分级,肝病专家始终没有放弃寻找一个真实、客观反映终末期肝病病情的方法。MELD分级是美国 Mayo Clinic的Malinchoc和Kamath于 2000 年创立的一个判断晚期肝病病情的新分级方式。此文就 MELD分级的产生、特点、临床应用和目前存在的问题作一综述。     

Ultrasound liver elastography beyond liver fibrosis assessment

Several guidelines have indicated that liver stiffness(LS) assessed by means of shear wave elastography(SWE) can safely replace liver biopsy in several clinical scenarios, particularly in patients with chronic viral hepatitis. However, an increase of LS may be due to some other clinical conditions not related to fibrosis,such as liver inflammation, acute hepatitis, obstructive cholestasis, liver congestion, infiltrative liver diseases. This review analyzes the role that SWE can play in cases of liver congestion due to right-sided heart failure, congenital heart diseases or valvular diseases. In patients with heart failure LS seems directly influenced by central venous pressure and can be used as a prognostic marker to predict cardiac events. The potential role of LS in evaluating liver disease beyond the stage of liver fibrosis has been investigated also in the hepatic sinusoidal obstruction syndrome(SOS) and in the Budd-Chiari syndrome. In the hepatic SOS, an increase of LS is observed some days before the clinical manifestations;therefore, it could allow an early diagnosis to timely start an effective treatment.Moreover, it has been reported that patients that were successfully treated showed a LS decrease, that reached pre-transplantation value within two to four weeks. It has been reported that, in patients with Budd-Chiari syndrome, LS values can be used to monitor short and long-term outcome after angioplasty.     

中国肝癌肝移植的现状与展望

肝癌行肝移植治疗的指征、效果和相关问题一直存在争论,国际上已经有数个通用的肝癌肝移植标准,如Milan标准、Pittsburgh标准、UCSF标准等等,中国的移植学家们也在纷纷探讨适合中国的肝癌肝移植标准.本文收集并分析近年来国内外的文献,结合本移植中心460例肝移植的病例,对肝癌的分期标准、晚期肝癌行肝移植的指征进行了探讨,笔者认为影响我国肝癌肝移植的主要因素有:供肝的来源、术后乙肝及肿瘤的复发及相关社会因素等.     

Recurrent nonviral liver disease following liver transplantation

Recurrent disease after liver transplantation is well recognized and remains a potential cause of premature graft loss. The rates of recurrence are difficult to establish because of the lack of consistency in diagnostic criteria and approaches to diagnosis. Owing to the fact that recurrent parenchymal disease may occur in the presence of normal liver tests, those centers that use protocol biopsies will report greater rates of recurrence. It is important to recognize that rates of recurrence vary according to indication and show little correlation with rates of graft loss from recurrent disease. Recurrance rates are greatest for primary sclerosing cholangitis and autoimmune hepatitis, and low reccurrance rates are reported for alcoholic liver disease and recurrent primary biliary cirrhosis. The impact of recurrent nonalcoholic fatty liver disease is not yet clear. Patients and clinicians need to be aware of the possibility of recurrent disease in the differential diagnosis of abnormal liver tests, and management stategies may require alteration to reduce the impact of disease recurrence on outcome. Finally, an understanding of which diseases do recur after transplantation and identification of the risk factors may lead to a better understanding of the pathogenetic mechanisms of these conditions.     

Chronic liver diseases as liver tumor precursors

Liver cancer is a major global health problem and hepatocellular carcinoma (HCC) accounts for 75% of all liver carcinoma. HCC occurs more often in men than in women and mostly in people 50 to 60 years old. The disease is more common in parts of sub-Saharan Africa and Asia than in North and South America and Europe. Nevertheless its incidence increased over the past 4 decades in some Western countries. Worldwide, liver carcinoma is the 5th most common cancer and 3rd most common cause of cancer mortality (behind only lung and colorectal cancer) with approximately 680,000 annual deaths. Unlike most of the other malignancies, HCC almost entirely develops in the context of inflammation and organ injury and is related to cirrhosis in about 85% of the cases. Among underlying etiologies of liver cirrhosis, most frequent are viral infection and toxic substances, mostly alcohol. The main HCC risk factor in Eastern Asia and Africa is hepatitis B virus infection. Hepatitis C virus infection is the main risk factor in Western countries. Hereditary hemochromatosis is not a very frequent cause of liver cirrhosis, but these patients are at higher risk for HCC compared with other etiologies of cirrhosis. Aflatoxins, cancer-causing substances made by a type of plant mold, can play a role in some countries in Asia and Africa, and can have a synergistic effect with hepatitis B infection.     

Fatty liver in liver transplantation and surgery

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (> 60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (< 30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.     

Orthotopic liver transplantation for alcoholic liver disease

Alcohol abuse is the most common cause of end-stage liver disease in the United States, but many transplant centers are unwilling to accept alcoholic patients because of their supposed potential for recidivism, poor compliance with the required immunosuppression regimen and resulting failure of the allograft. There is also concern that alcohol-induced injury in other organs will preclude a good result. From July 1, 1982, to April 30, 1988, 73 patients received orthotopic liver transplants at the University of Pittsburgh for end-stage alcoholic liver disease. Fifty-two (71%) of these were alive at 25 +/- 9 mo (mean +/- S.D.) after transplantation, when a phone survey of these patients, their wives/husbands, and their physicians was performed to evaluate their subsequent use of alcohol, current medical condition and employment. Data obtained were compared with those for nonalcoholic patients selected as transplant controls. The recidivism rate has been 11.5%, with most patients drinking only socially. Fifty-four percent of the survivors are employed, 21% classify themselves as homemakers and only 11 (21%) are unable to work. Twenty-one patients died after transplantation; the most frequent cause of death was sepsis (43%), and intraoperative death was the next most common cause (28.6%). These data demonstrate that alcoholic patients can be transplanted successfully and achieve good health not significantly different from that of individuals transplanted for other causes. Thus orthotopic liver transplantation is a therapeutic option that should be considered for individuals with end-stage alcoholic liver disease who desire such therapy.     

Adult liver transplantation for metabolic liver disease

Liver replacement provides an effective method of replacing a failing liver, and corrects the underlying defect in many metabolic conditions. Results of liver transplantation for metabolic diseases have been encouraging, with the exception of hereditary hemochromatosis, in which infectious and for which cardiac complications appear to increase posttransplant mortality. An improved understanding of the underlying genetic and molecular defect will lead to advances in medical therapy and perhaps will decrease the need for liver replacement. The prospects of gene therapy are being pursued for many metabolic disorders, however until this research leads to direct clinical application, liver transplantation remains the only effective option for many patients with metabolic liver disease.