肝移植在中国的发展现状

作为治疗各种终末期肝病唯一有效的方法,肝移植近年在国内发展迅速。叙述了肝移植在国内的最新发展成果,包括肝癌肝移植受者选择标准——杭州标准的确立;挽救性肝移植及降期治疗在肝癌肝移植中的最新应用;肝移植联合人工肝技术治疗急性重症肝衰竭的进展;活体肝移植技术创新和心脏死亡器官捐献移植在中国的突破性发展。面临器官短缺,应建立符合中国国情的科学规范的器官捐献体系,在造福于广大人民的同时也将进一步提升我国器官移植学界在国际上的声誉。     

肝再生增强因子在肝脏中的作用

肝再生增强因子（ALR）除了促进肝再生，保护肝损伤之外，可能在肝脏的器官形成和发育中也发挥着重要作用。介绍了ALR在肝脏中的生物学功能和机制研究的最新进展，并归纳总结了ALR在肝脏疾病的诊断和治疗中的应用。指出ALR可能通过线粒体途径调控肝细胞的凋亡，从而参与肝脏的修复和再生。未来ALR可能作为肝衰竭患者肝再生及预后评估的候选分子，并有望成为临床治疗严重肝病和肝衰竭的有效药物。     

药物性肝损伤的研究现状及存在问题

药物性肝损伤是由于药物和（或）其代谢产物引起的肝细胞毒性损伤,或药物及其代谢产物引起的过敏反应所致的疾病。因其发生范围广,预测性差,且无特异性治疗方案,日益成为威胁人类健康的“隐形杀手”。本文针对药物性肝损伤的研究现状和存在问题进行探讨,以期加强临床医生在用药时的关注。     

某传染病医院11年问药物性肝损伤住院病例状况分析

目的探讨药物性肝损伤（drug-indUeedliverinjury,DILl）在非感染性肝病患者中的分布情况。方法回顾性研究某院2002年1月一2012年12月3848例DILI住院患者的资料,分析年度分布情况、患者性别、年龄及预后。结果DILl患者年住院数由88例（2002年）升至835例（2012年）,在非感染性肝病中的构成比由13．19％升至21．52％。10～49岁的患者随着年龄的增加,发生DILI的人数呈上升趋势;50～89岁的患者随着年龄的增加,发生DILI的人数呈下降趋势。〈10、10～19、20～29、30．39、40～49、50～59、60。69、70～79和≥80岁各年龄组DILl患者构成比分别为1．65％、5．11％、12．10％、19．08％、25．45％、20．62％、10．42％、4．58％和0．98％。各年龄组女性构成比分别为30．16％、44．90％、49．46％、55．10％、58．37％、64．28％、58．85％、52．00％和27．78％。药物性肝硬化患者构成比为7．7％,药物性肝衰竭为4．1％,药物性肝炎为88．2％。3848例中总无效死亡率为7．61％,2010年开始DILl无效死亡率呈下降趋势,2012年为2．87％。结论DILl正逐渐成为肝病中的常见病,30。59岁为DILl高发年龄．30～79岁的nTlll患者以奇件为丰。     

复方牛胎肝提取物治疗非酒精性脂肪性肝病的多中心临床研究

目的观察复方牛胎肝提取物片治疗非酒精性脂肪性肝病（NAFLD）的近期效果及其安全性。方法多中心、开放、非随机临床试验,在综合治疗的基础上,应用复方牛胎肝提取物片（3片/次,2次/日,口服,共3个月）治疗240例NAFLD,其中男195例,女45例,平均年龄为（42.2±11.3）岁,基础疾病为超重和/或中心性肥胖。结果有240例被纳入本研究,临床症状改善率85.9%（164/191）,其中以肝区不适感改善效果最为显著;ALT复常率62.5%（115/184）,从治疗前的（79.59±43.63）U/L下降至（43.99±14.83）U/L,P〈0.01,同时AST、GGT和TG、TC和LDL-C也明显下降,P〈0.01;而HDL-C以及空腹血糖、HOMA-IR无明显改变,P〉0.05。35.4%（85/240）的患者B超脂肪肝程度下降1个或1个以上等级;74例患者肝/脾CT值从治疗前的0.78±0.18升高到治疗后的0.93±0.16,P〈0.001。未进行饮食控制和增加运动的患者BMI、腰/臀围以及ALT、AST、GGT、TG、TC较治疗前均明显下降,P〈0.001,但饮食控制和增加运动的患者下降更快,P〈0.001。全组病例不良反应发生率为4.58%（11/240）,主要表现为消化道症状。结论复方牛胎肝提取物片对NAFLD有一定治疗效果,且不良反应轻微。     

Role of Kupffer cells in the outgrowth of colorectal cancer liver metastases

Colorectal cancer is one of the commonest malignancies in the "developed" world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines. Subsequently, colorectal metastasising cells are destroyed either by KC-performed phagocytosis or via the stimulation of other immune cells which migrate into the sinusoids and act accordingly. On the contrary, KC products, including cytokines, growth factors and matrix-degrading enzymes may promote liver metastasis, supporting tumour cell extravasation, motility and invasion. Current research aims to exploit the antineoplastic properties of KCs in new therapeutic approaches of colorectal cancer liver metastasis. Numerous agents, such as the granulocyte macrophage-colony stimulating factor, interferon gamma, muramyl peptide analogues and various antibody based treatments, have been tested in experimental models with promising results. Future trials may investigate their use in everyday clinical practice and compare their therapeutic value with current treatment of the disease.     

Laparoscopic resection of hepatic colorectal metastases

BackgroundLiver resection for secondary malignancy has become the standard of care in appropriately staged patients, offering 5-year survival rates of >40%. Reports of laparoscopic liver resection have been published with increasing frequency over the last few years. In these small series approximately one-third of all operations have been for malignancy, but survival figures cannot be assessed yet.MethodsA retrospective review of all laparoscopic liver resections performed by four surgeons in Brisbane between 1997 and 2004 was done. Follow-up was by regular patient review and telephone confirmation.ResultsOf 84 laparoscopic liver resections, 33 (39%) were for malignancy; 28 of these were for metastases (22 colorectal). Thirteen patients had left lateral sectionectomy with minimal morbidity; nine right hepatectomies were attempted and six cases of segmental or subsegmental resection were performed. Survival rates in 12 patients followed for 2 years with colorectal secondaries were 75% with 67% disease-free.DiscussionLaparoscopic liver resection is feasible in highly selected cases of malignant disease. Patients need to be appropriately staged and surgeons need a broad experience of open liver surgery and advanced laparoscopic procedures.     

Realistic expectations for cryoablation of liver tumors

While cryoablation has been shown to be an effective method of destruction of primary and metastatic liver tumors, there is a disturbingly high incidence of recurrence at the cryoablated site and there are conflicting reports concerning long-term survival. For this reason, resection remains the preferred surgical treatment of liver tumors. However, there is a population of patients who, because of age, pre-existing liver disease, or likely systemic dissemination, present a higher risk for major resection, and for whom cryoablation may be favored. This study examined the safety and effectiveness of cryoablation in patients thought to be at higher risk for conventional hepatic resection, or in whom resection would not eradicate all known disease. Twenty-eight consecutive patients underwent cryoablation, with or without resection, of 39 hepatic tumors for primary (n = 9) or metastatic (n = 19) disease. Their postoperative course and long-term follow-up were examined for complications, survivability, and recurrence of disease. With the use of cryoablation, a major hepatic resection was avoided in 20 patients, 11 of whom were 70 years or older, 4 who likely had disseminated cancer even though the liver was the only site of detectable disease, 2 who were cirrhotic, and 2 with bilobar disease. An additional 7 patients had recurrence of disease in a previously resected liver, for whom additional resection would be hazardous. There was one operative death from an exaggerated systemic inflammatory response syndrome. Seven patients developed complications, including 2 patients with cryoablation-induced coagulopathy. Excluding 2 patients (including the postoperative death) the average hospital length of stay was 6.7 ± 2.8 days. Seven patients required some intensive care unit (ICU) care. Three patients with primary liver cancer are alive 29 to 47 months after cryoablation. Two patients with metastatic disease are alive without recurrence at 12 and 16 months, and 9 are alive with disease from 13 to 58 months after cryoablation. Fifteen patients developed liver recurrence, 5/27 (19%) at the cryoablated site. Cryoablation appears to be a safe treatment modality for primary and metastatic liver cancer. It is particularly appealing in those patients who may be at higher risk for major hepatectomy because of age, pre-existing liver disease, type of metastatic disease, previous resection, or bilobar tumors. Most disturbing is the high incidence of recurrence at the cryoablated site, which may reflect problems with ultrasound localization or proximity of tumors to major vasculature. Disease-free survival is low. From this standpoint the procedure should be considered palliative, even though all hepatic tumors can be eradicated. However, these limitations should not deter the use of cryoablation in selected patients. There is the potential for long-term survival, just as there is with resection.     

Reappraisal of surgical treatment of small hepatocellular carcinomas in cirrhosis: Clinicopathological study of resection or transplantation

Thirty-two patients with hepatocellular carcinoma (HCC) occurring in individuals with cirrhosis had a potentially curative surgical procedure. Twenty-two had segmental hepatic resections (HR), and 10 underwent orthotopic liver transplantation (OLTx). The diagnosis of hepatic malignancy was established in each case preoperatively, and each case was studied intraoperatively by means of sonography. Postoperatively each surgical specimen was examined pathologically with attention to the possibility of intrahepatic tumor spread. Twenty-three of the 32 patients had single small HCC lesion (<5 cm diameter) identified preoperatively. Sixteen of these underwent HR and seven underwent OLTx. Multiple additional neoplastic lesions were found in 19% of the 16 HR cases and in 14% of those undergoing OLTx when the resection specimens were examined pathologically. Vascular invasion was present in 43% of the OLTx patients and in 25% of the HR patients. Subtotal hepatic resection for small HCC occurring in cirrhosis has produced few long-term survivals. Both pre- and intraoperative sonography have been shown to underestimate the extent and distribution of these tumors. Based upon this experience that (1) vascular spread occurs often in HCC and (2) a high risk of postoperative hepatic failure can be expected after HR in cirrhotic individuals, OLTx is the most rational surgical procedure for such cases as it has the potential to cure.     

Efficacy and safety of moderately steatotic donor liver in transplantation

BACKGROUND:The discrepancy between available livers and requests for transplantation has forced many centers to use marginal donors in order to expand the donor pool. Many previous studies have demonstrated controversial results of the application of steatotic liver grafts.The aim of the present study was to summarize our experience and evaluate the value of steatotic liver grafts. METHODS:The clinical and follow-up data of 24 adult patients receiving moderately steatotic liver grafts (30%-60%)from May 2003...     

Nomenclature of hepatic anatomy and resections: a review of the Brisbane 2000 system

The Brisbane 2000 system of nomenclature of hepatic anatomy and resections was introduced to provide a universal terminology in an area that was plagued by confusing and inappropriate terminology. The article describes historical developments central to the emergence of the new terminology and describes the terminology, its attributes, and rules of application.     

Liver transplant for 70 patients with end-stage liver diseases

Introduction Progress in immunosuppression, surgical techniques, and perioperative care has promoted orthotopic liver transplantation from an experimental procedure to an accepted clinical treatment. Liver transplantation is considered the standard therapeutic approach for end-stage liver disease[1-4] with a postoperative survival rate increasing to 80% in 5 5] years.[1, However, there are a wide range of possible postoperative complications of technical and medical origin.[6-9] Based on ortho…     

FibroScan评估纤维化、筛查肝脏疾病、监测慢性肝病进展及预测预后的新证据

FibroScan是目前应用最广泛的无创纤维化诊断手段之一.人们对FibroScan的应用已经不仅仅是评估纤维化,而且可以预测肝硬化相关并发症和肝细胞癌( HCC)的存在,更重要的是可以预测临床预后.换句话说,FibroScan不仅可以评估已经发生的临床事件,而且可以预测将要发生的临床事件.本文就FibroScan对纤维化评估、肝脏疾病筛查及疾病进展的预测等方面作一综述.     

Fine - Needle Aspiration Biopsy Smears in the Diagnosis of Liver Diseases

The different opinions concerning the value of fine-needle biopsy may partly be explained by divergencies in results between examiners. 103 coded fine-needle aspiration biopsy smears were stained by the May-Grünwald-Giemsa's method and examined independently by two investigators by light microscopy. Complete agreement in classification or slight disagreement occurred in 94–98% of the smears for recognition of the degree of vacuolization, granulation, bile accumulation, and nuclear size variation. Similar results were obtained in 83 and 90% for bile epithelium and connective tissue, respectively. Correlation between the clinical diagnoses and the cytological alterations did not show any characteristic ‘profile'. In 5 cases with acute alcoholic hepatitis and in patients with cirrhosis and chronic hepatitis high grades of bile duct epithelium were present. A correct diagnosis of liver cancer was made by both examiners in the same percentage of cases in the smears as in the conventional liver biopsies.     

非酒精性脂肪性肝病与肝细胞恶性转化的关系

非酒精性脂肪性肝病(NAFLD)是除酒精和其他明确的肝损伤因素所致的以弥漫性肝细胞大泡性脂肪变性为主,肝脏脂质蓄积过多的临床病理综合征,包括单纯性脂肪肝、演变的脂肪性肝炎和肝硬化。随着NAFLD发病率的不断上升,其在肝细胞癌(HCC)中的发病风险也在增加,但其确切的机制尚不清楚。总结了NAFLD中脂质积累、各种相关细胞、蛋白、激素、代谢产物等与肝细胞恶性转化之间关系,以及NAFLD、HCC和脂肪代谢三者间的联系,为临床上预防HCC提供新的思路。     

Immediate-Early Protooncogene Expression and Liver Function Following Various Extents of Partial Hepatectomy in the Rat

Immediate–early protooncogenes (IEP) are thought to play an important role in hepatocyte replication. Whether the extent of their expression correlates with the strength of the proliferative stimulus and subsequent regenerative activity has yet to be documented in vivo. Data are also lacking with respect to the level at which liver disease is associated with biochemical evidence of hepatic dysfunction. Thus, the objectives of this study were to determine whether a correlation exists between IEP gene mRNA expression and varying extents of partial hepatectomy (PHx) and to document the extent of resection required to result in increases in serum bilirubin levels. Eighty-nine adult, male Sprague-Dawley rats underwent either sham surgery or 20%, 35%, 55%, 70% or 90% PHx. Postoperatively, rats were killed (N = 3–6/group) at 15 and 30 mins and 8 and 24 hrs for c-fos, c-jun, and c-myc mRNA expression by northern blot analyses. Rats killed at 24 hrs also had hepatic regenerative activity documented by [³H]thymidine incorporation into hepatic DNA and serum bilirubin determinations. While c-fos mRNA expression at 15 mins and c-myc mRNA expression at 8 hrs after PHx did not correlate with the extent of PHx (r² = 0.478 and 0.018, respectively), a weak correlation existed between c-jun mRNA expression at 30 mins and the extent of PHx (r² = 0.662, P < 0.05). In terms of IEP mRNA expression and hepatic regenerative activity, a strong correlation existed between c-fos mRNA expression and [³H]thymidine incorporation (r² = 0.851, P < 0.01) but not c-jun or c-myc mRNA expression. Compared to sham operated controls, [³H]thymidine incorporation was 2.0×, 3.4×, 3.2×, 7.8×, and 2.2× increased following 20%, 35%, 55%, 70%, and 90% PHx, respectively. Serum bilirubin levels remained unchanged until 70% PHx, when they increased from baseline values of 0.54 ± 0.05 mg/dl to 1.02 ± 0.15 mg/dl (P < 0.05). A further increase occurred following 90% PHx (1.83 ± 0.30 mg/dl, P < 0.01). In conclusion these findings indicate that c-fos mRNA expression 15 mins after PHx correlates with hepatic regenerative activity but not the strength of the regenerative stimulus and that hepatic parenchymal loss of 55–70% must occur prior to the detection of elevated serum bilirubin levels. The results also indicate that relative to a 70% PHx, 90% PHx is associated with decreased rather than increased hepatic regenerative activity.