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…     

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。     

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。     

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。     

Natural killer T cells in liver injury,inflammation and cancer

The liver is an organ that has the largest amount of natural killer T(NKT) cells, which play critical roles in the pathogenesis of liver diseases. In this article, the authors summarize recent findings about the roles of NKT cells in liver injury, inflammation, fibrosis, regeneration and cancer. In brief, NKT cells accelerate liver injury by producing pro-inflammatory cytokines and directly killing hepatocytes. NKT cells are involved in complex roles in liver fibrogenesis. For instance, NKT cells inhibit liver fibrosis via suppressing hepatic stellate cell activation and can also promote liver fibrosis via enhancing liver inflammation and injury. Inactivated or weakly activated NKT cells play a minimal role in controlling liver regeneration, whilst activated NKT cells have an inhibitory effect on liver regeneration. In liver cancer, NKT cells play both pro-tumor and anti-tumor roles in controlling tumor progress.     

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。     

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。     

肝癌肝移植的临床及基础研究

肝移植是对于肝癌最为有效的治疗方式。因为其可以根除肿瘤主体及镜下微小肿瘤病灶并提供给患者一个具备良好功能的肝脏。如今肝移植治疗小肝癌的5年成活率已经高达80%。但是由于肝移植手术仅能提供给一些本就预期预后良好的肝癌初期患者,所以只有小部分符合条件的肝癌患者能够受惠     

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.     

Liver transplantation: the Italian experience

BACKGROUND: Liver transplantation is the standard treatment for patients with end-stage liver disease no longer responsive to conventional medical treatment AIMS: To report the long-term experience of liver transplantation in Italy. PATIENTS AND METHODS: Data were obtained retrospectively by means of a multiple-item form collected from 15 Italian liver transplant centres. The filing centre was centralized. RESULTS: A total of 3323 liver transplants were performed on 3026 patients, with a cumulative proportional survival of 72.4%. Three, 5 and 10 years' patient survival rates were 72.3%, 68.8% and 61.3%, respectively. The most common indication for liver transplantation were hepatitis B virus (+/- hepatitis D virus)- and hepatitis C virus-related cirrhosis (59.4%). Excellent survival rates were observed particularly in controversial indications, such as alcoholic cirrhosis, hepatitis B virus-related cirrhosis and hepatocellular carcinoma. Retransplantation was required in 8.9% of the cases. The overall prevalence of acute cellular rejection episodes was 43.5%. In our study population, primary non-function and disease recurrence were the most common causes of graft failure (28.7% and 25.4%, respectively). Infections and/or sepsis were the most common causes of death after transplantation (42%). CONCLUSION: This study confirms that patients with controversial indications to liver transplantation such as alcoholic cirrhosis, HBV-related cirrhosis and hepatocellular carcinoma can achieve excellent survival when properly selected.     

Liver failure after major hepatic resection

Introduction

The consequence of excessive liver resection is the inexorable development of progressive liver failure characterised by the typical stigmata associated with this condition, including worsening coagulopathy, hyperbilirubinaemia and encephalopathy. The focus of this review will be to investigate factors contributing to hepatocyte loss and impaired regeneration.

Methods

A literature search was undertaken of Pubmed and related search engines, examining for articles relating to hepatic failure following major hepatectomy.

Results

In spite of improvements in adjuvant chemotherapy and increasing surgical confidence and expertise, the parameters determining how much liver can be resected have remained largely unchanged. A number of preoperative, intraoperative and post-operative factors all contribute to the likelihood of liver failure after surgery.

Conclusions

Given the magnitude of the surgery, mortality and morbidity rates are extremely good. Careful patient selection and preservation of an obligate volume of remnant liver is essential. Modifiable causes of hepatic failure include avoidance of sepsis, drainage of cholestasis with restoration of enteric bile salts and judicious use of portal triad inflow occlusion intra-operatively. Avoidance of post-operative sepsis is most likely to be achieved by patient selection, meticulous intra-operative technique and post-operative care. Modulation of portal vein pressures post-operatively may further help reduce the risk of liver failure.     

MARS: a futile tool in centres without active liver transplant support.

BACKGROUND AND AIM: Studies on Molecular Adsorbent Recycling Systems (MARS) showed inconclusive survival benefits. PATIENTS AND METHOD: We evaluated the efficacy of MARS for patients with either acute liver failure (ALF) or acute-on-chronic liver failure (AoCLF) at our centre, from February 2002 till April 2006 retrospectively. RESULTS: Fifty ALF patients underwent median (range) three (1-10) sessions of MARS. Acute exacerbations of chronic hepatitis B (n=26) and drug-induced liver injury (n=12) were the commonest causes. Living donors were available in 6, 2 paediatric patients underwent left lobe and four adults underwent right lobe living donor liver transplant. Among the 44 ALF patients without a suitable living donor, one underwent deceased donor liver transplant and survived, another 19-year-old male with acute exacerbations of chronic hepatitis B recovered without transplant, and the rest died. Twenty-six had AoCLF and underwent four (1-10) MARS sessions. Sepsis (n=16) and upper gastrointestinal bleeding (n=4) were the commonest precipitating factors. None had a suitable living or deceased donor, suitable for transplantation during their hospitalization. Only one of 26 AoCLF patients survived the hospitalization, but the survivor died of sepsis 1 month later. CONCLUSION: In this non-randomized study, survival after MARS was related to the availability of transplant, and in patients where living or deceased donor transplant was unavailable, MARS was of little benefit. Randomized-controlled trials on MARS((R)) are urgently needed to clarify its clinical utility.     

肝活检对82例肝病诊断的临床价值

本文对82例肝病患者做肝活检，并以病理诊断与临床诊断进行对比。结果临床与病理诊断符合者49例，占59．8％，不符合33例占40．2％，其中肝硬化患者临床与病理诊断符合率69．7％，慢性活动性肝炎诊断符合率60％，慢性迁延性肝炎符合率66．7％，肝脓疡及亚急性重症肝炎符合率50％。慢性无症状乙肝病毒携带者8例，病理确诊为慢性迁延性肝炎5例，慢性活动性肝炎1例，肝轻微病变2例。以上资料表明，对肝病患者做肝活检是非常必要的，既可明确诊断，又可早期预防和治疗。     

Variation in Hepatic Estrogen Receptor Concentrations in Patients with Liver Disease a Multivariate Analysis

Hepatic estrogen receptor concentrations were measured in liver biopsy specimens from 102 patients (58 women and 44 men) with liver disease and correlated to several clinical, biochemical, and histologic background variables by means of multiple regression analysis. Half of the tissue was processed for histologic evaluation with a semiquantitative registration of histologic characteristics, whereas the other part was used for receptor analysis by enzyme immunoassay. Fifteen patients with no or minimal histologic changes served as controls. The analysis shows that the reduced estrogen receptor concentrations observed in patients with chronic liver diseases reflect the degree of liver dysfunction and not the specific type of liver disease. Serum albumin, log serum bilirubin, log serum alkaline phosphatases, and the degree of parenchymal fibrosis were significantly related to hepatic estrogen receptor level in the final regression model, but only part of the variation can be explained by these variables, and other factors must be of importance.     

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.     

Right hepatectomy in living donors with previous abdominal surgery

BACKGROUND:Few studies have evaluated the impact of previous abdominal surgery (PAS) on living donor right hepatectomy (LDRH).The aim of this study was to investigate the outcomes of liver transplantation using right lobe grafts of living donors with PAS.METHODS:Data were reviewed from LDRH patients at the authors' institution between March 2008 and November 2014.LDRH patients with PAS were divided into two groups according to upper PAS (group 1) or lower PAS (group 2),and they were compared to those without PAS (group 3) who were matched 1:1 based on age,gender,and body mass index.Perioperative data,complications by the Clavien classification,and the outcomes with more than 14 months follow-up were compared.RESULTS:Twenty-three (4.9％) of a total of 471 LDRH donors had PAS.Eleven donors were assigned to group 1,12 to group 2,and 23 to group 3.Intraperitoneal adhesions were found in 20 (87.0％) of 23 donors with PAS,of whom 5 (21.7％) had adhesiolysis-related injuries that happened more commonly in group I than in group 2 (P=0.025).LDRH was successfully completed under upper midline laparotomy in all donors.No donors received perioperative blood transfusion.The peak postoperative AST,ALT,INR,and total bilirubin levels made no difference between the three groups.Compared with group 3,groups 1 and 2 had a longer operative time (P=0.012) and a higher grade I complication rate (P=0.047).All donors recovered fully to their routine activities.The 23 recipients of grafts from donors with PAS showed good liver function with 1-year graft and patient survivals of 100％.CONCLUSION:A history of PAS is not a contraindication to LDRH in the current era of advanced surgical techniques.