重症酒精性肝炎与肝移植

饮酒相关性肝病包括酒精性脂肪肝（alcoholic steatosis,AS）、酒精性肝炎（alcoholic hepatitis,AH）和酒精性肝硬化（alcoholic liver cirrhosis,ALC）等一组疾病[1]。重症酒精性肝炎（severe alcoholic hepatitis, SAH）是AH的严重类型,可发生于无肝病史的人群（急性酒精中毒）,也可发生在AS或ALC患者。主要表现为发热、肝脏肿大伴触痛、血清胆红素和外周血白细胞显著升高,可伴有慢性肝损伤和门脉高压的表现。 SAH 患者Maddrey 判别函数（Maddrey discrimi-nant function,MDF）［MDF=4.6x（PT-正常对照）＋TBIL （mg/dl）］通常≥32分,极易并发感染和多器官功能衰竭[2]。即使积极治疗,SAH 患者近期病死率仍可高达35%至50%[3]。     

脂肪性肝病的肝移植

随着肥胖症发病率在美国乃至全球的持续上升,非酒精性脂肪性肝病（NAFLD）和非酒精性脂肪性肝炎（NASH）的诊断日益增多,并被认为是终末期肝病（ESLD）的病因之一。     

非酒精性脂肪性肝病与肝移植

随着生活水平的提高,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)在人群中的发病率越来越高.非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是NAFLD的最严重类型,在发达国家已成为临床上最常见的慢性肝病类型.     

酒精性肝病诊断现状

酒精性肝病（Alcoholic liver disease,ALD）是西方国家最常见的肝病。在法国,l/3以上肝硬化病因是过量饮酒。在美国,酒精性肝硬化是最常见死亡原因的第8位,在胃肠道疾病中,其死亡率位列第二[1]。我国酒精的消耗量也在不断增加。尽管中国缺乏大规模ALD的流行病学调查资料,但几个局部地区的报道发现ALD的发病比例在不断上升[2,3]。同时,我国还面临较多的酒精性肝病和/或非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）合并病毒性肝病的现实问题。     

自身免疫性肝病肝移植术后的治疗

自身免疫性肝病(autoimmune liver disease,ALD)是一组免疫介导的肝脏损伤的自身免疫性疾病,包括以肝炎为主的自身免疫性肝炎(autoimmune hepatitis.AIH),以胆管病变为主的原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC).ALD最终可以进展为肝硬化,导致肝功能衰竭,肝移植术是终末期ALD唯一有效的治疗方法.     

内蒙古通辽市酒精性肝炎临床诊断现状

目的:探讨基层医生对酒精性肝炎诊断的现状。方法:回顾性分析2018年6月1日至2019年5月31日,内蒙古通辽市传染病医院诊断明确的酒精（乙醇）相关性肝病住院患者的临床资料,按照美国国家酒精滥用和酒精中毒研究所推荐的酒精性肝炎诊断标准,对临床诊断的酒精性肝炎进行一致性判断,然后应用国际指南推荐的酒精性肝炎严重程度评估模...     

非酒精性脂肪性肝病与肝移植

非酒精性脂肪性肝病（NAFLD）患病率日益增高,目前已成为西方国家肝移植的第二大适应证。虽然目前我国肝移植的主要适应证仍是乙型病毒性肝炎以及酒精性肝炎相关终末期肝病,但随着人们生活水平的提高以及代谢综合征的流行,与之相关的NAFLD患者也逐渐增加。同时,随着乙型肝炎疫苗接种的普及以及核苷类似物等药物的应用,可以预见,在...     

Systematic review with meta-analysis on transplantation for alcohol-related liver disease:Very low evidence of improved outcomes

BACKGROUND Alcohol-related liver disease(ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder(AUD). Previous reviews of transplantation for ALD are limited in scope of outcomes and type of ALD studied. A comprehensive systematic review could improve use of transplantation in ALD and improve future research. We hypothesize that while transplanting ALD may improve mortality and relapse,findings will be limited by pre-specified causes of heterogeneity-assessment and treatment of AUD, definition of ALD, spectrum of ALD studied, assessment and rates of relapse, and study quality and bias.AIM To optimize liver transplantation for ALD, understanding existing research to guide future research, we conducted a systematic review with meta-analysis.METHODS We conducted a systematic review, comparing liver transplant to no-transplant in patients with ALD, with a primary outcome of both short-and long-term mortality and relapse. We performed a comprehensive search of MEDLINE,EMBASE, Web of Science, and The Cochrane Library databases for peer-reviewed journal articles comparing use of liver transplant in ALD to no-transplant. Two reviewers independently conducted screening, full text review, and data extraction according to the PRISMA guidelines. We report the quality of the evidence according to the GRADE criteria.RESULTS We analyzed data from 10 studies. Of 1332 participants, 34.2%(456/1332) had undergone liver transplantation, while 65.8%(876/1332) had not. While random effects meta-analysis suggested transplant in comparison to no-transplant had an association of reduced mortality that did not reach statistical significance, relative risk(RR) = 0.51(0.25-1.05), but not relapse risk, RR = 0.52(0.18-1.53), significant heterogeneity limited these findings. When restricted to prospective data,transplant compared to no-transplant significantly reduced mortality, RR = 0.25(0.13-0.46, P < 0.01), and relapse, RR = 0.25(0.14-0.45, P < 0.01), with insignificant heterogeneity but persistent small-study effects. The overall quality of the evidence was Very Low. Heterogeneity analysis suggested that AUD assessment and treatment was often not reported while ALD, relapse assessment and rate,and data collection were institutionally rather than standardly defined.CONCLUSION Systematic review of liver transplantation for ALD suggests reduced mortality and relapse in heterogeneous, institution-specific populations with inherent bias.To understand efficacy of transplanting ALD, our research approach must change.     

Long-term survival after liver transplantation for alcoholic liver disease

Currently,alcoholic cirrhosis is the second leading indication for liver transplantation in the United States and Europe.The quality of life and survival after a liver transplantation(LT)in patients with alcoholic liver disease(ALD)are similar to those in patients with other cirrhosis etiologies.The alcoholic relapse rate after a LT varies from 10%-50%,and these relapse patients are the ones who present a reduced long-term survival,mainly due to cardiovascular diseases and the onset of de novo neoplasms,including lung and upper aerodigestive tract.Nearly 40%of ALD recipients resume smoking and resume it early post-LT.Therefore,our pre-and post-LT follow-up efforts regarding ALD should be focused not only on alcoholic relapse but also on treating and avoiding other modifiable risk factors such as tobacco.The psychiatric and psychosocial pre-LT evaluation and the post-LT follow-up with physicians,psychiatrists and addiction specialists are important for reversing these problems because these professionals help to identify patients at risk for relapse as well as those patients who have relapsed,thus enabling responsive actions.     

Challenges in transplantation for alcoholic liver disease

Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist’s assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient’s pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key factor determining the outcome of transplantation for alcoholic cirrhosis is intensive lifelong medical and psychological care. Post-transplant surveillance might be much more important than pre-transplant selection.     

人工肝联合肝移植治疗重型肝炎的初步研究

目的 观察并评价混合人工肝支持系统联合肝移植在救治重型病毒性肝炎（重型肝炎）中的作用与疗效。方法 采用自行研制的体外混合人工肝支持系统对8例中晚期重型肝炎患者进行人工肝过渡支持治疗,3－14d后行原位肝移植术。结果 8例重型肝炎患者经混合人工肝支持,肝衰竭得到有效控制,均成功等到肝移植。肝移植后4例存活,存活率为50％,另4例因肺部感染、肝肾综合征等死亡。结论 人工肝支持系统与肝移植联合可作为中晚期重型肝炎肝衰竭患者治疗的有效手段。     

非生物人工肝在重型肝炎患者过渡肝移植中的应用价值

目的　评价非生物人工肝对重型病毒性肝炎 (重型肝炎 )患者等待肝移植的过渡支持作用与价值。方法　采用血浆置换和血浆吸附两种非生物人工肝支持疗法 ,对 8例拟定肝移植的中晚期重型肝炎患者进行人工肝过渡支持。结果　 8例重型肝炎患者经人工肝支持 ,4例肝衰竭得到较好的控制 ,4～ 13d后成功等到供肝。另 4例肝衰竭控制不明显 ,病情呈进行性加重 ,在待肝过程中 (人工肝支持后 3～ 8d)死亡。结论　非生物人工肝对等待肝移植的重型肝炎患者有一定的过渡支持作用 ,能否最终成功过渡与患者肝衰竭程度、并发症及待肝时间密切相关。     

Oxidative stress in alcohol-related liver disease

Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs. Heavy alcohol misuse leads to alcohol-related liver disease, which is responsible for a significant proportion of alcohol-attributable deaths globally. Other than reducing alcohol consumption, there are currently no effective treatments for alcohol-related liver disease. Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants. It plays important roles in several aspects of alcohol-related liver disease pathogenesis. Here, we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species, acetaldehyde and protein and DNA adducts. These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis. Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling. There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation. Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes. This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation. Improved understanding of these processes may identify novel targets for therapy.     

终末期酒精性肝病的肝移植

西方国家常见的酒精性肝病（ALD）近年来在我国也有明显的增加.由于没有疗效确切的药物,肝移植成为目前治疗终末期酒精性肝病（EALD）最有效的手段,而与其他良性终末期肝病肝移植比较,EALD肝移植存在诸多特殊的临床问题.我们回顾分析我院11例EALD肝移植的临床资料及随访结果,对受者的选择、术前的评估及围手术期的处理等问题进行探讨.     

Liver regeneration as treatment target for severe alcoholic hepatitis

Severe alcoholic hepatitis (AH) is a distinct entity in the spectrum of alcohol-related liver disease, with limited treatment options and high mortality. Supportive medical care with corticosteroids in selected patients is the only currently available treatment option, often with poor outcomes. Based on the insights into the pathogenetic mechanisms of AH, which are mostly obtained from animal studies, several new treatment options are being explored. Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target. Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor (G-CSF) on liver regeneration and immunomodulation in animal models, several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH. Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH, these effects were not confirmed by a recently published multicenter randomized trial, suggesting that other options should rather be pursued. Stem cell transplantation represents another option for improving liver regeneration, but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing, with established lack of efficacy in patients with compensated cirrhosis. In this review, we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration. The lack of high-quality studies and evidence is a major obstacle in further treatment development. New insights into the pathogenesis of not only liver injury, but also liver regeneration processes are mandatory for the development of new treatment options. A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing, and data obtained from animal studies are essential for future research.