Acute-on-chronic liver failure in chronic hepatitis B

Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is most commonly caused by acute severe exacerbation of CHB. The pathophysiology of ACLF in CHB is still poorly understood. Despite the identification of important predisposing factors and prognostic markers, ACLF in CHB remains a disease associated with high mortality. The majority of studies using nucleoside analog therapy did not show any significant improvement in survival, although larger prospective studies are needed. Liver transplantation is the definitive treatment for ACLF in CHB. The challenge ahead would be prognosticating cases with favorable or unfavorable outcomes in order to streamline patients for early transplantation or for medical therapy.     

Acute-on-chronic liver failure: A comparison of three different diagnostic criteria

Introduction and aimDifferent criteria are applied for the diagnosis of acute-on-chronic liver failure (ACLF). Our aim was to compare the performance of different ACLF diagnostic criteria for predicting mortality.Materials and methodsThis was a prospective cohort study of adult cirrhotic patients admitted to a tertiary hospital for acute decompensation (AD) of cirrhosis. The evaluated outcome was mortality at 28 and 90 days, according to the different ACLF diagnostic criteria: Chronic Liver Failure Consortium (CLIF-C), Asian Pacific Association for the Study of the Liver-ACLF Research Consortium (AARC) and North American Consortium for the Study of End-Stage Liver Disease (NACSELD). Prognostic performance was evaluated using receiver operating characteristic (ROC) curves.Results146 patients were included. 43 (29.5%) with ACLF according to CLIF-C definition, 14 (9.6%) with ACLF by AARC definition, and 6 (4.1%) by NACSELD definition. According to Kaplan–Meier survival analyses median survival of patients with ACLF by CLIF-C definition was 27.0 days, median survival of patients with ACLF by AARC definition was 27.0 days, and median survival of patients with ACLF by NACSELD definition was 4.0 days. The areas under the ROC curves for performance evaluation in predicting mortality at 28 days for CLIF-C, AARC and NACSELD criteria were, respectively, 0.710, 0.560 and 0.561 (p = 0.002). Regarding 90-day mortality, the areas under the ROC curves were 0.760, 0.554 and 0.555 respectively (p < 0.001).ConclusionACLF definition proposed by CLIF-C had better performance in predicting mortality at 28 and 90 days when compared to criteria proposed by AARC and NACSELD.     

Comparison scoring model of severe viral hepatitis and model of end stage liver disease for the prognosis of patients with liver failure in China

AIM:To estimate the prognosis of patients with liver failure using a scoring model of severe viral hepatitis (SMSVH) and a model of end stage liver disease (MELD) to provide a scientific basis for clinical decision of treatment. METHODS:One hundred and twenty patients with liver failure due to severe viral hepatitis were investigated with SMSVH established. Patients with acute,subacute,and chronic liver failure were 40,46 and 34,respectively. The follow-up time was 6 mo. The survival rates of patients with liver failure in 2 wk,4 wk,3 mo and 6 mo were estimated with Kaplan-Meier method. Comparison between SMSVH and MELD was made using ROC statistic analysis. RESULTS:The survival curves of group A (at low risk,SMSVH score ≤ 4) and group B (at high risk,SMSVH score ≥ 5) were significantly different (The 4-wk,3-mo,6-mo survival rates were 94.59%,54.05%,43.24% in group A,and 51.81%,20.48%,12.05% in group B,respectively,P < 0.001). The survival curves of group C (SMSVH scores unchanged or increased),group D (SMSVH scores decreased by 1) and group E (SMSVH scores decreased by 2 or more) were significantly different .The survival rates of groups C,D and E were 66.15%,100%,100% in 2-wk; 40.0%,91.18%,100% in 4-wk; 0%,58.82%,80.95% in 3-mo and 0%,38.24%,61.90% in 6-mo,respectively,P < 0.001). The area under the ROC curve (AUC) of SMSVH scores at baseline and after 2 wk of therapy was significantly higher than that under the ROC curve of MELD scores (0.804 and 0.934 vs 0.689,P < 0.001). CONCLUSION:SMSVH is superior to MELD in theestimation of the prognosis of patients with severe viral hepatitis within 6 mo. SMSVH may be regarded as a criterion for estimation of the efficacy of medical treatment and the decision of clinical treatment.     

Acute-on-chronic liver failure:Pathogenesis,prognostic factors and management

Acute-on-chronic liver failure(ACLF) is increasingly recognized as a complex syndrome that is reversiblein many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure(OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept(Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.     

重型肝炎及肝衰竭的人工肝个体化治疗

人工肝是重型肝炎肝衰竭治疗的重要方法之一[1].目前临床上应用的人工肝有多种,每一种的原理不尽相同,适应证也有很大差异,同时患者的病情也千差万别.因此,当为患者确定人工肝治疗方案时,应综合考虑人工肝方法和患者病情两个方面的因素,根据患者的病情特点和主观愿望,明确治疗目的,并结合每一种人工肝的原理和特点,为特定的患者选择最合适的治疗方法,以取得最好的疗效,并避免严重并发症的发生.在进行人工肝治疗时,也要根据患者病情特点和人工肝的原理制定个体化的操作方案,确保治疗安全有效.此外,特别需要指出的是,人工肝治疗不是孤立的,必须与内、外科治疗结合起来,才能取得更好的疗效.     

Development of a Widely Applicable and Simple Prognostic Score for Patients with Acute-on-chronic Liver Failure

Background and AimsAcute-on-chronic liver failure (ACLF) tends to progress rapidly with high short-term mortality. We aimed to create a widely applicable, simple prognostic (WASP) score for ACLF patients.MethodsA retrospective cohort of ACLF cases recruited from three centers in China were divided into training and validation sets to develop the new score. A prospective longitudinal cohort was recruited for further validation.ResultsA total of 541 cases were included in the training set, and seven independent ACLF prognostic factors were screened to construct a new quantitative WASP-ACLF table. In the validation set of 671 cases, WASP-ACLF showed better predictive ability for 28-day and 90-day mortality than the currently used prognostic scores at baseline, day 3, week 1, and week 2. The predictive efficacy and clinical validity of the model improved over time. Patients were assigned to low-, intermediate-, and high-risk groups by their WASP-ACLF scores. Compared with the other two groups, intermediate-risk patients had a more uncertain prognosis, with a 90-day mortality of 44.4–50.6%. Sequential assessments at weeks 1 and 2 found the 90-day mortality of intermediate-risk groups was <20% for patients with a ≥2 point decrease in WASP-ACLF and was up to 56% for patients with a ≥2 points increase. Similar results were observed in prospective data.ConclusionsThe new ACLF prognostic score was simple, widely applicable, and had good predictive efficacy. Continuous assessments and trend of change in WASP-ACLF need to be considered, especially for intermediate-risk patients.     

应用糖皮质激素治疗肝衰竭临床疗效研究进展

肝衰竭(liver failure)是一种严重的肝损伤,包括肝脏合成、解毒、代谢和生物转化功能严重障碍或失代偿,可能由多种病因导致,主要特征为出现黄疸、凝血功能障碍、肝性脑病和腹水等[1]。目前,内科支持治疗仍是治疗肝衰竭的主要手段,但探索更经济更有效的治疗方法的脚步从未停止,特别是应用糖皮质激素治疗,虽然充满了争议,但是临床上的应用始终没有停止过。糖皮质激素(glucocorticoids,GCs)属甾体类化合物,是由肾上腺以昼夜节律方式合成和释放的类固醇激素。     

非生物人工肝支持系统治疗肝功能衰竭的血清氨基酸谱变化

目的 分析肝功能衰竭患者接受非生物人工肝支持系统(ALSS)治疗引起的血清氨基酸谱变化,阐述非生物ALSS治疗肝功能衰竭的有效性.方法 对2009年6月至2010年8月间146例肝功能衰竭患者行非生物ALSS治疗,观察治疗前后患者血清氨基酸谱的变化情况,并对不同预后、不同肝功能衰竭类型以及处于不同肝功能衰竭时期患者的血清氨基酸水平的变化进行研究.计量资料采用配对样本的t检验.结果 非生物ALSS治疗后,血清谷氨酸和赖氨酸下降明显[(395.62±200.24)μumol/L比(260.05±169.56)μmol/L,(436.73±326.18)μmol/L比(407.12±292.01)μmol/L;t＝8.611,t＝2.659;均P＜0.01],苏氨酸、支链氨基酸/芳香族氨基酸显著上升[(1302.90±1288.70)μmol/L比(1406.70±1272.34)μmol/L,1.23±0.53比1.36±0.57;t＝2.895,t＝1.061;均P＜0.01].在预后不同的患者间、不同肝功能衰竭类型以及处于不同时期的肝功能衰竭患者间,谷氨酸、酪氨酸、精氨酸以及蛋氨酸等治疗前后差异有统计学意义.结论 非生物ALSS治疗可以改善肝功能衰竭患者血清氨基酸紊乱状况.不同肝功能衰竭分类、分期以及不同预后患者的血清氨基酸谱在非生物ALSS治疗后有显著不同的变化.

Abstract：

Objective To analyze the patterns of amino acid changes in liver failure patients treated with non-bioartificial liver support system (ALSS), and to explore the efficacy of ALSS in liver failure treatment. Methods A total of 146 liver failure patients treated with ALSS from June 2009 to August 2010 were recruited in this study. Paired blood samples were collected from every patient and serum amino acids and ammonia were tested by automatic amino acid analyzer. The changes of amino acids in patients with different prognoses, different types/phases of liver failure were evaluated.Measurement data were compared by paired t test. Results After ALSS treatment, liver failure patients experienced a significant decrease in serum glutamic acid and lysine [(395.62±200.24)μmol/Lvs (260. 05±169.56) μmol/L and (436. 73±326. 18)μmol/L vs (407. 12±292.01) μmol/L,respectively; t= 8. 611 and 2. 659, respectively; both P＜0.01)], while experienced greatly increases in threonine and branched-chain amino acids/aromatic amino acid ratio [( 1302. 90 ±1288.70) μmol/L vs (1406.70 ±1272. 34) μmol/L and 1. 23 ± 0. 53 vs 1. 36 ± 0.57, respectively; t = 2. 895 and 1. 061,respectively; both P＜0. 01)]. The changes of glutamic acid, tyrosine, arginine and methionine before and after ALSS treatment in patients with different prognoses, different types/phases of liver failure were all significantly different. Conclusions ALSS treatment could improve the serum amino acid disorder in liver failure patients. The amino acids in patients with different types/phases or different prognoses of liver failure change significantly after ALSS treatment.     

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL)

The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia–Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22–23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.

慢加急性肝衰竭患者血清中乳酸脱氢酶的临床意义

目的研究慢加急性肝衰竭(ACLF)患者血清中乳酸脱氢酶(LDH)的变化特点及其临床意义。方法比较我院37例ACLF患者病程早、中、晚期血清中LDH的变化;并比较存活组与死亡组血清LDH水平的差异;分析患者血清LDH与总胆红素、凝血酶原时间、全身炎症反应综合征(SIRS)发生率、终末期肝病(MELD)评分及病死率的相关性。结果血清LDH值在ACLF早、中、晚期逐渐升高(F=10.93,P0.001);ALT/LDH值逐渐降低(F=21.09,P0.001);死亡组LDH(365.0 u/L±237.6 u/L)显著高于存活组(209.6 u/L±71.7 u/L)(t=4.88,P0.001);LDH升高程度与凝血酶原时间、MELD评分、SIRS发生率、病死率具有相关性(r值分别为0.63、0.856、0.97、0.96;P值分别为0.001、0.001、0.02、0.035)。结论LDH在ACLF早、中、晚期逐渐升高;LDH升高提示ACLF预后不良。     

给予肾上腺糖皮质激素治疗肝衰竭患者的时机与疗效观察

目的：观察在不同时间应用肾上腺皮质激素（GC）治疗肝衰竭患者的疗效。方法将40例肝衰竭患者分为观察组19例和对照组21例,观察组在起病2周内使用GC治疗,对照组在起病2周后使用GC。两组患者均使用抗炎保肝、对症支持等治疗措施。有抗病毒指征的慢性乙型肝炎患者在知情同意基础上加用核苷类药物抗病毒治疗。观察两组患者治疗后肝功能变化。应用SPSS 13.0统计软件进行统计分析,采用t检验和x2检验。结果在治疗4 w后,观察组和对照组患者血清总胆红素分别为（68.5±46.7）μmol/L和（118.6±61.3）μmol/L,白蛋白分别为（42.8±4.7） g/L和（38.4±5.1） g/L,凝血酶原时间分别为（13.3±3.2）秒和（17.5±4.7）秒,MELD评分分别为（17.6±4.5）和（22.4±5.1）,均有显著性统计学差异（P〈0.01）,病死率分别为10.5%和52.4%,差异有统计学意义（P〈0.05）。结论在肝衰竭患者早期给予GC干预,可明显改善临床症状,促进肝功能恢复,提高患者生存率。     

序贯器官衰竭评分判断肝衰竭患者预后价值

目的通过序贯器官衰竭评分（SOFA）探讨肝衰竭并发多器官功能障碍综合征（MODS）患者预后的价值。方法对118例符合MODS诊断标准的肝衰竭患者进行SOFA评分,比较存活与死亡者临床特征的差异,评判其对肝衰竭合并MODS死亡的判断能力。结果死亡组与生存组患者呼吸系统SOFA得分分别为0.78±0.91和0.13±0.34（P〈0.01）,循环系统为0.55±0.85和0.0±0.0（P〈0.05）,肾脏得分1.43±1.12和0.38±0.81（P〈0.01）;死亡组与生存组患者SOFA总得分分别为10.93±2.21和8.31±1.20（P〈0.05）,受试者工作特征（ROC）曲线下面积为0.857（标准误0.040,渐进显著性水平P＜0.01）,渐进95%可信区间为0.778～0.936。当截断点为8分、9分和10分时,阳性预测值分别为89.2%、92.9%和96.0%,阴性预测值分别为57.1%、45.0%和30.2%。结论 MODS患者呼吸、循环和肾脏功能障碍是肝衰竭死亡的独立危险因素,SOFA评分对肝衰竭的预后具有良好的判断能力。     

肝衰竭患者血浆置换治疗后血清胆红素和凝血酶原活动度变化规律浅探

目的 研究血浆置换(PE)治疗肝衰竭患者血清胆红素和凝血酶原活动度变化规律。方法 2015年2月～2018年8月安徽医科大学第二附属医院肝病科住院的肝衰竭患者47例,分别接受3次以上PE治疗。采用二元多因素Logistic回归分析影响肝衰竭患者短期预后的因素。结果 在治疗12 w末,本组47例患者生存22例(46.8%),死亡25例;25例死亡患者年龄为(47.5±13.4)岁、基线MELD评分为(33.5±6.1)分、PTA为(23.8±10.1)%、APTT为(93.8±40.6)s,与22例生存患者比,差异显著,死亡组肝性脑病发生率为64.0%,显著高于生存组的27.3%(P＜0.05);多因素 Logistic 回归分析提示年龄和基线PTA是影响肝衰竭患者短期预后的独立危险因素;经线性回归分析发现,PE术后TBIL下降与术前TBIL 水平呈正相关(r=0.866,P＜0.05),首次PE术后PTA升高最显著(P＜0.05)。结论 年龄和凝血酶原活动度是影响肝衰竭患者预后的独立危险因素,了解这些重要的指标对判断病情和及时地给予处理对改善预后很有帮助。     

慢加急性(亚急性)肝衰竭及慢性肝衰竭预后危险因素分析

目的 探讨慢加急性(亚急性)肝衰竭及慢性肝衰竭预后不良危险因素.方法 收集我院近3年收治的慢加急性(亚急性)肝衰竭及慢性肝衰竭患者临床资料;根据预后分为好转组与恶化组;重点分析病程超过1周的122例肝衰竭患者预后不良的危险因素,应用Logistic回归分析得出独立危险因素,构建预后方程,并应用ROC曲线下面积(AUC)评价其对预后的预测效能.结果 慢加急性(亚急性)肝衰竭与慢性肝衰竭预后比较差异无统计学意义(P＞0.05).乙肝病毒感染与非乙肝病毒感染者预后比较差异无统计学意义(P＞0.05).48例应用核苷类药物的乙肝相关肝衰竭自行停药者预后差(P＜0.05).恶化组自发性细菌性腹膜炎(SBP)、肝性脑病(HE)、肝肾综合征(HRS)的发生率高于好转组(P＜0.05),基线凝血酶原国际标准化比值(INR)明显高于好转组(P＜0.01),基线血清白蛋白(ALB)、血红蛋白(Hb)、血小板(PLT)水平明显低于好转组(P＜0.05).对上述因素行Logistic回归分析,发现INR及HE是预后的独立危险因素;Logit(P) ＜0.1648者,恶化的可能性为95.1％;INR＜ 1.75者,好转可能性为76.6％.结论 乙肝相关肝衰竭自行停用核苷类药物是预后不良的危险因素.ALB、INR、Hb、PLT、SBP、HE、HRS的发生影响肝衰竭预后.INR及HE是肝衰竭患者预后不良的独立危险因素.     

不同真菌感染对肝衰竭患者病情及预后的影响

目的研究不同真菌感染对肝衰竭患者病情及预后的影响。方法总结肝衰竭合并不同真菌感染患者的临床资料,分析后者对患者病情和转归的影响。结果在资料完整的200例患者中,亚急性肝衰竭3例,慢加急性肝衰竭92例,慢性肝衰竭105例。其中浅部真菌感染39例,侵袭性念珠菌感染89例,侵袭性曲霉菌感染72例。感染前三组患者的终末期肝病模型（MELD）评分分别为25.3±6.0、25.1±6.4和26.2±6.2（P〉0.05）,感染后则分别为25.8±8.7、28.7±9.8和32.9±7.7（P〈0.05）。MELD评分分别增加0.46、3.66和6.75,感染后三组间MELD评分比较,有显著性统计学差异（P=0.000）。浅部真菌感染出院时生存18例（46.1%）,死亡21例（53.9%）,侵袭性念珠菌感染生存34例（38.2%）,死亡55例（61.8%）,侵袭性曲霉菌感染生存11例（15.3%）,死亡61例（84.7%）,三组间病死率比较,差异显著（P〈0.05）。结论侵袭性曲霉菌感染对肝衰竭患者病情恶化的影响最明显,其次是侵袭性念珠菌感染,浅部真菌感染影响较小。     

Acute-on-chronic liver failure in chronic hepatitis B: an update

Introduction: Acute-on-chronic liver failure is a common pattern of end-stage liver disease in clinical practice and occurs frequently in patients with chronic hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a better understanding of this disease.

Areas covered: This review updates the current comprehensive knowledge about HBV-ACLF from epidemiological studies, experimental studies, and clinical studies and provide new insights into the definition, diagnostic criteria, epidemiology, nature history, pathogenesis, treatment and prognostication of HBV-ACLF.

Expert commentary: Patients with chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on-chronic liver failure, with multi-organ failure and high short-term mortality. The precipitating events can be intra-hepatic or extra-hepatic and the underlying chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is the driver of HBV-ACLF, which can be attributed to non-sterile and sterile factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell therapy is a promising alternative to LT, but requires validation and still has concern of long-term safety. Other medical therapies, such as nucleoside analogue, artificial liver supporting and glucocorticoid may improve survival in a specific subgroup. New scoring systems improve the accuracy of prognostication in HBV-ACLF, which is critical for early identification of candidates for LT.     

Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis

AIMTo assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting short-term mortality among patients with alcoholic hepatitis.METHODSWe retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey’s discriminant function (DF), age, bilirubin, international normalized ratio and creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end-stage liver disease (MELD), and MELD-Na.RESULTSOf 264 patients, 32 (12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90), 0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83 (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality.CONCLUSIONCLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.     

代谢相关脂肪性肝病慢加急性肝衰竭的过去、现状与未来

代谢相关脂肪性肝病(MAFLD)是目前脂肪性肝病领域的热议话题,它已成为全球最常见的慢性肝病。预计在未来的20年内,MAFLD及相关肝硬化的发病率仍将不断增加,成为新的全球性健康问题。慢加急性肝衰竭(ACLF)是指在慢性肝病基础上,短期内发生的急性或亚急性肝功能失代偿状态,以腹水、黄疸、凝血功能障碍和肝性脑病为主要表现的临床症候群。在有限的资料基础上,对MAFLD-ACLF的流行病学、发病机制和治疗管理策略等问题进行讨论和展望。