Prognostic factors and treatment effect of standard-volume plasma exchange for acute and acute-on-chronic liver failure: A single-center retrospective study

Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n?=?45) and ALF (n?=?10) who received standard-volume PE (1–1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P?=?0.008), post-PE hemoglobin (P?=?0.039), and post-PE CLIF-C ACLF scores (P?=?0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve?=?0.719, P?=?0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.     

Bench-to-bedside review: Current evidence for extracorporeal albumin dialysis systems in liver failure

Acute liver failure (ALF) and acute on chronic liver failure (AoCLF) carry a high mortality. The rationale for extracorporeal systems is to provide an environment facilitating recovery or a window of opportunity for liver transplantation. Recent technologies have used albumin as a scavenging molecule. Two different albumin dialysis systems have been developed using this principle: MARS (Molecular Adsorbent Recirculation System) and SPAD (Single-Pass Albumin Dialysis). A third system, Prometheus (Fractionated Plasma Separation and Adsorption), differs from the others in that the patient's albumin is separated across a membrane and then is run over adsorptive columns. Although several trials have been published (particularly with MARS), currently there is a lack of controlled studies with homogenous patient populations. Many studies have combined patients with ALF and AoCLF. Others have included patients with different etiologies. Although MARS and Prometheus have shown biochemical improvements in AoCLF and ALF, additional studies are required to show conclusive benefit in short- and long-term survival. The appropriate comparator is standard medical therapy rather than head-to-head comparisons of different forms of albumin dialysis.     

Herpes simplex virus load to monitor antiviral treatment after liver transplantation for acute herpetic hepatitis

Herpes simplex virus (HSV) hepatitis is an uncommon cause of acute liver failure (ALF), primarily affecting immunocompromised patients. So far, 148 cases have been published, of which 9 underwent liver transplantation (LT). The reported post-transplant survival is poor, with over 60% dying in the first year. Dosing and duration of antiviral therapy after LT are not established. Concerns include both the risk of hepatic recurrence after LT and emergence of viral resistance during prolonged therapy. HSV DNA plasma levels might be helpful to monitor therapeutic response and guide duration of therapy. We present a case of ALF complicating a primary HSV-1 infection in an immunocompetent host, who required emergency LT. We further discuss the value of measuring serial HSV DNA plasma loads to monitor antiviral therapy.     

Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.     

Pediatric Wilson disease presenting as acute liver failure: Prognostic indices

BACKGROUNDAcute liver failure (ALF) can be a primary presentation of Wilson disease (WD). Mortality rates are high in WD with ALF (WDALF). Predictions of mortality in WDALF vary by model and are sometimes contradictory, perhaps because few patients are studied or WD diagnoses are questionable. AIMTo determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODSWe reviewed the medical records of our pediatric WDALF patients (n = 41 over 6-years-old, single-center retrospective study) and compared seven prognostic models (King’s College Hospital Criteria, model for end-stage liver disease/pediatric end-stage liver disease scoring systems, Liver Injury Unit [LIU] using prothrombin time [PT] or international normalized ratio [INR], admission LIU using PT or INR, and Devarbhavi model) with one another.RESULTSAmong the 41 Han Chinese patients with ALF, WD was established by demonstrating ATP7B variants in 36. In 5 others, Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis. Three died during hospitalization and three underwent liver transplantation (LT) within 1 mo of presentation and survived (7.3% each); 35 (85.4%) survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis. Parameters significantly correlated with mortality included encephalopathy, coagulopathy, and gamma-glutamyl transpeptidase activity, bilirubin, ammonia, and serum sodium levels. Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSIONWDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis, even after enlisting for LT.     

Liver support in fulminant liver failure after hemorrhagic shock

Acute liver failure (ALF) is a rare clinical syndrome associated with a mortality of up to 80% and its management remains an interdisciplinary challenge. Despite recent improvements in intensive care management, the mortality of patients with ALF remains high and is related to complications such as cerebral edema, sepsis and multiple organ failure. Emergency orthotopic liver transplantation (OLT) is currently the only effective treatment for those patients who are unlikely to recover spontaneously. Nevertheless, OLT is not always possible because of the shortage of the organs and/or complications related to ALF. Newly introduced liver-assist devices can temporarily support the patient's liver until native liver recovers or can serve as a bridging device until a liver graft is available. The support devices use both cell-based and non-cell-based techniques. One of the latest non-cell-based extracorporeal hepatic support devices, the molecular adsorbent recycling system (MARS), is based on the concept of albumin dialysis. MARS utilises selective hemodiafiltration with countercurrent albumin dialysis aiming to selectively remove both water-soluble and albumin-bound toxins of the low and middle molecular-weight range. We report on a young patient who presented with clinical symptoms of ischemic hepatitis and multi-organ failure (APACHE II score 38-->predicted postoperative mortality 87%) due to prolonged hemorrhagic shock. OLT was contraindicated because of history of pancreas cancer with metastases. It was necessary to use aggressive conservative therapy and an extracorporeal liver-assist device until liver regeneration began and hemodynamic conditions were stable. The patient underwent five treatments with MARS. During the treatment, there were improvements of hemodynamics, respiratory function, acid-base disturbances and laboratory parameters. The plasma disappearance rate of indocyanine green, a parameter of dynamic liver function, improved during MARS treatment. Although repeated neurological examination predicted diffuse brain damage (brain oedema, decreased cerebral blood flow), the patient recovered without any neurological deficits. The patient survived and was discharged from the hospital in good condition. In this case MARS treatment was successful in supporting the patient through the most critical period of ALF.     

肝移植治疗重型肝炎/肝衰竭的手术时机

肝移植已成为治疗各种原因所致的急慢性肝功能衰竭患者的一种有效治疗手段,但是关于重型肝炎/肝衰竭肝移植治疗的手术时机选择问题,目前国内外尚无统一标准。本文旨在通过总结国内外肝移植治疗肝衰竭的相关文献,结合我中心肝移植治疗重型肝炎/肝衰竭的经验,探讨肝移植治疗重型肝炎/肝衰竭的手术时机。     

Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).

OBJECTIVE: The primary purpose of this review article is to familiarize critical care practitioners with newly developing techniques of hybrid artificial liver support. Implantable and extracorporeal hepatocyte culture systems are emphasized based on their current experimental and clinical status. DATA SOURCES: Data used to prepare this document were obtained from the authors' personal files, as well as the computerized MEDLINE database. Medical headings used include: liver, artificial organs, cell culture, growth hormones, extracellular matrix, and transplantation. Only articles published in English have been cited. STUDY SELECTION: All studies are discussed in which hepatocyte culture systems have been used to support human patients with liver failure. All studies reported the patient's condition before therapy, duration of therapy, and outcome after therapy in order to be included in this review. Since the number of clinical trials is small at this time, animal studies were used to demonstrate application of other systems in the treatment of experimentally induced liver failure. Similar selection criteria were used to select animal studies for review. All initially identified human studies met these selection criteria. DATA EXTRACTION: Independent extraction by multiple observers. DATA SYNTHESIS: Liver failure, resulting from infection, drugs, or as a part of the multiple organ failure syndrome, remains a major cause of morbidity, mortality, and resource allocation. Current therapy is limited to supportive care, along with liver transplantation. Because of these therapeutic limitations, hybrid artificial liver systems have been proposed for temporary and long-term hepatic support. Several animal studies and a small number of preliminary human studies indicate that hepatocyte culture systems are capable of supporting nearly all essential hepatic functions and may supply biologically active substances that promote regeneration and repair of the damaged liver being supported. Hybrid systems may be constructed from materials that serve as immunoprotective barriers against host defenses. CONCLUSIONS: During the past decade, important progress has been made with hybrid artificial liver support systems. Cell culture technology has progressed sufficiently so that an artificial liver, composed of metabolically active hepatocytes, may be a potential reality in the foreseeable future. Both implantable and extracorporeal artificial liver support systems have been developed to provide metabolic support during acute liver failure, or to serve as a bridge to solid organ transplantation. Implantable hepatocyte systems, however, require a prolonged period for intraperitoneal engraftment and vascularization, not typically available to patients with acute liver failure. For this reason, extracorporeal hybrid designs offer the greatest hope for on-line treatment of acute liver failure. Such systems are entering the final stages of animal testing.     

Equipment review: the molecular adsorbents recirculating system (MARS)

The molecular adsorbents recirculating system (MARS) is a form of artificial liver support that has the potential to remove substantial quantities of albumin-bound toxins that have been postulated to contribute to the pathogenesis of liver cell damage, haemodynamic instability and multi-organ failure in patients with acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF). These toxins include fatty acids, bile acids, tryptophan, bilirubin, aromatic amino acids and nitric oxide. Data from controlled clinical trials are limited so far. One of two studies performed on small numbers of patients with AoCLF suggest a survival benefit, but no controlled data are available in the ALF setting. Our preliminary experience with MARS therapy, instituted late in the clinical course of five patients with severely impaired liver function, including three with AoCLF precipitated by sepsis and two with liver dysfunction due to sepsis in the absence of pre-existing chronic liver disease, indicates some clinical efficacy. However, the overall survival rate (1 of 5; 20%) remained poor. More data obtained from larger cohorts of patients enrolled in randomised controlled studies will be required in both the AoCLF and ALF settings to identify categories of liver failure patients who might benefit most from MARS treatment, to ascertain the most appropriate timing of intervention and to determine the overall impact on outcome, including cost-effectiveness.     

Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition?

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.     

Acute liver failure: liver support therapies

PURPOSE OF REVIEW: We summarize the therapeutic approach to patients with acute liver failure with the main focus on bioartificial and artificial liver support. We also describe specific and general therapeutic approaches based upon recent advances in the understanding of the pathophysiology of acute liver failure. RECENT FINDINGS: Bioartificial liver support systems use hepatocytes in an extracorporeal device connected to the patient's circulation. Artificial liver support is intended to remove protein-bound toxins and water-soluble toxins without providing synthetic function. Both systems improve clinical and biochemical parameters and can be applied safely to patients. Although bioartificial liver-assist devices have not been shown to improve the survival of patients with acute liver failure, further development is underway. Artificial liver support systems have been shown to alter several pathophysiological mechanisms involved in the development of acute liver failure but survival data are still limited. SUMMARY: Mortality in patients with acute liver failure is still unacceptably high. The most effective treatment, liver transplantation, is a limited resource and so other therapeutic options to bridge patients to recovery or stabilization have to be considered. Better understanding of the pathophysiology of acute liver failure and device development is necessary to achieve the elusive goal of effective extracorporeal liver assist.     

重型蝮蛇咬伤患者在ICU早期血液净化治疗分析

目的：探讨重型蝮蛇咬伤患者在ICU早期血液净化治疗效果。方法：选择我院ICU收治的重型蝮蛇咬伤患者28例,分为对照组和血液净化组,两组患者早期急救措施及治疗原则相同,血液净化组在咬伤后24h内行血液灌流（HP）＋连续静脉-静脉血液透析滤过（CVVHDF）治疗。检测两组患者入院治疗前和治疗3d后的白细胞计数、C反应蛋白（CRP）、肝功能（ALT与AST）、肾功能（BUN与Cr）、肌酸激酶同工酶（CK-MB）、血清肌红蛋白（MB）水平,并统计两组患者的多器官功能衰竭发生率。将所得数据做统计学分析。结果：血液净化组患者治疗3d后,血白细胞计数、CRP、心、肝、肾功能等指标与对照组比较明显好转,且多器官衰竭发生率也低于对照组,相关数据差异有统计学意义。结论：重型蝮蛇咬伤患者早期行血液净化治疗,可有效地保护器官功能、减轻全身炎症反应,防止多器官功能衰竭的发生,提高救治的成功率。     

急性肝功能衰竭的综合治疗

急性肝功能衰竭(ALF)是一种病因多样、病理生理变化复杂、临床表现凶险的综合征,患者自然死亡率高。ALF的治疗包括祛除病因、维持血流动力学和内环境稳定、保护重要脏器功能、人工肝支持和肝脏移植。及早综合利用各种治疗手段可有效地改善患者预后。     

Hodgkin’s lymphoma coexisting with liver failure secondary to acute on chronic hepatitis B

Acute on chronic liver failure (ACLF) is rarely the initial manifestation of a malignant process or precipitated by the initiation of anti-viral treatment with a nucleoside or nucleotide agent. We report an unusual case of ACLF temporally associated with initiation of Entecavir for treatment of chronic hepatitis B. Early Hodgkin’s lymphoma (HL) was unmasked with initiation of the anti-viral treatment which may have exacerbated ACLF. To the best of our knowledge, this has not been described in the literature. In reviewing our patients clinical course and liver autopsy, he developed a severe acute exacerbation of his chronic hepatitis B virus coinciding with the institution of antiviral therapy and the underlying HL perhaps modulating the overall degree of hepatic injury.     

Bridging to transplantation in acute liver failure in a 7-month-old infant

BACKGROUND: Acute liver failure (ALF) in children is a rare but often fatal event. At present, liver transplantation is the only successful therapy in most cases. In the face of deteriorating hepatic encephalopathy in these children, some bridging therapy using artificial detoxification can be necessary to enable successful transplantation. In adults, albumin dialysis using the molecular absorbent recycling system (MARS) has been described as effective for bridging to liver transplantation. CASE REPORT: A previously healthy 7-month-old infant was admitted with ALF due to autoimmune hepatitis. King's College criteria for children with ALF indicated the need for transplantation (bilirubin 13.7 mg/dl, leukocytes 18,980/mm3, INR 5.83, age<2 years). Despite moderate hyperammonemia (75 microm/l) along with the development of pneumonia, the child deteriorated hemodynamically and neurologically, showing grade III encephalopathy proven by EEG. Albumin dialysis using MARS was used to bridge 36 hours to successful living-donor split-liver transplantation, and resulted in improvements in EEG, plasma levels of amino acids and hemodynamics. Twenty-four months after transplantation the child shows normal liver function and normal neuropsychological development. The explanted liver showed 80 % tissue destruction from autoimmune hepatitis. CONCLUSION: Albumin dialysis as described can be used successfully in infants < 1 year old for bridging to liver transplantation in cases of acute hepatic failure with deteriorating encephalopathy.     

Bench-to-beside review: Acute-on-chronic liver failure - linking the gut,liver and systemic circulation

The concept of acute-on-chronic liver failure (ACLF) was introduced recently to describe a subset of patients with chronic liver disease presenting with profound deterioration of liver function and rapidly evolving multi-organ failure. ACLF is frequently accompanied by the development of severe inflammatory response syndrome and has a high mortality. To date, treatment options are limited and exclusively supportive. Over the last few years, some insights have been generated in the pathophysiology of ACLF. A key role for the interaction of innate immune dysfunction, enhanced bacterial translocation from the gut, and circulatory dysfunction has been proposed. In this respect, therapeutic strategies have been examined, with variable success, in experimental studies in animals and humans. This review focuses on potentially relevant pathophysiological elements in the development of ACLF and points out promising treatment modalities in ACLF.     

慢加急性肝衰竭患者低血糖发生现状及危险因素分析

目的 了解慢加急性肝衰竭患者空腹血糖的临床特点,分析其发生空腹低血糖的危险因素,为临床早期识别和预防低血糖提供参考.方法 回顾性分析2013年5月—2019年12月在广州市某三级甲等医院感染科住院的931例慢加急性肝衰竭患者的临床资料,描述慢加急性肝衰竭患者空腹血糖的情况,根据血糖结果 分为低血糖组和非低血糖组,采用单...     

Quality of life following emergency liver transplantation for acute liver failure

INTRODUCTION: Liver transplantation is an accepted and successful therapy for both acute and chronic liver diseases (CLDs), with good survival outcomes. Whilst the study of health-related quality of life (HRQoL) post transplantation for CLDs have been well documented, there is little data measuring HRQoL following liver transplantation for acute liver failure (ALF) patients. PATIENTS AND METHODS: Data were collected using between-method triangulation; however, only the quantitative element of the study is reported here. Measuring eight health domains, we distributed the short form 36 (SF-36) questionnaire by post to 96 acute and chronic transplant recipients. Differences between the groups were measured using both parametric and non-parametric t-tests. RESULTS: Overall, the patients showed a satisfactory HRQoL; there were no differences between either acute or chronic transplant groups in seven of the eight domains of quality of life. Among the patients transplanted for ALF, there were no differences in HRQoL between patients transplanted for paracetamol hepatotoxicity compared with other indications, and no variations in HRQoL related to recipient gender, employment or length of survival post transplantation. When compared with the UK SF-36 normal values to the ALF transplant recipients, there was a significantly lower physical functioning and role emotional scores. CONCLUSION: Regardless of aetiology, most of recipients transplanted for ALF have a HRQoL comparable with chronic transplant recipients.     

Extracorporeal support of the failing liver

Successes in machine-based extracorporeal support for different organ functions stimulated research in the field of liver support approximately 50 years ago. Initial failure to improve outcome using detoxification methods like dialysis, blood and plasma exchange, or plasmapheresis over sorbents fueled interest in biologic liver support concepts using bioreactors or combined methods. New device configurations, technical improvement of existing detoxification methods, and the refinement in cell culture techniques led to a boost in research on biologic and nonbiologic approaches. Currently, many systems are in the preclinical phase or have entered clinical studies. A number of completed clinical trials have reported a favorable therapeutic impact of the most advanced solutions on the course and outcome of liver failure. Often, findings must be reconfirmed. However, current knowledge suggests that extracorporeal liver support can successfully stabilize liver function, improve the clinical condition of patients, and considerably improve survival in certain subgroups of patients with fulminant hepatic failure and acute decompensation of chronic hepatic failure. Although the initial focus of liver support methods was bridging to liver transplantation, bridging to recovery of organ function and treatment of intractable pruritus are now valuable indications.     

人工肺膜材料的生物相容性评价

人工肺又名氧合器,集氧合、变温、储血、过滤、回收血等功能于一体,将含氧量低的静脉血经过氧合后成为含氧量高的动脉血,是一种接近人体生理状态,较为理想的人工脏器.膜式人工肺已广泛应用于心血管手术的体外循环,也广泛应用于呼吸衰竭的抢救治疗,即体外生命支持或体外膜氧合,血管内氧合器也已初步应用于临床.尤其对病重、心功能差、估计手术时间长的患者,膜式氧合器的使用更为必要.当前,通过改进膜材料、优化设计以及对各种性能的实验评估和临床评价,人工肺的研究着力于提高气体交换能力和生物相容性,为抢救患者的生命提供更可靠的手段.