Aetiology and outcome of acute liver failure

Background:

Acute liver failure (ALF) is a clinical syndrome characterized by the sudden onset of coagulopathy and encephalopathy. The outcome is unpredictable and is associated with high morbidity and mortality. We reviewed our experience to identify the aetiology and study the outcome of acute liver failure.

Methods:

A total of 1237 patients who presented with acute liver failure between January 1992 and May 2008 were included in this retrospective study. Liver transplantation was undertaken based on the King''s College Hospital criteria. Data were obtained from the units prospectively collected database. The following parameters were analysed: patient demographics, aetiology, operative intervention, overall outcome, 30-day mortality and regrafts.

Results:

There were 558 men and 679 women with a mean age of 37 years (range: 8–78 years). The most common aetiology was drug-induced liver failure (68.1%), of which 90% was as a result of a paracetamol overdose. Other causes include seronegative hepatitis (15%), hepatitis B (2.6%), hepatitis A (1.1%), acute Budd–Chiari syndrome (1.5%), acute Wilson''s disease (0.6%), subacute necrosis(3.2%) and miscellaneous (7.8%). Three hundred and twenty-seven patients (26.4%) were listed for liver transplantation, of which 263 patients successfully had the procedure (80.4%). The current overall survival after transplantation was 70% with a median follow-up of 57 months. After transplantation for ALF, the 1-year, 5-year and 10-year survival were 76.7%, 66% and 47.6%, respectively. The 30-day mortality was 13.7%. Out of the 974 patients who were not transplanted, 693 patients are currently alive. Among the 281 patients who died without transplantation, 260 died within 30 days of admission (26.7%). Regrafting was performed in 31 patients (11.8%), the most common indication being hepatic artery thrombosis (11 patients).

Conclusion:

Paracetamol overdose was the most common cause of acute liver failure. Liver transplantation, when performed for acute liver failure, has good long-term survival.     

Experimental research on TECA-I bioartificial liver support system to treat canines with acute liver failure

AIM To evaluate the efficacy and safety of the TECA-Ibloartificial liver support system(BALSS)in treatingcanines with acute liver failure(ALF).METHODS Ten canines with ALF induced by 80% liverresection received BALSS treatment(BALSS group).Blood was perfused through a hollow fiber tube containing1×10~(10) porcine hepatocytes.Four canines with ALF weretreated with BALSS without porcine hepatocytes(controlgroup),and five canines with ALF received drugtreatment(drug group).Each treatment lasted 6 hours.RESULTS BALSS treatment yielded beneficial effects forpartial liver resection-induced ALF canines with survivaland decreased plasma ammonia,ALT,AST and BIL.Therewas an obvious decrease in PT level and increase in PAlevel,and there were no changes in the count oflymphocytes,immunoglobulins(IgA,IgG and IgM)andcomplement(C3 and CA)levels after BALSS treatment.Incontrast,for the canines with ALF in non-hepatocyteBALSS group(control group)and drug group,there wereno significant changes in ammonia,ALT,AST,BIL,PTand PA levels.ALF canines in BALSS group,controlgroup and drug group lived respectively an average timeof 108.0h±12.0h,24.0h±6.0h and 20.4h±6.4h,andthree canines with ALF survived in BALSS group.CONCLUSION TECA-I BALSS is efficacious and safe forALF canines induced by parcial liver resection.     

Inappropriate pemoline therapy leading to acute liver failure and liver transplantation

A 36-year-old female, presenting with jaundice, developed acute liver failure requiring orthotopic liver transplantation. On admission, none of the known causative factors for acute hepatitis, including use of drugs, were found to be present. Several days after hospitalization, the patient admitted taking therapy prescribed by a "non-traditional" physician, that she had been using for several years due to overweight and which had recently been modified with the introduction of pemoline. A considerable body of evidence exists in the medical literature showing that pemoline, which is a central nervous system stimulant, has variable hepatotoxic effects, ranging from a mild transient increase of serum transaminases to liver failure, including some lethal cases.     

TECA hybrid artificial liver support system in treatment of acute liver failure

AIM:To assess the efficacy and safety of TECA type hybridartificial liver support system(TECA-HALSS)in providingliver function of detoxification,metabolism and physiologyby treating the patients with acute liver failure(ALF).METHODS:The porcine liver cells(1-2)×10~(10) wereseparated from the Chinese small swine and cultured in thebloreoctor of TECA-BALSS at 37.0℃ and circulated throughthe outer space of the hollow fiber tubes in BALSS.The sixliver failure patients with vadous degree of hepatic comawere treated by TECA-HALSS and with conventionalmedicines.The venous plasma of the patients wasseparated by a plasma separator and treated by charcoaladsorbent or plasma exchange.The plasma circulatedthrough the inner space of the hollow fiber tubes of BALSSand mixed with the patients' blood cells and flew back totheir blood circulation.Some small molecular weightsubstances were exchanged between the plasma andporcine liver cells.Each treatment lasted 6.0-7.0h.Physiological and biochemical parameters were measuredbefore,during and after the treatment.RESULTS:The average of porcine liver cells was(1.0-3.0)×10~(10) obtained from each swine liver using our modifiedenzymatic digestion method.The survival rate of the cellswas 85%-93% by trypan blue stain and AO/PI fluorescentstain.After cultured in TECA-BALSS bioreactor for 6 h,thesurvival rate of cells still remained 70%-85%.At the end ofTECA-HALSS treatment,the levels of plasma NH_3,ALT,TBand DB were significantly decreased.The patients who werein the state of drowsiness or coma before the treatmentimproved their appetite significantly and regainedconsciousness,some petients resumed light physical workon a short period after the trestment.One to two days afterthe treatment,the ratio of PTA increased warkedly.Duringthe treatment,the heart rates,blood pressure,respirationcondition and serum electrolytes(K~ ,Na~ and cr)werestable without thrombosis and bleeding in all the sixpatients.CONCLUSION:TECA-HALSS treatment could be a rapid,safe and efficacious method to provide temporary liversupport for patients with ALF.     

Ratio of circulating follistatin and activin A reflects the severity of acute liver injury and prognosis in patients with acute liver failure

BACKGROUND AND AIM: The activin A-follistatin system is known to play a critical role in hepatocyte regeneration during the repair of liver tissue. However, the relationship between blood levels of these compounds and the severity and prognosis of acute liver injury remains unclear. The aim of this study was to evaluate the clinical significance of circulating activin A and follistatin in patients with acute liver disease. METHODS: Serum activin A and plasma follistatin levels were determined on admission by enzyme-linked immunosorbent assay in 32 patients with acute hepatitis (AH), 23 patients with acute severe hepatitis (ASH) and 16 patients with acute liver failure (ALF). RESULTS: Both serum activin A and plasma follistatin levels were significantly elevated in patients with ASH and ALF when compared with those in patients with AH and normal controls (NC). Although plasma follistatin levels were significantly and positively correlated with serum activin A levels (r = 0.413, P < 0.001), the follistatin and activin A (F/A) ratio showed distinct deviation from NC between AH and ALF patients. The F/A ratio in AH patients was significantly elevated when compared with NC, but was significantly reduced in ALF patients. Furthermore, the F/A ratio in non-surviving ALF patients was significantly lower than that in survivors. Levels of serum activin A and plasma follistatin were significantly and negatively correlated with prothrombin time (PT) and normotest (NT) levels, while the F/A ratio showed significant and positive correlations with PT and NT. CONCLUSIONS: Decreased blood F/A ratio in ALF patients may be a reliable indicator of the severity of acute liver injury and prognosis in ALF.     

儿童急性肝衰竭

儿童急性肝衰竭是一种以肝性脑病、黄疸、凝血障碍和腹水为主要表现的临床综合征,常导致多器官功能障碍,病死率较高,是重症医学面临的救治难题。由于儿童这个群体的特殊性,儿童急性肝衰竭和成人相比在定义、病因以及诊治过程中均有其独特性。近年来随着医学技术的发展,尤其是重症医学的发展使得急性肝衰竭的预后有所改善。儿童肝移植的发展也为儿童急性肝衰竭的治疗提供了更多的机会。     

Imatinib mesylate as a cause of acute liver failure

A 46-year-old patient diagnosed with chronic myeloid leukemia in whom cytogenetic and molecular remission had never been achieved was commenced on Imatinib Mesylate (Gleevec, Novartis Pharmaceuticals Corp., East Hanover, NJ). After 18 months of treatment, she developed abnormal liver function tests and subsequently acute liver failure, requiring transfer to the regional liver unit. The patient proceeded to liver transplantation but later died. The explanted liver had histological features of severe hepatic necrosis. This is the first case described of fatal hepatic necrosis in a patient who has have been on long-term imatinib therapy. This may have implications for long-term use of the drug and emphasizes the need for regular monitoring of liver function.     

Acute liver failure as the initial manifestation of acute leukaemia

Abstract: Background/Aims: Haematological malignancies seldom cause clinically significant liver disease. Acute liver failure as the initial manifestation of acute leukaemia is very rare and carries a very poor prognosis. Methods/Results: Three cases of acute liver failure secondary to acute leukaemia are described. Each case presented initially as acute liver failure of uncertain cause. Specific treatment for the leukaemia was instituted; however, all three patients died as a consequence of the liver failure. We describe the clinical course and relevant investigations of these patients and discuss possible mechanisms of acute liver failure in this setting. Conclusion: Acute leukaemia presenting as acute liver failure has a very poor prognosis. Although a rare cause of acute liver failure, it should be considered in any patient presenting with acute liver failure with prodromal symptoms and a raised peripheral white cell count, lactate dehydrogenase and uric acid.     

妊娠急性脂肪肝并发急性肝衰竭12例临床分析

目的分析妊娠急性脂肪肝（acute fatty liver of pregnancy。AFLP）并发急性肝衰竭（acute liver failure,AtY）的Il缶床特征。方法以我院1996年9月-2009年2月收治的12例APLP合并ALF患者为研究对象,回顾性分析其临床表现、实验室检查及治疗等相关资料。结果12例年龄23～33（28．0＋3．2）岁。发病时孕周34～38（35．8±1．4）周,均为妊娠晚期发病。主要症状有恶心、乏力、呕吐和纳差。主要实验室检查指标异常,12例均WBC、TBIL、ALT或AST、Cr升高及PTA降低,9例PLT降低。主要并发症为急性肾衰竭（10例）、低血糖（10例）、弥散性血管内凝血（disseminated intravascular coagulation,DIC）（9例）、产后出血（7例）和肝性脑病（5例）。10例痊愈出院,2例死亡,新生儿死亡2例。结论AFLP并发ALF易发生急性肾衰竭和DIC等多脏器功能衰竭。早诊断、及早进行剖宫产手术及加强对症支持治疗可改善预后。经过治疗,大部分患者肝、肾功能可恢复正常。     

Acute kidney injury in acute liver failure: a review

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.     

急性肝衰竭的治疗进展

急性肝衰竭(ALF)是一种罕见的危及生命的疾病,病情发展迅速并影响多个器官系统功能,生存率低。早期识别病因及保护重要脏器功能对生存至关重要。近年来,随着人工肝、干细胞移植及肝移植技术不断发展,ALF疗效有明显提高。主要从ALF的病因和累及的主要器官系统两大方面阐述了ALF的治疗,并介绍了人工肝及干细胞移植的最新进展。     

Hyperlactatemia in patients with non-acetaminophen-related acute liver failure

AIM:To characterize hyperlactatemia in patients withnon-acetaminophen acute liver failure(ALF)in anattempt to clarify the mechanisms implicated and therole as a prognosis factor.METHODS:In the setting of liver transplantation,63consecutive patients with non-acetaminophen acute liverfailure were studied in relation to tissue oxygenation,hemodynamic and metabolic parameters.Before andafter transplantation,the number of infected patientsand outcome were registered.RESULTS:Acute ALF showed higher levels of lactatethan subacute ALF(5.4±1 mmol/L versus 2.2±0.6mmol/L,P=0.01).Oxygenation parameters were withinthe normal range.Lactate levels showed good correlationwith respiratory quotient(r=0.759,P<0.005),meanglucose administration(r=0.664,P=0.01)andencephalopathy(r=0.698,P=0.02),but not withsplanchnic arteriovenous difference in PCO2,pH and thepresence of infection(P=0.1).Portal vein lactate washigher(P<0.05)than arterial and mixed venous lactate,suggesting its production of hyperlactatemia in theintestine and spleen.The presence of infection was anindependent predictor of survival.CONCLUSION:Hyperlactatemia is not a prognosisfactor due to byproduct of the overall acceleration inglycolysis.     

Prognostic models for acute liver failure

BACKGROUND:Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES:Five English-language medical databases,MEDLINE,ScienceDirect,OVID,Springer Link and Wiley Interscience were searched for articles on acute liver failure, prognosis,and related topics. RESULTS:Multi-variable prognostic models including the King's College Hospital cr...     

Indicators and outcome of liver transplantation in acute liver decompensation after flares of hepatitis B

Summary. Non‐cirrhotic patients having acute liver decompensation in flares of hepatitis B can recover spontaneously or die without liver transplantation. Criteria for identifying patients in need of liver transplantation are lacking. Fifty‐one non‐cirrhotic patients having acute liver decompensation in flares of hepatitis B were retrospectively reviewed. The patients were divided into three groups: group A patients (n = 18) recovered from acute liver decompensation spontaneously; group B patients (n = 22) died of acute liver failure; and group C patients (n = 11) had liver transplantation. Model of end‐stage liver disease (MELD) scores were evaluated to identify the criteria for liver transplantation. The cut‐off point of MELD scores for liver transplantation was evaluated by receiver operating characteristic (ROC) curve. Comparing group A and B patients, MELD score was an independent factor to predict prognosis. By analysing ROC curve, a MELD score > 30 was the most optimal cut‐off point to indicate liver transplantation; however, the false positive rate was 11.1%. By weekly measurement of MELD scores, subsequent increase in MELD scores could help to avoid false positives. Moreover, a MELD score > 34 yielded 0% false positive rate and indicated the necessity of definite liver transplantation. For group C patients, ten of 11 patients were saved by liver transplantation. In conclusion, for the patients having acute liver decompensation in flares of hepatitis B, liver transplantation is definitely indicated by MELD scores > 34. Liver transplantation is also indicated if the MELD score increases in the subsequent 1–2 weeks. Liver transplantation has a good outcome if performed on time.     

Listeria monocytogenes-associated acute hepatitis in a liver transplant recipient

ABSTRACT— We report a case of Listeria monocytogenes bacteriemia with liver involvement mimicking acute viral hepatitis in a liver transplant recipient. The patient presented with fever, jaundice and alanine aminotransferase levels ten times the upper limit of normal. Liver biopsy showed signs of acute hepatitis and occasional granulomas. Both blood and liver biopsy cultures were positive for Listeria monocytogenes. The patient received a 3 week course of ampicillin and gentamicin with clinical and biochemical recovery. Liver involvement during Listeria infections is unusual, and most cases occur in patients with underlying hepatic disease and impaired cell-mediated immunity. To our knowledge only one such case has previously been reported in a liver transplant patient. Furthermore, in the present case we isolated the causal agent from the liver biopsy specimen.     

Effects of a bioartificial liver support system on acetaminophen induced acute liver failure canines

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