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Acute liver failure (ALF) is a rare condition in the pediatric population. Patients who present with severe failure of liver synthetic function have a high mortality with medical therapy alone. The main causes of death are cerebral edema, hemorrhage, renal failure and sepsis. The etiology of ALF is age specific, with a significant number due to inborn errors of metabolism especially in neonates and infants. Treatment of children with ALF is supportive, aimed at preventing and managing associated complications until the native liver recovers or liver transplantation. Sedation should not be administered unless a decision for artificial ventilation has been made. As all children are potential transplant candidates, transfer to and management in a liver transplant centre is recommended. Prognostic criteria for mortality are less well defined compared to the adult population, although a significantly elevated INR > or = 4 carries a high chance of death, and liver transplantation should be considered at this stage. Auxiliary transplantation is an attractive option in selected individuals and provides the chance to stop immunosuppression should sufficient hepatic regeneration occur. The use of various liver assist devices and hepatocyte transplantation as a bridge to liver transplantation show promise, although when used in isolation, they do not have an impact on overall patient survival.
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PMID:Acute liver failure. 1187 28

As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score between 6 and 11. The reduction of bilirubin and ammonia were very significant (P < 0.01), whereas the changes of International Normalized Ratio (INR) were not significant. Also the modifications of albumin, total protein, sodium, potassium and calcium were not significant. In conclusion, four out of nine patients with PNF are alive without a second transplantation and were discharged after about 48 days; four out of nine underwent OLT, while one out of nine died; five out of six patients with DF are alive without a second transplantation, and they were discharged after an average time of 55.5 days, one out of six died; six out of nine patients with fulminant hepatitis underwent OLT and four of these are alive, while two died due to sepsis; three patients are alive without OLT. Four patients with AOCHF underwent OLT and are alive, three patients are alive and on a waiting list, two died while on a waiting list and one patient who experienced reactivation of HBV infection during chemotherapy for non-Hodgkin's lymphoma is alive. In spite of the limited number of cases of our study, we believe that MARS can be applied with high tolerance for a very long period of time. In addition, its repeatability allows it to be used in patients with DNF and FH as a bridge to transplant. In patients with DNF, it is used while waiting for complete recovery of the transplanted organ.
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PMID:MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure. 1222 Mar 3

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.
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PMID:Liver support in fulminant liver failure after hemorrhagic shock. 1453 Nov 74

Acute liver failure (ALF) is a severe, life-threatening condition associated with a high mortality rate. The objective of this study is to present the experience of a Chilean liver transplant program with orthotopic liver transplantation (OLT) for ALF. All patients with the diagnosis of ALF evaluated in our program between January 1995 and May 2003 were included in the analyses of etiology and outcomes. Candidates for OLT activated on a national waiting list were transplanted with cadaveric or living-related donor (LRD) organs. Twenty-seven patients age 1 to 19 years (median, 7.4 years) were transplanted at a median weight of 30.7 kg including 17 cadaveric and 10 with LRD livers. Most frequent etiologies were hepatitis A in 10 cases (37%) and unknown in 12 (48.1%). One donor experienced superficial phlebitis. Four patients were retransplanted (14.8%). Twenty patients are alive with 1- and 5-year survival rates of 74.1% At a median follow up of 34 months (range = 2 to 120). Seven patients died due to sepsis, multiorganic failure, graft primary nonfunction, intracranial hemorrhage, and intraoperative cardiac arrest. This experience revealed results comparable to international reports, allowing survival of patients destined to die.
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PMID:Epidemiology and results of liver transplantation for acute liver failure in Chile. 1461 98

Acute liver failure is a rare and life-threatening clinical syndrome following severe hepatic injury. Depending on the rapidity of its development, two distinct complications contribute to a high mortality: in hyperacute liver failure, rapid development of massive hepatic necrosis and apoptosis gives rise to severe hyperammonemia, hepatic encephalopathy and life-threatening cerebral edema. The high risk of cerebral herniation requires early listing for emergency liver transplantation. Patients with hyperacute liver failure surviving the initial episode of cerebral edema have a substantial potential for hepatic recovery. If progressive hepatic failure develops more slowly, astrocytic osmoregulation prevents cerebral herniation in most instances. Unfortunately, these patients have a small potential of hepatic regeneration and transplantation should be performed before renal failure, sepsis or multiorgan failure emerge. Experimental treatment methods including detoxification by artificial or bioartificial liver support or by stimulating hepatic regeneration are currently evaluated. Recognition of ammonia toxicity has stimulated the search for early ammonia-lowering strategies and strongly renewed the interest in dialytic therapies. Anti-apoptotic interventions are among the most promising pharmacological options for the near future.
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PMID:Acute liver failure. 1500 14

Acute liver failure is a rare disease that can cause death in the majority of untreated cases. Sudden loss of liver function in the absence of a preexisting liver disease is considered the true form and has to be distinguished from impaired function following exacerbation of an underlying liver disease (acute or chronic failure). Common causes include acute viral hepatitis, drug induced liver injury (DILI) and toxins. The loss of the excretory and synthetic function of the liver marks the clinical presentation and results in icterus, coagulopathy and encephalopathy. Additionally impairment of renal function and sepsis occur and contribute to the high mortality of this disease. The activation of cell death mechanisms (apoptosis) leading to a reductio of viable, functional liver tissue is considered to be an important pathophysiologic mechanism. Curative therapy of this disease includes liver transplantation that has been performed in Germany for the first time in 1969. In the year 2004 a total of 91 liver transplantation were performed for acute liver failure (10.3% of all transplants) in German transplant centers.
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PMID:[Acute liver failure--medical viewpoints]. 1717 26

1. Acute liver failure is a paradigm for multiple system organ failure that develops as a consequence of sepsis. 2. In the United States, systemic inflammatory response, sepsis, and septic shock are common reasons for intensive care unit admission. Intensive care management of these patients serves as a template for the management of patients with acute liver failure. 3. Acute liver failure is attended by high mortality. Although intensive care results in improved survival, the key treatment is liver transplantation. Intensive care unit intervention may open a "window of opportunity" and enable successful liver transplantation in patients who are too ill at presentation. 4. Intracranial hypertension complicates the course for many patients with acute liver failure. Initially, intracranial hypertension results from hyperemia, which is cerebral edema that reduces cerebral blood flow and eventuates in herniation. The precepts of neurocritical care-monitoring cerebral perfusion pressure, cerebral blood flow, and cortical activity-with rapid response to hemodynamic abnormalities, maintenance of normoxia, euglycemia, control of seizures, therapeutic hypothermia, osmotic therapy, and judicious hyperventilation are key to reducing mortality attributable to neurologic failure.
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PMID:Application of intensive care medicine principles in the management of the acute liver failure patient. 1882 85

Acute liver failure is a life threatening disease mostly triggered by drug-induced or toxic liver damage or viral hepatitis. Herpes Simplex virus (HSV) hepatitis is rare and accounts for only 1% of all acute liver failures. The importance of HSV-induced acute liver failure is based on its extremely severe clinical course with lethality rates of almost 75%. HSV hepatitis is just one of several clinical manifestations of HSV sepsis leading more frequently to encephalitis, pneumonia and esophagitis. Local herpes infection or recurrence of dermal lesions (herpes labialis, herpes genitalis), however, is common and account for the high prevalence of HSV-1 or HSV-2 infection in adults. Another rare entity is visual dissemination, which mostly affects immunocompromised patients. Compromised cellular immunity is a major risk factor for HSV sepsis because of either primary infection or reactivation of occult chronic HSV infection. Delayed diagnosis without antiviral therapy significantly contributes to the unfavorable outcome. Typically, anicteric hepatitis is seen in patients with HSV hepatitis. Because of its low incidence, however, and the lack of dermal manifestations, HSV hepatitis is rarely considered in the context of acute liver failure. In addition, diagnostic tests might not always be available. Therefore, it is a generally accepted consensus to begin antiviral therapy pre-emptively with acyclovir in cases of acute liver failure of unknown origin, in which high urgency (HU) liver transplantation remains the only therapeutical option. Even in the case of early specific therapy, sepsis may prevail and the indication for HU transplantation must be evaluated carefully. The outcome after liver transplantation for HSV-induced liver failure with reported survival rates of more than 40% is good. Because of the risk of recurrence, lifelong prophylaxis with acyclovir is recommended.
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PMID:Herpes simplex virus sepsis and acute liver failure. 1993 Mar 15

Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ transplanted recipients. Here, we present a thought-provoking case of HSV hepatitis in a high-risk recipient after living-related liver transplantation (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis. Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4 years of age. Viral infections were ruled out as the cause of FHF. Intensive care including plasma exchange (PE) was started, and the preoperative treatments for ABO incompatibility were performed. Thereafter, LRLT was performed emergently. Although strong immunosuppression for ABO incompatibility was continued after LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE was repeated and improvements were obtained. However, liver dysfunction appeared on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV hepatitis, although the results of HSV DNA and antibody titer in blood sample did not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA) occurred and the plasma and immunoglobulin were replenished. Our pediatric recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated sepsis. We conclude that well considered therapy based on the real-time detection of HSV hepatitis is indispensable for the further improvements of outcome in HSV hepatitis after LRLT.
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PMID:Herpes simplex virus hepatitis after pediatric liver transplantation. 2003 Jul 95

Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We have summarized the Hungarian Liver Transplant Program experience for ALF among 412 consecutive orthotopic liver transplantations (OLTs). All OLTs were performed without an extended international donor background. The proportion of ALF among the indications for OLT was lower (5.8% vs 9%) and early mortality higher than the European Liver Transplant Registry (1 year cumulative patients survival is 70% in ELTR vs 60% in the HU LT Program). The waiting time for a donor was longer than expected in the Eurotransplant community. Regarding postoperative complications, there was a higher incidence of initial poor function, bacterial infection, sepsis, and multiorgan failure. We conclude that ALF can be managed with reasonable results but requires an extended donor pool with an integrated international network to improve postoperative morbidity and mortality.
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PMID:Liver transplantation for acute liver failure: the Hungarian experience. 2162 Jan 10


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