Predictive value of actin-free Gc-globulin in acute liver failure.

Serum concentrations of the actin scavenger Gc-globulin may provide prognostic information in acute liver failure (ALF). The fraction of Gc-globulin not bound to actin is postulated to represent a better marker than total Gc-globulin but has been difficult to measure. We tested a new rapid assay for actin-free Gc-globulin to determine its prognostic value when compared with the King's College Hospital (KCH) criteria in a large number of patients with ALF. A total of 252 patients with varying etiologies from the U.S. ALF Study Group registry were included; the first 178 patients constituted the learning set, and the last 74 patients served as the validation set. Actin-free Gc-globulin was determined with a commercial enzyme-linked immunosorbent assay kit. The median (range) actin-free Gc-globulin level at admission for the learning set was significantly reduced compared with controls (47 [0-183] mg/L vs. 204 [101-365] mg/L, respectively, P < 0.001). Gc-globulin levels were significantly higher in spontaneous survivors than in patients who died or were transplanted (53 [0-129] mg/L vs. 37 [0-183] mg/L, P = 0.002). A receiver operating characteristic curve analysis showed that a 40 mg/L cutoff level carried the best prognostic information, yielding positive and negative predictive values of 68% and 67%, respectively, in the validation set. The corresponding figures for the KCH criteria were 72% and 64%. A new enzyme-linked immunosorbent assay for actin-free Gc-globulin provides the same (but not optimal) prognostic information as KCH criteria in a single measurement at admission.     

Detection of the actin scavenger system in burn wound fluid

The intravascular actin scavenger system depolymerizes and sequesters actin released after tissue injury. Studies were carried out to determine if this system is active in the extracellular space during wound repair. Using burn wound fluid as a noninvasive means for analyzing the wound environment, we measured actin accumulation and actin complex formation with the plasma proteins responsible for scavenger function. Actin at concentrations as high as 0.25 mg/ml ( approximately 5 micromol/L) was found in burn wound fluid samples from 9 of 11 patients. Wound fluid also contained the two plasma proteins that bind actin-gelsolin (both plasma and cytoplasmic forms) and Gc protein. Because actin in wound fluid was complexed with gelsolin and Gc protein, we conclude that the components of the actin scavenger system are functional in wound tissue. In addition, proteolysis of gelsolin, but not actin or Gc protein, appeared to occur at the wound site. Gelsolin proteolysis was accompanied by the appearance of 49 kd gelsolin fragments, and wound fluid samples lacking intact gelsolin also contained high metalloproteinase levels.     

Inflammation is an important determinant of levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) in acute liver failure.

Acute liver failure (ALF) is characterized by rapid progressive organ failure and poor outcome. The pathophysiology of multiorgan dysfunction in ALF remains unclear but increased systemic inflammatory response is believed to be an important determining factor. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, results from proteolysis and the liver is a major site for its metabolism. ADMA has been shown to independently predict outcome in multiorgan failure associated with severe liver dysfunction. In this study, we tested the hypothesis that proinflammatory cytokine driven responses are important in modulating ADMA levels in patients with acetaminophen-induced ALF. Blood samples were collected from 10 ALF patients (grade IV encephalopathy) from admission until the time of transplantation or death, and assayed for cytokines and ADMA. A total of 8 patients required treatment for raised intracranial pressure and all patients were managed with standard of care, including full mechanical ventilation and veno-venous hemofiltration. ADMA levels were markedly higher in ALF patients compared to age-matched controls (P < 0.001) and correlated with the levels of proinflammatory cytokines. In pretransplantation patients undergoing hepatic venous catheterization, we demonstrated no significant uptake of ADMA across the failing liver. However, following liver transplantation, ADMA levels reduced acutely. A timed study of ADMA levels during transplantation demonstrated a slight increase during the anhepatic phase but a marked and sustained reduction in ADMA following liver reperfusion. In conclusion, our data show a significant correlation between ADMA levels and proinflammatory cytokines, supporting a hypothesis that proinflammatory cytokines may regulate ADMA metabolism in ALF.     

Immunonephelometric quantification of group-specific component protein in patients with acute liver failure

Serum levels of group-specific component (Gc) protein are useful in evaluating the likelihood of survival in patients with acute liver failure (ALF) who may be candidates for liver transplant surgery. Most methods for quantifying Gc protein concentration are either isotopic, manual, technically demanding, and/or time consuming to perform, and thus are not well suited for routine clinical use in a hospital setting. We modified and evaluated a recently described nonisotopic, fully automated, immunonephelometric method for quantifying serum Gc protein concentration and compared it to our previous immunoblotting method. In addition, we evaluated the effect of G-actin on the immunonephelometric measurement of Gc protein. Serum samples from 20 patients with ALF and from 20 age- and sex-matched clinic patients without liver disease were quantified by both immunoblotting and immunonephelometry. We assessed the intra-assay precision, correlation, and diagnostic accuracy of these methods in discriminating between individuals with no preexisting liver disease and those with ALF. Actin in 1.3- to 4-fold excess of Gc protein levels demonstrated minimal to no interference in the quantification of Gc protein by immunonephelometry. Immunonephelometry was more precise than immunoblotting. Gc protein values by immunonephelometry were similar to those obtained by immunoblotting, and the diagnostic accuracy of Gc protein concentration by immunonephelometry was similar to that observed by immunoblotting. Immunonephelometry provides a nonisotopic, fully automated, rapid, precise, accurate, and cost-effective method for quantifying serum levels of total Gc protein that is well suited for routine use in a hospital-based clinical laboratory. (Liver Transpl Surg 1997 Jan;3(1):28-33)     

Acute liver failure in chronic hepatic disease. Clinico-therapeutic evaluation

Chronic liver diseases are potentially evolving clinical situations which, independently by the etiology, could proceed towards progressive liver structural and functional impairments. The only efficient treatment is orthotopic liver transplantation. Chronic liver diseases, and up to 40% of liver cirrhosis, are initially asymptomatic, but cirrhosis is the most frequent cause of death among non-neoplastic digestive diseases. Important elements complicating a decompensated liver cirrhosis are ascites, hepatic encephalopathy, digestive bleeding and jaundice. Acute liver failure (ALF) is the expression of a clinical state, that is common to many conditions sharing severe liver structural and functional impairments. In patients affected by decompensated liver cirrhosis, ALF could be triggered by several factors, while the death is caused by bleeding episodes, hepato-renal syndrome, spontaneous bacterial peritonitis or hepatocarcinoma. In patients affected by chronic liver diseases, the diagnosis of ALF is based on progressively increasing jaundice, encephalopathy and coagulopathy. Recent clinical trials have evaluated the efficacy of extrahepatic liver support systems, either artificial or bio-artificial, in treating episodes of ALF in chronic liver patients. The preliminary results indicate a potential use of such systems in blood detoxification, but they also showed limits in increasing patient survival.     

Abdominal imaging can misdiagnose submassive hepatic necrosis as cirrhosis in acute liver failure

Patients with acute liver failure (ALF) can be listed status I for liver transplantation (LT) whereas patients with cirrhosis must follow the MELD scoring system. Liver imaging can mistakenly diagnose submassive hepatic necrosis in ALF as cirrhosis. The purpose of our study was to assess the accuracy of ultrasound (US) and computed tomography (CT) in distinguishing cirrhosis from ALF. All patients listed for ALF and transplanted during the study period were included. Controls were age‐ and gender‐matched cirrhotic patients who underwent LT during the same period. Abdominal US or CT scans obtained on all patients were independently reviewed by three blinded abdominal radiologists. Explants from all patients were reviewed by two blinded pathologists, and histological diagnosis was correlated with radiological diagnosis. Forty‐one patients with ALF and 42 patients with cirrhosis were analyzed. Univariate and multivariate analyses both revealed overall accuracy of 85% for ultrasound and 93% for CT. US and CT scans both provide high levels of accuracy in terms of discriminating ALF from cirrhosis but measures taken to determine whether a patient has ALF vs. cirrhosis needs to approach 100% accuracy. Thus, imaging studies alone should not definitively diagnosis one etiology of liver failure over the other.     

Cytokine profiles in acute liver failure treated with albumin dialysis

Abstract:  Cytokines are released within the liver in response to hepatic injury, and acute liver failure (ALF) triggers systemic inflammation. Pro-inflammatory (tumor necrosis factor-alpha [TNF-α] and interleukin-8 [IL-8]) and anti-inflammatory (interleukin-10 [IL-10] and interleukin-6 [IL-6]) cytokines and the lymphocyte activation marker (interleukin-2-soluble receptor alpha chain [IL-2sRα]) were monitored in 49 ALF patients considered for liver transplantation and treated with albumin dialysis (molecular adsorbent recirculating system [MARS]). Twenty-six patients were categorized by clinical outcome as "good" (native liver recovered) and 23 as "poor" (patient bridged to liver transplantation or deceased). MARS did not clearly affect cytokine profiles during treatment; only IL-10 levels decreased in the whole patient population and mostly in patients with the worst prognosis. In the good outcome group, IL-8 and IL-6 levels decreased during treatment; on the contrary, in poor outcome patients IL-6 levels even increased. Initial IL-2sRα levels were higher in poor outcome patients relative to the good outcome subset. Cytokine profiles seem to differ in ALF according to patient outcome. A deeper understanding of cytokine patterns during pathogenesis could reveal prognostic markers and aid the development of immunomodulating ALF therapies.     

Gc-globulin and prognosis in acute liver failure.

Serum concentrations of the actin scavenger Gc-globulin are reduced in acute liver failure (ALF). Prospectively, we tested Gc-globulin's value to predict outcome following ALF using sera from 182 patients with ALF from the U.S. ALF Study Group. Admission serum levels of Gc-globulin (normal range: 350-500 mg/L) were studied by an immunonephelometric method. The median (range) serum Gc-globulin level on admission for the entire group was 91 (5-307) mg/L. Gc-globulin levels were significantly higher in spontaneous survivors than in patients who died or underwent transplantation (113 [5-301] mg/L vs. 73 [5-307] mg/L, P < 0.001). Those surviving non-acetaminophen (paracetamol)-induced ALF without transplantation had higher Gc-globulin levels than nonsurvivors (102 [5-301] mg/L vs. 61 [5-232] mg/L, P = 0.002), whereas there was no significant difference in levels between the groups in patients with acetaminophen-induced ALF. A cutoff level of 80 mg/L in the non-acetaminophen group yielded positive and negative predictive values of 85% and 43%, respectively. The corresponding figures for the King's College criteria were 90% and 49%, respectively. In conclusion, we found that Gc-globulin levels were markedly decreased in patients with ALF; the lowest levels were observed in patients who died or were transplanted. In contrast to previous studies, this study demonstrated that Gc-globulin has prognostic value in patients with non-acetaminophen-induced ALF, in the same range as the King's College criteria. Further refinements of the assay would be necessary to make it more accurate and of practical utility.     

Technical aspects of portal vein arterialization for acute liver failure: from rat lab to man

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.     

Effect of donor-disseminated intravascular coagulation in liver transplantation

It is not known whether disseminated intravascular coagulation, present in a large percentage of organ donors, affects patient outcome after liver transplantation. We reviewed our first 55 liver transplantations and identified 10 donors with disseminated intravascular coagulation. We compared the perioperative courses of the 10 recipients of these transplanted livers with those of 10 matched controls whose donors did not have disseminated intravascular coagulation. Disseminated intravascular coagulation recipients did not require more blood products during or after surgery; their hepatic enzyme levels and prothrombin times after surgery were not statistically significantly higher than those of the controls. There was no difference in hospital stay, number of episodes of rejection, retransplantations, or deaths. The presence of disseminated intravascular coagulation in donors did not adversely affect graft function or patient outcome and should not be a sole criterion for rejecting a liver for transplantation.     

Portal vein arterialization: a new surgical option against acute liver failure?

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself, avoiding transplantation, is a major goal in the treatment of ALF. We report our clinical experience of portal vein arterialization in one case of massive liver necrosis after liver transplantation and in two patients with ALF caused by idiosyncratic drug reaction and mushroom intoxication. Portal vein arterialization, at least in two cases, was a turning point in the course of the disease since a close temporal association between surgery and clinical improvement was clearly evident. We believe that this novel approach, which should promote liver regeneration by providing an additional oxygen supply to the liver, may disclose a new possibility in the treatment of ALF and prompt new clinical and experimental research.     

Acute liver failure

Acute liver failure (ALF) is a life-threatening condition with many possible causes. In developed countries, common causes include paracetamol overdose, toxin exposure (e.g. mushrooms) and idiosyncratic drug reactions. Viral hepatitis is much more common in developing countries, although must be considered in any location. The clinical syndrome of ALF is remarkably independent of the cause and comprises the following key features: jaundice, encephalopathy with cerebral oedema, coagulopathy, vasodilatory state, renal dysfunction, hypoglycaemia and immune dysfunction. Management of the patient with severe ALF is threefold in aim: (i) prevent further liver damage by treating the underlying cause of ALF where possible; (ii) prevent and treat complications of ALF (e.g. cerebral oedema, shock and infection); and (iii) early referral to specialist centre for consideration of liver transplantation. Despite modern intensive care practices, the mortality of severe ALF remains high. Optimal supportive care aims to extend the period available to source an organ for transplantation and/or to allow full recovery. This article provides a practical approach to the diagnosis and management of critically ill patients with ALF.     

Results of Surgical Treatment (Modified Sugiura-Futagawa Operation) of Portal Hypertension Associated to Complete Splenomesoportal Thrombosis and Cirrhosis

Background Hemorrhagic portal hypertension, secondary to both intrahepatic and extrahepatic portal hypertension, is an uncommon entity. In this condition, the extrahepatic and the intrahepatic obstruction of the portal vein, due to chronic liver disease, produce a more severe form of hemorrhagic portal hypertension that is more difficult to control. The results of surgical treatment (modified Sugiura- Futagawa operation) in this subset of patients is analyzed.Methods Among 714 patients with a history of hemorrhagic portal hypertension, 14 cases were found with histologically proven liver cirrhosis and complete splenomesoportal thrombosis demonstrated by means of preoperative angiography. Patients with incomplete (partial) splenomesoportal thrombosis were excluded. There were nine males and 5 females with a mean age of 51 years. Alcoholic cirrhosis was demonstrated in 50% of the cases, post hepatitic cirrhosis in 28%, primary biliary cirrhosis in 7%, and cryptogenic cirrhosis in 14%. There were nine Child-Pugh A and 5 B cases. All cases were treated by means of our modified Sugiura-Futagawa procedure.Results Bleeding recurrence from esophagogastric varices was shown in one case, colonic varices in one case and hypertensive gastropathy in another of the survivors. Post operative encephalopathy was shown in 3 of the cases. The thirty-six month survival rate was 30% (Kaplan-Meier).Conclusions The combination of intrahepatic plus extrahepatic portal hypertension has a worse prognosis. Treatment options are limited (sclerotherapy and/or devascularization), because shunt surgery, TIPS and liver transplantation have a very restricted role and postoperative outcome is poor.     

Leukemia after liver transplant.

INTRODUCTION: Acute leukemia is rare after solid organ transplantation. METHODS: Review of data on 3 patients with acute leukemia identified among 1365 who underwent liver transplantation at our center, and a review of the literature. RESULTS: In patient 1, AML-M4 developed 19 months after transplant for cryptogenic cirrhosis. In patient 2, B cell acute lymphoid leukemia was diagnosed 10 months after liver transplant for fulminant hepatitis. Both patients had normal cytogenetics, and achieved complete remission with chemotherapy. In patient 3, acute monocytic leukemia-M3 with t(15;17) arose 18 months after transplant for hepatitis C cirrhosis. This patient received treatment with retinoic acid and chemotherapy, but developed a disseminated intravascular coagulation and died before completing therapy. No patient presented with chromosomal abnormalities commonly seen in secondary leukemia. The latency period to diagnosis after transplant was 10-19 months. CONCLUSIONS: Acute leukemia, although rare after liver transplantation, should be considered in the differential diagnosis of hematological complications.     

The decrease in cytokine concentration during albumin dialysis correlates with the prognosis of patients with acute on chronic liver failure

BACKGROUND AND AIM: The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-alpha, IL-6, and IL-1beta in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. MATERIALS AND METHODS: Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-alpha, IL-6, and IL-1beta, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). RESULTS: MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-alpha, IL-6, and IL-1beta (P < .05). Moreover, the reduction in inflammatory cytokines levels and improved prognosis were related. CONCLUSIONS: We confirmed the therapeutic efficacy of MARS treatment for ALF, which appeared to be related to removal of toxins and inflammatory cytokines determine that which patients prognosis.     

Surgical experience in children with biliary atresia treated with portoenterostomy

OBJECTIVE: Biliary atresia is the result of a fibrosing destructive inflammatory process affecting intrahepatic and extrahepatic bile ducts, which lead to cirrhosis and portal hypertension. Without surgical intervention, mortality reaches 100%. The 5-year survival rate after portoenterostomy ranges from 13% to 60%, with approximately 60% of patients requiring liver transplantation at a later stage because of insufficient bile flow. METHODS: This retrospective analysis includes 30 consecutive patients undergoing portoenterostomy for biliary atresia at our hospital. RESULTS: The 5-year actuarial survival of the 30 patients was 68%. Thirteen patients (43.3%) died 3 days to 7 years after portoenterostomy. Four patients (13.3%) underwent liver transplantation 3 to 24 months after the Kasai procedure with a 100% survival. In 65% of patients without presence of cirrhosis, the portoenterostomy was successful, compared with 35% of cases with liver cirrhosis (p = 0.0148). Liver cirrhosis with extrahepatic biliary atresia alone was present in 5 of 17 patients (29%) as compared with 8 of 12 patients (66%) with intrahepatic biliary hypoplasia in addition to extrahepatic biliary atresia and cirrhosis. CONCLUSIONS: Portoenterostomy remains the treatment of choice for patients with extrahepatic biliary atresia. However, the presence of cirrhosis portends a poorer prognosis and may be an indication for early transplantation. Cirrhosis is more commonly present in the setting of intrahepatic biliary hypoplasia and may account for the lower success rates of portoenterostomy in this group of patients. Five-year survival of the female patients was 88% as compared with 55% of the male patients.     

肝移植治疗成人慢加急性肝功能衰竭的现状

慢加急性肝功能衰竭(ACLF)是慢性肝病或肝硬化急性失代偿期的最严重形式, 往往同时合并肝外器官功能衰竭, 患者短期预后极差。ACLF的触发病因复杂多样, 其分期及器官功能衰竭的类型和定义各不相同, 目前尚无统一的ACLF诊断标准, 难以直接预测和比较不同地域ACLF的总体发病率和预后情况。越来越多的研究证据表明, 肝移植在ACLF外科治疗中发挥重要作用, 但其价值尚存争议。目前ACLF具体的入院处理和治疗方案, 包括ICU的监护治疗、器官功能的支持维护、肝移植手术指征和时机选择等方面, 尚未形成统一的标准化流程或意见。ACLF患者是否应较其他潜在的肝移植等待受者在供者分配方面更具有优先权亦无定论。此外, 人工肝支持系统在ACLF移植前桥接治疗中的应用价值尚需更多的前瞻性对照研究来进一步证实。因此, 本文就肝移植在成人ACLF外科治疗中的指征选择、手术疗效及影响因素、手术时机选择、供肝资源分配及移植前桥接治疗等方面进行探讨, 以期为ACLF肝移植治疗的未来临床研究提供新的方向。     

Are there certified indications for the use of antithrombin III in intensive care

The serine-protease-inhibitor antithrombin III (AT III) has often been recommended for the therapy of septic patients as it provides anticoagulant and antiinflammatory actions. In animal studies the prophylactic treatment with AT III in a dose > 250 U/kg prevented the development of disseminated intravascular coagulopathy and vital organ dysfunction during sepsis and lowered the mortality rate. In clinical studies with septic patients therapy usually was started several hours after the start of the disease in dosages much lower than those used in animal studies. In these patients AT III-therapy improved laboratory changes of disseminated intravascular coagulopathy but was unable to lower the mortality rate. Hereditary AT III deficiency, lack of heparin effect due to low AT III levels, disseminated intravascular coagulation disorders are indications for the use of AT III while beneficial effects of AT III in patients suffering from SIRS, sepsis or septic shock have not yet been demonstrated.     

Chronic Kidney Disease After Liver Transplantation for Acute Liver Failure Is Not Associated With Perioperative Renal Dysfunction

Renal dysfunction of acute liver failure (ALF) may have distinct pathophysiological mechanisms to hepatorenal syndrome of cirrhosis. Yet, the impact of perioperative renal function on posttransplant renal outcomes in ALF patients specifically has not been established. The aims of this study were ( 1 ) to describe the incidence and risk factors for chronic renal dysfunction following liver transplantation for ALF and ( 2 ) to compare renal outcomes with age–sex‐matched patients transplanted for chronic liver disease. This was a single‐center study of 101 patients transplanted for ALF. Fifty‐three‐and‐a‐half percent had pretransplant acute kidney injury and 64.9% required perioperative renal replacement therapy. After transplantation the 5‐year cumulative incidence of chronic kidney disease (eGFR <60 mL/min/1.73 m²) was 41.5%. There was no association between perioperative acute kidney injury (p = 0.288) or renal replacement therapy (p = 0.134) and chronic kidney disease. Instead, the independent predictors of chronic kidney disease were older age (p = 0.019), female gender (p = 0.049), hypertension (p = 0.031), cyclosporine (p = 0.027) and nonacetaminophen‐induced ALF (p = 0.039). Despite marked differences in the perioperative clinical condition and survival of patients transplanted for ALF and chronic liver disease, renal outcomes were the same. In conclusion, in patients transplanted for ALF the severity of perioperative renal injury does not predict posttransplant chronic renal dysfunction.     

Phosphorus ans an early predictive factor in patients with acute liver failure

BACKGROUND: This study analyzes the prognostic significance of serum phosphorus in patients with acute liver failure (ALF). METHODS: We performed a retrospective analysis of 112 patients with ALF. Univariate and bivariate analyses based on Kaplan-Meier recovery curves and a multivariate Classification Tree Structure Survival Analysis were performed to identify independent predictors of outcome. The variables analyzed were age, gender, race, ABO blood group, etiology of liver disease, grade of encephalopathy, serum bilirubin, prothrombin time, creatinine, serum phosphorus, phosphorus administered, phosphorus binders, and hemodialysis. RESULTS: The median follow-up time was 5 days, the median age was 28 years, and 62% of the patients were female. The patients' outcomes were as follows: 28% recovered, 52% required orthotopic liver transplantation, and 20% died. White patients showed the best prognosis (58% recovered in the first week), and Hispanics showed the worst prognosis (0.3% recovered at 1 week) (P=0.0001). Encephalopathy and bilirubin were significant predictors of recovery (P<0.0001 and P=0.004). The analysis of the serum phosphorus showed a statistically significant better prognosis in patients with low phosphorus (P<0.001). The recovery rate at 1 week was 74% in patients with serum phosphorus less than 2.5 mg/dL, 45% if phosphorus ranged between 2.5 to 5 mg/dL, and 0% if phosphorus was more than 5 mg/dL. The bivariate analysis on the effects of phosphorus administration showed that phosphorus replacement was associated with a significant improvement in recovery in patients with low (P<0.004) or normal serum phosphorus levels (P<0.017) CONCLUSIONS: Hypophosphatemia and early phosphorus administration are associated with a good prognosis in ALF, whereas hyperphosphatemia is predictive of poor recovery.