Management Of Fulminant Hepatic Failure Research Articles

2315 Early Detection and IR Intervention in a Case of Fulminant Budd-Chiari Syndrome

INTRODUCTION: Budd-Chiari syndrome (BCS) is a relatively rare cause of abnormal LFTs, and infrequently progresses to fulminant hepatic failure. BCS requires a high degree of suspicion and can be easily confused with other causes of rapidly worsening liver enzymes. We present a case that illustrates successful management of fulminant hepatic failure by interventional radiology (IR) guided thrombolysis and thrombectomy, followed by TIPS placement in a rapidly decompensating 34-year-old woman who initially presented with mildly abnormal LFTs. CASE DESCRIPTION/METHODS: A 34-year-old white woman with past medical history of acid reflux, and family history of venous thromboembolism, presented to an outside hospital with a 5-day history of nausea, vomiting, diarrhea. She was subsequently was transferred to our facility for a higher level of care after worsening liver function testing and mentation. Patient had reported 5 days of epigastric tenderness, nausea, and abdominal distension prior to admission. Her LFTs continued to worsen, and clinically, she became progressively more hypotensive and tachycardic (BP 74/44, HR 112) requiring vasopressor support without significant improvement in her vital signs. Within 48 hours, she had acute onset of ascites and worsening encephalopathy. On arrival to our facility, she underwent CT abdomen/pelvis with and without IV contrast showing complete thrombosis of the right, left, and middle hepatic veins. Her liver function and transaminases continued to worsen prompting IR intervention. She underwent IR-guided thrombolysis and thrombectomy and TIPS with pre- and post- intervention pressures showing marked improvement in the transhepatic pressures (Table 1). (Pre- and post-intervention imaging in Figures 1 and 2). As part of her hypercoagulable workup, she was found to be deficient in protein C activity (46%). She had no OCP use for over 10 years. DISCUSSION: It was later discovered that patient’s mother had a history of saddle pulmonary embolism and other maternal relatives have had a pro-coagulative history, most of whom presented with significant lower extremity DVTs. This case illustrates that a high clinical suspicion is needed to make an early diagnosis of BCS, which can lead to early intervention and minimize the need for emergent liver transplantation. This case emphasizes the significant of a thorough history, and particularly a family history of venous thromboembolism.

Dynamic Patterns of serum metabolites in fulminant hepatic failure pigs

Fulminant hepatic failure (FHF) is still an intractable disease associated with serious metabolic disorder. Investigating the dynamic changes of serum metabolites during the development of FHF would facilitate revealing the pathogenesis and also promote its treatment. Therefore, this study characterized the dynamic metabonome of serum from FHF Pigs using ultra performance liquid chromatography–mass spectrometry. Based on multiple statistical analysis of the resulting dataset, three types of up-regulated and one type of down-regulated patterns were delineated. Each pattern demonstrated distinct trends at different stages during the whole process of FHF, implying the differential clinical significance of them. Specifically, aromatic amino acids (Pattern 1) and lysophosphatidylcholines (LPCs) (Pattern 4) might be good markers for evaluating the severity of FHF, while some conjugated bile acids, long chain acylcarnitines (Pattern 2) and Glycocholic acid (Pattern 3) could indicate liver injury in the early stage. Inspired from the PCA plot that the pathogenetic condition of FHF aggravated with sampling time, a linear discriminant analysis (LDA) model based on phenylalanine and LPC 18:1 were further constructed for evaluating the severity of FHF. The leave-one-out cross-validation accuracy of 91.67% for the training set and the prediction accuracy of 92.31% for the external validation set confirmed its excellent performance. In conclusion, findings obtained from the present study, including four types of Dynamic Patterns of serum metabolites during FHF development and an LDA model for evaluating the severity of FHF, will be of great help to the research and management of FHF in the future.

Signaling pathways involved in liver injury and regeneration in rabbit hemorrhagic disease, an animal model of virally-induced fulminant hepatic failure

Management of fulminant hepatic failure (FHF) continues to be one challenging problem, and experimental animal models resembling its clinical conditions are still needed. Rabbit hemorrhagic disease (RHD) fullfils many requirements of an animal model of FHF. This work investigated changes in MAPK, NF-κB, AP-1 and STAT pathways during RHD-induced liver injury. Rabbits were infected with 2 × 104 hemagglutination units of an RHD virus isolate. Apoptosis was documented by the presence of caspase-3 activity and substantial PARP proteolysis at 36 and 48 h postinfection (pi). Infection induced a marked and maintained expression of TNF-α from 12 h pi, while there was only a transitory increase in IL-6 expression. Expression of phosphorylated (p)-JNK, p-p38 and p-ERK1/2 was significantly elevated at 12 h pi. At 48 h pi p-JNK expression was maintained at a maximum level, while that of p-p38 returned to normality and there was no p-ERK1/2 expression. Activation of NF-κB and AP-1 and increased expression of VCAM-1 and COX-2 were observed. No significant changes were detected in activation of STAT1 and STAT3, while SOCS3 expression increased significantly. The current findings suggest that activation of JNK is an essential component in liver injury mediated by the RHD virus and that lack of activation of STAT3, probably mediated by SOCS3 over-expression, would contribute to the inhibition of the regenerative response. Data show the presence of molecular mechanisms contributing to liver damage and the lack of regeneration and they support the usefulness of this model to investigate novel therapeutical modalities in FHF.

Intracranial Pressure Monitoring in Patients with Fulminant Hepatic Failure Treated with Plasma Exchange and Continuous Hemodiafiltration

Background/Aims: To study the influence of our artificial liver support (ALS) on intracranial pressure (ICP) and to evaluate the significance of ICP monitoring in fulminant hepatic failure (FHF) patients treated with ALS. Methods:ICP was measured in 13 consecutive FHF patients treated with ALS. Maximum value in ICP every day was employed as ICP_max of the day. We analyzed the correlation: (a) between ICP_maxand consciousness level; (b) between ICP and colloid osmotic pressure (COP), and (c) between ICP and PaCO₂. Results: ICP in 11 patients of 13 was controlled <20 mm Hg through our ALS. A significant positive correlation between ICP_max and consciousness level was found (p < 0.01). Although there was a significantly negative correlation between ICP and COP (p < 0.001), there was no correlation between ICP and PaCO₂. Conclusions:We conclude that our ALS does not have any adverse effects on ICP and that ICP monitoring is one of the inevitable monitorings in the management of FHF.

A liver transplant center experience with liver dialysis in the management of patients with fulminant hepatic failure: a preliminary report

Among extracorporeal liver support devices, liver dialysis is cleared by the U.S. Food and Drug Administration to be used for the management of fulminant hepatic failure (FHF). The outcomes of patients following liver dialysis need to be clearly evaluated.Among the 25 patients with FHF admitted to the Liver ICU between May 2000 and November 2002, 12 underwent liver dialysis, including 6 men and 6 women, of mean age 32 years. The causes of FHF were identified as acetaminophen (n = 10), herbal medications (n = 1) and autoimmune disease (n = 1). At presentation, the mean total bilirubin was 9.35 mg/dL (range, 0 to 1.3), mean ALT 3015 U/L (range, 0 to 48), mean AST 3457 (range, 0 to 42), mean ammonia 98 μmol/L (range, 10 to 60) and mean INR 1.88. A control group including 13 patients (2 men and 11 women), of mean age 27.8 years mean total bilirubin 5.66, mean ALT 3494, mean AST 3528, mean ammonia 113 and mean INR 3, were not treated with liver dialysis, due to the lack of machine availability or physician’s choice. The causes of FHF were acute hepatitis B (n = 1), acetaminophen (n = 10) or unknown (n = 2). There was no statistically significant difference in the baseline characteristics of the two groups (P > .05). Among the liver dialysis group, 1 patient died, 2 underwent OLTx, and 9 were discharged home. Among the control group; 4 patients died, 2 underwent OLTx, and 7 were discharged home. Preliminary results seem to support survival benefit among patients who underwent liver dialysis compared to non–liver dialysis; however, further randomized control trials are warranted to verify this observation.

Fulminant hepatic failure and liver transplantation: experience of Virgen de la Arrixaca Hospital

Introduction For patients with fulminant hepatic failure who show a poor evolution despite medical treatment, liver transplantation is an option, with survival rates of greater than 50%. The ideal time to perform the transplant is controversial, as it must not be done too soon (when the liver disease is still reversible) or too late (when the patient is in an irreversible clinical situation). Patients and methods Retrospective review of the clinical histories of 34 patients admitted to our hospital with a diagnosis of fulminant hepatic failure included 26 who underwent transplantation. The most frequent cause was viral ( n = 10, 38%); with no etiology established in 11 cases (42%). Thirteen patients had preoperative complications, the most frequent being renal insufficiency. As for degree of AB0/DR compatibility, 13 cases were identical (40%), 17 compatible (51%), and the other three incompatible (9%). Results Thirty-three transplants were performed in 26 patients: four were retransplants due to chronic rejection, two for primary graft failure, and one for hyperacute rejection. The overall mortality rate was 46% (12 patients). The most frequent cause of death was infection (50%). The overall actuarial survival rate was 68% at 1 year, 63% at 3 years, and 59% at 5 years. The factors associated with a poor prognosis were renal and respiratory insufficiency, a grade D electroencephalogram, and encephalopathy grades III and IV, the last being the only prognostic factor identified in the multivariate analysis. The prognostic factors for mortality were a grade D electroencephalogram, encephalopathy grades III and IV and respiratory insufficiency, the last being the only prognostic factor identified in the multivariate analysis. Conclusion Good results of transplantation for the management of fulminant hepatic failure depends on optimal selection of transplant candidates, which means identifying them early, reducing the waiting time, and excluding factors associated with a poor prognosis.

Hepatic stimulator substance administration ameliorates liver regeneration in an animal model of fulminant hepatic failure and encephalopathy.

Hepatic stimulator substance (HSS) is a liver-specific growth factor implicated in hepatocellular proliferation and hepatoprotection in models of acute liver injury. In the present study, we examined the effect of exogenous HSS administration on liver proliferating capacity and survival outcome in an experimental animal model of fulminant hepatic failure (FHF) and encephalopathy, induced by repeated injections of thioacetamide (TAA) in rats. Fulminant hepatic failure was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA (400 mg/kg of body weight), at 24 h time intervals. The animals received intraperitoneally either a saline solution or HSS (50 mg protein/kg of body weight), 2 h after the second and third TAA injections. The animals were killed at 6, 12 and 18 h post the last injection of TAA. Levels of liver enzymes and urea in serum, blood ammonia values, liver histology, stage of hepatic encephalopathy and survival were statistically significantly improved in TAA-intoxicated and HSS-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, HSS ameliorated liver regenerative indices--DNA biosynthesis, thymidine kinase activity and hepatocyte mitotic activity--in a statistically significant manner. Our data suggest the beneficial effect of HSS administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of HSS as supportive therapy, by increasing hepatocellular proliferation, in management of FHF.

Granulocyte-colony stimulating factor administration ameliorates liver regeneration in animal model of fulminant hepatic failure and encephalopathy.

It has previously been shown that recombinant granulocyte-colony stimulating factor (rG-CSF) accelerates and enhances hepatocyte proliferation in partially hepatectomized rats. In the present study, we examined the effect of rG-CSF administration on liver injury, regeneration, and survival outcome in an experimental rat model of fulminant hepatic failure (FHF) and encephalopathy induced by repeated injections of thioacetamide (TAA). FHF was induced in adult male Wistar rats by three consecutive intraperitoneal injections of TAA, at intervals of 24 hr. The animals were also injected with either saline or rG-CSF. Serum biochemical parameters and blood ammonia levels, liver histology, stage of hepatic encephalopathy, and survival were statistically significantly improved in TAA-intoxicated and rG-CSF-treated rats compared to TAA-intoxicated and saline-treated ones. Furthermore, rG-CSF not only ameliorated the histologically evident liver injury in a statistically significant manner but also enhanced the proliferative capacity of the hepatocytes. Our data confirm the beneficial effect of rG-CSF administration in this animal model of FHF and encephalopathy, supporting evidence for a possible use of rG-CSF as supportive therapy in the management of FHF.

Etiology and management of fulminant hepatic failure.

Fulminant hepatic failure (FHF) remains a rare but devastating disease. Viruses and drug-induced hepatotoxicity are the most common causes of the syndrome, but the relevance of each differs depending on the geographic area. In a large proportion of patients no cause for FHF can be identified. Good intensive care is critical for patient survival. Orthotopic liver transplantation (OLT) remains a definitive therapeutic option. Prognostic indices have helped to optimize patient selection and timing for performance of OLT. However, the accuracy of these prognostic indices decreases when they are applied to different populations, probably because of regional differences in etiology and peculiar native host factors. More accurate prognostic criteria and new therapeutic alternatives to OLT are required.

Fracaso hepático fulminante y trasplante hepático. Experiencia del Hospital Virgen de la Arrixaca

Medical treatment for fulminat hepatic failure seeks spontaneous recovery of the liver function, but the results are very discouraging (50-80% mortality). Liver transplantation is an option in patients with a poor evolution despite medical treatment, with survival rates of > 50%. The ideal moment for performing the transplant is controversial, as it should not be done too soon, when the liver disease is still reversible, or tool late, when the patient is in an irreversible clinical situation. A retrospective review was made of the clinical histories of 34 patients admitted to our hospital with a diagnosis of fulminant hepatic failure, of whom 26 underwent transplantation. The most frequent cause was viral, with 10 cases (38%); no aetiology at all could be established in 11 cases (42%). Thirteen patients had preoperative complications, the most frequent being renal insufficiency. As for degree of ABO/DR compatibility, 13 cases were identical (40%), 17 compatible (51%) and the other 3 incompatible (9%). Thirty-three transplants were performed in 26 patients: 4 were retransplants due to chronic rejection, 2 for primary graft failure and 1 for hyperacute rejection. The overall mortality rate was 46% (12 patients), the most frequent cause of death being infection (50%). The overall actuarial survival rate was 68% at 1 year, 63% at 3 years and 59% at 5 years. The factors of poor prognosis were renal and respiratory insufficiency, a grade D electroencephalogram, and encephalopathy grades III and IV, the latter being the only prognostic factor identified in the multivariate analysis. The prognostic factors for mortality were a grade D electroencephalogram, encephalopathy grades III and IV and respiratory insufficiency, the latter being the only prognostic factor identified in the multivariate analysis. The achievement of good results with the use of transplantation in the management of fulminant hepatic failure depends on an optimum selection of transplant candidates, which means identifying them early, i.e. early indication for transplant, reduction in mean waiting time and exclusion of factors of poor prognosis.

Management of fulminant hepatic failure in the USA: Results from a survey of 14 liver transplant programs

Acute liver failure (ALF) is an uncommon condition of high mortality requiring urgent diagnosis and facilities for intensive care and liver transplantation (OLT). With few therapeutic trials in the USA, little is known about standard management of ALF. Aims: To assess the therapeutic approach to ALF in USA and to identify accepted and controversial aspects of care. Methods: A questionnaire to assess the management of ALF was completed by the physician representative of each of 14 liver transplant centers participating in the muiticenter Acute Liver Failure Study Group; these centers perform 30% of all liver transplants in USA. Results: The following care is instituted in most centers (# of centers): peptic ulcer prophylaxis, mainly H2 blockers (13); enteral nutrition if tolerated (13); hemostatic monitoring by PT/INR and platelet count (14); FFP (14) and platelets (13) prior to invasive procedure; use of N-acetylcysteine in acetaminophen overdose (13); surveillance cultures of blood and urine (12); elevation of head of bed (11 ); liver biopsy only with clinical suspicion of unusual diagnosis (11). With stages Ill/IV encephalopathy and/or need for mechanical ventilation, therapy includes hemodynamic monitoring by arterial (14), central venous (14) and pulmonary artery catheters (13); intracranial pressure monitoring (ICP) with epidural or subdural catheters in OLT candidates (13); head scanning by CT (14); hyperventilation as first line therapy to treat Cerebral edema (11); mannitol therapy to treat cerebral edema (14); renal dialysis by CWHD (13); and use of King's College criteria for assessment for OLT (13). More controversial areas include use of medical agents for PSE (10), barbiturate coma to treat cerebral edema (10), prophylactic therapy of cerebral edema (6), vitamin K therapy (10), surveillance cultures, use and type of prophylactic antibiotics, blood products to prevent bleeding (4), and nutritional support with TPN (6) or BCAA (4). Conclusions: The patient with ALF requires specialized care in a liver transplant center where aggressive measures intensive hemodynamic, ICP monitoring, use of CWHD are almost universal. Also universal are some less invasive measures (e.g. surveillance cultures, peptic ulcer prophylaxis) which can be instituted early in the referring center prior to transfer. Many areas of supportive care remain controversial and optimal therapy for ALF requires further investigation.

Management of fulminant hepatic failure in the USA: Results from a survey of 14 liver transplant programs

Management of fulminant hepatic failure in the USA: Results from a survey of 14 liver transplant programs

Herpes Simplex Type 2 Causing Fulminant Hepatic Failure

Although exceedingly rare, fulminant hepatic failure (FHF) in immunocompetent patients can develop with primary or recurrent infection due to herpes simplex virus (HSV). The diagnosis is frequently obscured by the absence of mucocutaneous involvement. Elevated transaminase values with leukopenia and a relatively low bilirubin level may provide clues to the diagnosis. We describe an immunocompetent woman who died of FHF before a definitive diagnosis of HSV type 2 hepatitis was established. Herpes simplex virus hepatitis is one of the few causes of FHF for which potentially effective therapy is available. Thus, early diagnosis is paramount and usually requires liver biopsy. Recent studies suggest that transjugular liver biopsy is safe and effective in establishing the cause of FHF. Since the diagnosis and management of FHF are frequently influenced by the results of transjugular liver biopsy, it may become a standard diagnostic tool for managing FHF in centers where such expertise exists.

Current management of fulminant hepatic failure

Current management of fulminant hepatic failure

Nonsurgical management of fulminant hepatic failure

Nonsurgical management of fulminant hepatic failure

Fulminant Hepatic Failure

Fulminant hepatic failure is a devastating complication of viral hepatitis, hepatotoxic exposures, and a variety of other acute liver diseases. Although this syndrome is associated with high mortality, liver transplantation can be life saving. This article discusses the medical management of fulminant hepatic failure and emphasizes complications, determinants of survival, and patient selection for liver transplantation.

Review of support systems used in the management of fulminant hepatic failure.

Fulminant hepatic failure has an exceedingly high mortality. Liver transplantation is the treatment option of choice. Unfortunately, one-third of patients with fulminant hepatic failure die awaiting a donor liver. For over 35 years attempts to remove or dilute putative toxins in the blood have been unsuccessful in improving survival rates. The use of biocompatible interfaces with blood or plasma and current hepatocyte culture techniques have led to the development of new support systems. This generation of bioartificial livers will hopefully provide the necessary hepatic functions and prevent many of the complications associated with fulminant hepatic failure. This paper will review the support systems tried and currently under investigation, with an emphasis on bioartificial livers.

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Noninvasive Monitoring of Cerebral Perfusion by Transcranial Doppler During Fulminant Hepatic Failure and Liver Transplantation

Survival in patients with fulminant hepatic failure (FHF) treated medically, rather than surgically, ranges from 12%-67% (mean 39%), depending on the cause of the disease (1). The major cause of mortality is increased intracranial pressure (ICI’) from brain edema (2). For patients with a poor prognosis (3), orthotopic liver transplantation may be the definitive treatment (41, even though, only a few years ago, some considered this treatment ineffective by the time patients reached Grade 4 encephalopathy (5). ICI’ monitoring allows physicians to use specific therapy to control intracranial hypertension. Continuous measurement of ICI’ perioperatively in the management of FHF has been associated with a survival rate of 54%74% in a series of six to 23 patients (6-9), which is generally higher than with medical means (l), and was as high as 92% for the selected group who had undergone liver transplantation (6). Such invasive monitoring, however, is especially risky in FHF patients with coagulopathy, in whom the incidence of bleeding from ICI’ monitoring ranges from 5%-22% (6,8) with a mortality rate of 60% (6). Although the use of ICI’ monitoring for FHF has become more routine (8), not all centers support the use of this invasive monitoring. We describe a patient with FHF and brain edema who underwent liver transplantation and whose cerebral perfusion was monitored noninvasively by transcranial Doppler (TCD) imaging, as well as invasively by ICI’. The noninvasive technique provided adequate information when cerebral perfusion was low, comparable with the invasive technique, and allowed intracranial hypertension to be diagnosed and treated effectively.

Extracorporeal Liver Support

Artificial liver support is urgently needed. Mechanical devices such as hemodialysis and hemoperfusion do not correct the metabolic abnormalities that exist in endstage liver disease, and biologically active devices have been impracticable because of limitations in the availability and viability of cultured liver cells. This deficit in the medical armamentarium is a major concern best illustrated by current management of fulminant hepatic failure (FHF). Medical treatment for FHF is largely unsuccessful, and orthotopic liver transplantation (OLT) is the intervention against which all future therapeutic interventions must be judged. The OLT procedure, however, is not benign. The cost is high, and survivors face a lifetime of immunosuppression and medical supervision. By comparison, patients who survive without surgery recover full liver function and have a normal life expectancy. A device that provides liver support during the critical stages of FHF would stabilize patients until a suitable donor organ was found and might negate the need for transplant altogether if the liver were able to regenerate. We review theoretical and practical aspects of biologically active devices using FHF as a paradigm of liver disease.