Home About us Contact
|
Home About us Contact | ||
|
|
||
Acute Liver Failure (acute + liver_failure)
Selected AbstractsAcute liver failure and living donor liver transplantationHEPATOLOGY RESEARCH, Issue 2008Nobuhisa Akamatsu Acute liver failure (ALF) is defined by the presence of hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality of ALF without liver transplantation is over 80%, the survival rates of ALF patients have improved considerably with the advent of liver transplantation, up to 60,80% in the last decade. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT is 60% to 90%. Although there is still controversy regarding the graft type, the optimal graft volume, and ethical issues of defining the indications for LDLT in ALF patients with respect to donor risk, LDLT has become an established treatment option for ALF in areas where the use of deceased donors organs is severely restricted. [source] Acute liver failure in Sweden: etiology and outcomeJOURNAL OF INTERNAL MEDICINE, Issue 3 2007G. Wei Abstract. Objective., To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994,2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score with transplant-free deaths as a positive outcome. Research design and methods., Adult patients in Sweden with international normalized ratio (INR) of ,1.5 due to severe liver injury with and without encephalopathy at admission between 1994,2003 were included. Results., A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive-predictive value (PPV) of 67%, negative-predictive value (NPV) of 84% in the acetaminophen group. Positive-predictive value and negative-predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score >30 had a positive-predictive value of 21%, negative-predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively. Conclusions., Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score <30 predicts a good prognosis in acetaminophen patients without transplantation. [source] Review article: the current management of acute liver failureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010D. G. N. CRAIG Aliment Pharmacol Ther,31, 345,358 Summary Background, Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. Aim, To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. Methods, Literature review using Ovid, PubMed and recent conference abstracts. Results, Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and ,buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. Conclusion, Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT. [source] Aetiology and prognostic factors in acute liver failure in IndiaJOURNAL OF VIRAL HEPATITIS, Issue 3 2003M. S. Khuroo Summary., The early prognostic indicators for acute liver failure in endemic zones for hepatitis E virus have not been determined. All consecutive patients with acute liver failure from a geographically defined region endemic for hepatitis E virus were studied over the period April 1989,April 1996. Demographic, clinical and biochemical parameters were recorded at presentation and serum samples were analysed for known viral hepatitis (A,E) markers. Multiple parameters were compared in survivors and non-survivors in a univariate analysis. All significant factors on univariate analysis were entered into a stepwise logistic regression analysis to identify independent variables of prognosis. The sensitivity and specificity of significant prognostic factors was then assessed. A total of 180 [69 males and 111 females: age (mean ± SD) 31.1 ± 14.7 years] with acute liver failure were studied. Of these, 131 (72.8%) patients died. Hepatitis E virus was the aetiological cause in 79 (43.9%) patients, while hepatitis A virus, hepatitis B virus, hepatitis C virus and non-A, non-E agent/'s could be incriminated in four (2.1%), 25 (13.9%), 13 (7.2%) and 56 (31.1%) patients respectively. Of 83 women in childbearing age, 49 (59.0%) were pregnant, 33 (67.3%) of these were in the third trimester. Forty-seven (95.8%) pregnant women had HEV infection. Nine variables differed significantly between survivors and non-survivors on univariate analysis. Of these, four variables which predicted the adverse outcome on multivariate analysis were non-hepatitis-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years in that order of significance. Pregnancy per se or duration of gestation did not adversely affect the prognosis. In endemic areas, hepatitis E virus is the commonest cause of acute liver failure. Acute liver failure occurs in a high proportion of pregnant women, mostly in third trimester. Early predictors of a poor outcome are non-E aetiology, prothrombin time >30 s, grade of coma >2 and age >40 years. [source] Application of Molecular Adsorbent Recirculating System® in patients with severe liver failure after hepatic resection or transplantation: initial single-centre experiencesLIVER INTERNATIONAL, Issue 2002R Kellersmann Abstract: Acute liver failure after hepatic surgery is still plaqued with high mortality rate. Recently, a liver dialysis system (MARS®) that allows detoxification of albumin-bound substances and may hereby support liver regeneration and patient's recovery has been developed. In the present study, we report our experiences with MARS® dialysis in patients with liver failure after hepatic resection or transplantation. Between September 1999 and January 2001, five patients were treated with MARS® (2,5 courses). Though beneficial effects such as improvement of encephalopathy and renal function as well as reduced bilirubin levels were recorded during MARS® therapy, only one patient survived. Neither significant technical problems nor adverse effects occurred by using MARS® dialysis. We conclude that in surgical patients, acute liver failure is usually part of a complicated clinical course affecting multipleorgan systems. Thus, it is difficult to determine the specific influence of MARS® on patient's outcome. However, beneficial effects observed in our patients justify its continuous use and may stimulate further evaluation in controlled studies with surgical patients. [source] Effect of hospital volume and teaching status on outcomes of acute liver failureLIVER TRANSPLANTATION, Issue 9 2008Ashwin N. Ananthakrishnan Acute liver failure (ALF) often requires multidisciplinary support. Higher hospital volumes have been associated with better outcomes for surgical procedures, but whether such a relationship exists for ALF has not been explored previously. In this study, our aim was to examine if hospital volume affects mortality from ALF. Using data from the Nationwide Inpatient Sample for the years 2001 to 2004, we identified cases by the presence of a primary discharge diagnosis of ALF (International Classification of Diseases, 9th revision, Clinical Modification code 570.x). Hospitals were divided into low-, medium-, and high-volume hospitals on the basis of 1 to 5, 6 to 20, and more than 20 annual ALF discharges. There were 17,361, 6756, and 1790 discharges with ALF from low-, medium-, and high-volume hospitals, respectively. There was no difference in adjusted mortality between low- and high-volume hospitals (odds ratio 0.94, 95% confidence interval 0.68-1.28). Teaching hospitals had a trend toward lower mortality among patients with hepatic encephalopathy (odds ratio 0.69, 95% confidence interval 0.47-1.01). High-volume centers had a higher rate of orthotopic liver transplantation (OLT) primarily because they were transplant centers, had better in-hospital post-OLT survival, and showed a trend toward a shorter time to OLT. In conclusion, patients with ALF receiving care at teaching hospitals and high-volume centers tend to be sicker. However, teaching hospitals and high-volume centers have equivalent in-hospital survival despite caring for this more severely ill cohort. Liver Transpl 14:1347,1356, 2008. © 2008 AASLD. [source] Acute liver failure induced by green tea extracts: Case report and review of the literatureLIVER TRANSPLANTATION, Issue 12 2006Michele Molinari In industrialized countries, over-the-counter dietary supplements have become popular in preventing and treating an expanding list of medical conditions. Although most commercially available supplements have not been rigorously tested for safety and efficacy, they have found an enlarging market because they are considered natural. Oral supplements containing green tea extract have been marketed as effective for weight loss and to prevent and cure some solid tumors. Although there is little scientific evidence of the effectiveness of green tea extracts to improve the quality of health of regular consumers, there is an increasing body of medical literature supporting the hypothesis that they can cause serious side effects. Our experience adds to previous reports of acute liver toxicity observed in individuals consuming supplements containing green tea extract. We highlight the importance of obtaining a detailed history of dietary supplement consumption when evaluating a patient presenting with acute liver dysfunction. Liver Transpl 12:1892,1895, 2006. © 2006 AASLD. [source] Neonatal liver failure and haemophagocytic lymphohistiocytosis caused by a new perforin mutationACTA PAEDIATRICA, Issue 5 2010O Danhaive Abstract Acute liver failure is a rare heterogeneous syndrome in neonates. We report of a newborn with haemophagocytic lymphohistiocytosis presenting as acute liver failure. Pancytopenia and multi-organ failure occurred later in the course. He carried two mutations of the perforin gene (PRF-1), one of which not previously described, causing a complete loss of perforin expression and natural killer cell function. Conclusion:, Perforin expression and function should be promptly assessed in neonatal/infantile acute liver failure, as haemophagocytic lymphohistiocytosis requires specific treatment and represents a contra-indication to liver transplant. [source] A reversibly immortalized human hepatocyte cell line as a source of hepatocyte-based biological supportADDICTION BIOLOGY, Issue 4 2001Naoya Kobayashi The application of hepatocyte transplantation (HTX) is increasingly envisioned for temporary metabolic support during acute liver failure and provision of specific liver functions in inherited liver-based metabolic diseases. Compared with whole liver transplantation, HTX is a technically simple procedure and hepatocytes can be cryopreserved for future use. A major limitation of this form of therapy in humans is the worldwide shortage of human livers for isolating an adequate number of transplantable human hepatocyes when needed. Furthermore, the numbers of donor livers available for hepatocyte isolation is limited by competition for their use in whole organ transplantation. Considering the cost of hepatocyte isolation and the need for immediate preparation of consistent and functional cells, it is unlikely that human hepatocytes can be obtained on such a scale to treat a large number of patients with falling liver functions. The utilization of xenogenic hepatocytes will result in additional concerns regarding transmission of infectious pathogens and immunological and physiological incompatibilities between animals and humans. An attractive alternative to primary human hepatocytes is the use of tightly regulated human hepatocyte cell lines. Such cell lines can provide the advantages of unlimited availability, sterility and uniformity. We describe here methods for creating transplantable human hepatocyte cell lines using currently available cell cultures and gene transfer technology. [source] Assessment of drug-induced liver injury in clinical practiceFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2008Ma Isabel Lucena Abstract Currently, pharmaceutical preparations are serious contributors to liver disease, with hepatotoxicity ranking as the most frequent cause for acute liver failure and post-marketing regulatory decisions. The diagnostic approach of drug-induced liver injury (DILI) is still rudimentary and inaccurate because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favour a toxic aetiology. Clinical and laboratory data may also be assessed with algorithms or clinical scales, which may add consistency to the clinical judgment by translating the suspicion into a quantitative score. The CIOMS/RUCAM instrument is considered at present the best method for assessing causality in DILI, although it could be improved through the use of large database of bona fide DILI cases for validation criteria. [source] Deletion of interleukin-6 in mice with the dominant negative form of transforming growth factor , receptor II improves colitis but exacerbates autoimmune cholangitis,HEPATOLOGY, Issue 1 2010Weici Zhang The role of interleukin-6 (IL-6) in autoimmunity attracts attention because of the clinical usage of monoclonal antibodies to IL-6 receptor (IL-6R), designed to block IL-6 pathways. In autoimmune liver disease, activation of the hepatocyte IL-6/STAT3 (signal transducer and activator of transcription 3) pathway is associated with modulating pathology in acute liver failure, in liver regeneration, and in the murine model of concanavalin A,induced liver inflammation. We have reported that mice expressing a dominant negative form of transforming growth factor , receptor II (dnTGF,RII) under control of the CD4 promoter develop both colitis and autoimmune cholangitis with elevated serum levels of IL-6. Based on this observation, we generated IL-6,deficient mice on a dnTGF-,RII background (dnTGF,RII IL-6,/,) and examined for the presence of antimitochondrial antibodies, levels of cytokines, histopathology, and immunohistochemistry of liver and colon tissues. As expected, based on reports of the use of anti,IL-6R in inflammatory bowel disease, dnTGF,RII IL-6,/, mice manifest a dramatic improvement in their inflammatory bowel disease, including reduced diarrhea and significant reduction in intestinal lymphocytic infiltrates. Importantly, however, autoimmune cholangitis in dnTGF,RII IL-6,/, mice was significantly exacerbated, including elevated inflammatory cytokines, increased numbers of activated T cells, and worsening hepatic pathology. Conclusion: The data from these observations emphasize that there are distinct mechanisms involved in inducing pathology in inflammatory bowel disease compared to autoimmune cholangitis. These data also suggest that patients with inflammatory bowel disease may not be the best candidates for treatment with anti,IL-6R if they have accompanying autoimmune liver disease and emphasize caution for therapeutic use of anti,IL-6R antibody. HEPATOLOGY 2010 [source] Disease-specific autoantibodies in patients with acute liver failure: The King's College London Experience,HEPATOLOGY, Issue 3 2008William Bernal No abstract is available for this article. [source] Mitochondrial hepatopathies: Advances in genetics and pathogenesis,HEPATOLOGY, Issue 6 2007Way S. Lee Hepatic involvement is a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period. Respiratory chain disorders may present as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. In recent years, specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and the deletion or rearrangement of mitochondrial DNA) have been identified, with the promise of genetic and prenatal diagnosis. The current treatment of mitochondrial hepatopathies is largely ineffective, and the prognosis is generally poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease, which does not respond to transplantation. Prospective, longitudinal, multicentered studies will be needed to address the gaps in our knowledge in these rare liver diseases. (HEPATOLOGY 2007;45:1555,1565.) [source] Bioartificial liver in acute liver failure: Impostor or simply misunderstood?HEPATOLOGY, Issue 2 2005FRCPI, John O'Grady M.D. No abstract is available for this article. [source] The systemic inflammatory response syndrome in acute liver failureHEPATOLOGY, Issue 4 2000Nancy Rolando The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis. [source] Efficacy and limitation of bone marrow transplantation in the treatment of acute and subacute liver failure in ratsHEPATOLOGY RESEARCH, Issue 11 2009Hirotaka Tokai Aim:, Recent reports have shown that bone marrow cells (BMC) retain the potential to differentiate into hepatocytes. Thus, the BMC have been recognized as an attractive source for liver regenerative medicine. However, it has not been clarified whether BMC transplantation can be used to treat liver damage in vivo. In the present study, we explored whether BMC possess therapeutic potential to treat acute and/or subacute liver failure. Methods:, Fulminant hepatic failure (FHF) was induced by 70% hepatectomy with ligation of the right lobe pedicle (24% liver mass), followed by transplantation of BMC into the spleen. Dipeptidyl peptidase IV-positive (DPPIV+) BMC were then transplanted into DPPIV-negative (DPPIV - ) recipients following hepatic irradiation (HIR) in which 70% of the liver was resected and the remnant liver irradiated. Results:, There was no benefit of BMC transplantation towards survival in the FHF model. DPPIV+ hepatocytes appeared in the liver tissues of the DPPIV - HIR model rats, but DPPIV+ hepatocytes replaced less than 13% of the recipient liver. Conclusion:, BMC transplantation may have limitations in the treatment of fulminant or acute liver failure because they do not have sufficient time to develop into functional hepatocytes. Preparative HIR may be beneficial in help to convert the transplanted BMC into host hepatocytes, and provide a survival benefit. Although, However, the precise mechanism warrants further studies. [source] Urgent liver transplantation for acute liver failure due to parvovirus B19 infection complicated by primary Epstein,Barr virus and cytomegalovirus infections and aplastic anaemiaINTERNAL MEDICINE JOURNAL, Issue 3 2007K. So Abstract An 11-year-old boy presented with hepatic failure secondary to parvovirus B19 infection, requiring urgent liver transplantation. His recovery was complicated by primary Epstein,Barr virus and cytomegalovirus infections. He subsequently developed aplastic anaemia that has been refractory to antithymocyte globulin and cyclosporine therapy and may now require bone marrow transplantation. We present this case to emphasize parvovirus as a rare cause of hepatic failure and of aplastic anaemia as a complication of the virus. [source] Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2001Toru Mizuguchi Liver transplantation is the only clinically effective method of treating acute liver failure. However, wider application of this therapeutic modality is restricted primarily by shortage of donor organs. In the search for alternative methods of liver replacement therapy, investigators have focused on transplantation of normal allogeneic hepatocytes and on the development of liver support systems utilizing isolated hepatocytes. Since all human livers suitable for cell harvest are being used for transplantation, hepatocyte therapy using human tissue would require growing of cells in vitro. Unfortunately, although hepatocytes have tremendous capacity to proliferate in vivo, their ability to grow in culture is severely limited. Stromal cells from bone marrow and other blood-forming organs have been found to support hematopoiesis. In this paper, we show that bone marrow-derived stromal cells (BMSCs) enhance proliferation and support differentiation of rat hepatocytes in culture. Further, we demonstrate that in hepatocyte/BMSC co-cultures, clonal expansion of small hepatocytes (SH) is increased. Using semipermeable membrane cultures, we established that direct cell,cell contact is necessary for stimulation of cell proliferation. We also show that BMSCs which are in direct contact with hepatocytes and SH colonies express Jagged1. This suggests a potential role for Notch signaling in the observed effects. Finally, we present evidence that the expression and activity of liver specific transcirption factors, CCAAT/enhancer binding proteins and liver specific key enzymes such as tryptophan 2,3-dioxygenase, are improved in hepatocyte/BMSC co-cultures. In conclusion, results of this study indicate that BMSCs could facilitate proliferation and differentiation of primary rat hepatocytes and their progenitors (SH) in vitro. © 2001 Wiley-Liss, Inc. [source] Th17 cells: The emerging reciprocal partner of regulatory T cells in the liverJOURNAL OF DIGESTIVE DISEASES, Issue 3 2010Li ZHAO T helper cells that produce interleukin-17 (IL-17) (Th17 cells) have recently been identified as the third distinct subset of effector T cells, the differentiation of which depends on specific transcription nuclear factor retinoic acid-related orphan nuclear receptor-,t. Emerging data have suggested that Th17 cells play an important role in innate immunity, adaptive immunity and autoimmunity. Interestingly, there is a reciprocal relationship between Th17 cells and regulatory T cells (Treg), not only in development, but also in their effector function. Transforming growth factor (TGF)-, induces Treg-specific transcription factor Forkhead box P3(FOXP3), while the addition of IL-6 to TGF-, inhibits the generation of Treg cells and induces Th17 cells. It is proposed that the fine balance between Th17 and Treg cells is crucial for maintenance of immune homeostasis. In addition to IL-6, other factors such as retinoic acid, rapamycin, or cytokines (e.g., IL-2 and IL-27) could dictate the balance between Th17 and Treg cells. Since Treg cells play an important role in hepatic immunity with overregulation in chronic viral hepatitis and hepatic carcinoma, and inadequate inhibition in autoimmune liver diseases, graft rejection and acute liver failure, it is reasonable to assume that Th17 cells may play a reciprocal role in these diseases. Thus, future research on the Treg/Th17 balance may provide an opportunity to illustrate the pathogenesis of hepatic inflammation and to explore new therapeutic targets for immune-related liver diseases. [source] Acute liver failure in Sweden: etiology and outcomeJOURNAL OF INTERNAL MEDICINE, Issue 3 2007G. Wei Abstract. Objective., To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994,2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score with transplant-free deaths as a positive outcome. Research design and methods., Adult patients in Sweden with international normalized ratio (INR) of ,1.5 due to severe liver injury with and without encephalopathy at admission between 1994,2003 were included. Results., A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive-predictive value (PPV) of 67%, negative-predictive value (NPV) of 84% in the acetaminophen group. Positive-predictive value and negative-predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score >30 had a positive-predictive value of 21%, negative-predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively. Conclusions., Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score <30 predicts a good prognosis in acetaminophen patients without transplantation. [source] Fatal liver failure with the emergence of hepatitis B surface antigen variants with multiple stop mutations after discontinuation of lamivudine therapyJOURNAL OF MEDICAL VIROLOGY, Issue 3 2006Ji-Ming Zhang Abstract Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is effective and well-tolerated. However, discontinuation of the treatment is associated frequently with acute exacerbation of liver diseases. A patient suffering from acute liver failure after discontinuation of lamivudine treatment is described. The patient was treated with lamivudine for 4 months and ceased the treatment without consulting. After receiving lamivudine, the patient developed anti-HBs and became negative for hepatitis B surface antigens (HBsAg). However, HBV DNA reappeared to a level of 6.47,×,105 copies/ml. The patient died due to acute liver failure. Sequencing of HBV isolates revealed that mutations including G145R and stop codons occurred within the HBsAg coding region. In conclusion, HBV replication resumed after the uncontrolled cessation of lamivudine treatment in this patient and may have triggered the process leading to liver failure. Anti-HBs antibody appeared and may be the selective force for the emergence of HBV mutants. J. Med. Virol. 78:324,328, 2006. © 2006 Wiley-Liss, Inc. [source] Calcium in the mechanism of ammonia-induced astrocyte swellingJOURNAL OF NEUROCHEMISTRY, Issue 2009Arumugam R. Jayakumar Abstract Brain edema, due largely to astrocyte swelling, is an important clinical problem in patients with acute liver failure. While mechanisms underlying astrocyte swelling in this condition are not fully understood, ammonia and associated oxidative/nitrosative stress appear to be involved. Mechanisms responsible for the increase in reactive oxygen/nitrogen species (RONS) and their role in ammonia-induced astrocyte swelling, however, are poorly understood. Recent studies have demonstrated a transient increase in intracellular Ca2+ in cultured astrocytes exposed to ammonia. As Ca2+ is a known inducer of RONS, we investigated potential mechanisms by which Ca2+ may be responsible for the production of RONS and cell swelling in cultured astrocytes after treatment with ammonia. Exposure of cultured astrocytes to ammonia (5 mM) increased the formation of free radicals, including nitric oxide, and such increase was significantly diminished by treatment with the Ca2+ chelator 1,2-bis-(o -aminophenoxy)-ethane- N,N,- N,,N, -tetraacetic acid tetraacetoxy-methyl ester (BAPTA). We then examined the activity of Ca2+ -dependent enzymes that are known to generate RONS and found that ammonia significantly increased the activities of NADPH oxidase (NOX), constitutive nitric oxide synthase (cNOS), and phospholipase A2 (PLA2) and such increases in activity were significantly diminished by BAPTA. Pre-treatment of cultures with 7-nitroindazole, apocyanin, and quinacrine, respective inhibitors of cNOS, NOX, and PLA2, all significantly diminished RONS production. Additionally, treatment of cultures with BAPTA or with inhibitors of cNOS, NOX, and PLA2 reduced ammonia-induced astrocyte swelling. These studies suggest that the ammonia-induced rise in intracellular Ca2+ activates free radical producing enzymes that ultimately contribute to the mechanism of astrocyte swelling. [source] Pre-admission consultation and late referral in infants with neonatal cholestasisJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2008Way Seah Lee Aims: To study factors leading to delayed referral in neonatal cholestasis at a tertiary centre in Malaysia. Methods: A prospective, observational study on consecutive infants with neonatal cholestasis referred to a tertiary unit paediatric liver unit in Malaysia. Results: Thirty-one of the 65 (43%) patients studied encountered delay or had an inappropriate action taken before referral. Factors leading to delayed referral, which adversely affected the outcome of biliary atresia (BA) and neonatal acute liver failure, were repeated reassurances by medical and paramedical staff (n = 17, 26%), failure of hospital services at the referring hospital (n = 7, 11%) and parental refusal for referral (n = 5, 8%). Only three (14%) of the 22 patients who developed liver failure had liver transplantation (LT). The 1-year survival rate with native liver for BA was 35%, while overall 1-year survival rate (native liver and LT) was 41%. Conclusions: Repeated false reassurance, failure of hospital services and parental refusal all contributed to delayed referral in neonatal cholestasis. In addition to education of medical and public health workers, and parents on the importance of early referral in neonatal cholestasis, health authorities in Malaysia should consider the feasibility of universal stool colour screening in newborn infants to improve the outcome of BA. [source] Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010P. Jepsen Aliment Pharmacol Ther 2010; 32: 894,900 Summary Background, The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown. Aim, To examine whether paracetamol-induced acute liver failure increases long-term mortality. Methods, We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984,2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not. Results, We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02,2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure. Conclusions, Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself. [source] Review article: drug-induced liver injury in clinical practiceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010E. Björnsson Aliment Pharmacol Ther 2010; 32: 3,13 Summary Background, Drug-induced liver injury (DILI) is an important differential diagnosis in many patients in clinical hepatology. DILI is the leading cause of acute liver failure and is an important safety issue when new drugs are developed. Aims, To provide a review of the recent data on DILI with particular focus on the most common and relevant issues seen in clinical practice. Methods, A Medline search was undertaken to identify relevant literature using search terms including ,drug-induced liver injury' and ,hepatotoxicity'. Results, The true incidence of DILI remains unknown but incidence up to 14 cases per 100 000 inhabitants and year has been reported. Antibiotics, analgesics and NSAIDs are the most common drugs causing liver injury. Idiosyncratic DILI has been shown to have a dose-dependent component and drugs without significant hepatic metabolism rarely cause DILI. Chronic elevation in liver enzymes can develop after DILI but this is rarely associated with clinical morbidity or mortality. Conclusions, Drug-induced liver injury remains a diagnostic challenge. Multicentre studies and international collaborative work with well-characterized patients will increase our understanding of liver injury associated with drugs. New therapies for acute liver failure resulting from drugs are needed. [source] Systematic review: prognostic tests of paracetamol-induced acute liver failureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010D. G. N. CRAIG Aliment Pharmacol Ther,31, 1064,1076 Summary Background, Paracetamol (acetaminophen) toxicity remains the leading cause of acute liver failure (ALF) in the developed world. In the UK, the recently modified King's College Criteria are used to list patients for emergency liver transplantation, but these criteria have been criticized for their low sensitivity and for spectrum bias in their application. Aim, To evaluate existing prognostic criteria critically for predicting death without transplantation in paracetamol-induced ALF. Methods, MEDLINE, EMBASE and CINAHL were searched to identify studies containing adult patients with paracetamol-induced ALF. Selected studies were evaluated and data were pooled if appropriate, to calculate sensitivity, specificity and diagnostic odds ratios (DORs) of applied prognostic tests. Results, Of 6507 studies identified, 14 were eligible for inclusion, evaluating 1960 patients. The original King's College Criteria had a pooled sensitivity of 58.2% and specificity of 94.6%, with a DOR of 27.7. Addition of arterial lactate to the King's College Criteria reduced the DOR to 26.1. Several other clinical and laboratory variables had higher DORs than the King's College Criteria, but were only evaluated in single studies of limited quality. Conclusions, The original King's College Criteria remain well-validated criteria with high prognostic accuracy. Other potential prognostic variables should be prospectively assessed in multicentre studies to refine the criteria further. [source] Review article: the current management of acute liver failureALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010D. G. N. CRAIG Aliment Pharmacol Ther,31, 345,358 Summary Background, Acute liver failure is a devastating clinical syndrome with a persistently high mortality rate despite critical care advances. Orthotopic liver transplantation (OLT) is a life-saving treatment in selected cases, but effective use of this limited resource requires accurate prognostication because of surgical risks and the requirement for subsequent life-long immunosuppression. Aim, To review the aetiology of acute liver failure, discuss the evidence behind critical care management strategies and examine potential treatment alternatives to OLT. Methods, Literature review using Ovid, PubMed and recent conference abstracts. Results, Paracetamol remains the most common aetiology of acute liver failure in developed countries, whereas acute viral aetiologies predominate elsewhere. Cerebral oedema is a major cause of death, and its prevention and prompt recognition are vital components of critical care support, which strives to provide multiorgan support and ,buy time' to permit either organ regeneration or psychological and physical assessment prior to acquisition of a donor organ. Artificial liver support systems do not improve mortality in acute liver failure, whilst most other interventions have limited evidence bases to support their use. Conclusion, Acute liver failure remains a truly challenging condition to manage, and requires early recognition and transfer of patients to specialist centres providing intensive, multidisciplinary input and, in some cases, OLT. [source] Phosphorus and phosphate metabolism in veterinary patientsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2007Diana M. Schropp DVM Abstract Objective: To review phosphorus and phosphate metabolism and the importance of phosphate abnormalities in veterinary patients. Data sources: A review of recent human and veterinary medical literature. Human data synthesis: There is a significant amount of original research on human patients with phosphate abnormalities. Hypophosphatemia has been studied in patients with diabetic ketoacidosis (DKA), head trauma, refeeding syndrome, hypothermia and in ventilator patients that fail to wean. Hyperphosphatemia has been studied in patients with renal failure and malignancy. Phosphate levels have also been evaluated for prognostic value in sepsis and acute liver failure. Veterinary data synthesis: Although animal models were used in early experimental research, fewer studies have been published on the effects of phosphate abnormalities in veterinary patients. Hypophosphatemia has been studied in animals with DKA, with refeeding syndrome and with hyperparathyroidism. Hyperphosphatemia has been studied in animals with renal failure and with secondary hypoparathyroidism. Conclusion: Phosphorus and phosphate are important in many biological functions. This paper is a review of their role in normal metabolism and the clinical importance of phosphate imbalances for our emergency and critical care patients. [source] Regulatory polymorphisms in the IL-10 gene promoter and HBV-related acute liver failure in the Chinese populationJOURNAL OF VIRAL HEPATITIS, Issue 11 2009Z. Yan Summary., Recent reports indicated that high levels of interleukin 10 (IL-10) contribute to the monocytes paralysis and poor clinical outcome in acute liver failure (ALF). Polymorphisms in the promoter region of IL-10 affect IL-10 production and confer susceptibility to inflammatory diseases. The aim of this study was to determine the possible association of the three polymorphisms (A-1082G, T-819C, A-592C) in the IL-10 gene promoter with the susceptibility to hepatitis B virus (HBV)-related ALF in a Chinese population. The IL-10 gene promoter polymorphisms were genotyped in 414 unrelated healthy blood donors, 367 asymptomatic HBV carriers and 345 HBV-related ALF patients. Functional analyses were conducted to verify the biological significances of the associated genetic variations. The allele frequencies of IL-10,592C and ,819C were significantly higher in HBV-related ALF patients than in blood donors and asymptomatic HBV carriers. Logistic regression analysis and stratification analysis with adjustment for age and sex indicated that the polymorphisms of A-592C and T-819C were associated with susceptibility to HBV-related ALF (P = 6.9 × 10,7), and the -1082A-819C-592C haplotype in the IL-10 gene promoter were associated with an increased susceptibility to ALF in HBV carriers (dominant model, P = 0.0002, odds ratio = 1.60, 95% CI 1.25,2.07). Functional analyses showed that the A-592C polymorphism is a nuclear proteins binding site, and the disease susceptible ,592C allele had a higher transcription activity compared with ,592A allele. This study emphasizes the importance of IL-10 in the pathophysiology of HBV-related ALF on the population level. [source] Hepatitis A acute liver failure: follow-up of paediatric patients in southern BrazilJOURNAL OF VIRAL HEPATITIS, Issue 2008C. T. Ferreira Summary., We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 ± 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 ± 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area. [source] | ||||||||||||||||||||||||||||||||||||||||