Immune mediated liver failure

OpenAIRE

Wang, Xiaojing; Ning, Qin

2014-01-01

Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

Nonacetaminophen Drug-Induced Acute Liver Failure.

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Thomas, Arul M; Lewis, James H

2018-05-01

Acute liver failure of all causes is diagnosed in between 2000 and 2500 patients annually in the United States. Drug-induced acute liver failure is the leading cause of acute liver failure, accounting for more than 50% of cases. Nonacetaminophen drug injury represents 11% of all cases in the latest registry from the US Acute Liver Failure Study Group. Although rare, acute liver failure is clinically dramatic when it occurs, and requires a multidisciplinary approach to management. In contrast with acetaminophen-induced acute liver failure, non-acetaminophen-induced acute liver failure has a more ominous prognosis with a lower liver transplant-free survival. Copyright © 2018 Elsevier Inc. All rights reserved.

Immune mediated liver failure.

Science.gov (United States)

Wang, Xiaojing; Ning, Qin

2014-01-01

Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report.

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Nacif, Lucas Souto; Waisberg, Daniel R; Pinheiro, Rafael Soares; Lima, Fabiana Roberto; Rocha-Santos, Vinicius; Andraus, Wellington; D'Albuquerque, Luiz Carneiro

2018-03-10

There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment. We report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases.

Characterization of acute-on-chronic liver failure and prediction of mortality in Asian patients with active alcoholism.

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Kim, Hwi Young; Chang, Young; Park, Jae Yong; Ahn, Hongkeun; Cho, Hyeki; Han, Seung Jun; Oh, Sohee; Kim, Donghee; Jung, Yong Jin; Kim, Byeong Gwan; Lee, Kook Lae; Kim, Won

2016-02-01

Alcoholic liver diseases often evolve to acute-on-chronic liver failure (ACLF), which increases the risk of (multi-)organ failure and death. We investigated the development and characteristics of alcohol-related ACLF and evaluated prognostic scores for prediction of mortality in Asian patients with active alcoholism. A total of 205 patients who were hospitalized with severe alcoholic liver disease were included in this retrospective cohort study, after excluding those with serious cardiovascular diseases, malignancy, or co-existing viral hepatitis. The Chronic Liver Failure (CLIF) Consortium Organ Failure score was used in the diagnosis and grading of ACLF, and the CLIF Consortium ACLF score (CLIF-C ACLFs) was used to predict mortality. Patients with ACLF had higher Maddrey discriminant function, model for end-stage liver disease (MELD), and MELD-sodium scores than those without ACLF. Infections were more frequently documented in patients with ACLF (33.3% vs 53.0%; P = 0.004). Predictive factors for ACLF development were systemic inflammatory response syndrome (odds ratio [OR], 2.239; P alcohol-related ACLF in Asian patients with active alcoholism. The CLIF-C ACLFs may be more useful for predicting mortality in ACLF cases than liver-specific scoring systems. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

OpenAIRE

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen; Wang, Fu-Sheng

2012-01-01

This study assessed the safety and initial efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transfusions for acute-on-chronic liver failure (ACLF) patients associated with hepatitis B virus (HBV) infection. No significant side effects were observed, and the UC-MSC transfusions significantly increased the survival rates in ACLF patients. It was found that UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients.

Clinical features of HBV-associated acute-on-chronic liver failure induced by discontinuation of nucleoside analogues

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LIU Xiaoyan

2016-09-01

Full Text Available Objective To investigate the clinical features of patients with HBV-associated acute-on-chronic liver failure (HBV-ACLF induced by the discontinuation of necleos(tide analogues. Methods A retrospective analysis was performed for 698 patients with a definite diagnosis of HBV-ACLF in The 302 Hospital of PLA from January 2014 to April 2016, and among these patients, 150 (discontinuation group had acute-on-chronic liver failure (ACLF induced by discontinuation, 396 (previously untreated group had not received antiviral therapy when they developed this disease for the first time, and the other 152 patients with ACLF caused by other reasons were enrolled as controls. The causative factors, underlying diseases, family history, serum hepatitis B markers, prognosis, and initial onset were summarized, and the drugs used and discontinuation time were recorded for patients who stopped taking necleos(tide analogues. The chi-square test was used for the comparison of categorical data between groups. Results Among the 698 patients, 355(50.86% had a family history of chronic hepatitis B (CHB, and 93 patients (62.00% in the discontinuation group had a family history of CHB. Among the 150 patients in the discontinuation group, 27 (18.00% had an underlying disease of chronic hepatitis, among whom 12 (44.44% had a family history of CHB, which was significantly lower than the overall level (χ2=2.57, P=0.07; 123 (82.00% had an underlying disease of liver cirrhosis (compensated, among whom 81 (65.85% had a family history of CHB, which was significantly higher than the overall level (χ2=48.77, P＜0.001. Of all the patients in the discontinuation group, 77.33% (116/150 developed the disease within 1 year after discontinuation, and 21.33% (32/150developed the disease during the second year after discontinuation. The HBeAg-negative patients accounted for 47.33% (71/150. In the discontinuation group and previously untreated group, the patients with an underlying disease

Artificial and bioartificial support systems for liver failure

DEFF Research Database (Denmark)

Liu, J P; Gluud, L L; Als-Nielsen, B

2004-01-01

Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery.......Artificial and bioartificial liver support systems may 'bridge' patients with acute or acute-on-chronic liver failure to liver transplantation or recovery....

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

Science.gov (United States)

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

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Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

When the heart kills the liver: acute liver failure in congestive heart failure

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Saner FH

2009-12-01

Full Text Available Abstract Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases. Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach. As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST, bilirubin, and international normalized ratio (INR did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m2 vs. 1.6 L/min/m2, p = 0.04. Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock. In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.

Plasma Glutamine Concentrations in Liver Failure.

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Gunnel Helling

Full Text Available Higher than normal plasma glutamine concentration at admission to an intensive care unit is associated with an unfavorable outcome. Very high plasma glutamine levels are sometimes seen in both acute and chronic liver failure. We aimed to systematically explore the relation between different types of liver failure and plasma glutamine concentrations.Four different groups of patients were studies; chronic liver failure (n = 40, acute on chronic liver failure (n = 20, acute fulminant liver failure (n = 20, and post-hepatectomy liver failure (n = 20. Child-Pugh and Model for End-stage Liver Disease (MELD scores were assessed as indices of liver function. All groups except the chronic liver failure group were followed longitudinally during hospitalisation. Outcomes were recorded up to 48 months after study inclusion.All groups had individuals with very high plasma glutamine concentrations. In the total group of patients (n = 100, severity of liver failure correlated significantly with plasma glutamine concentration, but the correlation was not strong.Liver failure, regardless of severity and course of illness, may be associated with a high plasma glutamine concentration. Further studies are needed to understand whether high glutamine levels should be regarded as a biomarker or as a contributor to symptomatology in liver failure.

Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot: case report

Science.gov (United States)

2010-01-01

Background Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases. Case Presentation We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation. Conclusions This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important. PMID:20707932

Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF)

DEFF Research Database (Denmark)

Grønbæk, Henning; Rødgaard-Hansen, Sidsel; Aagaard, Niels Kristian

2016-01-01

BACKGROUND & AIMS: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose receptor......-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy: In ACLF patients sCD163 improved prediction of short-term mortality (C-index: 0.74 (0.67-0.80)) and in patients without ACLF sMR improved prediction of long-term mortality (C-index: 0.......80 (0.76-0.85)). CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform...

EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure

DEFF Research Database (Denmark)

Wendon,, Julia; Cordoba, Juan; Dhawan, Anil

2017-01-01

abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately...... necessary when the patient presents for medical attention. These, as well as additional clinical procedures will be the subject of these clinical practice guidelines.......The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute...

Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot: case report

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Shen Chuan

2010-08-01

Full Text Available Abstract Background Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases. Case Presentation We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation. Conclusions This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important.

Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

NARCIS (Netherlands)

Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

2012-01-01

. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

NARCIS (Netherlands)

Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

Acute Liver Failure

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... can cause acute liver failure. It is an industrial chemical found in refrigerants and solvents for waxes, varnishes ... measures when spraying insecticides, fungicides, paint and other toxic chemicals. Follow product instructions carefully. Watch what gets on ...

Acute liver failure and self-medication.

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de Oliveira, André Vitorio Câmara; Rocha, Frederico Theobaldo Ramos; Abreu, Sílvio Romero de Oliveira

2014-01-01

Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. To warn about how the practice of self-medication can be responsible for acute liver failure. Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute liver failure [tiab] AND acetaminophen [tiab]; self-medication [tiab] AND acetaminophen [tiab]; acute liver failure [tiab] AND dietary supplements [tiab]; self-medication [tiab] AND liver failure [tiab] and self-medication [tiab] AND green tea [tiab]. In Lilacs and SciELO used the descriptor self medication in Portuguese and Spanish. From total surveyed were selected 27 articles and five sites specifically related to the purpose of this review. Legislation and supervision disabled and information inaccessible to people, favors the emergence of cases of liver failure drug in many countries. In the list of released drugs that deserve more attention and care, are some herbal medicines used for the purpose of weight loss, and acetaminophen. It is recommended that institutes of health intensify supervision and better orient their populations on drug seemingly harmless, limiting the sale of products or requiring a prescription for release them.

Economic evaluation of the artificial liver support system MARS in patients with acute-on-chronic liver failure

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Hessel Franz P

2006-10-01

Full Text Available Abstract Background Acute-on-chronic liver failure (ACLF is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS. Methods In a clinical cohort trial with a prospective follow-up of 3 years 33 ACLF-patients treated with MARS were compared to 46 controls. Survival, health-related quality of life as well as direct medical costs for in- and outpatient treatment from a health care system perspective were determined. Based on the differences in outcome and indirect costs the cost-effectiveness of MARS expressed as incremental costs per life year gained and incremental costs per QALY gained was estimated. Results The average initial intervention costs for MARS were 14600 EUR per patient treated. Direct medical costs over 3 years follow up were overall 40000 EUR per patient treated with MARS respectively 12700 EUR in controls. The 3 year survival rate after MARS was 52% compared to 17% in controls. Kaplan-Meier analysis of cumulated survival probability showed a highly significant difference in favour of MARS. Incremental costs per life-year gained were 31400 EUR; incremental costs per QALY gained were 47200 EUR. Conclusion The results after 3 years follow-up of the first economic evaluation study of MARS based on empirical patient data are presented. Although high initial treatment costs for MARS occur the significantly better survival seen in this study led to reasonable costs per live year gained. Further randomized controlled trials investigating the medical efficacy and the cost-effectiveness are recommended.

Acute liver failure

DEFF Research Database (Denmark)

Bernal, William; Lee, William M; Wendon, Julia

2015-01-01

Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver...

Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV-related acute-on-chronic liver failure

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YOU Shaoli

2013-09-01

Full Text Available ObjectiveTo construct a hybrid bioartificial liver support system and to investigate its safety and efficacy in patients with hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF. MethodsA hollow fiber bioreactor was constructed using cultured HepG2 cells transfected with human augmenter of liver regeneration gene. Patients with HBV-related ACLF who were hospitalized in our hospital from May 2009 to August 2011 were randomly divided into treatment group (n=10 and control group (n=10. The treatment group was treated using the hybrid bioartificial liver support system, while the control group was treated with conventional plasma exchange. Comparison of means between the two groups was made by independent-samples t test, and comparison of variables before and after treatment was made by paired t test. ResultsOf the 10 patients in treatment group, 7 had improvement in clinical symptoms and were discharged, 1 died of hepatic encephalopathy, 1 died of hepatorenal syndrome, and 1 died of liver failure after discharge. Of the 10 patients in control group, 5 survived, 1 underwent liver transplantation, and 4 died of liver failure. Before treatment, the treatment group and control group had model for end-stage liver disease (MELD scores of 24.26±2.54 and 24.71±2.79, respectively, without significant difference between the two groups (t=1.971, P=0.064. The treatment group had MELD scores of 21.71±2.92, 22.10±4.46, and 19.90±5.43 after 3 days, 1 week, and 4 weeks, respectively, of treatment. At the end of one-year follow-up, the mean serum alpha-fetoprotein levels were 14.24 ng/ml in treatment group and 11.32 ng/ml in control group, and no space-occupying lesions in the liver were found through abdominal ultrasound. ConclusionThe constructed hybrid bioartificial liver support system is effective and safe in the treatment of HBV-related ACLF.

Acute liver failure and self-medication

OpenAIRE

OLIVEIRA, André Vitorio Câmara de; ROCHA, Frederico Theobaldo Ramos; ABREU, Sílvio Romero de Oliveira

2014-01-01

INTRODUCTION: Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. AIM: To warn about how the practice of self-medication can be responsible for acute liver failure. METHOD: Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute l...

Acute Liver Failure among Patients on Efavirenz-Based Antiretroviral Therapy

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Innocent Lule Segamwenge

2018-01-01

Full Text Available Objectives. To describe the clinical characteristics of patients presenting with fulminant liver failure after varying periods of exposure to Efavirenz containing antiretroviral medications. Methods. We report a series of 4 patients with human immunodeficiency virus (HIV infection who were admitted with acute liver failure (ALF over a 6-month period. All these patients had been treated with a range of Efavirenz containing antiretroviral regimens and were negative for hepatitis A, B, and C infections as well as other opportunistic infections, all were negative for autoimmune hepatitis, and none had evidence of chronic liver disease or use of alcohol or herbal medications. Information on patient clinical characteristics, current antiretroviral regimen, CD4 count, HIV-1 RNA levels, and clinical chemistry parameters was collected. Informed consent was provided. Results. During a 6-month period, four patients without other known risk factors for acute hepatitis presented with symptomatic drug-induced liver injury with varying symptoms and outcomes. The pattern of liver injury was hepatocellular for all the 4 cases. Liver biopsies were done for all the four cases and the results showed a heavy mixed inflammatory cell infiltrate with eosinophils. For three patients withdrawal of Efavirenz from their antiretroviral regimen was sufficient to restore transaminase levels to normal and led to improvement of clinical symptoms. For one patient his clinical course was characterized by fulminant liver failure and fluctuating episodes of hepatic encephalopathy which ultimately resulted in his death. Conclusion. Hepatotoxicity of Efavirenz is not as rare as previously described in the literature and does actually present with fatal outcomes. The key message to note is that frequent monitoring of liver enzymes should be done at initiation of antiretroviral therapy and should continue throughout the treatment period.

The effect of plasma exchange on entecavir-treated chronic hepatitis B patients with hepatic de-compensation and acute-on-chronic liver failure.

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Yue-Meng, Wan; Yang, Li-Hong; Yang, Jin-Hui; Xu, Ying; Yang, Jing; Song, Gui-Bo

2016-05-01

Various studies showed that entecavir (ETV) failed to improve the short-term survival in chronic hepatitis B (CHB) patients with severe acute exacerbation (SAE) and hepatic de-compensation or acute-on-chronic liver failure (ACLF). One study concluded that plasma exchange (PE) significantly decreased the short-term mortality of CHB patients with ACLF who were treated with lamivudine (LAM). Our study was designed to examine the effect of PE on CHB patients with ACLF who were treated with ETV. From August 2010 to January 2015, 38 (PE group) and 120 (control group) consecutive CHB-naïve patients with hepatic de-compensation and ACLF treated with PE plus ETV and ETV, respectively, were recruited. The primary endpoint was liver-related mortality at week 12. Biochemical and virological responses were also studied. At baseline, the PE group had higher serum alanine aminotransferase (ALT) levels and model for end-stage liver disease (MELD) scores, and had lower albumin levels than the control group. The cumulative survival rate at week 4 and week 12 in the PE group and control group were, respectively, 37 and 18 %, and 29 and 14 % (p  0.05). Univariate analysis showed that the control group had a higher liver-related mortality (p = 0.038) at week 12 than the PE group. Multivariate analysis showed that hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12. PE significantly improved the short-term survival of CHB patients with hepatic de-compensation and ACLF who were treated with ETV. Hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12.

Acute liver failure in Cuban children.

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Silverio, César E; Smithen-Romany, Chleo Y; Hondal, Norma I; Díaz, Hetzel O; Castellanos, Marlen I; Sosa, Oramis

2015-01-01

Acute liver failure is rare in pediatric patients and is one of the most challenging medical emergencies due to its prognostic and therapeutic implications. The best scientific evidence worldwide comes from multicenter studies in developed countries. In Cuba, there are no prior studies of this disorder in children. Describe the main clinical features of Cuban children treated at a national referral center for acute liver failure, as defined by recognized diagnostic criteria for pediatric patients. A case series study was conducted comprising patients diagnosed with acute liver failure treated from 2005 to 2011 in the hepatology and liver transplant service at Havana's William Soler University Children's Hospital. Variables were age group, etiology of acute liver failure, grade of hepatic encephalopathy, blood chemistry variables, and clinical outcome (whether or not spontaneous recovery of liver function occurred). Associations between variables were assessed using contingency tables, and case fatality was calculated, as well as relative risk with its 95% confidence interval. The Mann-Whitney U test was used to compare means of laboratory test results. Median age of the 31 patients studied (14 boys and 17 girls) was 24 months (range 1-180). Time between symptom onset and diagnosis of acute liver failure was 25.1 days (SD 16.8). Infection was the most common etiology, present in 61.3% of cases (19/31); nonhepatotropic viruses, especially cytomegalovirus, predominated in infants. Spontaneous recovery occurred in 15 patients (48.4%), 3 (9.7%) received transplants, and 13 died, for a case fatality of 41.9%. Outcome was not associated with etiology (p = 0.106), but was statistically associated with degree of hepatic encephalopathy (p failure in Cuban children calls for further epidemiologic study and identification of local underlying determinants of this phenomenon.

Acute Liver Failure Secondary to Niacin Toxicity

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Marc A. Ellsworth

2014-01-01

Full Text Available A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

Evaluation of the therapeutic efficacy of lamivudine combined with plasma exchange for treating acute-on-chronic hepatitis B liver failure

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HU Qijiang

2013-02-01

Full Text Available ObjectiveTo observe the clinical effects of lamivudine antiviral therapy combined with plasma exchange in patients with acute-on-chronic hepatitis B liver failure. MethodsForty-seven patients (treatment group were administered lamivudine and underwent plasma exchange. An additional forty-five patients (control group were administered lamivudine but no plasma exchange. Otherwise, all patients received the same basic medical treatment. The two groups were further divided into three sub-groups according to the model for end-stage liver disease (MELD score: ＜30, 30-39, and ≥40. The significance of differences in survival rates between the groups and sub-groups was determined by the χ2 test. ResultsThe overall survival rate was significantly better in the treatment group (63.82% vs. control group: 44.44%; χ2=4.31, P＜0.05. Within the treatment group, the survival rates were highest in the 30-39 MELD score sub-group (71.42%, which was significantly different from survival rate in the same sub-group of the controls (vs. 38.10%; χ2=4.71, P＜005. The other two MELD score sub-groups showed no significant differences between the treatment and control groups (all P＞0.05. ConclusionCombined therapy consisting of lamivudine treatment and plasma exchange can improve the survival rate of patients with acute-on-chronic hepatitis B liver failure who have MELD scores between 30 and 39.

Low Platelet to White Blood Cell Ratio Indicates Poor Prognosis for Acute-On-Chronic Liver Failure.

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Jie, Yusheng; Gong, Jiao; Xiao, Cuicui; Zhu, Shuguang; Zhou, Wenying; Luo, Juan; Chong, Yutian; Hu, Bo

2018-01-01

Background. Platelet to white blood cell ratio (PWR) was an independent prognostic predictor for outcomes in some diseases. However, the prognostic role of PWR is still unclear in patients with hepatitis B related acute-on-chronic liver failure (ACLF). In this study, we evaluated the clinical performances of PWR in predicting prognosis in HBV-related ACLF. Methods. A total of 530 subjects were recruited, including 97 healthy controls and 433 with HBV-related ACLF. Liver function, prothrombin time activity (PTA), international normalized ratio (INR), HBV DNA measurement, and routine hematological testing were performed at admission. Results . At baseline, PWR in patients with HBV-related ACLF (14.03 ± 7.17) was significantly decreased compared to those in healthy controls (39.16 ± 9.80). Reduced PWR values were clinically associated with the severity of liver disease and the increased mortality rate. Furthermore, PWR may be an inexpensive, easily accessible, and significant independent prognostic index for mortality on multivariate analysis (HR = 0.660, 95% CI: 0.438-0.996, p = 0.048) as well as model for end-stage liver disease (MELD) score. Conclusions . The PWR values were markedly decreased in ACLF patients compared with healthy controls and associated with severe liver disease. Moreover, PWR was an independent prognostic indicator for the mortality rate in patients with ACLF. This investigation highlights that PWR comprised a useful biomarker for prediction of liver severity.

Steroid use in acute liver failure

DEFF Research Database (Denmark)

Karkhanis, Jamuna; Verna, Elizabeth C; Chang, Matthew S

2014-01-01

UNLABELLED: Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indete......UNLABELLED: Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug......-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS......% versus 66%, P = 0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P = 0...

Clinical heterogeneity in autoimmune acute liver failure

Science.gov (United States)

Chavez-Tapia, Norberto C; Martinez-Salgado, Julio; Granados, Julio; Uribe, Misael; Tellez-Avila, Felix I

2007-01-01

AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids. PMID:17465474

Therapeutic hypothermia for acute liver failure

DEFF Research Database (Denmark)

Stravitz, R.T.; Larsen, Finn Stolze

2009-01-01

transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...... insults, hypothermia reduces cerebral edema and intracranial hypertension in patients with acute liver failure by decreasing splanchnic ammonia production, restoring normal regulation of cerebral hemodynamics, and lowering oxidative metabolism within the brain. Hypothermia may also ameliorate the degree...... of liver injury. Hypothermia has not been adequately studied for its safety and theoretically may increase the risk of infection, cardiac dysrhythmias, and bleeding, all complications independently associated with acute liver failure. Therefore, although an ample body of experimental and human data...

Acute liver failure during treatment of interferon alpha 2a chronic hepatitis B and coinfection of parvovirus B19

Science.gov (United States)

Sobala-Szczygieł, Barbara; Boroń-Kaczmarska, Anna; Kępa, Lucjan; Oczko-Grzesik, Barbara; Piotrowski, Damian; Stolarz, Wojciech

Parvovirus B19 infection is associated with a broad spectrum of clinical manifestations among which some are well known but others remain controversial. The role of this infection as a cause of acute hepatitis or exacerbation of chronic liver disease requires discussion regarding its significance in a strategy of prevention and treatment of patients with chronic hepatitis. Clinical importance of this infection in patients with chronic hepatitis B treated with pegylated interferon alpha 2a is still unclear but exactly in this population significant complications during treatment may arise. Parvovirus B19 infection is not rare among persons with chronic hepatitis B, therefore searching for co-infection should be placed in standard diagnostic procedures especially in case of exacerbation of chronic hepatitis, pancytopaenia or anaemia of unknown origin. Pegylated interferon alpha 2a still remains a gold standard of therapy of patients with chronic hepatitis B according to European (EASL) and Polish guidelines. We present a case of 35 years old woman treated with pegylated interferon alpha 2a who developed acute liver failure in 23rd week of chronic hepatitis B therapy. An exacerbation of hepatitis with encephalopathy and pancytopaenia have been observed. Parvovirus B19 and HBV co-infection does not increase the frequency of liver function abnormalities in patients with chronic hepatitis B. Further investigations should be done to describe the natural course of co-infection with parvovirus B19 and HBV and to establish possible association between parvovirus B19 infection and chronic hepatitis B and also the influence of interferon alpha 2a on the infections course.

[Brain oedema and acute liver failure].

Science.gov (United States)

Spahr, L

2003-04-01

Brain oedema leading to intracranial hypertension occurs in a significant proportion of patients with acute liver failure in whom it is a leading cause of death. Although precise pathogenic mechanisms associated to this severe complication remain incompletely understood, increasing evidence points to gut-derived neurotoxins including ammonia as key mediators in cerebral osmotic and perfusion disturbances. The management of brain oedema and intracranial hypertension requires a multidisciplinar approach in a center where liver transplantation is available, as this option is the only treatment modality that provides improvement in outcome. This article reviews the most common causes of acute liver failure and the standard of supportive care management, and describes future potential therapeutic aspects of brain oedema and intracranial hypertension.

Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF).

Science.gov (United States)

Cordoba, Juan; Ventura-Cots, Meritxell; Simón-Talero, Macarena; Amorós, Àlex; Pavesi, Marco; Vilstrup, Hendrik; Angeli, Paolo; Domenicali, Marco; Ginés, Pere; Bernardi, Mauro; Arroyo, Vicente

2014-02-01

In spite of the high incidence of hepatic encephalopathy (HE) in cirrhosis, there are few observational studies. We performed an analysis to define the characteristics of HE and associated features using the database of the Canonic Study. Clinical, laboratory and survival data of 1348 consecutive cirrhotic patients admitted with an acute decompensation were compared according to the presence (n=406) or absence of HE and of acute-on-chronic liver failure (ACLF) (n=301). HE development was independently associated with previous HE episodes; survival probabilities worsen in relation to the presence and grade of HE. There were marked differences between HE associated (n=174) and not associated (n=286) to ACLF. HE not associated with ACLF occurred in older cirrhotics, inactive drinkers, without severe liver failure or systemic inflammatory reaction and in relation to diuretic use. In contrast, HE associated with ACLF occurred in younger cirrhotics, more frequently alcoholics, with severe liver failure and systemic inflammatory reaction, and in relation to bacterial infections, active alcoholism and/or dilutional hyponatremia. Prognosis was relatively preserved in the first and extremely poor in the second group. Independent risk factors of mortality in patients with HE were age, bilirubin, INR, creatinine, sodium, and HE grade. In cirrhosis, previous HE identifies a subgroup of patients that is especially vulnerable for developing new episodes of HE. The course of HE appears to be different according to the presence of ACLF. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Experimental models of hepatotoxicity related to acute liver failure

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Maes, Michaël [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Vinken, Mathieu, E-mail: mvinken@vub.ac.be [Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels (Belgium); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City (United States)

2016-01-01

Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.

Acute Liver Failure Due to Regorafenib May Be Caused by Impaired Liver Blood Flow: A Case Report.

Science.gov (United States)

Akamine, Takaki; Ando, Koji; Oki, Eiji; Saeki, Hiroshi; Nakashima, Yuichiro; Imamura, Y U; Ohgaki, Kippei; Maehara, Yoshihiko

2015-07-01

Regorafenib has been approved for treatment of patients with unresectable or recurrent gastrointestinal stromal tumors resistant to imatinib or sunitinib. However, regorafenib has severe side-effects, including acute liver failure. We describe the case of a patient with multiple liver metastases of a small intestinal stromal tumor who experienced acute liver failure while being treated with regorafenib. A 50-year-old patient with an unresectable small intestinal stromal tumor resistant to prior treatment with imatinib and sunitinib was started on regorafenib, but experienced acute liver failure 10 days later. Plasma exchange and steroid pulse treatment improved her liver function. During liver failure, abdominal ultrasonography showed to-and-fro flow in the portal vein. Lactate dehydrogenase concentration was markedly elevated to 1633 U/l. These findings indicate that liver failure in this patient was due to impaired liver blood flow. Regorafenib may impair liver blood flow, inducing acute liver failure. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Plasma osteopontin in acute liver failure

DEFF Research Database (Denmark)

Srungaram, Praveen; Rule, Jody A; Yuan, He Jun

2015-01-01

BACKGROUND: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function...... in the setting of massive hepatocyte injury. METHODS: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1...... and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation. RESULTS: Median plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055ng/mL; range: 33-19,127), when compared to healthy controls (median in pre-SF patients: 41ng...

Patients with HBV-related acute-on-chronic liver failure have increased concentrations of extracellular histones aggravating cellular damage and systemic inflammation.

Science.gov (United States)

Li, X; Gou, C; Yao, L; Lei, Z; Gu, T; Ren, F; Wen, T

2017-01-01

Acute-on-chronic liver failure (ACLF) is the most common type of liver failure and associated with grave consequences. Systemic inflammation has been linked to its pathogenesis and outcome, but the identifiable triggers are absent. Recently, extracellular histones, especially H4, have been recognized as important mediators of cell damage in various inflammatory conditions. This study aimed to investigate whether extracellular histones have clinical implications in patients with hepatitis B virus (HBV)-related ACLF. One hundred and twelve patients with HBV-related ACLF, 90 patients with chronic hepatitis B, 88 patients with HBV-related liver cirrhosis and 40 healthy volunteers were entered into this study. Plasma histone H4 levels, cytokine profile and clinical data were obtained. Besides, patient's sera were incubated overnight with human L02 hepatocytes or monocytic U937 cells in the presence or absence of antihistone H4 antibody, and cellular damage and cytokine production were evaluated. We found that plasma histone H4 levels were greatly increased in patients with ACLF as compared with chronic hepatitis B, liver cirrhosis and healthy control subjects and were significantly associated with disease severity, systemic inflammation and outcome. Notably, ACLF patients' sera incubation decreased cultured L02 cell integrity and induced profound cytokine production in the supernatant of U937 cells. Antihistone H4 antibody treatment abrogated these adverse effects, thus confirming a cause-effect relationship between extracellular histones and organ injury/dysfunction. The data support the hypothesis that the increased extracellular histone levels in ACLF patients may aggravate disease severity by inducing cellular injury and systemic inflammation. Histone-targeted therapies may have potentially interventional value in clinical practice. © 2016 John Wiley & Sons Ltd.

Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

Science.gov (United States)

Hoefer, Judith; Ulmer, Hanno; Kilo, Juliane; Margreiter, Raimund; Grimm, Michael; Mair, Peter; Ruttmann, Elfriede

2017-06-01

There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria. Clinical characteristics of heart failure together with hemodynamic and laboratory values were analyzed by logistic regression. A total of 45 patients (27.4%) with heart failure developed subsequent acute liver failure with a hospital mortality of 88.9%. Duration of heart failure, cause, cardiopulmonary resuscitation, use of vasopressors, central venous pressure, pulmonary capillary wedge pressure, pulmonary pulsatility index, cardiac index, and transaminases were not significantly associated with acute liver failure. Repeated decompensation, atrial fibrillation (P failure in univariate analysis only. In multivariable analysis, decreased antithrombin III was the strongest single measurement indicating acute liver failure (relative risk per %, 0.84; 95% confidence interval, 0.77-0.93; P = .001) and remained an independent predictor when adjustment for the Model for End-Stage Liver Disease score was performed (relative risk per %, 0.89; 95% confidence interval, 0.80-0.99; P = .031). Antithrombin III less than 59.5% was identified as a cutoff value to predict acute liver failure with a corresponding sensitivity of 81% and specificity of 87%. In addition to the Model for End-Stage Liver Disease score, decreased antithrombin III activity tends to be superior in predicting acute liver failure compared with traditionally thought predictors. Antithrombin III measurement may help to identify patients more precisely who are developing acute liver failure during mechanical

Clinical observation on the treatment of acute liver failure by combined non-biological artificial liver.

Science.gov (United States)

Li, Maoqin; Sun, Jingxi; Li, Jiaqiong; Shi, Zaixiang; Xu, Jiyuan; Lu, Bo; Cheng, Shuli; Xu, Yanjun; Wang, Xiaomeng; Zhang, Xianjiang

2016-12-01

The clinical efficacy and safety of different combinations of non-bio artificial liver in the treatment of acute liver failure was examined. A total of 61 cases were selected under blood purification treatment from the patients with severe acute liver failure admitted to the severe disease department of the hospital from December, 2010 to December, 2015. Three types of artificial liver combinations were observed, i.e., plasma exchange plus hemoperfusion plus continuous venovenous hemodiafiltration (PE+HP+CVVHDF), PE+CVVHDF and HP+CVVHDF. The heart rate (HR), mean arterial pressure (MAP), respiratory index (PaO 2 /FiO 2 ), liver and kidney function indicator, as well as platelet and coagulation function were compared. A comparison before and after the treatment using the three methods, showed improvement in the HRs, MAPs, PaO 2 /FiO 2 , total bilirubins (TBIL) and alanine aminotransferases (ALT) (Prate of 62.3% (38/61), and a viral survival rate of 35.0% (7/20); with the non-viral survival rate being 75.6% (31/41). In conclusion, following the treatment of three types of artificial livers, the function was improved to varying degrees, with the PE+HP+CVVHDF and the PE+CVVHDF method being better. By contrast, after the treatment of non-viral liver failure, the survival rate was significantly higher than the patients with viral liver failure.

Outcome of acute liver failure in the elderly

DEFF Research Database (Denmark)

Schiødt, Frank V; Chung, Raymond T; Schilsky, Michael L

2009-01-01

Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age > or = 60 years, on outcomes in patients with ALF. One thousand one...

Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases

DEFF Research Database (Denmark)

Almdal, T; Schroeder, T; Ranek, L

1989-01-01

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method......, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range...

Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic liver failure and survival in decompensated cirrhosis

DEFF Research Database (Denmark)

Praktiknjo, Michael; Book, Marius; Luetkens, Julian

2018-01-01

of sarcopenia using magnetic resonance imaging (MRI) in decompensated cirrhotic patients with transjugular intrahepatic portosystemic shunt (TIPS). METHODS: The total erector spinae muscle area and the intramuscular fat tissue area were measured and subtracted to calculate the fat-free muscle area (FFMA) in 116...... in a validation cohort of 45 patients. RESULTS: FFMA correlated with follistatin and TPMT and showed slightly better association with survival than TPMT. Gender-specific cut-off values for FFMA were determined for sarcopenia. Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS...... in the sarcopenia group but resolved in the non-sarcopenia group. Sarcopenic patients showed no clinical improvement after TIPS as well as higher mortality, mainly due to development of acute-on-chronic liver failure (ACLF). FFMA was an independent predictor of survival in these patients. CONCLUSION: This study...

Pyruvate dehydrogenase complex and lactate dehydrogenase as targets for therapy of acute liver failure.

Science.gov (United States)

Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola

2018-03-23

Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate in the nucleus to regulate histone acetylation and gene expression. Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-Ab, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by Gene Ontology Enrichment Analysis. Efficacy of histone acetyltransferase inhibitor garcinol and LDH inhibitor galloflavin at reducing liver damage was evaluated in mice with induced hepatotoxicity. Levels and activities of PDHC and LDH were increased in cytoplasmatic and nuclear fractions of livers of mice with acute liver failure. The increase of nuclear PDHC and LDH was associated with increased concentrations of acetyl-coA and lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression in livers of mice with acute liver failure suggested that increased histone H3 acetylation induces the expression of genes related to response to damage. Reduced histone acetylation by the histone acetyltransferase inhibitor garcinol decreased liver damage and improved survival in mice with acute liver failure. Knock-down of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus. Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC, reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines in mice with acute liver failure. Mice treated with galloflavin also showed a dose-response increase in survival. PDHC and LDH translocate to the nucleus and are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive and life-threatening deterioration of liver function resulting in high mortality and

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review.

Science.gov (United States)

Kok, Beverley; Lester, Erica L W; Lee, William M; Hanje, A James; Stravitz, R Todd; Girgis, Safwat; Patel, Vaishali; Peck, Joshua R; Esber, Christopher; Karvellas, Constantine J

2018-03-21

Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported. To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases. The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases. The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic-hepatitic features; none showed clear autoimmune features. Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic-hepatitic features were frequently found on pre-transplant and explant histology.

Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

Directory of Open Access Journals (Sweden)

Honglei eWeng

2015-06-01

Full Text Available Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called second pathway of liver regeneration. The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

Science.gov (United States)

Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

2015-01-01

Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

Acute liver failure after recommended doses of acetaminophen in patients with myopathies

NARCIS (Netherlands)

Ceelie, Ilse; James, Laura P.; Gijsen, Violette; Mathot, Ron A. A.; Ito, Shinya; Tesselaar, Coranne D.; Tibboel, Dick; Koren, Gideon; de Wildt, Saskia N.

2011-01-01

To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Retrospective analysis. Level III pediatric intensive care unit. Two pediatric patients with myopathies and acute liver failure. CLINICAL INVESTIGATIONS: We

Nuclear medicine in acute and chronic renal failure

Energy Technology Data Exchange (ETDEWEB)

Sherman, R.A.; Byun, K.J.

1982-07-01

The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. /sup 131/I OIH, /sup 67/gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease.

Nuclear medicine in acute and chronic renal failure

International Nuclear Information System (INIS)

Sherman, R.A.; Byun, K.J.

1982-01-01

The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. 131 I OIH, 67 gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease

Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure

DEFF Research Database (Denmark)

Jepsen, P; Schmidt, L E; Larsen, F S

2010-01-01

The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown.......The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown....

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study.

Science.gov (United States)

Lee, Karla C L; Baker, Luisa A; Stanzani, Giacomo; Alibhai, Hatim; Chang, Yu Mei; Jimenez Palacios, Carolina; Leckie, Pamela J; Giordano, Paola; Priestnall, Simon L; Antoine, Daniel J; Jenkins, Rosalind E; Goldring, Christopher E; Park, B Kevin; Andreola, Fausto; Agarwal, Banwari; Mookerjee, Rajeshwar P; Davies, Nathan A; Jalan, Rajiv

2015-09-01

In acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure. Pigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure. The Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen. The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder.

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Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

2009-06-21

Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

Dengue hemorrhagic fever complicated with acute liver failure: a case report.

Science.gov (United States)

Dalugama, Chamara; Gawarammana, Indika Bandara

2017-12-08

Dengue is a common arboviral infection with a clinically diverse spectrum of presentations. Although hepatic dysfunction is commonly identified in patients will dengue illness, acute liver failure is rare. The etiopathogenesis of hepatic dysfunction is multifactorial and related to direct viral invasion of hepatocytes, immunological factors and hypoxia particularly in cases of shock in dengue hemorrhagic fever. Ideal management of dengue-related hepatic dysfunction and acute liver failure is still debated. We report a 53-year-old Sri Lankan Sinhalese male with serologically confirmed dengue fever presenting with evidence of plasma leakage developing acute liver failure evidenced by deranged liver functions, coagulopathy and altered sensorium. In addition to the 'standard care', the patient was managed with intravenous N-acetyl cysteine and blood transfusions even in the absence of bleeding or dropping packed cell volume (PCV), targeting a higher PCV in anticipation of better oxygenation at tissue level. He made a full recovery with no sequential infections. N-acetyl cysteine and packed cell transfusion aiming at a higher PCV to maintain adequate tissue perfusion during shock may be beneficial in acute liver failure due to dengue virus. Large randomized trials should be carried out to establish the efficacy of these treatment strategies to support these observations and change the current practice.

Bridging a patient with acute liver failure to liver transplantation by the AMC-bioartificial liver

NARCIS (Netherlands)

van de Kerkhove, Maarten-Paul; di Florio, Ernesto; Scuderi, Vincenzo; Mancini, Antonio; Belli, Antonello; Bracco, Adele; Scala, Daniela; Scala, Simona; Zeuli, Laura; Di Nicuolo, Giuseppe; Amoroso, Pietro; Calise, Fulvio; Chamuleau, Robert A. F. M.

2003-01-01

Recently a phase I clinical trial has been started in Italy to bridge patients with acute liver failure (ALF) to orthotopic liver transplantation (OLT) by the AMC-bioartificial liver (AMC-BAL). The AMC-BAL is charged with 10 X 109 viable primary porcine hepatocytes isolated from a specified

The significance of parenchymal changes of acute cellular rejection in predicting chronic liver graft rejection

NARCIS (Netherlands)

Gouw, ASH; van den Heuvel, MC; van den Berg, AP; Slooff, NJH; de Jong, KP; Poppema, S

2002-01-01

Background. Chronic rejection (CR) in liver allografts shows a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition

Liver failure in total artificial heart therapy.

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Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

Epidemiology of invasive pulmonary aspergillosis in patients with liver failure: Clinical presentation, risk factors, and outcomes.

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Zhang, Xuan; Yang, Meifang; Hu, Jianhua; Zhao, Hong; Li, Lanjuan

2018-02-01

Objective Invasive pulmonary aspergillosis (IPA) is a severe and often lethal infection. The possible risk factors, clinical presentation, and treatment of patients with simultaneous liver failure and IPA have received little attention in previous studies. The aim of this study was to investigate the epidemiology of IPA in patients with liver failure in an effort to reduce patient mortality. Methods The patients with liver failure (including acute liver failure , sub-acute liver failure , acute-on-chronic liver failure and chronic liver failure) were recruited from 2011 to 2016. The clinical data of these patients were retrieved for the study. Results In total, 1077 patients with liver failure were included in this study. Of the 1077 patients, 53 (4.9%) had IPA. Forty-four (83%) patients with IPA died. Independent risk factors for IPA were male sex (hazard ratio [HR] = 2.542), hepatorenal syndrome (HR = 2.463), antibiotic use (HR = 4.631), and steroid exposure (HR = 18.615). Conclusions IPA is a fatal complication in patients with liver failure. Male sex, hepatorenal syndrome, antibiotic use, and steroid exposure were independent risk factors for IPA. When patients with liver failure have these risk factors and symptoms of pneumonia such as cough or hemoptysis, clinicians should be cautious about the possibility of IPA.

A Systematic Review on Prognostic Indicators of Acute Liver Failure and Their Predictive Value for Poor Outcome

NARCIS (Netherlands)

Wlodzimirow, Kama A.; Eslami, Saeid; Abu-Hanna, Ameen; Nieuwoudt, Martin; Chamuleau, Robert A. F. M.

2014-01-01

This review provides a large amount of information, including the extensive list of worldwide used indicators to predict outcome in patients with acute liver failure. There is large heterogeneity in prognostic indicators of acute liver failure, methods of measurement, complexity of calculation and

Advances in the treatment of acute liver failure

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LUO Ling

2018-02-01

Full Text Available Acute liver failure (ALF is a rare life-threatening disease with rapid progression and a low survival rate and affects the function of multiple organ systems. Early identification of cause and protection of vital organs are critical for patients' survival. With the development in artificial liver, stem cell transplantation, and liver transplantation in recent years, the outcome of ALF has been greatly improved. This article elaborates on the treatment of ALF from the aspects of the etiology of ALF and major organ systems involved and introduces the latest advances in artificial liver and stem cell transplantation.

Living Donor Liver Transplantation for Acute Liver Failure : Comparing Guidelines on the Prediction of Liver Transplantation.

Science.gov (United States)

Yoshida, Kazuhiro; Umeda, Yuzo; Takaki, Akinobu; Nagasaka, Takeshi; Yoshida, Ryuichi; Nobuoka, Daisuke; Kuise, Takashi; Takagi, Kosei; Yasunaka, Tetsuya; Okada, Hiroyuki; Yagi, Takahito; Fujiwara, Toshiyoshi

2017-10-01

Determining the indications for and timing of liver transplantation (LT) for acute liver failure (ALF) is essential. The King's College Hospital (KCH) guidelines and Japanese guidelines are used to predict the need for LT and the outcomes in ALF. These guidelines' accuracy when applied to ALF in different regional and etiological backgrounds may differ. Here we compared the accuracy of new (2010) Japanese guidelines that use a simple scoring system with the 1996 Japanese guidelines and the KCH criteria for living donor liver transplantation (LDLT). We retrospectively analyzed 24 adult ALF patients (18 acute type, 6 sub-acute type) who underwent LDLT in 1998-2009 at our institution. We assessed the accuracies of the 3 guidelines' criteria for ALF. The overall 1-year survival rate was 87.5%. The new and previous Japanese guidelines were superior to the KCH criteria for accurately predicting LT for acute-type ALF (72% vs. 17%). The new Japanese guidelines could identify 13 acute-type ALF patients for LT, based on the timing of encephalopathy onset. Using the previous Japanese guidelines, although the same 13 acute-type ALF patients (72%) had indications for LT, only 4 patients were indicated at the 1st step, and it took an additional 5 days to decide the indication at the 2nd step in the other 9 cases. Our findings showed that the new Japanese guidelines can predict the indications for LT and provide a reliable alternative to the previous Japanese and KCH guidelines.

Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

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S. V. Gautier

2017-01-01

Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

Effects of grape seed polyphenols on oxidative damage in liver tissue of acutely and chronically exercised rats.

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Belviranlı, Muaz; Gökbel, Hakkı; Okudan, Nilsel; Büyükbaş, Sadık

2013-05-01

The objective of the present study was to investigate the effects of grape seed extract (GSE) supplementation on oxidative stress and antioxidant defense markers in liver tissue of acutely and chronically exercised rats. Rats were randomly assigned to six groups: Control (C), Control Chronic Exercise (CE), Control Acute Exercise (AE), GSE-supplemented Control (GC), GSE-supplemented Chronic Exercise(GCE) and GSE-supplemented Acute Exercise (GAE). Rats in the chronic exercise groups were subjected to a six-week treadmill running and in the acute exercise groups performed an exhaustive running. Rats in the GSE supplemented groups received GSE (100 mg.kg(-1) .day(-1) ) in drinking water for 6 weeks. Liver tissues of the rats were taken for the analysis of malondialdehyde (MDA), nitric oxide (NO) levels and total antioxidant activity (AOA) and xanthine oxidase (XO) activities. MDA levels decreased with GSE supplementation in control groups but increased in acute and chronic exercise groups compared to their non-supplemented control. NO levels increased with GSE supplementation. XO activities were higher in AE group compared to the CE group. AOA decreased with GSE supplementation. In conclusion, while acute exercise triggers oxidative stress, chronic exercise has protective role against oxidative stress. GSE has a limited antioxidant effect on exercise-induced oxidative stress in liver tissue.

Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

Science.gov (United States)

Jin, Lei; Gao, Yufeng; Ye, Jun; Zou, Guizhou; Li, Xu

2017-09-01

The red blood cell distribution width (RDW) is increased in chronic liver disease, but its clinical significance in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is still unclear. The aim of the present study was to investigate the clinical significance of RDW in HBV-ACLF patients. The medical records of HBV-ACLF patients who were admitted to The Second Affiliated Hospital of Anhui Medical University between April 2012 and December 2015 were retrospectively reviewed. Correlations between RDW, neutrophil lymphocyte ratio (NLR), and the model for end-stage liver disease (MELD) scores were analyzed using the Spearman's approach. Multivariable stepwise logistic regression test was used to evaluate independent clinical parameters predicting 3-month mortality of HBV-ACLF patients. The association between RDW and hospitalization outcome was estimated by receiver operating curve (ROC) analysis. Patient survival was estimated by Kaplan-Meier analysis and subsequently compared by log-rank test. Sixty-two HBV-ACLF patients and sixty CHB patients were enrolled. RDW were increased in HBVACLF patients and positively correlated with the NLR as well as MELD scores. Multivariate analysis demonstrated that RDW value was an independent predictor for mortality. RDW had an area under the ROC of 0.799 in predicting 3-month mortality of HBV-ACLF patients. Patients with HBV-ACLF who had RDW > 17% showed significantly poorer survival than those who had RDW ≤ 17%. RDW values are significantly increased in patients with HBV-ACLF. Moreover, RDW values are an independent predicting factor for an in-hospital mortality in patients with HBV-ACLF.

Parvovirus B19 Infection in a Fatal Case of Acute Liver Failure.

Science.gov (United States)

Leon, Luciane Almeida Amado; Alves, Arthur Daniel Rocha; Garcia, Rita de Cássia Nasser Cubel; Melgaço, Juliana Gil; de Paula, Vanessa Salete; Pinto, Marcelo Alves

2017-12-01

B19V has been proposed as an etiologic agent for hepatitis, mainly in children, but this is a rare clinical occurrence. In this article, we report a case of non-A-E acute liver failure in an immunocompetent child with B19 infection. The clinical findings of severe anemia and pancytopenia combined with the detection of anti-B19 Immunoglobulin G (IgG), B19 DNA and B19 mRNA in liver indicate a persistent infection and suggest a diagnosis of parvovirus B19-associated acute liver failure.

Study on TCM syndromes of liver failure and yang-supporting therapy

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MAO Dewen

2015-01-01

Full Text Available This paper reviews traditional Chinese medicine (TCM physicians′understanding of liver failure including its TCM causes, mechanisms, positions, and syndrome differentiation in various dynasties. The results suggest that modern researchers agree with ancient physicians on these aspects of liver failure. Based on achievements of ancient TCM physicians, modern researchers have further developed and improved their understanding of TCM causes, mechanisms, positions, and syndrome differentiation of liver failure. Moreover, this paper discusses the treatment of chronic liver failure with yang-supporting therapy, which provides a novel perspective and method for treating chronic liver failure.

A case of acute liver failure in dengue hemorrhagic fever

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Rama Biswas

2013-07-01

Full Text Available Dengue is an arboviral disease endemic in many parts of the world. The clinical presentation of dengue viral infection ranges from asymptomatic illness to fatal dengue shock syndrome. Although, it is known to cause hepatic involvement, it occasionally results in acute hepatic failure. We report a case of dengue hemorrhagic fever presenting with acute liver failure. The case recovered completely after treatment. Ibrahim Med. Coll. J. 2013; 7(2: 41-42

Apolipoprotein and lipid abnormalities in chronic liver failure

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Spósito A.C.

1997-01-01

Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

Yogi Detox Tea: A Potential Cause of Acute Liver Failure.

Science.gov (United States)

Kesavarapu, Keerthana; Kang, Mitchell; Shin, Jaewook James; Rothstein, Kenneth

2017-01-01

We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects.

Change of liver echogenicity in chronic renal failure: Correlation with serologic test and pathologic findings

International Nuclear Information System (INIS)

Eun, Hyo Won; Cho, Kyoung Sik; Kim, Jeong Kon; Kim, Jung Hoon

2002-01-01

To correlate serologic test and pathologic findings with change of hepatic parenchymal echogenicity on ultrasound (US) in patients with chronic renal failure. From January 1995 to April 2000, among eight hundred eighty four patients with kidney transplantation due to chronic renal failure, sixty seven patients who underwent US-guided liver biopsy were selected. Change of liver echogenicity on US was analyzed, and this change was compared with serologic test and pathologic findings. Among sixty seven patients, pathologic findings of thirty four patients with the normal liver echogenicity on US revealed normal in 15 patients (44%), viral hepatitis in 18 (53%), and liver cirrhosis in one patient (3%). Meanwhile, twenty seven patients with chronic liver disease on US were pathologically confirmed as normal in 13 patients (48%), viral hepatitis in 11 (40%), liver cirrhosis in four patients (11%); six patients with cirrhotic change on US, liver cirrhosis in four patients (67%) and viral hepatitis on two patients (33%). Serologic test of thirty four patients with the normal liver echogenicity on US showed positive HBs Ag in 17 patients (50%), positive anti-HCV Ab in 11 (32%), positive in both HBs Ag and anti-HCV Ab in one (3%), and normal result in five patients (15%). In patients with chronic renal failure, it is nor enough to determine the presence of liver disease only based on change of echogenicity on US. A careful correlation with serologic test and, if needed, pathologic confirmation are recommended for the accurate preoperative evaluation of the liver.

Etiology and Outcome of Acute Liver Failure: Experience from a Liver Transplantation Centre in Montreal

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Geneviève Tessier

2002-01-01

Full Text Available BACKGROUND: Acute liver failure is a rare condition in which massive liver injury is associated with the rapid development of hepatic encephalopathy. Although viral hepatitis and drug-induced liver injury are the most common causes, no specific etiology is found in a substantial proportion of cases reported from Europe and the United States.

Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure.

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Jody A Rule

Full Text Available Because acute liver failure (ALF patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD subjects served as controls.Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups-non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169. PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001. Subjects with acetaminophen (APAP toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL.While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.

Scrub typhus causing neonatal hepatitis with acute liver failure-A case series.

Science.gov (United States)

Vajpayee, Shailja; Gupta, R K; Gupta, M L

2017-05-01

Neonatal hepatitis with acute liver failure due to varied etiology including various infections is reported in the past. Scrub typhus as a cause of neonatal hepatitis has rarely been reported in literature. A high index of clinical suspicion is required for early diagnosis and timely treatment. Severity and prognosis of the disease varies widely because several different strains of Orientia tsutsugamushi exist with different virulence. Delayed diagnosis can result in complication and significant morbidity and mortality. Here, we report three cases of neonatal hepatitis with acute liver failure caused by scrub typhus to increase awareness.

Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

DEFF Research Database (Denmark)

Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise

2016-01-01

BACKGROUND & AIMS: Non-selective beta blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute-on-chronic liver failure (ACLF......) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether ongoing use of NSBBs reduced 28-day mortality in ACLF patients. METHODS...... at enrollment significantly associated with treatment and mortality were taken into account as potential confounders to adjust for treatment effect. A logistic regression model was fitted. RESULTS: 164 (47%) ACLF patients received NSBBs whereas 185 patients did not. Although the CLIF-C ACLF scores were similar...

Celiac artery trunk thrombosis presenting as acute liver failure

International Nuclear Information System (INIS)

Akbarian, M.A.; Kahrom, M.; Kahrom, H.

2011-01-01

Acute mesenteric ischemia is a life-threatening vascular emergency that requires early diagnosis and intervention to adequately restore mesenteric blood flow and to prevent bowel necrosis and patient death. While, almost always superior and inferior mesenteric arteries are involved, we report a 57-year-old male with an unusual celiac artery trunk thrombosis leading to gastero-duodenal and hepato-splenic infarction, and presenting an acute liver failure. (author)

Yogi Detox Tea: A Potential Cause of Acute Liver Failure

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Keerthana Kesavarapu

2017-01-01

Full Text Available We present a case of acute fulminant liver failure from a liver detoxification tea. We present a 60-year-old female with weakness, lethargy, scleral icterus, jaundice, and worsening mental status. She drank herbal tea three times a day for 14 days prior to symptom development. Liver tests were elevated. Remaining laboratory tests and imaging were negative for other etiologies. An ultrasound-guided liver biopsy showed submassive necrosis. A literature search on the ingredients shows six ingredients as having hepatotoxic effects and remaining ingredients as having very sparse hepatoprotective data. Healthcare professionals should discuss herbal medication and tea use and report adverse effects.

Development and validation of a dynamic outcome prediction model for paracetamol-induced acute liver failure

DEFF Research Database (Denmark)

Bernal, William; Wang, Yanzhong; Maggs, James

2016-01-01

: The models developed here show very good discrimination and calibration, confirmed in independent datasets, and suggest that many patients undergoing transplantation based on existing criteria might have survived with medical management alone. The role and indications for emergency liver transplantation......BACKGROUND: Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver...... transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death. METHODS: Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK...

Clinical performance of stem cell therapy in patients with acute-on-chronic liver failure: a systematic review and meta-analysis.

Science.gov (United States)

Xue, Ran; Meng, Qinghua; Dong, Jinling; Li, Juan; Yao, Qinwei; Zhu, Yueke; Yu, Hongwei

2018-05-10

Stem cell therapy has been applied in the treatment of acute-on-chronic liver failure (ACLF). However, its clinical efficiency is still debatable. The aim of this systematic review and meta-analysis is to evaluate the clinical efficiency of stem cell therapy in the treatment of ACLF. The Cochrane Library, OVID, EMBASE, and PUBMED were searched to December 2017. Both randomized and non-randomized studies, assessing stem cell therapy in patients with ACLF, were included. The outcome measures were total bilirubin (TBIL), alanine transaminase (ALT), international normalized ratio (INR), albumin (ALB), and the model for end-stage liver disease (MELD) score. The quality of evidence was assessed by GRADEpro. Four randomized controlled trials and six non-randomized controlled trials were included. The TBIL levels significantly decreased at 1-, 3-, 12-month after the stem cell therapy (p = 0.0008; p = 0.04; p = 0.007). The ALT levels decreased significantly compared with the control group in the short-term (p stem cell therapy and control groups (p = 0.008). Further subgroup analysis for 3-month clinical performance according to the stem cell types have also been performed. This study suggests that the clinical outcomes of stem cell therapy were satisfied in patients with ACLF in the short-term. MSCs may be better than BM-MNCs in the stem cells transplantation of ACLF. However, more attention should focus on clinical trials in large-volume centers.

Extracorporal hemodialysis with acute or decompensated chronical hepatic failure

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Wasem, Jürgen

2006-04-01

Full Text Available Background: Conventional diagnostic procedures and therapy of acute liver failure (ALF and acute-on-chronic liver failure (ACLF focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can only marginally be substituted by conventional conservative therapy. To improve this component of the liver function is the main objective of extracorporal liver support systems. The following principles of liver support systems can be differentiated: Artificial systems, bioartifical systems and extracorporal liver perfusion systems. This HTA report focuses on artificial systems (e.g. BioLogic-DT/-DTPF, MARS, Prometheus, because only these approaches currently are relevant in the German health care system. In 2004 a category "Extracorporal liver assist device" was introduced in the list of "additional payments" in the German DRG-system, which makes reimbursement for hospitals using the technology in inpatient care possible, based on an hospital's individual contract with statutory sickness funds. Objectives: To report the present evidence and future research need on medical efficacy and economic effectiveness of extracorporal liver support devices for treatment of patients with ALF or ACLF based on published literature data. Are artificial liver support systems efficient and effective in the treatment of ALF or ACLF? Methods: An extensive, systematic literature search in medical, economic, and HTA literature data bases was performed. Relevant data were extracted and synthesised. Results: Relevant controlled trials were detected for BioLogic-DT and MARS. No randomised controlled trial on Prometheus was found. None of the included studies on BioLogic-DT showed

Risk factors associated with prognosis of progressive stages of acute-on-chronic hepatitis B liver failure

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YE Peiyan

2013-04-01

Full Text Available ObjectiveTo identify the risk factors associated with progression of acute-on-chronic liver failure (ACLF occurring in patients with chronic hepatitis B virus (HBV infection (CHB. MethodsThe clinical, demographic, treatment and outcome data of 180 ACLF patients with concomitant CHB managed in our hospital between June 2009 and September 2012 were retrospectively reviewed. Clinical data, taken at baseline, included markers of inflammation/infection (white blood cell (WBC count, coagulation (prothrombin time (PT and prothrombin activity (PTA, and liver function (alanine aminotransferase (ALT, aspartate aminotransferase (AST, total bilirubin (TBil, direct bilirubin (DBil, choninesterase (CHE, albumin (Alb, globulin (Glb, total cholesterol (TC, and ammonia. In-hospital treatments included supplementation with traditional Chinese medicine-based therapies, such as Tuihuang decoction and detoxification enema. The primary outcome was survival during hospitalization. The patients were grouped for analysis according to ACLF stage (early, n=93; mid, n=61; late, n=26 and the risk factors associated with each stage were identified by using univariate (log-rank test and multivariate (Cox’s test regression analyses. The association of risk factors with patient survival was assessed by Kaplan-Meier curve analysis. ResultsThe three ACLF groups showed significantly different amounts of leukocytes, with the late ACLF group showing the highest WBC. The late ACLF group also showed significantly lower Glb and TC. There was a trend in reduced cumulative survival rate and shorter time to death that significantly corresponded to progressive stages of ACLF (early ACLF＞mid ACLF＞late ACLF; all P＜0.001. One-hundred-and-twenty-six (70.0% of the patients died during their hospitalization, and multivariate regression analysis of this entire patient population identified absence of colonic enema, presence of hepatic encephalopathy, presence of hepatorenal syndrome, PTA

Acute liver failure after recommended doses of acetaminophen in patients with myopathies

NARCIS (Netherlands)

I. Ceelie (Ilse); L.P. James (Laura); V.M.G.J. Gijsen (Violette); R.A.A. Mathôt (Ron); S. Ito (Shinya); C.D. Tesselaar (Coranne); D. Tibboel (Dick); G. Koren (Gideon); S.N. de Wildt (Saskia)

2011-01-01

textabstractObjective: To determine the likelihood that recommended doses of acetaminophen are associated with acute liver failure in patients with myopathies. Design: Retrospective analysis. Setting: Level III pediatric intensive care unit. Patients: Two pediatric patients with myopathies and acute

Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

DEFF Research Database (Denmark)

Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral

2012-01-01

The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.......The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....

Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome

International Nuclear Information System (INIS)

Cavet, Madeleine; Balu, Marie; Garel, Catherine; Ducou le Pointe, Hubert; Mitanchez, Delphine; Alexandre, Marie; Renolleau, Sylvain; Pariente, Daniele

2008-01-01

Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia. (orig.)

Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome

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Cavet, Madeleine; Balu, Marie; Garel, Catherine; Ducou le Pointe, Hubert [Universite Pierre et Marie Curie Paris VI, Service de Radiologie, Hopital d' enfants Armand-Trousseau, Paris (France); Mitanchez, Delphine; Alexandre, Marie [Universite Pierre et Marie Curie Paris VI, Service de Neonatologie, Hopital d' enfants Armand-Trousseau, Paris (France); Renolleau, Sylvain [Universite Pierre et Marie Curie Paris VI, Service de Reanimation, Hopital d' enfants Armand-Trousseau, Paris (France); Pariente, Daniele [Hopital de Bicetre, Service de Radiologie Pediatrique, Paris (France)

2008-10-15

Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia. (orig.)

Spectral Electroencephalogram Analysis for the Evaluation of Encephalopathy Grade in Children With Acute Liver Failure.

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Press, Craig A; Morgan, Lindsey; Mills, Michele; Stack, Cynthia V; Goldstein, Joshua L; Alonso, Estella M; Wainwright, Mark S

2017-01-01

Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure. Retrospective cohort study. Tertiary care pediatric hospital. Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU. None. Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative β, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p > 0.05). Spectral electroencephalogram classification correlated with outcome (p encephalopathy and correlates with outcome. Spectral electroencephalogram may allow improved quantitative and reproducible assessment of hepatic encephalopathy grade in children with acute liver failure.

Acute liver failure due to natural killer-like T-cell leukemia/lymphoma: A case report and review of the Literature

Institute of Scientific and Technical Information of China (English)

Evan S Dellon; Shannon R Morris; Wozhan Tang; Cherie H Dunphy; Mark W Russo

2006-01-01

Acute liver failure (ALF) is a medical emergency requiring immediate evaluation for liver transplantation. We describe an unusual case of a patient who presented with ascites, jaundice, and encephalopathy and was found to have ALF due to natural killer (NK)-like T cell leukemia/lymphoma. The key immunophenotype was CD2+, CD3+, CD7+, CD56+. This diagnosis, which was based on findings in the peripheral blood and ascitic fluid, was confirmed with liver biopsy, and was a contraindication to liver transplantation. A review of the literature shows that hematologic malignancies are an uncommon cause of fulminant hepatic failure, and that NK-like T-cell leukemia/lymphoma is a relatively recently recognized entity which is characteristically CD3+ and CD56+. This case demonstrates that liver biopsy is essential in diagnosing unusual causes of acute liver failure, and that infiltration of the liver with NK-like T-cell lymphoma/leukemia can cause acute liver failure.

Analysis of influencing factors for short-term outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

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ZHANG Xin

2015-05-01

Full Text Available ObjectiveTo investigate the effects of antiviral drugs, lamivudine (LAM and entecavir (ETV, on the short-term outcome in patients with hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF. MethodsThe demographic and clinical data of 445 patients with HBV-related ACLF (LAM∶ETV, 333∶112 who were hospitalized in the First Clinical Medical College of Fujian Medical University from January 2004 to December 2010 were collected, including age, sex, complications, clinical biochemical parameters, coagulation parameters, the use of antiviral drug, artificial liver treatment, and the survival at 24 weeks. The independent risk factors for the outcome at 24 weeks were determined by univariate and multivariate logistic regression analyses. ResultsThe univariate analysis indicated that the LAM group had significantly higher globulin, total bilirubin (TBil, alanine aminotransferase, international normalized ratio (INR, serum creatinine, and model for end-stage liver disease (MELD score than the ETV group (P＜0.05, but had significantly lower cholinesterase and prothrombin time activity (PTA than the ETV group (P＜0.05. The death group had significantly older age, higher incidence rates of liver cirrhosis, hepatic encephalopathy, spontaneous bacterial peritonitis, pulmonary infection, mycotic infection, electrolyte disturbance, hepatorenal syndrome, and upper gastrointestinal hemorrhage, and higher TBil, INR, white blood count, and MELD score than the survival group (P＜0.05, but had significantly lower albumin, gamma-glutamyl transpeptidase, cholesterol, cholinesterase, serum sodium, PTA, alpha-fetoprotein, hemoglobin, platelet, and positive rate of HBeAg than the survival group (P＜0.05. And there was no significant difference in the use of antiviral drugs (LAM∶ETV between the death group and the survival group (P=0.21. The multivariate logistic regression analysis showed that older age, hepatic encephalopathy, hepatorenal syndrome

Lactate metabolism in chronic liver disease

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Jeppesen, Johanne B; Mortensen, Christian; Bendtsen, Flemming

2013-01-01

Background. In the healthy liver there is a splanchnic net-uptake of lactate caused by gluconeogenesis. It has previously been shown that patients with acute liver failure in contrast have a splanchnic release of lactate caused by a combination of accelerated glycolysis in the splanchnic region...... and a reduction in hepatic gluconeogenesis. Aims. The aims of the present study were to investigate lactate metabolism and kinetics in patients with chronic liver disease compared with a control group with normal liver function. Methods. A total of 142 patients with chronic liver disease and 14 healthy controls...... underwent a liver vein catheterization. Blood samples from the femoral artery and the hepatic and renal veins were simultaneously collected before and after stimulation with galactose. Results. The fasting lactate levels, both in the hepatic vein and in the femoral artery, were higher in the patients than...

An analysis of predictive factors for concurrent acute-on-chronic liver failure and hepatorenal syndrome

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CHEN Yanfang

2015-09-01

Full Text Available ObjectiveTo learn the clinical characteristics of concurrent acute-on-chronic liver failure (ACLF and hepatorenal syndrome (HRS, and to investigate the predictive factors for HRS in patients with ACLF. MethodsA total of 806 patients with ACLF who were admitted to our hospital from January 2012 to May 2014 were selected and divided into two groups according to the incidence of concurrent HRS. Clinical indices and laboratory test results were analyzed in the two groups, and the multivariate logistic regression analysis was used to figure out independent indices for the prediction of HRS in patients with ACLF. A prediction model was established and the receiver operating characteristic curve was drawn to evaluate the accuracy of the prediction model. Comparison of continuous data between the two groups was made by t test, and comparison of categorical data between the two groups was made by χ2 test. ResultsIn all patients with ACLF, 229 had HRS and 577 had no HRS. The univariate logistic regression analysis showed that hepatic encephalopathy, peritonitis, infection, age, cystatin C (Cys-C, serum creatinine (SCr, blood urea nitrogen, albumin, prealbumin, total bilirubin, direct bilirubin, total cholesterol, K+, Na+, phosphorus, Ca2+, prothrombin time, prothrombin activity, international normalized ratio, and hematocrit were significant predictive factors for HRS. The multivariate logistic regression analysis showed that concurrent peritonitis, Cys-C, SCr, and HCO3- were independent predictive factors for HRS in patients with ACLF (OR=3.155, P＜0.01; OR=30.773, P＜0.01; OR=1062, P＜0.01; OR=0.915, P＜0.05. The model was proved of great value in prediction. ConclusionConcurrent peritonitis, Cys-C, SCr, and HCO3- are effective predictive factors for HRS in patients with ACLF.

Complement Factor 3 Could Be an Independent Risk Factor for Mortality in Patients with HBV Related Acute-on-Chronic Liver Failure

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Geng-lin Zhang

2016-01-01

Full Text Available The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF remains unclear. Serum levels of the third and fourth complement components (C3, C4 and complement function (CH50 were examined in this prospective, observational study. Associations between their expression and disease activity were analyzed. Survival was analyzed by Kaplan-Meier curves. Predictors of clinical outcome were determined by Cox regression analysis. C3, C4, and CH50 levels were significantly lower in HBV-ACLF patients compared to controls. C3, C4, and CH50 levels were negatively correlated with Tbil levels but positively associated with PTA levels. C3 levels were negatively associated with MELD-Na. C3 levels were significantly lower in HBV-ACLF patients who died compared to patients who survived. In a median hospital stay of 39 days, mortality occurred in 41 patients with a progressive increase based on C3 grade (P=0.008. The actuarial probability of developing mortality was significantly higher in patients with low C3 grade compared to those with high C3 grade (P<0.001. Multivariate Cox regression analysis showed that C3 levels were an independent predictor of mortality. Complement played a pathogenic role in HBV-ACLF patients and C3 was an independent predictor of mortality.

Etiology of pediatric acute liver failure

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GUO Jing

2017-10-01

Full Text Available Pediatric acute liver failure (PALF is a complex syndrome with rapid progression, and the cause of PALF is age-dependent. This article analyzes the common causes of PALF in clinical practice, including infection factors, inherited metabolic factors, poisoning and drugs, abnormal perfusion, and autoimmune diseases, among which infection factors are the most common cause. With the improvement in diagnosis and treatment techniques, the diagnostic rate of PALF caused by inherited metabolic diseases and autoimmune diseases keeps increasing. Due to the small number of PALF patients, there lacks experience in etiological diagnosis. This article summarizes related reports, in order to provide a reference for screening the causes of PALF.

Prevention and management of brain edema in patients with acute liver failure

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Wendon, J.; Larsen, Finn Stolze

2008-01-01

1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema...

In Vivo Acute on Chronic Ethanol Effects in Liver: A Mouse Model Exhibiting Exacerbated Injury, Altered Metabolic and Epigenetic Responses

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Shivendra D. Shukla

2015-11-01

Full Text Available Chronic alcoholics who also binge drink (i.e., acute on chronic are prone to an exacerbated liver injury but its mechanism is not understood. We therefore investigated the in vivo effects of chronic and binge ethanol ingestion and compared to chronic ethanol followed by three repeat binge ethanol on the liver of male C57/BL6 mice fed ethanol in liquid diet (4% for four weeks followed by binge ethanol (intragastric administration, 3.5 g/kg body weight, three doses, 12h apart. Chronic followed by binge ethanol exacerbated fat accumulation, necrosis, decrease in hepatic SAM and SAM:SAH ratio, increase in adenosine levels, and elevated CYP2E1 levels. Histone H3 lysine acetylation (H3AcK9, dually modified phosphoacetylated histone H3 (H3AcK9/PS10, and phosphorylated H2AX increased after binge whereas phosphorylation of histone H3 ser 10 (H3S10 and H3 ser 28 (H3S28 increased after chronic ethanol-binge. Histone H3 lysine 4 and 9 dimethylation increased with a marked dimethylation in H3K9 in chronic ethanol binge group. Trimethylated histone H3 levels did not change. Nuclear levels of histone acetyl transferase GCN5 and histone deacetylase HDAC3 were elevated whereas phospho-CREB decreased in a distinctive manner. Taken together, acute on chronic ethanol ingestion caused amplification of liver injury and elicited characteristic profiles of histone modifications, metabolic alterations, and changes in nuclear protein levels. These findings demonstrate that chronic ethanol exposure renders liver more susceptible to repeat acute/binge ethanol induced acceleration of alcoholic liver disease.

Changes in cerebral oxidative metabolism in patients with acute liver failure

DEFF Research Database (Denmark)

Bjerring, P N; Larsen, F S

2013-01-01

acid cycle, induces substrate depletion through marked glutamate utilization for glutamine synthesis and leads to mitochondrial dysfunction. In patients with acute liver failure cerebral microdialysis studies show a linear correlation between the lactate to pyruvate ratio and the glutamine...

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents.

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Nicaise, Charles; Prozzi, Deborah; Viaene, Eric; Moreno, Christophe; Gustot, Thierry; Quertinmont, Eric; Demetter, Pieter; Suain, Valérie; Goffin, Philippe; Devière, Jacques; Hols, Pascal

2008-10-01

Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed. Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.

Modification in CSF specific gravity in acutely decompensated cirrhosis and acute on chronic liver failure independent of encephalopathy, evidences for an early blood-CSF barrier dysfunction in cirrhosis.

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Weiss, Nicolas; Rosselli, Matteo; Mouri, Sarah; Galanaud, Damien; Puybasset, Louis; Agarwal, Banwari; Thabut, Dominique; Jalan, Rajiv

2017-04-01

Although hepatic encephalopathy (HE) on the background of acute on chronic liver failure (ACLF) is associated with high mortality rates, it is unknown whether this is due to increased blood-brain barrier permeability. Specific gravity of cerebrospinal fluid measured by CT is able to estimate blood-cerebrospinal fluid-barrier permeability. This study aimed to assess cerebrospinal fluid specific gravity in acutely decompensated cirrhosis and to compare it in patients with or without ACLF and with or without hepatic encephalopathy. We identified all the patients admitted for acute decompensation of cirrhosis who underwent a brain CT-scan. Those patients could present acute decompensation with or without ACLF. The presence of hepatic encephalopathy was noted. They were compared to a group of stable cirrhotic patients and healthy controls. Quantitative brain CT analysis used the Brainview software that gives the weight, the volume and the specific gravity of each determined brain regions. Results are given as median and interquartile ranges and as relative variation compared to the control/baseline group. 36 patients presented an acute decompensation of cirrhosis. Among them, 25 presented with ACLF and 11 without ACLF; 20 presented with hepatic encephalopathy grade ≥ 2. They were compared to 31 stable cirrhosis patients and 61 healthy controls. Cirrhotic patients had increased cerebrospinal fluid specific gravity (CSF-SG) compared to healthy controls (+0.4 %, p encephalopathy did not modify CSF-SG (-0.09 %, p = 0.1757). Specific gravity did not differ between different brain regions according to the presence or absence of either ACLF or HE. In patients with acute decompensation of cirrhosis, and those with ACLF, CSF specific gravity is modified compared to both stable cirrhotic patients and healthy controls. This pattern is observed even in the absence of hepatic encephalopathy suggesting that blood-CSF barrier impairment is manifest even in absence of overt

Logistic regression analysis of prognostic factors in 106 acute-on-chronic liver failure patients with hepatic encephalopathy

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CUI Yanping

2014-10-01

Full Text Available ObjectiveTo analyze the prognostic factors in acute-on-chronic liver failure (ACLF patients with hepatic encephalopathy (HE and to explore the risk factors for prognosis. MethodsA retrospective analysis was performed on 106 ACLF patients with HE who were hospitalized in our hospital from January 2010 to July 2013. The patients were divided into improved group and deteriorated group. The univariate indicators including age, sex, laboratory indicators ［total bilirubin (TBil, albumin (Alb, alanine aminotransferase (ALT, aspartate amino-transferase (AST, and prothrombin time activity (PTA］, the stage of HE, complications ［persistent hyponatremia, digestive tract bleeding, hepatorenal syndrome (HRS, ascites, infection, and spontaneous bacterial peritonitis (SBP］, and plasma exchange were analyzed by chi-square test or t-test. Indicators with statistical significance were subsequently analyzed by binary logistic regression. ResultsUnivariate analysis showed that ALT (P=0.009, PTA (P=0.043, the stage of HE (P=0.000, and HRS (P=0.003 were significantly different between the two groups, whereas differences in age, sex, TBil, Alb, AST, persistent hyponatremia, digestive tract bleeding, ascites, infection, SBP, and plasma exchange were not statistically significant (P＞0.05. Binary logistic regression demonstrated that PTA (b=-0097, P=0.025, OR=0.908, HRS (b=2.279, P=0.007, OR=9.764, and the stage of HE (b=1873, P=0.000, OR=6.510 were prognostic factors in ACLF patients with HE. ConclusionThe stage of HE, HRS, and PTA are independent influential factors for the prognosis in ACLF patients with HE. Reduced PTA, advanced HE stage, and the presence of HRS indicate worse prognosis.

Hepatitis A related acute liver failure by consumption of contaminated food

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Chi, Heng; Haagsma, Elizabeth B.; Riezebos-Brilman, Annelies; van den Berg, Arie P.; Metselaar, Herold J.; de Knegt, Robert J.

We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the

Effects of Acute Exercise and Chronic Exercise on the Liver Leptin-AMPK-ACC Signaling Pathway in Rats with Type 2 Diabetes

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Xuejie Yi

2013-01-01

Full Text Available Aim. To investigate the effects of acute and chronic exercise on glucose and lipid metabolism in liver of rats with type 2 diabetes caused by a high fat diet and low dose streptozotocin (STZ. Methods. Animals were classified into control (CON, diabetes (DC, diabetic chronic exercise (DCE, and diabetic acute exercise (DAE groups. Results. Compared to CON, the leptin levels in serum and liver and ACC phosphorylation were significantly higher in DC, but the levels of liver leptin receptor, AMPKα1/2, AMPKα1, and ACC proteins expression and phosphorylation were significantly lower in DC. In addition, the levels of liver glycogen reduced significantly, and the levels of TG and FFA increased significantly in DC compared to CON. Compared to DC, the levels of liver AMPKα1/2, AMPKα2, AMPKα1, and ACC phosphorylation significantly increased in DCE and DAE. However, significant increase of the level of liver leptin receptor and glycogen as well as significant decrease of the level of TG and FFA were observed only in DEC. Conclusion. Our study demonstrated that both acute and chronic exercise indirectly activated the leptin-AMPK-ACC signaling pathway and increased insulin sensitivity in the liver of type 2 diabetic rats. However, only chronic and long-term exercise improved glucose and lipid metabolism of the liver.

HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure

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Runkuan Yang

2017-01-01

Full Text Available Acute liver failure (ALF is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT. BT triggers/induces systemic inflammatory responses syndrome (SIRS, which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

HMGB1 and Extracellular Histones Significantly Contribute to Systemic Inflammation and Multiple Organ Failure in Acute Liver Failure.

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Yang, Runkuan; Zou, Xiaoping; Tenhunen, Jyrki; Tønnessen, Tor Inge

2017-01-01

Acute liver failure (ALF) is the culmination of severe liver cell injury from a variety of causes. ALF occurs when the extent of hepatocyte death exceeds the hepatic regenerative capacity. ALF has a high mortality that is associated with multiple organ failure (MOF) and sepsis; however, the underlying mechanisms are still not clear. Emerging evidence shows that ALF patients/animals have high concentrations of circulating HMGB1, which can contribute to multiple organ injuries and mediate gut bacterial translocation (BT). BT triggers/induces systemic inflammatory responses syndrome (SIRS), which can lead to MOF in ALF. Blockade of HMGB1 significantly decreases BT and improves hepatocyte regeneration in experimental acute fatal liver injury. Therefore, HMGB1 seems to be an important factor that links BT and systemic inflammation in ALF. ALF patients/animals also have high levels of circulating histones, which might be the major mediators of systemic inflammation in patients with ALF. Extracellular histones kill endothelial cells and elicit immunostimulatory effect to induce multiple organ injuries. Neutralization of histones can attenuate acute liver, lung, and brain injuries. In conclusion, HMGB1 and histones play a significant role in inducing systemic inflammation and MOF in ALF.

Protective role of hypoxia-inducible factor-1α-dependent CD39 and CD73 in fulminant acute liver failure

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Tak, Eunyoung [Asan Institute for Life Sciences and Asan-Minnesota Institute for Innovating Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jung, Dong-Hwan; Kim, Seok-Hwan; Park, Gil-Chun [Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jun, Dae Young; Lee, Jooyoung [Asan Institute for Life Sciences and Asan-Minnesota Institute for Innovating Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Jung, Bo-hyun [Department of Surgery, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Kirchner, Varvara A. [Division of Transplantation, Department of Surgery and Asan-Minnesota Institute for Innovating Transplantation, University of Minnesota, Minneapolis, MN (United States); Hwang, Shin [Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Song, Gi-Won, E-mail: drsong71@amc.seoul.kr [Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Sung-Gyu [Division of Liver Transplantation and Hepatobiliary Surgery, Asan-Minnesota Institute for Innovating Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2017-01-01

Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5′-nucleotidase, Ecto5′NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF. To test our hypothesis, liver biopsies were obtained and we found that CD39 and CD73 mRNA and proteins from human specimens were dramatically elevated in ALF. We investigated that induction of CD39 and CD73 in ALF-related with wild type mice. In contrast, deletion of cd39 and cd73 mice has severe ALF. In this study, we concluded that CD39 and CD73 are molecular targets for the development of drugs for ALF patients care. - Highlights: • HIF-1a is stabilized during acute liver failure • Upregulation of CD39 and CD73 following acute liver failure • CD39 and CD73 are transcriptionally induced by HIF-1a • Deletion of Cd39 and CD73 aggravates murine acute liver failure • DMOG treatment induces HIF-1a stabilization, CD39 and CD73 during acute liver failure in WT mice.

Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure.

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Matsue, Yuya; Ter Maaten, Jozine M; Struck, Joachim; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A

2017-03-01

Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131 I-Hippuran and 125 I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Circulating mannan-binding lectin, M-, L-, H-ficolin and collectin-liver-1 levels in patients with acute liver failure

DEFF Research Database (Denmark)

Laursen, Tea Lund; Sandahl, Thomas D; Støy, Sidsel

2015-01-01

BACKGROUND & AIMS: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL),...

Endothelial-astrocytic interactions in acute liver failure.

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Jayakumar, A R; Norenberg, M D

2013-06-01

Brain edema and the subsequent increase in intracranial pressure are major neurological complications of acute liver failure (ALF), and swelling of astrocytes (cytotoxic brain edema) is the most prominent neuropathological abnormality in ALF. Recent studies, however, have suggested the co-existence of cytotoxic and vasogenic mechanisms in the brain edema associated with ALF. This review 1) summarizes the nature of the brain edema in humans and experimental animals with ALF; 2) reviews in vitro studies supporting the presence of cytotoxic brain edema (cell swelling in cultured astrocytes); and 3) documents the role of brain endothelial cells in the development of astrocyte swelling/brain edema in ALF.

Parvovirus B19 in an Immunocompetent Adult Patient with Acute Liver Failure: An Underdiagnosed Cause of Acute Non-A-E Viral Hepatitis

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J Kee Ho

2005-01-01

Full Text Available There are occasional pediatric reports of parvovirus B19-associated transient acute hepatitis and hepatic failure. A case of a 34-year-old immunocompetent woman who developed severe and prolonged but self-limited acute hepatitis and myelosuppression following acute parvovirus B19 infection is reported. Parvovirus B19 may be the causative agent in some adult cases of acute non-A-E viral hepatitis and acute liver failure.

Acute alcohol-induced liver injury

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Gavin Edward Arteel

2012-06-01

Full Text Available Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, that also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

Acute liver failure caused by hepatitis E virus genotype 3 and 4: A systematic review and pooled analysis.

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Haffar, Samir; Shalimar; Kaur, Ravinder J; Wang, Zhen; Prokop, Larry J; Murad, Mohammad H; Bazerbachi, Fateh

2018-04-19

Acute liver failure caused by hepatitis E virus genotype 3 and 4 has been rarely described. Because of the presence of a short golden therapeutic window in patients with viral acute liver failure from other causes, it is possible that early recognition and treatment might reduce the morbidity and mortality. We performed a systematic review and pooled analysis of acute liver failure caused by hepatitis E virus genotype 3 and 4. Two reviewers appraised studies after searching multiple databases on June 12th, 2017. Appropriate tests were used to compare hepatitis E virus genotype 3 vs 4, suspected vs confirmed genotypes, hepatitis E virus-RNA positive vs negative, and to discern important mortality risk factors. We identified 65 patients, with median age 58 years (range: 3-79), and a male to female ratio of 1.2:1. The median bilirubin, ALT, AST and alkaline phosphatase (expressed by multiplication of the upper limit of normal) levels were 14.8, 45.3, 34.8 and 1.63 respectively. Antihepatitis E virus IgG, antihepatitis E virus IgM and hepatitis E virus-RNA were positive in 84%, 91% and 86% of patients respectively. The median interval from symptoms onset to acute liver failure was 23 days, and 16 patients underwent liver transplantation. Final outcome was reported in 58 patients and mortality was 46%. Age was a predictor of poor prognosis in multivariate analysis. No important differences were found between patients infected with genotype 3 vs 4, patients with confirmed vs suspected genotypes, or patients with positive vs negative RNA. Acute liver failure caused by hepatitis E virus genotype 3 and 4 is rare, similar between genotypes, occurs commonly in middle-aged/elderly patients and has a very high mortality. Age is predictive of poor prognosis in multivariate analysis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Risk of acute hepatic insufficiency in children due to chronic accidental overdose of paracetamol (acetaminophen)

NARCIS (Netherlands)

Hameleers-Snijders, P.; Hogeveen, M.; Smeitink, J.A.M.; Kramers, C.; Draaisma, J.M.T.

2007-01-01

Two girls aged 4 and 3 years, respectively, experienced acute liver failure due to accidental ingestion of supratherapeutic doses of paracetamol (90 mg/kg/day or more). Recognition of chronic paracetamol intoxication as a cause of acute hepatic failure is often delayed. It is important to consider

Single-centre validation of the EASL-CLIF consortium definition of acute-on-chronic liver failure and CLIF-SOFA for prediction of mortality in cirrhosis.

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Silva, Pedro E Soares E; Fayad, Leonardo; Lazzarotto, César; Ronsoni, Marcelo F; Bazzo, Maria L; Colombo, Bruno S; Dantas-Correa, Esther B; Narciso-Schiavon, Janaína L; Schiavon, Leonardo L

2015-05-01

The idea of acute-on-chronic liver failure (ACLF) has emerged to identify those subjects with organ failure and high mortality rates. However, the absence of a precise definition has limited the clinical application and research related to the ACLF concept. We sought to validate the ACLF definition and the CLIF-SOFA Score recently proposed by the EASL-CLIF Consortium in a cohort of patients admitted for acute decompensation (AD) of cirrhosis. In this prospective cohort study, patients were followed during their hospital stay and thirty and 90-day mortality was evaluated by phone call, in case of hospital discharge. All subjects underwent laboratory evaluation at admission. Between December 2010 and November 2013, 192 cirrhotic patients were included. At enrollment, 46 patients (24%) met the criteria for ACLF (Grades 1, 2 and 3 in 18%, 4% and 2% respectively). The 30-day mortality was 65% in ACLF group and 12% in the remaining subjects (P Logistic regression analysis showed that 30-day mortality was independently associated with ascites and ACLF at admission. The Kaplan-Meier survival probability at 90-day was 92% in patients without ascites or ACLF and only 22% for patients with both ascites and ACLF. The AUROC of CLIF-SOFA in predicting 30-day mortality was 0.847 ± 0.034, with sensitivity of 64%, specificity of 90% and positive likelihood ratio of 6.61 for values ≥9. In our single-centre experience the CLIF-SOFA and the EASL-CLIF Consortium definition of ACLF proved to be strong predictors of short-term mortality in cirrhotic patients admitted for AD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acute liver failure in a term neonate after repeated paracetamol administration

OpenAIRE

Bucaretchi, Fabio; Fernandes, Carla Borrasca; Branco, Maira Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araujo; Porta, Gilda

2014-01-01

Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL)...

Chronic liver disease related mortality pattern in northern Pakistan

International Nuclear Information System (INIS)

Khokhar, N.; Niazi, S.A.

2003-01-01

Objective: To describe the mortality pattern pertaining to chronic liver disease (CLD) in Northern Pakistan. Results: There were a total of 8529 admissions in twelve months period from August 2001 to July 2002. There were 283 (3.31%) total deaths. Out of these, 160 deaths were pertaining to medical causes. Out of these medical cases, 33 (20.6%) patients had died of chronic liver disease. Other major causes of death were cerebro-vascular accident (18.7%), malignancy (18.1%) and acute myocardial infarction (10.6%). Out of 33 patients of CLD, 12 (36%) presented with acute gastrointestinal (Gl) bleeding, 9(27%) presented with Ascites and 6(18%) presented with altered mental status due to hepatic encephalopathy. Rest of them had jaundice and fever as their initial presentation. Out of these 33 patients with CLD, 23 (70%) had hepatitis C virus (HCV) as cause of their liver disease, 4 (12%) had hepatitis B virus (HBV) infection, 3(9%) had both hepatitis B and hepatitis C virus infections and 3 (9%) had no known cause of their chronic liver disease. Conclusion: Chronic liver disease is a major cause of mortality in this part of Pakistan at a tertiary care hospital. HCV infection is the main cause of chronic liver disease followed by either HBV or a combination of these viruses. Major manifestations of CLD have been gastrointestinal bleeding, hepatic failure and portal hypertension.(author)

Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group.

Science.gov (United States)

Ng, Vicky L; Li, Ruosha; Loomes, Kathleen M; Leonis, Mike A; Rudnick, David A; Belle, Steven H; Squires, Robert H

2016-09-01

Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P liver failure prognostication schema are needed.

Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

Science.gov (United States)

Ramos-Tovar, Erika; Hernández-Aquino, Erika; Casas-Grajales, Sael; Buendia-Montaño, Laura D.; Tsutsumi, Víctor

2018-01-01

The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases. PMID:29849889

The management of neonatal acute and chronic renal failure: A review.

Science.gov (United States)

Coulthard, Malcolm G

2016-11-01

Most babies with chronic renal failure are identified antenatally, and over half that are treated with peritoneal dialysis receive kidney transplants before school age. Most infants that develop acute renal failure have hypotension following cardiac surgery, or multiple organ failure. Sometimes the falls in glomerular filtration and urine output are physiological and reversible, and sometimes due to kidney injury, but (illogically) it is now common to define them all as having 'acute kidney injury'. Contrary to widespread opinion, careful interpretation of the plasma creatinine concentrations can provide sensitive evidence of early acute renal failure. Conservative management frequently leads to under-nutrition or fluid overload. Acute peritoneal dialysis is often technically fraught in very small patients, and haemotherapies have been limited by vascular access and anticoagulation requirements, the need to blood-prime circuits, and serious limitations in regulating fluid removal. Newer devices, including the Nidus, have been specifically designed to reduce these difficulties. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Etiologies and Outcomes of Acute Liver Failure in a Spanish Community

Directory of Open Access Journals (Sweden)

Emilio Fábrega

2013-01-01

Full Text Available Previous retrospective study (1992 to 2000 performed in Spain showed that drug toxicity, viral hepatitis, and indeterminate etiology were the most prevalent causes of acute liver failure (ALF. In the last decade, there is no information about ALF in our country. For these reasons we analyze retrospectively, in a ten-year period (2000 to 2010, the presumed causes, clinical characteristics, course, and outcome of ALF in a Spanish community. Causes of ALF were indeterminate in 4 patients (24%, acute hepatitis B infection in 4 patients (24%, drug or toxic reactions in 4 patients (24%, including one case of acetaminophen overdose, followed by miscellaneous causes. The overall short-term survival (6 weeks after admission was 65%. Liver transplantation was performed in 11 patients with a survival of 82%. Despite fulfilling criteria, 2 patients were not transplanted because of contraindications; they both died. In summary, acute hepatitis B and indeterminate cause are still being the most frequent causes of ALF in our region, and patients with ALF have an excellent chance of survival after emergency liver transplantation. Acetaminophen overdose still represents a very rare cause of ALF in our community.

Use of Renal Replacement Therapy May Influence Graft Outcomes following Liver Transplantation for Acute Liver Failure: A Propensity-Score Matched Population-Based Retrospective Cohort Study.

Science.gov (United States)

Knight, Stephen R; Oniscu, Gabriel C; Devey, Luke; Simpson, Kenneth J; Wigmore, Stephen J; Harrison, Ewen M

2016-01-01

Acute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal replacement therapy. A retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use. Three-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (Prenal replacement therapy was a predictor of both patient death (hazard ratio (HR) 1.59, 95% CI 1.01-2.50, P = 0.044) but not graft loss (HR 1.39, 95% CI 0.92-2.10, P = 0.114). In groups fully matched on baseline covariates, those not receiving renal replacement therapy with a serum creatinine greater than 175 μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy. In patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.

Acute Liver Failure: Pathophysiologic Basis, and The Current and Emerging Therapies

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Graziella Privitera

2014-05-01

Full Text Available Acute liver failure (ALF is a devastating condition that occurs in patients who previously had a normal liver. Although the outcome of patients with ALF has improved, without liver transplantation (LT mortality rates remain in the range of 35-50% in different geographical areas and therefore, its treatment remains an unmet need. In the Western world toxic liver injury from acetaminophen remains one of the common causes but, in the East, hepatitis of unknown aetiology remains the most common cause. Treatment options are limited to meticulous attention to multi-organ support, use of N-acetyl cysteine, judicious use of antibiotics, and timely LT. This review describes the state-of-the-art techniques in the issues related to prognosis, outcome, and treatment of this devastating syndrome.

Flumazenil does not improve hepatic encephalopathy associated with acute ischemic liver failure in the rabbit

NARCIS (Netherlands)

C.C.D. van der Rijt (Carin); R.J. de Knegt (Robert); S.W. Schalm (Solko); O.T. Terpstra (Onno); K. Mechelse (Karel)

1990-01-01

textabstractThe effect of flumazenil, a benzodiazepine antagonist, on hepatic encephalopathy was studied in rabbits with acute hepatic failure induced by a two-stage liver devascularization procedure. The rabbits were randomized for treatment with 5 mg/kg of flumazenil or the placebo. The drug was

Tacrolimus Aggravated Tube Feeding Syndrome with Acute Renal Failure in a Pediatric Liver Transplant Recipient

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R. Kula

2017-01-01

Full Text Available Acute renal failure can be caused by calcineurin inhibitors (CNIs, due to arteriolopathy and altered tubular function. Within this context, we present the case of a 14-month-old liver transplant recipient who suffered an acute polyuric renal failure during a short episode of hypercaloric feeding. In our case, CNI-induced distal RTA led to nephrocalcinosis and therefore to secondary nephrogenic diabetes insipidus. The diet with high renal solute load consequently resulted in an acute polyuric renal failure with severe hypernatremic dehydration. In conclusion, a hypercaloric diet in children with potentially impaired renal function due to therapy with CNIs requires precise calculation of the potential renal solute load and the associated fluid requirements.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

Science.gov (United States)

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or

Impact of preoperative chronic renal failure on liver transplantation: a population-based cohort study

Science.gov (United States)

Chung, Peter Chi-Ho; Chen, Hsiu-Pin; Lin, Jr-Rung; Liu, Fu-Chao; Yu, Huang-Ping

2016-01-01

Purpose The purpose of this study was to assess whether preoperative chronic renal failure (CRF) affects the rates of postoperative complications and survival after liver transplantation. Methods This population-based retrospective cohort study included 2,931 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. Patients were divided into two groups, based on the presence or absence of preoperative CRF. Results The overall estimated survival rate of liver transplantation recipients (LTRs) with preoperative CRF was significantly lower than that of patients without preoperative CRF (P=0.0085). There was no significant difference between the groups in terms of duration of intensive care unit stay, total hospital stay, bacteremia, postoperative bleeding, and pneumonia during hospitalization. Long-term adverse effects, including cerebrovascular disease and coronary heart disease, were not different between patients with versus without CRF. Conclusion These findings suggest that LTRs with preoperative CRF have a higher rate of mortality. PMID:28008264

The brain in acute liver failure. A tortuous path from hyperammonemia to cerebral edema

DEFF Research Database (Denmark)

Bjerring, Peter Nissen; Eefsen, Martin; Hansen, Bent Adel

2008-01-01

Acute liver failure (ALF) is a condition with an unfavourable prognosis. Multiorgan failure and circulatory collapse are frequent causes of death, but cerebral edema and intracranial hypertension (ICH) are also common complications with a high risk of fatal outcome. The underlying pathogenesis has...... been extensively studied and although the development of cerebral edema and ICH is of a complex and multifactorial nature, it is well established that ammonia plays a pivotal role. This review will focus on the effects of hyperammonemia on neurotransmission, mitochondrial function, oxidative stress...

Low serum transferrin correlates with acute-on-chronic organ failure and indicates short-term mortality in decompensated cirrhosis.

Science.gov (United States)

Bruns, Tony; Nuraldeen, Renwar; Mai, Martina; Stengel, Sven; Zimmermann, Henning W; Yagmur, Eray; Trautwein, Christian; Stallmach, Andreas; Strnad, Pavel

2017-02-01

Iron represents an essential, but potentially harmful micronutrient, whose regulation has been associated with poor outcome in liver disease. Its homeostasis is tightly linked to oxidative stress, bacterial infections and systemic inflammation. To study the prognostic short-term significance of iron parameters in a cohort study of patients with decompensation of cirrhosis at risk of acute-on-chronic liver failure (ACLF). Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were determined in sera from 292 German patients hospitalized for decompensation of cirrhosis with ascites, of which 78 (27%) had ACLF. Short-term mortality was prospectively assessed 30 and 90 days after inclusion. Transferrin concentrations were significantly lower, whereas ferritin and TSAT were higher in patients with ACLF compared to patients without ACLF (P≤.006). Transferrin, TSAT and ferritin differentially correlated with the severity of organ failure, active alcoholism and surrogates of systemic inflammation and macrophage activation. As compared with survivors, 30-day non-survivors displayed lower serum transferrin (P=.0003) and higher TSAT (P=.003), whereas 90-day non-survivors presented with higher ferritin (P=.03) and lower transferrin (P=.02). Lower transferrin (continuous or dichotomized at 87 mg/dL) and consecutively higher TSAT (continuous or dichotomized >41%) indicated increased mortality within 30 days and remained significant after adjustment for organ failure and inflammation in multivariate regression models and across subgroups of patients. Among the investigated indicators of iron metabolism, serum transferrin concentration was the best indicator of organ failure and an independent predictor of short-term mortality at 30 days. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Therapeutic plasma exchange versus double plasma molecular absorption system in hepatitis B virus-infected acute-on-chronic liver failure treated by entercavir: A prospective study.

Science.gov (United States)

Wan, Yue-Meng; Li, Yu-Hua; Xu, Zhi-Yuan; Yang, Jing; Yang, Li-Hong; Xu, Ying; Yang, Jin-Hui

2017-12-01

Therapeutic plasma exchange (TPE) and double plasma molecular absorption system (DPMAS) were two extracorporeal liver support systems. Few studies compared their efficacy profile. This study was to compare the efficacy of TPE and DPMAS on acute-on-chronic liver failure (ACLF) caused by hepatitis B virus (HBV-ACLF). 60 HBV-ACLF patients were enrolled and prospectively studied. All patients received entecavir therapy, and were assigned to TPE group (n = 33) and DPMAS group (n = 27). Primary end-points were the effects of TPE and DPMAS on liver function and serum inflammatory markers. Serum procalcitonin, interleukin (IL)-6, and high sensitive C-reactive protein (hsCRP) were significantly elevated in patients with HBV-ACLF. TPE achieved significantly higher removal rates of total bilirubin (TBIL, P = .002), direct bilirubin (DBIL, P = .006), and hsCRP (P = .010) than DPMAS, but DPMAS displayed lower loss rate of albumin (P = .000). TPE and DPMAS resulted in similarly increased serum IL-6 levels and comparable 12-week survivals (P > .05). Multivariate analysis showed that hospital stay (Relative Risk [RR]: 1.062, 95% Confidence Interval [CI]: 1.011-1.115, P = .016), prothrombin time (RR: 1.346, 95% CI: 1.077-1.726, P = .010), and international normalized ratio (RR: 0.013, 95% CI: 0.006-0.788, P = .041) were independent predictors for 12-week survival. Both TPE and DPMAS treatments were well-tolerated. Compared to DPMAS, TPE was more efficient in eliminating TBIL, DBIL, and hsCRP, but it was associated with higher loss rate of albumin. TPE and DPMAS were similar in improving 12-week survivals in HBV-ACLF. © 2017 Wiley Periodicals, Inc.

Causes of liver failure and impact analysis of prognostic risk factors

Directory of Open Access Journals (Sweden)

WU Xiaoqing

2013-04-01

Full Text Available ObjectiveTo perform a retrospective analysis of patients with liver failure to investigate the causative factors and related risk factors that may affect patient prognosis. MethodsThe clinical, demographic, and laboratory data of 79 consecutive patients diagnosed with liver failure and treated at our hospital between January 2010 and January 2012 (58 males and 21 females; age range: 16-74 years old were collected from the medical records. To identify risk factors of liver failure, the patient variables were assessed by Student’s t-test (continuous variables or Chi-squared test (categorical variables. Multivariate logistic regression analysis was used to investigate the relation between patient outcome and independent risk factors. ResultsThe 79 cases of liver failure were grouped according to disease severity: acute liver failure (n=6; 5 died, subacute liver failure (n=35; 19 died, and chronic liver failure (n=38; 28 died. The overall rate of death was 66%. The majority of cases (81% were related to hepatitis B virus infection. While the three groups of liver failure severity did not show significant differences in sex, mean age, occupation, presence of potassium disorder, total bilirubin (TBil or total cholesterol (CHO at admission, or lowest recorded level of CHO during hospitalization, there were significant intergroup differences in highest recorded TBil level, prothrombin activity (PTA at admission, and highest and lowest recorded PTA, and highest recorded level of CHO. Five independent risk factors were identified: the highest recorded TBil level during hospitalization, presence of infection, hepatorenal syndrome, gastrointestinal bleeding, and hepatic encephalopathy. ConclusionThe major cause of liver failure in this cohort of patients was hepatitis infection, and common biomarkers of liver function, such as TBil, CHO and PTA, may indicate patients with poor prognosis despite clinical intervention. Complications should be addressed as

Cardiac Arrythmias in Acute and Chronic Renal Failure

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Ali A. Handjani

1966-01-01

Full Text Available Cardiac arrythmias are frequent complications in acute and chronic renal failure and they may well account for sudden unexplained death in these patients. Based upon our recent study, we strongly believe that among other causative factors, focal degeneration of myocardium is the commonest and the most potentially dangerous cause of cardiac arrythmias. We suggest in emergency instances, ouabain to be used instead of digitalis which appears to be quite safe with dramatic results in cardiac arrythmias of these group.

Protective effect of genetic deletion of pannexin1 in experimental mouse models of acute and chronic liver disease.

Science.gov (United States)

Willebrords, Joost; Maes, Michaël; Pereira, Isabel Veloso Alves; da Silva, Tereza Cristina; Govoni, Veronica Mollica; Lopes, Valéria Veras; Crespo Yanguas, Sara; Shestopalov, Valery I; Nogueira, Marina Sayuri; de Castro, Inar Alves; Farhood, Anwar; Mannaerts, Inge; van Grunsven, Leo; Akakpo, Jephte; Lebofsky, Margitta; Jaeschke, Hartmut; Cogliati, Bruno; Vinken, Mathieu

2018-03-01

Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation. To this end, wild-type and pannexin1 -/- mice were overdosed with acetaminophen for 1, 6, 24 or 48h or were fed a choline-deficient high-fat diet for 8weeks. Evaluation of the effects of genetic pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, lipid accumulation, protein adduct formation, oxidative stress and inflammation. In parallel, in order to elucidate molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. The results of this study show that pannexin1 -/- diseased mice present less liver damage and oxidative stress, while inflammation was only decreased in pannexin1 -/- mice in which non-alcoholic steatohepatitis was induced. A multitude of genes related to inflammation, oxidative stress and xenobiotic metabolism were differentially modulated in both liver disease models in wild-type and in pannexin1 -/- mice. Overall, the results of this study suggest that pannexin1 may play a role in the pathogenesis of liver disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute renal dysfunction in liver diseases

OpenAIRE

Betrosian, Alex P; Agarwal, Banwari; Douzinas, Emmanuel E

2007-01-01

Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver dise...

Acute respiratory failure requiring mechanical ventilation in severe chronic obstructive pulmonary disease (COPD).

Science.gov (United States)

Gadre, Shruti K; Duggal, Abhijit; Mireles-Cabodevila, Eduardo; Krishnan, Sudhir; Wang, Xiao-Feng; Zell, Katrina; Guzman, Jorge

2018-04-01

There are limited data on the epidemiology of acute respiratory failure necessitating mechanical ventilation in patients with severe chronic obstructive pulmonary disease (COPD). The prognosis of acute respiratory failure requiring invasive mechanical ventilation is believed to be grim in this population. The purpose of this study was to illustrate the epidemiologic characteristics and outcomes of patients with underlying severe COPD requiring mechanical ventilation.A retrospective study of patients admitted to a quaternary referral medical intensive care unit (ICU) between January 2008 and December 2012 with a diagnosis of severe COPD and requiring invasive mechanical ventilation for acute respiratory failure.We evaluated 670 patients with an established diagnosis of severe COPD requiring mechanical ventilation for acute respiratory failure of whom 47% were male with a mean age of 63.7 ± 12.4 years and Acute physiology and chronic health evaluation (APACHE) III score of 76.3 ± 27.2. Only seventy-nine (12%) were admitted with a COPD exacerbation, 27(4%) had acute respiratory distress syndrome (ARDS), 78 (12%) had pneumonia, 78 (12%) had sepsis, and 312 (47%) had other causes of respiratory failure, including pulmonary embolism, pneumothorax, etc. Eighteen percent of the patients received a trial of noninvasive positive pressure ventilation. The median duration of mechanical ventilation was 3 days (interquartile range IQR 2-7); the median duration for ICU length of stay (LOS) was 5 (IQR 2-9) days and the median duration of hospital LOS was 12 (IQR 7-22) days. The overall ICU mortality was 25%. Patients with COPD exacerbation had a shorter median duration of mechanical ventilation (2 vs 4 days; P = .04), ICU (3 vs 5 days; P = .01), and hospital stay (10 vs 13 days; P = .01). The ICU mortality (9% vs 27%; P respiratory failure. A 1-unit increase in the APACHE III score was associated with a 1% decrease and having an active cancer was associated

Estimation of liver parameters and oxidative stress in chronic renal failure patients on hemodialysis in Erbil governorate

Science.gov (United States)

Kakey, Musher Ismail Salih; Abdoulrahman, Kamaran Kaiani

2017-09-01

The present study aims to evaluate iron related parameters in chronic renal failure (CRF) patients on hemodialysis (HD). The study was carried out in Kidney Dialysis Center of Hawler Teaching Hospital in Erbil governorate. This study comprised (76) patients with chronic renal failure on hemodialysis and 41 healthy subjects as a control group of same ages. All hemodialysis patients were taking erythropoietin. The blood samples were taken from the patients before and after the process of hemodialysis for liver parameters and oxidative stress estimations. The results of this study showed lower levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total bilirubin, total protein and total antioxidant capacity (TAC), while higher levels of alkaline phosphatase (ALP), direct bilirubin and malondialdeyhde (MDA) before analysis was seen. Hemodialysis causes increasing in AST, ALT, albumin, total bilirubin, total protein and decreasing in ALP, direct bilirubin MDA and TAC.

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy.

Science.gov (United States)

Brusilow, Saul W; Cooper, Arthur J L

2011-11-01

Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure, is a contributing factor: the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Case report. Johns Hopkins Hospital. A 22-yr-old woman who, 36 hrs before admission, ingested 15 g acetaminophen was admitted to the Johns Hopkins Hospital. She was treated with N-acetylcysteine. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hrs after ingestion when she became confused, irritable, and agitated. She was intubated, ventilated, and placed on lactulose. Shortly thereafter, she was noncommunicative, unresponsive to painful stimuli, and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure was made. She improved very slowly until 180 hrs after ingestion when she moved all extremities. She woke up shortly thereafter. Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in acute liver failure, the patient's plasma ammonia peaked when she exhibited no obvious neurologic deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurologic status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high but began to normalize several hours after plasma ammonia had returned to normal. The patient only started to recover as her plasma glutamine began

Tumor-Like Liver Abscess Mimicking Malignancy With Lung Metastases in a Patient With Acute Renal Failure: A Case Report.

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Wang, Chih Hsin; Sun, Cheuk-Kay; Jiang, Jiunn-Song; Tsai, Ming Hsien

2016-03-01

The worldwide incidence of Klebsiella pneumoniae liver abscess (KLA) is increasing. It is important to accurately diagnose this life-threatening disease to provide timely and appropriate treatment. Here we report the case of a 38-year-old man with acute renal failure and a tumor-like liver abscess and septic pulmonary embolism. Initially, his clinical symptoms, laboratory tests, and radiological findings presented equivocal results of malignancy with metastases. Fine needle aspiration of liver tumor was performed, which showed purulent material with a culture positive for K pneumoniae. KLA symptoms are atypical, and radiological findings may mimic a malignancy with tumor necrosis. In some circumstances, liver aspiration biopsy may be necessary to confirm the real etiology, leading to prompt and timely treatment. Moreover, we should be alert for the impression of KLA when facing a diabetic patient with liver mass lesion and acute renal failure.

Quantitative multivoxel H-1 MR spectroscopy of the brain in children with acute liver failure

NARCIS (Netherlands)

Sijens, Paul E.; Alkefaji, Heyder; Lunsing, Roelineke J.; van Spronsen, Francjan J.; Meiners, Linda C.; Oudkerk, Matthijs; Verkade, Henkjan J.

Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx)

Are de novo acute heart failure and acutely worsened chronic heart failure two subgroups of the same syndrome?

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Banović Marko

2010-01-01

Full Text Available Introduction. Acute heart failure (AHF is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. Objective. To investigate clinical presentation of patients with de novo AHF and acute worsening of chronic heart failure (CHF and to identify differences in blood levels of biomarkers and echocardiography findings. Methods. This prospective study comprised 64 consecutive patients being grouped according to the onset of the disease into patients with the de novo AHF (45.3%, and patients with acute worsening of CHF (54.7%. Results. Acute congestion (60% was the most common manifestation of de novo AHF, whereas pulmonary oedema (43.1% was the most common manifestation of acutely decompensated CHF. Patients with acutely decompensated CHF had significantly higher blood values of creatinine (147.10 vs 113.16 μmol/l; p<0.05, urea (12.63 vs 7.82 mmol/l; p<0.05, BNP (1440.11 vs 712.24 pg/ml; p<001 and NTproBNP (9097.00 vs 2827.70 pg/ml; p<0.01 on admission, and lower values of M-mode left ventricular ejection fraction (LVEF during hospitalization (49.44% vs 42.94%; p<0.05. The follow-up after one year revealed still significantly higher BNP (365.49 vs 164.02 pg/ ml; p<0.05 and lower average values of both LVEF in patients with acutely worsened CHF (46.62% vs 54.41% and 39.52% vs 47.88%; p<0.05. Conclusion. Considering differences in clinical severity on admission, echocardiography and natriuretic peptide values during hospitalization and after one year follow-up, de novo AHF and acutely worsened CHF are two different subgroups of the same syndrome.

DRESS syndrome secondary to ibuprofen as a cause of hyperacute liver failure

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Valentín Roales-Gómez

2014-08-01

Full Text Available Acute liver failure has a high mortality and its most frequent cause in Spain is viral infection. In this article, we present a case of fulminant liver failure. The failure is secondary to an idiosyncratic reaction to ibuprofen, an entity included in the DRESS syndrome. This syndrome plays a key role in the differential diagnosis of acute liver failure, since its unfortunate course often requires liver transplantation as the only useful therapeutic weapon. This case illustrates the need for an efficient coordination between hospitals as a key factor for improving the prognosis.

Japanese-style intensive medical care improves prognosis for acute liver failure and the perioperative management of liver transplantation.

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Inoue, K; Watanabe, T; Maruoka, N; Kuroki, Y; Takahashi, H; Yoshiba, M

2010-12-01

The Japanese style of intensive medical care for acute liver failure has yielded high survival rates. The care system comprises artificial liver support (ALS) together with treatment for the underlying disease. Plasma exchange in combination with high-volume hemodiafiltration using an high performance membrane has become the standard ALS system. It is safe, efficiently removing more low and middle molecular weight toxic substances than other methods because of the large volumes of buffer (more than 200 L per session), resulting in recovery from coma in patients with severe fulminant hepatitis, a status comparable with the ahepatic state. This ALS is therefore an effective tool to sustain patients with fulminant hepatitis in a favorable condition until liver function recovers or liver transplantation becomes available. The accompanying treatment for underlying disease serves to limit the liver destruction that hampers regeneration. The treatment has remarkably improved the prognosis for patients with subacute types of fulminant hepatitis, which generally carry a less favorable prognosis than the acute type. This treatment system thus provides more time for physicians to assess the indications for liver transplantation as well as giving the patient a greater chance of undergoing transplantation. Copyright © 2010 Elsevier Inc. All rights reserved.

Acute liver failure following recreational use of psychotropic "head shop" compounds.

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Fröhlich, S; Lambe, E; O'Dea, J

2011-03-01

The recreational use of the so-called "legal-highs" has been in both the medical and political arena over the last year as a result of the appearance of "head shops" in many towns in Ireland. These shops specialized in selling new psychotropic compounds that circumvented established drug legislation. Little is known about the potentially harmful effects of these substances but case reports suggest a plethora of harmful psychological and physical effects. Our case describes for the first time acute liver failure associated with the ingestion of two of these amphetamine type compounds.

Circulating histones are major mediators of systemic inflammation and cellular injury in patients with acute liver failure.

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Wen, Zongmei; Lei, Zhen; Yao, Lu; Jiang, Ping; Gu, Tao; Ren, Feng; Liu, Yan; Gou, Chunyan; Li, Xiuhui; Wen, Tao

2016-09-29

Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production. d-galactosamine plus lipopolysaccharide (GalN/LPS), concanavalin A (ConA), and acetaminophen (APAP) were given to C57BL/6N mice to induce liver injury, respectively, and the pathogenic role of circulating histones was studied. Besides, the protective effect of nonanticoagulant heparin, which can bind histones, was evaluated with in vivo and ex vivo investigations. We observed that circulating histones were significantly increased in patients with ALF, and correlated with disease severity and mortality. Significant systemic inflammation was also pronounced in ALF patients, which were associated with histone levels. ALF patients' sera induced significant L02 cell death and stimulated U937 cells to produce cytokines, which were abrogated by nonanticoagulant heparin. Furthermore, circulating histones were all released remarkably in GalN/LPS, ConA, and APAP-treated mice, and associated with high levels of inflammatory cytokines. Heparin reduced systemic inflammation and liver damage in mice, suggesting that it could interfere with histone-associated liver injury. Collectively, these findings demonstrate that circulating histones are critical mediators of systemic inflammation and cellular damage in ALF, which may be potentially translatable for clinical use.

DEP domain-containing mTOR-interacting protein suppresses lipogenesis and ameliorates hepatic steatosis and acute-on-chronic liver injury in alcoholic liver disease.

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Chen, Hanqing; Shen, Feng; Sherban, Alex; Nocon, Allison; Li, Yu; Wang, Hua; Xu, Ming-Jiang; Rui, Xianliang; Han, Jinyan; Jiang, Bingbing; Lee, Donghwan; Li, Na; Keyhani-Nejad, Farnaz; Fan, Jian-Gao; Liu, Feng; Kamat, Amrita; Musi, Nicolas; Guarente, Leonard; Pacher, Pal; Gao, Bin; Zang, Mengwei

2018-02-19

Alcoholic liver disease (ALD) is characterized by lipid accumulation and liver injury. However, how chronic alcohol consumption causes hepatic lipid accumulation remains elusive. The present study demonstrates that activation of the mechanistic target of rapamycin complex 1 (mTORC1) plays a causal role in alcoholic steatosis, inflammation, and liver injury. Chronic-plus-binge ethanol feeding led to hyperactivation of mTORC1, as evidenced by increased phosphorylation of mTOR and its downstream kinase S6 kinase 1 (S6K1) in hepatocytes. Aberrant activation of mTORC1 was likely attributed to the defects of the DEP domain-containing mTOR-interacting protein (DEPTOR) and the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1) in the liver of chronic-plus-binge ethanol-fed mice and in the liver of patients with ALD. Conversely, adenoviral overexpression of hepatic DEPTOR suppressed mTORC1 signaling and ameliorated alcoholic hepatosteatosis, inflammation, and acute-on-chronic liver injury. Mechanistically, the lipid-lowering effect of hepatic DEPTOR was attributable to decreased proteolytic processing, nuclear translocation, and transcriptional activity of the lipogenic transcription factor sterol regulatory element-binding protein-1 (SREBP-1). DEPTOR-dependent inhibition of mTORC1 also attenuated alcohol-induced cytoplasmic accumulation of the lipogenic regulator lipin 1 and prevented alcohol-mediated inhibition of fatty acid oxidation. Pharmacological intervention with rapamycin alleviated the ability of alcohol to up-regulate lipogenesis, to down-regulate fatty acid oxidation, and to induce steatogenic phenotypes. Chronic-plus-binge ethanol feeding led to activation of SREBP-1 and lipin 1 through S6K1-dependent and independent mechanisms. Furthermore, hepatocyte-specific deletion of SIRT1 disrupted DEPTOR function, enhanced mTORC1 activity, and exacerbated alcoholic fatty liver, inflammation, and liver injury in mice. The dysregulation of SIRT1

Liver transplantation for acute liver failure: a 5 years experience Transplante hepático na hepatite fulminante: uma experiência de 5 anos

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Cyntia Ferreira Gomes Viana

2008-09-01

Full Text Available BACKGROUND: Fulminant hepatic failure carries a high morbidity and mortality. Liver transplantation has markedly improved the prognosis of patients with fulminant hepatic failure. AIM: To evaluate the outcome of 20 patients with acute liver failure and indication for liver transplantation. METHODS: A retrospective review of 20 patients with acute liver failure and indication for liver transplantation was performed. Patients were divided into two groups: group A with 12 patients who underwent liver transplantation and group B with 8 patients who did not receive liver transplantation. Both groups were analyzed according to age, sex, ABO blood type, etiology of acute liver failure, time on list until transplantation or death, and survival rates. Group A patients were additionally analyzed according to preoperative INR, AST, and ALT peak values and MELD (Model for End-stage Liver Disease scores; intraoperative red blood cells and plasma transfusion and cold ischemia time; postoperative lenght of intensive care unit and hospital stay, and needed for dialysis. RESULTS: Group A: there were four men and eight women with an average age of 24.6 years. The average liver waiting time period was 3.4 days and MELD score 36. Seven patients are alive with good hepatic function at a medium follow-up of 26.2 months. The actuarial survival rate was 65.2% at 1 year. Group B: There were two men and six women with an average age of 30.9 years. The mean waiting time on list until death was 7.4 days. All patients died while waiting for a liver donor. CONCLUSION: Despite the improvements in intensive care management, most patients with acute liver failure and indication for liver transplantation ca not survive long without transplant. Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of those patients.RACIONAL: OBJETIVO: Avaliar a evolução de 20 pacientes com insuficiência hepática aguda e indicação de

Acetaminophen (Paracetamol) induced acute liver failure - A social problem in an era of increasing tendency to self-treatment.

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Wróblewski, Tadeusz; Kobryń, Konrad; Kozieł, Sławomir; Ołdakowska-Jedynak, Urszula; Pinkas, Jarosław; Danielewicz, Roman; Ziarkiewicz-Wróblewska, Bogna; Krawczyk, Marek

2015-01-01

The widespread availability of medication without prescription, so-called over the counter (OTC), and the rapid development of health consciousness of Poles is associated with broad access to medical information in the mass media. This causes patients to recognize their own disease, cancel doctor's appointments, and begin self-treatment. This time and money-saving behavior, often signaled by pain, usually leads to the treatment of symptoms alone, without seeking the cause of the disease.The aim of the study was to present life-threatening paracetamol poisoning, and the treatment of acute liver failure. In 2002-2014, 35 patients were hospitalized due to acute paracetamol poisoning: 17 female and 18 male patients aged between 17-59 (mean 32.3 years). Patients were treated in the surgical intensive care unit, where their parameters of liver and renal function were continuously monitored. If there was no improvement in the liver function, patients underwent albumin dialysis with the Prometheus system and were qualified for liver transplantation (LTx). 26 patients were treated pharmacologically and 7 out of 9 patients who underwent LTx were dialyzed. Overall, 11 patients had 26 albumin dialysis in total; 4 patients died - 1 post-transplant and 3 pre-transplant. Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial.

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Larsen, Fin Stolze; Schmidt, Lars Ebbe; Bernsmeier, Christine; Rasmussen, Allan; Isoniemi, Helena; Patel, Vishal C; Triantafyllou, Evangelos; Bernal, William; Auzinger, Georg; Shawcross, Debbie; Eefsen, Martin; Bjerring, Peter Nissen; Clemmesen, Jens Otto; Hockerstedt, Krister; Frederiksen, Hans-Jørgen; Hansen, Bent Adel; Antoniades, Charalambos G; Wendon, Julia

2016-01-01

Acute liver failure (ALF) often results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken. For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP vs. 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI), 0.36-0.86; p=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; p=0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (pHVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Late-onset acute rejection after living donor liver transplantation

Institute of Scientific and Technical Information of China (English)

Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Junichi Keneko; Yuichi Matsui; Kiyoshi Hasegawa; Masatoshi Makuuchi

2006-01-01

AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids.METHODS: Adult living donor liver transplantation recipients (n = 204) who survived more than 6 mo after living donor liver transplantation were enrolled.Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation,tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration.Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median followup period was 34 mo.RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset posttransplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporinebased regimen was significantly associated with LAR.CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

[Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat].

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Song, Min-ning; Song, Yu-na; Chen, Fu; Luo, Mei-lan

2007-01-01

To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(Pliver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26) micromol/L, both Pencephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,Pencephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.

Acetaminophen (Paracetamol induced acute liver failure – A social problem in an era of increasing tendency to self-treatment

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Tadeusz Wróblewski

2015-12-01

Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

Molecular adsorbents recirculating system treatment in acute-on-chronic hepatitis patients on the transplant waiting list improves model for end-stage liver disease scores.

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Novelli, G; Rossi, M; Pugliese, F; Poli, I; Ruberto, E; Martelli, S; Nudo, F; Morabito, V; Mennini, G; Berloco, P B

2007-01-01

The aim of our study was to show an improvement in Model for End-Stage Liver Disease (MELD) score after treatment with Molecular adsorbents recirculating system (MARS) in acute-on-chronic hepatitis (AoCHF) patients. MELD was adopted to determine the prognosis of patients with liver chronic desease. We evaluated the possibility to improve the MELD score of patients awaiting liver transplantation using a liver support device, namely, MARS. From September 1999 to April 2006, we treated 80 patients whose diagnoses were hepatitis C, 41.25%; hepatitis B, 27.5%; alcholic, 17.5%; intoxication, 8.75%; primary biliary cirrhosis, 5%. The overall mean age was 45 years (23 to 62), the cohort included 56 men and 24 women. Inclusion criteria were bilirubin >15 mg/dL; MELD >20; encephalopathy >II; and International Normalized Ratio, >2.1. Other parameters evaluated included ammonia, creatinine, lactate, glutamic oxalic transminase, and guanosine 5'-triphosphate. All patients were treated with a mean of 6-hour cycles of MARS (range, 5 to 8 hours) for a minimum of three treatments and a maximum of 20 treatments over 3 months. Clinical conditions were evaluated by improved hemodynamic parameters, kidney function, liver function, coagulation, neurologic status using the SOFA score, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II Criteria. The MELD score for all categories of living patients showed significant improvements at the end of treatment and at 3-months follow-up, but the small number of patients was a limitation to determine prediction of mortality. Our study shows that MARS treatment improved multiple organ functions-liver, renal, neurologic, and hemodynamic. The improved MELD score gave patients on the transplant waiting list longer survival, allowing them a greater opportunity for liver transplantation.

Acute Liver Failure in a Patient Travelling From Asia: The Other Face of the Coin of Infectious Disease.

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Abdulrahman, Balen; Ahmed, Mohamed H; Ramage, John

2017-08-01

We present a case of a 63-year-old male who had travelled from South India to United Kingdom (UK) visiting relatives. He had developed episodes of diarrhea, vomiting and fevers while travelling and on assessment in hospital, mild abdominal distension was noted with rapid deterioration to hypovolemic shock. Initial blood test showed a low platelet count with deranged liver function tests (LFTs). It was noted that during admission to intensive care unit (ICU), blood continued to ooze from a previous surgical laparoscopy wound, central and arterial line access sites. Blood results revealed ongoing derangement of clotting and LFT. Computed tomography (CT) scan showed possible acute cholecystitis and a laparoscopy showed an ischemic-looking liver and gut but no significant gallbladder abnormality. The virology screen was positive for dengue virus antibodies IgM and IgG. The patient developed multi-organ failure and deteriorated despite intensive support. Post mortem showed fulminant hepatic failure and acute tubular necrosis of kidneys.

The heart and the liver

DEFF Research Database (Denmark)

Møller, Søren; Dümcke, Christine Winkler; Krag, Aleksander

2009-01-01

Cardiac failure affects the liver and liver dysfunction affects the heart. Chronic and acute heart failure can lead to cardiac cirrhosis and cardiogenic ischemic hepatitis. These conditions may impair liver function and treatment should be directed towards the primary heart disease and seek...... against the heart failure. Transjugular intrahepatic portosystemic shunt insertion and liver transplantation affect cardiac function in portal hypertensive patients and cause stress to the cirrhotic heart, with a risk of perioperative heart failure. The risk and prevalence of coronary artery disease...

Auxiliary partial liver transplantation

NARCIS (Netherlands)

C.B. Reuvers (Cornelis Bastiaan)

1986-01-01

textabstractIn this thesis studies on auxiliary partial liver transplantation in the dog and the pig are reported. The motive to perform this study was the fact that patients with acute hepatic failure or end-stage chronic liver disease are often considered to form too great a risk for successful

A teenager presents with fulminant hepatic failure and acute hemolytic anemia.

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Bose, Somnath; Sonny, Abraham; Rahman, Nadeem

2015-03-01

A teenager was admitted to an outside hospital ED following an episode of melena. He had been complaining of intermittent abdominal pain, nausea, malaise, and easy fatigability for 2 months, with significant worsening of symptoms 2 weeks prior to this episode. He had no significant medical, surgical, or family history. On presentation at the outside ED, he was found to be profoundly icteric and encephalopathic. Initial laboratories suggested anemia, acute kidney injury, and acute liver failure, leading to a presumptive diagnosis of acute fulminant liver failure necessitating transfer to our institution.

Clinical effect of plasma perfusion combined with plasma exchange in treatment of patients with acute-on-chronic liver failure

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ZHOU Jian

2017-04-01

Full Text Available ObjectiveTo investigate the clinical effect of plasma perfusion (PP combined with plasma exchange (PE in the treatment of acute-on-chronic liver failure (ACLF. MethodsA total of 72 patients with ACLF who were admitted to The Second People’s Hospital of Lanzhou from January 2014 to December 2015 were enrolled. In addition to internal medication, all the patients were treated with the artificial liver support system (once every 3-4 days based on the patients’ conditions, 1-3 times on average for each patient. According to the difference in therapies, the patients were divided into combination group with 40 patients (PP combined with PE and a total of 107 case times and control group with 32 patients (PE alone and a total of 85 case times. Total bilirubin (TBil, alanine aminotransferase (ALT, and prothrombin time were recorded before treatment, after surgery, and at 72 hours after surgery. Clinical outcome was evaluated after 4 weeks of treatment. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe overall response rate of all patients was 63.89% (46/72. At 72 hours after surgery, there was a significant difference in the level of ALT between the combination group and the control group (319.54±86.23 U/L vs 354.75±100.76 U/L, t=2.60, P＜0.05. Both groups had significant reductions in TBil and ALT after surgery (combination group: t=6.69 and 15.84, P＜0.05; control group: t=5.34 and 14.38, P＜0.05 and at 72 hours after surgery (combination group: t=3.24 and 8.83, P＜0.05; control group: t=2.40 and 4.61, P＜0.05. Both groups had significant changes in prothrombin time activity after surgery (t=4.83 and 5.01, both P＜0.05. There were no significant differences in the incidence rates of pruritus and rash between the two groups, while there was a significant difference in the incidence rate of perioral or limb numbness between the

Adrenal Insufficiency as a Cause of Acute Liver Failure: A Case Report

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Jamshid Vafaeimanesh

2013-01-01

Full Text Available Introduction. Many diseases and conditions can contribute to elevated liver enzymes. Common causes include viral and autoimmune hepatitis, fatty liver, and bile duct diseases, but, in uncommon cases like liver involvement in endocrine disorders, liver failure is also seen. Adrenal insufficiency is the rarest endocrine disorder complicating the liver. In the previously reported cases of adrenal insufficiency, mild liver enzymes elevation was seen but we report a case with severe elevated liver enzymes and liver failure due to adrenal insufficiency. Based on our knowledge, this is the first report in this field. Case Report. A 39-year-old woman was referred to emergency ward due to drowsiness and severe fatigue. Her laboratory tests revealed prothrombin time: 21 sec, alanine aminotransferase (ALT: 2339 IU/L, aspartate aminotransferase (AST: 2002 IU/L, and ALP: 90 IU/L. No common cause of liver involvement was discovered, and eventually, with diagnosis of adrenal insufficiency and corticosteroid therapy, liver enzymes and function became normal. Finally, the patient was discharged with good general condition. Conclusion. With this report, we emphasize adrenal insufficiency (primary or secondary as a reason of liver involvement in unexplainable cases and recommend that any increase in the liver enzymes, even liver failure, in these patients should be observed.

Extracorporeal perfusion for the treatment of acute liver failure

NARCIS (Netherlands)

H.B.A.C. Stockmann; C.A. Hiemstra; R.L. Marquet (Richard); J.N.M. IJzermans (Jan)

2000-01-01

textabstractOBJECTIVE AND SUMMARY BACKGROUND DATA: Because of the shortage of available donor organs, death rates from liver failure remain high. Therefore, several temporary liver-assisting therapies have been developed. This article reviews various approaches to

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

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Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

2012-06-15

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure.

Science.gov (United States)

Frea, Simone; Pidello, Stefano; Bovolo, Virginia; Iacovino, Cristina; Franco, Erica; Pinneri, Francesco; Galluzzo, Alessandro; Volpe, Alessandra; Visconti, Massimiliano; Peirone, Andrea; Morello, Mara; Bergerone, Serena; Gaita, Fiorenzo

2016-05-01

The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure. A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient statistic from 0.59 to 0.73 (P advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

miRNA signatures can predict acute liver failure in hepatitis E infected pregnant females

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Nirupma Trehanpati

2017-04-01

Full Text Available Background: Acute viral hepatitis E (AVH-E can often result in acute liver failure (ALF during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E. Methods: We performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P self limiting AVH-E, ALF due to HEV (ALF-E and compared with AVH-E in non-pregnant (NP females and healthy controls. Findings: Eleven microRNAs were significantly expressed in response to HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005, but not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting AVH-E in pregnant females. miR-450b which affects cellular proliferation and metabolic processes through RNF20 and SECB was predominanlty upregulated and correlated with poor outcome (ROC 0.958, p = 0.001. Interpretation: Our results reveal that a specific microRNA profile can predict fatality in ALF-E in pregnancy. These microRNAs could be exploited as prognostic biomarkers and help in the development of new therapeutic interventions. Keywords: Health sciences, Virology

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

International Nuclear Information System (INIS)

Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

2012-01-01

In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p 4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl 4 , reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

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Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested

[Early detection, prevention and management of renal failure in liver transplantation].

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Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

2014-10-01

Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

ATTIRE: Albumin To prevenT Infection in chronic liveR failurE: study protocol for a single-arm feasibility trial.

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China, Louise; Muirhead, Nicola; Skene, Simon S; Shabir, Zainib; De Maeyer, Roel P H; Maini, Alexander A N; Gilroy, Derek W; O'Brien, Alastair J

2016-01-25

Circulating prostaglandin E2 levels are elevated in acutely decompensated cirrhosis and have been shown to contribute to immune suppression. Albumin binds and inactivates this hormone. Human albumin solution could thus be repurposed as an immune restorative drug in these patients.This feasibility study aims to determine whether it is possible and safe to restore serum albumin to >30 g/L and maintain it at this level in patients admitted with acute decompensated cirrhosis using repeated 20% human albumin infusions according to daily serum albumin levels. Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) stage 1 is a multicentre, open label dose feasibility trial. Patients with acutely decompensated cirrhosis admitted to hospital with a serum albumin of albumin solution will be infused, according to serum albumin levels, for up to 14 days or discharge in all patients. The primary end point is daily serum albumin levels for the duration of the treatment period and the secondary end point is plasma-induced macrophage dysfunction. The trial will recruit 80 patients. Outcomes will be used to assist with study design for an 866 patient randomised controlled trial at more than 30 sites across the UK. Research ethics approval was given by the London-Brent research ethics committee (ref: 15/LO/0104). The clinical trials authorisation was issued by the medicines and healthcare products regulatory agency (ref: 20363/0350/001-0001). Will be disseminated through peer reviewed journals and international conferences. Recruitment of the first participant occurred on 26/05/2015. The trial is registered with the European Medicines Agency (EudraCT 2014-002300-24) and has been adopted by the NIHR (ISRCTN 14174793). This manuscript refers to V.4.0 of the protocol; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Endothelins in chronic liver disease

DEFF Research Database (Denmark)

Møller, S; Henriksen, Jens Henrik Sahl

1996-01-01

renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension......This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation....... In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive...

Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange

DEFF Research Database (Denmark)

Stenbøg, Poul; Busk, Troels; Larsen, Fin Stolze

2013-01-01

Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain...... edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose......, and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE....

Acute heart failure

OpenAIRE

Sénior Sánchez, Juan Manuel; Gándara Ricardo, Jairo Alfonso

2015-01-01

We describe the clinical case of a 26 year-old woman who came to Hospital Universitario San Vicente Fundación (Medellín, Colombia) with symptoms and signs of acute heart failure. She had been previously diagnosed with chronic heart failure with reduced ejection fraction without clear origin, pulmonary thromboembolism and ischemic stroke, without optimal neurohormonal modulation. She was admitted with clinical findings of fluid overload and low tissue perfusion, with inotropic support requirem...

Propylthiouracil-induced liver failure and artificial liver support systems: a case report and review of the literature

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Wu DB

2017-01-01

Full Text Available Dong-Bo Wu,1,2 En-Qiang Chen,1,2 Lang Bai,1,2 Hong Tang1,2 1Center of Infectious Diseases, West China Hospital of Sichuan University, 2Division of Molecular Biology of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, People’s Republic of China Background: Antithyroid drugs carry a potential risk of hepatotoxicity. Propylthiouracil (PTU is commonly prescribed for patients with hyperthyroidism. PTU, however, can induce liver injury, ranging from mild asymptomatic elevation of aminotransferases to acute liver failure (ALF.Case presentation: This case reports on a 16-year-old Chinese girl with hyperthyroidism, who was admitted to our hospital for jaundice, nausea, and fatigue associated with severe hyperbilirubinemia and coagulopathy. She had been prescribed PTU 5 months earlier. There was no history of hypersensitivity to drugs, viral liver diseases, blood transfusion, or surgery. On the basis of her symptoms and the clinical data, she was diagnosed with PTU-induced ALF. Due to the limited number of available donor organs for liver transplantation, she was started on treatment with artificial liver support system (ALSS. After four sessions of ALSS, her clinical signs and symptoms were found to be markedly improved, and she was discharged 25 days after admission. Four months later, her liver function normalized.Conclusion: Although PTU-induced liver failure is rare in clinical practice, liver function should be appropriately monitored during treatment with PTU. PTU-induced ALF in this patient was successfully managed with an ALSS, suggesting that the latter may be an alternative to liver transplantation. Keywords: propylthiouracil, liver injury, acute liver failure, artificial liver support systems 

Positive pressure ventilation in the management of acute and chronic cardiac failure: a systematic review and meta-analysis.

Science.gov (United States)

Nadar, Sunil; Prasad, Neeraj; Taylor, Rod S; Lip, Gregory Y H

2005-03-18

Chronic heart failure (CHF) is a common condition and is associated with excess morbidity and mortality, in spite of the many advances in its treatment. Chronic stable heart failure is also associated with an increased incidence of sleep-related breathing disorders, such as central sleep apnoea (CSA) and Cheyne Stokes respiration (CSR). Continuous positive airways pressure (CPAP) has been shown to alleviate the symptoms of CHF, improve left ventricular function and oxygenation. To a certain extent, CPAP also abolishes sleep-related breathing disorders in patients with chronic heart failure. In patients with acute pulmonary oedema, the use of positive pressure ventilation improves cardiac haemodynamic indices, as well as symptoms and oxygenation, and is associated with a lower need for intubation. However, some studies have cast doubts about its safety and suggest a higher rate of myocardial infarction associated with its use. In our opinion, non-invasive positive pressure ventilation and CPAP offers an adjunctive mode of therapy in patients with acute pulmonary oedema and chronic heart failure, who may not be suitable for intubation and in those not responsive to conventional therapies. Non-invasive ventilation also helps to improve oxygenation in those patients with exhaustion and respiratory acidosis. Many trials are still ongoing and the results of these studies would throw more light on the present role of non-invasive ventilation in the management of CHF.

Crizotinib-induced fatal fulminant liver failure

NARCIS (Netherlands)

van Geel, Robin M J M; Hendrikx, Jeroen J M A; Vahl, Jelmer E.; van Leerdam, Monique E.; van den Broek, Daan; Huitema, Alwin D R; Beijnen, Jos H.; Schellens, Jan H M; Burgers, Sjaak A.

2016-01-01

Herein we describe a case of a 62-year-old female in good clinical condition with non-small-cell lung cancer who was treated with crizotinib. After 24 days of crizotinib therapy she presented with acute liver failure. Serum aspartate aminotransferase and alanine aminotransferase levels had increased

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

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Ip, Stephen; Hussaini, Trana; Daulat, Aliya; Partovi, Nilufar; Erb, Siegfried R; Yoshida, Eric M; Marquez, Vladimir

2017-01-01

Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. To examine the risk factors in the development of CRF in these patients. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

Science.gov (United States)

Tao, Ya-Chao; Wang, Meng-Lan; Chen, En-Qiang; Tang, Hong

2018-02-23

Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Alpha-fetoprotein as a prognostic marker in acute liver failure: a pilot study.

Science.gov (United States)

Varshney, Anshul; Gupta, Rohit; Verma, Sanjiv K; Ahmad, Sohaib

2017-07-01

Prognostic markers of acute liver failure (ALF) are based on clinical, laboratory or radiological parameters. Most of the biochemical markers are based on hepatic degeneration. We studied the impact of serial serum alpha-fetoprotein (AFP) levels, a marker of liver regeneration, on the outcome of the patients with ALF. AFP levels were estimated on days 1 and 3 of hospitalisation of 32 patients with ALF and the ratio (AFP day3/day1) was calculated. All subjects were categorised as group A (expired) or group B (survived). The AFP ratio was 0.84  +  0.15 in group A (n = 20) versus 1.55  +  0.70 in group B (n = 10); P < 0.001. However, the absolute initial AFP values were not associated with the outcome, favourable or unfavourable. We conclude that AFP levels change dynamically during ALF and have the potential to be used as a predictor of outcome in isolation or in combination with well-established prognostic markers.

Safety and efficacy of antibiotics among acutely decompensated cirrhosis patients.

Science.gov (United States)

Habib, Shahid; Patel, Nehali; Yarlagadda, Sandeep; Hsu, Chiu-Hsieh; Patel, Sarah; Schader, Lindsey; Walker, Courtney; Twesigye, Innocent

2018-04-26

Infection is a leading precipitant of acute-on-chronic liver failure. This study aims to determine the safety and efficacy of antibiotics within acute-on-chronic liver failure. Retrospective study of 457 acute-on-chronic liver failure patients admitted to the University of Arizona Health Network between January 1 and December 31, 2014. Eligibility criteria were as follows: at least 18 years of age and 6 months follow-up, data available to calculate systemic inflammatory response syndrome (SIRS), and acute-on-chronic liver failure. This study collected patient's clinical features and historical data. Key data points were infection, antibiotic use, and SIRS. This study used Cox proportional hazards to model the effects of clinical factors on risk of death. A total of 521 of 1243 met the inclusion criteria, and 64 had missing data, leaving 457 patients. Infection resulted in higher hazard (hazard ratio [HR] = 1.6, confidence interval [CI]: 1.1-1.3, P = 0.01). Patients with infections and antibiotics, compared with non-infected patients without antibiotics, had higher hazard (HR = 1.633, CI: 1.022-2.609, P = .04). Of those infected patients with antibiotics, SIRS patients experienced higher hazard (HR = 1.9, CI: 1.1-3.0, P = .007). Multivariable Cox proportional hazards associated the following with higher hazard: SIRS (HR = 1.866, CI: 1.242-2.804, P = 0.003), vancomycin (HR = 1.640, CI: 1.119-2.405, P = 0.011), Model for End-Stage Liver Disease (HR = 1.051, CI: 1.030-1.073, P < 0.001), gastrointestinal bleeding (HR = 1.727, CI: 1.180-2.527, P = 0.005), and hepatic encephalopathy (HR = 1.807, CI: 1.247-2.618, P = 0.002). Overall, treatment of infection with antibiotics did not improve survival; however, patients not meeting SIRS criteria had better outcomes, and vancomycin was associated with poorer survival among acute-on-chronic liver failure patients. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley

Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

International Nuclear Information System (INIS)

Kim, Ja Young; Yu, In Kyu

2015-01-01

Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

Acute hyperammonemic encephalopathy with features on diffusion-weighted images: Report of two cases

Energy Technology Data Exchange (ETDEWEB)

Kim, Ja Young; Yu, In Kyu [Dept. of Radiology, Eulji University Hospital, Daejeon (Korea, Republic of)

2015-02-15

Acute hyperammonemic encephalopathy is a rare toxic encephalopathy caused by accumulated plasma ammonia. A few literatures are reported about MRI findings of acute hyperammonemic encephalopathy. It is different from the well-known chronic hepatic encephalopathy. The clinical symptom and MRI findings of acute hyperammonemic encephalopathy can be reversible with proper treatment. Acute hepatic encephalopathy involves the cingulate cortex, diffuse cerebral cortices, insula, bilateral thalami on diffusion-weighted imaging (DWI), and fluid-attenuated inversion-recovery. Acute hepatic encephalopathy might mimic hypoxic-ischemic encephalopathy because of their similar predominant involving sites. We experienced 2 cases of acute hyperammonemic encephalopathy consecutively. They showed restricted diffusion at the cingulate cortex, cerebral cortices, insula, and bilateral dorsomedial thalami on DWI. One patient underwent acute fulminant hepatitis A, the other patient with underlying chronic liver disease had acute liver failure due to hepatotoxicity of tuberculosis medication. In this report, we presented the characteristic features of DWI in acute hyperammonemic encephalopathy. In addition, we reviewed articles on MRI findings of acute hyperammonemic encephalopathy.

What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Acute Respiratory Failure?

Science.gov (United States)

Kim, Deog Kyeom; Lee, Jungsil; Park, Ju Hee; Yoo, Kwang Ha

2018-04-01

Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to be critical and debilitating events leading to poorer outcomes in relation to chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute to a higher and earlier mortality rate in COPD patients. Besides pro-active preventative measures intended to obviate acquisition of AECOPD, early recovery from severe AECOPD is an important issue in determining the long-term prognosis of patients diagnosed with COPD. Updated GOLD guidelines and recently published American Thoracic Society/European Respiratory Society clinical recommendations emphasize the importance of use of pharmacologic treatment including bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is recommended as the treatment of choice as this therapy is thought to be most effective in reducing intubation risk in patients diagnosed with AECOPD with acute respiratory failure. Recently, a few adjunctive modalities, including NIV with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with respiratory failure. As yet, insufficient documentation exists to permit recommendation of this therapy without qualification. Although there are too few findings, as yet, to allow for regular andr routine application of those modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and physiological benefits connected with this therapy. High-flow nasal cannula oxygen therapy is another supportive strategy which serves to improve the symptoms of hypoxic respiratory failure. The therapy also produced improvement in ventilatory variables, and it may be successfully applied in cases of hypercapnic respiratory failure. Extracorporeal carbon dioxide removal has been successfully attempted in cases of adult respiratory distress syndrome, with protective hypercapnic ventilatory strategy. Nowadays, it is

Retrospective Identification of Herpes Simplex 2 Virus-Associated Acute Liver Failure in an Immunocompetent Patient Detected Using Whole Transcriptome Shotgun Sequencing.

Science.gov (United States)

Ono, Atsushi; Hayes, C Nelson; Akamatsu, Sakura; Imamura, Michio; Aikata, Hiroshi; Chayama, Kazuaki

2017-01-01

Acute liver failure (ALF) is a severe condition in which liver function rapidly deteriorates in individuals without prior history of liver disease. While most cases result from acetaminophen overdose or viral hepatitis, in up to a third of patients, no clear cause can be identified. Liver transplantation has greatly reduced mortality among these patients, but 40% of patients recover without liver transplantation. Therefore, there is an urgent need for rapid determination of the etiology of acute liver failure. In this case report, we present a case of herpes simplex 2 virus- (HSV-) associated ALF in an immunocompetent patient. The patient recovered without LT, but the presence of HSV was not suspected at the time, precluding more effective treatment with acyclovir. To determine the etiology, stored blood samples were analyzed using whole transcriptome shotgun sequencing followed by mapping to a panel of viral reference sequences. The presence of HSV-DNA in blood samples at the time of admission was confirmed using real-time polymerase chain reaction, and, at the time of discharge, HSV-DNA levels had decreased by a factor of 10 6 . Conclusions. In ALF cases of undetermined etiology, uncommon causes should be considered, especially those for which an effective treatment is available.

Retrospective Identification of Herpes Simplex 2 Virus-Associated Acute Liver Failure in an Immunocompetent Patient Detected Using Whole Transcriptome Shotgun Sequencing

Directory of Open Access Journals (Sweden)

Atsushi Ono

2017-01-01

Full Text Available Acute liver failure (ALF is a severe condition in which liver function rapidly deteriorates in individuals without prior history of liver disease. While most cases result from acetaminophen overdose or viral hepatitis, in up to a third of patients, no clear cause can be identified. Liver transplantation has greatly reduced mortality among these patients, but 40% of patients recover without liver transplantation. Therefore, there is an urgent need for rapid determination of the etiology of acute liver failure. In this case report, we present a case of herpes simplex 2 virus- (HSV- associated ALF in an immunocompetent patient. The patient recovered without LT, but the presence of HSV was not suspected at the time, precluding more effective treatment with acyclovir. To determine the etiology, stored blood samples were analyzed using whole transcriptome shotgun sequencing followed by mapping to a panel of viral reference sequences. The presence of HSV-DNA in blood samples at the time of admission was confirmed using real-time polymerase chain reaction, and, at the time of discharge, HSV-DNA levels had decreased by a factor of 106. Conclusions. In ALF cases of undetermined etiology, uncommon causes should be considered, especially those for which an effective treatment is available.

Liver regeneration signature in hepatitis B virus (HBV-associated acute liver failure identified by gene expression profiling.

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Oriel Nissim

Full Text Available The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC. The dramatic clinical course of acute liver failure (ALF has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV-associated ALF.Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients and submassive hepatic necrosis (SHN; 2 patients. We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7, whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between

Endothelins in chronic liver disease

DEFF Research Database (Denmark)

Møller, Søren; Henriksen, Jens Henrik

1996-01-01

This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation...... renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension...

Acute Hepatitis E: Two Sides of the Same Coin.

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Hartl, Johannes; Wehmeyer, Malte H; Pischke, Sven

2016-11-03

The relevance of acute hepatitis E virus (HEV) infections has been underestimated for a long time. In the past, HEV infection had been interpreted falsely as a disease limited to the tropics until the relevance of autochthonous HEV infections in the Western world became overt. Due to increased awareness, the incidence of diagnosed autochthonous HEV infections (predominantly genotype 3) in industrialized countries has risen within the last decade. The main source of infections in industrialized countries seems to be infected swine meat, while infections with the tropical HEV genotypes 1 and 2 usually are mainly transmitted fecal-orally by contaminated drinking water. In the vast majority of healthy individuals, acute HEV infection is either clinically silent or takes a benign self-limited course. In patients who develop a symptomatic HEV infection, a short prodromal phase with unspecific symptoms is followed by liver specific symptoms like jaundice, itching, uncoloured stool and darkened urine. Importantly, tropical HEV infections may lead to acute liver failure, especially in pregnant women, while autochthonous HEV infections may lead to acute-on-chronic liver failure in patients with underlying liver diseases. Immunosuppressed individuals, such as transplant recipients or human immunodeficiency virus (HIV)-infected patients, are at risk for developing chronic hepatitis E, which may lead to liver fibrosis and cirrhosis in the long term. Importantly, specific treatment options for hepatitis E are not approved by the regulation authorities, but off-label ribavirin treatment seems to be effective in the treatment of chronic HEV-infection and may reduce the disease severity in patients suffering from acute liver failure.

Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

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Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

2013-01-01

The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. Copyright © 2012 Wiley Periodicals, Inc.

Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

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Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

2015-08-28

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

[Liver transplantation].

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Pompili, Maurizio; Mirante, Vincenzo Giorgio; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

2004-01-01

Liver transplantation represents the first choice treatment for patients with fulminant acute hepatitis and for patients with chronic liver disease and advanced functional failure. Patients in the waiting list for liver transplantation are classified according to the severity of their clinical conditions (evaluated using staging systems mostly based on hematochemical parameters related to liver function). This classification, together with the blood group and the body size compatibility, remains the main criterion for organ allocation. The main indications for liver transplantation are cirrhosis (mainly HCV-, HBV- and alcohol-related) and hepatocellular carcinoma emerging in cirrhosis in adult patients, biliary atresia and some inborn errors of metabolism in pediatric patients. In adults the overall 5-year survival ranges between 60 and 70%, in both American and European series. Even better results have been reported for pediatric patients: in fact, the 5-year survival rate for children ranges between 70 and 80% in the main published series. In this study we evaluated the main medical problems correlated with liver transplantation such as immunosuppressive treatment, acute and chronic rejection, infectious complications, the recurrence of the liver disease leading to transplantation, and cardiovascular and metabolic complications.

Influence of acute and chronic administration of methadone hydrochloride on NADPH-cytochrome c reductase and cytochrome P-450 of mouse liver microsomes.

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Datta, R K; Johnson, E A; Bhattacharjee, G; Stenger, R J

1976-03-01

Administration of a single acute dose (20 mg/kg body weight) of methadone hydrochloride to both male and female mice increased the specific activity of NADPH-cytochrome c reductase and did not change much the content of cytochrome P-450 of their liver microsomes. Administration of multiple acute doses of methadone in male mice increased the specific activity of cytochrome c reductase and the content of cytochrome P-450 of their liver microsomes. Chronic administration of progressively increasing doses of methadone (up to 40 mg/kg body weight) to male mice increased the specific activity of c reductase. Similar chronic administration of methadone up to 28 mg/kg body weight also increased the microsomal content of P-450, but with higher doses of methadone, the content of P-450 declined and finally dropped slightly below control levels. The levels of c reductase activity and P-450 content returned to normal about two weeks after discontinuation of methadone administration.

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

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Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

Therapeutic effects of the traditional medicinal plant Ipomoea stolonifera for the treatment of liver diseases

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Bai, Xueting

2016-01-01

Liver diseases are categorized into acute liver failure (ALF) and chronic liver failure (CLF). Massive cell death is a hallmark of ALF and leads to a dramatic loss of liver function. Therefore, specific interventions targeted to prevent or attenuate this massive cell death may be very effective in

Binding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate receptor during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit

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R.J. de Knegt (Robert); J. Kornhuber (Johannes); S.W. Schalm (Solko); K. Rusche (K.); P.F. Riederer (Peter); J. Tan (J.)

1993-01-01

textabstractBinding of the ligand [3H]MK-801 to the MK-801 binding site of the N-methyl-D-aspartate (NMDA) receptor population on brain homogenates in rabbits was studied during experimental encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. Homogenates were

Acute Liver Failure from Herpes Simplex Virus in an Immunocompetent Patient Due to Direct Inoculation of the Peritoneum.

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Chaudhary, Dhruv; Ahmed, Shifat; Liu, Nanlong; Marsano-Obando, Luis

2017-01-01

Herpes simplex virus (HSV) hepatitis is a rare cause of acute liver failure (ALF). It carries a mortality rate of 80% if untreated, thus early identification and treatment are critical. Without high clinical suspicion, HSV hepatitis is difficult to diagnose. A 48-year-old Hispanic female presented with a 4-day history of abdominal pain and a vaginal cuff tear requiring laparoscopic repair. She subsequently developed postsurgical disseminated HSV, resulting in ALF. Acyclovir was initiated, but she was resistant to treatment. She was given additional foscarnet and responded without requiring a liver transplant.

A new liver function test using the asialoglycoprotein-receptor system on the liver cell membrane, 3

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Hazama, Hiroshi; Kawa, Soukichi; Kubota, Yoshitsugu

1986-01-01

We evaluated the vilidity of a new liver function test using liver scintigraphy based on the asialoglycoprotein (ASGP) receptor system on the liver cell membrane in rats with galactosamine-induced acute liver disorder and those with carbon tetra-chloride-induced chronic liver disorder. Neoglycoprotein (GHSA) produced by combining human serum albumin with 32 galactose units was labeled with 99m Tc and administered (50 μg/100 g body weight) to rats with acute or chronic liver disorder. Clearance curves were produced based on liver scintigrams and analysed using the two-compartment model to obtain parameters. In acute liver disorder, the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities correlated well to the increase in serum GOT and the decrease in the esterified to total cholesterol ratio (E/T ratio); in chronic liver disorder, they correlated significantly to the increase in the content of liver hydroxyproline (Hyp) which increased in proportion to the severity of liver fibrosis studied histologically, and to the decrease in the contents of cytochrome P-450 and cytochrome b 5 in liver microsomes. Significant correlation was observed between the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities in both acute and chronic liver disorders. These findings indicate that the measurement of 99m Tc-GHSA clearance can be a new liver function test sensitively reflecting the severity of liver damage. (author)

[Causes and management of severe acute liver damage during pregnancy].

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Sepulveda-Martinez, Alvaro; Romero, Carlos; Juarez, Guido; Hasbun, Jorge; Parra-Cordero, Mauro

2015-05-01

Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute liver damage can be an exclusive condition of pregnancy (dependent or independent of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver of pregnancy are the most severe liver diseases associated with pregnancy. Both appear during the third trimester and have a similar clinical presentation. Acute fatty liver may be associated with hypoglycemia and HELLP syndrome is closely linked with pre-eclampsia. Among concomitant conditions, fulminant acute hepatitis caused by medications or virus is the most severe disease. Its clinical presentation may be hyper-acute with neurological involvement and severe coagulation disorders. It has a high mortality and patients should be transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be managed with n-acetyl cysteine. Because of the high fetal mortality rate, the gestational age at diagnosis is crucial.

Transplant of Hepatocytes, Undifferentiated Mesenchymal Stem Cells, and In Vitro Hepatocyte-Differentiated Mesenchymal Stem Cells in a Chronic Liver Failure Experimental Model: A Comparative Study.

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El Baz, Hanan; Demerdash, Zeinab; Kamel, Manal; Atta, Shimaa; Salah, Faten; Hassan, Salwa; Hammam, Olfat; Khalil, Heba; Meshaal, Safa; Raafat, Inas

2018-02-01

Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure. Undifferentiated human cord blood mesenchymal stem cells were isolated, pro-pagated, and characterized by morphology, gene expression analysis, and flow cytometry of surface markers and in vitro differentiated into hepatocyte-like cells. Rat hepatocytes were isolated by double perfusion technique. An animal model of chronic liver failure was developed, and undifferentiated human cord blood mesenchymal stem cells, in vitro hepato-genically differentiated mesenchymal stem cells, or freshly isolated rat hepatocytes were transplanted into a CCL4 cirrhotic experimental model. Animals were killed 3 months after transplant, and liver functions and histopathology were assessed. Compared with the cirrhotic control group, the 3 cell-treated groups showed improved alanine aminotransferase, aspartate aminotransferase, albumin, and bilirubin levels, with best results shown in the hepatocyte-treated group. Histopathologic examination of the treated groups showed improved fibrosis, with best results obtained in the undifferentiated mesenchymal stem cell-treated group. Both adult hepatocytes and cord blood mesenchymal stem cells proved to be promising candidates for cell-based therapy in liver regeneration on an experimental level. Improved liver function was evident in the hepatocyte-treated group, and fibrosis control was more evident in the undifferentiated mesenchymal stem cell-treated group.

Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

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Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J

2013-12-01

Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.

Investigation of a Rise in Obstetric Acute Renal Failure in the United States, 1999-2011.

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Mehrabadi, Azar; Dahhou, Mourad; Joseph, K S; Kramer, Michael S

2016-05-01

To estimate whether the reported increase in obstetric acute renal failure in the United States was attributable to a concurrent rise in postpartum hemorrhage, a change in other risk factors, or changes in the diagnosis of acute renal failure. We conducted a retrospective cohort study to quantify temporal trends in acute renal failure among 10,969,263 hospital deliveries in the United States from 1999 to 2011 using data from the Nationwide Inpatient Sample. Dialysis and maternal death were used as markers of severe acute renal failure. Logistic regression was used to determine whether changes in risk factors explained the temporal rise in acute renal failure. Obstetric acute renal failure rose from 2.4 to 6.3 per 10,000 deliveries between 1999-2001 and 2010-2011, a 10% yearly increase (95% confidence interval [CI] 8-11%) and adjustment for risk factors only partially explained the rise (adjusted yearly increase 6%, 95% CI 5-8%). The overall severity of acute renal failure decreased, although acute renal failure with dialysis rose from 0.27 to 0.36 per 10,000 deliveries (P for trend=.01), and acute renal failure associated with maternal death increased from 0.13 to 0.23 per 10,000 deliveries (P for trend=.01). The temporal increase in acute renal failure with dialysis was abolished by adjustment for chronic kidney disease and chronic hypertension. Changes in diagnosis or ascertainment have led to substantial increases in obstetric acute renal failure, whereas increases in chronic kidney disease and chronic hypertension among pregnant women have resulted in modest but significant increases in acute renal failure with dialysis.

Noninvasive radiographic assessment of cardiovascular function in acute and chronic respiratory failure

International Nuclear Information System (INIS)

Berger, H.J.; Matthay, R.A.

1981-01-01

Noninvasive radiographic techniques have provided a means of studying the natural history and pathogenesis of cardiovascular performance in acute and chronic respiratory failure. Chest radiography, radionuclide angiocardiography and thallium-201 imaging, and M mode and cross-sectional echocardiography have been employed. Each of these techniques has specific uses, attributes and limitations. For example, measurement of descending pulmonary arterial diameters on the plain chest radiograph allows determination of the presence or absence of pulmonary arterial hypertension. Right and left ventricular performance can be evaluated at rest and during exercise using radionuclide angiocardiography. The biventricular response to exercise and to therapeutic interventions also can be assessed with this approach. Evaluation of the pulmonary valve echogram and echocardiographic right ventricular dimensions have been shown to reflect right ventricular hemodynamics and size. Each of these noninvasive techniques has been applied to the study of patients with respiratory failure and has provided important physiologic data

Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure.

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Clemmesen, J O; Kondrup, J; Nielsen, L B; Larsen, F S; Ott, P

2001-04-01

In acute liver failure (ALF), urea production is severely impaired, and detoxification of ammonia by glutamine synthesis plays an important protective role. The aim of this study was to examine the effects of therapeutic high-volume plasmapheresis (HVP) on arterial concentrations and splanchnic exchange rates of ammonia, urea, and amino acids-in particular, glutamine. A quantity of 8 L of plasma was exchanged over the course of 7 h in 11 patients with ALF after development of hepatic encephalopathy grade III-IV. Splanchnic exchange rates of ammonia, urea, and amino acids were measured by use of liver vein catheterization. HVP removed ammonia and glutamine at a rate of 1 micromol/min and 27 micromol/min, respectively. Arterial ammonia decreased from 160 +/- 65 to 114 +/- 50 micromol/L (p HVP) were as follows: for ammonia, -93 +/- 101 versus -70 +/- 80 micromol/min (NS); urea-nitrogen, 0.08 +/- 1.64 versus -0.31 +/- 0.45 mmol/min (NS); alanine, -73 +/- 151 versus 12 +/- 83 micromol/min (p HVP in patients with ALF. The data suggest that this effect of HVP could be explained by increased hepatic urea synthesis and possibly by increased glutamine synthesis in muscle tissue.

Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure

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DING Yitao

2017-09-01

Full Text Available The main features of liver failure are extensive necrosis of hepatocytes, rapid disease progression, and poor prognosis, and at present, there are no effective drugs and methods for the treatment of liver failure. This article summarizes four treatment methods for liver failure, i.e., medical treatment, cell transplantation, liver transplantation, and artificial liver support therapy, and elaborates on the existing treatment methods. The current medical treatment regimen should be optimized; cell transplantation has not been used in clinical practice; liver transplantation is the most effective method, but it is limited by donor liver shortage and high costs; artificial liver can effectively remove toxic substances in human body. Therefore, this article puts forward artificial liver as a transition for liver transplantation; artificial liver can buy time for liver regeneration or liver transplantation and prolong patients′ survival time and thus has a promising future. The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

Late Intensive Care Unit Admission in Liver Transplant Recipients: 10-Year Experience.

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Atar, Funda; Gedik, Ender; Kaplan, Şerife; Zeyneloğlu, Pınar; Pirat, Arash; Haberal, Mehmet

2015-11-01

We evaluated late intensive care unit admission in liver transplant recipients to identify incidences and causes of acute respiratory failure in the postoperative period and to compare these results with results in patients who did not have acute respiratory failure. We retrospectively screened the data of 173 consecutive adult liver transplant recipients from January 2005 through March 2015 to identify patients with late admission (> 30 d posttransplant) to an intensive care unit. Patients were divided into 2 groups: patients with and without acute respiratory failure. Acute respiratory failure was defined as severe dyspnea, respiratory distress, decreased oxygen saturation, hypoxemia or hypercapnia on room air, or need for noninvasive or invasive mechanical ventilation. Demographic, laboratory, clinical, and respiratory data were collected. Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores; lengths of intensive care unit and hospital stays; and hospital mortality were assessed. Among 173 patients, 37 (21.4%) were admitted to an intensive care unit, including 22 (59.5%) with acute respiratory failure. The leading cause of acute respiratory failure was pneumonia (n = 19, 86.4%). Patients with acute respiratory failure had significantly lower levels of albumin before intensive care unit admission (P = .003). In patients with acute respiratory failure, severe sepsis and septic shock were more frequently observed and tracheotomy was more frequently performed (P = .041). Acute respiratory failure developed in 59.5% of liver transplant recipients with late intensive care unit admission. The leading cause was pneumonia, with this group of patients having higher requirements for invasive mechanical ventilation and tracheotomy, longer stays in an intensive care unit, and higher mortality.

Mesenchymal Stromal Cells Cultured in Serum from Heart Failure Patients Are More Resistant to Simulated Chronic and Acute Stress

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Timo Z. Nazari-Shafti

2018-01-01

Full Text Available Despite regulatory issues surrounding the use of animal-derived cell culture supplements, most clinical cardiac cell therapy trials using mesenchymal stromal cells (MSCs still rely on fetal bovine serum (FBS for cell expansion before transplantation. We sought to investigate the effect of human serum from heart failure patients (HFS on cord blood MSCs (CB-MSCs during short-term culture under regular conditions and during simulated acute and chronic stress. Cell survival, proliferation, metabolic activity, and apoptosis were quantified, and gene expression profiles of selected apoptosis and cell cycle regulators were determined. Compared to FBS, HFS and serum from healthy donors (CS showed similar effects by substantially increasing cell survival during chronic and acute stress and by increasing cell yields 5 days after acute stress. Shortly after the termination of acute stress, both HFS and CS resulted in a marked decrease in apoptotic cells. Transcriptome analysis suggested a decrease in TNF-mediated induction of caspases and decreased activation of mitochondrial apoptosis. Our data confirm that human serum from both healthy donors and heart failure patients results in increased cell yields and increased resistance to cellular stress signals. Therefore, we consider autologous serum a valid alternative to FBS in cell-based therapies addressing severe heart disease.

Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

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Kazushige Nirei

2013-01-01

Full Text Available This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient’s jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.

Acetaminophen-induced acute liver injury in HCV transgenic mice

International Nuclear Information System (INIS)

Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

2013-01-01

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

Acetaminophen-induced acute liver injury in HCV transgenic mice

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Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: iir@unc.edu [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)

2013-01-15

The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

[Renal failure in patients with liver transplant: incidence and predisposing factors].

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Gerona, S; Laudano, O; Macías, S; San Román, E; Galdame, O; Torres, O; Sorkin, E; Ciardullo, M; de Santibañes, E; Mastai, R

1997-01-01

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

Risk factors for acute renal failure: inherent and modifiable risks.

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Leblanc, Martine; Kellum, John A; Gibney, R T Noel; Lieberthal, Wilfred; Tumlin, James; Mehta, Ravindra

2005-12-01

Our purpose is to discuss established risk factors in the development of acute renal failure and briefly overview clinical markers and preventive measures. Findings from the literature support the role of older age, diabetes, underlying renal insufficiency, and heart failure as predisposing factors for acute renal failure. Diabetics with baseline renal insufficiency represent the highest risk subgroup. An association between sepsis, hypovolemia, and acute renal failure is clear. Liver failure, rhabdomyolysis, and open-heart surgery (especially valve replacement) are clinical conditions potentially leading to acute renal failure. Increasing evidence shows that intraabdominal hypertension may contribute to the development of acute renal failure. Radiocontrast and antimicrobial agents are the most common causes of nephrotoxic acute renal failure. In terms of prevention, avoiding nephrotoxins when possible is certainly desirable; fluid therapy is an effective prevention measure in certain clinical circumstances. Supporting cardiac output, mean arterial pressure, and renal perfusion pressure are indicated to reduce the risk for acute renal failure. Nonionic, isoosmolar intravenous contrast should be used in high-risk patients. Although urine output and serum creatinine lack sensitivity and specificity in acute renal failure, they remain the most used parameters in clinical practice. There are identified risk factors of acute renal failure. Because acute renal failure is associated with a worsening outcome, particularly if occurring in critical illness and if severe enough to require renal replacement therapy, preventive measures should be part of appropriate management.

Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation

International Nuclear Information System (INIS)

Kovalchuk, Olga; Burke, Paula; Besplug, Jill; Slovack, Mark; Filkowski, Jody; Pogribny, Igor

2004-01-01

The biological and genetic effects of chronic low-dose radiation (LDR) exposure and its relationship to carcinogenesis have received a lot of attention in the recent years. For example, radiation-induced genome instability, which is thought to be a precursor of tumorogenesis, was shown to have a transgenerational nature. This indicates a possible involvement of epigenetic mechanisms in LDR-induced genome instability. Genomic DNA methylation is one of the most important epigenetic mechanisms. Existing data on radiation effects on DNA methylation patterns is limited, and no one has specifically studied the effects of the LDR. We report the first study of the effects of whole-body LDR exposure on global genome methylation in muscle and liver tissues of male and female mice. In parallel, we evaluated changes in promoter methylation and expression of the tumor suppressor gene p16 INKa and DNA repair gene O 6 -methylguanine-DNA methyltransferase (MGMT). We observed different patterns of radiation-induced global genome DNA methylation in the liver and muscle of exposed males and females. We also found sex and tissue-specific differences in p16 INKa promoter methylation upon LDR exposure. In male liver tissue, p16 INKa promoter methylation was more pronounced than in female tissue. In contrast, no significant radiation-induced changes in p16 INKa promoter methylation were noted in the muscle tissue of exposed males and females. Radiation also did not significantly affect methylation status of MGMT promoter. We also observed substantial sex differences in acute and chronic radiation-induced expression of p16 INKa and MGMT genes. Another important outcome of our study was the fact that chronic low-dose radiation exposure proved to be a more potent inducer of epigenetic effects than the acute exposure. This supports previous findings that chronic exposure leads to greater genome destabilization than acute exposure

CT findings of transfusional hemosiderosis in patients with chronic renal failure : clinical correlation

International Nuclear Information System (INIS)

Park, Tae Joon; Lee, Hae Kyung; Hong, Hyun Sook; Kim, Gun Woo; Kim, Hyung Hwan; Choi, Gyo Chang; Kwon, Kui Hyang; Choi, Deuk Lin

1997-01-01

The purpose of this study is to evaluate whether there is any correlation between the CT features of hemosiderosis and clinical findings in patients with chronic renal failure who have received multiple blood transfusion. Among chronic renal failure patients who had undergone long-tern dialysis and received multiple blood transfusions, CT findings in 16 cases in which increased liver attenuation was seen on images obtained for other purpose, were analyzed by three radiologic specialists. The attenuation values of liver, spleen and pancreas compared with that of back muscle were correlated with the amount and duration of transfusion, and blood ferritin level. There is no correlation between the CT features of hemosiderosis and clinical findings. In patients with chronic renal failure and no clinical symptoms, the status of iron overload was relatively easily detected on CT. Close observation of CT findings is thus thought to prevent significant permanent functional deformity of organs in patients with chronic renal failure who have received multiple blood transfusions. (author). 14 refs., 1 tab., 1 fig

Malaria induced acute renal failure: A single center experience

International Nuclear Information System (INIS)

KV Kanodia; AV Vanikar

2010-01-01

Malaria has protean clinical manifestations and renal complications, particularly acute renal failure that could be life threatening. To evaluate the incidence, clinical profile, ou come and predictors of mortality in patients with malarial acute renal failure, we retrospectively studied the last two years records of malaria induced acute renal failure in patients with peripheral smear positive for malarial parasites. One hundred (10.4%) (63 males, 37 females) malaria induced acute renal failure amongst 958 cases of acute renal failure were evaluated. Plasmodium (P). falciparum was reported in 85%, P. vivax in 2%, and both in 13% patients. The mean serum creatinine was 9.2 ± 4.2 mg%, and oligo/anuria was present in 82%; 78% of the patients required hemodialysis. Sixty four percent of the patients recovered completely, 10% incompletely, and 5% developed chronic kidney failure; mortality occurred in 21% of the patients. Low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coagulation, and high serum creatinine were the main predictors of mortality. We conclude that malaria is associated with acute renal failure, which occurs most commonly in plasmodium falciparum infected patients. Early diagnosis and prompt dialysis with supportive management can reduce morality and enhance recovery of renal function (Author).

Risk Factors, Clinical Presentation, and Outcomes in Overdose With Acetaminophen Alone or With Combination Products: Results From the Acute Liver Failure Study Group.

Science.gov (United States)

Serper, Marina; Wolf, Michael S; Parikh, Nikhil A; Tillman, Holly; Lee, William M; Ganger, Daniel R

2016-01-01

Acetaminophen (APAP) is the most common cause of acute liver failure (ALF) in the west. It is unknown if APAP overdose in combination with diphenhydramine or opioids confers a different clinical presentation or prognosis. Study objectives were to compare (1) baseline patient characteristics; (2) initial clinical presentation; and (3) clinical outcomes among patients with ALF due to APAP alone or in combination with diphenhydramine or opioids. We analyzed 666 cases of APAP-related liver failure using the Acute Liver Failure Study Group database from 1998 to 2012. The database contains detailed demographic, laboratory, and clinical outcome data, including hemodialysis, transplantation, and death and in-hospital complications such as arrhythmia and infection. The final sample included 666 patients with APAP liver injury. A total 30.3% of patients were overdosed with APAP alone, 14.1% with APAP/diphenhydramine, and 56.6% with APAP/opioids. Patients taking APAP with opioids were older, had more comorbidities, and were more likely to have unintentional overdose (all Ppresentation, 58% in the APAP/opioid group had advanced encephalopathy as compared with 43% with APAP alone (P=0.001) The APAP/diphenhydramine group presented with the highest serum aminotransferase levels, no differences in laboratory values were noted at 3 days postenrollment. No significant differences were observed in clinical outcomes among the groups. Most patients with APAP-induced ALF were taking APAP combination products. There were significant differences in patient characteristics and clinical presentation based on the type of product ingested, however, there were no differences noted in delayed hepatotoxicity or clinical outcomes.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

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Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Interactions of the heart and the liver

DEFF Research Database (Denmark)

Møller, Søren; Bernardi, Mauro

2013-01-01

There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting...... the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should...... be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic...

ACTION OF VITAMIN E ON EXPERIMENTAL SEVERE ACUTE LIVER FAILURE.

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Miguel, Fabiano Moraes; Schemitt, Elizângela Gonçalves; Colares, Josieli Raskopf; Hartmann, Renata Minuzzo; Morgan-Martins, Maria Isabel; Marroni, Norma Possa

2017-01-01

Severe Acute Liver Failure (ALF) is a life-threatening clinical syndrome characterized by hepatocyte necrosis, loss of hepatic architecture, and impairment of liver functions. One of the main causes of ALF is hepatotoxicity from chemical agents, which damage hepatocytes and result in increase of reactive oxygen species. The vitamin E isoform is the one with the strongest biological antioxidant activity. To evaluate the antioxidant effect of vitamin E in this ALF model. We used 56 rats (mean weight of 300 g) divided into eight groups, four groups assessed at 24 hours and 4 assessed at 48 hours after induction: control group (CO); Vitamin E (Vit. E); Thioacetamide (TAA) and Thioacetamide + Vitamina E (TAA+Vit.E). Rats were submitted to injections of thioacetamide (400 mg/kg i.p.) at baseline and 8 hours later. Vitamin E (100 mg/kg ip) was administered 30 minutes after the second dose of thioacetamide. The 48-hour group rats received two additional doses of vitamin E (24h and 36h). At 24h or 48 hours after the administration of the first dose of TAA, rats were weighed and anesthetized and their blood sampled for evaluation of liver integrity through enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver tissue was sampled for assessment of lipid peroxidation (LPO) by the technique TBARS, antioxidant enzymes SOD, CAT, GPx and GST activity, levels of the NO 2 /NO 3 and histology by H&E in two times. The results were expressed as mean ± standard deviation and statistically analyzed by ANOVA followed by Student-Newman-Keuls, with P E, we observed a reduction in liver enzymes AST (U/L) (101.32±19.45 in 24 hours and 97.85±29.65 in 48 hours) related to the TAA group (469.56± 0.69 in 24 hours and 598.23±55.45 in 48 hours) and ALT (U/L) (76.59±8.56 in 24 hours and 68.47±6.49 in 48 hours) compared to the TAA group (312.21±10.23 in 24 hours and 359.15±17.58 in 48 hours). There was a reduction of LPO (nmol/mg Prot) in the TAA+Vit.E group (0

Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir

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Rashmee Patil

2015-01-01

Full Text Available The fixed-dose combination of Efavirenz/Emtricitabine/Tenofovir is a first-line agent for the treatment of HIV; however few cases have reported hepatotoxicity associated with the drug. We report a case of Efavirenz/Emtricitabine/Tenofovir-associated hepatotoxicity presenting mainly with hepatocellular injury characterized by extremely elevated aminotransferase levels, which resolved without acute liver failure or need for liver transplant referral.

Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation

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Lu Li

2014-01-01

Full Text Available This study aimed to investigate the role of 5-lipoxygenase (5-LO in acute liver failure (ALF and changes in macrophage activation by blocking it. ALF was induced in rats by administration of D-galactosamine (D-GalN/lipopolysaccharide (LPS. Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor, 24 hr before D-GalN/LPS administration. After D-GalN/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT, aspartate transaminase (AST, total bilirubin (Tbil, and tumor necrosis factor- (TNF-α. Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8 hr after D-GalN/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF-α was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.

A multicentre randomized controlled trial of moderate hypothermia to prevent intracranial hypertension in acute liver failure

DEFF Research Database (Denmark)

Bernal, William; Murphy, Nicholas; Brown, Sarah

2016-01-01

BACKGROUND & AIMS: Animal models and human case series of acute liver failure (ALF) suggest moderate hypothermia (MH) to have protective effects against cerebral oedema (CO) development and intracranial hypertension (ICH). However, the optimum temperature for patient management is unknown...... by sealed envelope to targeted temperature management (TTM) groups of 34°C (MH) or 36°C (control) for a period of 72h. Investigators were not blinded to group assignment. The primary outcome was a sustained elevation in ICP >25mmHg, with secondary outcomes the occurrence of predefined serious adverse...

Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD)

Science.gov (United States)

McCurdy, BR

2012-01-01

Executive Summary In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions. After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses. The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html. Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive

Toluene inducing acute respiratory failure in a spray paint sniffer.

Science.gov (United States)

Peralta, Diego P; Chang, Aymara Y

2012-01-01

Toluene, formerly known as toluol, is an aromatic hydrocarbon that is widely used as an industrial feedstock and as a solvent. Like other solvents, toluene is sometimes also used as an inhalant drug for its intoxicating properties. It has potential to cause multiple effects in the body including death. I report a case of a 27-year-old male, chronic spray paint sniffer, who presented with severe generalized muscle weakness and developed acute respiratory failure requiring ventilatory support. Toluene toxicity was confirmed with measurement of hippuric acid of 8.0 g/L (normal <5.0 g/L). Acute respiratory failure is a rare complication of chronic toluene exposure that may be lethal if it is not recognized immediately. To our knowledge, this is the second case of acute respiratory failure due to toluene exposure.

Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls.

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Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

2015-01-01

The whole-body 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool.

Comparison of FDG-PET/CT images between chronic renal failure patients on hemodialysis and controls

Science.gov (United States)

Toriihara, Akira; Kitazume, Yoshio; Nishida, Hidenori; Kubota, Kazunori; Nakadate, Masashi; Tateishi, Ukihide

2015-01-01

The whole-body 2-deoxy-2-[18F]fluoro-D-glucose (FDG) distribution in chronic renal failure (CRF) patients on hemodialysis would be different from that in subjects with normal renal function, because they lack urinary FDG excretion and remain in a constant volume overload. We evaluated the difference in the physiological uptake pattern of FDG between chronic renal failure patients on hemodialysis and control subjects. The subjects for this retrospective study consisted of 24 chronic renal failure patients on hemodialysis (HD group) and 24 age- and sex-matched control subjects (NC group). Standardized uptake values normalized by the body weight (SUVbw), ideal body weight (SUVibw), lean body mass (SUVlbm), and body surface area (SUVbsa) in the cerebellum, lungs, liver, gluteal muscles and subcutaneous fat, spleen, thoracolumbar spine, thoracic and abdominal aorta, and right atrium were calculated in positron emission tomography/computed tomography (PET/CT) images. SUVbw in the gluteal muscles, subcutaneous fat, spleen and right atrium was significantly higher in the HD group as compared to that in the NC group (p chronic renal failure patients on hemodialysis show significantly higher physiological FDG uptake in the soft tissues, spleen and blood pool. PMID:25973341

Brain Aquaporin-4 in Experimental Acute Liver Failure

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Rama Rao, Kakulavarapu V.; Jayakumar, Arumugam R.; Tong, Xiaoying; Curtis, Kevin M.; Norenberg, Michael D.

2016-01-01

Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF. PMID:20720509

Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

NARCIS (Netherlands)

van Swelm, Rachel P. L.; Laarakkers, Coby M. M.; van der Kuur, Ellen C.; Morava-Kozicz, Eva; Wevers, Ron A.; Augustijn, Kevin D.; Touw, Daan J.; Sandel, Maro H.; Masereeuw, Rosalinde; Russel, Frans G. M.

2012-01-01

Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced

Nonalcoholic fatty liver disease

DEFF Research Database (Denmark)

Patrick-Melin, A J; Kalinski, M I; Kelly, K R

2009-01-01

Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage...... that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...

Quantitative multivoxel 1H MR spectroscopy of the brain in children with acute liver failure

International Nuclear Information System (INIS)

Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs; Lunsing, Roelineke J.; Spronsen, Francjan J. van; Verkade, Henkjan J.

2008-01-01

Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase). (orig.)

Activation of NMDA receptor by elevated homocysteine in chronic liver disease contributes to encephalopathy.

Science.gov (United States)

Choudhury, Sabanum; Borah, Anupom

2015-07-01

Liver diseases lead to a complex syndrome characterized by neurological, neuro-psychiatric and motor complications, called hepatic encephalopathy, which is prevalent in patients and animal models of acute, sub-chronic and chronic liver failure. Although alterations in GABAergic, glutamatergic, cholinergic and serotonergic neuronal functions have been implicated in HE, the molecular mechanisms that lead to HE in chronic liver disease (CLD) is least illustrated. Due to hepatocellular failure, levels of ammonia and homocysteine (Hcy), in addition to others, are found to increase in the brain as well as plasma. Hcy, a non-protein forming amino acid and an excitotoxin, activates ionotropic glutamate (n-methyl-d-aspartate; NMDA) receptors, and thereby leads to influx of Ca(2+) into neurons, which in turn activates several pathways that trigger oxidative stress, inflammation and apoptosis, collectively called excitotoxicity. Elevated levels of Hcy in the plasma and brain, a condition called Hyperhomocysteinemia (HHcy), and the resultant NMDA receptor-mediated excitotoxicity has been implicated in several diseases, including Parkinson's disease and Alzheimer's disease. Although, hyperammonemia has been shown to cause excitotoxicity, the role of HHcy in the development of behavioral and neurochemical alterations that occur in HE has not been illustrated yet. It is hypothesized that CLD-induced HHcy plays a major role in the development of HE through activation of NMDA receptors. It is further hypothesized that HHcy synergizes with hyperammonemia to activate NMDA receptor in the brain, and thereby cause oxidative stress, inflammation and apoptosis, and neuronal loss that leads to HE. Copyright © 2015 Elsevier Ltd. All rights reserved.

Changes of Treg and Th17 cells balance in the development of acute and chronic hepatitis B virus infection

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Xue-Song Liang

2012-05-01

Full Text Available Abstract Background Many studies suggest that in chronic hepatitis B virus (HBV infection regulate T (Treg cells and interlukin-17-producing T help cells (Th17 are mutually antagonistic in the immune response. This study is aimed to reveal the cell differentiation environment and the significance of Treg and Th17 balance in the development of acute and chronic HBV infection. Methods Ten patients with acute HBV infection (AHB and forty-eight patients with chronic HBV infection, including 12 asymptomatic HBV carriers (HBV carriers, 18 chronic hepatitis B patients (CHB and 18 acute-on-chronic HBV-related liver failure (ACHBLF were enrolled. Treg and Th17 cells differentiation related cytokine levels were detected by using ELISA. Flow cytometry was employed to count the Treg and Th17 frequency in peripheral blood. Results Compared to health controls both AHB and ACHBLF patients favoured Th17 cell differentiation, accompanied by a higher proportion of peripheral Th17 cells (P  Conclusions Th17 cells are involved in acute and chronic HBV infection, especially in AHB and ACHBLF. CHB and ACHBLF patients manifested obvious Treg/Th17 ratio imbalance, which might be linked to disease progression and the continuous HBV infection.

Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels

DEFF Research Database (Denmark)

Dao, Doan Y; Hynan, Linda S; Yuan, He-Jun

2012-01-01

Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements...... of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative...... immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P

Biomarker Guided Therapy in Chronic Heart Failure

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Bektas, Sema

2015-01-01

This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

Growth failure and nutrition considerations in chronic childhood wasting diseases.

Science.gov (United States)

Kyle, Ursula G; Shekerdemian, Lara S; Coss-Bu, Jorge A

2015-04-01

Growth failure is a common problem in many children with chronic diseases. This article is an overview of the most common causes of growth failure/growth retardation that affect children with a number of chronic diseases. We also briefly review the nutrition considerations and treatment goals. Growth failure is multifactorial in children with chronic conditions, including patients with cystic fibrosis, chronic kidney disease, chronic liver disease, congenital heart disease, human immunodeficiency virus, inflammatory bowel disease, short bowel syndrome, and muscular dystrophies. Important contributory factors to growth failure include increased energy needs, increased energy loss, malabsorption, decreased energy intake, anorexia, pain, vomiting, intestinal obstruction, and inflammatory cytokines. Various metabolic and pathologic abnormalities that are characteristic of chronic diseases further lead to significant malnutrition and growth failure. In addition to treating disease-specific abnormalities, treatment should address the energy and protein deficits, including vitamin and mineral supplements to correct deficiencies, correct metabolic and endocrinologic abnormalities, and include long-term monitoring of weight and growth. Individualized, age-appropriate nutrition intervention will minimize the malnutrition and growth failure seen in children with chronic diseases. © 2014 American Society for Parenteral and Enteral Nutrition.

Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

Directory of Open Access Journals (Sweden)

Alireza Hosseinnezhad

2011-05-01

Full Text Available Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL, thrombocytopenia (platelet count 74,000/UL, elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L and elevated creatine phosphokinase (CPK 5885 U/L. Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.

Acute renal failure in children

International Nuclear Information System (INIS)

Vergesslich, K.A.; Balzar, E.; Weninger, M.; Ponhold, W.; Sommer, G.; Wittich, G.R.; Vienna Univ.

1987-01-01

Acute renal failure (ARF) may be due to obstructive uropathy or renal parenchymal disease. Twenty-five children with acute renal failure secondary to renal parenchymal disease underwent ultrasonographic examination of the kidneys. Changes of renal size and cortical echogenicity were correlated with renal function. All patients presented with bilaterally enlarged kidneys with the exception in renal function resulted in normalization of renal size. With regard to cortical echogenicity two groups were formed. Group A comprised 11 patients whose kidneys had the same echogenicity as the liver, while in group B the kidneys were more echogenic (14 patients). Cortical echogenicity was always increased. Determination of creatinine levels showed a statistically significant difference between group A (3.32 mg% ± 1.40 S.D.) and group B (5.95 mg% ± 1.96 S.D.), p < 0.001. Changes in renal function were paralleled by rapid changes in renal size and cortical echogenicity. (orig.)

Effects of acute and chronic uremia on active cation transport in rat myocardium

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Druml, W.; Kelly, R.A.; England, B.K.; O' Hara, D.S.; Mitch, W.E. (Brigham and Women' s Hospital, Boston, MA (USA))

1990-12-01

As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

Diagnostic value of liver scintigraphy, computed tomography and ultrasonography of fatal hepatitis

International Nuclear Information System (INIS)

Komori, Hideshi; Hirasa, Masahiro; Ibuki, Yasuyoshi

1983-01-01

The purpose of this study was investigate the diagnostic value of liver scintigraphy, computed tomography (CT) and ultrasonography in acute hepatic failure, subacute hepatitis and acute hepatitis. By scintigraphy low uptake in the liver and high uptake in the spleen and bone marrow were observed in hepatic failure. However, uneven liver edge and heterogenous RI destribution were not corresponded to massive necrosis. In fulminant hepatitis, liver size and other findings were variable in patient by patient. But in subacute hepatitis, the findings were typical. The finding of left lobe swelling was observed in a half of patients with acute hepatic failure based on chronic hepatitis. Localized low density area by the CT was detected in most of the cases of subacute hepatitis, and acute hepatitis with submassive hepatic necrosis. But in fulminant hepatitis, that was rare. In these cases, irregular and strong lesion was also obsurved by ultrasonography. These findings by the CT and ultrasonography were corresponded to massive necrosis histrogically ultrasonography revealed narrowing of hepatic vein in fatal hepatitis. Localized low density area by the CT in subacute hepatitis was shown surrounding hepatic vein. We conclude that development of massine hepatic necrosis concern to secondary hepatic ischemia. (author)

Na+-K+ pump in chronic renal failure

International Nuclear Information System (INIS)

Deepak, K.; Kahn, T.

1987-01-01

This review summarizes the evidence for the defect in Na + -K + pump in chronic renal failure, considers the role of various factors in causing this defect, and discusses the clinical implications thereof. Intracellular Na is elevated in erythrocytes, leukocytes, and muscle cells from some patients with chronic renal failure (CRF). Recent evidence suggest that this elevation of cell Na may be, in large part, a consequence of decreased number of Na + -K + pump units per cell. Maintenance dialysis over a period of weeks ameliorates the defect in intracellular Na + , and this improvement is contemporaneous with an increase in the number of Na + -K + pump sites per cell. In erythrocytes with normal cell Na + , acute hemodialysis increases the rate of 22 Na + and 42 K + transport. Many factors such as the presence of retained toxic metabolite or circulating inhibitor in the uremic plasma, or biochemical changes produced by acute hemodialysis, may explain this finding. In cells with high cell Na + , the pump-mediated 42 K + transport is normalized at the expense of a raised cell Na + . The decreased muscle membrane potential in uremic subjects has been attributed to a decreased activity of Na + -K + pump. The authors discuss the role of hormonal abnormalities and circulating inhibitors, which may cause an acute inhibition of the pump and of other factors such as K + depletion, which may cause more chronic alterations. The implications of alteration of Na + and K + pump transport and raised cell Na + on other non-pump-mediated transport pathways are discussed. Raised cell Na + may be a marker for the adequacy of maintenance dialysis in patients with end-stage renal failure

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

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Howie Forbes

2010-03-01

Full Text Available Abstract Background The development of effective therapies for acute liver failure (ALF is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein. Control pigs (n = 4 survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8 +/- 5.9 vs 59 +/- 2.0 mmHg, increased cardiac output (7.26 +/- 1.86 vs 3.30 +/- 0.40 l/min and decreased systemic vascular resistance (8.48 +/- 2.75 vs 16.2 +/- 1.76 mPa/s/m3. Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636 +/- 95 vs 301 +/- 26.9 mPa/s/m3 observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23 +/- 0.05 vs 7.45 +/- 0.02 and prothrombin time (36 +/- 2 vs 8.9 +/- 0.3 seconds compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5 +/- 210 vs 42 +/- 8.14 coincided with a marked reduction in serum albumin (11.5 +/- 1.71 vs 25 +/- 1 g/dL in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2 +/- 36.5 vs 131.6 +/- 9.33 μmol/l. Liver histology revealed evidence of severe centrilobular necrosis

EVALUATION OF LIVER FAILURE STAGE IN CHILDREN

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G. V. Volynets

2013-01-01

Full Text Available Aim: to develop a system of evaluation of liver failure stage in children based on the International classification of functioning, disability and health (ICF. Patients and methods: based on the retrospective analysis of 14 biochemical markers, characterizing hepatic role in proteins, lipids and carbohydrates metabolism, of 115 children without liver diseases, 15 children who died of liver failure and 220 patients with various hepatic disorders, being followed-up in the SCCH of RAMS, a score system of evaluation of liver failure stage in children as an additional diagnostic tool was developed. Each of the biochemical markers was assessed according to the 5-point rating scale in dependence of its changes intensity. Results: the sum of points was considered to be a criterion of liver failure stage. According to the ICF recommendations, decrease of points on 0–4% (54–56 points corresponds with absence of liver failure; 5–24% (43–53 points — as mild dysfunction, 25–49% (29–42 points — as moderate; 50-95% (3–28 points — as severe; and 96–100% (0-2 points — as absolute failure. Conclusions: score system of evaluation of liver failure stage can be applied at any step of diagnostics and treatment of children of any age, due to independence of the used markers from the age. It can be used in assessment of the severity of disorder in dynamics, in determination of the prognosis and as criterion of indications to liver transplantation, as well as during medico-social examination.

Artificial liver support: a real step forward.

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Saliba, F; Samuel, D

2015-02-01

Since the early 1960s, several authors reported on the use of some experimental artificial liver devices in order to support patients with either acute liver failure (ALF) or end-stage chronic liver disease. In the 1980s, liver transplantation became an established real treatment replacing the whole liver with a major survival benefit. In the 1990s, the concept of albumin dialysis appeared as a new revolution in the concept of dialysis with the great capacity of removal of toxins, drugs and molecules strongly bound to albumin. Currently, three artificial liver support devices are available: The MARS®, the Prometheus® and the SPAD®. The most widely studied and used system is the MARS® that uses albumin dialysis to replace the detoxification function of the liver. MARS has shown in several uncontrolled studies and few randomized studies an improvement in the patient condition in terms of clinical symptoms (hepatic encephalopathy, pruritus, jaundice) and in liver and kidney biological parameters bringing these patients safely to liver transplantation. MARS® has shown for some patients with ALF (mainly paracetamol intoxication) an improvement of spontaneous or transplant free survival. The use of MARS in acute on chronic liver failure (ACLF) require further studies based on strict definition of the syndrome. The use of albumin dialysis technique, require the performance of multiple sessions of treatment or even (in situations of ALF) a continuous treatment in order to improve spontaneous recovery or bridge these patients to liver transplantation. The performance of these systems would need further improvement. Large randomized trials are still needed in both patients with ALF and ACLF to establish the indications, the timing and the real place of liver support therapies. Meanwhile, early use of these devices in patients with ALF and ACLF could be considered as an additional tool among others in the management of these patients in specialized liver units.

Quantitative multivoxel {sup 1}H MR spectroscopy of the brain in children with acute liver failure

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Sijens, Paul E.; Alkefaji, Heyder; Meiners, Linda C.; Oudkerk, Matthijs [University Medical Center Groningen and University of Groningen, Department of Radiology, Beatrix Children' s Hospital, Groningen (Netherlands); Lunsing, Roelineke J. [University Medical Center Groningen and University of Groningen, Department of Child Neurology, Beatrix Children' s Hospital, Groningen (Netherlands); Spronsen, Francjan J. van; Verkade, Henkjan J. [University Medical Center Groningen and University of Groningen, Department of Pediatrics, Beatrix Children' s Hospital, Groningen (Netherlands)

2008-11-15

Acute liver failure (ALF)-related encephalopathy was previously characterized by MR spectroscopy of single voxels containing both grey and white matter brain tissue. Quantitative multivoxel MRS was used here to compare grey and white matter brain tissue concentrations of glutamate/glutamine (Glx) and lactate in ALF and associate the results with other liver function parameters. Five pediatric patients with ALF-related encephalopathy and five controls, examined after successful liver transplantation, were examined by brain MRI/MRS. ALF patients had higher Glx and lactate concentrations in brain white matter than controls (Glx + 125%: P < 0.01; lactate + 33%, P < 0.05) and higher Glx in grey matter (Glx + 125%: P < 0.01). Within the group of ALF patients positive correlations were found between grey or white matter lactate concentration and serum ammonia (P < 0.05), and negative correlations between grey or white matter Glx and venous pH (P < 0.001). This is the first study presenting evidence of high Glx levels in both white and grey matter brain tissue in ALF-related encephalopathy. The elevations in CNS Glx and lactate concentrations appear to relate to hepatic detoxification (ammonia, venous pH), rather than to liver parenchymal integrity (aspartate aminotransferase, alanine aminotransferase) or biliary cholestasis (bilirubin, {gamma}-glutamyl transpeptidase, alkaline phosphatase). (orig.)

THE DIAGNOSIS OF LIVER ALLOGRAFT ACUTE REJECTION IN LIVER BIOPSIES

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L. V. Shkalova

2011-01-01

Full Text Available We performed histological examination of 80 liver allograft biopsies, the diagnosis of acute rejection was proved in 34 cases. Histological changes in liver biopsies in different grades of acute rejection were estimated according to Banff classification 1995, 1997 and were compared with current literature data. The article deals with the question of morphological value of grading acute rejection on early and late, also we analyze changes in treat- ment tactics after morphological verification of liver allograft acute rejection. 

Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.

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Chastre, Anne; Bélanger, Mireille; Nguyen, Bich N; Butterworth, Roger F

2014-03-01

Acute liver failure (ALF) is frequently complicated by infection leading to precipitation of central nervous system complications such as hepatic encephalopathy (HE) and increased mortality. There is evidence to suggest that when infection occurs in ALF patients, the resulting pro-inflammatory mechanisms may be amplified that could, in turn, have a major impact on blood-brain barrier (BBB) function. The aim of this study was to investigate the role of endotoxemia on the progression of encephalopathy in relation to BBB permeability during ALF. Adult male C57-BL6 mice with ALF resulting from azoxymethane-induced toxic liver injury were administered trace amounts of the endotoxin component lipopolysaccharide (LPS). Effects on the magnitude of the systemic inflammatory response, liver pathology and BBB integrity were measured as a function of progression of HE, defined as time to loss of corneal reflex (coma). Lipopolysaccharide caused additional two- to seven-fold (P liver pathology and associated increases of circulating transaminases as well as increased hyperammonaemia consistent with a further loss of viable hepatocytes. LPS treatment of ALF mice led to a rapid precipitation of hepatic coma and the BBB became permeable to the 25-kDa protein immunoglobulin G (IgG). This extravasation of IgG was accompanied by ignificant up-regulation of matrix metalloproteinase-9 (MMP-9), an endopeptidase known to modulate opening of the BBB in a wide range of neurological disorders. These findings represent the first direct evidence of inflammation-related BBB permeability changes in ALF. © 2013 John Wiley & Sons A/S. Publishing by John Wiley & Sons Ltd.

Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation.

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Cheong, Jaeyoun; Galanko, Joseph A; Arora, Sumant; Cabezas, Joaquin; Ndugga, Nambi J; Lucey, Michael R; Hayashi, Paul H; Barritt, Alfred Sidney; Bataller, Ramon

2017-02-01

Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P renal failure was less marked in patients with ALD (HR = 1.31, P renal failure had better long-term prognosis than non-ALD patients. Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen): the multinational case-population SALT study.

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Gulmez, Sinem Ezgi; Larrey, Dominique; Pageaux, Georges-Philippe; Lignot, Severine; Lassalle, Régis; Jové, Jérémy; Gatta, Angelo; McCormick, P Aiden; Metselaar, Harold J; Monteiro, Estela; Thorburn, Douglas; Bernal, William; Zouboulis-Vafiadis, Irene; de Vries, Corinne; Perez-Gutthann, Susana; Sturkenboom, Miriam; Bénichou, Jacques; Montastruc, Jean-Louis; Horsmans, Yves; Salvo, Francesco; Hamoud, Fatima; Micon, Sophie; Droz-Perroteau, Cécile; Blin, Patrick; Moore, Nicholas

2013-02-01

Most NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain. The aim of the study was to estimate population event rates for NSAID-associated ALFT METHODS: This was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY). In the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose). Event rates per MTY were 1.59 (95 % CI 1.1-2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2-3.9) for ibuprofen, 1.9 (95 % CI 0.8-3.7) for nimesulide, 1.6 (95 % CI 0.6-3.4) for diclofenac and 1.6 (95 % CI 0.3-4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6-4.1) without overdoses and 7.8 (95 % CI 6.8-9.0) including overdoses. ALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.

Hemoadsorption of high-mobility-group box 1 using a porous polymethylmethacrylate fiber in a swine acute liver failure model.

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Amemiya, Ryusuke; Shinoda, Masahiro; Yamada, Masayuki; Ueno, Yoshiyuki; Shimada, Kaoru; Fujieda, Hiroaki; Yagi, Hiroshi; Mizota, Takamasa; Nishiyama, Ryo; Oshima, Go; Yamada, Shingo; Matsubara, Kentaro; Abe, Yuta; Hibi, Taizo; Kitago, Minoru; Obara, Hideaki; Itano, Osamu; Kitagawa, Yuko

2018-04-01

High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber. First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model. Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column. The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.

Acute renal failure after rifampicin

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Adriana Weinberg

1984-12-01

Full Text Available A patient with miliary tuberculosis and a chronic urogenital focus is described, who had a borderline renal function at diagnosis and developed overt renal failure upon daily treatment with rifampin (RMP, isoniazid (INH and ethambutol (EMB. This is the first Brazilian report of BMP induced renal damage. A renal biopsy taken on the third day of oliguria showed recent tubular necrosis with acute interstitial inflammation and granuloma formation. The aspect of the granulomatous lesion hightly suggested drug etiology because of the lack of palisading, high incidence of neutrophils and absence of facid-fast bacilli. This is the first presentation of an acute granulomatous interstitial nephritis probably due to RMP. Furthermore the pathogenesis of the renal damage caused by tuberculosis and RMP are discussed.

Necrostatin-1 protects against reactive oxygen species (ROS-induced hepatotoxicity in acetaminophen-induced acute liver failure

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Kenji Takemoto

2014-01-01

Full Text Available Excessive acetaminophen (APAP use is one of the most common causes of acute liver failure. Various types of cell death in the damaged liver are linked to APAP-induced hepatotoxicity, and, of these, necrotic cell death of hepatocytes has been shown to be involved in disease pathogenesis. Until recently, necrosis was commonly considered to be a random and unregulated form of cell death; however, recent studies have identified a previously unknown form of programmed necrosis called receptor-interacting protein kinase (RIPK-dependent necrosis (or necroptosis, which is controlled by the kinases RIPK1 and RIPK3. Although RIPK-dependent necrosis has been implicated in a variety of disease states, including atherosclerosis, myocardial organ damage, stroke, ischemia–reperfusion injury, pancreatitis, and inflammatory bowel disease. However its involvement in APAP-induced hepatocyte necrosis remains elusive. Here, we showed that RIPK1 phosphorylation, which is a hallmark of RIPK-dependent necrosis, was induced by APAP, and the expression pattern of RIPK1 and RIPK3 in the liver overlapped with that of CYP2E1, whose activity around the central vein area has been demonstrated to be critical for the development of APAP-induced hepatic injury. Moreover, a RIPK1 inhibitor ameliorated APAP-induced hepatotoxicity in an animal model, which was underscored by significant suppression of the release of hepatic enzymes and cytokine expression levels. RIPK1 inhibition decreased reactive oxygen species levels produced in APAP-injured hepatocytes, whereas CYP2E1 expression and the depletion rate of total glutathione were unaffected. Of note, RIPK1 inhibition also conferred resistance to oxidative stress in hepatocytes. These data collectively demonstrated a RIPK-dependent necrotic mechanism operates in the APAP-injured liver and inhibition of this pathway may be beneficial for APAP-induced fulminant hepatic failure.

Case Characterization, Clinical Features and Risk Factors in Drug-Induced Liver Injury

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Aida Ortega-Alonso

2016-05-01

Full Text Available Idiosyncratic drug-induced liver injury (DILI caused by xenobiotics (drugs, herbals and dietary supplements presents with a range of both phenotypes and severity, from acute hepatitis indistinguishable of viral hepatitis to autoimmune syndromes, steatosis or rare chronic vascular syndromes, and from asymptomatic liver test abnormalities to acute liver failure. DILI pathogenesis is complex, depending on the interaction of drug physicochemical properties and host factors. The awareness of risk factors for DILI is arising from the analysis of large databases of DILI cases included in Registries and Consortia networks around the world. These networks are also enabling in-depth phenotyping with the identification of predictors for severe outcome, including acute liver failure and mortality/liver transplantation. Genome wide association studies taking advantage of these large cohorts have identified several alleles from the major histocompatibility complex system indicating a fundamental role of the adaptive immune system in DILI pathogenesis. Correct case definition and characterization is crucial for appropriate phenotyping, which in turn will strengthen sample collection for genotypic and future biomarkers studies.

Insuficiência Hepática Aguda da Gravidez Experiência Clínica com Sete Casos Acute Liver Failure of Pregnancy ¾ Clinical Experience with Seven Cases

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Marcelo Perosa

2001-04-01

Full Text Available Objetivos: avaliar a dificuldade diagnóstica, o tratamento e seu resultado em casos de insuficiência hepática aguda da gravidez. Métodos: sete pacientes com insuficiência hepática aguda da gravidez admitidas em nosso Serviço nos últimos quatro anos foram estudadas com ênfase nos sintomas presentes, achados laboratoriais, curso clínico, complicações maternas e sobrevida fetal. Resultados: a média de idade foi de 25,8 anos (sendo duas primigestas com idade gestacional média de 30,1. Destas, quatro receberam diagnóstico final de esteatose hepática aguda da gravidez e três de colestase intra-hepática da gravidez. Os principais sinais e sintomas encontrados foram: anorexia, náusea, dor abdominal, icterícia e encefalopatia. Ocorreu morte materna em dois casos: uma paciente por falência hepática enquanto aguardava órgão para transplante e outra por falência hepática, coagulopatia grave e choque hemorrágico após biópsia hepática. Uma paciente com esteatose hepática aguda evoluiu para cronicidade e encontra-se viva um ano após transplante hepático. Nos quatro casos restantes houve completa remissão do quadro com as medidas de suporte, associadas à interrupção da gravidez. As mortalidades materna e fetal foram, respectivamente, 28,6% e 57,1%. Conclusões: concluiu-se, nesta experiência inicial, que a insuficiência hepática aguda da gravidez constitui evento clínico grave, de elevada mortalidade materno-fetal, e que seu pronto reconhecimento e encaminhamento para centros terciários especializados em fígado, além da imediata interrupção da gestação, são fatores decisivos para o sucesso do tratamento.Purpose: to evaluate the diagnostic difficulties, treatment and outcome in cases of acute liver failure of pregnancy. Methods: seven patients with acute liver failure of pregnancy, managed during the past 4 years, were studied with emphasis on presenting symptoms, laboratory findings, clinical course, maternal

Acute liver failure in a term neonate after repeated paracetamol administration

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Fabio Bucaretchi

2014-03-01

Full Text Available Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L, hypoglycemia (18mg/dL, increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL after receiving oral paracetamol (10mg/kg/dose every 4 hours for three consecutive days (total dose around 180mg/kg; serum concentration 36-48 hours after the last dose of 77µg/ mL. Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. Comments: The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione - which provides greater resistance after overdoses -, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.

Acute Renal Failure Induced by Chinese Herbal Medication in Nigeria

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Effiong Ekong Akpan

2015-01-01

Full Text Available Traditional herbal medicine is a global phenomenon especially in the resource poor economy where only the very rich can access orthodox care. These herbal products are associated with complications such as acute renal failure and liver damage with a high incidence of mortalities and morbidities. Acute renal failure from the use of herbal remedies is said to account for about 30–35% of all cases of acute renal failure in Africa. Most of the herbal medications are not usually identified, but some common preparation often used in Nigeria includes “holy water” green water leaves, bark of Mangifera indica (mango, shoot of Anacardium occidentale (cashew, Carica papaya (paw-paw leaves, lime water, Solanum erianthum (Potato tree, and Azadirachta indica (Neem trees. We report a rare case of a young man who developed acute renal failure two days after ingestion of Chinese herb for “body cleansing” and general wellbeing. He had 4 sessions of haemodialysis and recovered kidney function fully after 18 days of admission.

Hypokalemic Rhabdomyolysis Induced Acute Renal Failure As a Presentation of Coeliac Disease

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Funda Sarı

2012-03-01

Full Text Available Adult coeliac disease commonly presents without classical symptoms as chronic diarrhea and weight loss. We describe the case of a 31-year-old woman with persistent life-threatening hypokalemia, acute renal failure, and acute quadriplegia due to diarrhea that had continued for one month. Although there are cases of coeliac disease diagnosed with hypokalemic rhabdomyolysis in the literature, none of the cases developed acute renal failure. This is the first case in the literature diagnosed with acute renal failure due to hypokalemic rhabdomyolysis as a presentation of coeliac disease. In acute renal failure cases that present with hypokalemic rhabdomyolysis due to severe diarrhea, coeliac disease should be considered as a differential diagnosis despite the negative antigliadin IgA antibody.

HE4 Serum Levels Are Associated with Heart Failure Severity in Patients With Chronic Heart Failure

NARCIS (Netherlands)

Piek, Arnold; Meijers, Wouter C.; Schroten, Nicolas F.; Gansevoort, Ron T.; de Boer, Rudolf A.; Sillje, Herman H. W.

Background: The novel biomarker human epididymis protein 4 (HE4) shows prognostic value in acute heart failure (HF) patients. We measured HE4 levels in patients with chronic heart failure (CHF) and correlated them to HF severity, kidney function, and HF biomarkers, and determined its predictive

Peak hyperammonemia and atypical acute liver failure: The eruption of an urea cycle disorder during hyperemesis gravidarum.

Science.gov (United States)

Weiss, Nicolas; Mochel, Fanny; Rudler, Marika; Demeret, Sophie; Lebray, Pascal; Conti, Filomena; Galanaud, Damien; Ottolenghi, Chris; Bonnefont, Jean-Paul; Dommergues, Marc; Bernuau, Jacques; Thabut, Dominique

2017-09-20

Inborn urea cycle disorders are under-recognised metabolic causes of hyperammonemia in adults. A 28-year-old primigravida, seven weeks pregnant, affected by hyperemesis gravidarum developed acute liver injury (ALI) and then acute liver failure (ALF) in less than 48 h. Because the patient developed atypical features, especially mildly elevated aminotransferases contrasting with very high blood ammonia levels (281 μmol/L), concomitant with normal serum creatinine, an inborn error of metabolism was suspected. We performed emergency metabolic analyses, stopped all protein intake and started with intravenous (i.v.) high caloric intake, nitrogen scavenger drugs and haemodialysis. The neurological and hepatic status of the patient quickly improved together with normalisation of her ammonemia levels. High plasma glutamine and urinary orotic acid, alongside low plasma arginine, citrulline and ornithine were suggestive of an ornithine transcarbamylase deficiency, later confirmed by molecular analyses. Foetal sex was female, as determined by foetal DNA analysis in maternal blood, and foetal development was unremarkable throughout the pregnancy. Delivery was induced at 39 weeks with a close monitoring of ammonemia levels and i.v. perfusion of carbohydrates and lipids during labour and immediately post-partum to avoid hypercatabolism. Delivery was uneventful and the patient delivered a healthy female baby. Urea cycle disorders should be contemplated in non-jaundiced patients with ALI or ALF, severe hyperammonemia and normal serum creatinine regardless of serum aminotransferase levels. The prompt recognition of this rare condition and the rapid initiation of adequate metabolic therapy are mandatory to prevent irreversible neurological sequelae and to avoid liver transplantation. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Role of autoimmunity in nonviral chronic liver disease.

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Amarapurkar, D N; Amarapurkar, A D

2000-11-01

To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50

Aetiology, maternal and foetal outcome in 60 cases of obstetrical acute renal failure

International Nuclear Information System (INIS)

Khalil, M.A.M.; Azhar, A.; Anwar, N.

2009-01-01

Acute renal failure is a serious complication in pregnancy. Not only does it result in significant maternal morbidity and mortality but also results in significant number of foetal loss. Although incidence of obstetrical acute renal failure has decreased in developed countries but still it is one of the major health problem of developing nations. The objective of this study was to study aetiology, maternal and foetal outcome in obstetrical acute renal failure. This study was conducted at Department of Nephrology, Khyber Teaching Hospital, Peshawar from August 2006 to December 2007. It was a descriptive, case series study. Female patients with pregnancy and acute renal failure, irrespective of age, were included in the study. Patients were thoroughly examined and baseline urea, creatinine, serum electrolytes, peripheral smear, prothrombin time, partial thromboplastin time, fibrinogen degradation products, renal and obstetrical ultrasound were performed on each patient and 24-hr urinary protein and bacterial culture sensitivity on blood, urine or vaginal swabs were done in selected patients. Foetal and maternal outcome were recorded. Data were analysed using SPSS. A total of 60 patients were included in the study. Mean age of the patients was 29 +- 5.4 years and duration of gestation was 33 +- 4.9 weeks. Mean gravidity was 4 +- 2.2. Sixteen patients (26.66%) were treated conservatively while 44 (73.33%) required dialysis. Postpartum haemorrhage was present in 14 (23.33%), postpartum haemorrhage and disseminated intravascular coagulation (DIC) in 11 (18.33%), eclampsia-preeclampsia in 8 (13.33%), antepartum haemorrhage in 8 (13.33%), antepartum haemorrhage with DIC in 6 (10%), DIC alone in 4 (6.66%), obstructed labour in 3 (5%), septic abortion in 3 (3.33%), HELLP (haemolysis elevated liver enzyme and low platelet) in 2 (3.33%), urinary tract infection with sepsis in 1 (1.66%) and puerperal sepsis in 1 (1.66%). Foetal loss was 40 (66.66%). Maternal mortality was 9 (15

Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands.

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Cremer, Jeroen; Hofstraat, Sanne H I; van Heiningen, Francoise; Veldhuijzen, Irene K; van Benthem, Birgit H B; Benschop, Kimberley S M

2018-05-24

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P < .01). Substitutions within the MHR were found in 8.5% of the acute strains and 18.6% of the chronic strains. Specific MHR substitutions described to have an impact on vaccine/immune escape and/or HBsAg test failure were found among 4.1% of the acute strains and 7.0% of the chronic strains. In conclusion, we show a high variation of HBsAg among acute and chronic hepatitis B virus-infected cases in The Netherlands, in particular among those infected with GtD, and compare, for the first time, variation in frequencies between acute and chronic cases. Additional studies on the impact of these variations on vaccination and test failure need to be conducted, as well as whether HBsAg false-negative variants have been missed. © 2018 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

Prognosis for recovery of function in acute renal failure

International Nuclear Information System (INIS)

Harwood, T.H. Jr.; Hiesterman, D.R.; Robinson, R.G.; Cross, D.E.; Whittier, F.C.; Diederich, D.A.; Grantham, J.J.

1976-01-01

Twenty-four survivors of acute, nonobstructive, nonnephritic renal failure had a renal scan using iodohippurate sodium I 131 performed early in the acute illness. Scans were judged according to whether the renal images were prominent, faint, or absent during the first 30 minutes after intravenous injection of 100 to 250 microcuries of iodohippurate sodium I 131. All ten patients with prominent renal images attained life-sustaining renal function with an average postrecovery creatinine clearance of 80 ml/min. Of the seven patients with faint renal images, six recovered life-sustaining renal function (average creatinine clearance of 39 ml/min), and one required chronic hemodialysis. Seven patients had no renal image initially; four recovered life-sustaining renal function with an average creatinine clearance of 25 ml/min; three required chronic hemodialysis. We conclude that, for patients with acute renal failure, the appearance of the renal image obtained using this substance is an important indicator of renal viability and of the likelihood for functional recovery

Chronic hepatitis E virus infection in liver transplant recipients

NARCIS (Netherlands)

Haagsma, Elizabeth B.; van den Berg, Arie P.; Porte, Robert J.; Benne, Cornelis A.; Vennema, Harry; Reimerink, Johan H. J.; Koopmans, Marion P. G.

Hepatitis E virus (HEV) infection is known to run a self-limiting course. Sporadic cases of acute hepatitis due to infection with HEV genotype 3, present in pig populations, are increasingly recognized. Zoonotic transmission seems infrequent. The entity of unexplained chronic hepatitis after liver

Nucleic acid metabolism in human chronic liver disease by in vitro autoradiography. I. Altered RNA metabolism

Energy Technology Data Exchange (ETDEWEB)

Yoshida, T [Okayama Univ. (Japan). School of Medicine

1976-06-01

Biopsy liver specimens from healthy control subjects (N=5) and patients with various liver diseases (N=43) were investigated by the vitro autoradiography. The Leevy technique of adding /sup 3/H-5-uridine (/sup 3/H-U) to the incubation medium was used. In healthy subjects labeling with /sup 3/H-U was observed mostly in hepatocytes and Kupffer cells and the frequency of /sup 3/H-U labeled cells was extremely high. Higher frequencies of labeled fibrocytes and endothelial cells of the blood vessel were found in acute hepatitis than in control subjects. In the active form of chronic hepatitis, significantly higher counts of labeled fibrocytes, ductular cells and lymphocytes were found. In patients with acute hepatitis or the inactive form of chronic hepatitis, only a few labeled lymphocytes were observed. Larger numbers of labeled fibrocytes were found in patients with chronic hepatitis with sublobular hepatic necrosis, than in patients with the active form of chronic hepatitis. In cirrhotic livers, marked increases of labeled ductular cells, fibrocytes and bile duct cells were found. No significant labeling differences were observed in the hepatocytes of various liver diseases. In chronic hepatitis with sublobular hepatic necrosis, a more significant decrease of labeled Kupffer cells was present than in the inactive form of chronic hepatitis. Labeled ductular cells and fibrocytes increased as the disease progressed from acute hepatitis to liver cirrhosis. The labeling index of rosettes cells was intermediate between the hepatocytes and ductular cells. The ratio of labeled parenchymal to non-parenchymal cells decreased proportionally from chronic hepatitis to cirrhosis.

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

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Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

2016-12-01

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

THE SUCCESSFUL TREATMENT OF A PERIPHERAL VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION FOR SEVERE ACUTE RESPIRATORY FAILURE IN THE EARLY PERIOD AFTER ADULT LIVER TRANSPLANTATION

Directory of Open Access Journals (Sweden)

V. N. Poptsov

2014-01-01

Full Text Available Aim: of our clinical study was to present own experience of veno-venous extracorporeal membrane oxygenation (VV ECMO for the treatment of an adult patient (female, 28 yrs, 150 cm, 35 kg with acute respiratory distress syndrome (ARDS in the early period after liver transplantation against satisfactory liver graft function. Materials and methods. Double-lumen cannula 22 F was placed percutaneously in the right internal jugular vein. The ext- racorporeal contour reduced in length and the polymethylpeptene oxygenator (priming volume 175 ml were also. Results. In 1 hour after the beginning of VV ECMO, we registered the noted improvement of arterial blood gas and acid-base balance (regress of respiratory acidosis, improvement of arterial oxygenation which allowed us to use the «protective» mode of mechanical ventilation. Improvement of gas exchange and regress of clinical and radiological manifestations of ARDS allowed for VV ECMO weaning and decannulation on day 7. The patient was discharged from ICU and then from our Centre to a homestay respectively on the 9th and 16th day after VV ECMO weaning with the satisfactory liver graft and lungs function. Conclusion. VV ECMO can be successfully applied to correct the life-threatening acute respiratory failure in the early period after liver transplantation. 

Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure

DEFF Research Database (Denmark)

Lewinter, Christian; Bland, John M; Crouch, Simon

2014-01-01

AIMS: Aspirin and statins are established therapies for acute myocardial infarction (MI), but their benefits in patients with chronic heart failure (HF) remain elusive. We investigated the impact of aspirin and statins on long-term survival in patients hospitalized with acute MI complicated by HF...

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

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Payancé, Audrey; Scotto, Béatrice; Perarnau, Jean-Marc; de Muret, Anne; Bacq, Yannick

2013-11-01

Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

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Dan Xu

2014-04-01

Full Text Available Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU] developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers.Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers.FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology

Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

Science.gov (United States)

Xu, Dan; Nishimura, Toshi; Nishimura, Sachiko; Zhang, Haili; Zheng, Ming; Guo, Ying-Ying; Masek, Marylin; Michie, Sara A; Glenn, Jeffrey; Peltz, Gary

2014-04-01

Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers. Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers. FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology studies could improve

Splenic CD11clowCD45RBhigh dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure

Science.gov (United States)

Zhang, Sai-Nan; Yang, Nai-Bin; Ni, Shun-Lan; Dong, Jin-Zhong; Shi, Chun-Wei; Li, Shan-Shan; Zhang, Sheng-Guo; Tang, Xin-Yue; Lu, Ming-Qin

2016-01-01

Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF. PMID:27625297

Can paracetamol (acetaminophen) be administered to patients with liver impairment?

Science.gov (United States)

Hayward, Kelly L; Powell, Elizabeth E; Irvine, Katharine M; Martin, Jennifer H

2016-02-01

Although 60 years have passed since it became widely available on the therapeutic market, paracetamol dosage in patients with liver disease remains a controversial subject. Fulminant hepatic failure has been a well documented consequence of paracetamol overdose since its introduction, while short and long term use have both been associated with elevation of liver transaminases, a surrogate marker for acute liver injury. From these reports it has been assumed that paracetamol use should be restricted or the dosage reduced in patients with chronic liver disease. We review the factors that have been purported to increase risk of hepatocellular injury from paracetamol and the pharmacokinetic alterations in different pathologies of chronic liver disease which may affect this risk. We postulate that inadvertent under-dosing may result in concentrations too low to enable efficacy. Specific research to improve the evidence base for prescribing paracetamol in patients with different aetiologies of chronic liver disease is needed. © 2015 The British Pharmacological Society.

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

International Nuclear Information System (INIS)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

2016-01-01

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure.

Science.gov (United States)

Garcia-Martinez, Rita; Andreola, Fausto; Mehta, Gautam; Poulton, Katie; Oria, Marc; Jover, Maria; Soeda, Junpei; Macnaughtan, Jane; De Chiara, Francesco; Habtesion, Abeba; Mookerjee, Rajeshwar P; Davies, Nathan; Jalan, Rajiv

2015-04-01

Liver failure is characterized by endothelial dysfunction, which results in hemodynamic disturbances leading to renal failure. Albumin infusion improves hemodynamics and prevents renal dysfunction in advance liver failure. These effects are only partly explained by the oncotic properties of albumin. This study was designed to test the hypothesis that albumin exerts its beneficial effects by stabilising endothelial function. In vivo: systemic hemodynamics, renal function, markers of endothelial dysfunction (ADMA) and inflammation were studied in analbuminaemic and Sprague-Dawley rats, 6-weeks after sham/bile duct ligation surgery. In vitro: human umbilical vein endothelial cells were stimulated with LPS with or without albumin. We studied protein expression and gene expression of adhesion molecules, intracellular reactive oxygen species, and cell stress markers. Compared to controls, analbuminaemic rats had significantly greater hemodynamic deterioration after bile duct ligation, resulting in worse renal function and shorter survival. This was associated with significantly greater plasma renin activity, worse endothelial function, and disturbed inflammatory response. In vitro studies showed that albumin was actively taken up by endothelial cells. Incubation of albumin pre-treated endothelial cells with LPS was associated with significantly less activation compared with untreated cells, decreased intracellular reactive oxygen species, and markers of cell stress. These results show, for the first time, that absence of albumin is characterised by worse systemic hemodynamics, renal function and higher mortality in a rodent model of chronic liver failure and illustrates the important non-oncotic properties of albumin in protecting against endothelial dysfunction. Copyright © 2015. Published by Elsevier B.V.

Diabetes mellitus and renal involvement in chronic viral liver disease.

Science.gov (United States)

Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

2015-01-01

Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with HCC and none of them presented diabetes mellitus. Our study revealed that there is a

January 2015 Phoenix pulmonary journal club: noninvasive ventilation in acute respiratory failure

Directory of Open Access Journals (Sweden)

Mathew M

2015-01-01

Full Text Available No abstract available. Article truncated after 150 words. Noninvasive positive pressure ventilation has expanded its role in the treatment of both chronic and acute respiratory failure. Its initial use in conditions such as obstructive sleep apnea, neuromuscular disease and tracheobronchomalacia, have been shown to improve quality of life and reduce mortality. Over the past 20 years studies have looked at using noninvasive ventilation in the management of acute respiratory failure from pulmonary edema, asthma and COPD exacerbations. During this month's journal club we reviewed 3 articles evaluating the efficacy of noninvasive ventilation in acute respiratory failure. Gupta D, Nath A, Agarwal R, Behera D. A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma. Respir Care. 2010;55(5:536-43. [PubMed] This was a small unblinded randomized controlled trial (RCT looking at the efficacy using noninvasive ventilation (NIV in acute asthma. A total of 53 patients were included and divided into 2 groups of 28 patients ...

Predicting Failure in Early Acute Prosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention: External Validation of the KLIC Score.

Science.gov (United States)

Löwik, Claudia A M; Jutte, Paul C; Tornero, Eduard; Ploegmakers, Joris J W; Knobben, Bas A S; de Vries, Astrid J; Zijlstra, Wierd P; Dijkstra, Baukje; Soriano, Alex; Wouthuyzen-Bakker, Marjan

2018-03-27

Debridement, antibiotics, and implant retention (DAIR) is a widely used treatment modality for early acute prosthetic joint infection (PJI). A preoperative risk score was previously designed for predicting DAIR failure, consisting of chronic renal failure (K), liver cirrhosis (L), index surgery (I), cemented prosthesis (C), and C-reactive protein >115 mg/L (KLIC). The aim of this study was to validate the KLIC score in an external cohort. We retrospectively evaluated patients with early acute PJI treated with DAIR between 2006 and 2016 in 3 Dutch hospitals. Early acute PJI was defined as infection-related death within 60 days after debridement. A total of 386 patients were included. Failure occurred in 148 patients (38.3%). Patients with KLIC scores of ≤2, 2.5-3.5, 4-5, 5.5-6.5, and ≥7 had failure rates of 27.9%, 37.1%, 49.3%, 54.5%, and 85.7%, respectively (P < .001). The receiver-operating characteristic curve showed an area under the curve of 0.64 (95% confidence interval 0.59-0.69). A KLIC score higher than 6 points showed a specificity of 97.9%. The KLIC score is a relatively good preoperative risk score for DAIR failure in patients with early acute PJI and appears to be most useful in clinical practice for patients with low or high KLIC scores. Copyright © 2018 Elsevier Inc. All rights reserved.

Amiodarone-Induced Liver Injury and Cirrhosis.

Science.gov (United States)

Buggey, Jonathan; Kappus, Matthew; Lagoo, Anand S; Brady, Carla W

2015-01-01

We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone-induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC.

Liver scintigraphy of fulminant hepatitis

International Nuclear Information System (INIS)

Tamaki, Nagara; Ishihara, Takashi; Mori, Toru

1980-01-01

The liver scintigraphies of five patients with fulminant hepatitis were examined. Scintiphotos using sup(99m)Tc-phytate were taken within two weeks after the onset. Scintiphotos of 12 normal subjects, 11 cases with acute hepatitis, 17 cases with liver cirrhosis were served as control. Their scintiphotos showed reduction of the size, well-maintained uptake, mostly homogenous RI distribution, and no left lobe enlargement, which could differentiate them from the chronic liver dysfunction. In one of the cases chronological changes in liver scintigraphy were observed. The size of the liver was reduced progressively until the 16th day and re-enlarged at the 30th day and thereafter. Three indices [S/W, (R + L)/W, and L/R] were calculated. S: area of liver, R or L: longitudinal length of the right or left lobe, W: body width. Relative size of the liver expressed by S/W or (R + L)/W showed significant reduction in fulminant hepatitis compared with acute hepatitis. However, they were not different significantly from those of normal subjects. Except for liver cirrhosis, L/R (left lobe swelling index) did not show significant differences among fulminant hepatitis, normal subjects, and acute hepatitis. These indices were also useful in follow-up study of the liver scintigraphy. The liver scintigraphy in the early phase of fulminant hepatitis seems to reflect the degree of massive hepatic necrosis. It is also useful to differentiate chronic hepatic failure. Apparant reduction in scintigraphical liver size seems to suggest poor prognosis, however, it should also kept in mind that the size of the liver in this condition might change quite rapidly and greatly. (author)

The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations.

Directory of Open Access Journals (Sweden)

Dong Ji

Full Text Available To investigate the frequency and determinants of liver stiffness measurement (LSM failure by means of FibroScan in "real-life" Chinese patients.A total of 38,464 "real-life" Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC, alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m and M probe (for adults were used. LSM failure defined as zero valid shots (unsuccessful LSM, or the ratio of the interquartile range to the median of 10 measurements (IQR/M greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM.LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464, among them, there were 958 cases (2.49% with unsuccessful LSM, and 328 patients (0.85% with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI greater than 30 kg/m(2, female sex, age greater than 50 years, intercostal spaces (IS less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001.The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.

Two cases of combined liver-kidney transplantation

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

Objectives To report the clinical experiences of srmultaneous hepatorenal transplantation. Methods We performed simultaneous hepatorenal transplantation in one patient with liver cirrhosis of hepatitis B and uremia of chronic nephritis on February 1,1999 and one patient with liver cirrhosis of hepatitis B complicated by hepatorenal syndrome on March 12, 1999.The donors were heart arrest cases. Rapid multiple organ harvesting techniques and UW solution infusion in situ were used. Liver and kidney transplantation were orthotopic and ordinary methods, respectively. Immunosuppressive drugs consisted of cyclosporine, Cellcept, ALG and sortstso steroids. Lamividine was used os day 50 and day 40 postoparation, respectively. Results Both transplanted organs rapidly achieved normal function postoperation and the patients recovered well but suffered mild kidney rejection day 110 postopemtion in No 1 patient. In No 2 patient, acute renal function failure, mental symptoms, muscle spasm,cerebral artery thrombosis, inhalation poeumonia and chronic liver graft rejection ensured sequentially but were controlled.The patients have survived for more than nine and eight months, respectively, with normal life quality. Conclusions Combined hepatorenal transplant is a radical treatment method for liver and kidney function failure and requires more comprehensive techniques than isolated single organ transplantation.Preventing the recurrence of hepatitis B by oral lamividine may be a kdy to long-term survival.

Chronic Liver Diseases in Children: Clinical Profile and Histology.

Science.gov (United States)

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

Galectin-3: a new biomarker for the diagnosis, analysis and prognosis of acute and chronic heart failure.

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Hrynchyshyn, Nataliya; Jourdain, Patrick; Desnos, Michel; Diebold, Benoit; Funck, François

2013-10-01

Heart failure constitutes an important medical, social and economic problem. The prevalence of heart failure is estimated as 2-3% of the adult population and increases with age, despite the scientific progress of the past decade, especially the emergence of natriuretic peptides, which have been widely used as reliable markers for diagnostic and prognostic evaluation. Identification of new reliable markers for diagnosis, analysis, prognosis of mortality and prevention of hospitalization is still necessary. Galectin-3 is a soluble β-galactoside-binding protein secreted by activated macrophages. Its main action is to bind to and activate the fibroblasts that form collagen and scar tissue, leading to progressive cardiac fibrosis. Numerous experimental studies have shown the important role of galectin-3 in cardiac remodelling due to fibrosis, independent of the fibrosis aetiology. Galectin-3 is significantly increased in chronic heart failure (acute or non-acute onset), independent of aetiology. Some clinical studies have confirmed the predictive value of galectin-3 in all-cause mortality in patients with heart failure. In our review, we aim to analyse the role of galectin-3 in the development of heart failure, its value in screening and clinical decision making and its possible predictive application in follow-up as a "routine" test in an addition to established biomarkers, such as B-type natriuretic peptide and N-terminal prohormone of B-type natriuretic peptide. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chronic heart failure

OpenAIRE

Hopper, Ingrid; Easton, Kellie

2017-01-01

1. The common symptoms and signs of chronic heart failure are dyspnoea, ankle swelling, raised jugular venous pressure and basal crepitations. Other conditions may be confused with chronic heart failure, including dependent oedema or oedema due to renal or hepatic disease. Shortness of breath may be due to respiratory disease or severe anaemia. Heart failure secondary to lung disease (cor pulmonale) should be distinguished from congestive cardiac failure. Heart failure may also present with l...

Lipopolysaccharide-induced acute renal failure in conscious rats

DEFF Research Database (Denmark)

Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

2002-01-01

In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure

DEFF Research Database (Denmark)

Khamri, Wafa; Abeles, Robin D; Hou, Tie Zheng

2017-01-01

, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood...... mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF......BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86...

Renal function and acute heart failure outcome.

Science.gov (United States)

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

[Liver and sport].

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Watelet, J

2008-11-01

The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

NARCIS (Netherlands)

Gonzalez Ponce, Herson Antonio; Consolacion Martinez-Saldana, Maria; Rosa Rincon-Sanchez, Ana; Teresa Sumaya-Martinez, Maria; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juarez, Fernando

2016-01-01

Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients

Oral and Dental Health in Children with Chronic Liver Disease in the ...

African Journals Online (AJOL)

2017-10-26

Oct 26, 2017 ... period in children with chronic liver disease (CLD) to prevent late complications. Therefore, we aimed .... After informed consent from the parents, a questionnaire ..... smoking, postnatal infections, anemia, and failure to thrive.

Cerebral Hemodynamics Patterns by Transcranial Doppler in Patients With Acute Liver Failure.

Science.gov (United States)

Abdo, A; Pérez-Bernal, J; Hinojosa, R; Porras, F; Castellanos, R; Gómez, F; Gutiérrez, J; Castellanos, A; Leal, G; Espinosa, N; Gómez-Bravo, M

2015-11-01

About half of patients with acute liver failure (ALF) show clinical signs of cerebral edema and intracranial hypertension. Neuroimaging diagnostics and electroencephalography have poor correlation with intracranial pressure measurement. The objective of this study was to characterize the cerebral hemodynamics patterns with transcranial Doppler (TCD) sonography in patients with ALF. We studied 21 patients diagnosed with ALF, admitted to the intensive care unit (ICU) at the Centro de Investigaciones Médico Quirúrgicas of Cuba. All of these patients had a TCD performed on arrival at ICU, evaluating the following: systolic (SV), diastolic (DV), and medium (MV) flows velocities and pulsatility index (PI) in right middle cerebral artery (RMCA) via temporal windows. The sonographic patterns of cerebral hemodynamics were as follows: low-flow, 12 patients (57.1%); high resistance, 5 patients (23.8%); and hyperemic, 4 patients (19%). Patients who died while waiting had lower MV RMCA (56.1 vs 58.1 cm/s) and higher PI (1.71 vs 1.41) than patients who could undergo transplantation (P = .800 and P = .787, respectively). In patients diagnosed with ALF admitted to the ICU the predominating cerebral hemodynamic pattern was low-flow with resistance increase. The TCD was shown to be a useful tool in the initial evaluation for prognosis and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

[Hepatic cell transplantation: a new therapy in liver diseases].

Science.gov (United States)

Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

2010-07-01

Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

Risk factors for postoperative liver failure after hepatectomy for hepatocellular carcinoma.

Science.gov (United States)

Maeda, Yoshitaka; Nishida, Minekatsu; Takao, Takashi; Mori, Naohide; Tamesa, Takao; Tangoku, Akira; Oka, Masaaki

2004-01-01

Selection of patients for hepatectomy for hepatocellular carcinoma conventionally has been based upon Child-Pugh grading. However, postoperative liver failure after hepatectomy is a major cause of hospital mortality. A new predictor of postoperative liver failure is required. The objective of this study was to identify risk factors for postoperative liver failure after hepatectomy. Perioperative risk factors for liver failure after hepatectomy were analyzed in 112 patients with hepatocellular carcinoma Eight of these patients died of liver failure. Stepwise multivariate logistic regression was performed to investigate significant independent factors among 17 variables, including the serum alkaline phosphatase ratio (ALPR) on the first day after hepatectomy. ALPR was calculated as the postoperative ALP level divided by the ALP level before surgery. Significant risk factors of postoperative liver failure were ALPR on postoperative day 1 (ALPR1), sex, operative blood loss, and operative procedure. As an indicator of liver failure, the diagnostic accuracy of the ALPR1 was 93.7% when the ALPR was less than 0.4 on the first postoperative day. The ALPR and the serum total bilirubin concentration after hepatectomy were uncorrelated. ALPR1 is a useful predictor of liver failure after hepatectomy.

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

Energy Technology Data Exchange (ETDEWEB)

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Uehara, Takeki; Kato, Yuki [Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka (Japan); Kono, Hiroshi [First Department of Surgery, University of Yamanashi, Yamanashi (Japan); Bataller, Ramon [Division of Gastroenterology & Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (United States); Rusyn, Ivan, E-mail: irusyn@tamu.edu [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States)

2016-11-01

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.

Acute kidney failure

Science.gov (United States)

... Renal failure - acute; ARF; Kidney injury - acute Images Kidney anatomy References Devarajan P. Biomarkers for assessment of renal function during acute kidney injury. In: Alpern RJ, Moe OW, Caplan M, ...

Serum Lipoprotein (a Levels in Chronic Renal Failure and Liver Cirrhosis Patients. Relationship with Atherosclerosis

Directory of Open Access Journals (Sweden)

Essam Mady

1999-01-01

Full Text Available This study was carried out to investigate the relationship between lipoprotein (a levels and the development of atherosclerosis in chronic renal failure (CRF patients with the possible role of the liver. Serum Lp (a levels were measured in samples from 20 CRF patients on hemodialysis (HD, 20 liver cirrhosis (LC patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Renal function (blood urea nitrogen (BUN and creatinine, hepatic function (transaminases (ALT and AST, alkaline phosphatase (ALP and total bilirubin investigations and serum cholesterol were carried out for all the subjects enrolled in this study. Serum Lp (a concentration in CRF patients without LC was 87.25 ± 6.17 mg/dl, which was significantly higher than all the investigated groups (P < 0.001. Lp(a concentration in patients with both CRF and LC was 24.65 ± 1.98 mg/dl, which was not significantly different from the controls, but was significantly higher than that in the subjects with LC only (P < 0.001 where the latter group had significantly low Lp (a values (11.1 ± 0.99 relative to all the other groups (P < 0.001. Lp (a correlated positively with cholesterol in all groups except the LC subjects, but did not correlate with age, or renal function in both CRF groups.

Biomarkers in acute heart failure.

Science.gov (United States)

Mallick, Aditi; Januzzi, James L

2015-06-01

The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure

DEFF Research Database (Denmark)

Bañares, Rafael; Nevens, Frederik; Larsen, Fin Stolze

2013-01-01

sessions were scheduled. The main endpoint was 28-day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event...

An unusual cause of acute renal failure in sickle cell disease

Science.gov (United States)

Rockx, Marie-Antoinette; Gibson, Ian W.; Reslerova, Martina

2009-01-01

A young female with sickle cell disease was treated for biopsy-proven IgA nephropathy. Serum creatinine levels resolved to normal range, but a year later, she presented with oedema, hypertension and acute renal failure. A repeat renal biopsy showed acute-on-chronic thrombotic microangiopathy (TMA). We suggest that circulating microparticles could be a pathophysiological link between sickle cell disease and the development of renal TMA. This case emphasizes the importance of a further biopsy for acutely declining renal function, even when a definite diagnosis has been made from a previous biopsy. PMID:25949348

Acute Alcoholic Hepatitis: Therapy.

Science.gov (United States)

Phillips, Paulina K; Lucey, Michael R

2016-08-01

Alcoholic hepatitis (AH) causes great morbidity and mortality in the United States and throughout the world. Advances in therapy have proven difficult. In part, this reflects challenges in diagnosis, including the distinction between AH and acute-on-chronic liver failure. Liver biopsy is the best method to clarify the cause in circumstances whereby conflicting clinical data confound the diagnosis. All treatment of AH begins with abstinence from alcohol. All patients with AH should be given sufficient nutrition. Prednisolone has become the principal agent for treating patients with severe AH. Copyright © 2016 Elsevier Inc. All rights reserved.

Current Understanding of Acute Bovine Liver Disease in Australia

Directory of Open Access Journals (Sweden)

Elizabeth Read

2016-12-01

Full Text Available Acute bovine liver disease (ABLD is a hepatotoxicity principally of cattle which occurs in southern regions of Australia. Severely affected animals undergo rapid clinical progression with mortalities often occurring prior to the recognition of clinical signs. Less severely affected animals develop photosensitization and a proportion can develop liver failure. The characteristic histopathological lesion in acute fatal cases is severe, with acute necrosis of periportal hepatocytes with hemorrhage into the necrotic areas. Currently there are a small number of toxins that are known to cause periportal necrosis in cattle, although none of these have so far been linked to ABLD. Furthermore, ABLD has frequently been associated with the presence of rough dog’s tail grass (Cynosurus echinatus and Drechslera spp. fungi in the pasture system, but it is currently unknown if these are etiological factors. Much of the knowledge about ABLD is contained within case reports, with very little experimental research investigating the specific cause(s. This review provides an overview of the current and most recently published knowledge of ABLD. It also draws on wider research and unpublished reports to suggest possible fungi and mycotoxins that may give rise to ABLD.

Impact of Nitrate Use on Survival in Acute Heart Failure: A Propensity-Matched Analysis.

Science.gov (United States)

Ho, Edwin C; Parker, John D; Austin, Peter C; Tu, Jack V; Wang, Xuesong; Lee, Douglas S

2016-02-12

There is limited evidence that the use of nitrates in acute decompensated heart failure early after presentation to a hospital can improve clinical outcomes. We aimed to determine whether early nitrate exposure is associated with improved survival in a large retrospective cohort study. We examined 11 078 acute decompensated heart failure patients who presented to emergency departments in Ontario, Canada, between 2004 and 2007, in the Enhanced Feedback For Effective Cardiac Treatment and the Emergency Heart failure Mortality Risk Grade studies. In propensity-matched analyses, we examined the effect of nitrate administration in the acute emergency department setting for its impact on death at 7, 30, and 365 days. In propensity-matched analyses, we found no difference in survival between those who received nitrates in the emergency department and the non-nitrate comparator group. Hazard ratios for mortality were 0.76 (95% CI; 0.51, 1.12) over 7 days, 0.97 (95% CI; 0.77, 1.21) over 30 days, and 0.91 (95% CI; 0.82, 1.02) over 1 year of follow-up. There was no significant difference in survival or hospital length of stay between nitrate and non-nitrate controls in extended follow-up. There was also no significant effect of nitrates in subgroups stratified by presence of chest pain, troponin elevation, chronic nitrate use, and known coronary artery disease. In acute decompensated heart failure, use of nitrates acutely in the emergency department setting was not associated with improvement in short-term or near-term survival. Our study does not support generalized use of nitrates when the primary goal of therapy is to reduce mortality. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effect of chronic renal failure with metabolic acidosis on alanine metabolism in isolated liver cells

NARCIS (Netherlands)

Cano, N.; Sturm, J. M.; Meijer, A. J.; El-Mir, M. Y.; Novaretti, R.; Reynier, J. P.; Leverve, X. M.

2004-01-01

Background Et aims: Decreased ureagenesis and gluconeogenesis from atanine have been reported during chronic renal failure in rat. This study addressed the respective roles of plasma-membrane transport and intracellular metabolism in these abnormalities of alanine pathways. Methods: In hepatocytes

Chronic Liver Disease : Value of Sonographic Study of the Liver Surface

International Nuclear Information System (INIS)

Chung, Jae Joon; Kim, Myeong Jin; Han, Kwang Hyub; Chon, Chae Yoon; Yoo, Hyung Sik; Lee, Jong Tae; Kim, Ki Whang

1995-01-01

To evaluate the diagnostic value of sonographic irregularities of liver surface in the differentiation of chronic liver disease. Fifty-eight patients with either chronic hepatitis or early stage of liver cirrhosis were examined with 5 MHz linear array transducer by observing the liver surface.We compared the sonographic findings with peritoneoscopic and pathologic findings. Thirty-five patients with smooth surface showed variable pathological results, including chronic active and persistent hepatitis, inactive hepatitis and alcoholic hepatitis without any evidence of cirrhosis. Nineteen patients with micronodules mostly revealed chronic active hepatitis and cirrhosis. All 4 patients with macronodules were proved pathologically ascirrhosis. High resolution ultrasonography(HRUS) showed smooth liver surface in 35 patients(60.3%),micronodular surface in l9(32.8%), and macronodular surface in 4 (6.9%). Twenty-one cases(60.0%) among 35 patients with smooth surface were peritoneoscopically normal and 12 cases(34.3%) showed dimpling surface. However among l9 patients with micronodular surface, only 5 cases(26.3%) showed micronodular surface on peritoneoscopy. while 8 cases(42.l%) showed nracronodular surface and 6 cases(3l.6%) dimpling surface. All 4 patients with macronodulesrevealed peritoneoscopically nracronodular surface. Observation of liver surface by HRUS was useful in predicting the progression of chronic hepatitis to cirrhosis. However, it was not helpful in the differentiation between normal liver and chronic hepatrtrs

MARS treatment in posthepatectomy liver failure

NARCIS (Netherlands)

van de Kerkhove, Maarten-Paul; de Jong, Koert P.; Rijken, Arjen M.; de Pont, Anne-Cornélie J. M.; van Gulik, Thomas M.

2003-01-01

Posthepatactomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver

Acute Hepatic Failure in a Dog after Xylitol Ingestion.

Science.gov (United States)

Schmid, Renee D; Hovda, Lynn R

2016-06-01

Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

Beyond pulmonary edema: diagnostic, risk stratification, and treatment challenges of acute heart failure management in the emergency department.

Science.gov (United States)

Collins, Sean; Storrow, Alan B; Kirk, J Douglas; Pang, Peter S; Diercks, Deborah B; Gheorghiade, Mihai

2008-01-01

The majority of heart failure hospitalizations in the United States originate in the emergency department (ED). Current strategies for acute heart failure syndromes have largely been tailored after chronic heart failure guidelines and care. Prospective ED-based acute heart failure syndrome trials are lacking, and current guidelines for disposition are based on either little or no evidence. As a result, the majority of ED acute heart failure syndrome patients are admitted to the hospital. Recent registry data suggest there is a significant amount of heterogeneity in acute heart failure syndrome ED presentations, and diagnostics and therapeutics may need to be individualized to the urgency of the presentation, underlying pathophysiology, and acute hemodynamic characteristics. A paradigm shift is necessary in acute heart failure syndrome guidelines and research: prospective trials need to focus on diagnostic, therapeutic, and risk-stratification algorithms that rely on readily available ED data, focusing on outcomes more proximate to the ED visit (5 days). Intermediate outcomes (30 days) are more dependent on inpatient and outpatient care and patient behavior than ED management decisions. Without these changes, the burden of acute heart failure syndrome care is unlikely to change. This article proposes such a paradigm shift in acute heart failure syndrome care and discusses areas of further research that are necessary to promote this change in approach.

Several issues regarding evaluation of renal injury and renal insufficiency in patients with liver disease

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HAO Kunyan

2016-07-01

Full Text Available In patients with liver disease such as viral hepatitis and liver cirrhosis, renal injury and renal insufficiency can be generally classified as acute kidney injury (AKI, chronic kidney disease, and acute-on-chronic nephropathy. AKI can be classified as stage 1 (risk stage, stage 2 (injury stage, and stage 3 (failure stage. Traditionally hepatorenal syndrome is classified as types Ⅰ and Ⅱ, and in recent years, type Ⅲ hepatorenal syndrome with organic renal injury has been proposed. Hepatorenal disorder(HRD is used to describe any renal disease which occurs in patients with liver cirrhosis. At present, sensitive and accurate biochemical parameters used to evaluate renal function in patients with liver disease in clinical practice include estimated glomerular filtration rate, increase in serum creatinine within unit time, and serum cystatin C level, and urinary microalbumin level also plays an important role in the early diagnosis of nephropathy. Causes of liver disease, severity, complications including infection, nutritional status, therapeutic drugs, and underlying nephropathy may be associated with renal injury and renal insufficiency in patients with liver disease and should be differentiated.

Definition of ACLF and inclusion criteria for extra-hepatic organ failure.

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Wang, Xiaojing; Sarin, Shiv Kumar; Ning, Qin

2015-07-01

A prominent characteristic of ACLF is rapid hepatic disease progression with subsequent extra-hepatic organ failure, manifesting as either hepatic coma or hepatorenal syndrome, which is associated with a high mortality rate in a short time. The APASL definition mainly emphasizes recognizing patients with hepatic failure. These patients may subsequently develop extra-hepatic multisystem organ failure leading to high mortality. It is therefore worthwhile to identify the short interim period between the development of liver failure and the onset of extra-hepatic organ failure, the potential therapeutic 'golden window.' Interventions during this period may prevent the development of complications and eventually change the course of the illness. Organ failure is suggested to be a central component of ACLF and may behave differently from chronic decompensated liver disease. Clear and practical criteria for the inclusion of organ failure are urgently needed so that patients with these life-threatening complications can be treated in a timely and appropriate manner. Recent studies suggested that the scoring systems evaluating organ failure [acute physiology, age and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) scores] work better than those addressing the severity of liver disease [Child-Pugh and model of end-stage liver disease (MELD) scores] in ACLF. However, a key problem remains that the former scoring systems are reflective of organ failure and not predictive, thus limiting their value as an early indication for intervention.

Effect of vitamin D supplementation on chronic liver disease: systematic literature review

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Hooman Mosannen Mozaffari

2017-01-01

Full Text Available Introduction: It is long known that vitamin D deficiency was common in patients with liver disease, but little is known on the therapeutic effects of vitamin D, especially in patients with chronic liver disease. In this study, we aimed to systematically review the literatures and study the evidences in which the effects of vitamin D supplementation had been investigated on the severity of chronic liver disease or liver cirrhosis.Methods: A systematic literature search was performed by using the following key terms “vitamin D supplementation” and “chronic liver disease” in the PubMed, Scopus and Google scholar to find relevant articles. After collecting the eligible documents, data were extracted and described based on the purpose of this review.Result: Of total 196 articles found, only 7 relevant documents with 518 studied patients were included. The results of this study showed that the levels of 25(OH D were considerably lower in patients with chronic liver disease. Findings showed that vitamin D supplementation can rise up the mean serum level of 25(OH D in patients with severe vitamin D deficiency, especially patients with liver cirrhosis.Conclusion:The results of this review showed that vitamin D deficiency is associated with the severity of liver disease and may have prognostic value in the assessment of liver disease. Also, it was shown that vitamin D supplementation may be helpful for the treatment of liver disease at least in certain groups of patients.