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Sample records for acute-on-chronic liver failure

  1. Acute-on-chronic Liver Failure.

    Science.gov (United States)

    Sarin, Shiv Kumar; Choudhury, Ashok

    2016-12-01

    Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.

  2. Predisposing Factors in Acute-on-Chronic Liver Failure

    DEFF Research Database (Denmark)

    Trebicka, J.

    2016-01-01

    Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality in patients with chronic liver disease. The definition of ACLF has been addressed recently in many publications, and despite regional differences the number and severity of organ failures are decisive...... factors might predispose in one setting and might be the precipitating event in another, thus rendering the generalization of predisposing factors difficult. However, genetic factors, lifestyle, past medical history, aging, latent chronic infections, and the severity of the liver disease and portal...

  3. Update on acute-on-chronic liver failure.

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    Solé, Cristina; Solà, Elsa

    2018-01-01

    Acute-on-chronic liver failure (ACLF) is a recently defined syndrome characterised by acute decompensation of chronic liver disease, associated with organ failures and high mortality. ACLF is a common condition and may affect up to 30% of patients admitted to hospital for cirrhosis complications. Bacterial infections, alcoholism and reactivation of viral hepatitis are the most common precipitating factors in ACLF, although in up to 40% of patients no precipitating factor can be identified. Although the pathophysiology of ACLF is not completely understood, the presence of an excessive inflammatory response appears to play a key role. There is no specific treatment for patients with ACLF and management is based on organ support and liver transplantation. New treatment strategies based on liver support systems and immunomodulatory treatments are being evaluated but existing data are still limited. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  4. Hepatic encephalopathy in acute-on-chronic liver failure.

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    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  5. Research advances in acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    JIANG Chengzhi

    2015-09-01

    Full Text Available Acute-on-chronic liver failure (ACLF is a severe liver disease with high mortality in China. Early diagnosis could reduce complications and improve the survival rate. In the present review, the definition, etiology, and pathogenesis related to inflammatory response, reactive oxygen species, and metabolism are reviewed. Also, the new approaches to the treatment of ACLF and prognostic factors are summarized. Generally, the development of ACLF is considered to be life-threatening for patients. Therefore, a universal definition of ACLF should be proposed, which would provide good guidance and standard for the clinical diagnosis and treatment of ACLF in China. In addition, the risk factors for ACLF in patients with chronic liver diseases need to be determined by prospective studies.

  6. Acute-on-chronic liver failure: an update

    Science.gov (United States)

    Solà, Elsa; Moreau, Richard; Ginès, Pere

    2017-01-01

    Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%–50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care. PMID:28053053

  7. Acute-on-chronic liver failure: an update.

    Science.gov (United States)

    Hernaez, Ruben; Solà, Elsa; Moreau, Richard; Ginès, Pere

    2017-03-01

    Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care. 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/.

  8. Overview on acute-on-chronic liver failure.

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    Zhang, Jing; Gao, Shan; Duan, Zhongping; Hu, Ke-Qin

    2016-03-01

    Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.

  9. Immunotherapy for acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    HAN Ying

    2017-09-01

    Full Text Available Inflammatory response and immune dysfunction play important roles in the progression of acute-on-chronic liver failure (ACLF and may lead to systemic inflammatory response syndrome. Excessive inflammatory and immune response may result in increased susceptibility to infection and finally lead to multiple organ dysfunction syndrome (MODS. Elimination of liver injury and correction of immune dysfunction can prevent sepsis and/or MODS and improve patients′ survival. Up to now, immunotherapy for ACLF has not been recommended in related guidelines. However, as an important pathophysiological change of ACLF and a key event closely associated with incidence rate and mortality rate, persistent activation of hepatic and systemic inflammatory response and immune cell dysfunction urges us to consider immunoregulatory treatment, in order to block and reverse disease progression. This article introduces potential immunoregulatory drugs for the treatment of ACLF, including albumin, glucocorticoids, granulocyte colony-stimulating factor, artificial liver support system, and mesenchymal stem cell transplantation, and discusses some promising targets for immunotherapy.

  10. 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

    Acute-on-chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189...

  11. Research progress in prognostic markers of acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    ZHANG Yuling

    2014-10-01

    Full Text Available Acute-on-chronic liver failure (ACLF is a clinical entity encompassing an acute deterioration of liver function and failure of one or more organs, which results in high short-term mortality rate. In recent years, a number of novel prognostic markers of ACLF have emerged and provided a basis for the treatment and prognostic evaluation of ACLF. Researches on both commonly used and novel makers for prognosis of ACLF are reviewed in order to improve the existing prognostic evaluation system and to provide a basis for the treatment and prognostic evaluation of ACLF.

  12. Reviewing the diagnostic criteria for acute-on-chronic liver failure.

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    Jindal, Ankur; Rastogi, Archana; Sarin, Shiv Kumar

    2016-12-01

    For over 20 years, acute-on-chronic liver failure (ACLF) has taken multiple definitions and/or classifications. The definition outlines the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific time frame. Early and accurate diagnosis is essential as this inflammation of the liver may tilt the balance of liver destruction and regeneration adversely. Various factors such as superadded systemic sepsis, liver reserve, cause of primary chronic liver disease, state of immune system or the state of gut microbial flora might determine the ultimate prognosis. Areas covered: To date, there has been no universally accepted definition of ACLF. In this review, we discuss the strengths and weaknesses, controversies and basis for early identification and accurate diagnosis of ACLF. PubMed and Google scholar database searches were conducted, search terms included 'acute on chronic liver failure,' 'ACLF,' and 'diagnostic criteria.' Expert commentary: With recent advances in the management of advanced cirrhosis, research will gradually shift towards ACLF in the near future, focusing on the pathogenesis, new treatment options and improving survival. Once we improve understanding of this syndrome, newer definitions will evolve, thereby enabling earlier diagnosis and novel therapeutic avenues.

  13. Removal of bile acids by two different extracorporeal liver support systems in acute-on-chronic liver failure

    NARCIS (Netherlands)

    Stadlbauer, Vanessa; Krisper, Peter; Beuers, Ulrich; Haditsch, Bernd; Schneditz, Daniel; Jung, Aleksandra; Putz-Bankuti, Csilla; Holzer, Herwig; Trauner, Michael; Stauber, Rudolf E.

    2007-01-01

    Acute-on-chronic liver failure (ACLF) is accompanied by marked intrahepatic cholestasis leading to accumulation of cytotoxic bile acids. Extracorporeal liver support systems efficiently remove bile acids, but their effect on bile acid composition in ACLF is unknown. The aim of the present study was

  14. The liver protective effect of methylprednisolone on a new experimental acute-on-chronic liver failure model in rats.

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    Hu, Chao; Shen, Shiqiang; Zhang, Aimin; Ren, Bo; Lin, Fusheng

    2014-10-01

    Acute-on-chronic liver failure is a severe, life-threatening entity and the comprehension of this disease is incomplete. Currently, a reasonable surgical model of acute-on-chronic liver failure is still lacking. The aim of this study was to establish a new model of acute-on-chronic liver failure in rats and to investigate the protective effects of methylprednisolone on this model. An obstructive jaundice model in rats was established. Two weeks later, the animals were subjected to a choledochoduodenostomy and a reduced-size hepatic ischaemia/reperfusion injury. Animals were randomly divided into a control group, a methylprednisolone injected via the tail vein group and a methylprednisolone injected via the portal vein group. The survival rates and serum levels of alanine transaminase, aspartate aminotransferase, total bilirubin, tumour necrosis factor alpha, and interferon gamma of the rats were measured and the pathological changes in liver tissues were observed. The survival rate was significantly improved in the methylprednisolone treatment groups. Serum levels of the biochemical indexes were the lowest in the portal vein injection group. Liver tissues under microscopy presented severe pathological injury in the control group. This model could be useful for further research into acute-on-chronic liver failure and methylprednisolone may be a potential therapeutic agent for this disease. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  15. Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure.

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    Maiwall, Rakhi; Sarin, Shiv Kumar; Kumar, Suman; Jain, Priyanka; Kumar, Guresh; Bhadoria, Ajeet Singh; Moreau, Richard; Kedarisetty, Chandan Kumar; Abbas, Zaigham; Amarapurkar, Deepak; Bhardwaj, Ankit; Bihari, Chhagan; Butt, Amna Subhan; Chan, Albert; Chawla, Yogesh Kumar; Chowdhury, Ashok; Dhiman, RadhaKrishan; Dokmeci, Abdul Kadir; Ghazinyan, Hasmik; Hamid, Saeed Sadiq; Kim, Dong Joon; Komolmit, Piyawat; Lau, George K; Lee, Guan Huei; Lesmana, Laurentius A; Jamwal, Kapil; Mamun-Al-Mahtab; Mathur, Rajendra Prasad; Nayak, Suman Lata; Ning, Qin; Pamecha, Viniyendra; Alcantara-Payawal, Diana; Rastogi, Archana; Rahman, Salimur; Rela, Mohamed; Saraswat, Vivek A; Shah, Samir; Shiha, Gamal; Sharma, Barjesh Chander; Sharma, Manoj Kumar; Sharma, Kapil; Tan, Soek Siam; Chandel, Shivendra Singh; Vashishtha, Chitranshu; Wani, Zeeshan A; Yuen, Man-Fung; Yokosuka, Osamu; Duseja, Ajay; Jafri, Wasim; Devarbhavi, Harshad; Eapen, C E; Goel, Ashish; Sood, Ajit; Ji, Jia; Duan, Z; Chen, Y

    2017-10-01

    There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (Pfailure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Impact of Hepatic and Extrahepatic Insults on the Outcome of Acute-on-Chronic Liver Failure.

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    Gupta, Tarana; Dhiman, Radha K; Rathi, Sahaj; Agrawal, Swastik; Duseja, Ajay; Taneja, Sunil; Chawla, Yogesh

    2017-03-01

    To study the differences in outcome and predictors of mortality in acute-on-chronic liver failure (ACLF) precipitated by hepatic or extrahepatic insults. Consecutive patients of cirrhosis with acute decompensation were prospectively included and followed up for 90 days from admission. ACLF was defined based on chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis (CANONIC study) criteria. Acute worsening due to acute viral hepatitis A and E, hepatitis B flare, alcoholic hepatitis, autoimmune hepatitis flare, or drug-induced liver injury were categorized as hepatic ACLF and that due to bacterial infection, upper gastrointestinal bleed or surgery as extrahepatic ACLF. Patients with both hepatic and extrahepatic insults were included in combined insult group. Of 179 patients of acute decompensation, 122 had ACLF (hepatic insults 47 and extrahepatic insults 51). Alcohol (64.8%) was the most common etiology of cirrhosis while infection (36%) was the most common acute insult followed by alcoholic hepatitis (24.6%). Higher proportion of extrahepatic ACLF patients had history of prior decompensation than hepatic ACLF patients (62.7% vs. 27.7%, P liver failure-sequential organ failure assessment (CLIF-SOFA), model for end stage liver disease (MELD), integrated MELD score (iMELD), acute physiology and chronic health evaluation score (APACHE-II), and Child-Turcotte-Pugh score scores, respectively. There is no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days. iMELD and CLIF-SOFA have highest AUROC to predict 28-day mortality in hepatic and extrahepatic ACLF groups, respectively.

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

    OpenAIRE

    Hessel Franz P

    2006-01-01

    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 I...

  18. [Clinical application of mesenchymal stem cells in treatment of acute-on-chronic liver failure and related research advances].

    Science.gov (United States)

    Feng, L Y; Zhang, D Z

    2017-09-20

    Acute-on-chronic liver failure is a syndrome characterized by acute exacerbation of chronic hepatitis, organ failure, and high mortality. Clinical treatment of acute-on-chronic liver failure included comprehensive medical treatment, artificial liver support system, and liver transplantation, but such methods have their own shortcomings and patients tend to have a poor prognosis. Mesenchymal stem cells (MSCs), as a new type of cell therapy, have wide sources and are easy to extract and culture. Many studies have shown that MSC treatment not only helps to achieve a high survival rate, but also has good tolerability and safety; therefore, the clinical value of MSCs has become a hot research topic. This article reviews the clinical studies on acute-on-chronic liver failure, related mechanisms, and research advances, in order to provide a reference for future clinical trials and application.

  19. Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management.

    Science.gov (United States)

    Blasco-Algora, Sara; Masegosa-Ataz, José; Gutiérrez-García, María Luisa; Alonso-López, Sonia; Fernández-Rodríguez, Conrado M

    2015-11-14

    Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.

  20. Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition

    Science.gov (United States)

    Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L.; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Kim, Jeong Han; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Lee, Byung Seok; Jang, Jae Young; Suh, Jeong Ill; Kim, Hyoung Su; Nam, Seong Woo; Kwon, Hyeok Choon; Kim, Young Seok; Kim, Sang Gyune; Chae, Hee Bok; Yang, Jin Mo; Sohn, Joo Hyun; Lee, Heon Ju; Park, Seung Ha; Han, Byung Hoon; Choi, Eun Hee; Kim, Chang H.; Kim, Dong Joon

    2016-01-01

    Background & Aim To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea. Results Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, Pdefinitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF. PMID:26789409

  1. 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.......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...

  2. Deregulation of Regulatory T Cells in Acute-on-Chronic Liver Failure: A Rat Model.

    Science.gov (United States)

    Ni, Shunlan; Li, Shanshan; Yang, Naibin; Tang, Xinyue; Zhang, Shengguo; Hu, Danping; Lu, Mingqin

    2017-01-01

    Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months. Then acute liver injury was induced by combined D-galactosamine and lipopolysaccharide. Six time points were examined before or after acute induction. Liver samples were performed with hematoxylin-eosin and Masson staining; circulatory Treg and Th17 cell frequencies were determined using flow cytometry assays; serum levels of alanine aminotransferase, aspartate aminotransferase, interleukin-10 (IL-10), and interferon-γ (IFN-γ) were examined. Results. In group ACLF, both Th17 cell proportion and IFN-γ level presented upgrade firstly and then descend latter tendency; the trends of Treg cell proportion and IL-10 level were observed to gradually decrease and became stable. Conclusion. The Treg cells played an important role in the immunologic mechanism during the process of ACLF. And the function of Treg cells in ACLF was defective.

  3. AKI in patients with acute on chronic liver failure is different from acute decompensation of cirrhosis.

    Science.gov (United States)

    Maiwall, Rakhi; Kumar, Suman; Chandel, Shivendra Singh; Kumar, Guresh; Rastogi, Archana; Bihari, Chhagan; Sharma, Manoj Kumar; Thakur, Bhaskar; Jamwal, K; Nayak, Suman; Mathur, R P; Sarin, S K

    2015-10-01

    The current definitions of acute kidney injury (AKI) including HRS have been derived from patients with decompensated cirrhosis. No studies have carefully addressed AKI in patients with acute on chronic liver failure (ACLF). We evaluated the prevalence, spectrum, natural history and mortality of AKI at admission and new-onset AKI in hospitalized patients with ACLF and compared the results with patients with acute decompensation of cirrhosis (ADC). Consecutive patients with ACLF (n = 382) and ADC (n = 451) were prospectively studied. Serial renal and liver functions were recorded and correlated with the disease course and outcome. AKI at admission and new onset AKI in the hospital were not different in patients with ACLF and ADC (p > 0.05). However, a significant difference in the spectrum of AKI was noted; functional volume-responsive AKI was more common (p liver failure. Patients with ACLF with AKI have more structural AKI, greater potential for reversibility despite higher progression as well as higher mortality compared to patients with ADC. Prevention and early detection of AKI should be considered in patients with ACLF.

  4. Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition.

    Directory of Open Access Journals (Sweden)

    Tae Yeob Kim

    Full Text Available To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium definitions.We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea.Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001. Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192. Patients with previous acute decompensation (AD within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001. Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391.The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.

  5. Characterization of Cerebral Edema in Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Gupta, Tarana; Dhiman, Radha K; Ahuja, Chirag K; Agrawal, Swastik; Chopra, Madhu; Kalra, Naveen; Duseja, Ajay; Taneja, Sunil; Khandelwal, Niranjan; Chawla, Yogesh

    2017-09-01

    The nature of cerebral edema in acute-on-chronic liver failure (ACLF) is not well studied. We aimed to characterize cerebral edema in ACLF using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI). Forty-six patients with cirrhosis and acute decompensation were included. Patients were divided into groups A (no cerebral failure, n = 39) and B (cerebral failure, n = 7). Group A was subdivided into no-ACLF (n = 11), grade 1 (n = 10), grade 2 (n = 9) and grade 3 (n = 9) ACLF as per CANONIC study. MRI brain and plasma TNF-alpha, IL-1beta and IL-6 were measured at baseline and 7-10 days after admission. Ten age- and sex-matched healthy controls were also included. Mean diffusivity (MD) values, an MRI marker of water content, progressively increased from controls to no-ACLF to ACLF grade 1, 2 and 3 in group A in frontal white matter (FWM) and basal ganglia (P 8 × 10(-9) M(2)/s) in FWM were independent predictors of 90-day mortality. There was no significant difference in clinical and MRI parameters between group A and B. Cerebral edema increases with severity of ACLF. Correlation between MD values and IL-6 levels suggests pathogenic role of inflammation in cerebral edema. Patients with grade 3 ACLF have cerebral edema irrespective of presence of clinically evident cerebral failure. MELD score and cerebral edema have prognostic significance in ACLF.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Artificial liver support system combined with liver transplantation in the treatment of patients with acute-on-chronic liver failure.

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    Xiao Xu

    Full Text Available BACKGROUND: The search for a strategy to provide temporary liver support and salvage the patients with acute-on-chronic liver failure (ACLF remains an important issue. This study was designed to evaluate the experience in artificial liver support system (ALSS combined with liver transplantation (LT in the treatment of ACLF. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and seventy one patients with HBV related ACLF undergoing LT between January 2001 and December 2009 were included. Of the 171 patients, 115 received 247 sessions of plasma exchange-centered ALSS treatment prior to LT (ALSS-LT group and the other 56 received emergency LT (LT group. The MELD score were 31±6 and 30±7 in ALSS-LT group and LT group. ALSS treatment resulted in improvement of liver function and better tolerance to LT. The average level of serum total bilirubin before LT was lower than that before the first time of ALSS treatment. The median waiting time for a donor liver was 12 days (2-226 days from the first run of ALSS treatment to LT. Compared to LT group, the beneficial influences of ALSS on intraoperative blood loss and endotracheal intubation time were also observed in ALSS-LT group. The 1-year and 5-year survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6%. CONCLUSIONS/SIGNIFICANCE: Plasma exchange-centered ALSS is beneficial in salvaging patients with ACLF when a donor liver is not available. The consequential LT is the fundamental treatment modality to rescue these patients and lead to a similar survival rate as those patients receiving emergency transplantation.

  8. Pediatric Acute-on-Chronic Liver Failure in a Specialized Liver Unit: Prevalence, Profile, Outcome, and Predictive Factors.

    Science.gov (United States)

    Alam, Seema; Lal, Bikrant B; Sood, Vikrant; Rawat, Dinesh

    2016-10-01

    The aim of the study was to assess the prevalence, profile, outcome, and predictive factors of pediatric acute-on-chronic liver failure (ACLF). All children 3 months to 18 years satisfying the Asia Pacific Association for the Study of Liver Diseases definition of ACLF were included. Data were both extracted from records (January 2011 to December 2014) and prospectively collected (January to October 2015). Successful outcome was defined as survival with native liver at 90 days, whereas poor outcome included those who died or received liver transplantation. Of the 499 children with chronic liver disease (CLD), 56 (11.2%) presented as ACLF, with a mean age of 9.35 (±4.39) years. Wilson disease and autoimmune hepatitis were the commonest underlying CLDs accounting for 24 (42.8%) and 18 (32.1%) cases, respectively. The most frequent events precipitating ACLF were a flare up of the underlying disease in 27 (48.2%) and acute viral hepatitis in 17 (30%). Poor outcome occurred in 22 (39.3%) children: 17 (30.4%) died and 5 (8.9%) received liver transplantation. Poor outcome was associated with grades 3 to 4 hepatic encephalopathy, bilirubin ≥17.5, international normalized ratio ≥3.5, and presence of 2 or more organ failures. On multivariate analysis, a Chronic Liver Failure-Sequential Organ Failure Assessment score ≥10 best predicted mortality (odds ratio 20.45, 95% confidence interval 3.9-106.7). ACLF is present in 11.2% of childhood CLD, with a 90-day native liver survival of 61%. A Chronic Liver Failure-Sequential Organ Failure Assessment score of ≥10 best predicts mortality at day 90.

  9. Clinical features of hepatitis E virus infection in Ibaraki, Japan: autochthonous hepatitis E and acute-on-chronic liver failure.

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    Inagaki, Yuki; Oshiro, Yukio; Hasegawa, Naoyuki; Fukuda, Kuniaki; Abei, Masato; Nishi, Masaaki; Okamoto, Hiroaki; Ohkohchi, Nobuhiro

    2015-04-01

    Hepatitis E caused by hepatitis E virus (HEV) is a serious public health concern in developing countries where HEV is mainly transmitted through contaminated water. Recently, in industrialized countries, autochthonous hepatitis E, a porcine zoonosis, has been increasingly recognized. In Japan, the number of national notifications of acute hepatitis E has increased since the introduction of anti-HEV IgA antibody measurement, covered by the national health insurance program, in 2011. In the past three years, we examined five patients of acute hepatitis or acute-on-chronic liver failure caused by HEV infection who presented various clinical courses in the southern area of Ibaraki prefecture in Japan. Of these patients, 78-year-old and 63-year-old male patients presented acute hepatitis E and recovered by only bed rest. The latter patient had a history of consuming grilled or undercooked pork and shellfish prior to the onset of hepatitis E. Among the five patients examined, the infection route was detected only in this patient. Of note, a 65-year-old female patient presented severe hepatitis associated with painless thyroiditis. The patient was diagnosed with probable autoimmune hepatitis and was successfully treated with prednisolone (40 mg/day). Lastly, 58-year-old and 62-year-old male patients, both of whom had a history of diabetes mellitus and alcoholic liver disease, developed acute-on-chronic liver failure, and the latter patient with pre-existing liver cirrhosis died due to liver failure. Thus, patients with clinical HEV infection who display multiple underlying diseases can develop acute-on-chronic liver failure. In conclusion, HEV infection manifests the diverse clinical courses.

  10. Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome

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    Dhiman, Radha K; Agrawal, Swastik; Gupta, Tarana; Duseja, Ajay; Chawla, Yogesh

    2014-01-01

    AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF.

  11. Serum 1H-NMR metabolomic fingerprints of acute-on-chronic liver failure in intensive care unit patients with alcoholic cirrhosis.

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    Roland Amathieu

    Full Text Available INTRODUCTION: Acute-on-chronic liver failure is characterized by acute deterioration of liver function in patients with compensated or decompensated, but stable, cirrhosis. However, there is no accurate definition of acute-on-chronic liver failure and physicians often use this term to describe different clinical entities. Metabolomics investigates metabolic changes in biological systems and identifies the biomarkers or metabolic profiles. Our study assessed the metabolomic profile of serum using proton nuclear magnetic resonance ((1H-NMR spectroscopy to identify metabolic changes related to acute-on-chronic liver failure. PATIENTS: Ninety-three patients with compensated or decompensated cirrhosis (CLF group but stable liver function and 30 patients with cirrhosis and hospitalized for the management of an acute event who may be responsible of acute-on-chronic liver failure (ACLF group, were fully analyzed. Blood samples were drawn at admission, and sera were separated and stored at -80°C until (1H-NMR spectral analysis. Using orthogonal projection to latent-structure discriminant analyses, various metabolites contribute to the complete separation between these both groups. RESULTS: The predictability of the model was 0.73 (Q(2 Y and the explained variance was 0.63 (R(2 Y. The main metabolites that had increased signals related to acute-on-chronic liver failure were lactate, pyruvate, ketone bodies, glutamine, phenylalanine, tyrosine, and creatinine. High-density lipids were lower in the ALCF group than in CLF group. CONCLUSION: A serum metabolite fingerprint for acute-on-chronic liver failure, obtained with (1H-NMR, was identified. Metabolomic profiling may aid clinical evaluation of patients with cirrhosis admitted into intensive care units with acute-on-chronic liver failure, and provide new insights into the metabolic processes involved in acute impairment of hepatic function.

  12. Experience of combined liver-kidney transplantation for acute-on-chronic liver failure patients with renal dysfunction.

    Science.gov (United States)

    Xing, T; Zhong, L; Chen, D; Peng, Z

    2013-01-01

    The aim of this study was to evaluate the outcomes of orthotopic liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for acute-on-chronic liver failure (ACLF) patients with renal dysfunction. From January 2001 to December 2009, 133 patients underwent OLT for ACLF at our center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients, 12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined according to the Asian Pacific Association for the Study of Liver Consensus Meeting. Clinical data were reviewed for survival outcomes. The median model for end-stage liver disease score (MELD) of patients with ACLF was 28. Among the 133 patients, all of whom received deceased donor liver grafts, 12 also got the kidney grafts from the same deceased donor. The hospital mortality rate was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for patients without renal dysfunction and 70% for patients with renal dysfunction. The results of patients with ESRD who underwent CLKT were better than those of subjects without renal dysfunction or patients with HRS1 who underwent OLT alone. OLT alone improved renal function in most patients with HRS1, including those requiring short-term hemodialysis. Simultaneous liver-kidney transplantation was an excellent strategy for patients with both ACLF and ESRD. It provided protection to the kidney allograft for liver-based metabolic diseases affecting the kidney. The rate of acute rejection episodes in kidneys was low. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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.

  14. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures.

    Science.gov (United States)

    Bajaj, Jasmohan S; O'Leary, Jacqueline G; Reddy, K Rajender; Wong, Florence; Biggins, Scott W; Patton, Heather; Fallon, Michael B; Garcia-Tsao, Guadalupe; Maliakkal, Benedict; Malik, Raza; Subramanian, Ram M; Thacker, Leroy R; Kamath, Patrick S

    2014-07-01

    Infections worsen survival in cirrhosis; however, simple predictors of survival in infection-related acute-on-chronic liver failure (I-ACLF) derived from multicenter studies are required in order to improve prognostication and resource allocation. Using the North American Consortium for Study of End-stage Liver Disease (NACSELD) database, data from 18 centers were collected for survival analysis of prospectively enrolled cirrhosis patients hospitalized with an infection. We defined organ failures as 1) shock, 2) grade III/IV hepatic encephalopathy (HE), 3) need for dialysis and mechanical ventilation. Determinants of survival with these organ failures were analyzed. In all, 507 patients were included (55 years, 52% hepatitis C virus [HCV], 15.8% nosocomial infection, 96% Child score ≥ 7) and 30-day evaluations were available in 453 patients. Urinary tract infection (UTI) (28.5%), and spontaneous bacterial peritonitis (SBP) (22.5%) were the most prevalent infections. During hospitalization, 55.7% developed HE, 17.6% shock, 15.1% required renal replacement, and 15.8% needed ventilation; 23% died within 30 days and 21.6% developed second infections. Admitted patients developed none (38.4%), one (37.3%), two (10.4%), three (10%), or four (4%) organ failures. The 30-day survival worsened with a higher number of extrahepatic organ failures, none (92%), one (72.6%), two (51.3%), three (36%), and all four (23%). I-ACLF was defined as ≥ 2 organ failures given the significant change in survival probability associated at this cutoff. Baseline independent predictors for development of ACLF were nosocomial infections, Model for Endstage Liver Disease (MELD) score, low mean arterial pressure (MAP), and non-SBP infections. Independent predictors of poor 30-day survival were I-ACLF, second infections, and admission values of high MELD, low MAP, high white blood count, and low albumin. Using multicenter study data in hospitalized decompensated infected cirrhosis patients, I

  15. 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.

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

    Science.gov (United States)

    Hessel, Franz P

    2006-10-05

    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. 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. 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. 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.

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

    Science.gov (United States)

    Hessel, Franz P

    2006-01-01

    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. PMID:17022815

  18. Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival.

    Science.gov (United States)

    Kerbert, Annarein J C; Verspaget, Hein W; Navarro, Àlex Amorós; Jalan, Rajiv; Solà, Elsa; Benten, Daniel; Durand, François; Ginès, Pere; van der Reijden, Johan J; van Hoek, Bart; Coenraad, Minneke J

    2017-12-21

    Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up. ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF.

  19. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation.

    Science.gov (United States)

    Li, Hai; Xia, Qiang; Zeng, Bo; Li, Shu-Ting; Liu, Heng; Li, Qi; Li, Jun; Yang, Shu-Yin; Dong, Xiao-Jun; Gao, Ting; Munker, Stefan; Liu, Yan; Liebe, Roman; Xue, Feng; Li, Qi-Gen; Chen, Xiao-Song; Liu, Qiang; Zeng, Hui; Wang, Ji-Yao; Xie, Qing; Meng, Qin-Hua; Wang, Jie-Fei; Mertens, Peter R; Lammert, Frank; Singer, Manfred V; Dooley, Steven; Ebert, Matthias P A; Qiu, De-Kai; Wang, Tai-Ling; Weng, Hong-Lei

    2015-07-01

    Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence. A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses. SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p<0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN. SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  20. 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

  1. Management of sepsis during MARS treatment in acute on chronic liver failure.

    Science.gov (United States)

    Novelli, G; Morabito, V; Pugliese, F; Ferretti, G; Novelli, S; Ianni, S; Lai, Q; Rossi, M; Berloco, P B

    2011-05-01

    The aim of our study was a 30-day follow-up of the use of early detection of endotoxin by the endotoxin activity assay (EAA) for patients with acute liver failure superimposed on chronic liver disease (AoCLF) and treated with polymyxin-B hemoperfusion-based (PMX-DHP) treatment and albumin dialysis in the molecular adsorbent recirculating system (MARS). From February 2008 to July 2010, we evaluated 10 AoCLF patients experiencing systemic inflammatory response syndrome (SIRS) in association with suspected infection and an EAA-positive test (>0.60). These patients awaiting liver transplantation (OLT) showed similar Model End-Stage Liver Disease (MELD) scores (range, 19-25) and encephalopathy grade ≤ 2. Five patients received therapy to remove endotoxins with PMX-DHP with MARS treatment for liver failure (group A); the other 5 patients received MARS treatment only (group B). Two PMX-DHP treatments were performed in 4 group A patients (average EA=0.66 [range, 0.61-0.70]) and 3 treatments for 1 patient (EA=0.92). All 5 subjects underwent an average of 4 MARS treatments (range, 3-5). At the end of therapy, the median EA level was 0.42 (range, 0.37-0.48). As reported in the literature, we achieved a significant improvement in liver and kidney functions using MARS. Measurements of lactate, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were significantly improved among patients treated with the extracorporeal therapies. At 30 days of observation, all 5 patients treated with MARS plus PMX-DHP are alive. In group B, a mean of 7.5 MRAS treatments were performed. We observed an improvement in hemodynamic and liver functions with reduced levels of proinflammatory cytokines and lactates in 4 patients. One patient showed no improvement in clinical status with the development of sepsis and subsequent multiorgan failure after 24 days. The possibility of an early diagnosis using the EAA in AoCLF patients could prevent the progression of the sepsis cascade. The use of PMX

  2. Molecular Adsorbent Recirculating System Can Reduce Short-Term Mortality Among Patients With Acute-on-Chronic Liver Failure-A Retrospective Analysis.

    Science.gov (United States)

    Gerth, Hans U; Pohlen, Michele; Thölking, Gerold; Pavenstädt, Hermann; Brand, Marcus; Hüsing-Kabar, Anna; Wilms, Christian; Maschmeier, Miriam; Kabar, Iyad; Torner, Josep; Pavesi, Marco; Arroyo, Vicente; Banares, Rafael; Schmidt, Hartmut H J

    2017-10-01

    Acute-on-chronic liver failure is associated with numerous consecutive organ failures and a high short-term mortality rate. Molecular adsorbent recirculating system therapy has demonstrated beneficial effects on the distinct symptoms, but the associated mortality data remain controversial. Retrospective analysis of acute-on-chronic liver failure patients receiving either standard medical treatment or standard medical treatment and molecular adsorbent recirculating system. Secondary analysis of data from the prospective randomized Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial by applying the recently introduced Chronic Liver Failure-criteria. Medical Departments of University Hospital Muenster (Germany). This analysis was conducted in two parts. First, 101 patients with acute-on-chronic liver failure grades 1-3 and Chronic Liver Failure-C-Organ Failure liver subscore equals to 3 but stable pulmonary function were identified and received either standard medical treatment (standard medical treatment, n = 54) or standard medical treatment and molecular adsorbent recirculating system (n = 47) at the University Hospital Muenster. Second, the results of this retrospective analysis were tested against the Recompensation of Exacerbated Liver Insufficiency with Hyperbilirubinemia and/or Encephalopathy and/or Renal Failure trial. Standard medical treatment and molecular adsorbent recirculating system. Additionally to improved laboratory variables (bilirubin and creatinine), the short-term mortality (up to day 14) of the molecular adsorbent recirculating system group was significantly reduced compared with standard medical treatment. A reduced 14-day mortality rate was observed in the molecular adsorbent recirculating system group (9.5% vs 50.0% with standard medical treatment; p = 0.004), especially in patients with multiple organ failure (acute-on-chronic liver failure grade 2-3). Concerning the

  3. Validation of Prognostic Scores to Predict Short-term Mortality in Patients with Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Song, Do Seon; Kim, Tae Yeob; Kim, Dong Joon; Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Jang, Jae Young; Kim, Hyoung Su; Kim, Sang Gyune; Yang, Jin Mo; Sohn, Joo Hyun; Choi, Eun Hee; Cho, Hyun Chin; Jeong, Soung Won; Kim, Moon Young

    2017-09-16

    The aim of this study was to validate the Chronic Liver Failure-Sequential Organ Failure Assessment score (CLIF-SOFAs), CLIF consortium organ failure score (CLIF-C OFs), CLIF-C acute-on-chronic liver failure score (CLIF-C ACLFs), and CLIF-C acute decompensation score (CLIF-C ADs) in Korean chronic liver disease patients with acute deterioration. ACLF was defined by either the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) or CLIF-C criteria. The diagnostic performances for short-term mortality were compared by the area under the receiver operating characteristics (AUROC) curve. Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF-C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The AUROCs of the CLIF-SOFAs, CLIF-C OFs and CLIF-C ACLFs were significantly higher than those of the Child-Pugh, Model for End-stage Liver Disease (MELD), and MELD-Na scores in ACLF patients according to the CLIF-C definition (all Pliver specific scores in ACLF patients according to the CLIF-C definition, but not in ACLF patients according to the AARC definition. The CLIF-SOFAs, CLIF-C OFs, and CLIF-C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF-C definition, but not the AARC definition. This article is protected by copyright. All rights reserved.

  4. Mechanism of cell death in acute-on-chronic liver failure: a clinico-pathologic-biomarker study.

    Science.gov (United States)

    Adebayo, Danielle; Morabito, Vincenzo; Andreola, Fausto; Pieri, Giulia; Luong, Tu-Vin; Dhillon, Amar; Mookerjee, Rajeshwar; Jalan, Rajiv

    2015-12-01

    Mortality of patients who develop acute-on-chronic liver failure (ACLF) is unacceptably high but the predominant mode of cell death is unknown. The aim of this study was to evaluate whether plasma levels of caspase-cleaved cytokeratin M30 (marker of apoptosis) and uncleaved cytokeratin M65 (marker of total cell death) are altered in ACLF patients and relate this to liver histology. Twenty-seven patients with acute decompensation of liver disease were divided into two groups: no-ACLF (n = 11) or ACLF (n-16). Healthy controls (n = 8) and acute liver failure (ALF) patients (n = 10) were also enrolled. Cell death was assessed in plasma using an ELISA kit (M30 and M65). Simultaneous biopsy samples were analysed for M30 and caspase-3 staining. Plasma M30 value was significantly elevated in ACLF patients compared with healthy volunteers (P = 0.0001), it was also significantly higher in ACLF patients compared with no-ACLF patients (P = 0.002). M65 levels were higher in ALF compared with ACLF patients (P = 0.002) but the apoptotic index defined by M30/M65 ratio was significantly higher in ACLF patients. Patients with extra-hepatic failure had higher M30 levels compared with patients without organ failure (P = 0.03). M30 staining in liver was more marked in the patients with ACLF and was observed in all the patients that died. The results of this study suggest that hepatocyte apoptosis is the predominant mode of cell death in ACLF, which can be identified in the peripheral blood. Further studies are required to validate our findings and to determine whether M30 can be used as a biomarker of apoptosis or as a target for therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. 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 char...

  6. A novel dynamic model for predicting outcome in patients with hepatitis B virus related acute-on-chronic liver failure.

    Science.gov (United States)

    Xue, Ran; Duan, Zhonghui; Liu, Haixia; Chen, Li; Yu, Hongwei; Ren, Meixin; Zhu, Yueke; Jin, Chenggang; Han, Tao; Gao, Zhiliang; Meng, Qinghua

    2017-12-12

    It is challenging to predict the outcome of patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) through existing prognostic models. Our aim was to establish a novel dynamic model to improve the predictive efficiency of 30-day mortality in HBV-ACLF patients. 305 patients who were diagnosed as HBV-ACLF (derivation cohort, n=211; validation cohort, n=94) were included in this study. The HBV-ACLF dynamic (HBV-ACLFD) model was constructed based on the daily levels of predictive variables in 7 days after diagnosis combined with baseline risk factors by multivariate logistic regression analysis. The HBV-ACLFD model was compared with the Child-Turcotte-Pugh (CTP) score, end-stage liver disease (MELD) score, and MELD within corporation of serum sodium (MELD-Na) score by the area under the receiver-operating characteristic curves (AUROC). The HBV-ACLFD model demonstrated excellent discrimination with AUROC of 0.848 in the derivation cohort and of 0.813 in the validation cohort (p=0.620). The performance of the HBV-ACLFD model appeared to be superior to MELD score, MELD-Na score and CTP score (P<0.0001). The HBV-ACLFD model can accurately predict 30-day mortality in patients with HBV-ACLF, which is helpful to select appropriate clinical procedures, so as to relieve the social and economic burden.

  7. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Kjaergard, Lise L; Liu, Jianping; Als-Nielsen, Bodil

    2003-01-01

    Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation.......Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation....

  8. Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats.

    Science.gov (United States)

    Gao, Dan-Dan; Fu, Jia; Qin, Bo; Huang, Wen-Xiang; Yang, Chun; Jia, Bei

    2016-04-28

    To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF). The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes. Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter group. This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.

  9. Aberrant GSTP1 promoter methylation predicts poor prognosis of acute-on-chronic hepatitis B pre-liver failure.

    Science.gov (United States)

    Qiao, Chen-Yang; Li, Feng; Teng, Yue; Zhao, Jing; Hu, Na; Fan, Yu-Chen; Wang, Kai

    2017-07-04

    It has been demonstrated that glutathione-S-transferase P1 (GSTP1) could protect cells from DNA damage mediated by oxidizing agents or electrophiles in hepatic inflammatory response. Our study evaluated the methylation status and the predictive value for prognosis of GSTP1 promoter region in patients with acute-on-chronic hepatitis B pre-liver failure (pre-ACHBLF). Methylation status of GSTP1 promoter in peripheral blood mononuclear cells (PBMCs) and plasma was measured in 103 patients with pre-ACHBLF, 80 patients with chronic hepatitis B (CHB) and 30 healthy controls (HCs) by methylation-specific polymerase chain reaction. The mRNA level of GSTP1 was detected by quantitative real-time polymerase chain reaction. The methylation frequency of GSTP1 promoter region in patients with pre-ACHBLF (35/103 in PBMCs and 33/103 in plasma) was significantly higher than CHB (2/80) and HCs (0/30), respectively. The mRNA level of GSTP1 in patients with pre-ACHBLF was significantly lower than CHB and HCs. Additionally, pre-ACHBLF patients with methylated GSTP1 presented strikingly higher incidence of ACHBLF than those without. Of note, GSTP1 methylation presented distinctly better performance than model for end-stage liver disease score [area under the receiver operating characteristic curves (AUCs) 0.825 in PBMCs and 0.798 in plasma VS 0.589; AUC 0.804 in PBMCs and 0.779 in plasma VS 0.622; AUC 0.767 in PBMCs and 0.744 in plasma VS 0.602, respectively] when used to predict the 1-, 2- or 3-month incidence of ACHBLF in patients with pre-ACHBLF. Aberrant methylation of GSTP1 has potential to be a prognostic biomarker for pre-ACHBLF.

  10. Chronic liver failure-consortium acute-on-chronic liver failure and acute decompensation scores predict mortality in Brazilian cirrhotic patients.

    Science.gov (United States)

    Picon, Rafael Veiga; Bertol, Franciele Sabadin; Tovo, Cristiane Valle; de Mattos, Ângelo Zambam

    2017-07-28

    To validate prognostic scores for acute decompensation of cirrhosis and acute-on-chronic liver failure in Brazilian patients. This is a prospective cohort study designed to assess the prognostic performance of the chronic liver failure-consortium (CLIF-C) acute decompensation score (CLIF-C AD) and CLIF-C acute-on-chronic liver failure score (CLIF-C ACLF), regarding 28-d and 90-d mortality, as well as to compare them to other prognostic models, such as Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na), Child-Pugh (CP) score, and the CLIF-C Organ Failure score (CLIF-C OF). All participants were adults with acute decompensation of cirrhosis admitted to the Emergency Department of a tertiary hospital in southern Brazil. Prognostic performances were evaluated by means of the receiver operating characteristic (ROC) curves, area under the curves (AUC) and 95%CI. One hundred and thirteen cirrhotic patients were included. At admission, 18 patients had acute-on-chronic liver failure (ACLF) and 95 individuals had acute decompensation (AD) without ACLF, of which 24 eventually developed ACLF during the course of hospitalization (AD evolving to ACLF group). The AD group had significantly lower 28-d (9.0%) and 90-d (18.3%) mortality as compared to the AD evolving to ACLF group and to the ACLF group (both P < 0.001). On the other hand, 28-d and 90-d mortalities were not significantly different between AD evolving to ACLF group and ACLF group (P = 0.542 and P = 0.708, respectively). Among patients with ACLF, at 28 d from the diagnosis, CLIF-C ACLF was the only score able to predict mortality significantly better than the reference line, with an AUC (95%CI) of 0.71 (95%CI: 0.54-0.88, P = 0.021). Among patients with AD, all prognostic scores performed significantly better than the reference line regarding 28-d mortality, presenting with similar AUCs: CLIF-C AD score 0.75 (95%CI: 0.63-0.88), CP score 0.72 (95%CI: 0.59-0.85), MELD score 0.75 (95%CI: 0.61-0.90), MELD

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis.

    Science.gov (United States)

    Markwardt, Daniel; Holdt, Lesca; Steib, Christian; Benesic, Andreas; Bendtsen, Flemming; Bernardi, Mauro; Moreau, Richard; Teupser, Daniel; Wendon, Julia; Nevens, Frederik; Trebicka, Jonel; Garcia, Elisabet; Pavesi, Marco; Arroyo, Vicente; Gerbes, Alexander L

    2017-10-01

    The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. We investigated whether cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality. We determined the plasma levels of CysC and NGAL in 429 patients hospitalized for acute decompensation of cirrhosis in the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study. The patients were followed for 90 days. Patients without RD or ACLF at inclusion but with development of either had significantly higher baseline concentrations of CysC and NGAL compared to patients without. CysC, but not NGAL, was found to be predictive of RD (odds ratio, 9.4; 95% confidence interval [CI], 1.8-49.7), HRS (odds ratio, 4.2; 95% CI, 1.2-14.8), and ACLF (odds ratio, 5.9; 95% CI, 1.3-25.9). CysC at day 3 was not found to be a better predictor than baseline CysC. CysC and NGAL were both predictive of 90-day mortality, with hazard ratios for CysC of 3.1 (95% CI, 2.1-4.7) and for NGAL of 1.9 (95% CI, 1.5-2.4). Baseline CysC is a biomarker of RD, HRS, and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis, though determining CysC at day 3 did not provide any benefit; while NGAL is also associated with short-term mortality, it fails to predict development of RD, HRS, and ACLF. Baseline CysC may help to identify patients at risk earlier and improve clinical management. (Hepatology 2017;66:1232-1241). © 2017 by the American Association for the Study of Liver Diseases.

  14. Cost-effectiveness of the artificial liver support system MARS in patients with acute-on-chronic liver failure.

    Science.gov (United States)

    Hessel, Franz P; Bramlage, Peter; Wasem, Jürgen; Mitzner, Steffen R

    2010-02-01

    For patients with an acute exacerbation of chronic liver failure (ACLF), the molecular adsorbent recirculating system (MARS) can result in a prolongation of life, but data on costs and cost-effectiveness are lacking. A health economic evaluation of a prospective controlled cohort trial in patients with ACLF not eligible for liver transplantation with 3 years follow-up and consecutive modelling of long-term costs, outcomes and cost-effectiveness was conducted. Costs were calculated from the perspective of the German health-care system. One hundred and forty-nine patients with ACLF were included of which 67 (44.9%) were treated with MARS and 82 (55.1%) assigned to the control group. Mean survival was 692 days in MARS-treated patients (33% survival after 3 years) and 453 days in control patients (15% after 3 years, logrank P = 0.022). MARS patients gained 0.66 [95% confidence interval (CI): -0.12 to 1.46] life years (LYs), determined by the bootstrap method. The mean cost difference was 19.835 euro (95% CI: 13.308-25.429) with 35639 euro for MARS-treated patients and 15804 euro for controls. Incremental costs per LY gained were 29.985 euro (95% CI: 9.441-321.761) and 43.040 euro (95% CI: 13.551-461.856) per quality-adjusted LY gained. There is an acceptable cost-effectiveness of MARS, compared with other medical technologies presently reimbursed. Randomized controlled trials with sufficient sample size are necessary before a final recommendation for MARS can be given.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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...

  17. Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure.

    Science.gov (United States)

    Zheng, Su-Jun; Liu, Shuang; Liu, Mei; McCrae, Malcolm A; Li, Jun-Feng; Han, Yuan-Ping; Xu, Chun-Hui; Ren, Feng; Chen, Yu; Duan, Zhong-Ping

    2014-03-07

    To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF.

  18. Sorafenib-induced acute-on-chronic liver failure in a patient with hepatocellular carcinoma after transarterial chemoembolization and radiofrequency ablation: A case report.

    Science.gov (United States)

    Wang, Qing-Liang; Li, Xiao-Jie; Yao, Zhi-Cheng; Zhang, Peng; Xu, Shi-Lei; Huang, He; Hu, Kun-Peng

    2017-10-01

    Comprehensive treatments together with sorafenib provide a survival benefit for patients with advanced hepatocellular carcinoma (HCC). Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct entity; however, only few cases induced by sorafenib have been reported to date. We herein present a rare case of ACLF in a patient under treatment with sorafenib. A 63-year-old woman who suffered from hepatitis B for 10 years was admitted to our hospital. A computed tomography (CT) scan led to a diagnosis of HCC in the V/VIII hepatic segment, with invasion of the middle hepatic and the right portal veins. The patient received multidisciplinary treatment, including transarterial chemoembolization, radiofrequency ablation and sorafenib. Two months after sorafenib treatment, the patient was readmitted due to progressive jaundice and ACLF was diagnosed by liver biopsy shortly thereafter. Although aggressive treatment was administered, the patient succumbed to the disease following rapid deterioration of her clinical condition. The majority of patients with HCC have underlying liver disease and combination therapy with sorafenib should be administered with caution, as it may increase the risk of severe hepatotoxicity. The present case suggests that patients treated with sorafenib may require a dose reduction following interventional treatment.

  19. Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis.

    Science.gov (United States)

    Kim, Hee Yeon; Kim, Chang Wook; Kim, Tae Yeob; Song, Do Seon; Sinn, Dong Hyun; Yoon, Eileen L; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Kim, Jeong Han; Yim, Hyung Joon; Kim, Sung Eun; Baik, Soon Koo; Lee, Byung Seok; Jang, Jae Young; Kim, Young Seok; Kim, Sang Gyune; Yang, Jin Mo; Sohn, Joo Hyun; Lee, Heon Ju; Park, Seung Ha; Choi, Eun Hee; Kim, Dong Joon

    2016-11-07

    To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting short-term mortality among patients with alcoholic hepatitis. We retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey's discriminant function (DF), age, bilirubin, international normalized ratio and creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end-stage liver disease (MELD), and MELD-Na. Of 264 patients, 32 (12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90), 0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83 (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality. CLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.

  20. The dysregulation of endoplasmic reticulum stress response in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B.

    Science.gov (United States)

    Ren, F; Shi, H; Zhang, L; Zhang, X; Wen, T; Xie, B; Zheng, S; Chen, Y; Li, L; Chen, D; Duan, Z

    2016-01-01

    Although endoplasmic reticulum (ER) stress is critical in various liver diseases, its role in acute-on-chronic liver failure (AoCLF) caused by acute exacerbation of chronic hepatitis B (CHB) is still elusive. This study aimed to analyse ER stress responses in the progression of HBV-related AoCLF. Normal liver tissues (n = 10), liver tissues of CHB (n = 12) and HBV-related patients with AoCLF (n = 19) were used. Electron microscopy of the ultrastructure of the ER was carried out on liver specimens. The gene and protein expression levels of ER stress-related genes were measured. We further analysed the correlation between the expression levels of ER stress-related molecules and liver injury. Electron microscopy identified typical features of the ER microstructure in AoCLF subjects. Among the three pathways of unfolded protein responses, the PKR-like ER kinase and inositol-requiring enzyme 1 signalling pathway were activated in CHB subjects and inactivated in AoCLF subjects, while the activating transcription factor 6 signalling pathway was sustained in the activated form during the progression of AoCLF; the expression of glucose-regulated protein (Grp)78 and Grp94 was gradually decreased in AoCLF subjects compared to healthy individuals and CHB subjects, showing a negative correlation with serum ALT, AST and TBIL; moreover, the ER stress-related apoptosis molecules were activated in the progression of acute exacerbation of CHB. The dysregulated ER stress response may play a complicated role in the pathogenesis of AoCLF, and a severe ER stress response may predict the occurrence of AoCLF caused by acute exacerbation of CHB. © 2015 John Wiley & Sons Ltd.

  1. APACHE II score is superior to SOFA, CTP and MELD in predicting the short-term mortality in patients with acute-on-chronic liver failure (ACLF).

    Science.gov (United States)

    Duseja, Ajay; Choudhary, Narendra S; Gupta, Sachin; Dhiman, Radha Krishan; Chawla, Yogesh

    2013-09-01

    The aim of the study was to assess the performance of various prognostic scores including the acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores in predicting short-term mortality in patients with acute-on-chronic liver failure (ACLF). Altogether 100 consecutive patients with ACLF were evaluated prospectively. The diagnosis of ACLF was based on the Asian-Pacific Association for the Study of the Liver criteria except for the inclusion of non-hepatic insults as acute events. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for predicting short-term mortality was calculated for APACHE II, SOFA, CTP and MELD in all patients and Maddrey's discriminant function (DF) and Glasgow alcoholic hepatitis scores (GAHS) for patients with alcoholic hepatitis only. Most patients had alcohol-related cirrhosis and alcoholic hepatitis as acute insults for ACLF. A total of 53 patients either died or left hospital in very sick status and were confirmed to have died the same day after leaving hospital. Overall, the area under the receiver operating characteristic curve of APACHE II was higher than those of MELD, SOFA and CTP scores for predicting short-term mortality. Even for patients with alcoholic hepatitis, APACHE II performed better than DF and GAHS. Short-term mortality is high in patients with ACLF. APACHE II scoring system is superior to other prognostic scores in predicting its short-term mortality. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  2. Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK.

    Science.gov (United States)

    Bernsmeier, Christine; Pop, Oltin T; Singanayagam, Arjuna; Triantafyllou, Evangelos; Patel, Vishal C; Weston, Christopher J; Curbishley, Stuart; Sadiq, Fouzia; Vergis, Nikhil; Khamri, Wafa; Bernal, William; Auzinger, Georg; Heneghan, Michael; Ma, Yun; Jassem, Wayel; Heaton, Nigel D; Adams, David H; Quaglia, Alberto; Thursz, Mark R; Wendon, Julia; Antoniades, Charalambos G

    2015-03-01

    Characteristics of decompensated cirrhosis and acute-on-chronic liver failure (ACLF) include susceptibility to infection, immuneparesis, and monocyte dysfunction. MER receptor tyrosine kinase (MERTK) is expressed by monocytes and macrophages and contributes to down-regulation of innate immune responses. We investigated whether MERTK expression is altered on monocytes from patients with liver failure. We analyzed blood and liver samples collected from patients admitted to the liver intensive therapy unit at King's College Hospital in London from December 2012 through July 2014. Patients had either ACLF (n = 41), acute decompensation of cirrhosis without ACLF (n = 9), cirrhosis without decompensation (n = 17), or acute liver failure (n = 23). We also analyzed samples from healthy individuals (controls, n = 29). We used flow cytometry to determine the level of innate immune function, and associated the findings with disease severity. We developed an assay to measure recruitment and migration of immune cells from the tissue parenchyma. Immunohistochemistry and confocal microscopy were used to determine levels of MERTK in bone marrow, liver, and lymph node tissues. We performed immunophenotype analyses and measured the production of tumor necrosis factor and interleukin 6 and intracellular killing of Escherichia coli by monocytes and peritoneal macrophages incubated with lipopolysaccharide, with or without an inhibitor of MERTK (UNC569). The number of monocytes and macrophages that expressed MERTK was greatly increased in the circulation, livers, and lymph nodes of patients with ACLF, compared with patients with stable cirrhosis and controls. MERTK expression (mean fluorescence intensity) correlated with the severity of hepatic and extrahepatic disease and systemic inflammatory responses. Based on immunophenotype, migration, and functional analyses, MERTK-expressing monocytes migrate across the endothelia to localize into tissue sites and regional lymph nodes

  3. Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acute-on-chronic liver failure.

    Science.gov (United States)

    Duan, Xue-Zhang; Liu, Fang-Fang; Tong, Jing-Jing; Yang, Hao-Zhen; Chen, Jing; Liu, Xiao-Yan; Mao, Yuan-Li; Xin, Shao-Jie; Hu, Jin-Hua

    2013-02-21

    To evaluate the safety and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy in patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF). Fifty-five patients with HBV-associated ACLF were randomized into two groups: the treatment group and the control group. Twenty-seven patients in the treatment group received G-CSF (5 μg/kg per day, six doses) treatment plus standard therapy, and 28 patients in the control group received standard therapy only. The peripheral CD34(+) cell count was measured consecutively by flow cytometry. Circulating white blood cell count, biochemical parameters, and other clinical data of these patients were recorded and analyzed. All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate. The peripheral neutrophil and CD34(+) cell counts in the G-CSF group increased on day 3 from the onset of therapy, continued to rise on day 7, and remained elevated on day 15 compared to those of the control group. Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy, compared to that in the controls (P = 0.041). Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7 (P = 0.004) and remained high on day 30 from the onset of G-CSF therapy (P liver function and the survival rate of these patients.

  4. Correlation between high mobility group box-1 protein and chronic hepatitis B infection with severe hepatitis B and acute-on-chronic liver failure: a meta-analysis.

    Science.gov (United States)

    Hu, Yi-Bing; Hu, Dan-Ping; Fu, Rong-Quan

    2017-06-01

    The aim of this study was to evaluate the correlation of High-mobility group box 1 (HMGB1) expression in the serum with chronic hepatitis B (CHB) related liver fibrosis, severe hepatitis B and acute-on-chronic liver failure (ACLF). We made a literature search in PubMed, Embase, Web of Science, Medline, Google Scholar, China National Knowledge Infrastructure, WanFang with no language restriction. Pooled data were analyzed and mean difference with corresponding 95% confidence intervals were calculated. A total of 16 relevant studies were identified. HMGB1 serum levels were higher in severe hepatitis B or ACLF patients than those in CHB patients. Pooled mean differences of HMGB1 in severe hepatitis B and ACLF patients compared with CHB patients were 4.32 (95% CI: 0.34-8.29, Z=2.13, I2=59%, P=0.03) and 15.96 (95% CI: -0.37-32.28, Z=1.92, P=0.06). Four studies showed there was a different HMGB1 expression in mild, moderate and severe CHB patients (P values were <0.05, <0.05, <0.05 and <0.01, respectively). Pooled mean difference of HMGB1 in low liver fibrosis patients compared with high liver fibrosis was -125.38 (95% CI: -539.44-288.68, Z=0.59, I2=98%, P=0.55). The results suggested that HMGB1 levels in the serum were statistically higher in severe hepatitis B and ACLF patients. Therefore, HMGB1 may be a useful therapeutic target for severe hepatitis B and ACLF diagnosis.

  5. Association of Toll-like receptor 3 polymorphisms with chronic hepatitis B and hepatitis B-related acute-on-chronic liver failure.

    Science.gov (United States)

    Rong, Yihui; Song, Haihan; You, Shaoli; Zhu, Bing; Zang, Hong; Zhao, Yi; Li, Yongli; Wan, Zhihong; Liu, Hongling; Zhang, Aimin; Xiao, Long; Xin, Shaojie

    2013-04-01

    Hepatitis B virus (HBV) infection is one of the major causes of chronic liver inflammation. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and is responsible for recognizing viral pathogens. It has been reported that the TLR3 C1234T polymorphism is associated with various diseases. The aim of this study was to investigate whether TLR3 polymorphisms were correlated with susceptibility to chronic HBV infection. Two polymorphisms in the TLR3 gene, A952T and C1234T, were tested by direct sequencing in 452 chronic hepatitis B (CHB) patients and 462 healthy controls. Data showed that subjects carrying 1234CT genotype and TT genotype had 1.42-fold and 2.31-fold increased risk of chronic HBV infection compared to those with CC genotype (95 % confidence interval [CI] = 1.08-1.86, p = 0.012; 95 % CI = 1.34-3.96, p = 0.002, respectively). Further analysis revealed that the prevalence of 1234CT genotype and T allele was significantly increased in CHB patients with acute-on-chronic liver failure (ACLF) than those without ACLF (odds ratio [OR] = 1.55, p = 0.030; OR = 1.43, p = 0.040, respectively). These results indicate that TLR3 C1234T polymorphism could be a risk factor for the development of chronic HBV infection, especially the CHB-related ACLF.

  6. Combining serum cystatin C with total bilirubin improves short-term mortality prediction in patients with HBV-related acute-on-chronic liver failure.

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    Zhihong Wan

    Full Text Available BACKGROUND & AIMS: HBV-related acute-on-chronic liver failure (HBV-ACLF is a severe liver disease which results in a high mortality in China. To early predict the prognosis of the patients may prevent the complications and improve the survival. This study was aimed to develop a new prognostic index to estimate the survival related to HBV-ACLF. METHODS: Consecutive patients with HBV-ACLF were included in a prospective observational study. Serum Cystatin C concentrations were measured by using the particle-enhanced immunonephelometry assay. All of the patients were followed for at least 3 months. Cox regression analysis was carried out to identify which factors were predictive of mortality. The area under the receiver operating characteristic curve (AUC was used to evaluate the efficacy of the variates for early predicting mortality. RESULTS: Seventy-two patients with HBV-ACLF were recruited between January 2012 and January 2013. Thirty patients died (41.7% during 3-months followed up. Cox multivariate regression analysis identified serum cystatin C (CysC and total bilirubin (TBil were independent factors significantly (P < 0.01 associated with survival. Our results further showed that new prognostic index (PI combining serum CysC with TBil was a good indicator for predicting the mortality of patients with HBV-ACLF. Specifically, the PI had a higher accuracy than the CTP, MELD, or MELD-Na scoring for early prediction short-term survival of HBV-ACLF patients with normal levels of serum creatinine (Cr. The survival rate in low risk group (PI < 3.91 was 94.3%, which was markedly higher than those in the high-risk group (PI ≥ 3.91 (17.4%, P < 0.001. CONCLUSION: We developed a new prognostic index combining serum CysC with TBil which early predicted the short-term mortality of HBV-ACLF patients.

  7. CD14(+)CD15(-)HLA-DR(-) myeloid-derived suppressor cells impair antimicrobial responses in patients with acute-on-chronic liver failure.

    Science.gov (United States)

    Bernsmeier, Christine; Triantafyllou, Evangelos; Brenig, Robert; Lebosse, Fanny J; Singanayagam, Arjuna; Patel, Vishal C; Pop, Oltin T; Khamri, Wafa; Nathwani, Rooshi; Tidswell, Robert; Weston, Christopher J; Adams, David H; Thursz, Mark R; Wendon, Julia A; Antoniades, Charalambos Gustav

    2017-06-07

    Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14(+)HLA-DR(-) myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses. Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30). CD14(+)CD15(-)CD11b(+)HLA-DR(-) cells were identified as per definition of M-MDSC and detailed immunophenotypic analyses were performed. Suppression of T cell activation was assessed by mixed lymphocyte reaction. Assessment of innate immune function included cytokine expression in response to Toll-like receptor (TLR-2, TLR-4 and TLR-9) stimulation and phagocytosis assays using flow cytometry and live cell imaging-based techniques. Circulating CD14(+)CD15(-)CD11b(+)HLA-DR(-) M-MDSCs were markedly expanded in patients with ACLF (55% of CD14+ cells). M-MDSC displayed immunosuppressive properties, significantly decreasing T cell proliferation (p=0.01), producing less tumour necrosis factor-alpha/interleukin-6 in response to TLR stimulation (all pDR during disease evolution was linked to secondary infection and 28-day mortality. Recurrent TLR-2 and TLR-4 stimulation expanded M-MDSC in vitro. By contrast, TLR-3 agonism reconstituted HLA-DR expression and innate immune function ex vivo. Immunosuppressive CD14(+)HLA-DR(-) M-MDSCs are expanded in patients with ACLF. They were depicted by suppressing T cell function, attenuated antimicrobial innate immune responses, linked to secondary infection, disease severity and prognosis. TLR-3 agonism reversed M-MDSC expansion and innate immune function and merits further evaluation as potential immunotherapeutic agent. © Article author(s) (or

  8. Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome.

    Science.gov (United States)

    Dhiman, Radha K; Agrawal, Swastik; Gupta, Tarana; Duseja, Ajay; Chawla, Yogesh

    2014-10-28

    To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF) in predicting short-term prognosis of patients with ACLF. Consecutive patients of cirrhosis with acute decompensation were prospectively included. They were grouped into ACLF and no ACLF groups as per CLIF-SOFA and APASL criteria. Patients were followed up for 3 mo from inclusion or mortality whichever was earlier. Mortality at 28-d and 90-d was compared between no ACLF and ACLF groups as per both criteria. Mortality was also compared between different grades of ACLF as per CLIF-SOFA criteria. Prognostic scores like CLIF-SOFA, Acute Physiology and Chronic Health Evaluation (APACHE)-II, Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were evaluated for their ability to predict 28-d mortality using area under receiver operating curves (AUROC). Of 50 patients, 38 had ACLF as per CLIF-SOFA and 19 as per APASL criteria. Males (86%) were predominant, alcoholic liver disease (68%) was the most common etiology of cirrhosis, sepsis (66%) was the most common cause of acute decompensation while infection (66%) was the most common precipitant of acute decompensation. The 28-d mortality in no ACLF and ACLF groups was 8.3% and 47.4% (P = 0.018) as per CLIF-SOFA and 39% and 37% (P = 0.895) as per APASL criteria. The 28-d mortality in patients with no ACLF (n = 12), ACLF grade 1 (n = 11), ACLF grade 2 (n = 14) and ACLF grade 3 (n = 13) as per CLIF-SOFA criteria was 8.3%, 18.2%, 42.9% and 76.9% (χ(2) for trend, P = 0.002) and 90-d mortality was 16.7%, 27.3%, 78.6% and 100% (χ(2) for trend, P < 0.0001) respectively. Patients with prior decompensation had similar 28-d and 90-d mortality (39.3% and 53.6%) as patients without prior decompensation (36.4% and 63.6%) (P = NS). AUROCs for 28-d mortality were 0.795, 0.787, 0.739 and 0.710 for CLIF-SOFA, APACHE

  9. TLR2 Expression in Peripheral CD4+ T Cells Promotes Th17 Response and Is Associated with Disease Aggravation of Hepatitis B Virus-Related Acute-On-Chronic Liver Failure

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    Chunli Xu

    2017-11-01

    Full Text Available Th17 responses have been shown to play crucial roles in the pathogenesis of hepatitis B virus (HBV-associated acute-on-chronic liver failure (ACLF. The mechanism underlying the enhanced Th17 responses in these patients remains largely unclear. Here we investigated toll-like receptors (TLRs expression in peripheral T cells and their roles in Th17 cell differentiation and disease aggravation in ACLF patients. 18 healthy subjects (HS, 20 chronic HBV-infected (CHB patients, and 26 ACLF patients were enrolled and examined for TLRs expression in peripheral blood mononuclear cells (PBMCs. The correlations of T cell TLR2 expression with the antigen non-specific Th17 responses and disease aggravation, as well as the Th17 response to TLR2 ligand stimulation were evaluated in ACLF patients. Compared to HS and CHB patients, ACLF patients showed a distinct TLRs expression pattern in PBMCs. Significantly increased TLR2 expression in T cells was observed in ACLF patients. The TLR2 expression in CD4+ T cells was correlated with the Th17 responses and the clinical markers for disease aggravation in ACLF patients. Moreover, TLR2 ligands stimulation promoted Th17 cell differentiation and response in PBMCs of ACLF patients. These findings implicate that TLR2 signaling plays critical roles in Th17 cell differentiation and disease aggravation of HBV-related ACLF.

  10. Short-term efficacy of treating hepatitis B virus-related acute-on-chronic liver failure based on cold pattern differentiation with hot herbs: A randomized controlled trial.

    Science.gov (United States)

    Guo, Yu-Ming; Li, Feng-Yi; Gong, Man; Zhang, Lin; Wang, Jia-Bo; Xiao, Xiao-He; Li, Jun; Zhao, Yan-Ling; Wang, Li-Fu; Zhang, Xiao-Feng

    2016-08-01

    To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction (, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus (HBV-ACLF) with cold pattern in Chinese medicine (CM). This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine (WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM (integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease (MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. The mortality was decreased 14.28% in the integrative treatment group compared with WM group (χ(2) =6.156, P=0.013). The integrative treatment was found to signifificantly improve the MELD score (t=2.353, P=0.020). There were statistically signifificant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups (P<0.05 or P<0.01). The complications of ascites (χ(2)=9.033, P=0.003) and spontaneous bacteria peritonitis (χ(2)=4.194, P=0.041) were improved signifificantly in the integrative treatment group. No serious adverse event was reported. The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy. (Trial registration No. ChiCTR-TRC-10000766).

  11. Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study.

    Science.gov (United States)

    Li, Yu-Hua; Xu, Ying; Wu, Hua-Mei; Yang, Jing; Yang, Li-Hong; Yue-Meng, Wan

    2016-12-01

    Search for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remains an important issue. This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation in patients with HBV-ACLF. 45 consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among these patients, 11 received both plasma exchange (PE) and a single transplantation of UC-MSCs (group A), while 34 received only PE (group B). The primary endpoint was survival at 24 months. Compared with group B, levels of albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin time (PT), international normalized ratio (INR) and model for end-stage liver disease score in group A improved significantly at 4 weeks after transplantation (p < 0.05). Levels of albumin, PT and INR in group A were also markedly improved at 24 months (p < 0.05). Group A had significantly higher cumulative survival rate at 24 months (54.5 % v.s. 26.5 %, p = 0.015 by log rank test). Between the two groups, levels of creatinine, White blood cell, hemoglobin and platelet were similar. HBeAg loss and hepatocellular carcinoma incidence were similar at 24 months. Group assignment (relative risk: 2.926, 95%confidence interval: 1.043-8.203, p = 0.041) was an independent predictor for survival at 24 months. Success rate of UC-MSC transplantation was 100 % in group A. No severe adverse event was observed in any patient. UC-MSC transplantation is safe and effective for HBV-ACLF patients treated with PE and entecavir. It further improves the hepatic function and survival.

  12. 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.

    Science.gov (United States)

    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

  13. NKP30-B7-H6 Interaction Aggravates Hepatocyte Damage through Up-Regulation of Interleukin-32 Expression in Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

    Science.gov (United States)

    Zou, Yong; Bao, Junjie; Pan, Xingfei; Lu, Ying; Liao, Sihong; Wang, Xicheng; Wang, Guoying; Lin, Dongjun

    2015-01-01

    Previous work conducted by our group has shown that the accumulation of hepatic natural killer (NK) cells and the up-regulation of natural cytotoxicity receptors (NKP30 and NKP46) on NK cells from patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) were correlated with disease progression in HBV-ACLF. The natural cytotoxicity receptors expressed on NK cells are believed to be probable candidates involved in the NK cell-mediated hepatocyte damage in HBV-ACLF. However, the underlying mechanisms remain to be elucidated. In the present study, we aimed to discover the role of NKP30-B7-H6 interaction in NK cells-mediated hepatocyte damage in HBV-ACLF. Hepatic expressions of B7-H6 and interleukin-32 (IL-32) were examined by immunochemistry staining in samples from patients with HBV-ACLF or mild chronic hepatitis B (CHB). The cytotoxicity of NK-92 cell against target cells (Huh-7 and LO2) was evaluated by CCK8 assay. Expression of IL-32 in liver NK cell, T cells and NK-92 cell line was detected by the flow cytometric analysis. The effect of IL-32 on the apoptosis of Huh7 cells was evaluated using Annexin V/PI staining analysis. An enhancement of hepatic B7-H6 and IL-32 expression was associated with the severity of liver injury in HBV-ACLF. And there was a positive association between hepatic B7-H6 and IL-32 expression. Expressions of IL-32 in liver NK cells and T cells were increased in HBV-ACLF patients. In vitro NK-92 cells are highly capable of killing the high B7-H6 expressing Huh7 cells and B7-H6-tansfected hepatocyte line LO2 cells dependent on NKP30 and B7-H6 interaction. Furthermore, NK-92 cells exhibited elevated IL-32 expression when stimulated with anti-NKP30 antibodies or when co-cultured with Huh7 cells. IL-32 can induce the apoptosis of Huh7 cells in a dose-dependent manner. Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up-regulation of IL-32 expression in HBV-ACLF.

  14. Urinary biomarkers for the prediction of reversibility in acute-on-chronic renal failure.

    Science.gov (United States)

    Luk, Cathy Choi-Wan; Chow, Kai-Ming; Kwok, Jeffrey Sung-Shing; Kwan, Bonnie Ching-Ha; Chan, Michael Ho-Ming; Lai, Ka-Bik; Lai, Fernand Mac-Moune; Wang, Gang; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

    2013-01-01

    There is no reliable clinical test to predict the reversibility of acute-on-chronic renal failure. We study whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal failure. We studied 39 adult patients with pre-existing chronic renal impairment presenting to us with acute-on-chronic renal failure. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level was measured. The mRNA of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), alpha-1-microglobulin (α1M), sodium/hydrogen exchanger-3 (NHE3), beta-2 microglobulin (β2M), and N-acetyl-β-D-glucosaminidase (NAG) in urinary sediment were quantified. Urinary NGAL level significantly correlated with the serum creatinine at presentation (r=0.762, pacute tubular necrosis than other causes of acute kidney injury (prenal function (r=0.387, p=0.026), as well as the estimated GFR 6 months later (r=0.386, p=0.027). In patients with acute-on-chronic renal failure, urinary NGAL level correlates with the severity of renal failure, while urinary α1M expression correlates with the degree of renal function recovery. Quantification of urinary α1M mRNA may be developed as an non-invasive tool for risk stratification of this group of patients.

  15. Analysis of TCM deficiency and excess attributes in patients with HBV-related acute-on-chronic liver failure based on phenotype of dendritic cells and function of T lymphocytes

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    YIN Sihan

    2016-04-01

    Full Text Available ObjectiveTo summarize the traditional Chinese medicine (TCM deficiency and excess attributes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF, and to analyze its association with the phenotype of dendritic cells (DCs and T lymphocyte subsets. MethodsThe basic information, stages, and TCM syndromes of 30 patients who were diagnosed with HBV-ACLF in The First Affiliated Hospital of Hunan University of Chinese Medicine from March to November, 2012 were collected, and according to their deficiency and excess attributes, they were divided into excess group and deficiency group. Ten healthy volunteers were enrolled as the control group. Flow cytometry was used to measure the percentage of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood and the expression rate of CD4+CD25highCD127low cells, as well as the expression rates of DCs with phenotypes of CD1α, HLA-DR, CD80, CD83, and CD86 which were isolated from peripheral blood mononucleated cells, induced, and cultured in vitro, and its association with TCM deficiency and excess attributes. The t-test was used for comparison of normally distributed continuous data between groups, the Wilcoxon rank sum test was used for comparison of continuous data which were not normally distributed between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsCompared with the healthy control group, the HBV-ACLF patients showed significant reductions in the percentages of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood and the expression rates of DCs with phenotypes of CD1α, HLA-DR, CD80, CD83, and CD86, as well as a significant increase in the expression rate of CD4+CD25highCD127lowcells (all P<0.01. Compared with the excess group, the deficiency group showed significant reductions in the percentages of CD3+ and CD4+ T lymphocytes and the expression rate of CD4+CD25highCD127low cells (all P<0.05. Compared with the deficiency group, the

  16. 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....

  17. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

    Liu, Jianping; Kjaergard, Lise Lotte; Als-Nielsen, Bodil

    2002-01-01

    Liver support systems may bridge patients to liver transplantation or recovery from liver failure. This review is to evaluate the beneficial and harmful effects of artificial and bioartificial support systems for acute and acute-on-chronic liver failure....

  18. Natural Killer Group 2A Expressed on Both Peripheral CD3-CD56+NK Cells and CD3+CD8+T Cells Plays a Pivotal Negative Regulatory Role in the Progression of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Yi, Rui-Tian; Niu, Ying-Hua; Liu, Hong-Li; Zhang, Tie-Ying; Yang, Yu-Cong; Zhang, Yu; Yin, Dong-Lin; Chen, Tian-Yan; Zhao, Ying-Ren

    2016-12-01

    To explore the role of surface receptors natural killer group 2A (NKG2A) and natural killer group 2D (NKG2D) on CD3+CD8+T cells and CD3-CD56+NK cells in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), we measured the expression of NKG2A and NKG2D on the surface of these 2 types of circulating cells by flow cytometry in 3 groups. One group consists of 36 patients with chronic hepatitis B (CHB), another one consists of 22 patients with HBV-related ACLF, and the last one has 12 normal controls (NC). The experimental result indicated that there was no significant difference in the proportion of CD3+CD8+T cells in total lymphocytes between the 3 groups. However, the percentage of CD3-CD56+NK cells in ACLF group was evidently higher than that in the CHB group (P NK cells between the 3 groups. The expression of NKG2A on CD3+CD8+T cells in the ACLF group was significantly higher than that in the NC group (P NK cells was significantly higher than that in the CHB group (P NK cells in the ACLF group was significantly more than that in the CHB group and NC group. The results indicate that the imbalance between NKG2A and NKG2D may contribute to the progression of HBV-related ACLF mediated by CD3-CD56+NK cells and CD3+CD8+T cells. Compared with NKG2D, NKG2A expressed on both peripheral CD3-CD56+NK cells and CD3+CD8+T cells plays a more pivotal negative regulatory role in the progression of HBV-related ACLF.

  19. Acute liver failure and acute kidney injury: Definitions, prognosis, and outcome

    NARCIS (Netherlands)

    Włodzimirow, K.A.

    2013-01-01

    The objective of this thesis was to investigate definitions, prognostic indicators and their association with adverse events, mainly mortality for acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute kidney injury (AKI).

  20. Perihepatic nodes detected by point-of-care ultrasound in acute hepatitis and acute-on-chronic liver disease.

    Science.gov (United States)

    Feng, I Che; Wang, Szu Jen; Sheu, Ming Jen; Koay, Lok-Beng; Lin, Ching Yih; Ho, Chung Han; Sun, Chi Shu; Kuo, Hsing Tao

    2015-11-28

    To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography. One hundred and seventy-six patients with an episode of acute hepatitis flare (ALT value > 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups (viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h (median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed Enlarged lymph nodes (width ≥ 5mm) were noticeable in 110 (62.5%) patients, mostly in acute on chronic hepatitis B (54.5%). The viral group had a higher prevalence rate (89/110 = 80.9%) and larger nodal size (median, 7 mm) than those of the non-viral group (21/66 = 31.8%; median, 0 mm) (P hepatitis A and non-hepatitis A viral groups (P hepatitis flare.

  1. Plasma Glutamine Concentrations in Liver Failure.

    Directory of Open Access Journals (Sweden)

    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.

  2. Acute Liver Failure

    Science.gov (United States)

    Acute liver failure Overview Acute liver failure is loss of liver function that occurs rapidly — in days or weeks — usually in a person who has no pre-existing liver disease. Acute liver failure is less common than ...

  3. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

    Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these.......Acute liver failure (ALF) results in a multitude of serious complications that often lead to multi-organ failure. This brief review focuses on the pathophysiological processes in ALF and how to manage these....

  4. 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...

  5. Acute Liver Failure.

    Science.gov (United States)

    Newland, Catherine D

    2016-12-01

    Pediatric acute liver failure (ALF) is a complex and rapidly progressive syndrome that results from a variety of age-dependent etiologies. It is defined by the acute onset of liver disease with no evidence of chronic liver disease. There must be biochemical or clinical evidence of severe liver dysfunction as defined by an international normalized ratio (INR) ≥2. If hepatic encephalopathy is present, INR should be ≥1.5. Unfortunately, due to the rarity of ALF in pediatric patients, there is a paucity of diagnostic and management algorithms and each patient must have an individualized approach. [Pediatr Ann. 2016;45(12):e433-e438.]. Copyright 2016, SLACK Incorporated.

  6. Auxiliary Liver Transplantation for Acute Liver Failure.

    Science.gov (United States)

    Shanmugam, Naresh P; Al-Lawati, Tawfiq; Kelgeri, Chaya; Rela, Mohamed

    2016-01-01

    Auxiliary partial orthotopic liver transplantation is a technique where part of diseased native liver is removed and replaced with healthy donor liver so that, the left behind native liver could later regenerate. 2 year 6 month old girl with acute liver failure due to Hepatitis A. She underwent a successful auxiliary partial orthotopic liver transplantation. Successful native liver regeneration and immunosuppression withdrawal after two and half years of surgery. In selective cases of acute liver failure, auxiliary partial orthotopic liver transplantation could provide a chance for native liver regeneration and immunosuppression-free life.

  7. Effect of noninvasive mechanical ventilation in elderly patients with hypercapnic acute-on-chronic respiratory failure and a do-not-intubate order

    Directory of Open Access Journals (Sweden)

    Paolo Scarpazza

    2008-10-01

    Full Text Available Paolo Scarpazza1, Cristoforo Incorvaia2, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Silvia Vanni1, Serena Bencini1, Chiara Pravettoni2, Giuseppe Di Cara3, Mona-Rita Yacoub4, Gian Galeazzo Riario-Sforza2, Enrico Guffanti5, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3University Department of Medical and Surgical Specialties and Public Health, Perugia, Italy; 4Allergy and Immunology Unit, IRCCS San Raffaele Hospital, Milan, Italy; 5Pulmonary rehabilitation, INRCA, Casatenovo, ItalyAbstract: Noninvasive mechanical ventilation (NIMV is effective in the treatment of patients with acute respiratory failure (ARF. It proved to reduce the need of endotracheal intubation (ETI, the incidence of ETI-associated pneumonia, and mortality compared to nonventilated patients. A particular aspect concerns the outcome of NIMV in patients referring to an emergency room (ER for ARF, and with a do-not-intubate (DNI status due to advanced age or critical conditions. The aim of our study is to assess the outcome of NIMV in a group of elderly patients with acute hypercapnic ARF who had a DNI status. An overall number of 62 subjects (30 males, 32 females, mean age 81 ± 4.8 years, range 79–91 years referred to our semi-intensive respiratory department were enrolled in the study. The underlying diseases were severe chronic obstructive pulmonary disease (COPD in 50/62 subjects, restrictive thoracic disorders in 7/62 subjects, and multiorgan failure in 5/62 subjects. Fifty-four/62 patients were successfully treated with NIMV while 2/62 did not respond to NIMV and were therefore submitted to ETI (one survived. Among NIMV-treated patients, death occurred in 6 patients after a mean of 9.9 days; the overall rate of NIMV failure was 12.9%. Negative prognostic factors for NIMV response

  8. Immune-mediated liver failure

    Directory of Open Access Journals (Sweden)

    WANG Xiaojing

    2014-10-01

    Full Text Available The primary causative factors of liver failure include direct damage and immune-mediated liver injury. Increasing evidence suggests that immune-mediated injury plays a pivotal role in the pathogenesis of liver failure. The new concepts concerning the mechanisms of immune-mediated liver injury in liver failure are reviewed with relevant basic and clinical studies in both humans and animals. The innate and adaptive immunity, particularly the interaction of various immune cells and molecules, as well as apoptosis-related molecules, are discussed in detail.

  9. Allocation of patients with liver cirrhosis and organ failure to intensive care

    DEFF Research Database (Denmark)

    Prier Lindvig, Katrine; Søgaard Teisner, Ane; Kjeldsen, Jens

    2015-01-01

    patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature...... on current available data we developed an algorithm, to determine if a patient is candidate to intensive care if needed, based on three scoring systems: premorbid Child-Pugh Score, Model of End stage Liver Disease score and the liver specific Sequential Organ Failure Assessment score. CONCLUSION......AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized...

  10. Acute Liver Injury and Failure.

    Science.gov (United States)

    Thawley, Vincent

    2017-05-01

    Acute liver injury and acute liver failure are syndromes characterized by a rapid loss of functional hepatocytes in a patient with no evidence of pre-existing liver disease. A variety of inciting causes have been identified, including toxic, infectious, neoplastic, and drug-induced causes. This article reviews the pathophysiology and clinical approach to the acute liver injury/acute liver failure patient, with a particular emphasis on the diagnostic evaluation and care in the acute setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Changes in serum electrolytes during treatment of patients in liver failure with molecular adsorbent recirculating system.

    Science.gov (United States)

    Doria, C; Doyle, H R; Mandalà, L; Marino, I R; Caruana, G; Gruttadauria, S; Lauro, A; Magnone, M; Scotti Foglieni, C; Lamonaca, V; Scott, V L

    2003-10-01

    To study the effect of MARS on serum electrolytes during liver failure. Twenty-three patients admitted to a quaternary health care facility from September 2000 to May 2002, 22 adults and 1 child, 11 males (48%) and 12 females (52%), age 15-70 (median 53), treated with MARS for: 12 acute-on-chronic liver failure (52%); 4 fulminant hepatic failure (17%); 3 intractable pruritus (13%); 2 primary-non-function (9%); 2 following major liver resection (9%). Sodium, potassium, chloride, phosphorus, calcium, and magnesium were measured in the serum, ultrafiltrate and albumin circuit before and after MARS. A comparison of electrolyte concentrations, before and after MARS, was performed using a paired t test. Serum electrolyte concentrations before and after MARS, while statistically significant in some cases, were very small, and of no clinical relevance. MARS exchanges potassium, chloride, calcium, and magnesium by ultrafiltration; sodium by the albumin dialysis.

  12. Mediastinal Pseudocyst in Acute on Chronic Pancreatitis.

    Science.gov (United States)

    Mishra, Sushil Kumar; Jain, Pawan Kumar; Gupta, Sukhdev

    2016-03-01

    Pseudocyst is a common complication of Acute and chronic pancreatitis. However, its extension into the mediastinum is a rare entity. We present a case of 52 years male with acute on chronic pancreatitis (alcohol related) who presented with dysphagia and dyspnoea and was found to have a pancreatic pseudocyst extending upto the neck. Ultrasound fails to pick up mediastinal pseudocysts and requires additional imaging modalities - CT and MRI. Management of Mediastinal pseudocyst depends upon underlying etiology, ductal anatomy, size of the pseudocyst, and availability of expertise. Small pseudocysts in asymptomatic patients may resolve spontaneously, but requires prolonged conservative therapy with somatostatin or its analogue and Total Parenteral Nutrition. Ruptured pseudocyst in a symptomatic unstable patient requires surgical resection. Endoscopic ultrasound guided drainage (transmural or transpapillary) and Main Pancreatic Duct stenting are safe and effective treatment modality. © Journal of the Association of Physicians of India 2011.

  13. related chronic liver disease

    African Journals Online (AJOL)

    Yomi

    2012-03-08

    Mar 8, 2012 ... Gelsolin, an actin-binding protein, which serves as a substrate of caspase in tissue injury has been proposed as a prognostic marker in acute .... hepatic cirrhosis patients together with hepatocellular carcinoma, and acute-on-chronic liver failure .... al., 2000). Cellular over-expression can inhibit the release ...

  14. 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

  15. Management in acute liver failure.

    Science.gov (United States)

    Shalimar; Acharya, Subrat K

    2015-03-01

    Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available.

  16. Acute liver failure : Spontaneous recovery or transplantation?

    NARCIS (Netherlands)

    Meerman, L; Zijlstra, JG; Schweizer, JJ; Verwer, R; Slooff, MJH; Haagsma, EB

    1997-01-01

    Background: Decision-making in acute liver failure. Acute liver failure is a disease with multiple organ involvement and a high mortality rate. Conservative management alone will only partly influence the outcome. The option of emergency liver transplantation has greatly improved survival rates, but

  17. Valproic Acid-Associated Liver Failure

    OpenAIRE

    J Gordon Millichap

    2011-01-01

    Researchers at the University of Maryland School of Medicine, Baltimore, and other centers analyzed the records of 17 children undergoing liver transplantation (LT) for valproic acid-associated liver failure (VPA-ALF) and 98 with ALF caused by other drugs (non-VPA-drug-induced acute liver failure [DIALF].

  18. Timing of glucocorticoid therapy for liver failure

    Directory of Open Access Journals (Sweden)

    MENG Qinghua

    2017-09-01

    Full Text Available There are still controversies over the use of glucocorticoids in the treatment of liver failure, and current guidelines for liver failure recommend that glucocorticoids should be used with great caution. However, some latest studies have shown that the use of glucocorticoid therapy in the early stage of liver failure can bring more benefits to patients. Age, disease progression rate and severity, and complications of liver failure may affect the treatment outcome. Further studies are still needed for the selection of right patients, drugs and dose, and treatment timing.

  19. 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

    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), is a negat......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...... through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals). Circulating CD4+T cells were isolated...

  20. Metabolic Liver Diseases Presenting as Acute Liver Failure in Children.

    Science.gov (United States)

    Alam, Seema; Lal, Bikrant Bihari

    2016-08-08

    Suspecting metabolic liver disease in an infant or young child with acute liver failure, and a protocol-based workup for diagnosis is the need of the hour. Data over the last 15 years was searched through Pubmed using the keywords Metabolic liver disease and Acute liver failure with emphasis on Indian perspective. Those published in English language where full text was retrievable were included for this review. Metabolic liver diseases account for 13-43% cases of acute liver failure in infants and young children. Etiology remains indeterminate in very few cases of liver failure in studies where metabolic liver diseases were recognized in large proportion. Galactosemia, tyrosinemia and mitochondrial disorders in young children and Wilsons disease in older children are commonly implicated. A high index of suspicion for metabolic liver diseases should be kept when there is strong family history of consanguinity, recurrent abortions or sibling deaths; and history of recurrent diarrhea, vomiting, failure to thrive or developmental delay. Simple dietary modifications and/or specific management can be life-saving if instituted promptly. A high index of suspicion in presence of red flag symptoms and signs, and a protocol-based approach helps in timely diagnosis and prompt administration of lifesaving therapy.

  1. Acute liver failure and self-medication.

    Science.gov (United States)

    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.

  2. Therapeutic hypothermia for acute liver failure

    DEFF Research Database (Denmark)

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Liver failure in total artificial heart therapy.

    Science.gov (United States)

    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.

  5. Celecoxib-induced cholestatic liver failure requiring orthotopic liver transplantation

    Science.gov (United States)

    El Hajj, Ihab I; Malik, Shahid M; Alwakeel, Hany R; Shaikh, Obaid S; Sasatomi, Eizaburo; Kandil, Hossam M

    2009-01-01

    Selective cyclooxygenase-2 (COX-2) inhibitors are widely used due to their efficacy and good safety profile. However, recent case reports have described varying degrees of liver injuries associated with the use of COX-2 inhibitors. We report the case of a patient who developed acute cholestatic hepatitis progressing to hepatic failure requiring liver transplantation, following a 3-d course of celecoxib for treatment of generalized muscle aches and pains. The clinical presentation, the laboratory data, as well as the liver histopathology were supportive of the putative diagnosis of drug induced liver injury. PMID:19701976

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Acute Liver Failure Secondary to Niacin Toxicity

    OpenAIRE

    Ellsworth, Marc A.; Anderson, Katelyn R.; Hall, David J.; Freese, Deborah K.; Lloyd, Robin M.

    2014-01-01

    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 l...

  8. Acute Ischemic Stroke and Acute on Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Raja Ahsan Aftab

    2016-06-01

    Full Text Available Ischemic stroke is due to either local thrombus formation or emboli that occlude a cerebral artery, together with chronic kidney disease represent major mortality and morbidity. Here wer present a case of 53 years old Malay man, admitted to a hospital in Malaysia complaining of sudden onset of weakness on right sided upper and lower limb associated with slurred speech. Patient was also suffering from uncontrolled hypertension, hyperlipidemia, chronic kidney disease stage 4, and diabetes mellitus(un controlled. He was diagnosed with acute ischemic stroke with cranial nerve 7 palsy (with right hemiparesis, acute on chronic kidney disease precipitated by dehydration and ACE inhibitor, and hyperkalemia. Patients with ischemic disease and chronic kidney disaese require constant monitering and carefull selected pharmacotherapy. Patient was placed under observation and was prescribed multiple pharamacotherpay to stabalise detoriating condition. Keywords: ischemic disease; chronic kidney disease; uncontrolled hypertension. | PubMed

  9. Mechanisms of fibrosis in acute liver failure.

    Science.gov (United States)

    He, Yingli; Jin, Li; Wang, Jing; Yan, Zhi; Chen, Tianyan; Zhao, Yingren

    2015-07-01

    Acute liver failure (ALF) is a condition with high mortality and morbidity. Fibrosis in chronic liver disease was extensively researched, whereas fibrosis and underlying mechanism in acute liver failure remains unclear. Hepatitis B virus related ALF patients were recruited to investigate if there was ongoing fibrosis by liver histology and liver stiffness measurement(LSM) analysis as well as fibrosis markers assay. Sera HMGB1 were kinetically detected in progression and remission stage of ALF. Hepatic stellate cell(HSC) activation by HMGB1 was explored by testing mRNA and protein level of α-SMA and collagen 1a1 by using qPCR and western blot. Autophagy induction by HMGB1 was explored by LC3-II conversion, autophagy flux and fluorescence. Firstly, ongoing fibrosis in progression stage of ALF was confirmed by histological analysis, LS measurement as well as fibrosis markers detection. HSC activation and autophagy induction in explanted liver tissue also revealed. Next, kinetic monitoring sera HMGB1 revealed elevated HMGB1 in progression stage of ALF vs HBsAg carrier, and drop back to base level in remission stage. Thirdly, rHMGB1 dose dependently activated HSCs, as indicated by increased mRNA and proteins level in α-SMA and collagen 1a1. Moreover, autophagy was induced in HSC treated with rHMGB1, as illustrated by increased LC3 lipidation, elevated autophagy flux and GFP-LC3 puncta. Acute liver failure is accompanied by ongoing fibrosis, HSC activation and autophagy induction. Increased HMGB1 activates HSC via autophagy induction. Those findings integrate HMGB1, HSCs activation, autophagy into a common framework that underlies the fibrosis in ALF. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

  10. Stem cells in acute liver failure.

    Science.gov (United States)

    Wesson, Russell N; Cameron, Andrew M

    2011-01-01

    Patients with acute liver failure are a particularly challenging group, with unique difficulties faced in treatment decisions. Life-saving therapy is available, but organ shortage, delays in transplantation, and complications in management result in a high mortality in this group of patients even after transplant. Any pharmacologic intervention that improved outcomes in this population of critically ill patients would be of great benefit. Based on available evidence, different scenarios of participation of HSCs in liver recovery are conceivable. Encouraging HSCs to differentiate into hepatocytes or supply paracrine and cellular level support to accelerate ongoing local repair mechanisms and assist a failing liver with inadequate mass and functional capacity might be directed to occur effectively in humans. Evidence within small animal models of liver injury and observations within the human population suggest that this might also be encouraged. The use of pharmacologic agents to mobilize hematopoietic stem cells is well established and effectively used in a different population of patients. As such, extending the use of these drugs, such as plerixafor, to the human population has a sound basis. However, there is a need for clarification of the mechanisms by which these cells exert their effect as well as which specific population of cells is involved in the regenerative process. To be clinically relevant in scenarios of acute liver failure, stem cell mobilizing strategies would have to impact survival when administered well after injury. Applications in other settings may also prove useful. Limits to liver resection exist where the size of the future liver remnant governs the extent of resection possible. Preexisting functional impairment may be restrictive, and strategies involving stem cells may assist the future liver remnant in both normal and functionally impaired livers. Benefit has already been reported from treatment with G-CSF in other injured tissues

  11. Acute Liver Failure Secondary to Niacin Toxicity

    Directory of Open Access Journals (Sweden)

    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.

  12. Prognostic modeling in pediatric acute liver failure.

    Science.gov (United States)

    Jain, Vandana; Dhawan, Anil

    2016-10-01

    Liver transplantation (LT) is the only proven treatment for pediatric acute liver failure (PALF). However, over a period of time, spontaneous native liver survival is increasingly reported, making us wonder if we are overtransplanting children with acute liver failure (ALF). An effective prognostic model for PALF would help direct appropriate organ allocation. Only patients who would die would undergo LT, and those who would spontaneously recover would avoid unnecessary LT. Deriving and validating such a model for PALF, however, encompasses numerous challenges. In particular, the heterogeneity of age and etiology in PALF, as well as a lack of understanding of the natural history of the disease, contributed by the availability of LT has led to difficulties in prognostic model development. Several prognostic laboratory variables have been identified, and the incorporation of these variables into scoring systems has been attempted. A reliable targeted prognostic model for ALF in Wilson's disease has been established and externally validated. The roles of physiological, immunological, and metabolomic parameters in prognosis are being investigated. This review discusses the challenges with prognostic modeling in PALF and describes predictive methods that are currently available and in development for the future. Liver Transplantation 22 1418-1430 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  13. 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

  14. 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...

  15. Acute liver failure complicating viral hepatitis A

    Directory of Open Access Journals (Sweden)

    Daniel Rui Diniz-Santos

    Full Text Available Hepatitis A is one of the most frequent infectious liver diseases affecting children worldwide. The disease is usually mild and self-limited, and complications are very rare. Nevertheless, hepatitis A can sometimes cause acute liver failure (ALF, a severe, life-threatening condition. Herein is reported a case of a child who presented ALF during a course of hepatitis A. The need for early identification of possible ALF cases among hepatitis A patients, and for effective ways of evaluating such a possibility, are discussed. We also emphasize the importance of prevention measures, especially vaccination.

  16. HEPATIC DIALYSIS IN NEONATES WITH ACUTE LIVER FAILURE

    OpenAIRE

    Stancu, Samantha Mc Kenzie; Cirstoveanu, Catalin Gabriel

    2016-01-01

    Hepatic dialysis is an artificial extracorporeal liver support device designed to filter out toxins accumulated in patients with acute liver failure. Although it is a rare entity encountered in neonates, acute liver failure is a highly fatal condition, with seventy percent resulting in mortality without liver transplantation. Scientific data on extracorporeal liver support concerning the pediatric population is scarce in literature. Artificial extracorporeal liver support devices in the form ...

  17. Use of the molecular adsorbent recirculating system (MARS™) for the management of acute poisoning with or without liver failure.

    Science.gov (United States)

    Wittebole, Xavier; Hantson, Philippe

    2011-11-01

    cardiovascular or neurological dysfunction has been shown both in acute liver failure and acute-on-chronic liver failure but no impact on mortality has been reported. ACUTE POISONING WITH LIVER FAILURE: Randomized controlled trials are very limited in number and patients poisoned by paracetamol or Amanita phalloides are usually included for outcome analysis in larger groups of acute liver failure patients. Initial results look promising but should be confirmed. Beyond its effect in liver failure, MARS™ could also enhance the elimination of the drug or toxin responsible for the failure, as is described with paracetamol. ACUTE POISONING WITHOUT LIVER FAILURE: Extracorporeal liver assist devices have also been used to promote elimination of drugs that are highly protein bound. Data in various case reports confirm a high elimination of phenytoin, theophylline and diltiazem. However, definite conclusions on the toxicokinetic or clinical efficacy cannot be drawn. Despite the lack of large multicentre randomized trials on the use of MARS™ in patients with acute liver failure, the literature shows clinical and biological benefit from this technique. In drug or toxin-induced acute liver failure, such as paracetamol or mushroom poisoning, MARS™ has been used extensively, confirming in a non-randomized fashion, the positive effect observed in the larger population of acute liver failure patients. Furthermore, as MARS™ has been shown in experimental studies to remove protein-bound substances, it is potentially a promising treatment for patients with acute poisoning from drugs that have high protein-binding capacity and are metabolized by the liver, especially, if they develop liver failure concomitantly.

  18. Rescue Living-donor Liver Transplantation for Liver Failure Following Hepatectomy for Hepatocellular Carcinoma

    OpenAIRE

    Chan, See Ching; Sharr, William Wei; Chan, Albert Chi Yan; Chok, Kenneth Siu Ho; Lo, Chung Mau

    2013-01-01

    Liver failure following major hepatectomy for hepatocellular carcinoma is a known but uncommon mode of early treatment failure. When post-hepatectomy liver failure becomes progressive, the only effective treatment for rescuing the patient is liver transplantation. Deceased-donor liver transplantation in this situation is often not feasible because of the shortage of deceased-donor liver grafts. Proceeding with living-donor liver transplantation is an ethical challenge because of the possibili...

  19. Etiology of pediatric acute liver failure

    OpenAIRE

    GUO Jing; SUN Mei

    2017-01-01

    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 disea...

  20. "ACUTE LIVER FAILURE" : THE HEART MAY BE THE MATTER

    NARCIS (Netherlands)

    de Leeuw, K.; van der Horst, I. C. C.; van der Berg, A. P.; Ligtenberg, J. J. M.; Tulleken, J. E.; Zijlstra, J. G.; Meertens, John H. J. M.

    2011-01-01

    Hypoxic hepatitis secondary to heart failure is a known and treatable cause of liver failure. The diagnosis may be difficult, especially when symptoms of heart failure are absent. We present two patients who were transferred to our hospital with the diagnosis of acute liver failure to be screened

  1. Research advances in liver failure of unknown etiology

    Directory of Open Access Journals (Sweden)

    ZHU Bing

    2015-09-01

    Full Text Available A high proportion of the causes of liver failure remain unknown. This paper reviews the progress in the epidemiology, etiology, treatment, and prognosis of liver failure of unknown etiology. The possible causes of liver failure of unknown etiology may include occult hepatitis B virus infection, herpesvirus infection, transfusion-transmitted virus infection, hepatitis G virus infection, human parvovirus Bl9 infection, autoimmune and hepatitis. Aciclovir can be considered in the empirical treatment for patients with liver failure of unknown etiology. The mortality in patients with liver failure of unknown etiology is high. The research on the etiology and treatments should be strengthened.

  2. Use of sodium polystyrene sulfonate in an acute-on-chronic lithium poisoned patient: A case report

    Directory of Open Access Journals (Sweden)

    Chakroun-Walha Olfa

    2016-03-01

    Full Text Available A 35-year-old woman with an acute-on-chronic lithium overdose received multiple oral doses of sodium polystyrene sulfonate totaling 120 g over a 24-h period. During the 72 h after the institution of therapy, the serum lithium level decreased from 3.80 to 0.42 mEq/L. Multiple doses of sodium polystyrene sulfonate may be useful in lowering the serum lithium level in severely ill patients with acute renal failure, and can substitute hemodialysis.

  3. 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....../mL; range 2.6-86.4). RA and SF post op patients had elevated OPN levels (37ng/mL and 198ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603ng/mL) and ischemia-related ALF (4102ng/mL) as opposed to viral hepatitis (706ng/mL), drug-induced liver...

  4. Intensive Care Management of Pediatric Acute Liver Failure.

    Science.gov (United States)

    Lutfi, Riad; Abulebda, Kamal; Nitu, Mara E; Molleston, Jean P; Bozic, Molly A; Subbarao, Girish

    2017-05-01

    Pediatric acute liver failure is rare but life-threatening illness that occurs in children without preexisting liver disease. The rarity of the disease, along with its severity and heterogeneity, presents unique clinical challenges to the physicians providing care for pediatric patients with acute liver failure. In this review, practical clinical approaches to the care of critically ill children with acute liver failure are discussed with an organ system-specific approach. The underlying pathophysiological processes, major areas of uncertainty, and approaches to the critical care management of pediatric acute liver failure are also reviewed.

  5. Etiology of pediatric acute liver failure

    Directory of Open Access Journals (Sweden)

    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.

  6. Liver failure after hepatocellular carcinoma surgery.

    Science.gov (United States)

    Motoyama, Hiroaki; Kobayashi, Akira; Yokoyama, Takahide; Shimizu, Akira; Furusawa, Norihiko; Sakai, Hiroshi; Kitagawa, Noriyuki; Ohkubo, Yohei; Tsukahara, Teruomi; Miyagawa, Shin-ichi

    2014-12-01

    The aim of this study was to construct a prediction model for posthepatectomy liver failure (PHLF), as defined by the International Study Group of Liver Surgery, and evaluate its accuracy in hepatocellular carcinoma (HCC) patients with cirrhosis or chronic hepatitis. A total of 277 consecutive hepatectomies for HCC between 2005 and 2013 were analyzed retrospectively. Multivariate logistic regression analysis was used to develop a predictive model for PHLF. The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were evaluated. The Hosmer-Lemeshow goodness-of-fit test was used to assess the model calibration. The constructed model was internally validated by k-fold cross-validation (k=5). PHLF developed in 12.6% of hepatectomies. Multivariate analysis identified the following variables as predictors of PHLF: elevated preoperative serum bilirubin level, elevated preoperative international normalized ratio, and intraoperative packed red blood cell transfusion. The predictive model allowed discrimination between patients who developed PHLF and those who did not, with a sensitivity of 82.9%, specificity of 72.3%, and AUROC curve of 0.81 (95% CI, 0.74 to 0.89). The Hosmer-Lemeshow test indicated a good fit (P=0.545). The AUROC curve of the developed model was significantly greater than that of the model for end-stage liver disease (MELD) score (P=0.014), suggesting that the former model is better at predicting the PHLF than the latter one. The developed model could be useful for predicting the occurrence of PHLF in HCC patients with underlying liver disease.

  7. Pediatric intestinal failure-associated liver disease.

    Science.gov (United States)

    Courtney, Cathleen M; Warner, Brad W

    2017-06-01

    The goal of this review is to provide updates on the definition, pathophysiology, treatment, and prevention of intestinal failure-associated liver disease (IFALD) that are relevant to care of pediatric patients. Current literature emphasizes the multifactorial nature of IFALD. The pathogenesis is still largely unknown; however, molecular pathways have been identified. Key to these pathways are proinflammatory cytokines involved in hepatic inflammation and bile acids synthesis such as Toll-like receptor 4 and farnesoid X receptor, respectively. Research for prevention and treatment is aimed at alleviating risk factors associated with IFALD, principally those associated with parental nutrition. Multiple nutrients and amino acids are relevant to the development of IFALD, but lipid composition has been the primary focus. Lipid emulsions with a lower ratio of omega-6-to-omega-3 polyunsaturated fatty acids (FAs) appear to improve bile flow and decrease intrahepatic inflammation. Long-term consequences of these alternative lipid emulsions are yet to be determined. IFALD remains the greatest contributor of mortality in patients with intestinal failure. Many factors contribute to its development, namely, alterations in the gut microbiome, sepsis, and lack of enteral intake. Novel combinations of lipid formulations are promising alternatives to purely soy-based formulas to reduce cholestasis.

  8. Liver transplantation in an adolescent with acute liver failure from acute lymphoblastic leukemia.

    Science.gov (United States)

    Reddi, D M; Barbas, A S; Castleberry, A W; Rege, A S; Vikraman, D S; Brennan, T V; Ravindra, K V; Collins, B H; Sudan, D L; Lagoo, A S; Martin, A E

    2014-03-01

    The most common identifiable causes of acute liver failure in pediatric patients are infection, drug toxicity, metabolic disease, and autoimmune processes. In many cases, the etiology of acute liver failure cannot be determined. Acute leukemia is an extremely rare cause of acute liver failure, and liver transplantation has traditionally been contraindicated in this setting. We report a case of acute liver failure in a previously healthy 15-yr-old male from pre-B-cell acute lymphoblastic leukemia. He underwent liver transplantation before the diagnosis was established, and has subsequently received chemotherapy for pre-B-cell acute lymphoblastic leukemia. He is currently alive 31 months post-transplantation. The published literature describing acute lymphoblastic leukemia as a cause of acute liver failure is reviewed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. CRRT Regional Anticoagulation Using Citrate in the Liver Failure and Liver Transplant Population.

    Science.gov (United States)

    Wonnacott, Rob; Josephs, Brandi; Jamieson, Jill

    2016-01-01

    Regional citrate for continuous renal replacement therapy (CRRT) use in patients with liver failure or post-liver transplant has been considered a contraindication because of the risk of citrate toxicity development. Regional citrate has the benefit of decreased bleeding risks over systemic anticoagulation; therefore, it is of great benefit to the coagulopathic and surgical populations. This article analyzes current empiric data and compares with a case study specifically related to liver failure, liver transplant, and CRRT use. We found that the use of a total serum to ionized calcium ratio was much more reliable in measuring liver function than liver enzyme figures. This when paired with a citrate-reduction guideline based on serum to ionized calcium ratios provided effective, early management of citrate toxicity. Using new measurements to calculate liver metabolism of citrate and using a new citrate-reducing guideline allow the bedside practitioner to use regional citrate anticoagulation in patients with liver failure and liver transplant who require CRRT.

  10. Cerebral blood flow autoregulation in experimental liver failure

    DEFF Research Database (Denmark)

    Dethloff, T.J.; Larsen, F.S.; Knudsen, Gitte Moos

    2008-01-01

    Patients with acute liver failure (ALF) display impairment of cerebral blood flow (CBF) autoregulation, which may contribute to the development of fatal intracranial hypertension, but the pathophysiological mechanism remains unclear. In this study, we examined whether loss of liver mass causes...... impairment of CBF autoregulation. Four rat models were chosen, each representing different aspects of ALF: galactosamine (GlN) intoxication represented liver necrosis, 90% hepatectomy (PHx90) represented reduction in liver mass, portacaval anastomosis (PCA) represented shunting of blood...... edema/high ICP. Nor does portacaval shunting or hyperammonemia impair autoregulation. Rather, massive liver necrosis and reduced liver mass are associated with loss of CBF autoregulation Udgivelsesdato: 2008/5...

  11. Acute renal failure in liver transplant patients: Indian study.

    Science.gov (United States)

    Naik, Pradeep; Premsagar, B; Mallikarjuna, M

    2015-01-01

    The acute renal failure is the frequent medical complication observed in liver transplant patients. The objective of this study was to determine the cause of acute renal failure in post liver transplant patients. A total of 70 patients who underwent (cadaveric 52, live 18) liver transplantation were categorized based on clinical presentation into two groups, namely hepatorenal failure (HRF, n = 29), and Hepatic failure (HF, n = 41). All the patients after the liver transplant had received tacrolimus, mycophenolate and steroids. We analyzed the modification of diet in renal disease, (MDRD) serum urea, creatinine and albumin before and after 5th and 30th day of liver transplant and data was categorized into survivors and non-survivors group. In HRF survivor group, serum creatinine, and urea levels were high and, albumin, MDRD were low in pre- transplant and reached to normal levels on 30th day of post transplant, and 79.3 % of patients in this group showed resumption of normal kidney function. On the contrary in HRF nonsurvivor group, we did not observed any significant difference and 20.7 % of patients showed irreversible changes after the liver transplant. In HF survivor group, 82.9 % of liver failure patients did not show any deviation in serum creatinine, urea, albumin and MDRD, whereas in HF non survivor group, 17.1 % of liver failure patients who had HCV positive before the transplant developed acute renal failure. The levels of creatinine, urea, albumin and MDRD were normal before the transplant and on day 30th, the levels of albumin and MDRD were significantly low whereas serum urea, creatinine levels were high. In conclusion, based on these observations, an diagnosis and treatment of Acute renal failure is important among the liver transplantation cases in the early postoperative period.

  12. Rescue Living-donor Liver Transplantation for Liver Failure Following Hepatectomy for Hepatocellular Carcinoma.

    Science.gov (United States)

    Chan, See Ching; Sharr, William Wei; Chan, Albert Chi Yan; Chok, Kenneth Siu Ho; Lo, Chung Mau

    2013-08-01

    Liver failure following major hepatectomy for hepatocellular carcinoma is a known but uncommon mode of early treatment failure. When post-hepatectomy liver failure becomes progressive, the only effective treatment for rescuing the patient is liver transplantation. Deceased-donor liver transplantation in this situation is often not feasible because of the shortage of deceased-donor liver grafts. Proceeding with living-donor liver transplantation is an ethical challenge because of the possibility of donor coercion. In addition, tumor status, as confirmed by histopathological examination of the resected specimen, may indicate aggressive cancer that warns against rescue transplantation because of the increased chance of tumor recurrence. Here we describe four cases of rescue living-donor liver transplantation for liver failure after hepatectomy for hepatocellular carcinoma. The patients all survived the transplantation and were free from tumor recurrence after follow-up periods ranging from 6 months to 9 years. Our experience has shown that rescue living-donor liver transplantation for post-hepatectomy liver failure is feasible. Tumor status should be considered carefully because large tumors and tumors with macrovascular invasion are strong contraindications to rescue living-donor liver transplantation.

  13. Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: A prospective cohort study.

    Science.gov (United States)

    Chong, Charing Ching-Ning; Wong, Grace Lai-Hung; Chan, Anthony Wing-Hung; Wong, Vincent Wai-Sun; Fong, Anthony Kwong-Wai; Cheung, Yue-Sun; Wong, John; Lee, Kit-Fai; Chan, Stephen L; Lai, Paul Bo-San; Chan, Henry Lik-Yuen

    2017-02-01

    Liver stiffness measurement using transient elastography appears to be an excellent tool for detection of liver fibrosis and cirrhosis with high accuracy. The aim of this study is to evaluate the efficacy of preoperative liver stiffness measurement in predicting post-hepatectomy liver failure. A prospective cohort study of all consecutive patients undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August 2014 was studied. All patients received detailed preoperative assessments including liver stiffness measurement. The primary outcome was post-hepatectomy liver failure according to the International Study Group of Liver Surgery definition. A total of 255 patients were included. Liver stiffness measurement showed significant correlation with grade B or C post-hepatectomy liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness measurement > 12 kPa was also an independent prognostic factor for both high-grade post-hepatectomy liver failure and major postoperative complications by multivariate analysis. The diagnostic accuracy was better in patients without right lobe tumor with an area under the receiver operating characteristic of 0.83 compared with an area under the receiver operating characteristic of only 0.62 in patients with right lobe tumor. Liver stiffness measurement using Fibroscan is good to predict high-grade post-hepatectomy liver failure especially in patients without right lobe tumor. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Treatment of acute liver failure in pigs reduces hepatocyte function in a bioartificial liver support system

    NARCIS (Netherlands)

    Abrahamse, S. L.; van de Kerkhove, M. P.; Sosef, M. N.; Hartman, R.; Chamuleau, R. A. F. M.; van Gulik, T. M.

    2002-01-01

    Several different types of bioartificial liver (BAL) support systems have been developed to bridge patients suffering from acute liver failure (ALF) to transplantation or liver regeneration. In this study we assessed the effects of ALF plasma on hepatocyte function in the BAL system that has been

  16. Enucleation after Embolization of Liver Failure-Causing Giant Liver Hemangioma

    Science.gov (United States)

    Sharma, Amit; Kaspar, Matthew; Siddiqui, Mohammad; Kim, Joohyun

    2015-01-01

    Patient: Female, 73 Final Diagnosis: Giant liver hemangioma Symptoms: Abdominal discomfort • abdominal enlargement • Icterus Medication: — Clinical Procedure: Enucleation after embolization of liver failure-causing giant liver Specialty: Surgery Objective: Unusual clinical course Background: Hepatic hemangioma is a congenital tumor of the mesenchymal tissues of the liver. While typically benign, these tumors can occasionally grow to sufficient size to cause a number of symptoms, including pain, severe hepatic dysfunction, or, rarely, consumptive coagulopathy. In such instances, surgical treatment may be warranted. Case Report: We present a case of a symptomatic giant hepatic hemangioma in an elderly patient who presented with impending liver failure. She was successfully treated with a combination of surgical enucleation and liver resection after preoperative arterial embolization. We also provide a brief discussion of current treatment options for giant hepatic hemangiomas. Conclusions: Early referral to experienced surgical centers before the onset of dire complications such as severe hepatic dysfunction and liver failure is recommended. PMID:26301888

  17. Liver failure following biliopancreatic diversions: a narrative review

    National Research Council Canada - National Science Library

    Everton Cazzo; José Carlos Pareja; Elinton Adami Chaim

    ABSTRACT CONTEXT AND OBJECTIVE: Occurrences of liver failure following jejunoileal bypass were extensively reported in the past and were one of the main factors that led to abandonment of this procedure...

  18. Subacute liver failure by pseudocirrhotic metastatic breast cancer infiltration.

    Science.gov (United States)

    Jüngst, Christoph; Krämer, Jens; Schneider, Günther; Lammert, Frank; Zimmer, Vincent

    2013-01-01

    Hepatic metastases are common in the clinical course of breast cancer and typically appear as mass lesions. This report describes the case of a 70-year-old woman with a history of breast cancer and no previously known liver disease presenting with the first episode of variceal bleeding and subacute hepatic failure. Imaging studies indicated liver cirrhosis without signs of malignant focal lesions. Comprehensive diagnostic work-up was negative for specific causes of liver disease and provided no evidence for tumor recurrence. Finally transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of metastatic, tumor spread representing a rare but important differential diagnosis of progressive liver failure. Liver biopsy is the key procedure to establish the diagnosis as imaging studies may mimic cirrhosis.

  19. Outcome from molecular adsorbent recycling system (MARS) liver dialysis following drug-induced liver failure.

    Science.gov (United States)

    Lee, Kang-Hoe; Lee, Margaret Kwee-Hiang; Sutedja, Dede Selamat; Lim, Seng-Gee

    2005-10-01

    Fulminant liver failure from drug ingestion is associated with a high mortality, and the introduction of liver transplantation has improved the mortality significantly if done in a timely fashion. Recently, molecular adsorbent recycling system (MARS) liver dialysis has been introduced as a support for liver failure with varying results. We review our experience with drug-induced liver failure and the impact of MARS liver dialysis on the outcome, in a setting where cadaveric liver transplantation is rarely available. A total of 13 patients were treated, and 40 sessions of MARS liver dialysis were conducted in the intensive care unit. The majority of cases were because of herbal medicine toxicity. Total bilirubin, conjugated bilirubin, and delta bilirubin were significantly reduced, with no change in unconjugated bilirubin. All patients satisfied the criteria for urgent liver transplantation with an average Model End Stage Liver Disease (MELD) score of 35. Only one patient received a liver transplantation from a live donor (right lobe). Overall mortality was 85%. Median time-to-death from the start of MARS was 8 days. MARS liver dialysis in a setting without timely liver transplantation is associated with a poor outcome. It does, however, provide a window of time for consideration of living donors in the setting of limited cadaveric donors.

  20. Lethal acute liver failure in a patient treated with sunitinib

    NARCIS (Netherlands)

    S.S. Guillen; M. Meijer; F.E. de Jongh (Felix)

    2016-01-01

    textabstractSunitinib is a tyrosine kinase inhibitor that is used as an anticancer drug in renal cell carcinoma (RCC), pancreatic neuroendocrine tumours (PNETs) and gastrointestinal stromal tumour. Elevated liver enzymes are frequently observed during treatment but acute liver failure is uncommon.

  1. Acute liver failure and transplantation in children | Horslen | South ...

    African Journals Online (AJOL)

    Acute liver failure (ALF) was relatively easy to recognise in the days before liver transplantation became available as rescue therapy, because the diagnosis was based on end-stage disease manifestations such as profound coagulopathy, jaundice, encephalopathy and cerebral oedema (in a patient with no history of ...

  2. Systemic Mastocytosis Associated with Liver Failure in an Adult ...

    African Journals Online (AJOL)

    A 10-year–old German shepherd dog was presented with right fore limb oedema, ascites and hepatomegaly. A clinical diagnosis of ehrlichiosis and liver failure was made. Response to therapy was unfavorable and with the owner's consent, euthanasia was performed. Necropsy findings revealed a markedly enlarged liver ...

  3. α-1-antitrypsin inhibits acute liver failure in mice.

    Science.gov (United States)

    Jedicke, Nils; Struever, Nina; Aggrawal, Nupur; Welte, Tobias; Manns, Michael P; Malek, Nisar P; Zender, Lars; Janciauskiene, Sabina; Wuestefeld, Torsten

    2014-06-01

    Acute liver failure remains a critical clinical condition, with high mortality rates, and increased apoptosis of hepatocytes represents a key event in the cause of liver failure. Alpha-1-antitrypsin (AAT) is synthesized and secreted mainly by hepatocytes, and plasma purified AAT is used for augmentation therapy in patients with AAT deficiency. Because AAT therapy exerts antiinflammatory and immune modulatory activities in various experimental models, and it was recently suggested that AAT exerts antiapoptotic activities, we aimed to explore whether administration of AAT may represent a therapeutic strategy to treat acute liver failure in mice. Well-established preclinical models of acute liver failure such as the Jo2 FAS/CD95 activating model and models of acetaminophen and α-amanitin poisoning were used. Therapeutic effects of AAT were evaluated by monitoring animal survival, histopathological changes, measurement of caspase activity, and serum cytokine levels. Systemic treatment with AAT significantly decreased Jo2-induced liver cell apoptosis and prolonged survival of mice. Native and oxidized (lacking elastase inhibitory activity) forms of AAT were equally effective in preventing acute liver injury and showed direct inhibition of active caspase-3 and -8 in liver homogenates and in a cell-free system in vitro. Concomitantly, mice treated with AAT showed significantly lower serum levels of tumor necrosis factor alpha (TNF-α), which also paralleled the reduced activity of ADAM17 (TACE). Noticeably, the increased survival and a reduction of apoptotic hepatocytes were also observed in the α-amanitin and acetaminophen-induced liver injury mouse models. Our data suggest that systemic administration of AAT can be a promising therapy to treat acute liver failure and clinical studies to explore this treatment in humans should be initiated. © 2014 by the American Association for the Study of Liver Diseases.

  4. Acute liver failure: An up-to-date approach.

    Science.gov (United States)

    Cardoso, Filipe S; Marcelino, Paulo; Bagulho, Luís; Karvellas, Constantine J

    2017-06-01

    Acute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Liver disease and heart failure: Back and forth.

    Science.gov (United States)

    Correale, Michele; Tarantino, Nicola; Petrucci, Rossella; Tricarico, Lucia; Laonigro, Irma; Di Biase, Matteo; Brunetti, Natale Daniele

    2017-10-31

    In their clinical practice, physicians can face heart diseases (chronic or acute heart failure) affecting the liver and liver diseases affecting the heart. Systemic diseases can also affect both heart and liver. Therefore, it is crucial in clinical practice to identify complex interactions between heart and liver, in order to provide the best treatment for both. In this review, we sought to summarize principal evidence explaining the mechanisms and supporting the existence of this complicate cross-talk between heart and liver. Hepatic involvement after heart failure, its pathophysiology, clinical presentation (congestive and ischemic hepatopathy), laboratory and echocardiographic prognostic markers are discussed; likewise, hepatic diseases influencing cardiac function (cirrhotic cardiomyopathy). Several clinical conditions (congenital, metabolic and infectious causes) possibly affecting simultaneously liver and heart have been also discussed. Cardiovascular drug therapy may present important side effects on the liver and hepato-biliary drug therapy on heart and vessels; post-transplantation immunosuppressive drugs may show reciprocal cardio-hepatotoxicity. A heart-liver axis is drafted by inflammatory reactants from the heart and the liver, and liver acts a source of energy substrates for the heart. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Advances in the treatment of acute liver failure

    Directory of Open Access Journals (Sweden)

    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.

  8. Urinary retinol-binding protein as a risk factor of poor prognosis in acute-on-chronic renal injury.

    Science.gov (United States)

    Yuan, Yanhong; Wang, Chunlin; Shao, Xinghua; Wang, Qin; Che, Xiajing; Zhang, Minfang; Xie, Yuanyuan; Tian, Lei; Ni, Zhaohui; Mou, Shan

    2016-12-01

    Acute-on-chronic renal injury was commonly seen in clinical practice. Reversibility of acute-on-chronic renal injury had not yet been carefully explored. This study tested whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal injury. 108 adult patients with pre-existing chronic kidney disease presenting with acute-on-chronic renal injury were included. Urinary retinol-binding protein (uRBP), N-Acetyl-b-D-Glucosaminidase (uNAG) and albumin (uALB) was quantified. Reversibility of renal function was achieved in 43 patients of the 108 included patients. The levels of urinary retinol-binding protein, N-Acetyl-b-D-Glucosaminidase and albumin for non-recovery acute-on-chronic renal injury patients were much higher than recovery patients. The fourth quartiles of urinary retinol-binding protein were significantly associated with at least 1.055-fold odds of non-recovery and the urinary retinol-binding protein was an independent risk factor for outcome of acute-on-chronic renal injury patients by multivariate logistic regression analysis. Quartiles of both urinary N-Acetyl-b-D-Glucosaminidase and albumin had a graded relationship with the risk for un-recovery AKI. However, after a multivariate logistic analysis, the urinary N-Acetyl-b-D-Glucosaminidase and albumin was not associated with reversibility of acute-on-chronic renal injury. In patients with acute-on-chronic renal injury, urinary retinol-binding protein was associated with the reversibility of kidney function. Quantification of urinary retinol-binding protein may be developed as a non-invasive tool for predicting outcome of acute-on-chronic renal injury patients.

  9. Salvage Plasmapheresis for Post-hepatectomy Liver Failure

    OpenAIRE

    Inayat, Faisal; Hussain, Qulsoom; Tasleem, Syed H; Farooq, Sajid; Hurairah, Abu

    2016-01-01

    In the latest decades, an important change has been registered in liver surgery related to the progress of surgical techniques, critical care, and postoperative treatment, allowing a sharp decrease in mortality and morbidity. However, management of post-hepatectomy liver failure (PHLF) still remains a challenge and no supportive treatment has been found to be generally effective.?The present study is a?reappraisal of plasmapheresis as a potential supportive measure in patients with PHLF follo...

  10. Wernicke encephalopathy in a patient with liver failure

    OpenAIRE

    Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

    2016-01-01

    Abstract Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice. A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, ...

  11. Salvage Plasmapheresis for Post-hepatectomy Liver Failure

    Science.gov (United States)

    Hussain, Qulsoom; Tasleem, Syed H; Farooq, Sajid; Hurairah, Abu

    2016-01-01

    In the latest decades, an important change has been registered in liver surgery related to the progress of surgical techniques, critical care, and postoperative treatment, allowing a sharp decrease in mortality and morbidity. However, management of post-hepatectomy liver failure (PHLF) still remains a challenge and no supportive treatment has been found to be generally effective. The present study is a reappraisal of plasmapheresis as a potential supportive measure in patients with PHLF following major liver resection.  PMID:28003948

  12. Reversal of intestinal failure-associated liver disease (IFALD)

    DEFF Research Database (Denmark)

    Hvas, Christian; Kodjabashia, Kamelia; Nixon, Emma

    2016-01-01

    Patients with intestinal failure (IF) and home parenteral nutrition commonly develop abnormal liver function tests. The presentations of IF-associated liver disease (IFALD) range from mild cholestasis or steatosis to cirrhosis and decompensated liver disease. We describe the reversal of IFALD...... in an adult patient with IF secondary to severe Crohn's disease and multiple small bowel resections. The patient developed liver dysfunction and pathology consistent with IFALD. Multiple causal factors were implicated, including nutrition-related factors, catheter sepsis and the use of hepatotoxic medications....... Multidisciplinary treatment in a tertiary IF referral centre included aggressive sepsis management, discontinuation of hepatotoxic medications and a reduction of parenteral nutrition dependency through optimisation of enteral nutrition via distal enteral tube feeding. Upon this, liver function tests normalised....

  13. Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

    NARCIS (Netherlands)

    Stravitz, R. Todd; Ellerbe, Caitlyn; Durkalski, Valerie; Reuben, Adrian; Lisman, Ton; Lee, William M.

    BACKGROUND & AIMS: Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We

  14. Immunophenotype predicts outcome in pediatric acute liver failure.

    Science.gov (United States)

    Bucuvalas, John; Filipovich, Lisa; Yazigi, Nada; Narkewicz, Michael R; Ng, Vicky; Belle, Steven H; Zhang, Song; Squires, Robert H

    2013-03-01

    We sought to determine whether markers of T-cell immune activation, including soluble interleukin 2 receptor alpha (sIL2Rα) levels predict outcome in pediatric acute liver failure and may target potential candidates for immunomodulatory therapy. We analyzed markers of immune activation in 77 patients with pediatric acute liver failure enrolled in a multinational, multicenter study. The outcomes were survival with native liver, liver transplantation (LT), and death without transplantation within 21 days after enrollment. Adjusting for multiple comparisons, only normalized serum sIL2Rα level differed significantly among the 3 outcomes, and was significantly higher in patients who died (P=0.02) or underwent LT (P=0.01) compared with those who survived with their native liver. The 37 patients with normal sIL2Rα levels all lived, 30 with their native liver. Of the 15 subjects with markedly high sIL2Rα (≥5000 IU/mL), 5 survived with their native liver, 2 died, and 8 underwent LT. Evidence of immune activation is present in some patients who die or undergo LT. Patients with higher sIL2Rα levels were more likely to die or undergo LT within 21 days than those with lower levels. Identifying a subset of patients at risk for poor outcome may form the foundation for targeted clinical trials with immunomodulatory drugs.

  15. A case of acute liver failure in dengue hemorrhagic fever

    Directory of Open Access Journals (Sweden)

    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

  16. [The role of liver transplantation in the treatment of acute liver failure following Amanita phalloides poisoning].

    Science.gov (United States)

    Beckurts, K T; Hölscher, A H; Heidecke, C D; Zilker, T R; Natrath, W; Siewert, J R

    1997-03-21

    To formulate the indications for liver transplantation in the treatment of acute liver failure after Amanita phalloides poisoning and to determine the results of this treatment. In 1994 twelve patients with acute Amanita phalloides poisoning were treated in the intensive care unit of our hospital's toxicology department. Three of them developed irreversible signs of poisoning and were given orthotopic liver transplants. The findings and course of this group of patients were analysed retrospectively and prognostic criteria defined on the basis of this personal experience and published data. Amanita phalloides poisoning differs from other causes of acute liver failure in several respects. The following criteria make it possible reliably to distinguish a lethal from a non-lethal course: a Quick value 1.4 mg%, even after correcting water and electrolyte abnormalities, serum bilirubin > 4.6 mg%, and progressive encephalopathy indicate a lethal course. Two of three patients survived severe poisoning by being given a liver transplant. Renal failure, pancreatitis and bone marrow suppression, in addition to liver failure, were signs relevant to treatment decisions. Liver transplantation is the procedure of choice in the treatment of acute Amanita phalloides poisoning, if the criteria for a probably lethal course under conservative treatment have been met. This should be taken into account when poisoned patients are to be transferred to a centre for treatment.

  17. Outcome of 200 Pediatric Living Donor Liver Transplantations in India.

    Science.gov (United States)

    Mohan, Neelam; Karkra, Sakshi; Rastogi, Amit; Dhaliwal, Maninder S; Raghunathan, Veena; Goyal, Deepak; Goja, Sanjay; Bhangui, Prashant; Vohra, Vijay; Piplani, Tarun; Sharma, Vivek; Gautam, Dheeraj; Baijal, S S; Soin, A S

    2017-11-15

    To describe our experience of pediatric living donor liver transplantation from India over a period of 12 years. A retrospective analysis of 200 living donor liver transplantation in children (18 years or younger) was done for demographic features, indications, donor and graft profile and outcome. Between September 2004 and July 2016, 200 liver transplants were performed on 197 children. Fifty transplants were done in initial 6 years and 150 in next 6 years. All donors (51% mothers) were discharged with a mean stay of 7 days. The leading indications of liver transplants were cholestatic liver disease (46%) followed by metabolic liver disease (33%) and acute liver failure/acute on chronic liver failure (28.5%). Biliary leakage (8.5%), biliary stricture (9%), hepatic artery thrombosis (4.5%) and portal vein thrombosis (4%) were the most common surgical complications; all could be managed by surgical or interventional radiological measures, except in one child who died. Sepsis, acute rejection and CMV hepatitis in first 6 months were seen in 14.5%, 25% and 17% cases, respectively. Post-transplant lymphoproliferative disease was seen in only 1.5%. Re-transplant rate was 1.5%. The overall 1 year survival rate was 94% and 5 year actuarial survival was 87% with no statistically significant difference between children weight 10 kg. Outcome in acute liver failure did not differ significantly between those with acute on chronic liver failure vs. those with chronic liver disease. Advances in medical and surgical techniques associated with multidisciplinary teams including skilled pediatric liver transplant surgeons, anesthetists, dedicated pediatric hepatologists, pediatric intensivists, interventional radiologists and pathologists resulted in an excellent outcome of living related liver transplants in children. Low age and weight of the baby does not seem to be a contraindication for liver transplantation as outcome were comparable in our experience.

  18. [The Importance of Early Referral in Pediatric Acute Liver Failure].

    Science.gov (United States)

    Jerónimo, Mónica; Moinho, Rita; Pinto, Carla; Carvalho, Leonor; Gonçalves, Isabel; Furtado, Emanuel; Farela Neves, José

    2015-01-01

    Acute liver failure is a rare disorder associated to high morbidity and mortality despite survival improvement through liver transplantation. The importance of a multidisciplinary approach and early referral to a pediatric liver transplantation center were important conclusions of a national meeting in 2008, from which resulted an actuation consensus. To characterize acute liver failure admissions in a Pediatric Intensive Care Unit of the portuguese pediatric livertransplantation center. To compare results before (A) and after (B) 2008. Observational, retrospective study during a 20 year period (1994-2014). age liver failure (INR ≥ 2 without vitamin K response and hepatocellular necrosis). Children with previous liver disease were excluded. Fifty children were included, with median age of 24.5 months. The most common etiology under 2 years old was metabolic (34.6%) and above that age was infectious (29.2%). Forty six percent were submitted to liver transplantation and 78% of them survived. Overall mortality was 34%. Median referral time was 7 days in period A (n = 35) and 2 days in period B (n = 15; p = 0.006). Pediatric risk of mortality's median was 14.7 in period A and 6.5 in B (p = 0.019). Mortality was 37% vs 26% in periods A and B, respectively (p = 0.474). Overall mortality was similar to the observed in other European centers. Liver transplantation is in fact the most effective therapeutic option. After 2008, there was a reduction in referral time and cases severity on admission; however, mortality has not reduced so far.

  19. Macrophages and dendritic cells in the development of liver injury leading to liver failure.

    Science.gov (United States)

    Ananiev, J; Penkova, M; Tchernev, G; Chokoeva, A A; Philipov, S; Tana, C; Gulubova, M; Wollina, U

    2014-01-01

    Liver failure (LF) continues to be a serious problem due to different underlying disorders. Not only hepatocytes but Kupffer cells (KCs) and dendritic cells (DCs) are of importance in this instance. We wanted to investigate the possible role of KCs and liver DCs in the development of liver injury in patients with liver failure. Liver specimens from 23 patients who died after liver failure were examined for the presence and distribution of CD68-positive KCs and CD83-positive DCs by immunohistochemistry. The distribution of the CD83-positive DC in the sinusoidal and the periportal spaces was not even. While 39.1% of patients had a high sinusoidal density of CD83-positive cells, 60.9% demonstrated a high density of CD83-positive cells in the periportal tract. The number of CD83-positive DCs in periportal tracts in patients with advanced liver fibrosis (n=5) were high, while those with mild liver fibrosis (n=18) had low numbers of mature dendritic cells (χ2=4.107; p=0.043). In addition, all patients with intensive fibrosis had low counts of CD68-positive KC’s in portal tracts vs patients with mild fibrosis of which 67% had high counts (χ2=6.97; p=0.008). In seven of the patients with moderate steatosis (87.5%) low numbers of CD68-positive KCs were found in sinusoids, in contrast to those with severe steatosis, where 12 patients (80%) had high KC counts (χ2=13.4; p less than 0.001). The distribution and number of CD68-positive KC and CD83-positive DC reflect the progression of liver fibrosis leading to liver failure.

  20. Successful treatment of a child with fulminant liver failure and coma due to Amanita phalloides poisoning using urgent liver transplantation.

    Science.gov (United States)

    Araz, C; Karaaslan, P; Esen, A; Zeyneloglu, P; Candan, S; Torgay, A; Haberal, M

    2006-03-01

    Intoxication due to eating wild mushrooms presents with a variety of signs, ranging from mild diarrhea to severe organ failure. We present the case of an 11-year-old boy with fulminant liver failure and hepatic coma due to Amanita phalloides poisoning treated with an urgent pediatric orthotopic liver transplantation. Successful treatment of patients with fulminant liver failure and hepatic coma caused by Amanita phalloides poisoning is possible using urgent orthotopic liver transplantation when conservative medical treatment modalities are ineffective.

  1. Arterial ammonia levels in the management of fulminant liver failure

    Directory of Open Access Journals (Sweden)

    Curry S

    2011-06-01

    Full Text Available Previous studies have suggested that an arterial ammonia level greater than 150 mmol/L is highly sensitive for predicting subsequent development of cerebral edema in patients with fulminant liver failure. We performed a prospective cohort study to confirm this relationship. We enrolled 22 consecutive patients who presented to our transplant hepatology service with grade 3-4 encephalopathy associated with fulminant liver failure. All patients underwent placement of an intraparenchymal ICP monitor, and every 12 hourly arterial ammonia levels. The prevalence of intracranial hypertension (IHTN in our population was 95% (21/22 patients, with 82 discrete episodes recorded. The sensitivity of arterial ammonia levels to predict the onset of IHTN was 62% (95% CI: 40.8 to 79.3 at a cut point of 150 mmol/L. Arterial ammonia levels preceding the first intracranial hypertension event were less than 150 mmol/L in 8 of 21 patients (39%. Fifty nine of 82 episodes of IHTN (73% occurred when arterial ammonia levels were less than 150 mmol/L. We conclude that the arterial ammonia level is not useful in making decisions regarding management related to cerebral edema in patients with fulminant liver failure. In fact, since almost all our study patients with grade III or IV encephalopathy secondary to fulminant liver failure went on to develop intracranial hypertension, our study supports the contention that all such patients might benefit from ICP monitoring regardless of arterial ammonia levels.

  2. Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure.

    Science.gov (United States)

    Zhang, Zhi; Zhao, Yi-Chao; Cheng, Yuan; Jian, Guo-Deng; Pan, Ming-Xin; Gao, Yi

    2014-12-14

    To evaluate a hybrid bioartificial liver support system (HBALSS) in cynomolgus monkeys with acute liver failure. To establish a model of acute liver failure, 0.3 g/kg of D-galactosamine was injected intravenously into cynomolgus monkeys. Chinese human liver cells were introduced into a perfusion bioreactor to carry out hybrid bioartificial liver support treatment. Forty-eight hours after the injection, one group of cynomolgus monkeys received HBALSS care, and a second experimental group received no treatment. Clinical manifestations of all animals, survival time, liver and kidney functions and serum biochemistry changes were recorded. Simultaneous detection of the number, viability and function of hepatocytes in the hybrid bioartificial liver were also performed. Forty-eight hours after the injection of D-galactosamine, serum biochemistry levels were significantly increased, whereas albumin levels and the Fischer index were significantly reduced compared to baseline (all Ps liver plays a significant role in liver support by significantly reducing serum biochemistry levels and extending animal survival time.

  3. PREDICTION AND PREVENTION OF LIVER FAILURE AFTER MAJOR LIVER PRIMARY AND METASTATIC TUMORS RESECTION

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

    Full Text Available Abstract Purpose of the study. Improvement of results of treatment in patients with primary and metastatic liver cancer by decreasing the risk of post-resection liver failure on the basis of the evaluation of the functional reserves of the liver.Materials and Methods. The study included two independent samples of patients operated about primary or metastatic lesions of the liver at the Department of abdominal Oncology, P. A. Hertsen MORI. The first group included 53 patients who carried out 13C-breath test metallimovie and dynamic scintigraphy of the liver in the preoperative stage in addition to the standard algorithm of examination. Patients of the 2nd group (n=35 had a standard clinical and laboratory examination, the patients were not performed the preoperative evaluation of the functional reserve of the liver, the incidences of total bilirubin, albumin and prothrombin time did not reveal a reduction of liver function. Post-resection liver failure have been established on the basis of the 50/50 criterion in the evaluation on day 5 after surgery.Results. Analysis of operating characteristics of the functional tests showed the absolute methacin breath test sensitivity (SE≥100%, high specificity (SP≥67% of scintigraphy of the liver and the negative predictive value of outcome (VP≥100% at complex use of two diagnostic methods. The incidence of PROPS in the study group was significantly 2 times higher in the control group –15,1% and 26.8%, respectively (p<0.001.Conclusion. The combination of preoperative dynamic scintigraphy of the liver with carrying out 13C-breath methacin test allows you to conduct a comprehensive evaluation of the liver functional reserve and can significantly improve preoperative evaluation and postoperative results of anatomic resection in patients with primary and metastatic liver lesions.

  4. 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...... and 48.2% in group 2 for non-acetaminophen patients (P liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P...... = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion...

  5. Acute Liver Failure Caused by Amanita phalloides Poisoning

    Directory of Open Access Journals (Sweden)

    Luca Santi

    2012-01-01

    Full Text Available Mushroom poisoning is a relatively rare cause of acute liver failure (ALF. The present paper analyzes the pathogenesis, clinical features, prognostic indicators, and therapeutic strategies of ALF secondary to ingestion of Amanita phalloides, which represents the most common and deadly cause of mushroom poisoning. Liver damage from Amanita phalloides is related to the amanitins, powerful toxins that inhibit RNA polymerase II resulting in a deficient protein synthesis and cell necrosis. After an asymptomatic lag phase, the clinical picture is characterized by gastrointestinal symptoms, followed by the liver and kidney involvement. Amatoxin poisoning may progress into ALF and eventually death if liver transplantation is not performed. The mortality rate after Amanita phalloides poisoning ranges from 10 to 20%. The management of amatoxin poisoning consists of preliminary medical care, supportive measures, detoxification therapies, and orthotopic liver transplantation. The clinical efficacy of any modality of treatment is difficult to demonstrate since randomized, controlled clinical trials have not been reported. The use of extracorporeal liver assist devices as well as auxiliary liver transplantation may represent additional therapeutic options.

  6. Acute Liver Failure Caused by Amanita phalloides Poisoning.

    Science.gov (United States)

    Santi, Luca; Maggioli, Caterina; Mastroroberto, Marianna; Tufoni, Manuel; Napoli, Lucia; Caraceni, Paolo

    2012-01-01

    Mushroom poisoning is a relatively rare cause of acute liver failure (ALF). The present paper analyzes the pathogenesis, clinical features, prognostic indicators, and therapeutic strategies of ALF secondary to ingestion of Amanita phalloides, which represents the most common and deadly cause of mushroom poisoning. Liver damage from Amanita phalloides is related to the amanitins, powerful toxins that inhibit RNA polymerase II resulting in a deficient protein synthesis and cell necrosis. After an asymptomatic lag phase, the clinical picture is characterized by gastrointestinal symptoms, followed by the liver and kidney involvement. Amatoxin poisoning may progress into ALF and eventually death if liver transplantation is not performed. The mortality rate after Amanita phalloides poisoning ranges from 10 to 20%. The management of amatoxin poisoning consists of preliminary medical care, supportive measures, detoxification therapies, and orthotopic liver transplantation. The clinical efficacy of any modality of treatment is difficult to demonstrate since randomized, controlled clinical trials have not been reported. The use of extracorporeal liver assist devices as well as auxiliary liver transplantation may represent additional therapeutic options.

  7. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in

  8. 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

  9. 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....

  10. Primary amyloidosis with spontaneous splenic rupture, cholestasis, and liver failure treated with emergency liver transplantation.

    Science.gov (United States)

    Sandberg-Gertzén, H; Ericzon, B G; Blomberg, B

    1998-11-01

    A 61-yr-old man with cholestatic jaundice soon after presentation had an emergency operation because of spontaneous rupture of the spleen. This was found to be caused by primary systemic amyloidosis. After the splenectomy, the patient deteriorated with liver failure and was successfully treated with liver transplantation. Osteopenic fractures of the thoracic columna developed after transplantation. Except for this, the patient is well 18 months after transplantation.

  11. 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

  12. Character and temporal evolution of apoptosis in acetaminophen-induced acute liver failure*.

    Science.gov (United States)

    Possamai, Lucia A; McPhail, Mark J W; Quaglia, Alberto; Zingarelli, Valentina; Abeles, R Daniel; Tidswell, Robert; Puthucheary, Zudin; Rawal, Jakirty; Karvellas, Constantine J; Leslie, Elaine M; Hughes, Robin D; Ma, Yun; Jassem, Wayel; Shawcross, Debbie L; Bernal, William; Dharwan, Anil; Heaton, Nigel D; Thursz, Mark; Wendon, Julia A; Mitry, Ragai R; Antoniades, Charalambos G

    2013-11-01

    To evaluate the role of hepatocellular and extrahepatic apoptosis during the evolution of acetaminophen-induced acute liver failure. A prospective observational study in two tertiary liver transplant units. Eighty-eight patients with acetaminophen-induced acute liver failure were recruited. Control groups included patients with nonacetaminophen-induced acute liver failure (n = 13), nonhepatic multiple organ failure (n = 28), chronic liver disease (n = 19), and healthy controls (n = 11). Total and caspase-cleaved cytokeratin-18 (M65 and M30) measured at admission and sequentially on days 3, 7, and 10 following admission. Levels were also determined from hepatic vein, portal vein, and systemic arterial blood in seven patients undergoing transplantation. Protein arrays of liver homogenates from patients with acetaminophen-induced acute liver failure were assessed for apoptosis-associated proteins, and histological assessment of liver tissue was performed. Admission M30 levels were significantly elevated in acetaminophen-induced acute liver failure and non-acetaminophen induced acute liver failure patients compared with multiple organ failure, chronic liver disease, and healthy controls. Admission M30 levels correlated with outcome with area under receiver operating characteristic of 0.755 (0.639-0.885, p acute liver failure were seen at admission then fell significantly but did not normalize over 10 days. A negative gradient of M30 from the portal to hepatic vein was demonstrated in patients with acetaminophen-induced acute liver failure (p = 0.042) at the time of liver transplant. Analysis of protein array data demonstrated lower apoptosis-associated protein and higher catalase concentrations in acetaminophen-induced acute liver failure compared with controls (p acute liver failure, peaking on day 1 of hospital admission, and correlates strongly with poor outcome. Hepatic regenerative/tissue repair responses prevail during the later stages of acute liver failure

  13. Significantly Elevated Liver Alkaline Phosphatase in Congestive Heart Failure.

    Science.gov (United States)

    Shamban, Leonid; Patel, Brijesh; Williams, Michael

    2014-04-01

    Congestive hepatopathy can have a mildly elevated liver profile, which should normalize with appropriate therapy. Liver specific alkaline phosphatase (ALP) in decompensated heart failure (HF) can be mildly elevated. The levels exceeding beyond the expected rise should be a concern and lead to further investigation. The literature reports insubstantial number of cases regarding significantly elevated levels of ALP and congestive hepatopathy. We report a case of a 45-year-old female with known history of severe cardiomyopathy that had persistently elevated levels of ALP. The extensive workup was negative for any specific pathology. The liver biopsy was consistent with congestive hepatopathy. The patient's ALP levels decreased with aggressive diuretic therapy but still remained elevated.

  14. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography

    NARCIS (Netherlands)

    Stravitz, R. Todd; Lisman, Ton; Luketic, Velimir A.; Sterling, Richard K.; Puri, Puneet; Fuchs, Michael; Ibrahim, Ashraf; Lee, William M.; Sanyal, Arun J.

    Background & Aims: Patients with acute liver injury/failure (ALI/ALF) are assumed to have a bleeding diathesis on the basis of elevated INR; however, clinically significant bleeding is rare. We hypothesized that patients with ALI/ALF have normal hemostasis despite elevated INR. Methods: Fifty-one

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Prediction of outcome and selection of the liver transplantat candidate in acute liver failure

    Science.gov (United States)

    Hadem, Johannes; Strassburg, Christian P.; Manns, Michael P.

    2012-01-01

    Acute liver failure (ALF) is characterized by a sudden and severe deterioration of liver function, typically mirrored by a marked increase of the international normalized ratio (INR) and hepatic encephalopathy (HE). Due to various possible causes hepatocytes get damaged via either apoptotic or necrotic pathways. Anticipating the natural prognosis of a patient with ALF is one of the most challenging tasks in hepatology critical care. Important factors that influence the chance of spontaneous recovery are the underlying etiology of acute liver failure, the acuity of disease, and the severity of HE. Once an estimation of the prognosis in the individual patient has been made, this quickly has to be integrated in the discussion whether high-urgency liver transplantation is necessary and justifiable. This decision has to cover several medical, social, and organizational issues. Well organized liver transplantation programs around the world have achieved an impressive improvement of the 1 year survival rate in ALF from around 40% without transplantation up to nearly 80% with transplantation. The recent debate on whether severe acute alcoholic hepatitis could represent a new candidate eligible for high-urgency liver transplantation shows that the topic is still open for discussion. PMID:22973230

  17. Outcomes of living versus deceased donor liver transplantation for acute liver failure in the United States.

    Science.gov (United States)

    Urrunaga, N H; Rachakonda, V P; Magder, L S; Mindikoglu, A L

    2014-01-01

    Clinical outcomes for living donor liver transplantation (LDLT) for acute liver failure (ALF) in the United States remain to be determined. To address this gap in knowledge, we examined post-liver transplantation outcomes of adults with ALF undergoing LDLT and deceased donor liver transplantation (DDLT) in the United States. We analyzed Organ and Procurement and Transplantation Network data for adults with ALF who were listed for liver transplantation as status 1 or 1A and who underwent LDLT (N = 21) or DDLT (N = 2316) between October 1987 and April 2011. We found no strong evidence that the survival probabilities for adults with ALF who underwent LDLT were inferior to those who underwent DDLT (P = .764). In adults with ALF who underwent LDLT, 1- and 5-year survival probabilities were both 71%; for DDLT these probabilities were 79% and 71%, respectively. In adults with ALF, 1- and 5-year liver graft survival probabilities, respectively, were 62% and 57% for LDLT, and 74% and 66% for DDLT. In these series of adults with ALF who were listed as status 1 or 1A, patient and graft survival rates for LDLT were similar to those for DDLT. Our findings suggest that if deceased donor livers are unavailable, LDLT is an acceptable option in experienced centers for adults with ALF. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Continuous renal replacement therapy (CRRT) in patients with liver disease: is circuit life different?

    Science.gov (United States)

    Agarwal, Banwari; Shaw, Steve; Shankar Hari, Manu; Burroughs, Andrew K; Davenport, Andrew

    2009-09-01

    Clotting of haemofiltration circuits is a major complication of continuous renal replacement therapies (CRRT), yet systemic anticoagulation risks haemorrhage. Traditionally, patients with liver failure are managed with no or minimal anticoagulation, because of abnormal clotting tests and the perceived, increased bleeding risk. We retrospectively reviewed CRRT circuit life in 50 patients; 3 groups of liver failure patients treated with CRRT (acute liver failure (ALF), acute on chronic liver disease (ACLD) and post-elective liver transplantation (LTx)), with two control groups; systemic sepsis (SS) and haematological malignancy (Haem). CCRT circuit life was significantly greater in the Haem group, compared to the others; 24.3+/-23.9h, vs. 11+/-10.5 ALF, 11.6+/-6.6 ACLF, 7.4+/-5.1 LTx and 9.2+/-6.5 SS, pCRRT circuit survival without an obvious increase in bleeding or blood transfusion requirement. Thus anticoagulation should be considered in these patients with repeated circuit clotting.

  19. MARS therapy, the bridging to liver retransplantation - Three cases from the Hungarian liver transplant program.

    Science.gov (United States)

    Pőcze, Balázs; Fazakas, János; Zádori, Gergely; Görög, Dénes; Kóbori, László; Dabasi, Eszter; Mándli, Tamás; Piros, László; Smudla, Anikó; Szabó, Tamás; Toronyi, Eva; Tóth, Szabolcs; Tőzsér, Gellért; Végső, Gyula; Doros, Attila; Nemes, Balázs

    2013-06-01

    Besides orthotopic liver transplantation (OLT) there is no long-term and effective replacement therapy for severe liver failure. Artificial extracorporeal liver supply devices are able to reduce blood toxin levels, but do not replace any synthetic function of the liver. Molecular adsorbent recirculating system (MARS) is one of the methods that can be used to treat fulminant acute liver failure (ALF) or acute on chronic liver failure (AoCLF). The primary non-function (PNF) of the newly transplanted liver manifests in the clinical settings exactly like acute liver failure. MARS treatment can reduce the severity of complications by eliminating blood toxins, so that it can help hepatic encephalopathy (HE), hepatorenal syndrome (HRS), and the high rate mortality of cerebral herniation. This might serve as a bridging therapy before orthotopic liver retransplantation (reOLT). Three patients after a first liver transplantation became candidate for urgent MARS treatment as a bridging solution prior to reOLT in our center. Authors report these three cases, fo-cusing on indications, MARS sessions, clinical courses, and final outcomes.

  20. [Adult-onset Still's disease with liver failure requiring liver transplantation].

    Science.gov (United States)

    Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando

    2009-12-01

    We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.

  1. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    Science.gov (United States)

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  2. Acute liver failure: a critical appraisal of available animal models.

    Science.gov (United States)

    Bélanger, Mireille; Butterworth, Roger F

    2005-12-01

    The availability of adequate experimental models of acute liver failure (ALF) is of prime importance to provide a better understanding of this condition and allow the development and testing of new therapeutic approaches for patients with ALF. However, the numerous etiologies and complications of ALF contribute to the complexity of this condition and render the development of an ideal experimental model of ALF more difficult than expected. Instead, a number of different models that may be used for the study of specific aspects of ALF have been developed. The most common approaches used to induce ALFin experimental animals are surgical procedures, toxic liver injury,or a combination of both. Despite the high prevalence of viral hepatitis worldwide, very few satisfactory viral models of ALF are available. Established and newly developed models of ALF are reviewed.

  3. Transient acute liver failure complicating transurethral resection syndrome.

    Science.gov (United States)

    Tuccori, Marco; Guidi, Benedetta; Montagnani, Sabrina; Fornai, Matteo; Antonioli, Luca; Blandizzi, Corrado; di Paolo, Marco

    2010-09-01

    Transurethral resection (TUR) syndrome, resulting from dilutional hyponatraemia for excessive absorption of irrigating fluid, represents the most relevant complication of transurethral resection of prostate (TURP). Ethanol is used as a tracer in the irrigant solution to monitor fluid absorption with a breathalyser. An unusual case of transient acute liver failure complicating TUR syndrome is reported. A 54-year-old male patient, without risk factors for the development of toxic hepatitis, was subjected to TURP for treatment of benign prostatic hyperplasia. Fluid absorption (2275 ml), estimated by breathalyser, exceeded maximum allowed absorption (2000 ml) only at the end of the surgical intervention. No signs of possible toxicity were evident in the few hours following the intervention. About 10 h after the end of TURP, the patient developed sweating, vomiting and diarrhoea. Laboratory analysis revealed severe hyponatraemia (116 meq/l) with signs of severe liver impairment (total bilirubin 5.8 mg/dl, alanine aminotransferase 56,500 U/l, aspartate aminotransferase 32,700 U/l), kidney failure (serum creatinine 1.93 mg/dl) and serum ethanol levels of 219 mg/dl (0.2%). The patient was treated with acetylcysteine 150 mg/kg i.v. and furosemide 50 mg i.v. Liver and renal functions improved in few days and recovered completely within 30 days. The TUR syndrome observed in this case was probably extravascular in nature, and could have been identified and prevented by measuring ethanol levels 10 min after ending the surgical procedure. The performance of such a test should be strongly recommended to all surgeons. The clinicians attributed the development of liver impairment in this case to ethanol toxicity. However, further studies are warranted to confirm whether hepatic injury can represent a possible complication of TUR syndrome when ethanol solution is used as irrigant fluid.

  4. Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group.

    Science.gov (United States)

    Davis, Brian C; Tillman, Holly; Chung, Raymond T; Stravitz, Richard T; Reddy, Rajender; Fontana, Robert J; McGuire, Brendan; Davern, Timothy; Lee, William M

    2017-04-01

    In the United States, nearly 1000 annual cases of heat stroke are reported but the frequency and outcome of severe liver injury in such patients is not well described. The aim of this study was to describe cases of acute liver injury (ALI) or failure (ALF) caused by heat stroke in a large ALF registry. Amongst 2675 consecutive subjects enrolled in a prospective observational cohort of patients with ALI or ALF between January 1998 and April 2015, there were eight subjects with heat stroke. Five patients had ALF and three had ALI. Seven patients developed acute kidney injury, all eight had lactic acidosis and rhabdomyolysis. Six patients underwent cooling treatments, three received N-acetyl cysteine (NAC), three required mechanical ventilation, three required renal replacement therapy, two received vasopressors, one underwent liver transplantation, and two patients died-both within 48 hours of presentation. All cases occurred between May and August, mainly in healthy young men because of excessive exertion. Management of ALI and ALF secondary to heat stroke should focus on cooling protocols and supportive care, with consideration of liver transplantation in refractory patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Endotoxin and interleukin-1 related hepatic inflammatory response promotes liver failure after partial hepatectomy

    NARCIS (Netherlands)

    Boermeester, M. A.; Straatsburg, I. H.; Houdijk, A. P.; Meyer, C.; Frederiks, W. M.; Wesdorp, R. I.; van Noorden, C. J.; van Leeuwen, P. A.

    1995-01-01

    Impairment of various functions of the liver and concomitantly increased levels of parameters of liver damage, a clinical entity termed liver failure, is commonly seen after partial hepatectomy. We investigated in a rat model whether damage of the remnant liver was due to local inflammatory

  6. Immediate postoperative Fibrosis-4 predicts postoperative liver failure for patients with hepatocellular carcinoma undergoing curative surgery.

    Science.gov (United States)

    Wang, Haiqing; Li, Lei; Bo, Wentao; Liu, Aixiang; Feng, Xielin; Hu, Yong; Tian, Lang; Zhang, Hui; Tang, Xiaoli; Zhang, Lixia; Zhang, Mingyi

    2018-01-01

    Postoperative liver failure remains the main complication and predominant cause of hepatectomy-related mortality for patients undergoing liver resection. Our aim is to investigate whether immediate postoperative Fibrosis-4 could predict postoperative liver failure. We retrospectively enrolled 1353 consecutive hepatocellular carcinoma patients undergoing radical resection. The characteristics and clinical outcomes were compared between patients with high and low immediate postoperative Fibrosis-4. Risk factors for hepatic failure were evaluated by univariate and multivariate analysis. Using a receiver operating characteristic curve, immediate postoperative Fibrosis-4 showed good prediction ability for postoperative liver failure (AUROC=0.647, Pfailure (13.9% vs 6.2%, Pfailure. Immediate postoperative Fibrosis-4 showed good prediction ability for postoperative liver failure, and required measure should be taken to prevent liver failure when high postoperative Fibrosis-4 appeared. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Pediatric acute liver failure of undetermined cause: A research workshop.

    Science.gov (United States)

    Alonso, Estella M; Horslen, Simon P; Behrens, Edward M; Doo, Edward

    2017-03-01

    Pediatric acute liver failure (PALF) is a potentially devastating condition that occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single-day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials. The clinical phenotype of indeterminate PALF shares important similarities to the hyperinflammatory state characteristic of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). A failure of cytotoxic T cells to limit or contract inflammatory responses may propagate injury and lead to a local and systemic milieu that does not support normal hepatic regeneration. Evidence was presented that bone marrow (BM)-derived Sinusoidal endothelial cell PROgenitor Cells (sprocs) play a vital role in hepatic regeneration. Overwhelming systemic inflammatory responses may suppress mobilization of BM sprocs and dampen hepatic recovery. Experience gained through treatment trials of HLH and MAS in childhood may inform study design for therapy of PALF. Successful approaches to limiting neuroinflammation through reduction of systemic inflammation and standardized neuroprotection protocols that limit glial injury could significantly improve intact survival. Finally, given that PALF is a rare disease, investigative efforts must include broad multicenter collaboration and careful stewardship of biorepository specimens. (Hepatology 2017;65:1026-1037). © 2016 by the American Association for the Study of Liver Diseases.

  8. Acute Liver Failure in Infants and Young Children in a Specialized Pediatric Liver Centre in India.

    Science.gov (United States)

    Alam, Seema; Lal, Bikrant Bihari; Khanna, Rajeev; Sood, Vikrant; Rawat, Dinesh

    2015-10-01

    To study the etiological spectrum of acute liver failure in infants and young children and to identify clinical and biochemical markers for metabolic liver disease (MLD). This study was conducted at Department of Pediatric Hepatology, in a tertiary care specialized centre for liver diseases. All children less than 3 y of age, with liver dysfunction and INR ≥2 were included in the study. They were managed as per the departmental protocol. Included children were divided based on the etiology into 2 groups: MLD and non MLD group. Comparison analysis (MLD vs. non MLD) of the clinical and biochemical parameters was done. There were 30 children under 3 y of age with acute liver failure (ALF) with median age of 12.5 mo. Fifteen children were less than 12 mo. MLD (33 %) and hemophagocytic lymphohistiocytosis (HLH) (17 %) together accounted for half of the cases of ALF in children below 3 y of age. The other common etiologies were drug induced liver injury and acute viral hepatitis A. Etiology remained indeterminate in 3 cases (10 %). Comparative analysis of the clinical and biochemical parameters between MLD and non MLD group showed significant difference between the two groups in the median values of age (p = 0.014), bilirubin (p = 0.017), jaundice to encephalopathy (JE) interval (p = 0.039) and blood sugar (p = 0.001). Suggestive family history (OR 3.73, 95 %CI 1.67-8.30), developmental delay (OR 4.4 95 %CI 2.03-9.51), presence of diarrhea/vomiting (OR 3.28, 95 %CI 1.32-8.13) in the history and presence of urinary non glucose reducing substance (NGRS) (OR 15.5, 95 %CI 2.26-106.87) were also significantly associated with MLD group. Only 40 % children survived with native liver. MLD and HLH account for majority of ALF in infants. About 10 % of cases remain indeterminate. Viral hepatitis is more common in young children. Apart from clinical indicators, young age, high bilirubin, synthetic dysfunction, low sugar and NGRS in urine indicate MLD

  9. The relationship between preoperative creatinine clearance and outcomes for patients undergoing liver transplantation: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Wenger Urs

    2013-02-01

    Full Text Available Abstract Background Renal failure with following continuous renal replacement therapy is a major clinical problem in liver transplant recipients, with reported incidences of 3% to 20%. Little is known about the significance of postoperative acute renal failure or acute-on-chronic renal failure to postoperative outcome in liver transplant recipients. Methods In this post hoc analysis we compared the mortality rates of 135 consecutive liver transplant recipients over 6 years in our center subject to their renal baseline conditions and postoperative RRT. We classified the patients into 4 groups, according to their preoperative calculated Cockcroft formula and the incidence of postoperative renal replacement therapy. Data then were analyzed in regard to mortality rates and in addition to pre- and peritransplant risk factors. Results There was a significant difference in ICU mortality (p=.008, hospital mortality (p=.002 and cumulative survival (p Conclusion This study shows that in liver transplant recipient’s acute renal failure with postoperative RRT is associated with mortality and the mortality rate is higher than in patients with acute-on-chronic renal failure and postoperative renal replacement therapy.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Pediatric liver failure: we came, we saw, but have we conquered? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sara Kathryn Smith

    2017-08-01

    Full Text Available Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this article, we will discuss our current understanding of liver failure and updated management strategies in children with acute liver failure.

  12. Pediatric liver failure: we came, we saw, but have we conquered?

    Science.gov (United States)

    Smith, Sara Kathryn; Rosenthal, Philip

    2017-01-01

    Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this article, we will discuss our current understanding of liver failure and updated management strategies in children with acute liver failure.

  13. Interpretation of Abdominal CT Findings in Patients Who Develop Acute on Chronic Mesenteric Ischemia.

    Science.gov (United States)

    Kärkkäinen, Jussi M; Saari, Petri; Kettunen, Hannu-Pekka; Lehtimäki, Tiina T; Vanninen, Ritva; Paajanen, Hannu; Manninen, Hannu

    2016-04-01

    We studied whether ischemia-specific computed tomography (CT) findings are consistently detectable in patients who develop acute on chronic mesenteric ischemia (AOCMI), whereas absent in chronic mesenteric ischemia (CMI). Consecutive patients with symptomatic angiography-verified atherosclerotic obstruction of the superior mesenteric artery (SMA) were categorized as AOCMI (n = 27) or CMI (n = 20). Three experienced radiologists blindly evaluated the contrast-enhanced CTs for vascular and intestinal findings. Kappa statistics was used to test interobserver agreement. Two observers had substantial agreement (k = 0.66) that two thirds of AOCMI patients showed ischemia-specific CT findings (decreased bowel wall enhancement, pneumatosis, or thrombotic SMA clot); the third observer agreed only fairly regarding pneumatosis and thrombosis (k = 0.3-0.4). All observers had substantial agreement (k = 0.65-0.71) that most patients with AOCMI had unspecific intestinal findings such as mesenteric fat stranding in up to 96%, bowel lumen dilatation in 93%, and bowel wall thickening in 70%, while only few patients with CMI had such findings (due to chronic ischemic colitis) (P ischemia-specific CT signs. However, any intestinal abnormality in CT together with SMA obstruction should raise suspicion of intestinal ischemia. Furthermore, clinicians need to be aware of the interobserver variability in the CT interpretation.

  14. Acute Liver Failure Associated with Levetiracetam and Lacosamide Combination Treatment for Unspecified Epileptic Disorder

    Directory of Open Access Journals (Sweden)

    Ylse Gutiérrez-Grobe

    2013-01-01

    Full Text Available Background and Aim. Levetiracetam is a second-generation antiepileptic drug. It is approved as an adjunctive treatment of partial onset seizures with or without secondary generalization. It is considered safe with less than 1% of patients with transient elevations of liver enzymes. Methods. We report a case of acute liver failure secondary to Levetiracetam in combination with Lacosamide documented with a liver biopsy. Results. Liver biopsy demonstrated acute liver injury with a predominant submassive necrosis pattern and features of a drug-induced hepatitis. Conclusions. This is the first published case of acute liver failure due to antiepileptic therapy with Levetiracetam in combination with Lacosamide.

  15. 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

    , 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.......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...

  16. Comparison of the prognostic value of Chronic Liver Failure Consortium scores and traditional models for predicting mortality in patients with cirrhosis.

    Science.gov (United States)

    Antunes, Artur Gião; Teixeira, Cristina; Vaz, Ana Margarida; Martins, Cláudio; Queirós, Patrícia; Alves, Ana; Velasco, Francisco; Peixe, Bruno; Oliveira, Ana Paula; Guerreiro, Horácio

    2017-04-01

    Recently, the European Association for the Study of the Liver - Chronic Liver Failure (CLIF) Consortium defined two new prognostic scores, according to the presence or absence of acute-on-chronic liver failure (ACLF): the CLIF Consortium ACLF score (CLIF-C ACLFs) and the CLIF-C Acute Decompensation score (CLIF-C ADs). We sought to compare their accuracy in predicting 30- and 90-day mortality with some of the existing models: Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), MELD-Na, integrated MELD (iMELD), MELD to serum sodium ratio index (MESO), Refit MELD and Refit MELD-Na. Retrospective cohort study that evaluated all admissions due to decompensated cirrhosis in 2 centers between 2011 and 2014. At admission each score was assessed, and the discrimination ability was compared by measuring the area under the ROC curve (AUROC). A total of 779 hospitalizations were evaluated. Two hundred and twenty-two patients met criteria for ACLF (25.9%). The 30- and 90-day mortality were respectively 17.7 and 37.3%. CLIF-C ACLFs presented an AUROC for predicting 30- and 90-day mortality of 0.684 (95% CI: 0.599-0.770) and 0.666 (95% CI: 0.588-0.744) respectively. No statistically significant differences were found when compared to traditional models. For patients without ACLF, CLIF-C ADs had an AUROC for predicting 30- and 90-day mortality of 0.689 (95% CI: 0.614-0.763) and 0.672 (95% CI: 0.624-0.720) respectively. When compared to other scores, it was only statistically superior to MELD for predicting 30-day mortality (p=0.0296). The new CLIF-C scores were not statistically superior to the traditional models, with the exception of CLIF-C ADs for predicting 30-day mortality. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  17. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

    OpenAIRE

    Shaqura, Mohammed; Mohamed, Doaa M.; Aboryag, Noureddin B.; Bedewi, Lama; Dehe, Lukas; Treskatsch, Sascha; Shakibaei, Mehdi; Schaefer, Michael; Mousa, Shaaban A

    2017-01-01

    Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for th...

  18. Assessment of emergency liver transplantation criteria in acute liver failure due to Amanita phalloides.

    Science.gov (United States)

    Ferreira, Rosa; Romãozinho, José Manuel; Amaro, Pedro; Ferreira, Manuela; Sofia, Carlos

    2011-11-01

    The emergency liver transplantation criteria for acute liver failure (ALF) due to Amanita phalloides (A. phalloides) intoxication are not consensual. The aims of this study were to evaluate the clinical outcomes, and to assess the accuracy of the current and specific criteria for emergency liver transplantation in predicting fatal outcome in ALF induced by A. phalloides. Ten patients admitted with ALF induced by A. phalloides in a Gastroenterology Intensive Care Unit were studied. Indications for liver transplant were based on Clichy and/or King's College criteria. Specific criteria of Ganzert and Escudié were tested retrospectively. A. phalloides intoxication represented 11.6% of all admissions for ALF. Patients were admitted at a mean time of 60 ± 20.4 h after ingestion. Eight patients met the Clichy and/or King's College criteria for emergency liver transplantation, seven of these patients were listed for transplant and only six patients were transplanted. Four (40%) patients died in a mean time of 4.8 ± 0.74 days after ingestion. When applied retrospectively, Escudié's criteria showed 100% of accuracy for predicting fatal outcome, whereas, King's College, Clichy's and Ganzert's criteria had an accuracy of 90, 80 and 70%, respectively. A prothrombin index of less than 10% at day 3 after ingestion showed a positive predictive value of 100% and a negative predictive value of 60%. Escudié's criteria show the best accuracy for emergency liver transplant in ALF induced by A. phalloides. The assessment of these criteria at day 3 after ingestion shows a maximum positive predictive value, although with a decline in its negative predictive value.

  19. Prediction of posthepatectomy liver failure based on liver stiffness measurement in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Nishio, Takahiro; Taura, Kojiro; Koyama, Yukinori; Tanabe, Kazutaka; Yamamoto, Gen; Okuda, Yukihiro; Ikeno, Yoshinobu; Seo, Satoru; Yasuchika, Kentaro; Hatano, Etsuro; Okajima, Hideaki; Kaido, Toshimi; Tanaka, Shiro; Uemoto, Shinji

    2016-02-01

    Posthepatectomy liver failure (PHLF) is a potentially fatal complication, and the accurate prediction of PHLF is essential. Liver stiffness measurement (LSM) has been accepted widely as a noninvasive assessment for liver fibrosis. We aimed to evaluate the usefulness of LSM in predicting PHLF. One hundred seventy-seven patients with hepatocellular carcinoma who underwent liver resection between August 2011 and October 2014 were analyzed prospectively. LSM was performed by Virtual Touch Tissue Quantification based on acoustic radiation force impulse imaging, and its value was expressed as the shear wave velocity (Vs) [m/s]. The remnant liver volume rate (Rem) was calculated by computed tomography volumetry. PHLF was diagnosed on the basis of the definition from the International Study Group of Liver Surgery. PHLF occurred in 38 patients (21.5%): grade A, 17 patients (9.6%); grade B, 15 patients (8.5%); and grade C, 6 patients (3.4%). The area under the receiver operating characteristic curve of the Vs for predicting PHLF was 0.67 for grade ≥A, 0.78 for grade ≥B, and 0.74 for grade C, which was greater than any other preoperative factor for each grade. Multivariate stepwise selection identified 2 significant factors associated with PHLF grade ≥B: Vs (odds ratio, 2.66; 95% confidence interval, 1.69-4.41, P < .01) and Rem (odds ratio, 0.47; 95% confidence interval, 0.27-0.79, P < .01). The logistic model that included the Vs and Rem resulted in an area under the receiver operating characteristic curve of 0.80 for predicting PHLF grade ≥B. LSM was useful for the prediction of PHLF and the estimation of the safe Rem range. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Pediatric acute liver failure in Brazil: Is living donor liver transplantation the best choice for treatment?

    Science.gov (United States)

    Tannuri, Ana Cristina Aoun; Porta, Gilda; Kazue Miura, Irene; Santos, Maria Merces; Moreira, Daniel de Albuquerque Rangel; de Rezende, Nathassia Mancebo Avila; Miyatani, Helena Thie; Tannuri, Uenis

    2016-07-01

    Acute liver failure (ALF) in children is a life-threatening condition that often leads to urgent liver transplantation (LT). The aim of the present investigation was to describe the experience in Brazil in treating pediatric ALF, with an emphasis on the role of living donor liver transplantation (LDLT) in treating this condition. All children with ALF who fulfilled the criteria for an urgent LT were admitted to the intensive care unit. Patients were divided into 2 groups based on the moment of admission: before and after June 2007, when the LDLT program for ALF was started. Statistical analyses were performed to identify prognostic factors of patients with ALF. For the study, 115 children with ALF were admitted. All patients had some degree of encephalopathy. Among the patients, 26% of them required intracranial pressure monitoring (IPM), 12.8% of the patients required hemodialysis, and 79 patients underwent transplantation (50 deceased donors and 29 living donors) corresponding to 12.4% of all pediatric LTs. Only 9 children recovered without LT. The need for IPM and nonperformance of LT were related to a higher mortality. The mortality rate of patients who underwent LT was significantly lower than that of children with ALF who did not undergo a LT (48.1% versus 75%; P = 0.02). The incidences of primary nonfunction and mortality were statistically higher among deceased donor liver transplantations than LDLTs. Finally, it was verified that the overall survival rate of transplanted patients was increased after the introduction of LDLT (P = 0.02). In conclusion, ALF in children continues to be a severe and devastating condition, and a LT should be performed promptly. The introduction of LDLT could increase the survival rate of patients in Brazil. Liver Transplantation 22 1006-1013 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

  1. [A case of liver failure associated with liver damage due to mFOLFOX 6 after resection for multiple liver metastases from colorectal cancer].

    Science.gov (United States)

    Ishizaki, Tetsuo; Abe, Tomomi; Koyanagi, Yasuhisa; Katsumata, Kenji; Wada, Tatehiko; Tsuchida, Akihiko; Aoki, Tatsuya

    2007-06-01

    A case of colorectal cancer in a 60-year-old man became resectable after downstaging was achieved with mFOLFOX 6 for multiple liver metastases from colorectal cancer. The patient received 8 cycles of mFOLFOX 6 on the basis of a diagnosis of multiple liver metastases in the right and left lobes and a single metastasis in the right lung. After chemotherapy, the liver metastases showed partial response, and the lung metastasis stable disease. Because the lung metastasis was controlled and radical cure of the liver metastases was thought possible by resection, we performed right lobectomy of the liver. Postoperative progress was good, and we then planned a staged partial resection of the lung. However,on postoperative day 28, the patient was hospitalized again with liver dysfunction, which evolved into liver failure, in spite of conservative treatment. The patient died on postoperative day 95. The needle biopsy specimens of the liver taken on readmission showed bile duct occlusion, portal hypertension, and perisinusoidal fibrosis, and histopathology of the surgical non-tumoral liver specimen showed the same findings. We think that liver failure was triggered by resection of the liver which had been damaged by mFOLFOX 6. Recently, liver damage due to oxaliplatin was reported, and evaluation of liver injury is considered important before liver resection for colorectal liver metastases with neoadjuvant FOLFOX.

  2. Glasgow coma scale and APACHE-II scores affect the liver transplantation outcomes in patients with acute liver failure.

    Science.gov (United States)

    Guler, Necdet; Unalp, Omer; Guler, Ayse; Yaprak, Onur; Dayangac, Murat; Sozbilen, Murat; Akyildiz, Murat; Tokat, Yaman

    2013-12-01

    The timing and selection of patients for liver transplantation in acute liver failure are great challenges. This study aimed to investigate the effect of Glasgow coma scale (GCS) and APACHE-II scores on liver transplantation outcomes in patients with acute liver failure. A total of 25 patients with acute liver failure were retrospectively analyzed according to age, etiology, time to transplantation, coma scores, complications and mortality. Eighteen patients received transplants from live donors and 7 had cadaveric whole liver transplants. The mean duration of follow-up after liver transplantation was 39.86+/-40.23 months. Seven patients died within the perioperative period and the 1-, 3-, 5-year survival rates of the patients were 72%, 72% and 60%, respectively. The parameters evaluated for the perioperative deaths versus alive were as follows: the mean age of the patients was 33.71 vs 28 years, MELD score was 40 vs 32.66, GCS was 5.57 vs 10.16, APACHE-II score was 23 vs 18.11, serum sodium level was 138.57 vs 138.44 mmol/L, mean waiting time before the operation was 12 vs 5.16 days. Low GCS, high APACHE-II score and longer waiting time before the operation (PAPACHE-II scores are related to poor outcomes in patients with acute liver failure after liver transplantation.

  3. Liver Stiffness Assessed by Shear Wave Elastography Predicts Postoperative Liver Failure in Patients with Hepatocellular Carcinoma.

    Science.gov (United States)

    Shen, Yinghao; Zhou, Chenhao; Zhu, Guodong; Shi, Guoming; Zhu, Xiaodong; Huang, Cheng; Zhou, Jian; Fan, Jia; Ding, Hong; Ren, Ning; Sun, Hui-Chuan

    2017-09-01

    Cirrhosis increases a patient's risk of developing postoperative liver failure (PLF). Liver stiffness (LS), assessed by two-dimensional shear wave elastography (SWE), indicates liver fibrosis with high accuracy. Whether LS is superior to portal hypertension (PHT) in predicting PLF remains to be studied. The study enrolled 280 patients who underwent hepatectomy for hepatocellular carcinoma from July 2015 to July 2016. All patients received preoperative assessments for LS, PHT, and serum markers of liver fibrosis in addition to other clinicopathological tests. Risk factors for grade A and grade B (or greater) PLF were subjected to univariate and multivariate analysis and receiver operating characteristic curve analysis. Fifty-five patients (19.6%) experienced PLF. The cutoff value of LS for predicting cirrhosis was 10.1 kPa. Multivariate analysis identified LS, hyaluronic acid, IV collagen, and the presence of splenomegaly as independent predictors of PLF. The cutoff value of LS for predicting PLF and grade B (or greater) PLF was 11.75 and 11.9 kPa, respectively. LS was superior to PHT in predicting PLF or greater than grade B PLF (0.72 vs. 0.60, 0.76 vs. 0.59, P < 0.05). LS measured by SWE can predict risk of PLF with greater accuracy than PHT.

  4. High-volume plasma exchange in patients with acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Schmidt, Lars Ebbe; Bernsmeier, Christine

    2016-01-01

    BACKGROUND & AIMS: 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...... organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (p

  5. Constitutive androstane receptor (Car)-driven regeneration protects liver from failure following tissue loss.

    Science.gov (United States)

    Tschuor, Christoph; Kachaylo, Ekaterina; Limani, Përparim; Raptis, Dimitri A; Linecker, Michael; Tian, Yinghua; Herrmann, Uli; Grabliauskaite, Kamile; Weber, Achim; Columbano, Amedeo; Graf, Rolf; Humar, Bostjan; Clavien, Pierre-Alain

    2016-07-01

    Liver can recover following resection. If tissue loss is too excessive, however, liver failure will develop as is known from the small-for-size-syndrome (SFSS). The molecular processes underlying liver failure are ill-understood. Here, we explored the role and the clinical potential of Nr1i3 (constitutive androstane receptor, Car) in liver failure following hepatectomy. Activators of Car, various hepatectomies, Car(-/-) mice, humanized CAR mice, human tissue and ex vivo liver slice cultures were used to study Car in the SFSS. Pathways downstream of Car were investigated by in vivo siRNA knockdown. Excessive tissue loss causing liver failure is associated with deficient induction of Car. Reactivation of Car by an agonist normalizes all features associated with experimental SFSS. The beneficial effects of Car activation are relayed through Foxm1, an essential promoter of the hepatocyte cell cycle. Deficiency in the CAR-FOXM1 axis likewise is evident in human SFSS. Activation of human CAR mitigates SFSS in humanized CAR mice and improves the culture of human liver slices. Impaired hepatic Car-Foxm1 signaling provides a first molecular characterization of liver that fails to recover after tissue loss. Our findings place deficient regeneration as a principal cause behind the SFSS and suggest CAR agonists may bear clinical potential against liver failure. The unique regenerative capacity of liver has its natural limits. Following tissue loss that is too excessive, such as through extended resection in the clinic, liver failure may develop. This is known as small-for-size-syndrome (SFSS) and represents the most frequent cause of death due to liver surgery. Here we show that deficient induction of the protein Car, a central regulator of liver function and growth, is a cause of liver failure following extended resection; reactivation of Car through pharmacological means is sufficient to prevent or rescue the SFSS. Copyright © 2016 European Association for the Study of the

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

    Science.gov (United States)

    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.

  7. Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Culleton Bruce

    2005-06-01

    Full Text Available Abstract Background Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. Case presentation A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5. Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. Conclusion We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver.

  8. Liver Failure due to Acute Viral Hepatitis (A-E)

    Science.gov (United States)

    Manka, Paul; Verheyen, Jens; Gerken, Guido; Canbay, Ali

    2016-01-01

    Background Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. Methods A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. Results Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. Conclusion Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF. PMID:27413724

  9. Chronic acetaminophen exposure in pediatric acute liver failure.

    Science.gov (United States)

    Leonis, Mike A; Alonso, Estella M; Im, Kelly; Belle, Steven H; Squires, Robert H

    2013-03-01

    Acetaminophen (N-acetyl-p-aminophenol [APAP]) is a widely used medication that can cause hepatotoxicity. We examined characteristics and outcomes of children with chronic exposure (CE) to APAP in the multinational Pediatric Acute Liver Failure (PALF) Study. A total of 895 children enrolled from 2002 to 2009 were grouped by APAP exposure history as: CE (received multiple doses \\x{2265}2 days; n = 83), single dose exposure (SE; n = 85), and no exposure (NE; n = 498). CE was the reference group for pairwise comparisons. Median values are shown. Patients with CE compared with those with SE were younger (3.5 vs 15.2 years, P liver transplantation at 21 days was worse for CE than for SE (68% vs 92%, P = .0004) but better than for NE (49%, P = .008). Children in the PALF study with CE had lower bilirubin and higher alanine aminotransferase than those with NE. Outcomes with CE were worse than with SE but better than with NE. Potential reasons for this outcomes advantage over non-APAP-exposed subjects should be explored.

  10. Wernicke encephalopathy in a patient with liver failure

    Science.gov (United States)

    Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

    2016-01-01

    Abstract Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice. A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1. To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians’ awareness of its possible onset. PMID:27399058

  11. Organ sharing in the management of acute liver failure.

    Science.gov (United States)

    Pezzati, D; Ghinolfi, D; De Simone, P; Tincani, G; Fiorenza, G; Filipponi, F

    2013-04-01

    Liver transplantation (OLT) for acute liver failure (ALF) is associated with high morbidity and mortality rates in the early posttransplant course. An efficient organ-sharing organization may grant favorable results. This is a retrospective analysis of prospectively collected data on patients wait listed for ALF at a single center. Patients were listed for OLT when matching King's College Criteria. Based on patients' clinical status, ABO-incompatible grafts were used. From January 2001 to December 2010, 37 patients were wait listed for ALF. Two patients were de-listed (5.4%) for improvement of their clinical conditions; two patients (5.4%) died on the list and 33 (89.2%) underwent OLT. Among these latter, 21 (63.6%) were Italian and 12 (36.4%) were foreign citizens, with four referred from their home country on the basis of international agreements on ALF management. Donors were procured in our region in 10 cases (30.3%), nationally in 22 (66.6%), and outside Italy in 1 (3.1%). Mean time from wait listing to OLT was 1 day (range 0-6), and seven patients received an ABO-incompatible graft. Graft and patient survivals at 1 month, 1 year, and 3 years were 78.8%, 72.7%, 66.5%, and 81.8%, 75.8%, and 72.7%, respectively. Five patients underwent retransplantation: two on postoperative day (POD) 2 for primary nonfunction of the liver graft, two on POD 8 and 95 for hepatic artery thrombosis, and one at 18 months for nonanastomotic biliary stenosis. Prompt referral to a OLT center and efficient organ-sharing system play a fundamental role in optimizing the outcome of the patient with ALF. Development of international organ exchange programs might further improve the results for this category of patients. In very selected cases, ABO-incompatible grafts may be a valuable resource. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

    Science.gov (United States)

    Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

  13. Fasting and postprandial plasma ghrelin levels are decreased in patients with liver failure previous to liver transplantation.

    Science.gov (United States)

    Diz-Lois, Maria Teresa; Garcia-Buela, Jesús; Suarez, Francisco; Sangiao-Alvarellos, Susana; Vidal, Ovidio; Cordido, Fernando

    2009-06-01

    Anorexia is a problem of paramount importance in patients with advanced liver failure. Ghrelin has important actions on feeding and weight homeostasis. Concentrations of ghrelin are controversial in liver cirrhosis. Our aim was to study fasting ghrelin and their response to an oral glucose tolerance test (OGTT) in liver failure patients and normal subjects. We included 16 patients with severe liver failure prior to liver transplantation. As a control group we included 10 age- and BMI-matched healthy subjects. After an overnight fast, 75 g of oral glucose were administered; glucose, insulin, and ghrelin were obtained at baseline and at times 30, 60, 90, and 120 min, respectively. Fasting ghrelin (median and range) were statistically significantly lower for patients compared to the controls, 527 (377-971) pg/ml vs. 643 (523-2163) pg/ml, P = 0.045, for patients and controls, respectively. The area under the curve for total ghrelin post-OGTT were lower in end-stage liver failure patients than in the control group, 58815 (44730-87420) pg/ml min vs. 76560 (56160-206385) pg/ml min, for patients and controls, respectively, P = 0.027. Ghrelin levels are significantly decreased both fasting and post-OGTT in patients with liver failure candidates for transplantation. Decreased ghrelin levels could contribute to anorexia in patients with cirrhosis.

  14. Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis.

    Science.gov (United States)

    Amir, Achiya Z; Ling, Simon C; Naqvi, Ahmed; Weitzman, Sheila; Fecteau, Annie; Grant, David; Ghanekar, Anand; Cattral, Mark; Nalli, Nadya; Cutz, Ernest; Kamath, Binita; Jones, Nicola; De Angelis, Maria; Ng, Vicky; Avitzur, Yaron

    2016-09-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic disease, characterized by overwhelming stimulation of the immune system and categorized as primary or secondary types. Occasionally, acute liver failure (ALF) may dominate the clinical presentation. Given the systemic nature of HLH and risk of recurrence, HLH is considered by many a contraindication to liver transplantation (LT). The aim of this study is to review our single-center experience with LT in children with secondary HLH and ALF (HLH-ALF). This is a cross-sectional, retrospective study of children with secondary HLH-ALF that underwent LT in 2005-2014. Of 246 LTs, 9 patients (3 males; median age, 5 years; range, 0.7-15.4 years) underwent LT for secondary HLH-ALF. Disease progression was rapid with median 14 days (range, 6-27 days) between first symptoms and LT. Low fibrinogen/high triglycerides, elevated ferritin, hemophagocytosis on liver biopsy, and soluble interleukin 2 receptor levels were the most commonly fulfilled diagnostic criteria; HLH genetic studies were negative in all patients. Immunosuppressive therapy after LT included corticosteroids adjusted to HLH treatment protocol and tacrolimus. Thymoglobulin (n = 5), etoposide (n = 4), and alemtuzumab (n = 2) were used in cases of recurrence. Five (56%) patients experienced HLH recurrence, 1 requiring repeat LT, and 3 died. Overall graft and patient survival were 60% and 67%, respectively. Six patients are alive and well at a median of 24 months (range, 15-72 months) after transplantation. In conclusion, LT can be beneficial in selected patients with secondary HLH-ALF and can restore good health in an otherwise lethal condition. Liver Transplantation 22 1245-1253 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  15. Validity of diagnostic codes and laboratory tests of liver dysfunction to identify acute liver failure events.

    Science.gov (United States)

    Lo Re, Vincent; Carbonari, Dena M; Forde, Kimberly A; Goldberg, David; Lewis, James D; Haynes, Kevin; Leidl, Kimberly B F; Reddy, Rajender K; Roy, Jason; Sha, Daohang; Marks, Amy R; Schneider, Jennifer L; Strom, Brian L; Corley, Douglas A

    2015-07-01

    Identification of acute liver failure (ALF) is important for post-marketing surveillance of medications, but the validity of using ICD-9 diagnoses and laboratory data to identify these events within electronic health records is unknown. We examined positive predictive values (PPVs) of hospital ICD-9 diagnoses and laboratory tests of liver dysfunction for identifying ALF within a large, community-based integrated care organization. We identified Kaiser Permanente Northern California health plan members (2004-2010) with a hospital diagnosis suggesting ALF (ICD-9 570, 572.2, 572.4, 572.8, 573.3, 573.8, or V42.7) plus an inpatient international normalized ratio ≥1.5 (off warfarin) and total bilirubin ≥5.0 mg/dL. Hospital records were reviewed by hepatologists to adjudicate ALF events. PPVs for confirmed outcomes were determined for individual ICD-9 diagnoses, diagnoses plus prescriptions for hepatic encephalopathy treatment, and combinations of diagnoses in the setting of coagulopathy and hyperbilirubinemia. Among 669 members with no pre-existing liver disease, chart review confirmed ALF in 62 (9%). Despite the presence of co-existing coagulopathy and hyperbilirubinemia, individual ICD-9 diagnoses had low PPVs (range, 5-15%); requiring prescriptions for encephalopathy treatment did not increase PPVs of these diagnoses (range, 2-23%). Hospital diagnoses of other liver disorders (ICD-9 573.8) plus hepatic coma (ICD-9 572.2) had high PPV (67%; 95%CI, 9-99%) but only identified two (3%) ALF events. Algorithms comprising relevant hospital diagnoses, laboratory evidence of liver dysfunction, and prescriptions for hepatic encephalopathy treatment had low PPVs for confirmed ALF events. Studies of ALF will need to rely on medical records to confirm this outcome. Copyright © 2015 John Wiley & Sons, Ltd.

  16. 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

  17. Clinical analysis and prognostic judgment of artificial extracorporeal liver support therapy for pediatric acute liver failure

    Directory of Open Access Journals (Sweden)

    ZHANG Zhen

    2015-08-01

    Full Text Available Objective To observe the clinical efficacy of artificial extracorporeal liver support therapy in the treatment of pediatric acute liver failure (PALF and to analyze the associated prognostic factors. Methods The clinical records of 23 patients with PALF treated from January 2012 to February 2015 in the Pediatric Intensive Care Unit of the First Hospital of Jilin University were analyzed retrospectively. After three-month follow-up, 15 patients survived (survival group, n=15, while 8 patients died (death group, n=8. The changes in biomarkers of liver function and coagulation function after treatment were evaluated within groups. At the same time, the above parameters and Model for End-Stage Liver Disease (MELD score before treatment were compared between the two groups. The efficacy of artificial extracorporeal liver support therapy was analyzed, and the prognostic factors were reviewed. The t test was applied in the comparison of continuous data. Results In the survival group, the levels of serum alanine aminotransferase (ALT, total bilirubin (TBil, ammonia, and lactic acid were significantly reduced after treatment (t=8.812, 6.243, 8.431, and 6.721, respectively; all P<0.01. However, in the death group, only ALT level was significantly reduced after treatment (t=2.532, P<0.05. Compared with the levels before treatment, the levels of prothrombin time (PT, prothrombin time activity (PTA, and international normalized ratio (INR were significantly improved after treatment (t=6.256, -2.738, and 6.711, respectively; all P<0.05. Before treatment, compared with the survival group, patients in the death group presented significantly lower level of ALT (t=6.283,P<0.01, significantly higher level of TBil (t=-3.938, P=0.001, significantly longer PT (t=-2.394, P=0.026, and significantly higher MELD score (t=-6.239, P<0.01. Conclusion Artificial extracorporeal liver support therapy is an effective way of treating PALF. Once patients with high ALT level

  18. Acute liver failure due to zinc phosphide containing rodenticide poisoning: Clinical features and prognostic indicators of need for liver transplantation.

    Science.gov (United States)

    Saraf, Vivek; Pande, Supriya; Gopalakrishnan, Unnikrishnan; Balakrishnan, Dinesh; Menon, Ramachandran N; Sudheer, O V; Dhar, Puneet; Sudhindran, S

    2015-07-01

    Zinc phosphide (ZnP) containing rodenticide poisoning is a recognized cause of acute liver failure (ALF) in India. When standard conservative measures fail, the sole option is liver transplantation. Records of 41 patients admitted to a single centre with ZnP-induced ALF were reviewed to identify prognostic indicators for requirement of liver transplantation. Patients were analyzed in two groups: group I (n = 22) consisted of patients who either underwent a liver transplant (n = 14) or died without a transplant (n = 8); group II (n = 19) comprised those who survived without liver transplantation. International normalized ratio (INR) in group I was 9 compared to 3 in group II (p Liver Disease (MELD) score in group I was 41 compared to 24 in group II (p liver transplantation.

  19. Preoperative prediction and prevention of intraoperative acute liver failure after major liver resection for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

    Full Text Available Objective: improve the results of treatment of patients with metastatic cancer of liver by reducing the risk of post-resection liver failure based on the assessment of liver functional reserve.Materials and methods. The study included 2 independent samples of patients underwent surgery for liver metastases in the department of abdominal oncology at the P. A. Herzen Moscow Oncological Research Institute. Group 1 included 47 patients: in addition to the standard treatment algorithm they underwent 13C methacetin breath test and dynamic scintigraphy of liver in the preoperative stage. Patients from the group 2 (n = 30 underwent standard clinical and laboratory examination, without preoperative evaluation of liver functional reserves; the level of total bilirubin, albumin and prothrombin time showed no decrease in liver function. Post-resection liver failure was established based on 50/50 criterion when evaluated on the 5th postoperative day.Results. The analysis of operational characteristics of functional tests showed absolute sensitivity of 13C methacetin breath test (SE ≥ 100 % and negative predictive value (–VP ≥ 100 % in case of integrated application of 2 diagnostic methods. An incidence of post-resection acute liver failure in the study group was significantly 2.2-fold lower than in the control group – 10.6 % and 23.3 %, respectively (p < 0.001.Conclusion. Combination of preoperative dynamic scintigraphy of liver with 13C methacetin breath test allows to perform comprehensive assessment of liver functional reserves, and it can greatly improve preoperative assessment and postoperative results of anatomic resections in patients with liver metastases.

  20. Pharmacologic cholinesterase inhibition improves survival in acetaminophen-induced acute liver failure in the mouse.

    Science.gov (United States)

    Steinebrunner, Niels; Mogler, Carolin; Vittas, Spiros; Hoyler, Birgit; Sandig, Catharina; Stremmel, Wolfgang; Eisenbach, Christoph

    2014-08-19

    Acetaminophen (APAP) is one of the most widely used analgesic and antipyretic pharmaceutical substances in the world and accounts for most cases of drug induced liver injury resulting in acute liver failure. Acute liver failure initiates a sterile inflammatory response with release of cytokines and innate immune cell infiltration in the liver. This study investigates, whether pharmacologic acetylcholinesterase inhibition with neostigmine diminishes liver damage in acute liver failure via the cholinergic anti-inflammatory pathway. Acute liver failure was induced in BALB/c mice by a toxic dose of acetaminophen (APAP). Neostigmine and/or N-acetyl-cysteine (NAC) were applied therapeutically at set time points and the survival was investigated. Liver damage was assessed by serum parameters, histopathology and serum cytokine assays 12 h after initiation of acute liver failure. Serum parameters, histopathology and serum cytokine assays showed pronounced features of acute liver failure 12 h after application of acetaminophen (APAP). Neostigmine treatment led to significant reduction of serum liver enzymes (LDH (47,147 ± 12,726 IU/l vs. 15,822 ± 10,629 IU/l, p = 0.0014) and ALT (18,048 ± 4,287 IU/l vs. 7,585 ± 5,336 IU/l, p = 0.0013), APAP-alone-treated mice vs. APAP + neostigmine-treated mice), inflammatory cytokine levels (IL-1β (147 ± 19 vs. 110 ± 25, p = 0.0138) and TNF-α (184 ± 23 vs. 130 ± 33, p = 0.0086), APAP-alone-treated mice vs. APAP + neostigmine-treated mice) and histopathological signs of damage.Animals treated with NAC in combination with the peripheral cholinesterase inhibitor neostigmine showed prolonged survival and improved outcome. Neostigmine is an acetylcholinesterase inhibitor that ameliorates the effects of APAP-induced acute liver failure in the mouse and therefore may provide new treatment options for affected patients.

  1. Altered fasting and postprandial plasma ghrelin levels in patients with liver failure are normalized after liver transplantation.

    Science.gov (United States)

    Diz-Lois, Maria Teresa; Garcia-Buela, Jesús; Suarez, Francisco; Sangiao-Alvarellos, Susana; Vidal, Ovidio; Cordido, Fernando

    2010-10-01

    Anorexia is a problem of paramount importance in patients with advanced liver failure. Ghrelin has important actions on feeding and weight homeostasis. Experimental data exist, which suggest that ghrelin could protect hepatic tissue. Both fasting and post-oral glucose tolerance test (OGTT) ghrelin concentrations are controversial in liver cirrhosis and are unknown after liver transplantation. Our aim was to study fasting ghrelin concentrations and their response to an OGTT in liver failure patients before and after liver transplantation. We included 21 patients with severe liver failure studied before (pretransplantation, PreT) and 6 months after liver transplantation (posttransplantation, PostT), and 10 age- and body mass index-matched healthy or overweight subjects as the control group (Cont). After an overnight fast, 75 g of oral glucose were administered; glucose, insulin, and ghrelin were obtained at baseline and at times 30, 60, 90, and 120 min. Fasting ghrelin (median and range, pg/ml) levels were lower in PreT: 539 (309-1262) than in Cont: 643 (523-2163), P=0.045. Fasting ghrelin levels increased after liver transplantation, 539 (309-1262) vs 910 (426-3305), for PreT and PostT respectively, P=0.001. The area under the curve (AUC) of ghrelin (pg/ml min) was lower in PreT: 63,900 (37,260-148,410) than in Cont: 76,560 (56,160-206,385), P=0.027. The AUC of ghrelin increased in PostT, 63,900 (37,260-148,410) vs 107,595 (59,535-357,465), for PreT and PostT respectively, P=0.001. Fasting levels and the AUC of ghrelin were similar in PosT and Cont. Decreased fasting and post-OGTT ghrelin levels in liver failure patients were normalized after liver transplantation.

  2. A Rare Case of Propofol-Induced Acute Liver Failure and Literature Review

    Directory of Open Access Journals (Sweden)

    G. Kneiseler

    2010-02-01

    Full Text Available The incidence of drug-induced acute liver failure is increasing. A number of drugs can inhibit mitochondrial functions, alter β-oxidation and cause accumulation of free fatty acids within the hepatocytes. This may result in hepatic steatosis, cell death and liver injury. In our case, propofol, an anesthetic drug commonly used in adults and children, is suspected to have induced disturbance of the mitochondrial respiratory chain, which in consequence led to insufficient energy supply and finally liver failure. We report the case of a 35-year-old Caucasian woman with acute liver failure after anesthesia for stripping of varicose veins. Liver histology, imaging and laboratory data indicate drug-induced acute liver failure, presumably due to propofol. Hepatocyte death and microvesicular fatty degeneration of 90% of the liver parenchyma were observed before treatment with steroids. Six months later, a second biopsy was performed, which revealed only minimal steatosis and minimal periportal hepatitis. We suggest that propofol led to impaired fatty acid oxidation possibly due to a genetic susceptibility. This caused free fatty acid accumulation within hepatocytes, which presented as hepatocellular fatty degeneration and cell death. Large scale hepatocyte death was followed by impaired liver function and, consecutively, progressed to acute liver failure.

  3. Evaluation of encapsulated liver cell spheroids in a fluidised-bed bioartificial liver for treatment of ischaemic acute liver failure in pigs in a translational setting.

    Directory of Open Access Journals (Sweden)

    Clare Selden

    Full Text Available Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2 cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4-6 × 10(10cells, were transported from preparation-laboratory to point-of-use operating theatre (6000 miles under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL, and those connected to circuit containing alginate capsules without cells (Empty-bead BAL. Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without

  4. Presenting Features and Prognosis of Ischemic and Nonischemic Neonatal Liver Failure.

    Science.gov (United States)

    Zozaya Nieto, Carlos; Fernández Caamaño, Beatriz; Muñoz Bartolo, Gema; Menéndez Suso, Juan J; Frauca Remacha, Esteban; Valverde Núñez, Eva

    2017-05-01

    To describe the epidemiological features, clinical characteristics and outcomes of neonates diagnosed with liver failure, as well as determine prognostic factors. Cohort study conducted at a single tertiary referral and university-affiliated pediatric center. Hospital records of all neonates diagnosed with liver failure between January 2003 and December 2015 were retrospectively reviewed, and data on clinical and laboratory findings, treatment, and outcomes were collected. Survival analysis (Kaplan-Meier) and Cox regression were performed to identify prognostic factors at diagnosis. Liver failure diagnosis was established using the pediatric acute liver failure study group's diagnostic criteria for every patient with coagulopathy and biochemical pattern of liver disease. Forty-five patients were included. In our series, most cases were secondary to ischemia (28.9%). Other causes were neonatal hemochromatosis (17.8%), viral infections (13.3%), and inborn errors of metabolism (13.3%). A total 55.6% (25/45) of the patients died (median age: 16 days; range 1-235 days). Alanine aminotransferase (ALT) at diagnosis was associated with higher mortality or the need for liver transplantation on day 21 after diagnosis (P = .006). For every 500 IU/L increase in ALT serum levels, the mortality/liver transplantation rate increased 1.3 times (hazard ratio 95% confidence interval: 1.1-1.6). Although ischemic neonatal acute liver failure presents with higher ALT levels, these cases appear to have better outcomes. Higher international normalized ratio tended to increase mortality/transplantation (hazard ratio 1.02; 95% confidence interval 0.91-1.2). Neonatal liver failure should perhaps be considered in the differential diagnoses of any coagulopathy. ALT and international normalized ratio levels at diagnosis could predict prognosis in the short term. Ischemic liver failure appears to have a better prognosis.

  5. Traditional Chinese medicine treatment of liver diseases

    Directory of Open Access Journals (Sweden)

    WANG Rongbing

    2015-01-01

    Full Text Available Traditional Chinese medicine (TCM treatment of liver diseases is derived from the regulation of liver function including storing blood and governing the free flow of qi, in which functional systems such as modern digestion, endocrine, and the gut-liver axis are involved, and is established on modern hepatic physiology, pathology, and etiology. To objectively reveal the characteristics and advantages of modern TCM treatment of liver diseases, we analyzed the clinical and research situation of TCM therapy for liver diseases in the last decade and collected major achievements that have been applied in clinical treatment of diseases, published in core journals, and confirmed by major scientific research programs. The results showed TCM combined with antiviral therapy can improve the clinical outcomes of chronic hepatitis B. TCM can help HBV carriers prevent disease progression. Integrated traditional Chinese and Western medicine therapy for acute-on-chronic liver failure can block the deterioration induced by endotoxin. TCM has been widely applied in protecting the liver through nonspecific anti-inflammation, alleviating hepatic fibrosis, and preventing non-alcoholic fatty liver. TCM plays an important role in treating some currently untreatable liver diseases. Therefore, it is our common responsibility to inherit and develop effective principle-method-recipe-medicines and create a better medical care system.

  6. Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients.

    Science.gov (United States)

    Jaeschke, Hartmut

    2015-01-01

    Drug-induced liver injury is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure at therapeutic doses in a very limited number of patients (liver injury, which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to idiosyncratic drug-induced liver injury, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and acute liver failure after intentional and unintentional overdoses. Key Messages: APAP overdose is responsible for more acute liver failure cases in the USA or UK than all other etiologies combined. Since APAP overdose in the mouse represents a model for the human pathophysiology, substantial progress has been made during the last decade in understanding the mechanisms of cell death, liver injury and recovery. More recently, emerging evidence based on mechanistic biomarker analysis in patients and studies of cell death in human hepatocytes suggests that most of the mechanisms discovered in mice also apply to patients. The rapid development of N-acetylcysteine as an antidote against APAP overdose was based on the early understanding of APAP toxicity in mice. However, despite the efficacy of N-acetylcysteine in patients who present early after APAP overdose, there is a need to develop intervention strategies for late-presenting patients. The challenges related to APAP toxicity are to better understand the mechanisms of cell death in order to limit liver injury and prevent acute liver failure, and also to develop biomarkers that better predict as early as possible who is at risk for developing acute liver failure with poor outcome. © 2015 S. Karger AG

  7. Continuous veno-venous single-pass albumin hemodiafiltration in children with acute liver failure.

    Science.gov (United States)

    Ringe, Hannelore; Varnholt, Verena; Zimmering, Miriam; Luck, Werner; Gratopp, Alexander; König, Kai; Reich, Susanne; Sauer, Igor M; Gaedicke, Gerhard; Querfeld, Uwe

    2011-05-01

    To investigate the applicability, efficacy, and safety of single-pass albumin dialysis in children. Retrospective data review of uncontrolled clinical data. University-based pediatric intensive care unit collaborating with a local center for liver transplantation. Nine children, aged 2 to 15 yrs, who were treated with single-pass albumin dialysis for acute liver failure of various origins under a compassionate-use protocol between 2000 and 2006. All patients met high-urgency liver transplantation criteria. Single-pass albumin dialysis was performed as rescue therapy for children with acute liver failure. The decrease in hepatic encephalopathy (grades 1-4) and the serum levels of bilirubin, bile acids, and ammonium were measured to assess the efficacy of detoxification. As a measure of liver synthesis function, thromboplastin time and fibrinogen were analyzed. The safety of the procedure was assessed by documenting adverse effects on mean arterial blood pressure, platelet count, and clinical course. Seven out of nine patients were bridged successfully to either native organ recovery (n = 1) or liver transplantation (n = 6), one of them twice. Six out of nine patients undergoing single-pass albumin dialysis (ten treatments) survived. In six patients, hepatic encephalopathy could be reduced at least by one degree. Ammonium, bilirubin, and bile acid levels decreased in all patients. One patient had an allergic reaction to albumin. In childhood acute liver failure, treatment with single-pass albumin dialysis was generally well tolerated and seems to be effective in detoxification and in improving blood pressure, thus stabilizing the critical condition of children before liver transplantation and facilitating bridging to liver transplantation. It may be beneficial in avoiding severe neurologic sequelae after acute liver failure and thereby improve survival. Single-pass albumin dialysis is an inexpensive albumin-based detoxification system that is easy to set up and

  8. Analysis of viral testing in nonacetaminophen pediatric acute liver failure.

    Science.gov (United States)

    Schwarz, Kathleen B; Dell Olio, Dominic; Lobritto, Steven J; Lopez, M James; Rodriguez-Baez, Norberto; Yazigi, Nada A; Belle, Steven H; Zhang, Song; Squires, Robert H

    2014-11-01

    Viral infections are often suspected to cause pediatric acute liver failure (PALF), but large-scale studies have not been performed. We analyzed the results of viral testing among nonacetaminophen PALF study participants. Participants were enrolled in the PALF registry. Diagnostic evaluation and final diagnosis were determined by the site investigator and methods for viral testing by local standard of care. Viruses were classified as either causative viruses (CVs) or associated viruses (AVs). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included "viral," "indeterminate," and "other." Of 860 participants, 820 had at least 1 test result for a CV or AV. A positive viral test was found in 166/820 (20.2%) participants and distributed among "viral" (66/80 [82.5%]), "indeterminate" (52/420 [12.4%]), and "other" (48/320 [15.0%]) diagnoses. CVs accounted for 81/166 (48.8%) positive tests. Herpes simplex virus (HSV) was positive in 39/335 (11.6%) who were tested 26/103 (25.2%) and 13/232 (5.6%) among infants 0 to 6 and >6 months, respectively. HSV was not tested in 61.0% and 53% of the overall cohort and those 0 to 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Viral testing in PALF occurs frequently but is often incomplete. The evidence for acute viral infection was found in 20.2% of those tested for viruses. HSV is an important viral cause for PALF in all age groups. The etiopathogenic role of CV and AV in PALF requires further investigation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Eun, Hyo Won; Cho, Kyoung Sik; Kim, Jeong Kon [Asan Medical Center, Ulsan University College of Medicine, Seoul (Korea, Republic of); Kim, Jung Hoon [Soonchunhyang University School of Medicine, Seoul (Korea, Republic of)

    2002-09-15

    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.

  10. Research advances in oxidative stress and mitochondrial permeability transition in liver failure

    Directory of Open Access Journals (Sweden)

    WANG Kefei

    2013-09-01

    Full Text Available Major treatment options for liver failure include clinical medical treatment, and prevention of complications, artificial liver, liver transplantation, and stem cell transplantation. While these means are known to have produced favorable outcomes, some patients died due to acute and severe onset of disease or treatment delays. Oxidative stress has emerged as a research hotspot in recent years and antioxidant treatment has been drawing increasing attention. Outlines research developments in recent years and reviews the association of oxidative stress injury and mitochondrial permeability transition pore (MPTP with liver failure, in an effort to shed light on the importance of oxidative stress in the pathogenesis of liver failure and offer a theoretical basis and ideas for antioxidant therapy in the future.

  11. TRANSPLANTATION OF CRYOPRESERVED FETAL LIVER CELLS SEEDED INTO MACROPOROUS ALGINATE-GELATIN SCAFFOLDS IN RATS WITH LIVER FAILURE

    Directory of Open Access Journals (Sweden)

    D. V. Grizay

    2015-01-01

    Full Text Available Aim. To study the therapeutic potential of cryopreserved fetal liver cells seeded into macroporous alginategelatin scaffolds after implantation to omentum of rats with hepatic failure.Materials and methods.Hepatic failure was simulated by administration of 2-acetyl aminofl uorene followed partial hepatectomy. Macroporous alginate-gelatin scaffolds, seeded with allogenic cryopreserved fetal liver cells (FLCs were implanted into rat omentum. To prevent from colonization of host cells scaffolds were coated with alginate gel shell. Serum transaminase activity, levels of albumin and bilirubin as markers of hepatic function were determined during 4 weeks after failure model formation and scaffold implantation. Morphology of liver and scaffolds after implantation were examined histologically. Results. Macroporous alginate-gelatin scaffolds after implantation to healthy rats were colonized by host cells. Additional formation of alginate gel shell around scaffolds prevented the colonization. Implantation of macroporous scaffolds seeded with cryopreserved rat FLCs and additionally coated with alginate gel shell into omentum of rats with hepatic failure resulted in signifi cant improvement of hepatospecifi c parameters of the blood serum and positive changes of liver morphology. The presence of cells with their extracellular matrix within the scaffolds was confi rmed after 4 weeks post implantation.Conclusion. The data above indicate that macroporous alginate-gelatin scaffolds coated with alginate gel shell are promising cell carriers for the development of bioengineered liver equivalents.

  12. A new mutation of Fanconi–Bickel syndrome with liver failure and ...

    Indian Academy of Sciences (India)

    2012-12-13

    -2 gene that causes Fanconi–Bickel syndrome. Moreover, we show that pseudotumour cerebri and liver failure might be novel presentations of Fanconi–. Bickel syndrome and they might be associated with this new mutation.

  13. Liver failure in a child receiving highly active antiretroviral therapy and voriconazole

    NARCIS (Netherlands)

    Scherpbier, Henriette J.; Hilhorst, Michaela I.; Kuijpers, Taco W.

    2003-01-01

    We describe a 10-year-old child with vertically transmitted acquired immunodeficiency syndrome who was receiving antiretroviral combination therapy and died of liver failure after beginning voriconazole therapy

  14. 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

  15. Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure.

    Science.gov (United States)

    McKenzie, Rebecca B; Berquist, William E; Nadeau, Kari C; Louie, Christine Y; Chen, Sharon F; Sibley, Richard K; Glader, Bertil E; Wong, Wendy B; Hofmann, Lawrence V; Esquivel, Carlos O; Cox, Kenneth L

    2014-08-01

    In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Pediatric liver failure: we came, we saw, but have we conquered?

    OpenAIRE

    Smith, Sara Kathryn; Rosenthal, Philip

    2017-01-01

    Although there have been advances made in the diagnosis and management of pediatric acute liver failure, there is still no consensus regarding the definition or standardized evaluation, and an inability to predict outcomes, specifically irreversible brain injury, in many patients exists. Much of the research surrounding pediatric acute liver failure in the last several years has centered on the development of predictive scoring systems to enhance diagnosis and treatment decisions. In this art...

  17. Prediction of Poor Outcome in Patients with Acute Liver Failure-Systematic Review of Prediction Models

    NARCIS (Netherlands)

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

    2012-01-01

    Introduction: Acute liver failure is a rare disease with high mortality and liver transplantation is the only life saving therapy. Accurate prognosis of ALF is crucial for proper intervention. Aim: To identify and characterize newly developed prognostic models of mortality for ALF patients, assess

  18. Pediatric liver transplantation for fulminant hepatic failure secondary to intentional iron overdose.

    Science.gov (United States)

    Lai, Joanne; Chu, Jaime; Arnon, Ronen

    2017-09-01

    Acute iron poisoning may lead to life-threatening hepatotoxicity. We present the cases of two pediatric patients with hepatotoxicity following intentional iron ingestion that progressed rapidly to fulminant hepatic failure despite treatment with deferoxamine. Liver transplantation was lifesaving in both patients. These cases emphasize the need for a high index of suspicion for iron ingestion, close monitoring for liver toxicity, and timely consideration for liver transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure

    Science.gov (United States)

    Rodriguez, Keila; Srivaths, Poyyapakkam R.; Tal, Leyat; Watson, Mary N; Riley, Alyssa A.; Himes, Ryan W.; Desai, Moreshwar S.; Braun, Michael C.

    2017-01-01

    Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT) as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA) is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA) was defined as total calcium (mg/dl) /ionized calcium (mmol/L) ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs) defined as bleeding, hemodynamic instability, arrhythmias). Fifty-one patients (median age 3.5 (IQR 0.75–14.2) years) received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29–74); 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention. PMID:28792509

  20. Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure.

    Directory of Open Access Journals (Sweden)

    Keila Rodriguez

    Full Text Available Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA was defined as total calcium (mg/dl /ionized calcium (mmol/L ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs defined as bleeding, hemodynamic instability, arrhythmias. Fifty-one patients (median age 3.5 (IQR 0.75-14.2 years received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29-74; 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention.

  1. Regional citrate anticoagulation for continuous renal replacement therapy in pediatric patients with liver failure.

    Science.gov (United States)

    Rodriguez, Keila; Srivaths, Poyyapakkam R; Tal, Leyat; Watson, Mary N; Riley, Alyssa A; Himes, Ryan W; Desai, Moreshwar S; Braun, Michael C; Akcan Arikan, Ayse

    2017-01-01

    Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT) as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA) is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA) was defined as total calcium (mg/dl) /ionized calcium (mmol/L) ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs) defined as bleeding, hemodynamic instability, arrhythmias). Fifty-one patients (median age 3.5 (IQR 0.75-14.2) years) received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29-74); 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention.

  2. NBAS mutations cause acute liver failure: when acetaminophen is not a culprit.

    Science.gov (United States)

    Calvo, Pier Luigi; Tandoi, Francesco; Haak, Tobias B; Brunati, Andrea; Pinon, Michele; Olio, Dominic Dell; Romagnoli, Renato; Spada, Marco

    2017-09-25

    Pediatric acute-liver-failure due to acetaminophen (APAP) administration at therapeutic dosage is rare, while viral infections and metabolic defects are the prevalent causes. Yet, as acetaminophen is routinely used in febrile illnesses, it may be mistakenly held responsible for the acute liver damage. An 11 month old boy had been on acetaminophen for 10 days (total dose 720 mg = 72 mg/kg) when he developed acute-liver-failure with encephalopathy. As he rapidly improved on N-acetylcysteine (NAC) infusion, it was concluded that chronic acetaminophen administration in an infant had lead to acute-liver-failure even at therapeutic doses, that N-acetylcysteine infusion had been life-saving and should be immediately started in similar circumstances. The child, however, had two further episodes of acute liver damage over a 34-month period, without having been given acetaminophen, as the parents carefully avoided using it. His clinical, laboratory and radiological findings between the acute episodes were unremarkable. His features and skeletal surveys were not suggestive of a syndromic condition. He then went on to suffer another episode of acute-liver-failure with multi-organ failure, necessitating an urgent liver transplant. All efforts to come to a diagnosis for the causes of his recurrent episodes of liver failure had been unsuccessful, until a biallelic mutation in the NBAS gene was reported to be associated with recurrent acute-liver-failure in children. The boy's DNA analysis revealed compound heterozygous pathogenic mutations in the NBAS gene. Liver failure episodes in these patients are triggered and worsened by fever, most likely due to thermal susceptibility of hepatocytes, hence APAP, rather than being a culprit, is part of the supportive treatment. We suggest that, in acute-liver-failure with a history of acetaminophen exposure at therapeutic dosage, clinicians should not be contented with administering NAC, but should consider an alternative etiology

  3. Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease.

    Science.gov (United States)

    Hong, Yun Soo; Sinn, Dong Hyun; Gwak, Geum-Youn; Cho, Juhee; Kang, Danbee; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-04-14

    To analyze characteristics and outcome of patients with acute-on-chronic liver failure (ACLF) according to the severity of underlying liver disease. One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis (type A), cirrhosis (type B) and cirrhosis with previous decompensation (type C). The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in types B and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate (85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate (55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different (85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02). There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF.

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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

    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...... normalised ratio (INR), and cardiovascular failure were used to derive an initial predictive model, with a second (day 2) model including additional changes in INR and lactate. FINDINGS: We developed and validated new high-performance statistical models to support decision making in patients with paracetamol...

  6. Deteriorated portal flow may cause liver failure in patients with hepatocellular carcinoma being treated with sorafenib.

    Science.gov (United States)

    Yamasaki, Akihiro; Umeno, Narihiro; Harada, Shigeru; Tanaka, Kosuke; Kato, Masaki; Kotoh, Kazuhiro

    2016-06-01

    We encountered two patients with hepatocellular carcinoma (HCC) who showed rapid progression of liver failure during sorafenib treatment. One had portal vein tumor thrombus (PVTT) and the other developed portal vein thrombosis (PVT) during the treatment, and both of them experienced the elevation of serum lactate dehydrogenase (LDH) concentration during the administration of sorafenib. Their clinical courses indicate that the liver failure might have been caused by sorafenib-induced liver hypoxia, being amplified in the circumstances with reduced portal flow. To our best knowledge, all the reported patients who achieved complete remission (CR) during sorafenib monotherapy had a condition that could decrease portal blood flow. We hypothesized that pathogenesis of disease may be similar in HCC patients who achieve CR and those who experience liver failure while on sorafenib. Sorafenib treatment of patients with HCC and deteriorated portal flow may be a double-edged sword.

  7. Percutaneous Liver Biopsy after Living Donor Liver Transplantation Resulting in Fulminant Hepatic Failure: The First Reported Case of Hepatic Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Nicholas N. Nissen

    2010-01-01

    Full Text Available A 28-year-old female who underwent live donor liver transplantation 3 years prior presented after percutaneous liver biopsy with abdominal and shoulder pain, nausea, vomiting, and elevated liver enzymes. Computed tomography (CT showed an intrahepatic and subcapsular hematoma. There was a progressive increase in liver enzymes, bilirubin, and INR and a decline in hemoglobin. Subsequent CT imaging revealed flattening of the portal vein consistent with compression by the enlarging hematoma. Liver failure ensued and the patient required urgent retransplantation. The explant demonstrated ischemic necrosis of greater than 90% of the liver parenchyma. We report this case of “Hepatic Compartment Syndrome” leading to fulminant hepatic failure.

  8. Is liver biopsy necessary in the management of alcoholic hepatitis?

    Science.gov (United States)

    Dhanda, Ashwin D; Collins, Peter L; McCune, C Anne

    2013-11-28

    Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accurate diagnosis. However, there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy. We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH. In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor. Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions, we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology. It also adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology. Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.

  9. Encephalopathy in Wilson disease: copper toxicity or liver failure?

    National Research Council Canada - National Science Library

    Ferenci, Peter; Litwin, Tomasz; Seniow, Joanna; Czlonkowska, Anna

    2015-01-01

    Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology...

  10. Acute Liver Failure Caused by Amanita phalloides Poisoning

    National Research Council Canada - National Science Library

    Santi, Luca; Maggioli, Caterina; Mastroroberto, Marianna; Tufoni, Manuel; Napoli, Lucia; Caraceni, Paolo

    2012-01-01

    ... and deadly cause of mushroom poisoning. Liver damage from Amanita phalloides is related to the amanitins, powerful toxins that inhibit RNA polymerase II resulting in a deficient protein synthesis and cell necrosis...

  11. Immunological consequences of the use of xenogeneic hepatocytes in a bioartificial liver for acute liver failure

    NARCIS (Netherlands)

    te Velde, A. A.; Flendrig, L. M.; Ladiges, N. C.; Chamuleau, R. A.

    1997-01-01

    The use of cells from xenogeneic origin in a bioartificial liver can have a number of immunological consequences, not only for the cells in the bioartificial liver but also for the patient receiving the bioartificial liver treatment. The impact of these consequences will depend on the immune status

  12. A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma.

    Science.gov (United States)

    Ichikawa, Tsuyoshi; Uenishi, Takahiro; Takemura, Shigekazu; Oba, Kazuki; Ogawa, Masao; Kodai, Shintaro; Shinkawa, Hiroji; Tanaka, Hiromu; Yamamoto, Takatsugu; Tanaka, Shogo; Yamamoto, Satoshi; Hai, Seikan; Shuto, Taichi; Hirohashi, Kazuhiro; Kubo, Shoji

    2009-01-01

    A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma. Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses. Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10. Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

  13. Living donor liver transplantation for acute liver failure in pediatric patients caused by the ingestion of fireworks containing yellow phosphorus.

    Science.gov (United States)

    Ates, Mustafa; Dirican, Abuzer; Ozgor, Dincer; Aydin, Cemalettin; Isik, Burak; Ara, Cengiz; Yilmaz, Mehmet; Ayse Selimoglu, M; Kayaalp, Cuneyt; Yilmaz, Sezai

    2011-11-01

    Yellow phosphorus is a protoplasmic toxicant that targets the liver. The ingestion of fireworks containing yellow phosphorus, either by children who accidentally consume them or by adults who are attempting suicide, often results in death due to acute liver failure (ALF). We present the outcomes of 10 children who ingested fireworks containing yellow phosphorus. There were 6 boys and 4 girls, and their ages ranged from 21 to 60 months. One patient remained stable without liver complications and was discharged. Three patients died of hepatorenal failure and cardiovascular collapse, and living donor liver transplantation (LDLT) was performed for 6 patients. The patients had grade II or III encephalopathy, a mean alanine aminotransferase level of 1148.2 IU/L, a mean aspartate aminotransferase level of 1437.5 IU/L, a mean total bilirubin level of 6.9 mg/dL, a mean international normalized ratio of 6.6, a mean Pediatric End-Stage Liver Disease score of 33.7, and a mean Child-Pugh score of 11.3. Postoperatively, 2 patients had persistent encephalopathy and died on the second or third postoperative day, and 1 patient died of cardiac arrest on the first postoperative day despite a well-functioning graft. The other 3 patients were still alive at a mean of 204 days. In conclusion, the ingestion of fireworks containing yellow phosphorus causes ALF with a high mortality rate. When signs of irreversible ALF are detected, emergency LDLT should be considered as a lifesaving procedure; however, if yellow phosphorus toxicity affects both the brain and the heart in addition to the liver, the mortality rate remains very high despite liver transplantation. Copyright © 2011 American Association for the Study of Liver Diseases.

  14. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  15. Use of hepatocyte and stem cells for treatment of post-resectional liver failure: are we there yet?

    NARCIS (Netherlands)

    Ezzat, T. M.; Dhar, D. K.; Newsome, P. N.; Malago, M.; Olde Damink, S.

    2011-01-01

    Post-operative liver failure following extensive resections for liver tumours is a rare but significant complication. The only effective treatment is liver transplantation (LT); however, there is a debate about its use given the high mortality compared with the outcomes of LT for chronic liver

  16. Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute Liver Failure.

    Science.gov (United States)

    Deep, Akash; Stewart, Claire E; Dhawan, Anil; Douiri, Abdel

    2016-10-01

    To establish the effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. Retrospective cohort study. Sixteen-bed PICU in a university-affiliated tertiary care hospital and specialist liver centre. All children (0-18 yr) admitted to PICU with pediatric acute liver failure between January 2003 and December 2013. Children with pediatric acute liver failure were managed according to a set protocol. The guidelines for continuous renal replacement therapy in pediatric acute liver failure were changed in 2011 following preliminary results to indicate the earlier use of continuous renal replacement therapy for both renal dysfunction and detoxification. Of 165 children admitted with pediatric acute liver failure, 136 met the inclusion criteria and 45 of these received continuous renal replacement therapy prior to transplantation or recovery. Of the children managed with continuous renal replacement therapy, 26 (58%) survived: 19 were successfully bridged to liver transplantation and 7 spontaneously recovered. Cox proportional hazards regression model clearly showed reducing hyperammonemia by 48 hours after initiating continuous renal replacement therapy significantly improved survival (HR, 1.04; 95% CI, 1.013-1.073; p = 0.004). On average, for every 10% decrease in ammonia from baseline at 48 hours, the likelihood of survival increased by 50%. Time to initiate continuous renal replacement therapy from PICU admission was lower in survivors compared to nonsurvivors (HR, 0.96; 95% CI, 0.916-1.007; p = 0.095). Change in practice to initiate early and high-dose continuous renal replacement therapy led to increased survival with maximum effect being visible in the first 14 days (HR, 3; 95% CI, 1.0-10.3; p = 0.063). Among children with pediatric acute liver failure who did not receive a liver transplant, use of continuous renal replacement therapy significantly improved survival (HR, 4; 95% CI, 1.5-11.6; p = 0.006). Continuous renal replacement

  17. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Carolina Roos Mariano da Rocha

    2017-01-01

    Full Text Available Neonatal liver failure (NLF is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment.

  18. Human Parechovirus as a Cause of Isolated Pediatric Acute Liver Failure.

    Science.gov (United States)

    Bigelow, Amee M; Scott, John P; Hong, Johnny C; Cronin, David C; Vitola, Bernadette E; Fons, Roger A; Petersen, Tara L

    2016-11-01

    Among infants, almost half of acute liver failure cases are classified as indeterminate, whereas only a small number of cases show a documented viral infection. We present the first reported case of isolated acute hepatic failure in an infant in the setting of a human parechovirus (HPeV) infection. HPeV also may have been contributory to the posttransplant complication of 2 intussusceptions. This is a 10-month-old girl who presented with only symptoms of fussiness and was noted to have progressive decline in synthetic liver function as well as worsening coagulopathy requiring a liver transplant. The acute liver failure was in the setting of a positive serum RNA HPeV, subtype 3 (HPeV-3), after extensive diagnostic testing with genetic, autoimmune, and infectious causes otherwise negative. After liver transplantation, the postoperative course was complicated by both an ileal-ileal intussusception as well as a jejunal intussusception. Viral testing in pediatric acute liver failure is often performed, but the workup is frequently incomplete. This case report would support more extensive viral testing in this population of patients. In the setting of HPeV, clinicians could be alerted to the possibility of delayed gastrointestinal pathology in the posttransplant phase. Wider use of routine HPeV testing may more clearly define the variable clinical presentations and outcomes. Copyright © 2016 by the American Academy of Pediatrics.

  19. Plasma Cystatin C is a predictor of renal dysfunction, ACLF and mortality in patients with acutely decompensated liver cirrhosis

    DEFF Research Database (Denmark)

    Markwardt, Daniel; Holdt, Lesca M; Steib, Christian

    2017-01-01

    BACKGROUND: The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. AIM: To investigate whether...... Cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF and mortality, respectively. METHODS: We determined the plasma levels of CysC and NGAL of 429 patients hospitalized for acute decompensation....... CONCLUSIONS: Baseline CysC is a biomarker of renal dysfunction, HRS and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis. Determining CysC at day 3 did not provide any benefit. While NGAL is also associated with short-term mortality, it fails to predict...

  20. Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure.

    Science.gov (United States)

    Thiel, Karolin; Klingert, Wilfried; Klingert, Kathrin; Morgalla, Matthias H; Schuhmann, Martin U; Leckie, Pamela; Sharifi, Yalda; Davies, Nathan A; Jalan, Rajiv; Peter, Andreas; Grasshoff, Christian; Königsrainer, Alfred; Schenk, Martin; Thiel, Christian

    2017-03-07

    To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose. Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy. Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 mL/min) increased to a maximum flow of 1873 ± 175 mL/min at manifestation of ALF, which was significantly elevated (P 0.01). Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.

  1. 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.

  2. Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.

    Science.gov (United States)

    Hanish, Steven I; Stein, Deborah M; Scalea, Joseph R; Essien, Eno-Obong; Thurman, Paul; Hutson, William R; Bartlett, Stephen T; Barth, Rolf N; Scalea, Thomas M

    2017-10-01

    Patients with severe acute liver failure (ALF) have extreme physiologic dysfunction and often die if transplantation is not immediately available. Patients may be supported with MARS (Baxter International Inc., Deerfield, IL) until transplantation or spontaneous recovery occurs. We present the largest series in the United States of MARS therapy as temporary hepatic replacement for ALF. MARS was used to support patients with severe liver trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a level 1 trauma center and large transplant center. Patient demographics, etiology of ALF, and laboratory values were recorded. Endpoints were patient survival ± liver transplant and/or recovery of liver function. Twenty-seven patients with severe ALF received MARS therapy. Five patients with SLT had a 60% survival with recovery of liver and renal function. Thirteen patients received MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78% (program overall survival 85% at 1 year). All 4 who were not transplanted expired. Nine patients with ALF from toxic ingestion received MARS as DT with liver recovery and survival in 67%. MARS therapy resulted in significant improvement in liver function, coagulation, incidence of encephalopathy, and creatinine. MARS therapy successfully replaced hepatic function in ALF allowing time for spontaneous recovery or transplantation. Spontaneous recovery was remarkably common if support can be sustained.

  3. Role of inflammation and infection in the pathogenesis of human acute liver failure: Clinical implications for monitoring and therapy.

    Science.gov (United States)

    Donnelly, Mhairi C; Hayes, Peter C; Simpson, Kenneth J

    2016-07-14

    Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multi-organ failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.

  4. Incidence and Clinical Outcome of Acute Liver Failure Caused by Dengue in a Hospital for Tropical Diseases, Thailand.

    Science.gov (United States)

    Kye Mon, Khin; Nontprasert, Apichart; Kittitrakul, Chatporn; Tangkijvanich, Pisit; Leowattana, Wattana; Poovorawan, Kittiyod

    2016-12-07

    Acute liver failure is an atypical manifestation of dengue with a high mortality. We performed a retrospective cohort study at the Hospital for Tropical Diseases, Bangkok, Thailand. In total, 1,926 patients with serologically confirmed dengue were enrolled in the study from 2011 to 2015. Of these, six patients presented with acute liver failure, four died, and two survived. The incidence of dengue-associated acute liver failure was 0.31%. Dengue-associated acute liver failure was most common among young adults (median age, 29 years). The median duration from onset of fever to development of acute liver failure was 7.5 days. Patients with the severe stage of dengue had a higher risk of developing acute liver failure (P acute liver failure were an age of ≤ 40 years (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, P 10% ratio of atypical lymphocytes (OR = 2.3, 95% CI = 1.8-3.0, P acute liver failure in patients with dengue was quite low, but its impact on morbidity, mortality, and poor clinical outcomes was significant. In summary, this study indicates that various baseline risk factors are associated with acute liver failure in patients with dengue. © The American Society of Tropical Medicine and Hygiene.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Liver transplantation for acute hepatic failure due to chemotherapy-induced HBV reactivation in lymphoma patients

    Science.gov (United States)

    Noterdaeme, Timothée; Longrée, Luc; Bataille, Christian; Deroover, Arnaud; Lamproye, Anne; Delwaide, Jean; Beguin, Yves; Honoré, Pierre; Detry, Olivier

    2011-01-01

    Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reactivation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft re-infection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignancies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good. PMID:21799656

  7. Pediatric acute liver failure: variations in referral timing are associated with disease subtypes.

    Science.gov (United States)

    Sturm, Ekkehard; Lexmond, Willem S; Verkade, Henkjan J

    2015-02-01

    In pediatric acute liver failure (PALF), rapid referral to a transplant center (TC) is advocated. Clinical variability of PALF may influence referral timing. We aimed to analyze early or late timing of referral in relation to clinical characteristics and outcome in PALF. We conducted a retrospective, single-center, comparative analysis of clinical and liver function parameters in two PALF cohorts (n = 23 per cohort): cohort 1 (early referral, duration of in-patient care before referral (DCR) liver failure (SLF >7 days between disease onset and development of encephalopathy) was independently associated with late referral (relative risk 9.48; 95 % CI 1.37-64.85, p liver function patterns. Early recognition of prognostic indicators and of SLF may help to improve referral timing and thus PALF management.

  8. Management of Pediatric Acute Liver Failure in a Region With Insufficient Deceased Donor Support: A Single-Center Experience.

    Science.gov (United States)

    Yankol, Yucel; Ertugrul, Mustafa; Kanmaz, Turan; Mecit, Nesimi; Ocak, Ilhan; Durmaz, Ozlem; Acarli, Koray; Kalayoglu, Munci

    2016-10-01

    Acute liver failure is a rapidly progressive and life-threatening disease in children, whose clinical features differ from those of adults. This is a review of a single center's experience with pediatric acute liver failure in a region with insufficient deceased donor support. The study is a retrospective review and analysis of 22 pediatric patients with acute liver failure between January 2007 and May 2013. The cause of acute liver failure was indeterminate in 45.4% of cases. Listing for liver transplant was required in 72.7% of patients, whereas 27.3% developed spontaneous remission. In the patients placed on the liver transplant wait list, 75% underwent liver transplant and 25% died before undergoing liver transplant. The presence of ascites, high-grade encephalopathy, and laboratory findings including high lactate dehydrogenase and phosphorous levels and international normalized ratio were significant parameters in selecting patients needing liver transplants. All liver transplants were from living donors. One- and 3-year patient survival rates after liver transplant were 75% and 75%. No serious donor complications occurred. Living-donor liver transplant may be the only option to save the lives of pediatric patients with acute liver failure, especially in regions with insufficient deceased-donor support. Timely referral to a multidisciplinary transplant center, expedient evaluation of living donors, and appropriate timing of transplant are crucial for a successful outcome.

  9. Pre-operative risk factors predict post-operative respiratory failure after liver transplantation.

    Directory of Open Access Journals (Sweden)

    Ching-Tzu Huang

    Full Text Available OBJECTIVE: Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF after liver transplantation and the impact on short-term survival rates. DESIGN: The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not. MEASUREMENTS AND MAIN RESULTS: Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS use, source of organ transplantation, model for end-stage liver disease score (MELD and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05. Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001. CONCLUSIONS: The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation.

  10. Acute Liver Failure Associated with Propylthiouracil in a Pregnant 26-Year-Old Woman

    Directory of Open Access Journals (Sweden)

    Tatsuo Miyamura

    2013-05-01

    Full Text Available It seems appropriate to use propylthiouracil to treat maternal hyperthyroidism during the first trimester of pregnancy. We present the case of a 26-year-old woman with acute liver failure associated with propylthiouracil during the first trimester of pregnancy. She was successfully treated without liver transplantation. Attention should be paid to the possible occurrence of propylthiouracil-induced hepatotoxicity even during the first trimester of pregnancy.

  11. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    OpenAIRE

    Robin Paudel; Prerna Dogra; Saurav Suman; Saurav Acharya; Jyoti Matta

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncrat...

  12. Fatal subacute liver failure after repeated administration of sevoflurane anaesthesia.

    Science.gov (United States)

    Zizek, David; Ribnikar, Marija; Zizek, Bogomir; Ferlan-Marolt, Vera

    2010-01-01

    Sevoflurane is a widely used halogenated inhalation anaesthetic. In comparison with other similar anaesthetics, it is not metabolized to potentially hepatotoxic trifluoroacetylated proteins. In this case report, we present a 66-year-old woman with breast carcinoma, who underwent sevoflurane general anaesthesia twice in 25 days. Soon after the second elective surgical procedure, jaundice and marked elevations in serum transaminases developed. The patient died 66 days thereafter. Autopsy results denied evidence of major cardiovascular abnormality, and histological examination confirmed massive liver cell necrosis with no feature of chronic liver injury. Sevoflurane anaesthesia was imputed as the cause after exclusion of other possible aetiological agents. Besides, coexistent malignant tumours found in the patient could have modulated the immunological response to the applied anaesthetic followed by fatal consequences.

  13. Potential Use of Biological Proteins for Liver Failure Therapy

    Directory of Open Access Journals (Sweden)

    Kazuaki Taguchi

    2015-08-01

    Full Text Available Biological proteins have unlimited potential for use as pharmaceutical products due to their various biological activities, which include non-toxicity, biocompatibility, and biodegradability. Recent scientific advances allow for the development of novel innovative protein-based products that draw on the quality of their innate biological activities. Some of them hold promising potential for novel therapeutic agents/devices for addressing hepatic diseases such as hepatitis, fibrosis, and hepatocarcinomas. This review attempts to provide an overview of the development of protein-based products that take advantage of their biological activity for medication, and discusses possibilities for the therapeutic potential of protein-based products produced through different approaches to specifically target the liver (or hepatic cells: hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells in the treatment of hepatic diseases.

  14. 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....

  15. Recovery from liver failure after hepatectomy for hepatocellular carcinoma in cirrhosis: meaning of the model for end-stage liver disease.

    Science.gov (United States)

    Cucchetti, Alessandro; Ercolani, Giorgio; Cescon, Matteo; Ravaioli, Matteo; Zanello, Matteo; Del Gaudio, Massimo; Lauro, Augusto; Vivarelli, Marco; Grazi, Gian Luca; Pinna, Antonio Daniele

    2006-11-01

    Hepatectomy for hepatocellular carcinoma in cirrhosis is followed by an impairment of liver function that can lead to patient death. The model for end-stage liver disease (MELD) is considered an index of hepatic functional reserve, and its assessment on postoperative course may properly identify individuals at risk of liver failure. Two hundred hepatectomies for hepatocellular carcinoma in cirrhosis were reviewed. Irreversible postoperative liver failure was defined as an impairment of liver function after hepatectomy that led to patient death or required transplantation. The MELD scores at postoperative days (POD) 1, 3, 5, and 7 were calculated and kinetics of changes investigated with t-test; logistic regression was applied to identify predictive variables of postoperative liver failure. Kinetics of postoperative MELD score showed an impairment of liver function between PODs 1 and 3; 185 patients in whom postoperative liver failure did not develop showed a considerable decrease in MELD score between PODs 3 and 5 (11.9+/-2.8 and 10.6+/-2.4, respectively, pfailure. Scores are reported as mean+/-SD. Recovery from liver impairment after hepatectomy for hepatocellular carcinoma in cirrhosis starts from POD 3; MELD scores increasing between PODs 3 and 5 may identify patients at risk of liver failure and represents the trigger for beginning intensive treatment or evaluating salvage transplantation.

  16. Acute Liver Failure: Outcome and Value of Pediatric End-Stage Liver Disease Score in Pediatric Cases.

    Science.gov (United States)

    Núñez-Ramos, Raquel; Montoro, Soledad; Bellusci, Marcello; Del Fresno-Valencia, María Rosa; Germán-Díaz, Marta; Urruzuno, Pedro; Medina, Enrique; Manzanares, Javier

    2016-09-30

    The aims of this study were to analyze the characteristics of patients with acute liver failure (ALF) in our center and evaluate the prognostic value of the Pediatric End-Stage Liver Disease (PELD) score calculated at admission. A retrospective analysis of patients with ALF younger than 15 years between 2005 and 2013 was performed. Information collected included age, sex, etiology of ALF, laboratory tests, PELD score, stage of encephalopathy, and need for liver support devices such as MARS and/or liver transplant (LT) and survival. A poor prognosis was defined as the need for LT or death. Twenty patients (10 male patients, 50%) with a median age of 2.6 years (3 days-14.5 y old) were included. Acute liver failure was of indeterminate cause in 5 cases (25%). Within the recognized causes, the most frequent were viral hepatitis (herpes simplex virus, adenovirus, influenza B, Epstein-Barr virus), autoimmune hepatitis, and metabolopathies. Sixty percent presented with encephalopathy at diagnosis. Four patients were aided by a MARS liver support device. Six patients received a total of 7 transplants, all from deceased donors. The rate of spontaneous recovery was 45%. Currently 13 patients (65%) are living, 4 of them with an LT. Six patients died because of ALF. The mean PELD score of patients with spontaneous recovery was 15.31 (5.3-27.6) compared with a mean of 29.5 (17.2-39.4) in LT patients and 31.55 (15.8-52.4) for nonsurvivors (P = 0.013). High PELD scores at diagnosis were accurate predictors of a poor prognosis in our patients with ALF. This model may help in the clinical management of this entity, although prospective validation is needed.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests

    DEFF Research Database (Denmark)

    Korman, J.D.; Volenberg, I.; Balko, J.

    2008-01-01

    Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF...... patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp

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

    OpenAIRE

    Kula, R.; Melter, M.; Kunkel, J.; D?rfler, C.; Alikadic, S.; Knoppke, B.; Zant, R.

    2017-01-01

    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...

  20. Hepatic failure in a rapidly involuting congenital hemangioma of the liver: failure of embolotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zenzen, Wendy; Alomari, Ahmad I. [Children' s Hospital Boston, Division of Vascular and Interventional Radiology, Department of Radiology, Boston, MA (United States); Perez-Atayde, Antonio R. [Children' s Hospital Boston and Harvard Medical School, Department of Pathology, Boston, MA (United States); Elisofon, Scott A. [Children' s Hospital Boston and Harvard Medical School, Division of Gastroenterology, Boston, MA (United States); Bae Kim, Heung [Children' s Hospital Boston and Harvard Medical School, Department of Surgery, Boston, MA (United States)

    2009-10-15

    We report the clinical course, imaging findings, and management of a rare case of rapidly involuting congenital hemangioma of the liver in a newborn girl. The baby presented with severe progressive hepatic dysfunction and cardiomegaly. Multimodality imaging demonstrated a large hypervascular solitary hepatic mass with marked transhepatic shunting, consistent with rapidly involuting congenital hemangioma. Because medical therapy failed, transarterial and transvenous embolization was performed with the main intention to improve the hepatic perfusion and function. Unfortunately, despite improvement in the cardiac overload, liver function continued to deteriorate. The baby eventually underwent successful liver transplantation. (orig.)

  1. [Current benefit of biological and non-biological methods in the treatment of acute liver failure].

    Science.gov (United States)

    Ryska, O; Pantoflícek, T; Lásziková, E; Prazák, J; Ryska, M

    2008-06-01

    There was an active interest in development of liver assist device in the last two decades. Using these devices to bridge patients with acute hepatic failure (AHF) to ortotopic liver transplantation (OLTx) or to liver regeneration might decrease the mortality rate. Several liver support systems have been described in different stages of experimental or clinical examination. PubMed (1986-2008) was searched using the keywords "artifitial livers", "liver support", "bioartifitial liver" and "cell transplantation". The own experience presenting by authors are the conclusions of their publications. Biological liver support (BAL) uses hepatocytes can support theoretically both detoxification and biosynthesis. Experimental study confirmed significant decrease in some of AHF metabolites. Nevertheless, randomized study didn't show any improvement in patient's survival. Source of viable hepatocytes and sufficient bioreactor capacity are some of unsolved problems. Nonbiological liver support as a plasma exchange, hemodialysis, hemofiltration, albumin dialysis or adsorbent recycling systems eliminate some of toxins, but other specific liver functions can't replace. MARS and Prometheus devices have been used successfully in treatment of AHF by human. However, the absence of randomized study still lasts. These devices remove some of toxins and cytokines unselectively and are also limited by adsorber capacity. Selective plasma filtration therapy and hybrid liver support systems which combine both of management advances present the possible solution. Authors themselves confirmed by application of both methods a significant decrease of bilirubin level. Intracranial pressure declines only by use of non-biological device - Prometheus. Effective liver assist device that gains a survival approval hasn't been developed till now. In confrontation with other current used cure possibilities, BAL didn't propose the original expectations. On the other hand, the non-biological devices seem to

  2. Prevalence, Severity, and Impact of Renal Dysfunction in Acute Liver Failure on the US Liver Transplant Waiting List.

    Science.gov (United States)

    Urrunaga, Nathalie H; Magder, Laurence S; Weir, Matthew R; Rockey, Don C; Mindikoglu, Ayse L

    2016-01-01

    Although renal dysfunction is a known complication of acute liver failure (ALF), its frequency, severity, and impact among patients with ALF on the US liver transplant list are not well defined. Organ Procurement and Transplantation data for ALF patients listed as status 1/1A from 2002 to 2012 were analyzed. The frequency and severity of renal dysfunction at the time of listing [the latter was categorized in 5 stages using estimated GFR (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation] were determined and the association between renal dysfunction and waiting list mortality was assessed using Cox proportional hazard regression analysis. There were a total of 2280 adult patients with ALF, including 56 % with renal dysfunction (defined as eGFR renal dysfunction was among those with ALF caused by hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome, fatty liver disease of pregnancy, heat stroke/hyperthermia, hepatitis A virus, and drug-induced liver injury due to acetaminophen APAP, phenytoin, trimethoprim-sulfamethoxazole, and macrolides. Despite the fact that 69 % (468/674) of patients with APAP-induced ALF listed as status 1/1A had renal dysfunction, only 0.9 % underwent simultaneous liver-kidney transplantation. Six-week survival probabilities in patients with ALF on the liver transplant waiting list were 71, 59, 56, 59, and 42 % with renal dysfunction stages of 1, 2, 3, 4, and 5, respectively. Multivariate analysis showed that after controlling for age, etiology of ALF, INR, total bilirubin, and region, the relative risk of death increased progressively as eGFR declined (P renal dysfunction was common (overall prevalence of 56 %). Most importantly, severe renal dysfunction was associated with significantly increased mortality.

  3. Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation?

    Science.gov (United States)

    Vondran, Florian Wolfgang Rudolf; Schumacher, Carsten; Johanning, Kai; Hartleben, Björn; Knitsch, Wolfgang; Wiesner, Olaf; Jaeckel, Elmar; Manns, Michael Peter; Klempnauer, Juergen; Bektas, Hueseyin; Lehner, Frank

    2016-01-01

    Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient. PMID:27274881

  4. Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation?

    Directory of Open Access Journals (Sweden)

    Florian Wolfgang Rudolf Vondran

    2016-01-01

    Full Text Available Background. Despite aggressive intensive medical management acute liver failure (ALF may require high-urgency liver transplantation (LTx. Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis, uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient.

  5. Salvage living-donor liver transplantation for liver failure following definitive radiation therapy for recurrent hepatocellular carcinoma: a case report.

    Science.gov (United States)

    Kitajima, T; Fujimoto, Y; Hatano, E; Nishida, H; Ogawa, K; Mori, A; Okajima, H; Kaido, T; Nakamura, A; Nagamatsu, H; Uemoto, S

    2015-04-01

    A 57-year-old man with a history of hepatitis B virus infection was referred to our hospital for living-donor liver transplantation (LDLT). Five years earlier, right lobectomy had been performed for solitary hepatocellular carcinoma (HCC) with bile duct tumor thrombus in segments 5 and 6 in the liver. Two years later, transarterial chemoembolization and radiofrequency ablation were performed for recurrent HCC. Two years after those local therapies, another recurrent HCC was treated with transhepatic arterial infusion chemotherapy with cisplatin and conventional radiation therapy (RT) with 60 Gy in 20 fractions, because the tumor was contiguous to the trunk of the portal vein. After the completion of RT, symptoms due to liver failure and severe infection caused by multiple liver abscesses developed despite the administration of antibiotics and percutaneous transhepatic cholangiodrainage. Therefore, LDLT was performed with the use of a right lobe graft donated by his wife. Vascular anastomosis was successfully performed with the use of normal procedures. The patient recovered uneventfully, and has since been doing well for 34 months, with no evidence of vascular complications. However, the degree of injury to the anastomotic vessels caused by definitive RT before LDLT remains unclear, whereas the safety and efficacy of some forms of RT as a bridge to deceased-donor LT have been reported. Salvage LDLT is effective for patients with liver failure after multidisciplinary treatment including radiation, while carefully taking radiation-induced vessel injury as a potential late complication into consideration, especially in LDLT cases. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Hepatitis A related acute liver failure by consumption of contaminated food

    NARCIS (Netherlands)

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

    2014-01-01

    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

  7. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure

    NARCIS (Netherlands)

    Korpela, K.; Mutanen, A.; Salonen, A.; Savilahti, E.; Vos, de W.M.; Pakarinen, M.P.

    2017-01-01

    BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent

  8. Pediatric acute liver failure : variations in referral timing are associated with disease subtypes

    NARCIS (Netherlands)

    Sturm, Ekkehard; Lexmond, Willem S.; Verkade, Henkjan J.

    2015-01-01

    In pediatric acute liver failure (PALF), rapid referral to a transplant center (TC) is advocated. Clinical variability of PALF may influence referral timing. We aimed to analyze early or late timing of referral in relation to clinical characteristics and outcome in PALF. We conducted a

  9. 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.

    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)

  10. Two-year outcomes in initial survivors with acute liver failure

    DEFF Research Database (Denmark)

    Fontana, Robert J; Ellerbe, Caitlyn; Durkalski, Valerie E

    2015-01-01

    likely to be employed and have a higher educational level (P relate to pre-existing medical comorbidities. Spontaneous survivors with APAP overdose......BACKGROUND & AIMS: The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. The aim of this study was to provide an overview of the 2-year clinical outcomes among initial survivors and liver transplant (LT) recipients that were alive 3 weeks after...... enrolment in the Acute Liver Failure Study Group (ALFSG). METHODS: Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. RESULTS: Two-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous...

  11. A unique presentation of acute liver failure from herpes simplex virus hepatitis.

    Science.gov (United States)

    Gutierrez, C; Kebriaei, P; Turner, K A; Yemelyanova, A; Ariza-Heredia, E J; Foo, W C

    2016-08-01

    We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  13. Liver transplantation in a case of steatohepatitis and subacute hepatic failure after biliopancreatic diversion for morbid obesity.

    Science.gov (United States)

    Castillo, J; Fábrega, E; Escalante, C F; Sanjuan, J C; Herrera, L; Hernánz, F; Martino, E; Casafont, F; Gómez Fleitas, M

    2001-10-01

    Biliopancreatic diversion (BPD) was designed to avoid the serious complications of jejunoileal bypass (steatohepatitis and hepatic failure). Although this is today considered a safe and effective procedure, a few reports of patients who developed steatohepatitis and subsequently died in hepatic failure exist. We report a morbidity obese patient who developed subacute hepatitis resulting in hepatic failure 1 year after BPD. Because of irreversible liver failure the decision to perform a liver transplantation was made. The patient underwent emergency liver transplant and lengthening of the common limb. The course of liver transplantation and the patient's recovery were uneventful. Severe liver disease may rarely follow BPD. Liver transplantation and lengthening of the common bowel may be performed to treat these patients.

  14. [Protective effect of astragaloside IV against acute liver failure in experimental mice].

    Science.gov (United States)

    Liu, L; Li, S J; Zhou, Y

    2016-10-20

    Objective: To investigate the clinical effect of astragaloside IV in the early treatment of mice with acute liver failure and possible mechanisms. Methods: A mouse model of acute liver failure induced by D-galactosamine/lipopolysaccharide (D-GalN/LPS) was established, and the mice were given astragaloside IV at different doses. The survival rate of mice, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver histopathological changes, apoptosis of hepatocytes, and the expression of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in each group. The least significant difference test was used for data with homogeneity of variances, the Dunnett's T3 test was used for data with heterogeneity of variance, and the Kaplan-Meier method was used for survival analysis. Results: Compared with the model group, the high-dose astragaloside IV group had a significant increase in the 48-hour survival rate [60% (9/15) vs 13.3% (2/15), P liver histopathological indices and the degree of apoptosis of hepatocytes (P liver homogenate (P acute liver injury in mice, and its mechanisms may be associated with its effects against cell apoptosis and oxidative damage.

  15. Etiologies, outcomes, and prognostic factors of pediatric acute liver failure: A single center's experience in Turkey.

    Science.gov (United States)

    Özçay, Figen; Karadağ Öncel, Eda; Barış, Zeren; Canan, Oğuz; Moray, Gökhan; Haberal, Mehmet

    2016-09-01

    Our aim was to determine the etiologies, outcomes, and prognostic indicators in children with acute liver failure. Ninety-one patients who were followed for pediatric acute liver failure (PALF) over a 15-year period were included. Patients who survived with supportive therapy were designated as Group 1, while those who died or underwent liver transplantation were designated as Group 2. There were 37 (40.6%) patients in Group 1 (spontaneous recovery) and 54 (59.4%) patients in Group 2. Thirty-two patients (35.2%) underwent liver transplantation. Infectious and indeterminate causes were the most common etiologies (33% each). Among the infectious causes, hepatitis A (76%) was the most frequent. Hepatic encephalopathy grade 3-4 on admission and during follow-up and high Pediatric Risk of Mortality (PRISM) and Pediatric End-Stage Liver Disease (PELD) scores within the first 24 h were related with a poor prognosis. Group 2 had a more prolonged prothrombin time, higher international normalized ratio, more prolonged activated partial thromboplastin time (aPTT), and higher levels of total and direct bilirubin, ammonia, and lactate (for all, pLiver transplantation was the only curative treatment for patients with poor prognoses and resulted in high survival rates (1-, 5-, and 10-year survival rates of 81.3%, 81.3%, and 75%, respectively) in our study.

  16. An Unusual Presentation of Liver Failure in a Patient with Primary Gastrointestinal Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Gabrielle B. Rocque

    2011-01-01

    Full Text Available Introduction. Hodgkin's lymphoma (HL presenting either with primary bowel involvement or with cholestasis is unusual. The combination of primary gastrointestinal HL presenting with cholestasis and ductopenia has not been previously described. Case Report. We present a case of primary gastrointestinal HL with evidence of liver involvement, but also with prominent ductopenia on liver biopsy and associated intrahepatic cholestasis. A 50-year-old man with a history of Crohn's disease presented with a bowel obstruction, for which he underwent a small bowel resection. Histology revealed HL. His course was complicated by cholestatic liver failure. A subsequent liver biopsy revealed both focal involvement by lymphoma and ductopenia, resembling vanishing bile duct syndrome (VBDS. He was treated with chemotherapy with improvement in his cholestasis, but he eventually succumbed due to further complications of his disease and treatment toxicities. Conclusion. This case of primary gastrointestinal HL associated with ductopenia does not meet classic criteria for VBDS, but the clinical presentation and pathology are suggestive of a VBDS-like paraneoplastic process. Therapies for HL in the setting of cholestatic liver failure require special consideration, but some reports of durable remissions and recovery of liver function have been reported.

  17. Early renal failure after domino liver transplantation using organs from donors with primary hyperoxaluria type 1.

    Science.gov (United States)

    Saner, Fuat H; Treckmann, Juergen; Pratschke, Johann; Arbogast, Helmut; Rahmel, Axel; Vester, Udo; Paul, Andreas

    2010-10-15

    Organ shortage is responsible for high mortality rates of patients awaiting liver transplantation (LT). Domino transplantation has had reported success in patients with metabolic disorders. Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder. There are a few case reports that suggest that PH1 livers originating from donors that have undergone combined liver-kidney transplantation can be successfully used for domino transplantation. In the last decade, five patients received a domino liver transplant from patients with PH1 in the EUROTRANSPLANT region. In this study, we report the clinical course and outcome of these five patients who were received a domino graft transplant. All patients, with the exception of one, suffered from multifocal hepatocellular carcinoma and underwent domino LT from patients undergoing combined liver-kidney transplantation for PH1. Within the first 4 weeks, all the domino recipients developed dialysis-dependent kidney failure despite good liver function. Four of the five patients died. The only survivor underwent retransplantation due to hepatic artery thrombosis. Twenty months after transplantation, this patient is doing well and has had no recurrence of hepatocellular carcinoma. Domino LT using donors with PH1 results in early renal failure and cannot be recommended for transplantation unless preventive strategies have been identified.

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

    Science.gov (United States)

    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.

  19. Administration of antithrombin III attenuates posthepatectomy liver failure in hepatocellular carcinoma.

    Science.gov (United States)

    Kuroda, Shintaro; Tashiro, Hirotaka; Kobayashi, Tsuyoshi; Hashimoto, Masakazu; Mikuriya, Yoshihiro; Ohdan, Hideki

    2015-01-01

    Coagulopathy can cause disseminated intravascular coagulation and posthepatectomy liver failure. Posthepatectomy liver failure predicts a poor prognosis after hepatectomy for hepatocellular carcinoma. Although antithrombin III reduces hypercoagulation, the impact of postoperative antithrombin III administration remains unknown. The aim of this study was to determine whether postoperative antithrombin III administration protects against the development of coagulation disorders. Data from 164 patients who received antithrombin III and 169 who did following curative hepatectomy for hepatocellular carcinoma were retrospectively collected and analyzed. To overcome bias due to different distributions of covariates for the two groups, a one-to-one match was created using propensity score analysis. After matching, patient outcomes were analyzed. A multivariate analysis of the whole group revealed that antithrombin III activity of failure. After one-to-one matching, the rate of posthepatectomy liver failure was significantly lower in the AT-III-treated group than in the non-AT-III-treated group (16.3% (7/43) vs. 44.2% (19/43), p failure in hepatocellular carcinoma, possibly by suppressing coagulopathy.

  20. Procalcitonin Impairs Liver Cell Viability and Function In Vitro: A Potential New Mechanism of Liver Dysfunction and Failure during Sepsis?

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    Martin Sauer

    2017-01-01

    Full Text Available Purpose. Liver dysfunction and failure are severe complications of sepsis and result in poor outcome and increased mortality. The underlying pathologic mechanisms of hepatocyte dysfunction and necrosis during sepsis are only incompletely understood. Here, we investigated whether procalcitonin, a biomarker of sepsis, modulates liver cell function and viability. Materials and Methods. Employing a previously characterized and patented biosensor system evaluating hepatocyte toxicity in vitro, human hepatocellular carcinoma cells (HepG2/C3A were exposed to 0.01–50 ng/mL procalcitonin for 2×72 h and evaluated for proliferation, necrosis, metabolic activity, cellular integrity, microalbumin synthesis, and detoxification capacity. Acetaminophen served as positive control. For further standardization, procalcitonin effects were confirmed in a cellular toxicology assay panel employing L929 fibroblasts. Data were analyzed using ANOVA/Tukey’s test. Results. Already at concentrations as low as 0.25 ng/mL, procalcitonin induced HepG2/C3A necrosis (P<0.05 and reduced metabolic activity, cellular integrity, synthesis, and detoxification capacity (all P<0.001. Comparable effects were obtained employing L929 fibroblasts. Conclusion. We provide evidence for procalcitonin to directly impair function and viability of human hepatocytes and exert general cytotoxicity in vitro. Therapeutical targeting of procalcitonin could thus display a novel approach to reduce incidence of liver dysfunction and failure during sepsis and lower morbidity and mortality of septic patients.

  1. Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

    Science.gov (United States)

    Mangus, Richard S; Bush, Weston J; Miller, Christina; Kubal, Chandrashekhar A

    2017-11-01

    Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores. Children younger than 19 years with end-stage liver, kidney, or intestine failure and with pretransplant computed tomography (CT) imaging were selected from the transplant database. Age- and sex-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences. There were 81 subjects included in the final analysis (liver [n = 35], kidney [n = 20], and intestine [n = 26]). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat, and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat, and a 46% increase in subcutaneous fat. These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients, which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney), or malabsorption (intestine).

  2. Acetaminophen Adducts Detected in Serum of Pediatric Patients With Acute Liver Failure.

    Science.gov (United States)

    Alonso, Estella M; James, Laura P; Zhang, Song; Squires, Robert H

    2015-07-01

    Previous studies in patients with acute liver failure identified acetaminophen (APAP) protein adducts in the serum of 12% and 19% of children and adults, respectively, with acute liver failure of indeterminate etiology. This article details the testing of APAP adducts in a subset (n = 393) of patients with varied diagnoses in the Pediatric Acute Liver Failure Study Group (PALFSG). Serum samples were available from 393 participants included in the PALFSG registry. Adduct measurement was performed using validated methods. Participants were grouped by diagnostic category as known APAP overdose, known other diagnosis, and indeterminate etiology. Demographic and clinical characteristics and participant outcomes were compared by adduct status (positive or negative) within each group. APAP adduct testing was positive in 86% of participants with known APAP overdose, 6% with other known diagnoses, and 11% with an indeterminate cause of liver failure. Adduct-positive participants were noted to have marked elevation of serum alanine aminotransferase and aspartate aminotransferase coupled with total serum bilirubin that was significantly lower than adduct-negative patients. In the indeterminate group, adduct-positive patients had different outcomes than adduct-negative patients (P = 0.03); spontaneous survival was 16 of 21 (76%) in adduct-positive patients versus 75 of 169 (44%) in adduct-negative patients. Prognosis did not vary by adduct status in patients with known diagnoses. Furthermore, study is needed to understand the relation of APAP exposure, as determined by the presence of APAP adducts, to the clinical phenotype and outcomes of children with acute liver failure.

  3. Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study).

    Science.gov (United States)

    Donnelly, M C; Davidson, J S; Martin, K; Baird, A; Hayes, P C; Simpson, K J

    2017-03-01

    Acute liver failure is a rare and devastating clinical condition resulting from sudden loss of hepatic parenchyma and metabolic function. The Scottish Liver Transplant Unit (SLTU) offers specialist management and emergency liver transplantation to patients with acute liver failure from across Scotland. To describe temporal changes in number of admissions, aetiology of acute liver failure, severity of disease at presentation and outcomes over a 22-year period. Retrospective analysis of the SLTU database, including all patients admitted with acute liver injury or acute liver failure between November 1992 and March 2014. There has been no change in the number of patients presenting with acute liver injury or failure secondary to paracetamol overdose, but a reduction in the number of admissions with acute liver injury or failure secondary to non paracetamol causes. Over time, disease severity at presentation has not changed in the paracetamol cohort; those with a non paracetamol aetiology have latterly presented with milder hepatic encephalopathy. Spontaneous survival rates improved significantly over time for those patients with acute liver failure due to paracetamol and non paracetamol aetiologies. The most marked improvement in survival is observed in the sickest patients meeting Kings College Hospital poor prognostic criteria. The number of admissions to the SLTU with acute liver failure is decreasing, due to reduced numbers of non paracetamol cases. Outcomes in this condition are improving, due to improvements in intensive care management and use of liver transplantation, and the increase in survival is most marked in patients meeting Kings College Hospital poor prognostic criteria. © 2017 John Wiley & Sons Ltd.

  4. 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.

  5. Sorafenib-Induced Liver Failure: A Case Report and Review of the Literature

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    Anneleen Van Hootegem

    2011-01-01

    Full Text Available In patients with hepatocellular carcinoma characterized by vascular invasion and/or extrahepatic disease, Sorafenib is considered treatment of choice. Although mild liver test abnormalities were reported in less than 1% of the patients in the two large randomized, controlled phase III trials, four cases of severe acute Sorafenib-induced hepatitis have been described. One of these four cases died from liver failure. In this paper, a patient with HCC with lung metastases developed high fever and a severe hepatitis that rapidly evolved into liver coma and death, two weeks after the initiation of Sorafenib. Biochemical parameters pointed to a hepatocellular type of injury. Clinical and biochemical presentations were compatible with a drug-induced hypersensitivity syndrome such as it has mainly been described for aromatic anticonvulsants, sulphonamides, and allopurinol. We hypothesize that an underlying cytochrome P450 dysfunction with the presence of reactive drug metabolites might lead to this potentially fatal Sorafenib-induced severe liver dysfunction.

  6. Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats.

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    Mohammed Shaqura

    Full Text Available Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

  7. The effects of modified sini decoction on liver injury and regeneration in acute liver failure induced by D-galactosamine in rats.

    Science.gov (United States)

    Luo, Jianxing; Zhang, Yang; Hu, Xiaoyu; Zhong, Sen; Chen, Guo; Wang, Yanyan; Lin, Wu; Yi, Cheng; Zhu, Hong

    2015-02-23

    Modified sini decoction (MSND) is a well-known traditional Chinese medical formula that has been used to treat cardiovascular and liver diseases for many years. We investigated the effects of MSND on acute liver failure and identified the possible mechanisms of these effects. Acute liver failure was induced by intraperitoneal injection of d-galactosamine (d-GalN) into specific pathogen-free male Wistar rats. Next, the rats were treated with Stronger Neo-Minophagen C and MSND via gavage. Biochemical parameters, histological changes in the liver, the survival of rats and the mRNA levels of toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) caspase-3 and proliferating cell nuclear antigen (PCNA) were analyzed. MSND prolonged the survival times of the acute liver failure rats. The biochemical parameters were improved, and necrosis in the liver tissues was reduced by both Stronger Neo-Minophagen C (SNMC) and MSND, but MSND induced greater effects. The mRNA expressions of HMGB1, TLR4, NF-κB, and Caspase-3 were remarkably decreased, and the expression of PCNA was remarkably increased by SNMC and MSND, and the effects of MSND were greater. MSND protected the liver and increased the survival rate of acute liver failure rats. These effects were likely mediated by the inhibitions of the inflammatory reaction and apoptosis and the promotion of liver tissue regeneration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Chronic kidney disease after liver transplantation for acute liver failure is not associated with perioperative renal dysfunction.

    Science.gov (United States)

    Leithead, J A; Ferguson, J W; Bates, C M; Davidson, J S; Simpson, K J; Hayes, P C

    2011-09-01

    Renal dysfunction of acute liver failure (ALF) may have distinct pathophysiological mechanisms to hepatorenal syndrome of cirrhosis. Yet, the impact of perioperative renal function on posttransplant renal outcomes in ALF patients specifically has not been established. The aims of this study were (1) to describe the incidence and risk factors for chronic renal dysfunction following liver transplantation for ALF and (2) to compare renal outcomes with age-sex-matched patients transplanted for chronic liver disease. This was a single-center study of 101 patients transplanted for ALF. Fifty-three-and-a-half percent had pretransplant acute kidney injury and 64.9% required perioperative renal replacement therapy. After transplantation the 5-year cumulative incidence of chronic kidney disease (eGFR kidney injury (p = 0.288) or renal replacement therapy (p = 0.134) and chronic kidney disease. Instead, the independent predictors of chronic kidney disease were older age (p = 0.019), female gender (p = 0.049), hypertension (p = 0.031), cyclosporine (p = 0.027) and nonacetaminophen-induced ALF (p = 0.039). Despite marked differences in the perioperative clinical condition and survival of patients transplanted for ALF and chronic liver disease, renal outcomes were the same. In conclusion, in patients transplanted for ALF the severity of perioperative renal injury does not predict posttransplant chronic renal dysfunction. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. Expression level of augmenter of liver regeneration in patients with hepatic failure and hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Hai-Ying; Xiang, Dai-Rong; Huang, Hai-Jun; Li, Jun; Sheng, Ji-Fang

    2010-10-01

    Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance. We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues. Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5+/-369.6 pmol/ml) than in 12 deteriorating patients (462.3+/-235.8 pmol/ml). Similar levels were found in 20 HCC patients (917.9+/-332.7 pmol/ml), 24 chronic hepatitis B patients (969.2+/-332.5 pmol/ml) and 10 healthy persons (806.9+/-240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74X10(6)) copies/μl] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82X10(3)) copies/μl] or in healthy liver tissues [10E4.31 (2.04X10(4)) copies/μl]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.

  10. Anakinra-Induced Acute Liver Failure in an Adolescent Patient with Still's Disease.

    Science.gov (United States)

    Taylor, Sarah A; Vittorio, Jennifer M; Martinez, Mercedes; Fester, Keith A; Lagana, Stephen M; Lobritto, Steven J; Ovchinsky, Nadia

    2016-01-01

    The interleukin-1 (IL-1) family consists of 11 cytokines that play key regulatory roles in many immune and inflammatory processes. Anakinra (Kineret, Amgen, Inc.) is an IL-1 receptor antagonist (IL-1ra). Increased levels of IL-1 are found in several disease states suggesting that anakinra may be beneficial in disorders associated with elevated IL-1 levels. Anakinra has been effectively used in the treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease (AOSD). Despite its therapeutic benefits, anakinra also has potential side effects, including hepatotoxicity. We present a case of AOSD in an adolescent male that was treated with anakinra. During treatment, the patient developed acute liver failure that resolved upon withdrawal of anakinra. Although anakinra-induced liver injury has been reported in adults, including one case of subacute liver failure, we believe our case is the first to show severe acute liver failure in an adolescent treated with anakinra. This case provides significant insight into a potentially serious complication associated with anakinra. It is important to further delineate these complications as the treatment indications for this drug expand. © 2016 Pharmacotherapy Publications, Inc.

  11. [Acute liver failure due to human herpesvirus 6 in an infant].

    Science.gov (United States)

    Tronconi, G M; Mariani, B; Pajno, R; Fomasi, M; Cococcioni, L; Biffi, V; Bove, M; Corsin, P; Garbetta, G; Barera, G

    2012-01-01

    We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  12. Fulminant Hepatic Failure Caused by Diffuse Liver Metastases following Gastrointestinal Stromal Tumor Resection

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    Abdel-Rauf Zeina

    2009-01-01

    Full Text Available Metastatic tumors to the liver resulting in fulminant hepatic failure are a rare occurrence and have not been previously described in patients with gastrointestinal stromal tumor (GIST. A 70 year-old man was referred to hospital with postprandial discomfort. On examination a 19.5 cm large epithelioid GIST of the stomach was diagnosed. The mass exhibited unfavorable prognostic features: mitotic index 18/50 high-power fields, large primary tumor size and male sex. Complete tumor resection with negative margins was achieved and metastases were not detected. The patient presented six months later with jaundice, asterixis and elevated liver enzymes. Computerized tomography showed multiple liver hypodense lesions representing metastases. Treatment with imatinib mesylate was of no avail and the patient died 3 days later as the result of hepatic failure. Massive liver metastases can, even though rarely, be responsible for fulminant hepatic failure. Clinical and radiological follow-up are crucial in patients with GIST even after surgical resection.

  13. The multicenter Belgian survey on liver transplantation for hepatocellular failure after bariatric surgery.

    Science.gov (United States)

    Geerts, A; Darius, T; Chapelle, T; Roeyen, G; Francque, S; Libbrecht, L; Nevens, F; Pirenne, J; Troisi, R

    2010-12-01

    The prevalence of obesity has grown dramatically over the last decades, with nonalcoholic steatohepatitis increasingly observed. Therapeutic options for morbid obesity include bariatric surgery. Fatal liver failure (LF) has been recorded after jejunoileal bypass (JIB) but is controversial after biliopancreatic diversion (BPD, Scopinaro operation). We performed a survey on the frequency of liver transplantation (LT) after bariatric surgery in Belgium. An enquiry was sent to all Belgian liver transplant centers to investigate the occurrence of subacute and chronic LF after bariatric surgery. After weight-reduction surgery, 10 patients in 3 Belgian transplant centers were listed for LT due to severe hepatocellular failure. Nine of them had undergone a Scopinaro operation and 1 a jejunoileal bypass. The median time to develop LF was 5 years. The patient with JIB developed chronic LF after 25 years. Seven patients were transplanted; two died awaiting a graft and one is still on the waiting list. After LT, 1 patient developed rapid reappearance of LF at 10 months, requiring retransplantation. Two recipients died after LT because of multiorgan failure shortly after transplantation. In another case, a de novo cancer was fatal at 6 years' follow-up. The remaining recipients were doing well. According to this survey, the BPD operation carries a potential risk of LF. However, because there were only 10 cases, we remain unaware of the actual incidence of Scopinaro operation-induced LF. We advise strict follow-up of liver function and timely dismantling of BPD. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. 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 pediatric acute liver failure prognostication schema are needed.

  15. Acute liver failure due to Human Herpesvirus 6 in an infant

    Directory of Open Access Journals (Sweden)

    G.M. Tronconi

    2012-10-01

    Full Text Available We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus, drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6 genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases’ review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus’s genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

  16. Patients with the worst outcomes after paracetamol (acetaminophen)-induced liver failure have an early monocytopenia.

    Science.gov (United States)

    Moore, J K; MacKinnon, A C; Man, T Y; Manning, J R; Forbes, S J; Simpson, K J

    2017-02-01

    Acute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome. To investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome. In a prospective case-control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non-paracetamol causes of ALF and 16 controls were recruited. The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome. On admission, patients with worst outcomes after POD-ALF had a significant monocytopenia, characterised by reduced classical and expanded intermediate monocyte population. This was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a 'cytokine storm' and increased concentrations of cytokines associated with monocyte egress from the bone marrow. Gene expression array did not differentiate patient outcome. At day 4, there was no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes. Severe paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes. This is not seen in patients with non-paracetamol-induced liver failure. Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention. © 2016 John Wiley & Sons Ltd.

  17. Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1.

    Science.gov (United States)

    Yang, Nai-Bin; Ni, Shun-Lan; Li, Shan-Shan; Zhang, Sai-Nan; Hu, Dan-Ping; Lu, Ming-Qin

    2015-01-01

    High mobility group box 1 (HMGB1) has been widely reported to mediate damage caused by inflammatory responses. The aim of our study is to investigate the role of HMGB1 in endotoxin tolerance (ET) alleviating inflammation of acute liver failure (ALF) rats and its possible signaling mechanism. To mimic ET, male Sprague-Dawley rats were pretreated with low dose of lipopolysaccharide (LPS) (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent ALF induction. ALF was induced by intraperitoneal administration of D-GalN/LPS. ET induced by LPS pretreatment significantly improved the survival rate of ALF rats. Moreover, after ALF induction, ET+ALF rats exhibited lower serum enzyme (ALT, AST and TBiL) levels, lower production of inflammatory cytokines (IL-6, TNF-a and HMGB1) and more minor liver histopathological damage than ALF rats. ET+ALF rats showed enhanced expression levels of HMGB1, decreased levels of STAT1 and p-STAT1, augmented expression of SOCS1 in liver tissues than ALF rats. These results indicated that ET induced by low-dose LPS pretreatment may alleviate inflammation and liver injury in experimental acute liver failure rats mainly through inhibition of hepatic HMGB1 translocation and release.

  18. Prediction of posthepatectomy liver failure using transient elastography in patients with hepatitis B related hepatocellular carcinoma.

    Science.gov (United States)

    Lei, Jie-Wen; Ji, Xiao-Yu; Hong, Jun-Feng; Li, Wan-Bin; Chen, Yan; Pan, Yan; Guo, Jia

    2017-12-29

    It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13-1.29; P hepatocellular carcinoma.

  19. Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts.

    Science.gov (United States)

    Staufner, Christian; Haack, Tobias B; Köpke, Marlies G; Straub, Beate K; Kölker, Stefan; Thiel, Christian; Freisinger, Peter; Baric, Ivo; McKiernan, Patrick J; Dikow, Nicola; Harting, Inga; Beisse, Flemming; Burgard, Peter; Kotzaeridou, Urania; Lenz, Dominic; Kühr, Joachim; Himbert, Urban; Taylor, Robert W; Distelmaier, Felix; Vockley, Jerry; Ghaloul-Gonzalez, Lina; Ozolek, John A; Zschocke, Johannes; Kuster, Alice; Dick, Anke; Das, Anib M; Wieland, Thomas; Terrile, Caterina; Strom, Tim M; Meitinger, Thomas; Prokisch, Holger; Hoffmann, Georg F

    2016-01-01

    Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency and in about 50% the etiology remains unknown. Recently biallelic mutations in NBAS were identified as a new molecular cause of ALF with onset in infancy, leading to recurrent acute liver failure (RALF). The phenotype and medical history of 14 individuals with NBAS deficiency was studied in detail and functional studies were performed on patients' fibroblasts. The phenotypic spectrum of NBAS deficiency ranges from isolated RALF to a multisystemic disease with short stature, skeletal dysplasia, immunological abnormalities, optic atrophy, and normal motor and cognitive development resembling SOPH syndrome. Liver crises are triggered by febrile infections; they become less frequent with age but are not restricted to childhood. Complete recovery is typical, but ALF crises can be fatal. Antipyretic therapy and induction of anabolism including glucose and parenteral lipids effectively ameliorates the course of liver crises. Patients' fibroblasts showed an increased sensitivity to high temperature at protein and functional level and a disturbed tethering of vesicles, pointing at a defect of intracellular transport between the endoplasmic reticulum and Golgi. Mutations in NBAS cause a complex disease with a wide clinical spectrum ranging from isolated RALF to a multisystemic phenotype. Thermal susceptibility of the syntaxin 18 complex is the basis of fever dependency of ALF episodes. NBAS deficiency is the first disease related to a primary defect of retrograde transport. Identification of NBAS deficiency allows optimized therapy of liver crises and even prevention of further episodes.

  20. Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure.

    Science.gov (United States)

    Narkewicz, Michael R; Horslen, Simon; Belle, Steven H; Rudnick, David A; Ng, Vicky L; Rosenthal, Philip; Romero, Rene; Loomes, Kathleen M; Zhang, Song; Hardison, Regina M; Squires, Robert H

    2017-02-01

    The purpose of the present study is to estimate autoantibody (auto-AB) frequency, clinical characteristics, and 21-day outcome of participants in the Pediatric Acute Liver Failure Study Group (PALFSG) by antinuclear antibody, smooth muscle antibody, and liver-kidney microsomal (LKM) antibody status. Auto-ABs were determined at local and/or central laboratories. Subjects were assigned to autoimmune hepatitis (AIH), indeterminate, and other diagnoses groups. Between 1999 and 2010, 986 subjects were enrolled in the PALFSG. At least 1 auto-AB result was available for 722 (73.2%). At least 1 auto-AB was positive for 202 (28.0%). Diagnoses for auto-AB+ subjects were AIH (63), indeterminate (75), and other (64). Auto-ABs were more common in Wilson disease (12/32, 37.5%) compared with other known diagnoses (52/253, 20.6%, P = 0.03). LKM+ subjects were younger (median 2.4 vs 9.1 years, P liver transplantation (53.3% vs 31.4% P = 0.02) than other auto-AB+/LKM- subjects. Steroid treatment of subjects who were auto-AB+ was not significantly associated with survival and the subgroup with known diagnoses other than AIH had a higher risk of death. Auto-ABs are common in children with acute liver failure, occurring in 28%. Auto-AB+ subjects have similar outcomes to auto-AB negative subjects. LKM+ children are younger and more likely to undergo liver transplantation compared with other auto-AB+ subjects. Although auto-AB may indicate a treatable condition, positivity does not eliminate the need for a complete diagnostic evaluation because auto-ABs are present in other conditions. The significance of auto-AB in pediatric acute liver failure remains uncertain, but LKM+ appears to identify a unique population of children who merit further study.

  1. Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

    Science.gov (United States)

    Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

    2014-09-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. © 2014 Wiley Periodicals, Inc.

  2. Prognosis for children with acute liver failure due to Amanita phalloides poisoning

    Science.gov (United States)

    Wachulski, Marcin F.; Kamińska-Gocał, Diana; Dądalski, Maciej; Socha, Piotr; Mulawka, Jan J.

    2011-10-01

    The primary objective of this article is to find new effective methods of diagnosis of urgent liver transplantation after Amanita phalloides intoxication amongst pediatric patients. The research was carried out using a medical database of pediatric patients who suffered from acute liver failure after amatoxin consumption. After data preprocessing and attribute selection steps, a two-phase experiment was conducted, which incorporated a wide variety of data mining algorithms. The results deliver two equivalent classification models with simple decision structure and reasonable quality of surgery prediction.

  3. Results of liver transplantation in patients with acute liver failure due to Amanita phalloides and paracetamol (acetaminophen) intoxication.

    Science.gov (United States)

    Krasnodębski, Maciej; Grąt, Michał; Hołówko, Wacław; Masior, Łukasz; Wronka, Karolina M; Grąt, Karolina; Stypułkowski, Jan; Patkowski, Waldemar; Krawczyk, Marek

    2016-01-01

    Amanita phalloides and paracetamol intoxications are responsible for the majority of acute liver failures. To assess survival outcomes and to analyse risk factors affecting survival in the studied group. Of 1369 liver transplantations performed in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw before December 2013, 20 (1.46%) patients with Amanita phalloides (n = 13, 0.95%) and paracetamol (n = 7, 0.51%) intoxication were selected for this retrospective study. Overall and graft survival at 5 years were set as primary outcome measures. Five-year overall survival after liver transplantation in the studied group was 53.57% and 53.85% in patients with paracetamol and Amanita phalloides poisoning, respectively (p = 0.816). Five-year graft survival was 26.79% for patients with paracetamol and 38.46% with Amanita phalloides intoxication (p = 0.737). Risk factors affecting patient survival were: pre-transplant bilirubin concentration (p = 0.023) and higher number of red blood cells (p = 0.013) and fresh frozen plasma (p = 0.004) transfused intraoperatively. Likewise, higher number of red blood cells (p = 0.012) and fresh frozen plasma (p = 0.007) transfused were risk factors affecting 5-year graft survival. Surprisingly, donor and recipient blood type incompatibility was neither the risk factor for 5-year overall survival (p = 0.939) nor the risk factor for 5-year graft survival (p = 0.189). In selected intoxicated patients urgent liver transplantation is the only successful modality of treatment. Risk factors affecting survival are in correspondence with the patient's pre-transplant status (bilirubin level in serum) and intraoperative status (number of red blood cells and fresh frozen plasma transfused).

  4. 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),...

  5. Liver Inflammation Relates to Decreased Canalicular Bile Transporter Expression in Pediatric Onset Intestinal Failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2017-02-23

    Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.

  6. Clinical Features and Outcomes of Complementary and Alternative Medicine Induced Acute Liver Failure and Injury.

    Science.gov (United States)

    Hillman, Luke; Gottfried, Michelle; Whitsett, Maureen; Rakela, Jorge; Schilsky, Michael; Lee, William M; Ganger, Daniel

    2016-07-01

    The increasing use of complementary and alternative medicines (CAMs) has been associated with a rising incidence of CAM-induced drug-induced liver injury (DILI). The aim of this study was to examine the clinical features and outcomes among patients with acute liver failure (ALF) and acute liver injury (ALI) enrolled in the Acute Liver Failure Study Group database, comparing CAM-induced with prescription medicine (PM)-induced DILI. A total of 2,626 hospitalized patients with ALF/ALI of any etiology were prospectively enrolled between 1998 and 2015 from 32 academic transplant centers. Only those with CAM or PM-induced ALI/ALF were selected for analysis. A total of 253 (9.6%) subjects were found to have idiosyncratic DILI, of which 41 (16.3%) were from CAM and 210 (83.7%) were due to PM. The fraction of DILI-ALF/ALI cases due to CAM increased from 1998-2007 to 2007-2015 (12.4 vs. 21.1%, P=0.047). There was no difference in the type of liver injury-hepatocellular, cholestatic, or mixed-between groups as determined by R score (P=0.26). PM-induced DILI showed higher serum alkaline phosphatase levels compared with the CAM group (median IU/L, 171 vs. 125, P=0.003). The CAM population had fewer comorbid conditions (1.0 vs. 2.0, Pliver injury and emphasizes the importance of early referral and evaluation for liver transplantation when CAM-induced liver injury is suspected.

  7. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study

    Science.gov (United States)

    2012-01-01

    Introduction Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Catot/Caion) ratio ≥2.5, and to describe the feasibility of citrate CVVHD in liver failure patients. Methods We conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run. Results Accumulation of citrate in serum correlated with an increase in the Catot/Caion ratio. Although the critical upper threshold of Catot/Caion ratio ≥2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Catot/Caion ratio ≥2.5. In contrast, serum lactate ≥3.4 mmol/l and prothrombin time ≤26% predicted an increase in the Catot/Caion ratio ≥2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time). Conclusions Despite substantial accumulation of citrate in serum, CVVHD with regional citrate

  8. Role and regulation of autophagy and apoptosis by nitric oxide in hepatic stellate cells during acute liver failure.

    Science.gov (United States)

    Jin, Li; Gao, Heng; Wang, JiuPing; Yang, ShuJuan; Wang, Jing; Liu, JingFeng; Yang, Yuan; Yan, TaoTao; Chen, Tianyan; Zhao, Yingren; He, Yingli

    2017-11-01

    We previously found that hepatic stellate cell activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure. Nitric oxide has shown to induce hepatic stellate cell apoptosis. Whether and how nitric oxide is involved in acute liver failure and autophagy remains unclear. Acute liver failure patients were recruited to investigate the correlation between plasma nitric oxide levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from acute liver failure patients who had undergone liver transplantation. The expression of nitric oxide synthases and hepatic stellate cell activation (alpha-SMA), and autophagic activity (LC3) were investigated by immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot analysis, confocal microscopy, and flow cytometry in hepatic stellate cells treated with nitric oxide donors. Plasma nitric oxide level was significantly increased in patients with acute liver failure compared to those with cirrhosis (53.60±19.74 μM vs 19.40±9.03 μM, Z=-7.384, Pfailure. At least some Nitric oxide was produced by overexpression of inducible nitric oxide synthases and endothelial nitric oxide synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo observation revealed that autophagy was inhibited in hepatic stellate cells based on decreased LC3 immunostaining, and in vitro experiments demonstrated that Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic stellate cell apoptosis, which was rescued by an autophagy inducer. Increased nitric oxide synthases/ nitric oxide promotes apoptosis through autophagy inhibition in hepatic stellate cells during acute liver failure, providing a novel strategy for the treatment of patients with acute liver failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Hepatitis A acute liver failure: follow-up of paediatric patients in southern Brazil.

    Science.gov (United States)

    Ferreira, C T; Vieira, S M G; Kieling, C O; Silveira, T R

    2008-10-01

    We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 +/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area.

  10. Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

    Science.gov (United States)

    Korpela, Katri; Mutanen, Annika; Salonen, Anne; Savilahti, Erkki; de Vos, Willem M; Pakarinen, Mikko P

    2017-02-01

    Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

  11. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.

    Science.gov (United States)

    Xiao, Yong-Tao; Cao, Yi; Zhou, Ke-Jun; Lu, Li-Na; Cai, Wei

    2016-12-15

    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.

  12. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  13. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure.

    Science.gov (United States)

    Lu, Brandy R; Zhang, Song; Narkewicz, Michael R; Belle, Steven H; Squires, Robert H; Sokol, Ronald J

    2013-05-01

    To examine the predictive value of the Liver Injury Units (LIU) and admission values (aLIU) of bilirubin and prothrombin time and international normalized ratio scores in a large cohort from the Pediatric Acute Liver Failure (PALF) Study Group, a multinational prospective study. LIU and aLIU scores were calculated for 461 and 579 individuals, respectively, enrolled in the PALF study from 1999 to 2008. Receiver operator characteristic curves were used to evaluate the scores with respect to survival without liver transplantation (LT), death, or LT by 21 days after enrollment. At 21 days, 50.3% of participants were alive without LT, 36.2% underwent LT, and 13.4% died. The c-indices for transplant-free survival were 0.81 based on the LIU score with the international normalized ratio (95% CI, 0.78-0.85) and 0.76 based on the aLIU score (95% CI, 0.72-0.79). The LIU score predicted LT better than it predicted death (c-index for LT 0.84, c-index for death 0.76). Based on data from a large, multicenter cohort of patients with PALF, the LIU score was a better predictor of transplant-free survival than was the aLIU score. The LIU score might be a helpful, dynamic tool to predict clinical outcomes in patients with PALF. Copyright © 2013 Mosby, Inc. All rights reserved.

  14. The impact of posthepatectomy liver failure on the recurrence of hepatocellular carcinoma.

    Science.gov (United States)

    Iguchi, Kohta; Hatano, Etsuro; Yamanaka, Kenya; Tanaka, Shiro; Taura, Kojiro; Uemoto, Shinji

    2014-01-01

    Patients with hepatocellular carcinoma (HCC) who underwent hepatectomy often developed an intrahepatic recurrence, even though it was a curative one. The relationship between surgery-induced liver damage and the recurrence of HCC has not been described. This study evaluated whether posthepatectomy liver failure, as defined by the International Study Group of Liver Surgery, affected the recurrence of HCC. We performed a retrospective cohort study of 488 patients with HCC who underwent hepatectomy between 2004 and 2012 at Kyoto University Hospital. Early posthepatectomy liver failure (EPLF) was defined as liver failure occurring between postoperative days 5 and 10. The patients were divided into an EPLF group and a non-EPLF group. Disease-free survival (DFS) was compared between these groups. The influences of host-related, surgery-related, and tumor-related factors on patient outcomes were evaluated using multivariate analyses. The EPLF group and the non-EPLF group contained 153 and 335 patients, respectively. The probability of DFS was significantly increased in the non-EPLF group (median: 574 days) compared to the EPLF group (median: 348 days) (hazard ratio, HR [95 % confidence interval, CI] 1.61 [1.29-2.00]). The multivariate analysis revealed that EPLF was an independent factor for DFS (HR [95 % CI] 1.43 [1.13-1.81]), besides the factors previously described, including fibrosis (1.32 [1.05-1.67]), stage (1.85 [1.34-2.51]), tumor differentiation (1.46 [1.11-1.89]), and des-γ-carboxyprothrombin (1.39 [1.10-1.74]). EPLF was associated with postoperative HCC recurrence. The prevention of EPLF might improve the prognosis of patients with HCC.

  15. Acute liver failure with amiodarone infusion: A case report and systematic review.

    Science.gov (United States)

    Jaiswal, P; Attar, B M; Yap, J E; Devani, K; Jaiswal, R; Wang, Y; Szynkarek, R; Patel, D; Demetria, M

    2018-02-01

    Amiodarone, a commonly used class III antiarrhythmic agent notable for a relatively long half-life of up to 6 months and its pronounced adverse effect profile, is used for both acute and chronic management of cardiac arrhythmias. Chronic use of amiodarone has been associated with asymptomatic hepatotoxicity; however, acute toxicity is thought to be uncommon. There are only six reported cases of acute liver failure (ALF) secondary to amiodarone. In all these cases the outcome of death during the same hospitalization resulted. We aimed to report the only case of acute liver failure secondary to amiodarone infusion in the existing literature where the patient survived. A 79-year-old woman admitted with atrial flutter was being treated with intravenous (IV) amiodarone when she abruptly developed coagulopathy, altered mental status and liver enzyme derangement. She was diagnosed with acute liver failure (ALF) secondary to an amiodarone adverse drug reaction, with a calculated score of seven on the Naranjo adverse drug reaction probability scale. Amiodarone was immediately withheld, and N-acetylcysteine (NAC) was initiated. Clinical improvement was seen within 48 hours of holding the drug and within 24 hours of initiating NAC. On post-hospital follow-up visit she was reported to have complete recovery. This report emphasizes the importance of monitoring liver enzymes and mental status while a patient is being administered IV amiodarone. N-acetylcysteine administration may have possibly contributed to the early and successful recovery from ALF in our patient. To date, she is the only patient in the existing literature who has been reported to survive ALF secondary to amiodarone administration. © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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 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 Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p 0.05). Spectral electroencephalogram classification correlated with outcome (p Spectral electroencephalogram analysis can be used to evaluate even young patients for hepatic encephalopathy and correlates with outcome. Spectral electroencephalogram may allow improved quantitative and reproducible assessment of hepatic encephalopathy grade in children with acute

  17. Acute liver failure in a pediatric patient with congenital dyserythropoietic anemia type I treated with deferasirox

    Directory of Open Access Journals (Sweden)

    Galina Ling

    2015-09-01

    Full Text Available Congenital dyserythropoietic anemias (CDA represent a heterogeneous group of disorders characterized by morphological abnormalities of erythroid precursor cells and various degrees of hemolysis. Iron overload is a result of continuous hemolysis and recurrent transfusions. It is treated with iron chelators, including deferasirox. We present here a case of acute liver failure in a 12 years old girl with CDA type I treated with deferasirox and discuss the approach to treatment.

  18. 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...... concentration, as well as to some of the adenosine triphosphate degradation products. However, clinical observations of cerebral exchange rates of oxygen, glucose, lactate and amino acids challenge the interpretation of these findings. In this review the conflicting data of cerebral metabolism during acute...

  19. Acute lymphocytic cholangitis and liver failure in an Amur tiger (Panthera tigris altaica).

    Science.gov (United States)

    Crook, Erika K; Carpenter, Nancy A

    2014-03-01

    An adult male Amur tiger (Panthera tigris altaica) with confirmed inflammatory bowel disease developed acute severe icterus, bilirubinuria, bilirubinemia, and elevated bile acids after a diet change. Liver biopsies showed moderate lymphoplasmacytic cholangiohepatitis (lymphocytic cholangitis). The tiger developed neurologic signs including ataxia, tremors, and seizures, as well as epistaxis. Therapy consisted of antibiotics, a steroid anti-inflammatory, vitamins, pro-coagulants, and liver-supportive medicines. The tiger improved from acute liver failure within 3 wk, while the epistaxis began at 3.5 wk and did not resolve until 10.5 wk. The long-term maintenance plan consists of oral prednisolone, metronidazole, ursodiol, and an all muscle-meat beef diet.

  20. Dirofilaria repens in a cat with acute liver failure : case report

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    E.V. Schwan

    2000-07-01

    Full Text Available Acute liver failure was diagnosed in a 12-year-old cat. Fine needle aspirate cytology revealed high numbers of unsheathed microfilariae and a hepatocellular reaction with no evidence of bacterial infection. The microfilariae were identified as those of Dirofilaria repens by acid phosphatase staining. The high number of microfilariae seen in both the blood and the liver aspirate samples as well as the favourable response to ivermectin amongst other drugs administered, is suggestive that D. repens was the cause of the liver insult. A positive result obtained with an antigen-capture ELISA (Dirochek (r for Dirofilaria immitis antigen was interpreted as false. This is the 1st report of Dirofilaria repens for South Africa.

  1. A Patient with Nafcillin-Associated Drug-Induced Liver Failure

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    Qin Rao

    2017-09-01

    Full Text Available Nafcillin-induced acute liver injury is a rare and potentially fatal complication that has been known since the 1960s but inadequately studied. At this time, the only proven treatment is early discontinuation of the drug. Because of the high prevalence of nafcillin class antibiotic use in the United States, it is important for clinicians to have a high clinical suspicion for this diagnosis. We present a case of liver failure attributable to nafcillin use in a 68-year-old male with a history methicillin-sensitive Staphylococcus and L3/L4 osteomyelitis. After starting long-term antibiotic therapy, he presented with painless jaundice which necessitated discontinuation of the drug. At the time of presentation, the patient’s lab work exhibited a bilirubin/direct bilirubin of 9.4/8.2 mg/dL, alkaline phosphatase of 311 IU/L, and aspartate transaminase/alanine transaminase of 109/127 IU/L. The patient was switched to i.v. vancomycin given the concern for drug-induced liver injury. Imaging did not show obstruction of the hepatobiliary or pancreaticobiliary trees. Serology was unremarkable for viral etiology, autoimmune processes, Wilson disease, and hemochromatosis. A liver biopsy showed findings consistent with drug-induced liver injury. The patient’s liver function tests peaked at day 7 of admission and trended towards normal levels with cessation of nafcillin therapy. The patient was discharged with a diagnosis of nafcillin-induced acute liver injury. Our case highlights the importance of early recognition of the diagnosis and careful monitoring of liver function when nafcillin is employed in the clinical setting.

  2. Posthepatectomy Liver Failure Affects Long-Term Function After Resection for Hepatocellular Carcinoma.

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    Nakamura, Naohiko; Hatano, Etsuro; Iguchi, Kohta; Seo, Satoru; Taura, Kojiro; Uemoto, Shinji

    2016-04-01

    This study examined whether the severity of posthepatectomy liver failure (PLF) affected the long-term postoperative liver recovery of patients with hepatocellular carcinoma (HCC). We performed a retrospective cohort study of 395 HCC patients who underwent hepatectomy from 2004 to 2012 at the Kyoto University Hospital. The severity of PLF between postoperative days 5 and 10 was categorized according to the International Study Group of Liver Surgery criteria. We compared the Child-Pugh (C-P) score, platelet count (PLT), and the ratio of future remnant liver volume (FRLV) to the total liver volume (%RLV) at 3, 6, and 12 months after hepatectomy in the non-PLF, grade A, and grade B groups. The non-PLF, grade A, and grade B groups contained 272, 63, and 56 patients, respectively. The C-P score in the grade A group recovered from 5.37 points before hepatectomy to 5.38 points at 12 months after hepatectomy. The C-P score in the grade B group increased from 5.51 to 6.81 points at 3 months and was significantly higher (6.00 points) at 12 months than in the non-PLF group (5.47 points). The PLT significantly decreased at 12 months in the grade B group compared with the non-PLF group. The %RLV at 12 months in the non-PLF, grade A, and grade B groups were 84, 83, and 78 %, respectively. The remnant liver hypertrophy in the grade B group was significantly slower than that in the non-PLF group. PLF severity affects long-term liver function recovery and remnant liver hypertrophy after hepatectomy.

  3. Intestinal failure-associated liver disease and the use of fish oil-based lipid emulsions.

    Science.gov (United States)

    Goulet, Olivier J

    2015-01-01

    Intestinal failure (IF) is caused by the critical reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements for maintenance in adults and growth in children. The advent of parenteral nutrition (PN) resulted in a dramatic improvement in life expectancy of patients suffering IF, but it has its own complications, such as catheter related sepsis. In pediatric patients suffering IF, intraluminal intestinal bacterial overgrowth may cause bacterial translocation and subsequent cholestasis and liver fibrosis. With our current understanding of the genesis of intestinal failure associated liver disease (IFALD), it should be prevented or at least early recognized and treated especially in patients experiencing prematurity and/or sepsis. Targeting harmful cytokine responses can be expected to reduce the severity and frequency of IFALD. In that view, prevention of sepsis, appropriate management of enteral feeding, prevention and treatment of intestinal bacterial overgrowth and the effects of fish oil, as providing omega-3 fatty with anti-inflammatory effects, are promising in avoiding or reversing cholestasis. This chapter aims to review both IF and PN related factors of liver disease with special emphasize on inflammation as cause of liver injury and on the use of fish oil based lipid emulsions as a provision of both alpha-tocopherol (200 g/l of 20% emulsion), as anti-oxidant agent and long-chain PUFAs. © 2015 S. Karger AG, Basel.

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

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    Chung PC

    2016-12-01

    Full Text Available Peter Chi-Ho Chung,1,2 Hsiu-Pin Chen,1,2 Jr-Rung Lin,3,4 Fu-Chao Liu,1,2 Huang-Ping Yu1,2 1Department of Anesthesiology, Chang Gung Memorial Hospital, 2College of Medicine, 3Clinical Informatics and Medical Statistics Research Center, 4Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan 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. Keywords: chronic renal failure, cohort study, survival rate, liver transplantation, population-based study

  5. Serum antithrombin III level is well correlated with multiple indicators for assessment of liver function and diagnostic accuracy for predicting postoperative liver failure in hepatocellular carcinoma patients.

    Science.gov (United States)

    Mizuguchi, Toru; Kawamoto, Masaki; Meguro, Makoto; Son, Seiichi; Nakamura, Yukio; Harada, Kohei; Shibata, Toshihito; Ota, Shigenori; Hirata, Koichi

    2012-01-01

    Evaluation of preoperative hepatic reserve is critical to avoid a fatal clinical course such as liver failure. We retrospectively evaluated 158 consecutive hepatocellular carcinoma (HCC) patients who underwent initial hepatectomy. The aim of this study was to determine the correlations of multiple indicators for assessment of liver function before hepatectomy. Furthermore, diagnostic probability for the pathological background and prediction of postoperative liver failure/dysfunction was compared between the antithrombin (AT) III level and indocyanine green retention rate at 15 minutes (ICGR15). Between January 2001 and March 2008, 158 HCC patients who underwent initial hepatectomy were enrolled in this study. Spearman's correlation coefficients (r values) were obtained for 15 clinical laboratory tests including ATIII and ICGR15. Receiver operating characteristic (ROC) curve analysis was used for calculating the probability and predictive ability of the tests. All 158 consecutive HCC patients were eligible for hepatectomy based on the Japanese guideline. ATIII is correlated with 13 of 14 other clinical tests, including albumin, bilirubin, prothrombin time, rapid turnover proteins, HGF, ICGR15 and others. The diagnostic probabilities to distinguish between normal liver and other pathological backgrounds of ATIII and ICGR15 were significantly different. The specificity of ATIII to predict postoperative liver failure/dysfunction was higher than that of ICGR15. The serum ATIII level before hepatectomy is valuable to estimate the pathological background and predict postoperative liver failure/ dysfunction. It should be possible to use ATIII as an additional indicator for liver function and substitute for ICGR15 in the future.

  6. Posterior reversible encephalopathy syndrome in a survivor of valproate-induced acute liver failure: a case report.

    Science.gov (United States)

    Mettananda, Sachith; Fernando, Asvini D; Ginige, Nimasari

    2013-05-31

    Posterior reversible encephalopathy syndrome is an extremely rare radiological diagnosis that has not been reported previously in association with acute liver failure. A 6-year-old Sri Lankan girl developed acute liver failure with severe hepatic encephalopathy due to sodium valproate. She was successfully treated medically with N-acetylcysteine and L-carnitine. During recovery she again developed features of encephalopathy and had repeated convulsions associated with moderate hypertension. The diagnosis of posterior reversible encephalopathy syndrome was made on clinical and radiological grounds and she showed a gradual improvement with control of blood pressure. This report adds to the evidence behind treatment of valproate-induced acute liver failure with N-acetylcysteine and L-carnitine and illustrates a rare but interesting association between acute liver failure and posterior reversible encephalopathy syndrome.

  7. Rodent animal models for surrogate analysis of cell therapy in acute liver failure

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    Bruno eChrist

    2012-04-01

    Full Text Available Without therapeutic intervention acute liver failure is the consequence of a progredient destruction of the liver parenchyma due to metabolic exhaustion of the hepatocytes. Perivenous hepatocytes are responsible for the detoxification of noxes via the cytochrome P450 enzyme system. Liver transplantation is the only remaining therapeutic option in the end-stage of the disease. Assuming that metabolic capacity could be provided by healthy hepatocytes and thus substitute for the genuine parenchymal cells hepatocyte transplantation since quite some time is considered to be an alternative to whole liver transplantaton. While this hypothesis achieved proof-of-concept in animal trials clinical breakthrough is still awaiting success, the reasons of which are ongoing matter of debate. In recent times mesenchymal stem cells came into focus as a transplantable cell source to treat ALF. Interestingly, as demonstrated in various rodent animal models their mode of action is rather based on trophic support of hepatocytes remaining in the damaged host parenchyma rather than substitution of tissue loss. Mechanistically, either direct or indirect paracrine effects from the transplanted cells acting pro-proliferative, anti-apoptotic and anti-inflammatory seem to trigger the regenerative response of the residual healthy hepatocytes in the otherwise lethally injured liver parenchyma. Thus, allogeneic mesenchymal stem cells may be the best choice for the treatment of ALF taking advantage of their short-term benefit to sustain the critical phase of the acute insult avoiding long-term immunosuppression.

  8. Trichostatin A protects against intestinal injury in rats with acute liver failure.

    Science.gov (United States)

    Zhang, Qian; Yang, Fan; Li, Xun; Zhang, Hai-Yue; Chu, Xiao-Gang; Zhang, Hong; Wang, Lu-Wen; Gong, Zuo-Jiong

    2016-09-01

    Histone deacetylase (HDAC) inhibitors have been widely applied in the clinic as anticancer drugs against multiple neoplasms and proved their anti-inflammation under different pathology recently. Trichostatin A (TSA) is an HDAC inhibitor specific in class I and II HDAC enzymes. The aim of the present study was to elucidate the protective effects of TSA on acute liver failure (ALF) in rats and its potential mechanism. A total of 18 female Sprague-Dawley rats were separated into control, model, and TSA groups. We used Western blotting to determine the expression of HDACs, inflammatory cytokines, and acetylation of histone in liver and small intestine. The gene expression of inflammatory factors and Cox-2 was detected by a polymerase chain reaction. Colonic motility was assessed by spatiotemporal mapping. Histologic analysis and immunohistochemistry were performed. Intestinal permeability examination and levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin were also observed. ALF procedure caused harm to histology of liver and small intestine, increased the intestinal permeability and serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin. It also interrupted the normal organization of colonic motor patterns by hurting enteric nervous system and pacemaker cells. Along with the decrease of inflammatory factors in ALF rats by TSA administration, all the damage to the liver, the small intestine, and the colon was repaired. TSA alleviates the lesion in liver, as well as in small intestine and colon in ALF rats by directly inhibiting inflammatory response. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 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.

  10. Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats.

    Science.gov (United States)

    Zhang, Yang; Luo, Jian-Xing; Hu, Xiao-Yu; Yang, Fang; Zhong, Sen; Lin, Wu

    2016-02-28

    To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats. Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed. D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/β-actin (0.06 ± 0.03, 0.11 ± 0.04 vs 0.25 ± 0.04, P liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 ± 4.91, 25.57 ± 2.94 vs 17.55 ± 2.40, P liver regeneration.

  11. Early predictor of mortality due to irreversible posthepatectomy liver failure in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Kim, Sung Hoon; Kang, Dae Ryong; Lee, Jae Gil; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub; Chon, Chae Yoon; Kim, Kyung Sik

    2013-05-01

    Although mortality after liver resection has declined, posthepatectomy liver failure (PHLF) remains a major cause of operative mortality. To date there is not consensus on a definition for PHLF. However, there have been many efforts to define PHLF causing operative mortality. In the present study we sought to identify early predictors of death from irreversible PHLF. We retrospectively analyzed the medical records of 359 patients with hepatocellular carcinoma who underwent liver resection between March 2000 and December 2010. Various biochemical parameters from postoperative days (POD) 1, 3, 5, and 7 were analyzed and compared with the "50-50" criterion. Operative mortality was 4.7 %. Prothrombin time (PT) <65 % and bilirubin ≥ 38 μmol/L on POD 5 showed the only significant difference as compared with "50-50" criterion. The new combination of bilirubin level and the international normalized ratio showed higher sensitivity, area under the curve, as well as similar accuracy (sensitivity 78.6 vs. 28.6 %; p = 0.002; area under the curve 0.8402 vs. 0.6396; p = 0.00176; accuracy 88.6 vs. 93.4 %; p = 0.090). Multivariate analysis revealed the combination of PT <65 % and bilirubin ≥ 38 μmol/L on POD 5 to be the only independent predictive factor of mortality (odds ratio, 82.29; 95 % confidence interval 8.69-779.64; p < 0.001). In patients with chronic liver disease who will undergo liver resection the combination of PT <65 % and bilirubin ≥ 38 μmol/L on POD 5 may be a more sensitive predictor than the "50-50" criterion of mortality from PHLF. Although it needs to validated by prospective study, this measure may be applied to select patients receiving artificial liver supports or liver transplantation.

  12. Significance of monitoring plasma concentration of voriconazole in a patient with liver failure: A case report.

    Science.gov (United States)

    Liu, Xiaoyan; Su, Haibin; Tong, Jingjing; Chen, Jing; Yang, Haozhen; Xiao, Long; Hu, Jinhua; Zhang, Lina

    2017-10-01

    Invasive pulmonary aspergillosis is associated with significant morbidity and mortality in patients with liver failure. Voriconazole (VRCZ) is recommended as a primary therapeutic agent for the treatment of invasive aspergillosis and metabolized in the liver. Now, data are still lacking on the safety and appropriate dosage of VRCZ in patients with liver failure. Here, we report a representative case of invasive pulmonary fungal infection in a patient with liver failure who was treated with low-dose VRCZ. A 21-year-old man, presented with subacute liver failure caused suspected by viral infection, was admitted on June 22, 2014. Liver function was not improved by the treatment of gancicolovir and methylprednisolone. The patient presented with fever, cough, and hyperpyrexia on July 14. Laboratory tests revealed raised neutrophil percentage (82.1%, normal range [NR] 50-70), international normalized ratio (INR) (2.32, NR 0.8-1.2) and levels of serum lactic acid (4.308 mmol/L, NR 0.6-2.2), alanine transaminase (165 U/L,NR 0-40), aspartate transaminase (99 U/L, NR 8-40), and total bilirubin (654 mmol/L, NR 3.4-20.5). Furthermore, CD4+ T cell, CD8+T cell, and B cell count were low (169, 221, and l8/mL, respectively). Sputum smear microscopy for bacteria was negative, but the direct observation for fungal elements was positive. Thoracic CT scan revealed bilateral pulmonary high-density shadow. Sputum cultures were positive 2 days later with the presence of Aspergillus fumigatus. Therefore, this patient diagnosed with suspected pulmonary a spergillosis. VRCZ was used on July 15th and its dosage was 400 mg twice on day 1 followed by a maintenance dose of 100 mg twice daily according to drug usage instruction. However, some side effects, such as tremors, lips twitching, and hair loss, occurred. Plasma VRCZ trough concentration was 8.1 mg/mL which was much higher than the recommend level. Therefore, VRCZ dosage was adjusted according to its plasma concentration

  13. Liver failure after transarterial chemoembolization for patients with hepatocellular carcinoma and ascites: incidence, risk factors, and prognostic prediction.

    Science.gov (United States)

    Hsin, I-Fang; Hsu, Chia-Yang; Huang, Hui-Chun; Huang, Yi-Hsiang; Lin, Han-Chieh; Lee, Rheun-Chuan; Chiang, Jen-Huey; Lee, Fa-Yauh; Huo, Teh-Ia; Lee, Shou-Dong

    2011-07-01

    Transarterial chemoembolization (TACE) is widely used in patients with hepatocellular carcinoma (HCC). Post-TACE liver failure may occur, especially in patients with poor hepatic reserve. Ascites is often present in patients with HCC with coexisting cirrhosis. This study investigated the incidence, risk factors, and prognostic predictors in patients with HCC and ascites receiving TACE. A total of 614 patients with HCC were enrolled and analyzed. Liver failure was defined as an increase of serum bilirubin level (≥2.0 mg/dL), increasing or newly developed ascites, or hepatic encephalopathy within 2 weeks of TACE. Ascites that were present in 100 (16.2%) patients at study entry, independently predicted a poor prognosis in the Cox proportional hazard model [relative risk (RR)=1.75, P=0.004]. Post-TACE liver failure occurred in 17 (17.3%) of 98 patients with HCC who had ascites and long-term follow-up. Child-Turcotte-Pugh class B (odds ratio=10.1, P=0.038) and post-TACE gastrointestinal bleeding (odds ratio=10.86, P=0.006) were independent risk factors associated with liver failure in the multivariate analysis. Of the 17 patients with post-TACE liver failure, 16 (94%) died within the first year of treatment. Liver failure (RR: 2.13, P=0.029), serum α-fetoprotein level >51 ng/mL (RR=2.0, P=0.013) and poor performance status (RR: 2.17, P=0.003) independently predicted a poor prognosis in patients with ascites receiving TACE. Preexisting ascites increases the mortality in patients with HCC receiving TACE. In patients with HCC and ascites, Child-Turcotte-Pugh class B and gastrointestinal bleeding are associated with liver failure after TACE. Post-TACE liver failure is a common event and predicts a decreased survival in patients with HCC and ascites.

  14. Posterior reversible encephalopathy syndrome in a survivor of valproate-induced acute liver failure: a case report

    OpenAIRE

    Mettananda, Sachith; Fernando, Asvini D; Ginige, Nimasari

    2013-01-01

    Introduction Posterior reversible encephalopathy syndrome is an extremely rare radiological diagnosis that has not been reported previously in association with acute liver failure. Case presentation A 6-year-old Sri Lankan girl developed acute liver failure with severe hepatic encephalopathy due to sodium valproate. She was successfully treated medically with N-acetylcysteine and L-carnitine. During recovery she again developed features of encephalopathy and had repeated convulsions associate...

  15. Use of serial assessment of disease severity and liver biopsy for indication for liver transplantation in pediatric Epstein-Barr virus-induced fulminant hepatic failure.

    Science.gov (United States)

    Nakazawa, Atsuko; Nakano, Natsuko; Fukuda, Akinari; Sakamoto, Seisuke; Imadome, Ken-Ichi; Kudo, Toyoichiro; Matsuoka, Kentaro; Kasahara, Mureo

    2015-03-01

    The decision to perform liver transplantation (LT) in patients with Epstein-Barr virus (EBV)-induced fulminant hepatic failure (FHF) relies on a precise assessment of laboratory and pathological findings. In this study, we analyzed clinical and laboratory data as well as the pathological features of the liver in order to evaluate the pathogenesis and the need for LT in 5 patients with EBV-induced FHF. According to the King's College criteria, the Acute Liver Failure Early Dynamic (ALFED) model, and the Japanese criteria (from the Acute Liver Failure Study Group of Japan), only 1 patient was considered to be a candidate for LT. However, explanted liver tissues in 3 cases exhibited massive hepatocellular necrosis together with diffuse CD8-positive T cell infiltration in both the portal area and the sinusoid. EBV was detected in the liver, plasma, and peripheral blood mononuclear cells (PBMNCs). In 2 cases indicated to be at moderate risk by the ALFED model, liver biopsy showed CD8-positive and EBV-encoded RNA signal-positive lymphocytic infiltration predominantly in the portal area, but massive hepatocellular necrosis was not observed. These patients were treated with immunosuppressants and etoposide under the diagnosis of EBV-induced hemophagocytic lymphohistiocytosis or systemic EBV-positive T cell lymphoproliferative disease of childhood. EBV DNA was detected at a high level in PBMNCs, although it was negative in plasma. On the basis of the pathological analysis of the explanted liver tissues, LT was proposed for the restoration of liver function and the removal of the EBV-infected lymphocytes concentrated in the liver. Detecting EBV DNA by a quantitative polymerase chain reaction in plasma and PBMNCs was informative. An accurate evaluation of the underlying pathogenesis is essential for developing a treatment strategy in patients with EBV-induced FHF. © 2015 American Association for the Study of Liver Diseases.

  16. Transplantation of Adipose-Derived Mesenchymal Stem Cells Efficiently Rescues Thioacetamide-Induced Acute Liver Failure in Mice.

    Science.gov (United States)

    Deng, L; Kong, X; Liu, G; Li, C; Chen, H; Hong, Z; Liu, J; Xia, J

    2016-01-01

    We aimed to investigate the efficacy of adipose-derived mesenchymal stem cell (ADMSC) transplantation in acute liver failure caused by thioacetamide in mice as well as its underlying mechanism by comparing transplantation routes. ADMSCs were isolated from inguinal fat pads of enhanced green fluorescent protein (EGFP) transgenic mice and analyzed regarding their surface markers and differentiation potential. Acute liver failure models were established by infusion of thioacetamide, and then we injected EGFP-ADMSCs or phosphate-buffered saline solution by intrasplenic or intravenous route. The restoration of biologic functions of the livers receiving transplantation was assessed by means of a variety of approaches, such as survival rates, live function parameters, histology, localization of EGFP-ADMSCs, and immunofluorescence analysis. ADMSCs were positive for CD90 and CD44 and negative for CD34 and had adipogenic and osteogenic differentiation potential. And they prevented the release of liver injury biomarkers. Transplantation via tail vein provided a significant survival benefit, but no significant differences were observed in the intrasplenic pathway and between the 2 pathways in our animal experiments. Furthermore, the transplanted cells were well integrated into injured livers and produced albumin and cytokeratin-8. Direct transplantation of ADMSCs is an effective treatment for acute liver failure rather than intrasplenic transplantation. The transplanted ADMSCs exhibit the potential to differentiate into hepatocyte-like cells in the injured livers. Thus, ADCMSCs would be a potential option for treatment of acute liver failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Early treatment with N-acetylcysteine in children with acute liver failure secondary to hepatitis A.

    Science.gov (United States)

    Sotelo, Norberto; de los Angeles Durazo, María; Gonzalez, Alejandro; Dhanakotti, Nagasharmila

    2009-01-01

    Hepatitis A virus can evolve to acute liver failure with a fatal outcome if it is not reversed. We describe the clinical course of 12 children who presented with hepatitis A acute liver failure and received treatment with oral N-acetylcysteine (NAC). Of the seventy-two patients with viral hepatitis A, 12 patients who had acute hepatic failure were included. The variables evaluated were age, sex, duration of clinical features prior to hospitalization, signs and symptoms, laboratory parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), partial thromboplastin time (PTT), internal normalization ratio and ammonia], treatment (oral NAC 100 mg/kg/day, lactulose, neomycin and general measures) and clinical course during hospitalization. Six males and six females were included. School-aged and adolescent children predominated. All presented with jaundice, nausea, vomiting and hepatomegaly. Two had stage 2 neurological signs as per the West-Haven scale. All had altered laboratory parameters. All received NAC, six patients for a week and the remaining six for 9-36 days. Treatment was not ceased until patients showed clinical and laboratory improvement. All data were analyzed using both student's t test and Wilcoxon signed rank with alpha = 0.05, the ALT with P = 0.0003 and 0.005, AST with P = 0.0001 and 0.0005, PT with P = 0.0237 and 0.0005, PTT with P = 0.0515 and 0.0039, ammonia with P = 0.0197 and 0.0015 and direct bilirubin with P = 0.0190 and 0.068. There was good tolerance to medications and a satisfactory clinical course. The use of oral NAC appears to be an effective therapeutic alternative for hepatitis A-induced liver failure if it is offered appropriately. It can modify the clinical course to a favorable one and prevent the fatal outcome of hepatic encephalopathy.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Recurrent elevated liver transaminases and acute liver failure in two siblings with novel bi-allelic mutations of NBAS.

    Science.gov (United States)

    Regateiro, Frederico S; Belkaya, Serkan; Neves, Nélson; Ferreira, Sandra; Silvestre, Paula; Lemos, Sónia; Venâncio, Margarida; Casanova, Jean-Laurent; Gonçalves, Isabel; Jouanguy, Emmanuelle; Diogo, Luísa

    2017-08-01

    Acute liver failure (ALF) in children can be life-threatening. Although many causes are known, ALF remains unexplained in about half of the cases. Recently, bi-allelic mutations in NBAS were reported to underlie recurrent episodes of elevated liver transaminases (ELT) and ALF in the context of diverse extrahepatic phenotypes. We here describe two sisters, born to non-consanguineous Portuguese parents, who had short stature and presented with recurrent episodes of severe ELT triggered by febrile respiratory viral infections since early childhood. Patient 1 had mild facial dysmorphism and died during the second ELT crisis at 3-11/12 years of age. Patient 2, currently 9 years old, had multiple episodes of ELT (>30), twice with ALF, often accompanied by extensive urticaria and facial angioedema. Whole-exome and Sanger sequencing revealed that both patients carried previously undescribed compound heterozygous mutations of NBAS (NM_015909.3): c.680A > C (p.His227Pro), affecting an evolutionarily conserved residue, and c.1749G > A (p.Trp583*), causing a premature stop codon. Both mutations are predicted to be highly damaging. The parents and two younger siblings are healthy and heterozygous for one or another mutant allele. The multiplex kindred reported herein expands the genotypic and phenotypic spectrum of this recently described clinical syndrome due to autosomal recessive NBAS deficiency. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Prognostic Factors Predicting Poor Outcome in Living-Donor Liver Transplantation for Fulminant Hepatic Failure.

    Science.gov (United States)

    Kim, T-S; Kim, J M; Kwon, C H D; Kim, S J; Joh, J-W; Lee, S-K

    2017-06-01

    Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF. From April 1999 to April 2011, 60 patients underwent LT for acute liver failure, including 42 patients for FHF at Samsung Medical Center, Seoul, Korea. Among 42 patients, 30 patients underwent LDLT for FHF, and the database of these patients was analyzed retrospectively to investigate the prognostic factors after LDLT for FHF. Among 30 patients, 7 patients (23%) died during the in-hospital period within 6 months, and 23 patients (77%) survived until recently. In univariate analyses, donor age (>35 years), graft volume (GV)/standard liver volume (SLV) (120 minutes), hepatic encephalopathy (grade IV), hepato-renal syndrome (HRS), and history of ventilator care were associated with fatal outcome after LDLT for FHF. In multivariate analyses, HRS, GV/SLV (35 years) were significantly associated with fatal outcome. Although the statistical significance was not shown in this analysis (P = .059), hepatic encephalopathy grade IV also appears to be a risk factor predicting fatal outcome. The survival of patients with FHF undergoing LDLT was comparable to that in published data. In this study, HRS, GV/SLV 35 years are the independent poor prognostic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Acute liver failure caused by mushroom poisoning: a case report and review of the literature

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    Erden A

    2013-11-01

    Full Text Available Abdulsamet Erden,1 Kübra Esmeray,1 Hatice Karagöz,1 Samet Karahan,1 Hasan Hüseyin Gümüsçü,1 Mustafa Basak,1 Ali Çetinkaya,1 Deniz Avci,1 Orhan Kürsat Poyrazoğlu2 1Internal Medicine Department, 2Gastroenterology Department, Kayseri Training and Research Hospital, Kayseri, Turkey Abstract: It is estimated that there are over 5,000 species of mushrooms worldwide. Some of them are edible and some are poisonous due to containing significant toxins. In more than 95% of mushroom toxicity cases, poisoning occurs as a result of misidentification of the mushroom by an amateur mushroom hunter. The severity of mushroom poisoning may vary, depending on the geographic location where the mushroom is grown, growth conditions, the amount of toxin delivered, and the genetic characteristics of the mushroom. Amanita phalloides is the most common and fatal cause of mushroom poisoning. This mushroom contains amanitins, which are powerful hepatotoxins that inhibit RNA polymerase II in liver. Mushroom poisoning is a relatively rare cause of acute liver failure. A 63-year-old male patient was admitted to the emergency room with weakness, nausea, vomiting, and diarrhea. He reported ingesting several wild mushrooms about 36 hours earlier. In this article we report a case of lethal Amanita phalloides intoxication from stored mushrooms. Keywords: acute liver failure, Amanita phalloides, mushroom, poisoning

  2. Recreational Exposure during Algal Bloom in Carrasco Beach, Uruguay: A Liver Failure Case Report.

    Science.gov (United States)

    Vidal, Flavia; Sedan, Daniela; D'Agostino, Daniel; Cavalieri, María Lorena; Mullen, Eduardo; Parot Varela, María Macarena; Flores, Cintia; Caixach, Josep; Andrinolo, Dario

    2017-08-31

    In January 2015, a 20-month-old child and her family took part in recreational activities at Carrasco and Malvín beaches (Montevideo, Uruguay). An intense harmful algae bloom (HAB) was developing along the coast at that time. A few hours after the last recreational exposure episode, the family suffered gastrointestinal symptoms which were self-limited except in the child's case, who was admitted to hospital in Uruguay with diarrhea, vomiting, fatigue, and jaundice. The patient had increased serum levels of liver enzymes and bilirubin and five days later presented acute liver failure. She was referred to the Italian Hospital in Buenos Aires, being admitted with grade II-III encephalopathy and hepatomegaly and requiring mechanical respiratory assistance. Serology tests for hepatitis A, B, and C, Epstein-Barr virus, and cytomegalovirus were negative. Laboratory features showed anemia, coagulopathy, and increased serum levels of ammonium, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. Autoimmune Hepatitis Type-II (AH-II) was the initial diagnosis based on a liver kidney microsomal type 1 antibodies (LKM-1) positive result, and twenty days later a liver transplant was performed. The liver histopathology had indicated hemorrhagic necrosis in zone 3, and cholestasis and nodular regeneration, which were not characteristic of AH-II. LC/ESI-HRMS (liquid chromatography electrospray ionization high-resolution mass spectrometry) analysis of MCs in the explanted liver revealed the presence of Microsytin-LR (MC-LR) (2.4 ng·gr(-1) tissue) and [D-Leu¹]MC-LR (75.4 ng·gr(-1) tissue), which constitute a toxicological nexus and indicate a preponderant role of microcystins in the development of fulminant hepatitis.

  3. Combination of liver biopsy with MELD-XI scores for post-transplant outcome prediction in patients with advanced heart failure and suspected liver dysfunction.

    Science.gov (United States)

    Farr, Maryjane; Mitchell, James; Lippel, Matthew; Kato, Tomoko S; Jin, Zhezhen; Ippolito, Paul; Dove, Lorna; Jorde, Ulrich P; Takayama, Hiroo; Emond, Jean; Naka, Yoshifumi; Mancini, Donna; Lefkowitch, Jay H; Schulze, P Christian

    2015-07-01

    Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI improves prediction of adverse outcomes in patients evaluated for HTx. Sixty-eight patients suspected of advanced liver disease underwent liver biopsy as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) × MELD-XI was generated for each patient. Fifty-two patients were listed, of whom 14 had mechanical circulatory support (MCS). Thirty-six patients underwent transplantation and 27 patients survived ≥1 year post-HTx (74%, as compared with 88% average 1-year survival in HTx patients without suspected liver disease; p liver risk score at evaluation for HTx (31.0 ± 20.4 vs 65.2 ± 28.6, p liver risk score was identified by receiver-operating-characteristic (ROC) analysis. In the analysis using Cox proportional hazards models, a liver risk score ≥45 at evaluation for HTx was associated with greater risk of death at 1 year post-HTx compared with a score of liver risk score at evaluation for HTx also predicted 1-year mortality after HTx listing (p liver dysfunction are high-risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk stratification of patients with advanced HF and suspected irreversible liver dysfunction. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children.

    Science.gov (United States)

    Laoprasopwattana, Kamolwish; Jundee, Puthachat; Pruekprasert, Pornpimol; Geater, Alan

    2016-06-01

    To determine clinical course and outcomes of liver functions in children with dengue viral infection-caused acute liver failure (ALF), the records of patients aged failure including respiratory failure, massive bleeding and acute kidney injury occurred in 80.0%, 96.0% and 84.0% of the ALF cases, respectively, with an overall fatality rate of 68.3%. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were highest on the day that the patient developed ALF. Lactate dehydrogenase levels had positive correlations with AST (r = 0.95) and ALT (r = 0.87) (all p < 0.01). The median (interquartile range) days before the AST and ALT levels returned to lower than 200 U/L after the ALF were 10.5 (8.8, 12.8) and 10.5 (7.8, 14.0) days, respectively. © The Author [2016]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. [Severe paracetamol poisoning complicated with liver and renal failure--case report and review of literature].

    Science.gov (United States)

    Mietka-Ciszowska, Aneta; Stojakowska, Magdalena; Groszek, Barbara

    2012-01-01

    Paracetamol is a widely known over-the-counter analgesic and antipyretic which, in acute poisoning usually causes liver damage, and less commonly damage to the kidney, heart, and pancreas. In the present paper we report a case of acute suicidal paracetamol intoxication complicated by acute hepatic and renal failure. The discussion covers the pathogenesis, clinical course, and treatment of acute renal failure in the course of paracetamol poisoning. A thirty-four-year-old woman was admitted to hospital in the second day after ingestion of nearly 17 g of acetaminophen. During admission to the hospital, the maximum values of transaminases (AST 19 350 U/L, ALT 11 760 U/L) were found; they have gradually normalized over the next few weeks. Sequentially monitored serum creatinine showed an upward trend, reaching a value of 588 micromol/L in the fifth day after drug ingestion. The patient underwent 1 haemodiafiltration and 4 haemodialysis treatments resulting in an improvement in renal function. In acute acetaminophen poisoning, in addition to standard monitoring of liver function, the monitoring of kidney function is necessary because of the risk of acute renal failure due to acute tubular necrosis. Kidney damage is likely to be transient and generally will not need long-term renal replacement therapy.

  6. The Role of Bone Marrow Mesenchymal Stem Cells in the Treatment of Acute Liver Failure

    Directory of Open Access Journals (Sweden)

    Shufang Yuan

    2013-01-01

    Full Text Available Objective. This study is to investigate the effects of bone marrow mesenchymal stem cell (BMSC transplantation on acute liver failure (ALF. Methods. BMSCs were separated from rat bone marrow, cultured, and identified by flow cytometry. Rat model with ALF was established by injecting D-galactosamine and lipopolysaccharide. Rats were randomly divided into the control group and BMSC transplantation group. The serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST were measured at 24 h, 120 h, and 168 h after BMSC transplantation. Apoptosis was detected by TUNEL assay. The expression of VEGF and AFP proteins was detected by immunofluorescence. Caspase-1 and IL-18 proteins and mRNA were detected by immunohistochemistry and RT-PCR. Results. Compared with the control group, levels of ALT, AST, caspase-1 and IL-18 proteins, and mRNA in the transplantation group were significantly lower at 120 h and 168 h after BMSCs transplantation. Apoptosis was inhibited by BMSCs transplantation. The VEGF protein levels were increased with the improvement of liver function, and the AFP protein levels were increased with the deterioration of the liver function after BMSCs transplantation. Conclusions. BMSCs transplantation can improve liver function and inhibit hepatocyte apoptosis as well as promote hepatocyte proliferation in rat model with ALF.

  7. Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD).

    Science.gov (United States)

    Laemmle, Alexander; Gallagher, Renata C; Keogh, Adrian; Stricker, Tamar; Gautschi, Matthias; Nuoffer, Jean-Marc; Baumgartner, Matthias R; Häberle, Johannes

    2016-01-01

    Acute liver failure (ALF) has been reported in ornithine transcarbamylase deficiency (OTCD) and other urea cycle disorders (UCD). The frequency of ALF in OTCD is not well-defined and the pathogenesis is not known. To evaluate the prevalence of ALF in OTCD, we analyzed the Swiss patient cohort. Laboratory data from 37 individuals, 27 females and 10 males, diagnosed between 12/1991 and 03/2015, were reviewed for evidence of ALF. In parallel, we performed cell culture studies using human primary hepatocytes from a single patient treated with ammonium chloride in order to investigate the inhibitory potential of ammonia on hepatic protein synthesis. More than 50% of Swiss patients with OTCD had liver involvement with ALF at least once in the course of disease. Elevated levels of ammonia often correlated with (laboratory) coagulopathy as reflected by increased values for international normalized ratio (INR) and low levels of hepatic coagulation factors which did not respond to vitamin K. In contrast, liver transaminases remained normal in several cases despite massive hyperammonemia and liver involvement as assessed by pathological INR values. In our in vitro studies, treatment of human primary hepatocytes with ammonium chloride for 48 hours resulted in a reduction of albumin synthesis and secretion by approximately 40%. In conclusion, ALF is a common complication of OTCD, which may not always lead to severe symptoms and may therefore be underdiagnosed. Cell culture experiments suggest an ammonia-induced inhibition of hepatic protein synthesis, thus providing a possible pathophysiological explanation for hyperammonemia-associated ALF.

  8. Effects of urotensin-II on cytokines in early acute liver failure in mice.

    Science.gov (United States)

    Liu, Liang-Ming; Zhao, Liang; Liang, Dong-Yu; Yu, Fang-Ping; Ye, Chang-Gen; Tu, Wen-Juan; Zhu, Tong

    2015-03-21

    To investigate urotensin-II (UII) and its effects on tumor necrosis factor (TNF)-α and interleukin (IL)-1β in early acute liver failure (ALF). We investigated the time-dependent alteration in UII levels and its effects on TNF-α and IL-1β in liver and blood in the early stage of lipopolysaccharide/D-galactosamine-induced ALF. After lipopolysaccharide/D-galactosamine challenge, UII rose very rapidly and reached a maximal level 0.5 h, and the level remained significantly elevated after 2 h (P liver and blood at 6 h after challenge (P liver and blood TNF-α increased from 1 to 6 h, and reached a peak at 1 and 2 h, respectively; however, IL-1β did not rise until 6 h after challenge. Urantide pretreatment inhibited the degree of TNF-α and IL-1β increase following downregulation of UII post-challenge (all P < 0.05). UII plays a role in the pathogenesis and priming of ALF by triggering an inflammatory cascade and driving the early release of cytokines in mice.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone.

    Science.gov (United States)

    Paudel, Robin; Dogra, Prerna; Suman, Saurav; Acharya, Saurav; Matta, Jyoti

    2016-01-01

    Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

  12. Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone

    Directory of Open Access Journals (Sweden)

    Robin Paudel

    2016-01-01

    Full Text Available Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

  13.  IL-1β siRNA adenovirus benefits liver regeneration by improving mesenchymal stem cells survival after acute liver failure.

    Science.gov (United States)

    Ma, Hucheng; Shi, Xiaolei; Yuan, Xianwen; Ding, Yitao

    2016-01-01

      Uncontrolled hapatic inflammatory response is regarded as the primary pathological mechanism of acute liver failure and impairs the regeneration of hepatocytes and stem cell grafts. Interleukin-1 plays a key role for activating immune and inflammatory response. Recently, siRNA has made quite a few progresses in treating inflammatory response. To assess the effect of IL-1? siRNA adenovirus on MSC and the therapeutic effect of MSC combined with IL-1? siRNA adenovirus in ALF. We implanted MSC or/and IL-1? siRNA adenovirus via the tail vein, using CCl4-induced ALF in a mice model. Mice were sacrificed at different time points. Blood samples and liver tissues were collected. Hepatic injury, liver regeneration, cytokines (CXCL1, IL-1?, IL-10, IL-6, VEGF and HGF), animal survival and vital MSC were assessed after cell transplantation. MSC combined with IL-1? siRNA reduced the inflammatory levels and prevented liver failure. These animals administrated with MSC and IL-1? siRNA also exhibited improved liver regeneration and increased survival rates. Immunohistochemistry and fluorescence microscopy revealed the number of vital MSC in ALF + MSC + IL-1? siRNA group were significantly more than that in ALF + MSC group. IL-1? siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL-1? siRNA adenovirus and MSC had a synergistic effect on acute liver failure.

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

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    pressure. 4. If intracranial hypertension evolves despite these first-tier interventions, increased sedation, induction of hypothermia (body temperature of 33 degrees C to 34 degrees C), and the use of anti-inflammatory drugs may help secure brain viability Udgivelsesdato: 2008/10......) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  15. Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Koivusalo, Antti I; Rintala, Risto J; Pakarinen, Mikko P

    2013-08-01

    The aim of this study was to evaluate the long-term effects of pediatric intestinal failure (IF) on liver histology. Altogether, 38 IF patients (median age: 7.2 years; range, 0.2-27) underwent liver biopsy, gastroscopy, abdominal ultrasound, and laboratory tests. Sixteen patients were on parenteral nutrition (PN) after 74 PN months (range, 2.5-204). Twenty-two had weaned off PN 8.8 years (range, 0.3-27) earlier, after 35 PN months (range, 0.7-250). Fifteen transplant donor livers served as controls. Abnormal liver histology was found in 94% of patients on PN and 77% of patients weaned off PN (P = 0.370). During PN, liver histology weighted with cholestasis (38% of patients on PN versus 0% of patients weaned off PN; P = 0.003) and portal inflammation (38% versus 9%; P = 0.050) were found. Fibrosis (88% versus 64%; P = 0.143; Metavir stage: 1.6 [range, 0-4] versus 1.1 [range, 0-2]; P = 0.089) and steatosis (50% versus 45%; P = 1.000) were equally common during and after weaning off PN. Plasma alanine aminotransferase (78 U/L [range, 19-204] versus 34 [range, 9-129]; P = 0.009) and conjugated bilirubin (43 μmol/L [range, 1-215] versus 4 [range, 1-23]; P = 0.037) were significantly higher during than after weaning off PN. Esophageal varices were encountered in 1 patient after weaning off PN. Metavir stage was associated with small bowel length (r = -0.486; P = 0.002) and number of septic episodes (r = 0.480; P = 0.002). In a multivariate analysis, age-adjusted small bowel length (ß = -0.533; P = 0.001), portal inflammation (ß = 0.291; P = 0.030), and absence of an ileocecal valve (ß = 0.267; P = 0.048) were predictive for fibrosis stage. Despite resolution of cholestasis and portal inflammation, significant liver fibrosis and steatosis persist after weaning off PN. Extensive small intestinal resection was the major predictor for liver fibrosis stage. Copyright © 2013 American Association for the Study of Liver Diseases.

  16. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis.

    Science.gov (United States)

    Leung, Patrick S C; Rossaro, Lorenzo; Davis, Paul A; Park, Ogyi; Tanaka, Atsushi; Kikuchi, Kentaro; Miyakawa, Hiroshi; Norman, Gary L; Lee, William; Gershwin, M Eric

    2007-11-01

    In our previous work, including analysis of more than 10,000 sera from control patients and patients with a variety of liver diseases, we have demonstrated that with the use of recombinant autoantigens, antimitochondrial autoantibodies (AMAs) are only found in primary biliary cirrhosis (PBC) and that a positive AMA is virtually pathognomonic of either PBC or future development of PBC. Although the mechanisms leading to the generation of AMA are enigmatic, we have postulated that xenobiotic-induced and/or oxidative modification of mitochondrial autoantigens is a critical step leading to loss of tolerance. This thesis suggests that a severe liver oxidant injury would lead to AMA production. We analyzed 217 serum samples from 69 patients with acute liver failure (ALF) collected up to 24 months post-ALF, compared with controls, for titer and reactivity with the E2 subunits of pyruvate dehydrogenase, branched chain 2-oxo-acid dehydrogenase, and 2-oxo-glutarate dehydrogenase. AMAs were detected in 28/69 (40.6%) ALF patients with reactivity found against all of the major mitochondrial autoantigens. In addition, and as further controls, sera were analyzed for autoantibodies to gp210, Sp100, centromere, chromatin, soluble liver antigen, tissue transglutaminase, and deaminated gliadin peptides; the most frequently detected nonmitochondrial autoantibody was against tissue transglutaminase (57.1% of ALF patients). The strikingly high frequency of AMAs in ALF supports the thesis that oxidative stress-induced liver damage may lead to AMA induction. The rapid disappearance of AMAs in these patients provides further support for the contention that PBC pathogenesis requires additional factors, including genetic susceptibility.

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

    Science.gov (United States)

    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.

  18. Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.

    Science.gov (United States)

    Sasbón, Jorge S; Buamscha, Daniel; Gianivelli, Silvina; Imventarza, Oscar; Devictor, Denis; Moreiro, Rita; Cambaceres, Carlos; Salip, Gonzalo; Ciocca, Mirta; Cuarterolo, Miriam; Vladimirsky, Sara; Otegui, Lucio; Castro, Raúl; Brajterman, Leonardo; Soto, Sonia; González, Jorge; Munné, María S

    2010-05-01

    To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. None. Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid

  19. Elevated FABP1 serum levels are associated with poorer survival in acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Karvellas, Constantine J; Speiser, Jaime L; Tremblay, Mélanie; Lee, William M; Rose, Christopher F

    2017-03-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality. Traditional prognostic scores lack sensitivity. Serum liver-type fatty acid binding protein (FABP1) early (day 1) or late (day 3-5) levels are associated with 21-day mortality in the absence of liver transplant. Serum samples from 198 APAP-ALF patients (nested case-control study with 99 survivors, 99 nonsurvivors) were analyzed by enzyme-linked immunosorbent assay with clinical data from the US Acute Liver Failure Study Group registry (1998-2014). APAP-ALF survivors had significantly lower serum FABP1 levels early (238.6 versus 690.8 ng/mL, P  350 ng/mL was associated with significantly higher risk of death at early (P = 0.0004) and late (P Liver Disease, vasopressor use). Areas under the receiver operating characteristic curve for early and late multivariable models were 0.778 and 0.907, respectively. The area under the receiver operating characteristic curve of the King's College criteria (early, 0.552 alone, 0.711 with FABP1; late, 0.604 alone, 0.797 with FABP1) and the Acute Liver Failure Study Group prognostic index (early, 0.686 alone, 0.766 with FABP1; late, 0.711 alone, 0.815 with FABP1) significantly improved with the addition of FABP1 (P Liver Diseases.

  20. Evaluation of a scoring system for assessing prognosis in pediatric acute liver failure.

    Science.gov (United States)

    Lu, Brandy R; Gralla, Jane; Liu, Edwin; Dobyns, Emily L; Narkewicz, Michael R; Sokol, Ronald J

    2008-10-01

    Pediatric acute liver failure (PALF) results in death or need for liver transplantation (LT) in up to 50% of patients. A scoring system for predicting death or LT (Liver Injury Units [LIU] score) in PALF was previously derived by our group, and used peak values during hospital admission of total bilirubin, prothrombin time/international normalized ratio, and ammonia as significant predictors of outcome. The aims of this study were to test the predictive value of the LIU score in a subsequent validation set of patients and to derive a hospital admission LIU (aLIU) score predictive of outcome. Data were obtained from 53 children admitted with PALF from 2002 to 2006. Outcome was defined at 16 weeks as alive without LT, death, or LT. Survival without LT at 16 weeks for each LIU score quartile was 92%, 44%, 60%, and 12%, respectively (P < .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 86.3. An admission LIU score was derived using admission total bilirubin and prothrombin time/international normalized ratio. Survival without LT at 16 weeks for each quartile using the aLIU score was 85%, 77%, 69%, and 31% (P = .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 83.7. The original LIU score is a valid predictor of outcome in PALF. The aLIU score is promising and needs to be validated in subsequent patients.

  1. Data-Driven Modeling for Precision Medicine in Pediatric Acute Liver Failure.

    Science.gov (United States)

    Zamora, Ruben; Vodovotz, Yoram; Mi, Qi; Barclay, Derek; Yin, Jinling; Horslen, Simon; Rudnick, David; Loomes, Kathleen M; Squires, Robert H

    2016-11-23

    Absence of early outcome biomarkers for Pediatric Acute Liver Failure (PALF) hinders medical and liver transplant decisions. We sought to define dynamic interactions among circulating inflammatory mediators to gain insights into PALF outcome sub-groups. Serum samples from 101 participants in the PALF study, collected over the first 7 days following enrollment, were assayed for 27 inflammatory mediators. Outcomes (Spontaneous survivors [S, n=61], Non-survivors [NS, n=12], and liver transplant patients [LTx, n=28]) were assessed at 21 days post-enrollment. Dynamic interrelations among mediators were defined using data-driven algorithms. Dynamic Bayesian Network inference identified a common network motif with HMGB1 as a central node in all patient sub-groups. The networks in S and LTx were similar, and differed from NS. Dynamic Network Analysis suggested similar dynamic connectivity in S and LTx, but a more highly-interconnected network in NS that increased with time. A Dynamic Robustness Index calculated to quantify how inflammatory network connectivity changes as a function of correlation stringency differentiated all three patient sub-groups. Our results suggest that increasing inflammatory network connectivity is associated with non-survival in PALF, and may ultimately lead to better patient outcome stratification.

  2. Etiologies and outcomes of acute liver failure in a spanish community.

    Science.gov (United States)

    Fábrega, Emilio; Mieses, Miguel Ángel; Terán, Alvaro; Moraleja, Irene; Casafont, Fernando; Crespo, Javier; Pons-Romero, Fernando

    2013-01-01

    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.

  3. 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.

  4. Transplantation of umbilical cord mesenchymal stem cells via different routes in rats with acute liver failure.

    Science.gov (United States)

    Zheng, Sheng; Yang, Juan; Yang, Jinhui; Tang, Yingmei; Shao, Qinghua; Guo, Ling; Liu, Qinghua

    2015-01-01

    This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats. hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein. The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (Pcells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (Pstem cells were comparable between H group and T group (P>0.05). hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection.

  5. Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

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    Lei Cai

    2016-01-01

    Full Text Available Models using large animals that are suitable for studying artificial liver support system (ALSS are urgently needed. Presently available acute liver failure (ALF models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT. Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr and prothrombin time (PT were significantly increased (all P<0.01 and albumin (ALB was markedly reduced (P<0.01 compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

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

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    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.

  7. Characterization of the Development of Acute-on-Chronic Exertional Compartment Syndrome A Case Report of Symmetric Compartment Syndromes and Review of the Literature.

    Science.gov (United States)

    Schwartz, Andrew; Poole, Claudette; Schleien, Charles

    2017-04-01

    Acute-on-chronic exertional compartment syndrome is a rare and severe progression of the likely common and more benign chronic exertional compartment syndrome. This is a report of one 17-year-old male on a pediatric inpatient service with bilateral anterior leg pain of unknown origin. Because of the nonspecific nature of pain, a high level of suspicion is required for timely diagnosis to avoid compartment ischemia and irreversible soft tissue and nerve damage. While high-energy orthopaedic trauma, orthopaedic surgery, or closed reduction and casting are common preceding events for compartment syndrome, this patient presented with acute-on-chronic exertional compartment syndrome. A dearth of literature of this condition hampered its morbiditysparing diagnosis. While there is a spectrum of clinical findings for the acute decompensation of chronic exertional compartment syndrome, like any compartment syndrome, pain disproportionate to physical exam is the most sensitive sign. Understanding the exertional compartment syndrome spectrum is tantamount to avoid the devastating complications of a missed diagnosis of acute compartment syndrome.

  8. Renal Dysfunction Is an Independent Risk Factor for Mortality after Liver Resection and the Main Determinant of Outcome in Posthepatectomy Liver Failure

    Directory of Open Access Journals (Sweden)

    M. G. Wiggans

    2013-01-01

    Full Text Available Introduction. The aim of this study was to assess the interaction of liver and renal dysfunction as risk factors for mortality after liver resection. Materials and Methods. A retrospective analysis of 501 patients undergoing liver resection in a single unit was undertaken. Posthepatectomy liver failure (PHLF was defined according to the International Study Group of Liver Surgery (ISGLS definition (assessed on day 5 and renal dysfunction according to RIFLE criteria. 90-day mortality was recorded. Results. Twenty-three patients died within 90 days of surgery (4.6%. The lowest mortality occurred in patients without evidence of PHLF or renal dysfunction (2.7%. The mortality rate in patients with isolated PHLF or renal dysfunction was 20% compared to 45% in patients with both. Diabetes (, renal dysfunction (, and PHLF on day 5 ( were independent predictors of 90-day mortality. Discussion. PHLF and postoperative renal dysfunction are independent predictors of 90-day mortality following liver resection but the predictive value for mortality is significantly higher when failure of both organ systems occurs simultaneously.

  9. Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity.

    Science.gov (United States)

    Park, Sun Hong; Kwak, Jeong-Ah; Jung, Sang-Hun; Ahn, Byeongwoo; Cho, Won-Jea; Yun, Cheong-Yong; Na, Chang Seon; Hwang, Bang Yeon; Hong, Jin Tae; Han, Sang-Bae; Kim, Youngsoo

    2017-11-17

    Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.

  10. Pathophysiology, prevention, treatment, and outcomes of intestinal failure-associated liver disease.

    Science.gov (United States)

    Al-Shahwani, Noora H; Sigalet, David L

    2017-04-01

    Intestinal failure-associated liver disease (IFALD) remains a serious problem in the treatment of infants with nutritional problems and short bowel syndrome. A review of the recent literature from 2010 to 2016, concentrating on articles related to the pathophysiology of IFALD and to outcomes of novel nutritional and pharmacological therapies for neonatal cholestasis in the post-surgical neonate. The pathophysiology of IFALD relates to an increase sensitivity of the neonatal liver to cholestasis in the non-fed state; prolonged cholestasis almost inevitably results in liver damage which will progress from fibrosis to cirrhosis. Clinically discerned risk factors include premature birth, inflammation, sepsis, disruption of the enterohepatic circulation by creation of a proximal stoma, and the duration and type of parenteral nutritional support. Within the hepatocyte, the regulatory enzyme farsanoid receptor X (FXR) appears to play a pivotal role in the development of cholestasis. Recent studies have shown that its activity is suppressed by sepsis, and by plant phytosterols found in soy-based lipid preparations. This paradigm is reflected in the emerging consensus for the care of post-surgical neonates, which is based around a multi-disciplinary team approach. Using an algorithm-driven approach, an appropriate balance between caloric support and prevention of IFALD can be achieved. Further prospective studies are required to further refine the optimal sequence of use of these therapies and the long-term effects on neurological development and hepatic function. However, with optimal care, the number of IF patients progressing to end-stage liver disease because of IFALD should be very low.

  11. New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure.

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    Nélson R Carvalho

    Full Text Available The acute liver failure (ALF induced by acetaminophen (APAP is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe2], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe2 to the N-acetylcysteine (NAC during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg, (PhSe2 (15.6 mg/kg, NAC (1200 mg/kg, APAP+(PhSe2 or APAP+NAC, where the (PhSe2 or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe2. The effectiveness of (PhSe2 was similar at a lower dose than NAC. In summary, (PhSe2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.

  12. Emerging role of liver X receptors in cardiac pathophysiology and heart failure.

    Science.gov (United States)

    Cannon, Megan V; van Gilst, Wiek H; de Boer, Rudolf A

    2016-01-01

    Liver X receptors (LXRs) are master regulators of metabolism and have been studied for their pharmacological potential in vascular and metabolic disease. Besides their established role in metabolic homeostasis and disease, there is mounting evidence to suggest that LXRs may exert direct beneficial effects in the heart. Here, we aim to provide a conceptual framework to explain the broad mode of action of LXRs and how LXR signaling may be an important local and systemic target for the treatment of heart failure. We discuss the potential role of LXRs in systemic conditions associated with heart failure, such as hypertension, diabetes, and renal and vascular disease. Further, we expound on recent data that implicate a direct role for LXR activation in the heart, for its impact on cardiomyocyte damage and loss due to ischemia, and effects on cardiac hypertrophy, fibrosis, and myocardial metabolism. Taken together, the accumulating evidence supports the notion that LXRs may represent a novel therapeutic target for the treatment of heart failure.

  13. A reproducible, clinically relevant, intensively managed, pig model of acute liver failure for testing of therapies aimed to prolong survival.

    Science.gov (United States)

    Lee, Karla C L; Palacios Jimenez, Carolina; Alibhai, Hatim; Chang, Yu-Mei; Leckie, Pamela J; Baker, Luisa A; Stanzani, Giacomo; L Priestnall, Simon; Mookerjee, Rajeshwar P; Jalan, Rajiv; Davies, Nathan A

    2013-04-01

    A clinically relevant, translational large animal model of acute liver failure (ALF) is required for testing of novel therapies to prolong survival in acute liver failure, to permit spontaneous liver recovery or to act as a bridge to transplantation. The aim was to establish a pig model of acetaminophen-induced ALF that mimics the human clinical syndrome, is managed as in a human intensive care unit and has a predictable survival time. Nine female pigs were anaesthetised and instrumented for continuous intensive care monitoring and management using: target-driven protocols for treatment of cardiovascular collapse, metabolic acidosis and electrolyte abnormalities; intermittent positive pressure ventilation; and continuous renal replacement therapy. Six animals were induced to ALF with acetaminophen (paracetamol). Three animals acted as controls. Irreversible acute liver failure, defined as rise in prothrombin time >3 times normal, occurred 19.3 ± 1.8 h after the onset of acetaminophen administration. Death occurred predictably 12.6 ± 2.7 h thereafter, with acute hepatocellular necrosis in all animals. Clinical progression of liver failure mimicked the human condition including development of coagulopathy, intracranial hypertension, hyperammonaemia, cardiovascular collapse, elevation in creatinine, metabolic acidosis and hyperlactataemia. In addition, cardiovascular monitoring clearly demonstrated progressive cardiac dysfunction in ALF. A reproducible, clinically relevant, intensively managed, large animal model of acute liver failure, with death as a result of multi-organ failure, has been successfully validated for translational studies of disease progression and therapies designed to prolong survival in man. © 2012 John Wiley & Sons A/S.

  14. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    NARCIS (Netherlands)

    Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as

  15. Model for end-stage liver disease predicts right ventricular failure in patients with left ventricular assist devices.

    Science.gov (United States)

    Yost, Gardner L; Coyle, Laura; Bhat, Geetha; Tatooles, Antone J

    2016-03-01

    High rates of right ventricular failure continue to affect postoperative outcomes in patients implanted with left ventricular assist devices (LVADs). Development of right ventricular failure and implantation with right ventricular assist devices is known to be associated with significantly increased mortality. The model for end-stage liver disease (MELD) score is an effective means of evaluating liver dysfunction. We investigated the prognostic utility of postoperative MELD on post-LVAD implantation outcomes. MELD scores, demographic data, and outcomes including length of stay, survival, and postoperative right ventricular failure were collected for 256 patients implanted with continuous flow LVADs. Regression and Kaplan-Meier analyses were used to investigate the relationship between MELD and all outcomes. Increased MELD score was found to be an independent predictor of both right heart failure and necessity for RVAD implantation (OR 1.097, CI 1.040-1.158, p = 0.001; OR 1.121, CI 1.015, p = 0.024, respectively). Patients with RV failure and who underwent RVAD implantation had reduced postoperative survival compared to patients with RV dysfunction (no RV failure = 651.4 ± 609.8 days, RV failure = 392.6 ± 444.8 days, RVAD = 89.3 ± 72.8 days; p < 0.001). In conclusion, MELD can be used to reliably predict postoperative right heart failure and the necessity for RVAD implantation. Those patients with RV failure and RVADs experience significantly increased postoperative mortality compared to those without RV dysfunction.

  16. S-100b and neuron-specific enolase in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Christiansen, Michael; Møller, Kirsten

    2001-01-01

    , the cerebral flux of S-100b and NSE was measured. We included 35 patients with FHF, 6 patients with acute on chronic liver disease (AOCLD), 13 patients with cirrhosis of the liver without hepatic encephalopathy, and 8 healthy subjects. Blood samples were obtained from catheters placed in the radial artery...

  17. [Pediatric acute liver failure. Working group of the Latinamerican Society of Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN).

    Science.gov (United States)

    Ciocca, Mirta; Costagdta, Alejandro; Cuarterolo, Miriam; Delgado, Laura; Garcete, Lidia; Godoy, Marcela; López, Carmen Esther; López, Carola; Ramonet, Margarita

    2016-03-01

    Pediatric acute liver failure is a syndrome ofsevere and sudden dysfunction of the hepatocytes which produces a failure in synthetic and detoxifyingfunction. It is an infrequent and severe disease butpotentiallyfatal, occurring in children with no prior history of liver disease. Etiology is related to the age and geographic region of the patient, recognizing the origin: metabolic, infectious, drug exposure, autoinmune, vascular and oncologic. Indeterminate cause where all the etiological search is negative, can range between 18 and 47%, depending on the center and access to the realization of etiological studies. The process which determines the liver injury is still not well known and is considered multifactorial. Essentially, it depends on host susceptibility, the cause and severity of the damage and the ability of liver regeneration. The clinical presentation depends on the etiology, which usually begins with an episode ofacute hepatitis, that in the following days or weeks presents unfavorable outcome, deepening jaundice, affecting the general state and presenting severe coagulopathy that characterizes the syndrome. The treatment consists of general measures which take into account the metabolic disorders, nutritional aspect, and the prevention and treatment of all complications that occur in the evolutionary course (infectious, neurological, etc). Besides it is also vital to implement the specific treatment of those diseases which can benefit from it (alloimmune hepatitis, galactosemia, tyrosinemia, herpes simplex infection, Wilson's disease, etc.). However, despite therapeutic advances, acute liver failure results in death or liver transplantation in over 45% ofcases.

  18. HBV-Associated Acute Liver Failure After Immunosuppression and Risk of Death.

    Science.gov (United States)

    Karvellas, Constantine J; Cardoso, Filipe S; Gottfried, Michelle; Reddy, K Rajender; Hanje, A James; Ganger, Daniel; Lee, William M

    2017-01-01

    Acute liver failure (ALF) caused by hepatitis B virus (HBV) infection can occur after immunosuppressive treatment and be fatal, although it might be preventable. We aimed to characterize the causes, clinical course, and short-term outcomes of HBV-associated ALF after immune-suppressive therapy, compared with patients with HBV-associated ALF without immunosuppression (control subjects). We performed a retrospective multicenter study of 156 consecutive patients diagnosed with HBV-associated ALF (22 with a solid or blood malignancy) enrolled in the Acute Liver Failure Study Group registry from January 1998 through April 2015. We collected data on results of serologic and hepatic biochemistry analyses, grade of hepatic encephalopathy, Model for End-Stage Liver Disease score, and King's College criteria. We also collected data on clinical features, medical therapies, and complications in the first 7 days following study enrollment. Logistic regression was used to identify factors associated with transplant-free survival at 21 days in HBV-associated ALF (the primary outcome). Among patients with HBV-associated ALF, 28 cases (18%) occurred after immunosuppressive therapy (15 patients received systemic corticosteroids and 21 received chemotherapy); and 128 cases did not (control subjects, 82%). Significantly greater proportions of patients with HBV-associated ALF after immunosuppression were nonwhite persons, and had anemia or thrombocytopenia than controls (P failure (based on MELD score), and complications (hepatic encephalopathy or need for mechanical ventilation, vasopressors, or renal replacement therapy) were similar between the groups (P > .17 for all). Factors associated with 21 day transplant-free survival were increased MELD score (odds ratio ∼OR, 0.894 (95% confidence interval 0.842-0.949 per increment), requirement for mechanical ventilation (OR 0.111(0.041-0.300), and immunosuppressive therapy (OR 0.274(0.082-0.923)). Within a cohort study of patients with

  19. Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Jørgensen, Linda

    2010-01-01

    The pathogenesis of cerebral edema in acute liver failure is suggested, in in vitro and animal studies, to involve a compromised oxidative metabolism with a decrease in cerebral ATP levels and an increase in purine concentrations. In this study we hypothesize that the cerebral concentrations...... of hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively)....

  20. A novel ATP7B gene mutation in a liver failure patient with normal ceruloplasmin and low serum alkaline phosphatase.

    Science.gov (United States)

    Chen, Li; Li, Xinhua; Zheng, Zhiyong; Lu, Xujiang; Lin, Minghua; Pan, Chen; Liu, Jingfeng

    2014-03-15

    Wilson's disease (WD) is a rare disorder of copper metabolism resulting in accumulation of copper in liver and other organs. We present a liver failure patient, who was misdiagnosed for two years, with normal ceruloplasmin and low serum alkaline phosphatase. Molecular testing revealed a novel p.Ala982Thr mutation within ATP7B gene. The pathology of liver sample showed a large amount of copper deposition in the hepatocytes and confirmed the diagnosis of WD. Our data highlighted the importance of molecular testing in the early diagnosis of atypical WD. © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Serum plant sterols, cholestanol, and cholesterol precursors associate with histological liver injury in pediatric onset intestinal failure.

    Science.gov (United States)

    Mutanen, Annika; Nissinen, Markku J; Lohi, Jouko; Heikkilä, Päivi; Gylling, Helena; Pakarinen, Mikko P

    2014-10-01

    Increased serum concentrations of plant sterols, including stigmasterol, during parenteral nutrition (PN) have been linked with serum biochemical signs of intestinal failure-associated liver disease (IFALD), whereas clinical data on their correlation to histologic liver injury have been limited. We studied interrelations between serum noncholesterol sterols and histologic liver injury in pediatric-onset intestinal failure (IF). Serum plant sterols (stigmasterol, avenasterol, sitosterol, and campesterol), cholestanol, and cholesterol precursors (cholestenol, lathosterol, and desmosterol) were measured in 50 IF patients at a median age 7.3 y and in 86 matched controls. Forty patients underwent liver biopsies. Sixteen patients had been receiving PN for 45 mo, and 34 patients had received PN for 9.1 mo but had not received PN for 5.4 y. Serum plant sterols were higher in patients who were currently receiving PN than in controls and were related to conjugated bilirubin (r = 0.799-0.541, P 2-fold higher in patients with persistent liver steatosis than in those without steatosis or controls (P liver steatosis after weaning off PN. Serum cholestanol reflects liver injury in IF patients. © 2014 American Society for Nutrition.

  3. Soluble CD163 from activated macrophages predicts mortality in acute liver failure

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Grønbaek, Henning; Schiødt, Frank V

    2007-01-01

    BACKGROUND/AIMS: Soluble CD163 (sCD163) is a scavenger receptor shed in serum during inflammatory activation of macrophages. We investigated if sCD163 was increased and predicted outcome in acute liver failure (ALF). METHODS: Samples from 100 consecutive patients enrolled in the U.S. ALF Study.......65-5.6), pliver cirrhosis (9.8mg/l (3.6-16.9), p=0.0002). sCD163 on day 1 correlated significantly with ALT, AST, bilirubin, and creatinine. sCD163 concentrations on day 3 were elevated in patients with fatal outcome of disease compared to spontaneous survivors, 29.0mg/l (7...

  4. 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....... In a prospective randomized controlled trial we investigated if maintenance of MH prevented development of ICH in ALF patients at high risk of the complication. METHODS: Patients with ALF, high-grade encephalopathy and intracranial pressure (ICP) monitoring in specialist intensive care units were randomized...... 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...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

    2011-01-01

    BACKGROUND AND PURPOSE 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-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH 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. KEY RESULTS 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. CONCLUSIONS AND IMPLICATIONS 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. PMID:21182490

  7. Development of a Model to Predict Transplant-free Survival of Patients With Acute Liver Failure.

    Science.gov (United States)

    Koch, David G; Tillman, Holly; Durkalski, Valerie; Lee, William M; Reuben, Adrian

    2016-08-01

    Patients with acute liver failure (ALF) have a high risk of death that can be substantially reduced with liver transplantation. It is a challenge to predict which patients with ALF will survive without liver transplant because available prognostic scoring systems are inadequate. We devised a mathematical model, using a large dataset collected by the Acute Liver Failure Study Group, which can predict transplant-free survival in patients with ALF. We performed a retrospective analysis of data from 1974 subjects who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) enrolled in the Acute Liver Failure Study Group database from January 1, 1998 through June 11, 2013. We randomly assigned the subjects to development and validation cohorts. Data from the development cohort were analyzed to identify factors associated with transplant-free survival (alive without transplantation by 21 days after admission to the study). Statistically significant variables were used to create a multivariable logistic regression model. Most subjects were women (70%) and white (78%); acetaminophen overdose was the most common cause (48% of subjects). The rate of transplant-free survival was 50%. Admission values of hepatic encephalopathy grade, ALF etiology, vasopressor use, and log transformations of bilirubin and international normalized ratio were significantly associated with transplant-free survival, based on logistic regression analysis. In the validation cohort, the resulting model predicted transplant-free survival with a C statistic value of 0.84, 66.3% accuracy (95% confidence interval, 63.1%-69.4%), 37.1% sensitivity (95% confidence interval, 32.5%-41.8%), and 95.3% specificity (95% confidence interval, 92.9%-97.1%). Using data from the Acute Liver Failure Study Group, we developed a model that predicts transplant-free survival of patients with ALF based on easily identifiable hospital admission

  8. Is MARS system enough for A. phalloides-induced liver failure treatment?

    Science.gov (United States)

    Sorodoc, Laurentiu; Lionte, Catalina; Sorodoc, Victorita; Petris, Ovidiu; Jaba, Irina

    2010-10-01

    Patients with Amanita phalloides-induced liver failure (LF) have a high mortality, despite significant advances in intensive care management. Our study evaluated the effect of Molecular Absorbents Recirculating System (MARS) comparative with optimal intensive care (OIC) in adults with this condition, in the absence of liver transplantation (LT). Six consecutive patients (women, range 16-61 years) affected by A. phalloides-induced LF were treated with OIC (3 patients) and MARS (3 patients). Laboratory parameters and hepeatic encephalopaty were evaluated 15 min before and 24 hours following each MARS treatment. Three 6-hour sessions per patient were performed in MARS group, with a statistically significant decrease in ammonia (p value 0.011), alaninaminotransferase (ALT) and prothrombin time (PT) (p value 0.004). Two patients had a significant rebound in bilirubin (+116%; p value 0. 04) 24 hours following MARS. Mortality in MARS group was 66.7%. Survival rate in OIC was 0%. Negative prognostic markers: lack of PT and hepatic encephalopaty improvement, rebound in bilirubin, and delay of MARS therapy initiation. No significant adverse reactions occurred during MARS. MARS is an effective depurative therapy in adults with A. phalloides-induced LF, but alone is not enough. Survival is predicted by the results of the initial MARS, amount of mushroom consumed, and time from toxin exposure.

  9. Acute liver failure caused by mushroom poisoning: a case report and review of the literature

    Science.gov (United States)

    Erden, Abdulsamet; Esmeray, Kübra; Karagöz, Hatice; Karahan, Samet; Gümüşçü, Hasan Hüseyin; Başak, Mustafa; Çetinkaya, Ali; Avcı, Deniz; Poyrazoğlu, Orhan Kürşat

    2013-01-01

    It is estimated that there are over 5,000 species of mushrooms worldwide. Some of them are edible and some are poisonous due to containing significant toxins. In more than 95% of mushroom toxicity cases, poisoning occurs as a result of misidentification of the mushroom by an amateur mushroom hunter. The severity of mushroom poisoning may vary, depending on the geographic location where the mushroom is grown, growth conditions, the amount of toxin delivered, and the genetic characteristics of the mushroom. Amanita phalloides is the most common and fatal cause of mushroom poisoning. This mushroom contains amanitins, which are powerful hepatotoxins that inhibit RNA polymerase II in liver. Mushroom poisoning is a relatively rare cause of acute liver failure. A 63-year-old male patient was admitted to the emergency room with weakness, nausea, vomiting, and diarrhea. He reported ingesting several wild mushrooms about 36 hours earlier. In this article we report a case of lethal Amanita phalloides intoxication from stored mushrooms. PMID:24294010

  10. Tamoxifen Attenuates Lipopolysaccharide/Galactosamine-induced Acute Liver Failure by Antagonizing Hepatic Inflammation and Apoptosis.

    Science.gov (United States)

    Zhang, Peng; Zhang, Meisheng; Wan, Mengqi; Huang, Xiaoliu; Jiang, Yan; Xu, Siying; Luo, Mansheng

    2017-04-01

    Bacterial lipopolysaccharide (LPS)-induced acute liver failure (ALF) is a common severe clinical syndrome in intensive care unit. No other methods are available for its prevention apart from supportive treatment and liver transplantation. Tamoxifen (TAM) was reported to attenuate ALF induced by excessive acetaminophen, while its effect on LPS-induced ALF remained unknown. For this, in the present study, we comprehensively assessed whether TAM can attenuate ALF induced by LPS/galactosamine (GaIN). Mice were given TAM once a day for three times. Twelve hours after the last treatment, mice were given LPS/GaIN (intraperitoneally [i.p.]). Survival, plasma transaminases, and histopathology were examined. Serum TNF-α and IL-1β were analyzed by ELISA. Hepatic apoptosis was analyzed by TUNEL and caspase-3 Western blotting, respectively. Compared to the model group, ALF induced by LPS/GaIN was alleviated remarkably following TAM administration, as evidenced by the improvement of survival (87.5% vs. 37.5%), hepatic swell, moderate transaminases, slightly increased serum TNF-α, IL-1β (P < 0.05), and moderate histopathology. In respect of apoptosis, severe hepatocellular apoptosis was reduced notably by TAM treatment confirmed by less TUNEL-positive hepatocytes and decreased caspase-3 cleavage. The results demonstrated that TAM could attenuate LPS/GaIN-induced ALF effectively, probably due to hepatic inflammation and apoptosis antagonism. Furthermore, it was the first report about the effect of TAM on LPS/GaIN-induced ALF.

  11. Sequential analysis of variable markers for predicting outcomes in pediatric patients with acute liver failure.

    Science.gov (United States)

    Uchida, Hajime; Sakamoto, Seisuke; Fukuda, Akinari; Sasaki, Kengo; Shigeta, Takanobu; Nosaka, Shunsuke; Kubota, Masaya; Nakazawa, Atsuko; Nakagawa, Satoshi; Kasahara, Mureo

    2017-11-01

    Our aim was to analyze serial changes in the predictive variables and a scoring system retrospectively adapted to evaluate outcomes in pediatric patients with acute liver failure (ALF). We retrospectively collected data on 65 patients with ALF. The 65 patients were divided into two groups according to the need for liver transplantation (LT) as follows: LT group (n = 54) and non-LT group (n = 11). The early determination scoring system of the indications for LT proposed by the Intractable Hepato-Biliary Diseases Study Group of Japan (JIHBDSG) was used in our study. The area under the receiver operating characteristic curve (AUROC) was calculated for the JIHBDSG score between the LT group and non-LT group at the time of diagnosis (day 0) and day 3, and day 5 after the diagnosis. A JIHBDSG score of >3 at day 5 was found to identify the patients requiring LT with 83.7% sensitivity, 81.8% specificity, and 83.3% diagnostic accuracy. Based on a comparison of AUROC values, the JIHBDSG score on day 5 (AUROC 0.91) was higher than that on day 0 (AUROC 0.75) and day 3 (AUROC 0.84). We showed that a serial analysis of the JIHBDSG score might be useful for predicting outcomes of ALF in pediatric patients who fulfilled the criteria of LT indication in our center. However, further studies are needed to validate our results. © 2016 The Japan Society of Hepatology.

  12. Hepatitis A as an etiologic agent of acute liver failure in Latin America.

    Science.gov (United States)

    Ciocca, Mirta; Moreira-Silva, Sandra Fagundes; Alegría, Sylvia; Galoppo, Maria Cristina; Ruttiman, Ricardo; Porta, Gilda; Da Silvera, Themis Reverbel; Rubio, Pilar; Macias, Mercedes; Cervantes, Yolanda; Avila-Aguero, Maria Luisa; Clemens, Sue Anne Costa; Clemens, Ralf; Weil, John

    2007-08-01

    This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). HAV was the main etiologic agent of ALF in the population studied.

  13. Acute liver failure caused by mushroom poisoning: a case report and review of the literature.

    Science.gov (United States)

    Erden, Abdulsamet; Esmeray, Kübra; Karagöz, Hatice; Karahan, Samet; Gümüşçü, Hasan Hüseyin; Başak, Mustafa; Cetinkaya, Ali; Avcı, Deniz; Poyrazoğlu, Orhan Kürşat

    2013-01-01

    It is estimated that there are over 5,000 species of mushrooms worldwide. Some of them are edible and some are poisonous due to containing significant toxins. In more than 95% of mushroom toxicity cases, poisoning occurs as a result of misidentification of the mushroom by an amateur mushroom hunter. The severity of mushroom poisoning may vary, depending on the geographic location where the mushroom is grown, growth conditions, the amount of toxin delivered, and the genetic characteristics of the mushroom. Amanita phalloides is the most common and fatal cause of mushroom poisoning. This mushroom contains amanitins, which are powerful hepatotoxins that inhibit RNA polymerase II in liver. Mushroom poisoning is a relatively rare cause of acute liver failure. A 63-year-old male patient was admitted to the emergency room with weakness, nausea, vomiting, and diarrhea. He reported ingesting several wild mushrooms about 36 hours earlier. In this article we report a case of lethal Amanita phalloides intoxication from stored mushrooms.

  14. Wernicke encephalopathy in a patient with liver failure: Clinical case report.

    Science.gov (United States)

    Zhao, Pan; Zhao, Yanling; Wei, Zhenman; Chen, Jing; Yan, Lilong

    2016-07-01

    Early recognition and diagnosis of Wernicke encephalopathy is pivotal for the prognosis of this medical emergency, especially in patients with liver failure which predisposes individuals to develop hepatic encephalopathy. For these patients, distinguishing between hepatic encephalopathy and Wernicke encephalopathy is a challenge in real-world clinical practice.A male patient with 21-year medical history of liver cirrhosis presented diarrhea and ascites. One month before this visit, he was noted to have poor appetite and progressive fatigue. After admission, although several major symptoms, including diarrhea, ascites, hyponatremia, and hypoproteinemia, were greatly improved through appropriate treatments, his laboratory indicators were not changed much. His appetite was not reversed at discharge. On the 5th day after discharge, the patient suddenly became reluctant to speak and did not remember the recent happenings. Simultaneously, unsteady gait and strabismus occurred. On the basis of clinical manifestations and brain magnetic resonance imaging scan results, the patient was diagnosed as Wernicke encephalopathy and these relative symptoms were resolved after intravenous vitamin B1.To our knowledge, this is the second case report of Wernicke encephalopathy developing in a critically ill cirrhotic patient without hepatocellular carcinoma or operative intervention. Wernicke encephalopathy may be underdiagnosed in these patients and this case raises physicians' awareness of its possible onset.

  15. Intraportal mesenchymal stem cell transplantation prevents acute liver failure through promoting cell proliferation and inhibiting apoptosis.

    Science.gov (United States)

    Sang, Jian-Feng; Shi, Xiao-Lei; Han, Bin; Huang, Tao; Huang, Xu; Ren, Hao-Zhen; Ding, Yi-Tao

    2016-12-01

    Transplantation of mesenchymal stem cells (MSCs) has been regarded as a potential treatment for acute liver failure (ALF), but the optimal route was unknown. The present study aimed to explore the most effective MSCs transplantation route in a swine ALF model. The swine ALF model induced by intravenous injection of D-Gal was treated by the transplantation of swine MSCs through four routes including intraportal injection (InP group), hepatic intra-arterial injection (AH group), peripheral intravenous injection (PV group) and intrahepatic injection (IH group). The living conditions and survival time were recorded. Blood samples before and after MSCs transplantation were collected for the analysis of hepatic function. The histology of liver injury was interpreted and scored in terminal samples. Hepatic apoptosis was detected by TUNEL assay. Apoptosis and proliferation related protein expressions including cleaved caspase-3, survivin, AKT, phospho-AKT (Ser473), ERK and phospho-ERK (Tyr204) were analyzed by Western blotting. The average survival time of each group was 10.7+/-1.6 days (InP), 6.0+/-0.9 days (AH), 4.7+/-1.4 days (PV), 4.3+/-0.8 days (IH), respectively, when compared with the average survival time of 3.8+/-0.8 days in the D-Gal group. The survival rates between the InP group and D-Gal group revealed a statistically significant difference (Pliver damage was the worst in the D-Gal group, while less injury in the InP group. Histopathological scores revealed a significant decrease in the InP group (3.17+/-1.04, Pliver function, inhibit apoptosis and prolong the survival time of swine with ALF. The transplanted MSCs may participate in liver regeneration via promoting cell proliferation and suppressing apoptosis during the initial stage of ALF.

  16. Pretreatment of lipopolysaccharide (LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway.

    Science.gov (United States)

    Zhang, Sainan; Yang, Naibin; Ni, Shunlan; Li, Wenyuan; Xu, Lanman; Dong, Peihong; Lu, Mingqin

    2014-01-01

    Endotoxin tolerance (ET) is an important phenomenon, which affects inflammation and phagocytosis. Pretreatment with low dose of lipopolysaccharide (LPS) can protect liver injury from various hepatotoxicants such as acetaminophen and pseudomonas aeruginosa exotoxin A. The current study aimed to investigate the protecting mechanisms of endotoxin tolerance in acute liver failure induced by D-galactosamine (D-GalN)/LPS and possible role of toll-like receptors 4 (TLR4) signaling pathway in this phenomenon. Acute liver failure was induced by Injection of D-GalN/LPS. To mimic endotoxin tolerance, male Sprague-Dawley rats were treated with low dose of LPS (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent injection of D-GalN/LPS. Rat survival was determined by survival rate. Liver injury was confirmed by serum biochemical and liver histopathological examination. Inflammatory cytokines were determined by ELISA and nuclear factor-kappa B (NF-κB) (P65), toll-like receptors 4 (TLR4) and Interleukin-1 receptor-associated kinase-1 (IRAK-1) were measured by reverse transcriptase polymerase chain reaction and western blot respectively. Pretreatment of LPS significantly improved rat survival. Moreover, rats pretreated with LPS exhibited lower serum enzyme (ALT, AST and TBiL) level, lower production of inflammatory cytokines and more minor liver histopathological damage than rats without pretreatment of LPS. LPS pretreatment suppressed production of TLR4 and IRAK-1. LPS pretreatment also inhibited activation of hepatic NF-κB. These results indicated that endotoxin tolerance contributed to liver protection against D-GalN/LPS induced acute liver failure through down-regulation of TLR4 and NF-κB pathway.

  17. Correlation between plasma endothelin-1 levels and severity of septic liver failure quantified by maximal liver function capacity (LiMAx test. A prospective study.

    Directory of Open Access Journals (Sweden)

    Magnus F Kaffarnik

    Full Text Available To investigate the relationship between the degree of liver dysfunction, quantified by maximal liver function capacity (LiMAx test and endothelin-1, TNF-α and IL-6 in septic surgical patients.28 septic patients (8 female, 20 male, age range 35-80y were prospectively investigated on a surgical intensive care unit. Liver function, defined by LiMAx test, and measurements of plasma levels of endothelin-1, TNF-α and IL-6 were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Patients were divided into 2 groups (group A: LiMAx ≥100 μg/kg/h, moderate liver dysfunction; group B: LiMAx <100 μg/kg/h, severe liver dysfunction for analysis and investigated regarding the correlation between endothelin-1 and the severity of liver failure, quantified by LiMAx test.Group B showed significant higher results for endothelin-1 than patients in group A (P = 0.01, d5; 0.02, d10. For TNF-α, group B revealed higher results than group A, with a significant difference on day 10 (P = 0.005. IL-6 showed a non-significant trend to higher results in group B. The Spearman's rank correlation coefficient revealed a significant correlation between LiMAx and endothelin-1 (-0.434; P <0.001, TNF-α (-0.515; P <0.001 and IL-6 (-0.590; P <0.001.Sepsis-related hepatic dysfunction is associated with elevated plasma levels of endothelin-1, TNF-α and IL-6. Low LiMAx results combined with increased endothelin-1 and TNF-α and a favourable correlation between LiMAx and cytokine values support the findings of a crucial role of Endothelin-1 and TNF-α in development of septic liver failure.

  18. 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.

  19. Pattern of diagnostic evaluation for the causes of pediatric acute liver failure: an opportunity for quality improvement.

    Science.gov (United States)

    Narkewicz, Michael R; Dell Olio, Dominic; Karpen, Saul J; Murray, Karen F; Schwarz, Kathy; Yazigi, Nada; Zhang, Song; Belle, Steven H; Squires, Robert H

    2009-12-01

    To describe the frequency of diagnostic testing for the 4 most common causes of pediatric acute liver failure (PALF) (drugs, metabolic disease, autoimmune process, and infections) in indeterminate PALF within the PALF Study Group Database. PALF was defined by severe hepatic dysfunction within 8 weeks of onset of illness, with no known underlying chronic liver disease in patients from birth through 17 years of age. Of the 703 patients in the database, 329 (47%) had indeterminate PALF. In this group, a drug history was obtained in 325 (99%) urine toxicology screenings performed in 118 (36%) and acetaminophen level measured in 124 (38%) patients. No testing for common metabolic diseases was done in 179 (54%) patients. Anti-nuclear antibody, anti-smooth muscle antibody, and anti-liver kidney microsomal autoantibodies associated with autoimmunity were determined in 239 (73%), 233 (71%), and 208 (63%) patients, and no tests were obtained in 70 (21%). Testing was performed for hepatitis A virus, hepatitis B virus, and Epstein Barr virus in 80%, 86%, and 68%, respectively. Current practice indicates that investigation for metabolic and autoimmune causes of PALF are infrequent in patients ultimately given a diagnosis of indeterminate acute liver failure. This offers an opportunity to improve diagnosis and potential treatment options in children with acute liver failure.

  20. Whole Blood Polymerase Chain Reaction in a Neonate with Disseminated Herpes Simplex Virus Infection and Liver Failure

    Directory of Open Access Journals (Sweden)

    Jennifer A. Scoble

    2013-10-01

    Full Text Available A late preterm neonate born by cesarean section with intact membranes presented at 9 days of life with shock and liver failure. Surface cultures were negative but whole blood polymerase chain reaction was positive for herpes simplex virus type 2, underscoring the value of this test in early diagnosis of perinatally acquired disseminated herpes simplex virus infection without skin lesions.

  1. Experience of Treatments of Amanita phalloides-Induced Fulminant Liver Failure with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange.

    Science.gov (United States)

    Zhang, Jicheng; Zhang, Ying; Peng, Zhiyong; Maberry, Donald; Feng, Xueqiang; Bian, Pengfei; Ma, Wenjuan; Wang, Chunting; Qin, Chengyong

    2014-01-01

    Ingestion of the mushroom containing Amanita phalloides can induce fulminant liver failure and death. There are no specific antidotes. Blood purifications, such as molecular adsorbent recirculating system (MARS) and therapeutic plasma exchange (TPE), are potential therapies. However, the extent to which these technologies avert the deleterious effects of amatoxins remains controversial; the optimal intensity, duration, and initiation criteria have not been determined yet. This study aimed to retrospectively observe the effects of MARS and TPE on nine patients with A. phalloides-induced fulminant liver failure. The survival rate for the nine patients was 66.7%. Both TPE and MARS might remove toxins and improve liver functions. However, a single session of TPE produced immediately greater improvements in alanine aminotransferase (-60% vs. -16.3%), aspartate aminotransferase (-47.6% vs. -15.4%), and total bilirubin (-37.3% vs. -17.1%) (compared with the values of pretreatment, all p < 0.05) than MARS compared with MARS. Early intervention may be more effective than delayed therapy. Additionally, the presence of severe liver failure and renal failure indicated worse outcome. Although these findings are promising, additional case-controlled, randomized studies are required to confirm our results.

  2. The effect of fractionated plasma separation and adsorption on cerebral amino acid metabolism and oxidative metabolism during acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Frederiksen, Hans-Jørgen

    2012-01-01

    Patients with acute liver failure have a disturbed amino acid metabolism and a compromised oxidative metabolism in the brain. A limited number of clinically neuroprotective interventions are available. This study aimed at assessing the effect of fractionated plasma separation and adsorption (FPSA...

  3. Autophagy-Modulated Human Bone Marrow-Derived Mesenchymal Stem Cells Accelerate Liver Restoration in Mouse Models of Acute Liver Failure.

    Science.gov (United States)

    Amiri, Fatemeh; Molaei, Sedigheh; Bahadori, Marzie; Nasiri, Fatemeh; Deyhim, Mohammad Reza; Jalili, Mohammad Ali; Nourani, Mohammad Reza; Habibi Roudkenar, Mehryar

    2016-07-01

    Mesenchymal stem cells (MSCs) have been recently received increasing attention for cell-based therapy, especially in regenerative medicine. However, the low survival rate of these cells restricts their therapeutic applications. It is hypothesized that autophagy might play an important role in cellular homeostasis and survival. This study aims to investigate the regenerative potentials of autophagy-modulated MSCs for the treatment of acute liver failure (ALF) in mice. ALF was induced in mice by intraperitoneal injection of 1.5 ml/kg carbon tetrachloride. Mice were intravenously infused with MSCs, which were suppressed in their autophagy pathway. Blood and liver samples were collected at different intervals (24, 48 and 72 h) after the transplantation of MSCs. Both the liver enzymes and tissue necrosis levels were evaluated using biochemical and histopathological assessments. The survival rate of the transplanted mice was also recorded during one week. Biochemical and pathological results indicated that 1.5 ml/kg carbon tetrachloride induces ALF in mice. A significant reduction of liver enzymes and necrosis score were observed in autophagy-modulated MSC-transplanted mice compared to sham (with no cell therapy) after 24 h. After 72 h, liver enzymes reached their normal levels in mice transplanted with autophagy-suppressed MSCs. Interestingly, normal histology without necrosis was also observed. Autophagy suppression in MSCs ameliorates their liver regeneration potentials due to paracrine effects and might be suggested as a new strategy for the improvement of cell therapy in ALF.

  4. Inhibition of sphingosine kinase 1 ameliorates acute liver failure by reducing high-mobility group box 1 cytoplasmic translocation in liver cells.

    Science.gov (United States)

    Lei, Yan-Chang; Yang, Ling-Ling; Li, Wen; Luo, Pan; Zheng, Pei-Fen

    2015-12-14

    To determine the therapeutic potential of sphingosine kinase 1 (Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver failure (ALF). Balb/c mice were randomly assigned to different groups, with ALF induced by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot. The expression of Sphk1 in liver tissue and PBMCs was upregulated in GalN/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells, the resident macrophages of the liver. The survival rates of mice in the N,N-dimethylsphingosine (DMS, a specific inhibitor of SphK1) treatment group were significantly higher than that of the control group (P liver cells were significantly decreased in the DMS treatment group compared to the control group (43.72% ± 5.51% vs 3.57% ± 0.83%, χ(2) = 12.81, P liver cells, and so might be a potential therapeutic strategy for this disease.

  5. 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.

  6. Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing.

    Science.gov (United States)

    Suzuki, Takako; Kawada, Jun-Ichi; Okuno, Yusuke; Hayano, Satoshi; Horiba, Kazuhiro; Torii, Yuka; Takahashi, Yoshiyuki; Umetsu, Syuichiro; Sogo, Tsuyoshi; Inui, Ayano; Ito, Yoshinori

    2017-11-01

    Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. This finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Neuropsychological functioning and health-related quality of life: pediatric acute liver failure study group results.

    Science.gov (United States)

    Sorensen, Lisa G; Neighbors, Katie; Zhang, Song; Limbers, Christine A; Varni, James W; Ng, Vicky L; Squires, Robert H; Alonso, Estella M

    2015-01-01

    Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF. This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale. A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P = 0.009), but motor coordination was worse (P = 0.04). Teachers (P = 0.04 to P < 0.0001) and parents (P = 0.005) reported more executive deficits versus norms, and participants had worse attention (P = 0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P = 0.001 to P < 0.0001) and parent proxy report was lower on the fatigue scales (P = 0.001 to P < 0.0001). Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.

  8. Acute liver failure in a term neonate after repeated paracetamol administration

    Directory of Open Access Journals (Sweden)

    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.

  9. Acute liver failure in a term neonate after repeated paracetamol administration.

    Science.gov (United States)

    Bucaretchi, Fábio; Fernandes, Carla Borrasca; Branco, Maíra Migliari; De Capitani, Eduardo Mello; Hyslop, Stephen; Caldas, Jamil Pedro S; Moreno, Carolina Araújo; Porta, Gilda

    2014-03-01

    Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1 mEq/L), hypoglycemia (18 mg/dL), increased serum aminotransferase activity (AST=4,039 IU/L; ALT=1,087 IU/L) and hyperbilirubinemia (total: 9.57 mg/dL; direct: 6.18 mg/dL) after receiving oral paracetamol (10 mg/kg/dose every 4 hours) for three consecutive days (total dose around 180 mg/kg; serum concentration 36-48 hours after the last dose of 77 µg/ 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. 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.

  10. Pathophysiological central nervous system changes in a porcine model of acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Thiel, Christian; Lauber, Johannes; Klingert, Wilfried; Klingert, Kathrin; Morgalla, Matthias H; Beschorner, Rudi; Peter, Andreas; Grasshoff, Christian; Königsrainer, Alfred; Schenk, Martin; Thiel, Karolin

    2017-11-05

    Critical care management of patients suffering from acute liver failure (ALF) continues to be challenging. Animal models studying the pathophysiological central nervous system alterations during the course of ALF provide an opportunity to improve diagnostic and therapeutic strategies. The aim of this study was to analyse the course of cerebral oxygenation in addition to conventional neuromonitoring during the course of acetaminophen-induced ALF. ALF was induced by intrajejunal acetaminophen administration in 20 German landrace pigs. All animals underwent invasive hemodynamic and neuromonitoring and were maintained under standardized intensive care support. Neuromonitoring consisted of continuous intraparenchymatous recording of intracranial pressure and brain partial oxygen pressure. Hemodynamic and ventilation parameters were continuously recorded; laboratory parameters were analysed every eight hours. Mean values were compared using the Wilcoxon test. Acute liver failure occurred in all intoxicated animals after 23±2h, resulting in death due to ALF after further 15±2h. Continuous neuromonitoring was performed in all animals during the whole experiment without observing signs of intracranial haemorrhage. Two hours after manifestation of ALF an increase in brain tissue oxygen (PtiO2) was observed. Brain oxygenation stayed stable until nine hours before death. Intracranial pressure (ICP) remained basically at a plateau level until manifestation of ALF. In the following ten hours a linear and slow increase was observed until five hours before death, followed by a fast and continuous rise in ICP to a final level of 35±1mmHg. Cerebral perfusion pressure (CPP) began to decrease 25h prior to exitus, further decreasing to 18±2mmHg at the end of the experiment. A strong negative linear correlation was found between PtiO2 and ICP (R=0.97). Arterial partial pressure of oxygen (PaO2) below 100mmHg was associated with lower PtiO2 levels. Changes in arterial partial

  11. TAFI deficiency promotes liver damage in murine models of liver failure through defective down-regulation of hepatic inflammation

    NARCIS (Netherlands)

    Hugenholtz, Greg C. G.; Meijers, Joost C. M.; Adelmeijer, Jelle; Porte, Robert J.; Lisman, Ton

    Emerging evidence indicates that various haemostatic components can regulate the progression of liver disease. Thrombin-activatable fibrinolysis inhibitor (TAFI) possesses anti-inflammatory properties besides its anti-fibrinolytic function. Here, we investigated the contribution of TAFI to the

  12. Efficacy of a chronic disease management model for patients with chronic liver failure.

    Science.gov (United States)

    Wigg, Alan J; McCormick, Rosemary; Wundke, Rachel; Woodman, Richard J

    2013-07-01

    Despite the economic impacts of chronic liver failure (CLF) and the success of chronic disease management (CDM) programs in routine clinical practice, there have been no randomized controlled trials of CDM for CLF. We investigated the efficacy of CDM programs for CLF patients in a prospective, controlled trial. Sixty consecutive patients with cirrhosis and complications from CLF were assigned randomly to groups given intervention (n = 40) or usual care (n = 20), from 2009 to 2010. The 12-month intervention comprised 4 CDM components: delivery system redesign, self-management support, decision support, and clinical information systems. The primary outcome was the number of days spent in a hospital bed for liver-related reasons. Secondary outcomes were rates of other hospital use measures, rate of attendance at planned outpatient care, disease severity, quality of life, and quality of care. The intervention did not reduce the number of days patients spent in hospital beds for liver-related reasons, compared with usual care (17.8 vs 11.0 bed days/person/y, respectively; incidence rate ratio, 1.6; 95% confidence interval, 0.5-4.8; P = .39), or affect other measures of hospitalization. Patients given the intervention had a 30% higher rate of attendance at outpatient care (incidence rate ratio, 1.3; 95% confidence interval, 1.1-1.5; P = .004) and significant increases in quality of care, based on adherence to hepatoma screening, osteoporosis and vaccination guidelines, and referral to transplant centers (P < .05 for all). In a pilot study to determine the efficacy of CDM for patients with CLF, patients receiving CDM had significant increases in attendance at outpatient centers and quality of care, compared with patients who did not receive CDM. However, CDM did not appear to reduce hospital admission rates or disease severity or improve patient quality of life. Larger trials with longer follow-up periods are required to confirm these findings and assess cost

  13. Changes in cellular proliferation and plasma products are associated with liver failure

    Institute of Scientific and Technical Information of China (English)

    Juliana; Gil; Melga?o; Frederico; Marianetti; Soriani; Pedro; Henrique; Ferreira; Sucupira; Leonardo; Assaf; Pinheiro; Yasmine; Rangel; Vieira; Jaqueline; Mendes; de; Oliveira; Lia; Laura; Lewis-Ximenez; Cristina; Carvalho; Vianna; Araújo; Lúcio; Filgueiras; Pacheco-Moreira; Gustavo; Batista; Menezes; Oswaldo; Gon?alves; Cruz; Claudia; Lamarca; Vitral; Marcelo; Alves; Pinto

    2016-01-01

    AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute hepatitis.METHODS Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTS The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death (mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027)In the cellular proliferation assay, NKbright, NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be

  14. Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats.

    Science.gov (United States)

    Matsushita, Yoshihiro; Ishigami, Masatoshi; Matsubara, Kohki; Kondo, Megumi; Wakayama, Hirotaka; Goto, Hidemi; Ueda, Minoru; Yamamoto, Akihito

    2017-06-01

    In acute liver failure (ALF), a poorly controlled innate immune response causes massive hepatic destruction, which elicits a systemic inflammatory response, progressive multiple organ failure and ultimate sudden death. Although the liver has inherent tissue-repairing activities, its regeneration during ALF fails, and orthotopic liver transplantation is the only curative approach. Here we show that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) into the d-galactosamine-induced rat model of ALF markedly improved the condition of the injured liver and the animals' survival rate. The engraftment of infused SHEDs was very low, and both SHEDs and SHED-CM exerted similar levels of therapeutic effect, suggesting that the SHEDs reversed ALF by paracrine mechanisms. Importantly, SHED-CM attenuated the ALF-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, which was accompanied by the induction of anti-inflammatory M2-like hepatic macrophages. Secretome analysis by cytokine antibody array revealed that the SHED-CM contained multiple tissue-regenerating factors with known roles in anti-apoptosis/hepatocyte protection, angiogenesis, macrophage differentiation and the proliferation/differentiation of liver progenitor cells. Taken together, our findings suggest that SHEDs produce factors that provide multifaceted therapeutic benefits for AFL. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Expert beliefs regarding novel lipid-based approaches to pediatric intestinal failure-associated liver disease.

    Science.gov (United States)

    Diamond, Ivan R; Grant, Robert C; Feldman, Brian M; Tomlinson, George A; Pencharz, Paul B; Ling, Simon C; Moore, Aideen M; Wales, Paul W

    2014-08-01

    To determine expert beliefs regarding the probability of intestinal failure-associated liver disease (IFALD) with novel lipid-based approaches (lipid minimization/ω-3 lipids) in managing IFALD to facilitate Bayesian analyses of clinical trials of these therapies. Structured interviews were conducted using a validated approach to belief elicitation with 60 intestinal failure (IF) experts from across North America. Participants were asked to estimate, in an average population of infants referred for management of IF with early IFALD, the probability of advanced IFALD at 3 months following referral in each of 3 scenarios: (1) conventional lipid, (2) ω-3 lipids, and (3) lipid minimization. Probability distributions of the risk of advanced IFALD with each strategy were developed. Distributions of the elicited treatment effect for the novel approaches, relative to conventional lipid, were calculated. Median duration of experience of participants managing patients with IF was 8.5 (range, 2-35) years. The median probability of advanced IFALD using conventional lipid was 32.5%; ω-3 lipids, 17.5%; and lipid minimization, 13%. The median of the elicited treatment effects relative to conventional lipid was a relative risk of 0.53 for the ω-3 lipid and 0.45 for lipid minimization. There was consistent expert opinion that the novel lipid-based approaches are superior to conventional therapy, with similar estimates of treatment efficacy for the 2 approaches. The distributions of the elicited treatment effects can be used as prior distributions in Bayesian analyses of clinical trials of these novel strategies. © 2013 American Society for Parenteral and Enteral Nutrition.

  16. Effect of bone marrow mesenchymal stem cells transplantation on the serum and liver HMGB1 expression in rats with acute liver failure.

    Science.gov (United States)

    Zheng, Sheng; Yang, Juan; Tang, Yingmei; Yang, Jinhui; Shao, Qinghua; Guo, Ling; Liu, Qinghua

    2015-01-01

    This study aimed to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of high mobility group box 1 protein (HMGB1) in the serum and liver of rats with acute liver failure (ALF). Healthy male SD rats were randomly divided into control group, ALF group and BMSCs group. ALF was induced by intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS. In BMSCs group, rats received BMSCs (1.0×10(7)) transplantation via the tail vein at 2 h after ALF induction. Intraperitoneal injection of 900 mg/kg D-GalN and 10 μg/kg LPS was able to induce ALF in rats. In ALF group, serum ALT and AST increased gradually over time. At 72 h, the serum ALT and AST in BMSCs group were significantly different from those in ALF group. HMGB1 expression in the serum and liver remained at a low level at any time point in control group, but increased significantly in ALF group and BMSCs group. The serum and liver HMGB1 expression increased progressively in ALF group, but reduced gradually in BMSCs group. Significant difference in serum and liver HMGB1 expression was observed between ALF group and BMSCs group at 24 h and 72 h. In addition, there was marked difference in the survival rate among three groups at 24 h (χ (2) =21.098, Pliver function and liver pathology in ALF rats and decrease the serum and liver HMGB1.

  17. Isoniazid-Induced Severe Hepatotoxicity: An Infrequent but Preventable Cause of Liver Failure in Children Treated for Latent Tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Dan Desrochers

    2011-01-01

    Full Text Available Isoniazid (INH monotherapy has gained widespread acceptance as an efficacious therapy for latent tuberculosis infection (LTBI especially in low-prevalence settings. Although INH related hepatotoxicity is well recognized, progression to severe liver dysfunction requiring care at a transplant center remains unpredictable. We report the management of a five year-old girl who developed progressive liver failure due to INH prophylaxis. This highlights the potential severity of INH related hepatic injury and underscores the significance of vigilant clinical monitoring throughout the duration of the therapy in children.

  18. Hepatitis E Virus Induced Acute Liver Failure with Scrub Typhus Coinfection in a Pregnant Woman.

    Science.gov (United States)

    Verma, Nipun; Sharma, Megha; Biswal, Manisha; Taneja, Sunil; Batra, Nitya; Kumar, Abhay; Dhiman, Radha K

    2017-06-01

    Coinfections contribute significantly to diagnostic challenges of acute febrile illnesses, especially in endemic areas. The confusion caused by overlapping clinical features impedes timely management. Herein, we report an unusual, previously unreported case of a pregnant woman suffering from a coinfection of scrub typhus and hepatitis E virus. A 25-year-old, 31-week pregnant woman presented with jaundice for 5 days and altered sensorium for 2 days. She had features of both viral acute liver failure (ALF) and tropical infections mimicking ALF, including hyperbilirubinemia, coagulopathy, anemia, thrombocytopenia, intravascular hemolysis, and hepatosplenomegaly. Etiological workup revealed rare coinfection of hepatitis E and scrub typhus. Despite all supportive measures, the patient succumbed to her illness (i.e., absent brainstem reflexes and intracranial bleed secondary to coagulopathy) and had poor fetal outcome, which resulted in stillbirth. ALF in a pregnant woman is a medical and obstetric emergency. It can result from varied etiologies that though differ in their incidence, mode of occurrence, and pregnancy outcome, can clinically masquerade as each other, causing diagnostic dilemma. This unusual case report highlights the significance of keeping all such possibilities in mind while managing a pregnant woman with ALF, especially in a country like India where maternal and perinatal mortality rates, the core indicators of national health, are still among the highest in the world.

  19. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P.N.; Hauerberg, J.; Frederiksen, Hans-Jørgen

    2008-01-01

    AIM: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated...... with a rise in the glutamine concentration and ICP. PATIENTS AND METHODS: In 13 patients with ALF (8F/5M; median age 46 (range 18-66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion...... pressure (CPP). RESULTS: The cerebral glutamine concentration was 4,396 (1,011-9,712) microM, lactate 2.15 (1.1-4.45) mM, and pyruvate 101 (43-255) microM. The lactate-pyruvate ratio was 21 (16-40), ICP 20 (2-28) mmHg, and CPP 72 (56-115) mmHg. Cerebral glutamine concentration correlated with the lactate...

  20. Lactate and Lactate: Pyruvate Ratio in the Diagnosis and Outcomes of Pediatric Acute Liver Failure.

    Science.gov (United States)

    Feldman, Amy G; Sokol, Ronald J; Hardison, Regina M; Alonso, Estella M; Squires, Robert H; Narkewicz, Michael R

    2017-03-01

    To assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P  ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days. Retrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day. Of 986 participants, 110 had lactate and pyruvate levels collected on the same day. Of the 110, the etiology of PALF was a mitochondrial disorder in 8 (7%), indeterminate in 65 (59%), and an alternative diagnosis in 37 (34%). Lactate, pyruvate, and L:P were similar among the 3 etiologic groups. There was no significant association between the initial lactate or L:P and biochemical variables of clinical severity or clinical outcome at 21 days. A serum lactate ≥ 2.5 mmol/L and/or elevated L:P was common in all causes of PALF, not limited to those with a mitochondrial etiology, and did not predict 21-day clinical outcome. ClinicalTrials.gov: NCT00986648. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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

  2. [Predictive value of pediatrics end-stage liver disease or model for end-stage liver disease score in the prognosis of pediatric acute liver failure treated with artificial liver support system].

    Science.gov (United States)

    Jinhao, Tao; Weiming, Chen; Jing, Hu; Jun, He; Jian, Ma; Peng, Shi; Zhujin, Lu; Guoping, Lu; Yimin, Zhu

    2015-04-01

    To investigate the predictive value of pediatrics end-stage liver disease (PELD) or the model for end-stage liver disease (MELD) in the prognosis of pediatric acute liver failure (PALF) treated with artificial liver support system (ALSS). The clinical data of 47 children with acute liver failure seen from August 2008 to July 2013 treated in Children's Hospital, Fudan University were analyzed. Thirty children were treated with ALSS in addition to conventional comprehensive medical treatment (ALSS group). Seventeen children were treated with only conventional comprehensive medical treatment (control group). The main biochemical parameters and coagulation function parameters before and after treatment were compared in the ALSS group and the mortality rates were compared between the two groups. The patients were graded by PELD or MELD when they were hospitalized and the relationship of PELD or MELD scores and mortalities of child patients with the receiver operating characteristic curve (ROC) were analyzed. There were significant differences in total bilirubin (TB) ((302 ± 208) vs. (161 ± 129) µmol/L); alanine aminotransferase (ALT) ((161 ± 225) vs. (761 ± 834) U/L); aspartate aminotransferase ( AST) (66 (35, 123 ) vs. 447 (184, 1,129 ) U/L) ; international normalized ratio (INR) ((2.6 ± 1.6) vs. (5.1 ± 4.0)); prothrombin time activity percentage (PTA) ((42 ± 25)% vs. (22 ± 13)%); albumin( ALB) ((35 ± 5) vs. (33 ± 6) g/L) in the ALSS group after treatment. Through the ROC curve analysis, the best PELD/MELD threshold was 25 to predict the patients survival after ALSS therapy, with a sensitivity of 92. 3% , and a specificity of 94.1% at the cutoff point. The area under the ROC curve was 0. 912. The mortality of patients with PELD or MELD score below 25 in the ALSS group (1/13) was lower than the control group (3/4) (P = 0.022), and the mortality of patients with PELD or MELD score over 25 (16/17) was higher than that of the control group (10/13) (P = 0

  3. [Breast Cancer with Multiple Liver Metastases Successfully Treated with Capecitabine Monotherapy after Failure of Combination Therapy Comprising Bevacizumab and Paclitaxel].

    Science.gov (United States)

    Ooe, Asako; Suganuma, Yasushi

    2016-03-01

    We report a case of breast cancer with multiple liver metastases successfully treated with capecitabine monotherapy after failure of combination therapy comprising bevacizumab (Bev) and paclitaxel (PTX). In March 2012, a 67-year-old woman was diagnosed with Stage IV breast cancer with massive pleural effusion. Histological examination showed invasive ductal carcinoma (scirrhous carcinoma) that was positive for hormonal receptor but negative for HER2 expression, and the nuclear grade was 1. She first received chemotherapy to decrease the tumor volume followed by hormonal therapy. After progression, imaging studies showed increased multiple lung and liver metastases and pleural effusion. Subsequently, treatment with combination of Bev and PTX was started from July 2014. After 4 courses of the combination therapy, multiple liver metastases were unchanged, but her liver function was impaired. Hence, she received capecitabine monotherapy (1,800 mg bis in die [BID]; 2-week administration followed by a week of rest). Her liver function improved early, and a partial response (PR) in the multiple liver metastases was achieved 3 months after initiation of therapy. Furthermore, the metastatic lesions were well controlled 4 months later. These findings suggest that the sensitivity to an anticancer agent greatly varies among patients.

  4. Platelet count is more useful for predicting posthepatectomy liver failure at surgery for hepatocellular carcinoma than indocyanine green clearance test.

    Science.gov (United States)

    Tomimaru, Yoshito; Eguchi, Hidetoshi; Gotoh, Kunihito; Kawamoto, Koichi; Wada, Hiroshi; Asaoka, Tadafumi; Noda, Takehiro; Yamada, Daisaku; Ogawa, Hisataka; Umeshita, Koji; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki

    2016-04-01

    Preoperatively evaluating reserved liver function is critical in preventing posthepatectomy liver failure (PHLF) in patients undergoing liver resection. The commonly used indocyanine green (ICG) clearance test has several drawbacks. Patients would benefit from a more reliable and straightforward means of assessing the risk of PHLF. This study included 277 patients with hepatocellular carcinoma (HCC) undergoing liver resection. The predictive value of known risk factors for PHLF was compared to that of ICG. PHLF was identified in 25 out of 277 patients (9.0%). Multivariate logistic regression analysis for identifying predictors for the PHLF development revealed platelet count and resected liver volume as significant independent predictors. In a subgroup analysis based on resected liver volume, platelet count was significantly correlated with PHLF in both larger volume (≥100 g) and smaller volume resection groups (<100 g), although ICG R15 level was associated with PHLF only in larger volume group. Platelet count is superior to ICG R15 level in predicting PHLF development in HCC patients. J. Surg. Oncol. 2016;113:565-569. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Valproic acid-associated acute liver failure in children: case report and analysis of liver transplantation outcomes in the United States.

    Science.gov (United States)

    Mindikoglu, Ayse L; King, Dale; Magder, Laurence S; Ozolek, John A; Mazariegos, George V; Shneider, Benjamin L

    2011-05-01

    To determine whether valproic acid (VPA)-associated acute liver failure (ALF; VPA-ALF) explains the poor outcomes after liver transplantation (LT) in children. Organ Procurement and Transplantation Network data of pediatric patients who underwent LT for VPA-ALF and ALF caused by other drugs (non-VPA-drug-induced acute liver failure [DIALF]) were analyzed. Pre- and post-transplant variables and post-LT survival were compared between VPA-ALF and non-VPA-DIALF. Seventeen children were transplanted for VPA-ALF. Of the 17 children, 82% died within 1 year of LT. Pre- and post-transplant parameters of VPA versus non-VPA-DIALF were comparable with two exceptions. The median alanine aminotransferase level at transplant was remarkably lower in VPA-ALF compared with non-VPA-DIALF (45 versus 1179 IU/L, P = .004). One-year survival probability was worse in VPA-ALF than non-VPA-DIALF (20% versus 69%, P < .0001). Median post-LT survival time for VPA-ALF was 2.8 months. Children who underwent LT for VPA-ALF had a significantly lower survival probability than children with non-VPA-DIALF. Current data suggest that VPA-ALF in children represents an "unmasking" of mitochondrial disease. VPA-ALF should be a contraindication for LT, even in the absence of a documented mitochondrial disease. Copyright © 2011 Mosby, Inc. All rights reserved.

  6. Utility of Aminotransferase/Platelet Ratio Index to Predict Liver Fibrosis in Intestinal Failure-Associated Liver Disease in Pediatric Patients.

    Science.gov (United States)

    Rumbo, Carolina; Martinez, María Inés; Cabanne, Ana; Trentadue, Julio; Fernández, Adriana; Gondolesi, Gabriel

    2017-07-01

    Intestinal failure-associated liver disease (IFALD) is a frequent indication for intestinal transplantation. Liver biopsy (LBX) is the gold standard test for its diagnosis. Identifying noninvasive markers of fibrosis progression would be of considerable clinical use. Aspartate aminotransferase/platelet ratio index (APRI) has a good correlation in adult patients with chronic liver disease; few studies have been performed in children with IFALD. To evaluate APRI in a cohort of children with IFALD. Retrospective analysis of a prospective database of patients failure and at least 1 LBX, registered in our unit from March 2006 to December 2014. Forty-nine LBX were done on 36 patients: 20 were male, and 31 had short gut. Fibrosis was found in 71% of LBX. Biopsies were grouped according to the fibrosis stage (METAVIR [M]): (1) group 1 (G1) LBX with M 0, 1, 2 (n = 33) and (2) group 2 (G2) LBX with M 3, 4 (n = 16). The median APRI score was 0.92 (interquartile range [IQR] 0.63-1.50) for G1 and 2.50 (IQR 1.81-5.82) for G2 ( P = .001) The c statistic of the receiving operating characteristic curve was 0.79 (95% CI 0.64-0.94; P 1.6 correlates with advanced fibrosis.

  7. Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

    Directory of Open Access Journals (Sweden)

    Cao Hongcui

    2012-06-01

    Full Text Available Abstract Background Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF. Methods hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis. Results hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig

  8. Usefulness of liver test and controlled attenuation parameter in detection of nonalcoholic fatty liver disease in patients with chronic renal failure and coronary heart disease.

    Science.gov (United States)

    Mikolasevic, Ivana; Orlic, Lidija; Zaputovic, Luka; Racki, Sanjin; Cubranic, Zlatko; Anic, Kata; Devcic, Bosiljka; Stimac, Davor

    2015-06-01

    In recent years, nonalcoholic fatty liver disease (NAFLD) was recognized as an important factor in chronic kidney disease (CKD) pathogenesis. The concentrations of serum aminotransferases in both chronic dialysis and chronic renal failure (CRF) patients most commonly fall within the lower end of the range of normal values. The aim of the present study was to investigate the usefulness of four liver tests and four biological scores in detection of NAFLD in comparison with transient elastography (TE) findings in different groups of patients. The study was cross-sectional analysis collected data from a single tertiary care center. Of 202 patents there were 52 patients with CKD, 50 patients with end-stage renal disease (ESRD) treated with haemodialysis (HD), 50 renal transplant recipients (RTRs) and 50 patients with proven coronary heart disease (CHD). Fifty sex- and age-matched individuals without NAFLD and with normal liver and kidney function tests served as controls. With the help of TE (FibroScan®, Echosense SA, Paris, France), liver stiffness was selected as the parameter to quantify liver fibrosis and Controlled Attenuation Parameter (CAP) was used to detect and quantify liver steatosis. According to the CAP findings 76.9 %CKD patients, 82 %HD patients, 74 %RTRs and 69.1 % CHD patients had CAP > 238 dB.m(-1) and thus by definition NAFLD. We have found that ALT, AST and GGT levels were positively correlated with CAP values while ALT and AST showed positive correlation with liver stiffness acquired with TE only in CHD patients. According to TE findings APRI (AUC 0.796) and FIB-4 (AUC 0.790) scores were correlated with the presence of fibrosis, while HIS score was correlated with the presence of steatosis (AUC 0.867) only in CHD patients. Liver tests and biological scores are not useful for NAFLD detection in CRF patients. TE with CAP provides the opportunity of noninvasive screening for NAFLD as well as liver fibrosis in patients with CRF.

  9. Evaluating the best time to intervene acute liver failure in rat models induced by d-galactosamine.

    Science.gov (United States)

    Éboli, Lígia Patrícia de Carvalho Batista; Netto, Alcides Augusto Salzedas; Azevedo, Ramiro Antero de; Lanzoni, Valéria Pereira; Paula, Tatiana Sugayama de; Goldenberg, Alberto; Gonzalez, Adriano Miziara

    2016-12-01

    To describe an animal model for acute liver failure by intraperitoneal d-galactosamine injections in rats and to define when is the best time to intervene through King's College and Clichy´s criteria evaluation. Sixty-one Wistar female rats were distributed into three groups: group 1 (11 rats received 1.4 g/kg of d-galactosamine intraperitoneally and were observed until they died); group 2 (44 rats received a dose of 1.4 g/kg of d-galactosamine and blood and histological samples were collected for analysis at 12 , 24, 48 , 72 and 120 hours after the injection); and the control group as well (6 rats) . Twelve hours after applying d-galactosamine, AST/ALT, bilirubin, factor V, PT and INR were already altered. The peak was reached at 48 hours. INR > 6.5 was found 12 hours after the injection and factor V acute liver failure animal model.

  10. Effect of noninvasive mechanical ventilation in elderly patients with hypercapnic acute-on-chronic respiratory failure and a do-not-intubate order

    OpenAIRE

    Incorvaia, Cristoforo

    2008-01-01

    Paolo Scarpazza1, Cristoforo Incorvaia2, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Silvia Vanni1, Serena Bencini1, Chiara Pravettoni2, Giuseppe Di Cara3, Mona-Rita Yacoub4, Gian Galeazzo Riario-Sforza2, Enrico Guffanti5, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3University Department of Medical and...

  11. AMPK activation ameliorates D-GalN/LPS-induced acute liver failure by upregulating Foxo3A to induce autophagy.

    Science.gov (United States)

    Liu, Yan-Min; Lv, Jun; Zeng, Qing-Lei; Shen, Shen; Xing, Ji-Yuan; Zhang, Ying-Ying; Zhang, Zhi-Hao; Yu, Zu-Jiang

    2017-09-15

    Acute liver failure (ALF) is an uncommon but serious disease still carrying a high mortality. This study aimed to investigate the mechanism of AMPK on D-GalN/LPS-induced ALF. In this study, we utilized intraperitoneal injection of D-GalN/LPS to induce ALF model, and analyzed the expression of AMPK, inflammatory cytokines (TNF-α, IL-1β and IL-6), Foxo3A and autophagy-related genes (Atg-5, Beclin-1, Atg-7) by real-time quantitative polymerase chain reaction (RT-PCR) in liver tissue. We also examined the level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of ALF mice. AMPK activation and inhibition of autophagy were induced by AICAR and 3-MA, respectively. Silence and overexpression of Foxo3A were performed by si-Foxo3A and pcDNA-Foxo3A, respectively. Lastly, the BMDM-conditioned medium (BMDM-CM) derived from BMDMs treated with AICAR and LPS were used to explore the effect of AMPK and Foxo3A on hepatocytes. The expression of AMPK was decreased in liver tissue and the level of ALT and AST were increased in serum of D-GalN/LPS-induced ALF mice. AMPK activation ameliorated ALF by inhibiting inflammation (downregulated TNF-α, IL-1β and IL-6 expression), activating autophagy (increased Atg-5, Beclin-1 and Atg-7 expression) and upregulating Foxo3A expression. Silence of Foxo3A decreased AMPK-activated autophagy, but overexpressing Foxo3A attenuated liver failure by activating autophagy. In addition, AMPK activation alleviated liver failure in vitro. Thus, AMPK/Foxo3A/autophagy pathway may be an effective treatment approach to ameliorate ALF. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  13. Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: a placebo-controlled clinical trial.

    Science.gov (United States)

    Squires, Robert H; Dhawan, Anil; Alonso, Estella; Narkewicz, Michael R; Shneider, Benjamin L; Rodriguez-Baez, Norberto; Olio, Dominic Dell; Karpen, Saul; Bucuvalas, John; Lobritto, Steven; Rand, Elizabeth; Rosenthal, Philip; Horslen, Simon; Ng, Vicky; Subbarao, Girish; Kerkar, Nanda; Rudnick, David; Lopez, M James; Schwarz, Kathleen; Romero, Rene; Elisofon, Scott; Doo, Edward; Robuck, Patricia R; Lawlor, Sharon; Belle, Steven H

    2013-04-01

    N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (P = 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (P = 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%; P = 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE. NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those pediatric drug trials, regardless of results in adults. Copyright © 2012 American Association for the Study of Liver Diseases.

  14. Prognostic value of (13)C-phenylalanine breath test on predicting survival in patients with chronic liver failure.

    Science.gov (United States)

    Gallardo-Wong, I; Morán, S; Rodríguez-Leal, G; Castañeda-Romero, B; Mera, R; Poo, J; Uribe, M; Dehesa, M

    2007-09-14

    To evaluate the prognostic value of percentage of (13)C-phenylalanine oxidation ((13)C-PheOx) obtained by (13)C-phenylalanine breath test ((13)C-PheBT) on the survival of patients with chronic liver failure. The hepatic function was determined by standard liver blood tests and the percentage of (13)C-PheOx in 118 chronic liver failure patients. The follow-up period was of 64 mo. Survival analysis was performed by the Kaplan-Meier method and variables that were significant (P < 0.10) in univariate analysis and subsequently introduced in a multivariate analysis according to the hazard model proposed by Cox. Forty-one patients died due to progressive liver failure during the follow-up period. The probability of survival at 12, 24, 36, 48 and 64 mo was 0.88, 0.78, 0.66, 0.57 and 0.19, respectively. Multivariate analysis demonstrated that Child-Pugh classes, age, creatinine and the percentage of (13)C-PheOx (HR 0.338, 95% CI: 0.150-0.762, P = 0.009) were independent predictors of survival. When Child-Pugh classes were replaced by all the parameters of the score, only albumin, bilirubin, creatinine, age and the percentage of (13)C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival. Percentage of (13)C-PheOx obtained by (13)C-PheBT is a strong predictor of survival in patients with chronic liver disease.