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Sample records for a-induced liver failure

  1. Immune mediated liver failure

    PubMed Central

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of “immune coagulation”, which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure. PMID:26417328

  2. Acute liver failure in children.

    PubMed

    Devictor, Denis; Tissieres, Pierre; Afanetti, Mickael; Debray, Dominique

    2011-06-01

    The management of children with acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but clinical studies have mainly concerned adult patients. There are no specific medical therapies, except for a few metabolic diseases presenting with acute liver failure. Liver transplantation still remains the only definitive therapy in most instances. Recent clinical studies suggest that hepatocyte transplantation may be useful for bridging patients to liver transplantation, for providing metabolic support during liver failure and for replacing liver transplantation in certain metabolic liver diseases.

  3. The role of intracellular high-mobility group box 1 in the early activation of Kupffer cells and the development of Con A-induced acute liver failure.

    PubMed

    Yang, Qiao; Liu, Yanning; Shi, Yu; Zheng, Min; He, Jiliang; Chen, Zhi

    2013-10-01

    Acute liver failure (ALF) is a highly complex syndrome characterized by devastating activation of early activation of Kupffer cells (KCs) has been implicated in the pathogenesis of ALF. However, the factors regulating KC early activation are virtually unexplored. The aim of present study was to determine the role of the intracellular high-mobility group box 1 (HMGB1) in modulating the early activation of KCs during ALF. The intravenous injection of Concanavalin A (Con A) was used to establish a mouse model of ALF. The dynamic pro-inflammatory properties and MHC II expression of KCs were measured by qRT-PCR and flow cytometry. HMGB1 expression in KCs was measured by qRT-PCR and Western blotting. The immunofluorescence was implemented to determine the relocation of HMGB1 in KCs, and the siRNA against HMGB1 was utilized to assess the impact of HMGB1 on KC pro-inflammatory properties. The peak of pro-inflammatory cytokines production and MHC II expression in KCs appeared at the early stage of ALF. The up-regulation of HMGB1 expression and the translocation of HMGB1 in KCs were in parallel with the early activation of KCs. The blockade of intracellular HMGB1 expression caused by siRNA significantly inhibited the production of KC-derived pro-inflammatory cytokines, and led to a down-regulation of MAP kinase activation in KCs. The self-derived HMGB1 is an "early alarmin" of KC activation during Con A-induced ALF. HMGB1 might be a potential target for cell-specific strategy in ALF.

  4. Liver transplantation in acute-on-chronic liver failure: lessons learnt from acute liver failure setting.

    PubMed

    Reddy, Mettu Srinivas; Rajalingam, Rajesh; Rela, Mohamed

    2015-10-01

    Acute-on-chronic liver failure is a clinical entity with high risk of mortality. These patients can have severe liver dysfunction complicated with multiple organ failure. Liver transplantation is the definitive treatment for these patients. Literature regarding management of acute liver failure with special emphasis on liver transplantation was reviewed. Lessons learnt from the management of patients with acute liver failure which could be extrapolated to the management of patients with acute-on-chronic liver failure are discussed. Significant improvement in outcomes of acute liver failure has been reported across the world. Several aspects in transplantation for acute liver failure were found to be relevant to the management of acute-on-chronic liver failure. These include defining criteria to identify patients needing early liver transplantation, prioritizing patients with acute liver failure on the waiting list, defining when to abandon transplantation in acute liver failure, emphasis on graft quality and the need for a multi-disciplinary approach to manage multiple organ dysfunction. Useful lessons can be learnt from the progress made in the management of acute liver failure and these can be extrapolated to the management of patients with acute-on-chronic liver failure. PMID:25788191

  5. Acute liver failure.

    PubMed

    Slack, Andy; Wendon, Julia

    2011-06-01

    ALF is a multisystem disorder necessitating both predictive and reactive management strategies to support and protect organs from the initial and subsequent insults encountered. Early referral to a specialist liver centre with the option of liver transplantation is recommended. Furthermore, a good understanding of the poor prognostic variables is necessary to determine those most at risk of developing ALF in order to facilitate timely, safe transfer and listing for liver transplantation. PMID:21902079

  6. Acute liver failure and liver transplantation.

    PubMed

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2013-08-01

    Acute liver failure (ALF) is defined by the presence of coagulopathy (International Normalized Ratio ≥ 1.5) and hepatic encephalopathy due to severe liver damage in patients without pre-existing liver disease. Although the mortality due to ALF without liver transplantation is over 80%, the survival rates of patients have considerably improved with the advent of liver transplantation, up to 60% to 90% in the last two decades. Recent large studies in Western countries reported 1, 5, and 10-year patient survival rates after liver transplantation for ALF of approximately 80%, 70%, and 65%, respectively. Living donor liver transplantation (LDLT), which has mainly evolved in Asian countries where organ availability from deceased donors is extremely scarce, has also improved the survival rate of ALF patients in these regions. According to recent reports, the overall survival rate of adult ALF patients who underwent LDLT ranges from 60% to 90%. Although there is still controversy regarding the graft type, optimal graft volume, and ethical issues, LDLT has become an established treatment option for ALF in areas where the use of deceased donor organs is severely restricted. PMID:25343108

  7. Post-hepatectomy liver failure

    PubMed Central

    Kauffmann, Rondi

    2014-01-01

    Hepatectomies are among some of the most complex operative interventions performed. Mortality rates after major hepatectomy are as high as 30%, with post-hepatic liver failure (PHLF) representing the major source of morbidity and mortality. We present a review of PHLF, including the current definition, predictive factors, pre-operative risk assessment, techniques to prevent PHLF, identification and management. Despite great improvements in morbidity and mortality, liver surgery continues to demand excellent clinical judgement in selecting patients for surgery. Appropriate choice of pre-operative techniques to improve the functional liver remnant (FLR), fastidious surgical technique, and excellent post-operative management are essential to optimize patient outcomes. PMID:25392835

  8. Protective effects of alpha1-acid glycoprotein and serum amyloid A on concanavalin A-induced liver failure via interleukin-6 induction by ME3738.

    PubMed

    Kuzuhara, Hiroyuki; Nakano, Yoshihisa; Yamashita, Nobuyuki; Imai, Masako; Kawamura, Yuji; Kurosawa, Tohru; Nishiyama, Shoji

    2006-07-17

    We examined whether the 22beta-methoxyolean-12-ene-3beta,24(4beta)-diol (ME3738)-mediated selective induction of interleukin-6 increased alpha1-acid glycoprotein and serum amyloid A expression, and whether these proteins protected against liver injury in vitro and in vivo. ME3738 treatment in male mice increased gene expression of alpha1-acid glycoprotein subtypes and serum amyloid A 2 genes, and plasma concentration of serum amyloid A. Treatment with alpha1-acid glycoprotein at 5 mg/animal or serum amyloid A at 0.03 and 0.1 mg/animal prior to concanavalin A administration reduced multifocal necrosis in the liver. Treatment with alpha1-acid glycoprotein and serum amyloid A, but not alpha1-antitrypsin, protected Hep G2 cells against cell injury. These results suggest that alpha1-acid glycoprotein and serum amyloid A, increased by ME3738-induced interleukin-6, might protect against concanavalin A-induced liver injury. PMID:16765939

  9. Plasma Glutamine Concentrations in Liver Failure

    PubMed Central

    Helling, Gunnel; Wahlin, Staffan; Smedberg, Marie; Pettersson, Linn; Tjäder, Inga; Norberg, Åke; Rooyackers, Olav; Wernerman, Jan

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:26938452

  10. Nutritional support during liver failure.

    PubMed

    Gecelter, G R; Comer, G M

    1995-07-01

    Critically ill patients in varying degrees of liver failure are catabolic and consequently require expeditious caloric support. Unique problems in this group of patients essentially revolve around the diagnosis and management of hepatic encephalopathy. From the overview provided in this text, it can be concluded that, only in overt hepatic coma, should all nitrogen products be withheld while precipitating causes are evaluated. Protein should be reintroduced as rapidly as possible to avoid the consequences of protein deprivation. Once the acute intercurrent illness has resolved, the cirrhotic patient returns to baseline energy and protein requirements indistinguishable from the population at large. PMID:7552976

  11. Acute liver failure and self-medication

    PubMed Central

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

    2014-01-01

    Introduction Not responsible self-medication refers to drug use in high doses without rational indication and often associated with alcohol abuse. It can lead to liver damage and drug interactions, and may cause liver failure. Aim To warn about how the practice of self-medication can be responsible for acute liver failure. Method Were used the Medline via PubMed, Cochrane Library, SciELO and Lilacs, and additional information on institutional sites of interest crossing the headings acute 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. Conclusions 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. PMID:25626943

  12. The Pathology of Acute Liver Failure.

    PubMed

    Lefkowitch, Jay H

    2016-05-01

    Acute liver failure (ALF) is a rare and severe liver disease that usually develops in 8 weeks or less in individuals without preexisting liver disease. Its chief causes worldwide are hepatitis virus infections (hepatitis A, B, and E) and drug hepatotoxicity (particularly intentional or unintentional acetaminophen toxicity). Massive hepatic necrosis is often seen in liver specimens in ALF and features marked loss of hepatocytes, variable degrees of inflammation, and a stereotypic proliferation of bile ductular structures (neocholangioles) derived from activated periportal hepatic progenitor cells. This paper reviews the liver pathology in ALF, including forms of zonal necrosis and their etiologies. PMID:27058243

  13. Liver transplantation in acute liver failure: A challenging scenario

    PubMed Central

    Mendizabal, Manuel; Silva, Marcelo Oscar

    2016-01-01

    Acute liver failure is a critical medical condition defined as rapid development of hepatic dysfunction associated with encephalopathy. The prognosis in these patients is highly variable and depends on the etiology, interval between jaundice and encephalopathy, age, and the degree of coagulopathy. Determining the prognosis for this population is vital. Unfortunately, prognostic models with both high sensitivity and specificity for prediction of death have not been developed. Liver transplantation has dramatically improved survival in patients with acute liver failure. Still, 25% to 45% of patients will survive with medical treatment. The identification of patients who will eventually require liver transplantation should be carefully addressed through the combination of current prognostic models and continuous medical assessment. The concerns of inaccurate selection for transplantation are significant, exposing the recipient to a complex surgery and lifelong immunosuppression. In this challenging scenario, where organ shortage remains one of the main problems, alternatives to conventional orthotopic liver transplantation, such as living-donor liver transplantation, auxiliary liver transplant, and ABO-incompatible grafts, should be explored. Although overall outcomes after liver transplantation for acute liver failure are improving, they are not yet comparable to elective transplantation. PMID:26819519

  14. Liver Transplantation after Exertional Heatstroke-Induced Acute Liver Failure

    PubMed Central

    Virk, Hafeez Ul Hasan

    2016-01-01

    Exertional heatstroke (EHS) is a life-threatening disease characterized clinically by central nervous system dysfunction and severe hyperthermia. It frequently occurs among athletes, soldiers, and laborers. While cardiopulmonary symptoms are common in patients undergoing EHS, irreversible acute liver failure is a rarely described phenomenon. When managing cases of EHS complicated by acute liver failure, it is crucial to act promptly with aggressive total body cooling in order to prevent progression of the clinical syndrome. However, an urgent liver transplantation can be a therapeutic strategy when patients fail to improve with supportive measures. PMID:27738568

  15. Acute-on-Chronic Liver Failure.

    PubMed

    Asrani, Sumeet K; Simonetto, Douglas A; Kamath, Patrick S

    2015-11-01

    Over the past 2 decades, the concept of acute-on-chronic liver failure (ACLF) has been proposed as an alternate path in the natural history of decompensated cirrhosis. ACLF thus is characterized by the presence of a precipitating event (identified or unidentified) in subjects with underlying chronic liver disease leading to rapid progression of liver injury and ending in multi-organ dysfunction characterized by high short-term mortality. Multiple organ failure and an increased risk for mortality are key to the diagnosis of ACLF. The prevalence of ACLF ranges from 24% to 40% in hospitalized patients. The pathophysiological basis of ACLF can be explained using the following 4-part model: predisposing event, injury caused by a precipitating event, response to injury, and organ failure. Although several mathematic scores have been proposed for identifying outcomes with ACLF, it is as yet unclear whether these organ failure scores are truly prognostic or only reflective of the dying process. Treatment paradigms continue to evolve but consist of early recognition, supportive intensive care, and consideration of liver transplantation before onset of irreversible multiple organ failure. PMID:26188138

  16. Acute Liver Failure including Acetaminophen Overdose

    PubMed Central

    Fontana, Robert J.

    2008-01-01

    Synopsis Acute liver failure (ALF) is a dramatic and highly unpredictable clinical syndrome defined by the sudden onset of coagulopathy and encephalopathy. Although many disease processes can cause ALF, acetaminophen overdose is the leading cause in the United States, and has a 66% chance of recovery with early N-acetylcysteine treatment and supportive care. Cerebral edema and infectious complications are notoriously difficult to detect and treat in ALF patients and may lead to irreversible brain damage and multi-organ failure. Emergency liver transplantation is associated with a 70% 1-year patient survival but 20% of listed patients die, highlighting the importance of early referral of ALF patients with a poor prognosis to a liver transplant center. PMID:18570942

  17. Prognostic modeling in pediatric acute liver failure.

    PubMed

    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. PMID:27343006

  18. Portal hypertension in acute liver failure.

    PubMed Central

    Navasa, M; Garcia-Pagán, J C; Bosch, J; Riera, J R; Bañares, R; Mas, A; Bruguera, M; Rodés, J

    1992-01-01

    Twenty five patients with acute liver failure were measured for hepatic venous pressure gradient as an index of portal pressure during the course of a transjugular liver biopsy. Hepatic venous pressure gradient ranged from 4 to 24.5 mm Hg with a mean of 12.8 (5.3) mm Hg (normal values less than 5 mm Hg). All patients but one had increased portal pressure gradient. Portal hypertension correlated with the degree of architectural distortion of the liver, as suggested by a direct correlation between hepatic venous pressure gradient and the area of reticulin collapse, evaluated by means of a morphometric analysis on Sirius red stained liver slides (r = 0.43, p less than 0.05). Hepatic venous pressure gradient was significantly higher in patients with ascites (15.1 (5) mm Hg, n = 15) or renal failure (14.4 (5.3) mm Hg, n = 16) than in those without (9.3 (3.4) mm Hg and 10.1 (4) mm Hg, respectively; p less than 0.05). Portal hypertension was associated with systemic vasodilation and a hyperkinetic circulatory state, with decreased arterial pressure, and peripheral resistance and increased cardiac output. PMID:1644339

  19. Tonsil-derived mesenchymal stem cells alleviate concanavalin A-induced acute liver injury.

    PubMed

    Ryu, Kyung-Ha; Kim, So-Yeon; Kim, Ye-Ryung; Woo, So-Youn; Sung, Sun Hee; Kim, Han Su; Jung, Sung-Chul; Jo, Inho; Park, Joo-Won

    2014-08-01

    Acute liver failure, the fatal deterioration of liver function, is the most common indication for emergency liver transplantation, and drug-induced liver injury and viral hepatitis are frequent in young adults. Stem cell therapy has come into the limelight as a potential therapeutic approach for various diseases, including liver failure and cirrhosis. In this study, we investigated therapeutic effects of tonsil-derived mesenchymal stem cells (T-MSCs) in concanavalin A (ConA)- and acetaminophen-induced acute liver injury. ConA-induced hepatitis resembles viral and immune-mediated hepatic injury, and acetaminophen overdose is the most frequent cause of acute liver failure in the United States and Europe. Intravenous administration of T-MSCs significantly reduced ConA-induced hepatic toxicity, but not acetaminophen-induced liver injury, affirming the immunoregulatory capacity of T-MSCs. T-MSCs were successfully recruited to damaged liver and suppressed inflammatory cytokine secretion. T-MSCs expressed high levels of galectin-1 and -3, and galectin-1 knockdown which partially diminished interleukin-2 and tumor necrosis factor α secretion from cultured T-cells. Galectin-1 knockdown in T-MSCs also reversed the protective effect of T-MSCs on ConA-induced hepatitis. These results suggest that galectin-1 plays an important role in immunoregulation of T-MSCs, which contributes to their protective effect in immune-mediated hepatitis. Further, suppression of T-cell activation by frozen and thawed T-MSCs implies great potential of T-MSC banking for clinical utilization in immune-mediated disease. PMID:24954408

  20. Acute liver failure in pregnancy: an overview.

    PubMed

    Jayanthi, V; Udayakumar, N

    2008-03-01

    Acute liver failure (ALF) in pregnancy is a common challenging clinical problem both in terms of correct diagnosis and management. Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute viral hepatitis is unaffected by pregnancy, except in patients with hepatitis E (HEV), particularly from endemic countries like India, where ALF carries a high mortality. In both HEV infection and herpes simplex infections, maternal and fetal mortality rates are significantly increased. ALF specific to pregnancy including pre-eclampsia, associated with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, acute fatty liver of pregnancy, and hepatic infarction result in increased maternal and fetal mortality if not recognized and acted on early. Early recognition of possible causes and prompt treatment are crucial for successful outcome of ALF in pregnancy. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. This review article addresses the present understanding of ALF in pregnancy reviewing the common causes of ALF and their management in pregnancy. PMID:18299670

  1. Plasma Osteopontin in Acute Liver Failure

    PubMed Central

    Srungaram, Praveen; Rule, Jody A.; Yuan, He Jun; Reimold, Andreas; Dahl, Benny; Sanders, Corron; Lee, William M.

    2015-01-01

    Background Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function in the setting of massive hepatocyte injury. Methods OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1 and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation. Results Median plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055 ng/mL; range: 33 – 19127), when compared to healthy controls (median in pre-SF patients: 41 ng/mL; range 2.6 – 86.4). RA and SF post op patients had elevated OPN levels (37 ng/mL and 198 ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603 ng/mL) and ischemia-related ALF (4102 ng/mL) as opposed to viral hepatitis (706 ng/mL), drug-induced liver injury (353 ng/mL) or autoimmune hepatitis (436 ng/mL), correlating with the degree of hepatocellular damage, as reflected by aminotransferase values (R value: 0.47 for AST, p < 0.001). Conclusions OPN levels appeared to correlate with degree of liver necrosis in ALF. Very high levels were associated with hyperacute injury and good outcomes. Whether OPN exerts a protective effect in limiting disease progression in this setting remains uncertain. PMID:25802196

  2. Gastrointestinal and Liver Issues in Heart Failure.

    PubMed

    Sundaram, Varun; Fang, James C

    2016-04-26

    Heart failure affects ≈23 million people worldwide and continues to have a high mortality despite advancements in modern pharmacotherapy and device therapy. HF is a complex clinical syndrome that can result in the impairment of endocrine, hematologic, musculoskeletal, renal, respiratory, peripheral vascular, hepatic, and gastrointestinal systems. Although gastrointestinal involvement and hepatic involvement are common in HF and are associated with increased morbidity and mortality, their bidirectional association with HF progression remains poorly fathomed. The current understanding of multiple mechanisms, including proinflammatory cytokine milieu, hormonal imbalance, and anabolic/catabolic imbalance, has been used to explain the relationship between the gut and HF and has been the basis for many novel therapeutic strategies. However, the failure of these novel therapies such as anti-tumor necrosis factor-α has resulted in further complexity. In this review, we describe the involvement of the gastrointestinal and liver systems within the HF syndrome, their pathophysiological mechanisms, and their clinical consequences.

  3. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure.

    PubMed

    Karvellas, Constantine J; Subramanian, Ram M

    2016-07-01

    Artificial (nonbiological) extracorporeal liver support devices aim to remove albumin-bound and water-soluble toxins to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. The following beneficial effects have been documented: improvement of jaundice, amelioration of hemodynamic instability, reduction of portal hypertension, and improvement of hepatic encephalopathy. The only randomized prospective multicenter controlled trial to show an improvement in transplant-free survival was for high-volume plasmapheresis. Biological (cell-based) extracorporeal liver support systems aim to support the failing liver through detoxification and synthetic function and warrant further study for safety and benefit. PMID:27339682

  4. A therapy for liver failure found in the JNK yard.

    PubMed

    Willenbring, Holger; Grompe, Markus

    2013-04-11

    In the liver, the hepatocyte mass is kept stable through a tight balance between hepatocyte death and proliferation that is frequently lost upon acute or chronic liver injury. Wuestefeld et al. (2013) now identify a potentially druggable target that enhances hepatocyte proliferation and promotes liver regeneration, thereby preventing liver failure.

  5. Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation. The Acute Liver Failure Study Group.

    PubMed

    Fontana, R J; McCashland, T M; Benner, K G; Appelman, H D; Gunartanam, N T; Wisecarver, J L; Rabkin, J M; Lee, W M

    1999-11-01

    Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase levels during clinical trials. The aim of this study is to describe the clinical, laboratory, and histological features of 4 patients with severe bromfenac hepatotoxicity identified at 3 tertiary care centers participating in the US Acute Liver Failure Study Group. Bromfenac was administered for chronic musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg/d for a minimum of 90 days. All patients reported a prodrome of malaise and fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia. None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction. Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation. Extensive confluent parenchymal necrosis that appeared to begin in the central zones and was accompanied by a predominantly lymphocytic infiltrate was noted in all the livers examined. Nodular regeneration was seen in the 2 patients with a more protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult women. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatotoxicity, preclude further use of bromfenac in the medical community.

  6. Acute Liver Failure After a Late TIPSS Revision

    SciTech Connect

    Radeleff, Boris Sommer, Christof-Matthias; Schawo, Simone; Lopez-Benitez, Ruben; Sauer, Peter; Schemmer, Peter; Kauffmann, Guenter W.; Richter, Goetz M.

    2008-01-15

    We report a rare case of late transjugular intrahepatic portosystemic stent shunt (TIPSS) occlusion due to progressive stent protrusion into the periportal liver parenchyma, which was a result of delayed liver shrinkage 2 years after TIPSS. The initial TIPSS procedure had been carried out in a 52-year-old man as a bridge for liver transplantation because of post-alcoholic liver cirrhosis. We describe the applied TIPSS recanalization and revision technique. Immediately after TIPSS revision acute liver failure developed, which required emergency liver transplantation.

  7. Acute liver failure associated with Garcinia cambogia use.

    PubMed

    Corey, Rebecca; Werner, K Tuesday; Singer, Andrew; Moss, Adyr; Smith, Maxwell; Noelting, Jessica; Rakela, Jorge

    2016-01-01

    Millions of Americans regularly use herbal supplements, but many are unaware of the potential hidden dangers. Numerous supplements have been associated with hepatotoxicity and, indeed dietary/herbal supplements represent an increasingly common source of acute liver injury. We report a case of acute liver failure requiring liver transplantation associated with the use of Garcinia cambogia, a supplement widely promoted for weight loss. When patients present with acute hepatitis or liver failure from an unknown etiology, a careful history of supplement use should be performed.

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

    PubMed

    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.

  9. Acute liver failure associated with occupational exposure to tetrachloroethylene.

    PubMed

    Shen, Chuan; Zhao, Cai-Yan; Liu, Fang; Wang, Ya-Dong; Wang, Wei

    2011-01-01

    Tetrachloroethylene is a chlorinated solvent that is primarily used in dry cleaning and degreasing operations. Although the hepatotoxicity caused by tetrachloroethylene has been well documented in literature, it is rarely considered as a cause of acute liver failure. We report a case of a 39-yr-old man who was admitted to our hospital for acute liver failure due to tetrachloroethylene exposure. Histological examination of the liver revealed massive hepatic necrosis, prominently, in zone 3 of the hepatic lobules. The patient underwent supportive treatment along with 3 sessions of plasmapheresis, and consequently, he presented a favorable outcome. Repeat liver biopsy performed 6 months after the patient's discharge showed architectural distortion with postnecrotic cirrhosis. Physicians should be aware of the possibility of acute liver failure induced by tetrachloroethylene. Early plasmapheresis can be effective for individuals with sufficient capacity for hepatocyte regeneration.

  10. Experimental models of hepatotoxicity related to acute liver failure.

    PubMed

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  11. Experimental models of hepatotoxicity related to acute liver failure

    PubMed Central

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2015-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. PMID:26631581

  12. Experimental models of hepatotoxicity related to acute liver failure.

    PubMed

    Maes, Michaël; Vinken, Mathieu; Jaeschke, Hartmut

    2016-01-01

    Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposure or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure.

  13. [Liver failure in a 27 years old female patient].

    PubMed

    Gertsch, T; Pfammatter, T; Braun, M; Hechelhammer, L; Meyenberger, C; Semela, D; Sawatzki, M

    2012-08-01

    We report about a 27-years old female patient with acute liver failure due to an acute Budd Chiari Syndrom (thrombosis of all three liver veins an vena cava inferior) with caval web, birth control pills and after long distance flight. After successfull aspiration of the caval thrombus and dilatation of caval web liver transplantation could be bypassed. Two weeks after intervention the patient was in a good healthy condition with normal laboratory values, normal liver size, normal perfusion of the V. cava inferior and signs of reperfusion of the middle liver vein. PMID:22878949

  14. Advances in the management of acute liver failure

    PubMed Central

    Wang, Da-Wei; Yin, Yi-Mei; Yao, Yong-Ming

    2013-01-01

    Acute liver failure (ALF) is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver. The causes of ALF encompass a wide variety of toxic, viral, metabolic, vascular and autoimmune insults to the liver, and identifying the correct cause can be difficult or even impossible. Many patients with ALF develop a cascade of serious complications involving almost every organ system, and death is mostly due to multi-organ failure, hemorrhage, infection, and intracranial hypertension. Fortunately, the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology, and the advanced intensive care management. For most severely affected patients who fail to recover after treatment, rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop. This review focuses on the recent advances in the understanding of various contributing etiologies, the administration of etiology-specific treatment to alleviate the liver injury, and the management of complications (e.g., encephalopathy, coagulopathy, cardiovascular instability, respiratory failure, renal failure, sepsis and metabolic disturbance) in patients with ALF. Assessment of the need for liver transplantation is also presented. PMID:24222950

  15. Management of Acute-on-Chronic Liver Failure.

    PubMed

    Durand, Francois; Nadim, Mitra K

    2016-05-01

    Acute-on-chronic liver failure (ACLF) is defined by the occurrence of organ failure(s) other than the liver in patients with cirrhosis. Even though mortality rates are high, there should no longer be reluctance to admit patients with ACLF in the intensive care unit. The prevalence of multidrug-resistant bacteria is high and broad spectrum antibiotics should be initiated as soon as infection is suspected. In patients with circulatory failure, the assessment of circulatory status is challenging due to the hyperkinetic state and an imbalance between the splanchnic and systemic blood volume. Acute kidney injury is common in patients with ACLF. Acute tubular necrosis should be differentiated from hepatorenal syndrome, which justifies vasoconstrictive agents. Renal replacement therapy and mechanical ventilation should be decided on clinical grounds. Recent trials on extracorporeal liver support failed to demonstrate a survival benefit. Aggressive management may serve as a bridge to transplantation provided patients are likely to survive after transplantation. PMID:27172356

  16. Liver dialysis in acute-on-chronic liver failure: current and future perspectives.

    PubMed

    Maiwall, Rakhi; Maras, Jaswinder Singh; Nayak, Suman Lata; Sarin, Shiv Kumar

    2014-09-01

    Patients with acute-on-chronic liver failure (ACLF) are known to have a very high mortality rate as the majority of these patients succumb to multiorgan failure. Liver transplant remains the only option for these patients; however, there are problems with its availability, cost and also the complications and side effects associated with immunosuppression. Unlike advanced decompensated liver disease, there is a potential for hepatic regeneration and recovery in patients with ACLF. A liver support system, cell or non-cell based, logically is likely to provide temporary functional support until the donor liver becomes available or the failing liver survives the onslaught of the acute insult and spontaneously regenerates. Understanding the pathogenesis of liver failure and regeneration is essential to define the needs for a support system. Removal of hepatotoxic metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell-based hepatic support, could help to provide a suitable microenvironment and support the failing liver. The current systems, i.e., MARS and Prometheus, have failed to show survival benefits in patients with ACLF based on which newer devices with improved functionality are currently under development. However, larger randomized trials are needed to prove whether these devices can enable restoration of the complex dysregulated immune system and impact organ failure and mortality in these patients. PMID:26201332

  17. [Acute liver failure after ingestion of death cap mushrooms].

    PubMed

    Zuliani, Anna-Maria; Kabar, Iyad; Mitchell, Todd; Heinzow, Hauke Sebastian

    2016-07-01

    Amatoxins, which are mainly found in Amanita phalloides, Amanita virosa, and Galerina autumnalis, are responsible for the majority of fatal intoxication with green death cap. The intoxication is associated with acute liver failure, which explains the poor prognosis. Acute liver injury is generally preceeded by a gastrointestinal phase with nausea, vomiting and diarrhea. In the course, pre-renal kidney failure due to the associated fluid deficit and fulminant liver failure may occur. General guidelines for the treatment of amatoxin poisoning are yet not available. We report on three patients who suffered from amatoxin mushroom poisoning after ingestion of green death cap mushrooms. Based on the pathophysiology of amatoxin poisoning, we discuss a potential therapeutic approach. PMID:27359312

  18. Angiosarcoma of the liver as a cause of fulminant liver failure

    PubMed Central

    Montell García, Marco; Romero Cabello, Raúl; Romero Feregrino, Raul; Atri Moises, Mercado; Trejo Estrada, Rafael; Alvaro, Padilla-Rodríguez; Moreno Manlio Gerardo, Gama; Feregrino Rodrigo, Romero

    2012-01-01

    Primary liver sarcomas make up 2% of all malignant neoplasms of the liver; of these, angiosarcoma is the most common type. Primary liver tumours rarely cause fulminant hepatic failure (FHF), which is most frequently caused by non-neoplasmic pathologies. In the case of neoplasms, the most frequent are lymphoma and metastatic carcinomas. We describe the case of a 76-year-old man who suffered from FHF as a result of a liver angiosarcoma and we present a review of the medical literature in which we found only two cases of liver angiosarcomas linked to FHF. PMID:22865805

  19. Bridge therapy to liver transplantation in fulminant hepatic failure.

    PubMed

    Merritt, W T

    2001-12-01

    The management of patients with fulminant hepatic failure is a major clinical endeavor. Early intensive care at an institution able to perform liver transplantation is essential. It is recognized that therapy focused solely on attempts at preventing/reversing increased intracranial pressure, and the treatment of other failing organs as they occur falls well short of ideal. This review covers the non-biological and biological techniques utilized in efforts to support liver function. The goal is to foster recovery, or to buy enough time for successful liver transplantation. Prospective, controlled trials are beginning to acknowledge subgroups of fulminant hepatic failure and properly randomize therapy. Our understanding of the essential elements of liver support is improving, but no single device has yet proved indispensable.

  20. Immunophenotype predicts outcome in pediatric acute liver failure

    PubMed Central

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

    2012-01-01

    Objectives We sought to determine if markers of T cell immune activation, including soluble interleukin 2 receptor alpha (sIL2Rα) levels predict outcome in pediatric acute liver failure (PALF) and might target potential candidates for immunomodulatory therapy. Methods We analyzed markers of immune activation in 77 patients with PALF enrolled in a multi-national, multi-center study. The outcomes were survival with native liver, liver transplantation, and death without transplantation within 21 days after enrollment. Results 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 liver transplantation (p=0.01) compared to 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 liver transplantation. Conclusions Evidence of immune activation is present in some patients who die or undergo liver transplantation. Patients with higher sIL2Rα levels were more likely to die or undergo liver transplantation 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. PMID:23111765

  1. Retraction-Related Acute Liver Failure after Urological Laparoscopic Surgery.

    PubMed

    Nozaki, Tetsuo; Kato, Tomonori; Komiya, Akira; Fuse, Hideki

    2014-10-01

    Liver retraction is necessary for optimal exposure during laparoscopic right renal surgery. We described a patient who developed fulminant liver failure as a result of liver retractor-induced excessive ischemic changes in the right lobe of the liver. A 37-year-old male underwent a right side laparoscopic pyeloplasty for ureteropelvic junction obstruction. At the beginning of the operation, a small snake retractor was placed through a 5-mm port under direct vision. The liver was lifted in the appropriate direction to optimize exposure by using the laparoscope holder. The operation was prolonged. However, we achieved significant improvements in the efficiency of liver retraction using the holder. On the first postoperative day, the patient's serum levels of GOT, GPT and LDH had remarkably increased. A computerized tomogram confirmed the presence of excessive ischemic changes of the right lobe of the liver. Our method which used a laparoscope holder device for liver retraction maintained a better surgical field. However, neglecting to make minor adjustments to the positioning of the retractor can cause significant pressure on the liver parenchyma in a single area. As surgical procedures increase in complexity, the surgeon should keep these potential side effects in mind and shift the retraction point at regular intervals. In this report, we discussed various types of retractor-related liver injuries and their management, and highlighted the importance of intermittent release of retraction during prolonged surgery.

  2. Current status of auxiliary partial orthotopic liver transplantation for acute liver failure.

    PubMed

    Rela, Mohamed; Kaliamoorthy, Ilankumaran; Reddy, Mettu Srinivas

    2016-09-01

    Auxiliary partial orthotopic liver transplantation (APOLT) is a technique of liver transplantation (LT) where a partial liver graft is implanted in an orthotopic position after leaving behind a part of the native liver. APOLT was previously considered technically challenging with results inferior to orthotopic liver transplantation. Results of this procedure have continued to improve with improving surgical techniques and a better understanding of the natural history of acute liver failure (ALF) and liver regeneration. The procedure is being increasingly accepted as a valid treatment option for ALF-especially in children. This article reviews the historical background to this operation, advances in the technique, and its current place in the management of ALF. Liver Transplantation 22 1265-1274 2016 AASLD. PMID:27357489

  3. Liver failure posthepatectomy and biliary fistula: multidisciplinar treatment.

    PubMed

    Calleja Kempin, Javier; Colón Rodríguez, Arturo; Machado Liendo, Pedro; Acevedo, Agustín; Martín Gil, Jorge; Sánchez Rodríguez, Teresa; Zorrilla Matilla, Laura

    2016-05-01

    The main cause of morbimor-mortality after major liver surgery is the development of liver failure posthepatectomy(LFPH). Treatment must involve multiple options and will be aggressive from the beginning. We report a case of a patient with cholangiocarcinoma perihilar treated with surgery: right hepatectomy extended to sI + IVb with develop of LFPH and biliary fistula and being management successfully in a multidisciplinary way.

  4. Mechanisms of Cell Death in Acute Liver Failure

    PubMed Central

    Bantel, Heike; Schulze-Osthoff, Klaus

    2012-01-01

    Acute liver failure (ALF) can be the consequence of various etiologies, that might vary between different geographic regions. Most frequent are intoxications with acetaminophen, viral hepatitis, or liver damage of unknown origin. ALF occurs when the extent of hepatocyte death exceeds the regenerative capacity of the liver. The mode of liver cell death that is predominantly induced in ALF, i.e., apoptosis or necrosis, is still controversial and presumably determined by the etiology, duration, and magnitude of liver injury. Severe liver damage involves oxidative stress and depletion of ATP resulting in necrosis. In contrast, maintenance of ATP stores is required for the execution of apoptosis. Recent data suggest that necrosis resulting from severe liver damage is associated with poor outcome of ALF patients. Discrimination between apoptosis and necrosis might be therefore useful for the identification of ALF patients requiring liver transplantation. Identification of the molecular cell death mechanisms remains an important issue not only for early prediction of ALF outcome, but also for therapeutic interventions. In view of the pleiotropic functions of critical mediators of cell death and tissue regeneration, a particular challenge will be to reduce hepatocellular death without inhibiting the regenerative capacity of the liver. Here, we review the molecular mechanisms of hepatocyte injury and the pathways leading to apoptosis and necrosis, which might represent potential diagnostic and therapeutic targets in ALF. PMID:22485095

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

    PubMed

    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.

  6. Acute kidney injury in acute liver failure: a review.

    PubMed

    Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

    2013-11-01

    Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

  7. Acute liver failure in pregnancy: Challenges and management.

    PubMed

    Pandey, Chandra Kant; Karna, Sunaina Tejpal; Pandey, Vijay Kant; Tandon, Manish

    2015-03-01

    Acute liver failure (ALF) in pregnancy negatively affects both maternal and foetal outcome. The spectrum of liver disease in pregnancy may range from mild asymptomatic transaminitis to fatal and irreversible deterioration in liver functions leading to significant morbidity and even mortality. In this comprehensive review, we searched articles published as review articles, clinical trials, and case series in the Medline from 1970 to 2012. The overall outcome of ALF in pregnancy depends on the aetiology, timely diagnosis, prompt management, and early referral to a centre equipped in managing medical or obstetric complication. The foetal outcome is affected by the stage of pregnancy in which the mother has a deterioration of the liver function, with a worst prognosis associated with first or second-trimester liver failure. When ALF complicates pregnancy, liver transplantation is the one of the viable options. Management protocols need to be individualised for each case keeping in mind the risk versus benefit to both the mother and the foetus. PMID:25838585

  8. Critical management decisions in patients with acute liver failure.

    PubMed

    Stravitz, R Todd

    2008-11-01

    Few admissions to the ICU present a greater clinical challenge than the patient with acute liver failure (ALF), the syndrome of abrupt loss of liver function in a previously unaffected individual. Although advances in the intensive care management of patients with ALF have improved survival, the prognosis of ALF remains poor, with a 33% mortality rate and a 25% liver transplant rate in the United States. ALF adversely affects nearly every organ system, with most deaths occurring from sepsis and subsequent multiorgan system failure, and cerebral edema, resulting in intracranial hypertension (ICH) and brainstem herniation. Unfortunately, the optimal management of ALF remains poorly defined, and practices are often based on local experience and case reports rather than on randomized, controlled clinical trials. The paramount question in any patient presenting with ALF remains defining an etiology, since specific antidotes can save lives and spare the liver. This article will consider recent advances in the assignment of an etiology, the administration of etiology-specific treatment to abate the liver injury, and the management of complications (eg, infection, cerebral edema, and the bleeding diathesis) in patients with ALF. New data on the administration of N-acetylcysteine to patients with non-acetaminophen ALF, the treatment of ICH, and assessment of the need for liver transplantation will also be presented. PMID:18988787

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

    PubMed

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

    2015-03-01

    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. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis.

  10. Kidney Failure and Liver Allocation: Current Practices and Potential Improvements.

    PubMed

    Saxena, Varun; Lai, Jennifer C

    2015-09-01

    In February 2002, the United Network for Organ Sharing implemented a system for prioritizing candidates for liver transplantation that was based on the risk of 90-day mortality as determined by the Model for End-Stage Liver Disease (MELD) score. As the MELD score is driven in part by serum creatinine as a marker of kidney function, the prevalence of kidney dysfunction and failure in patients with end-stage liver disease at the time of listing and at transplantation has steadily risen. In this review, we discuss current practices in liver transplantation in patients with kidney dysfunction focusing briefly on the decision to perform simultaneous liver-kidney transplantation. We then discuss pitfalls to the current practices of liver transplantation in patients with kidney dysfunction. We conclude by discussing potential improvements to current practices including the use of the MELD-Na score, alternatives to creatinine and creatinine-based equation for estimating kidney function, and the use of intraoperative kidney replacement therapy during liver transplantation.

  11. Prognostic indications of the failure to treat amoebic liver abscesses

    PubMed Central

    Sánchez-Aguilar, Martín; Morán-Mendoza, Onofre; Herrera-Hernández, Miguel F; Hernández-Sierra, Juan Francisco; Mandeville, Peter B; Tapia-Pérez, J Humberto; Sánchez-Reyna, Martín; Sánchez-Rodríguez, José Juan; Gordillo-Moscoso, Antonio

    2012-01-01

    Objectives To identify the variables that predict the failure to treat amoebic liver abscesses. Methods We prospectively carried out a case–control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure. Results Of 40 patients with amoebic liver abscess, 24 (mean age: 36.7±11.2 years) responded to medical treatment and 16 (41.8±11.6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P<0.05) on the bivariate analysis. The highest (>99%) sensitivity and negative predictive value were observed for an abscess volume >500 ml and diameter >10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter. Conclusions The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy. PMID:23265424

  12. Albumin Dialysis for Liver Failure: A Systematic Review.

    PubMed

    Tsipotis, Evangelos; Shuja, Asim; Jaber, Bertrand L

    2015-09-01

    Albumin dialysis is the best-studied extracorporeal nonbiologic liver support system as a bridge or destination therapy for patients with liver failure awaiting liver transplantation or recovery of liver function. We performed a systematic review to examine the efficacy and safety of 3 albumin dialysis systems (molecular adsorbent recirculating system [MARS], fractionated plasma separation, adsorption and hemodialysis [Prometheus system], and single-pass albumin dialysis) in randomized trials for supportive treatment of liver failure. PubMed, Ovid, EMBASE, Cochrane's Library, and ClinicalTrials.gov were searched. Two authors independently screened citations and extracted data on patient characteristics, quality of reports, efficacy, and safety end points. Ten trials (7 of MARS and 3 of Prometheus) were identified (620 patients). By meta-analysis, albumin dialysis achieved a net decrease in serum total bilirubin level relative to standard medical therapy of 8.0 mg/dL (95% confidence interval [CI], -10.6 to -5.4) but not in serum ammonia or bile acids. Albumin dialysis achieved an improvement in hepatic encephalopathy relative to standard medical therapy with a risk ratio of 1.55 (95% CI, 1.16-2.08) but had no effect survival with a risk ratio of 0.95 (95% CI, 0.84-1.07). Because of inconsistency in the reporting of adverse events, the safety analysis was limited but did not demonstrate major safety concerns. Use of albumin dialysis as supportive treatment for liver failure is successful at removing albumin-bound molecules, such as bilirubin and at improving hepatic encephalopathy. Additional experience is required to guide its optimal use and address safety concerns.

  13. Albumin Dialysis for Liver Failure: A Systematic Review.

    PubMed

    Tsipotis, Evangelos; Shuja, Asim; Jaber, Bertrand L

    2015-09-01

    Albumin dialysis is the best-studied extracorporeal nonbiologic liver support system as a bridge or destination therapy for patients with liver failure awaiting liver transplantation or recovery of liver function. We performed a systematic review to examine the efficacy and safety of 3 albumin dialysis systems (molecular adsorbent recirculating system [MARS], fractionated plasma separation, adsorption and hemodialysis [Prometheus system], and single-pass albumin dialysis) in randomized trials for supportive treatment of liver failure. PubMed, Ovid, EMBASE, Cochrane's Library, and ClinicalTrials.gov were searched. Two authors independently screened citations and extracted data on patient characteristics, quality of reports, efficacy, and safety end points. Ten trials (7 of MARS and 3 of Prometheus) were identified (620 patients). By meta-analysis, albumin dialysis achieved a net decrease in serum total bilirubin level relative to standard medical therapy of 8.0 mg/dL (95% confidence interval [CI], -10.6 to -5.4) but not in serum ammonia or bile acids. Albumin dialysis achieved an improvement in hepatic encephalopathy relative to standard medical therapy with a risk ratio of 1.55 (95% CI, 1.16-2.08) but had no effect survival with a risk ratio of 0.95 (95% CI, 0.84-1.07). Because of inconsistency in the reporting of adverse events, the safety analysis was limited but did not demonstrate major safety concerns. Use of albumin dialysis as supportive treatment for liver failure is successful at removing albumin-bound molecules, such as bilirubin and at improving hepatic encephalopathy. Additional experience is required to guide its optimal use and address safety concerns. PMID:26311600

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

    PubMed

    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.

  15. Acute Liver Failure and Hepatic Encephalopathy After Cleft Palate Repair.

    PubMed

    Kocaaslan, Nihal Durmuş; Tuncer, Fatma Betul; Tutar, Engin; Celebiler, Ozhan

    2015-09-01

    Paracetamol is the most commonly used analgesic after cleft palate repair. It has rarely caused acute hepatic failure at therapeutic or supratherapeutic doses. Only one case of therapeutic paracetamol toxicity after cleft palate repair had been reported previously. Here, we present a similar patient who developed acute liver failure and hepatic encephalopathy after an uncomplicated cleft palate surgery. Lack of large prospective trials in young children due to ethical concerns increases the value of the case reports of acetaminophen toxicity at therapeutic doses. The dosing recommendations of paracetamol may need to be reconsidered after cleft palate surgery.

  16. Liver transplantation for acute liver failure accompanied by severe acute pancreatitis.

    PubMed

    Kirino, Izumi; Fujimoto, Yasuhiro; Hata, Koichiro; Uemoto, Shinji

    2016-01-01

    The role of liver transplantation (LT) in acute liver failure (ALF) complicated by severe acute pancreatitis is still unclear. We here report a case of deceased-donor LT for idiopathic ALF accompanied by severe acute pancreatitis. A 58-year-old man with no history of liver disease presented with idiopathic ALF and acute pancreatitis. After careful consideration, he received a liver from a deceased donor. Following surgery, the patient's liver function rapidly reverted to normal level and the acute pancreatitis simultaneously subsided. The patient later developed a pancreatic pseudocyst, which was treated successfully with combination interventional radiology. LT can be considered for ALF associated with severe acute pancreatitis if there is no clinical evidence of an absolute contraindication for organ transplantation, such as systemic or local infection. Moreover, we recommend a close follow-up by ultrasonography to allow early detection and treatment of pancreatic pseudocysts following surgery. PMID:27600056

  17. Significantly Elevated Liver Alkaline Phosphatase in Congestive Heart Failure

    PubMed Central

    Shamban, Leonid; Patel, Brijesh; Williams, Michael

    2014-01-01

    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.

  18. Methods of Liver Stem Cell Therapy in Rodents as Models of Human Liver Regeneration in Hepatic Failure.

    PubMed

    Hashemi Goradel, Nasser; Darabi, Masoud; Shamsasenjan, Karim; Ejtehadifar, Mostafa; Zahedi, Sarah

    2015-09-01

    Cell therapy is a promising intervention for treating liver diseases and liver failure. Different animal models of human liver cell therapy have been developed in recent years. Rats and mice are the most commonly used liver failure models. In fact, rodent models of hepatic failure have shown significant improvement in liver function after cell infusion. With the advent of stem-cell technologies, it is now possible to re-programme adult somatic cells such as skin or hair-follicle cells from individual patients to stem-like cells and differentiate them into liver cells. Such regenerative stem cells are highly promising in the personalization of cell therapy. The present review article will summarize current approaches to liver stem cell therapy with rodent models. In addition, we discuss common cell tracking techniques and how tracking data help to direct liver cell therapy research in animal models of hepatic failure.

  19. Liver Transplantation in Antituberculosis Drugs-Induced Fulminant Hepatic Failure

    PubMed Central

    Li, Xiaoyan; Liu, Yujie; Zhang, Erhong; He, Qiong; Tang, Yong-Bo

    2015-01-01

    Abstract The antituberculosis drugs isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) usually expose patients to the risk of fulminant hepatic failure (FHF). This report presents a case of liver transplantation in antituberculosis drugs-induced FHF and reviews the relevant literature. A 39-year-old woman with pelvic and salpinx tuberculosis experienced complex pelvic exenteration. After the operation, she was administrated INH, RMP, PZA, and EMB to prevent tuberculosis. Two months later, examination revealed severe FHF and the antituberculosis therapy regimen was changed to ciprofloxacin and streptomycin. Subsequently, urgent orthotopic liver transplantation was performed. Posttransplantation, her serum transaminases improved gradually, but her total bilirubin level and direct bilirubin level continued to worsen, which may have been related to the rejection. However, irreversible damage from antituberulosis drugs was note excluded. Two liver biopsies and histological examinations were performed. One year after transplantation, she died as a consequence of ischemic cholangitis and pulmonary infection. A literature review revealed 9 other published cases of antituberculosis drugs-associated FHF with liver transplantation. This report suggests that, in most cases of antituberculosis drugs-induced FHF, discontinuation of toxic drugs and orthotopic liver transplantation are always sufficient treatment. PMID:26656321

  20. Extracorporeal support for patients with acute and acute on chronic liver failure.

    PubMed

    Aron, Jonathan; Agarwal, Banwari; Davenport, Andrew

    2016-01-01

    The number of patients developing liver failure; acute on chronic liver failure and acute liver failure continues to increase, along with the demand for donor livers for transplantation. As such there is a clinical need to develop effective extracorporeal devices to support patients with acute liver failure or acute-on-chronic liver failure to allow time for hepatocyte regeneration, and so avoiding the need for liver transplantation, or to bridge the patient to liver transplantation, and also potentially to provide symptomatic relief for patients with cirrhosis not suitable for transplantation. Currently devices can be divided into those designed to remove toxins, including plasma exchange, high permeability dialyzers and adsorption columns or membranes, coupled with replacement of plasma proteins; albumin dialysis systems; and bioartificial devices which may provide some of the biological functions of the liver. In the future we expect combinations of these devices in clinical practice, due to the developments in bioartificial scaffolds.

  1. Liver targeting of catalase by cationization for prevention of acute liver failure in mice.

    PubMed

    Ma, Shen-Feng; Nishikawa, Makiya; Katsumi, Hidemasa; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2006-01-10

    To achieve hepatic delivery of CAT for the prevention of CCl4-induced acute liver failure in mice, two types of cationized CAT derivatives, HMD- and ED-conjugated CAT, were developed. Slight structural changes occurred during cationization and the number of increased free amino groups was 3.1 in HMD-CAT and 13.6 in ED-CAT. 111In-cationized CAT derivatives showed an increased binding to HepG2 cells, and were rapidly taken up by the liver. H2O2-induced cytotoxicity in HepG2 cells was significantly prevented by preincubation of the cells with cationized CAT derivatives. A bolus intravenous injection of the cationized CAT derivatives reduced the hepatotoxicity induced by CCl4 in mice. The ED-CAT, which showed more rapid and greater binding to the liver than the HMD-CAT, exhibited more beneficial effects as far as all the parameters examined (serum GOT, GPT, LDH and hepatic GSH) were concerned, suggesting that a high degree of cationization is effective in delivering CAT to the liver to prevent CCl4-induced hepatotoxicity. These results suggest that cationized CAT derivatives are effective in preventing acute liver failure, and ED-based cationization is a suitable method for developing liver-targetable cationized CAT derivatives, because it provides CAT with a high degree of cationization and a high remaining enzymatic activity. PMID:16316705

  2. Exertional heat stroke and acute liver failure: a late dysfunction.

    PubMed

    Carvalho, Ana Sofia; Rodeia, Simão C; Silvestre, Joana; Póvoa, Pedro

    2016-01-01

    Heat stroke (HS) is defined as a severe elevation of core body temperature along with central nervous system dysfunction. Exertional heat stroke (EHS) with acute liver failure (ALF) is a rare condition. The authors report the case of a 25-year-old man with a history of cognitive enhancers' intake who developed hyperthermia and neurological impairment while running an outdoor marathon. The patient was cooled and returned to normal body temperature after 6 h. He subsequently developed ALF and was transferred to the intensive care unit. Over-the-counter drug intake may have been related to heat intolerance and contributed to the event. The patient was successfully treated with conservative measures. In the presence of EHS, it is crucial to act promptly with aggressive total body cooling, in order to prevent progression of the clinical syndrome. Liver function must also be monitored, since it can be a late organ dysfunction. PMID:26969359

  3. Liver Enzymes and Uric acid in Acute Heart Failure

    PubMed Central

    Vakilian, Farveh; Rafighdoost, Abbas Ali; Rafighdoost, Amir Hossein; Amin, Ahmad; Salehi, Maryam

    2015-01-01

    Background: Acute heart failure (AHF) is defined as the new onset or recurrence of gradual or rapidly worsening signs and symptoms of heart failure, requiring urgent or emergent therapy. Objectives: This study attempts to assess the association of liver function tests (LFT) and uric acid level with in hospital outcome and echocardiography parameters, in patients with acute decompensated heart failure. Patients and Methods: A total of 100 patients (aged 16 - 90 years, 60% men) admitted with AHF were enrolled. LFTs and uric acid levels were assessed on first day and before discharge, and patients were followed for 3 months. Results: In-hospital outcomes were considered. Mean Left Ventricular Ejection Fraction (LVEF) was 35% (20 - 45%). Mean Uric acid level was 8.4 mg/dL, significantly higher than chronic HF and normal groups (P < 0.02). Elevated liver enzymes were seen in 52% patients, mostly (87%) in transaminases. Liver enzymes were decreased in 85% patients before discharge. LFT and uric acid levels were inversely and significantly correlated with LVEF on echocardiography (P = 0.02), but not with diastolic parameters. Although there was no significant correlation between uric acid level and in-hospital mortality, risk of intubation and rehospitalization in 3 months, enzyme levels increased in these groups. Increased aspartate transaminase (AST level) was associated with inotrope infusion in AHF patients (42 vs. 82 mg/dL, P = 0.03). Conclusions: Abnormal transaminases and uric acid levels are seen in AHF patients. Increased AST levels may be a predictor of the need for inotrope during hospital course in these patients. PMID:26528447

  4. Acute kidney injury in acute on chronic liver failure.

    PubMed

    Maiwall, Rakhi; Sarin, S K; Moreau, Richard

    2016-03-01

    Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.

  5. Acute liver failure due to non-exertional heatstroke after sauna.

    PubMed

    Erarslan, Elife; Yüksel, Ilhami; Haznedaroglu, Serap

    2012-01-01

    Acute liver failure is defined as rapid loss of liver function that patients without previously recognized liver disease sustain a liver damage. Acute liver failure due to non-exertional heatstroke has rarely been reported. We reported here an unusual case of heat stroke induced acute liver failure (ALF) after sauna. A 63 year old man without previously recognized liver and other systemic disease was admitted for loss of consciousness and impaired liver function after sauna. Despite intensive supportive care, ALF developed. Liver transplantation was planned but the patient died on the sixth day of hospitalization. Non-exertional heatstroke induced ALF is a rare and serious condition. ALF caused by non-exertional heatstroke which requires liver transplantation for definitive solution should be kept in mind in early period.

  6. SlimQuick™-Associated Hepatotoxicity Resulting in Fulminant Liver Failure and Orthotopic Liver Transplantation

    PubMed Central

    Whitsett, Maureen; Rossi, Simona

    2014-01-01

    Green tea extract is a popular ingredient in herbal weight loss supplements. There have been reports of hepatotoxicity associated with the use of dietary supplements, some of these cases lead to fatal outcomes. To our knowledge, we report the first case of fulminant hepatic failure requiring orthotopic liver transplantation caused by SlimQuick™ (Wellnx Life Sciences, Wilmington, DE), a widely available weight loss supplement containing green tea extract. PMID:26157882

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

    PubMed Central

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

    2009-01-01

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure. PMID:19533818

  8. Immune mechanisms in acetaminophen-induced acute liver failure.

    PubMed

    Krenkel, Oliver; Mossanen, Jana C; Tacke, Frank

    2014-12-01

    An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease. PMID:25568858

  9. Epstein–Barr Virus (EBV) Related Acute Liver Failure: A Case Series from the US Acute Liver Failure Study Group

    PubMed Central

    Mellinger, Jessica L.; Rossaro, Lorenzo; Naugler, Willscott E.; Nadig, Satish N.; Appelman, Henry; Lee, William M.; Fontana, Robert J.

    2014-01-01

    Purpose Acute liver failure (ALF) is a rare clinical syndrome associated with a high case fatality rate. Asymptomatic primary infection with Epstein–Barr virus (EBV) is common in the general population while acute hepatitis and jaundice are much less common and ALF has been rarely reported. We reviewed the presenting features as well as clinical outcomes amongst consecutive adults with EBV-related ALF. Methods Amongst the 1,887 adult ALF patients enrolled into the US ALF Study Group from January 1998 to February 2012, there were four patients (0.21 %) with EBV-related ALF. Diagnostic criteria for acute EBV infection included compatible serologies and/or the detection of EBV-encoded RNA (EBER) in liver tissue. Results Median patient age was 30 years (range 18–44); 75 % were male, and only 25 % were immunosuppressed. The median presenting ALT was 504 IU/mL (range 156–4,920), median Alk P was 431 (range 136–1,009), and median bilirubin was 17 mg/dL (range 13–22.1). Liver biopsy findings ranged from cholestasis to submassive necrosis with EBER + staining in two of the three samples tested. Although all of the patients were treated with an antiviral agent, two died of ALF, one underwent liver transplantation (LT) and one survived with supportive care and is well at 5 years. A review of the literature identified four additional LT recipients with favorable long-term outcomes. Conclusion Primary EBV infection accounts for <1 % of consecutive adult ALF cases but is associated with a high case fatality rate. LT is associated with favorable short- and long-term outcomes. PMID:24464209

  10. What a Nephrologist Needs to Know About Acute Liver Failure.

    PubMed

    Leventhal, Thomas M; Liu, Kathleen D

    2015-09-01

    Although relatively rare in the United States, acute liver failure (ALF) is associated with very high rates of morbidity and mortality. A leading cause of morbidity and mortality is cerebral edema and intracranial hypertension. Hypothermia, osmotic diuretics, and hyperosmolar therapy are commonly used to manage these complications; however, when these are ineffective, renal replacement therapy may be needed for volume management. Acute kidney injury is a common complication of ALF and may arise from a number of etiologies, including hepatorenal syndrome and acute tubular necrosis. Acute kidney injury is most common in patients who develop ALF because of acetaminophen toxicity or ischemia. With regard to renal replacement therapy, we will review specific considerations relevant to the management of the patient with ALF. PMID:26311599

  11. Blood-brain barrier in acute liver failure

    PubMed Central

    Nguyen, Justin H.

    2011-01-01

    Brain edema remains a challenging obstacle in the management of acute liver failure (ALF). Cytotoxic mechanisms associated with brain edema have been well recognized, but evidence for vasogenic mechanisms in the pathogenesis of brain edema in ALF has been lacking. Recent reports have not only shown a role of matrix metalloproteinase-9 in the pathogenesis of brain edema in experimental ALF but have also found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. This article reviews and explores the role of the paracellular tight junction proteins in the increased selective BBB permeability that leads to brain edema in ALF. PMID:22100566

  12. What a Nephrologist Needs to Know About Acute Liver Failure.

    PubMed

    Leventhal, Thomas M; Liu, Kathleen D

    2015-09-01

    Although relatively rare in the United States, acute liver failure (ALF) is associated with very high rates of morbidity and mortality. A leading cause of morbidity and mortality is cerebral edema and intracranial hypertension. Hypothermia, osmotic diuretics, and hyperosmolar therapy are commonly used to manage these complications; however, when these are ineffective, renal replacement therapy may be needed for volume management. Acute kidney injury is a common complication of ALF and may arise from a number of etiologies, including hepatorenal syndrome and acute tubular necrosis. Acute kidney injury is most common in patients who develop ALF because of acetaminophen toxicity or ischemia. With regard to renal replacement therapy, we will review specific considerations relevant to the management of the patient with ALF.

  13. Contribution of Transjugular Liver Biopsy in Patients with the Clinical Presentation of Acute Liver Failure

    SciTech Connect

    Miraglia, Roberto Luca, Angelo; Gruttadauria, Salvatore; Minervini, Marta Ida; Vizzini, Giovanni; Arcadipane, Antonio; Gridelli, Bruno

    2006-12-15

    Purpose. Acute liver failure (ALF) treated with conservative therapy has a poor prognosis, although individual survival varies greatly. In these patients, the eligibility for liver transplantation must be quickly decided. The aim of this study was to assess the role of transjugular liver biopsy (TJLB) in the management of patients with the clinical presentation of ALF. Methods. Seventeen patients with the clinical presentation of ALF were referred to our institution during a 52 month period. A TJLB was performed using the Cook Quick-Core needle biopsy. Clinical data, procedural complications, and histologic findings were evaluated. Results. Causes of ALF were virus hepatitis B infection in 7 patients, drug toxicity in 4, mushroom in 1, Wilson's disease in 1, and unknown origin in 4. TJLB was technically successful in all patients without procedure-related complications. Tissue specimens were satisfactory for diagnosis in all cases. In 14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3 patients the initial diagnosis was altered by the presence of unknown cirrhosis. Seven patients with necrosis <60% were successfully treated with medical therapy; 6 patients with submassive or massive necrosis ({>=}85%) were treated with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had submassive necrosis. There was a strict statistical correlation (r = 0.972, p < 0.0001) between the amount of necrosis at the frozen section examination and the necrosis found at routine histologic examination. The average time for TJLB and frozen section examination was 80 min. Conclusion. In patients with the clinical presentation of ALF, submassive or massive liver necrosis and cirrhosis are predictors of poor prognosis. TLJB using an automated device and frozen section examination can be a quick and effective tool in clinical decision-making, especially in deciding patient selection and the best timing for liver transplantation.

  14. Liver function test results and outcomes in children with acute liver failure due to dengue infection.

    PubMed

    Chongsrisawat, Voranush; Hutagalung, Yanee; Poovorawan, Yong

    2009-01-01

    This retrospective study compared the liver function test results and outcomes between children with acute liver failure (ALF) due to dengue hemorrhagic fever (DHF) and due to other causes. We retrospectively reviewed patients less than 15 years old with a diagnosis of ALF admitted to 13 participating centers from different parts of Thailand for the years 2000 and 2001, and those admitted to King Chulalongkorn Memorial Hospital for the year 1997 to 2004. The diagnosis of ALF was based on prothrombin time (PT) prolongation to greater than 2 times the normal control value and the presence of encephalopathy without pre-existing liver disease. The patients were divided into 2 groups: group I (n=16) had DHF with ALF and group II (n=37) had ALF due to other causes. DHF patients had AST levels significantly higher than ALT levels. The mortality rate in group I (50%) was lower than in group II (72.9%), although the difference was not statistically significant. The non-DHF patients who died had a significantly longer duration of jaundice before the onset of encephalopathy and a significantly higher PT ratio compared to survivors. There were no significant differences in the duration of jaundice before the onset of encephalopathy and liver function between dengue patients who died and those who survived.

  15. Preterm delivery in a parturient candidate for emergency liver transplantation after hepatitis B virus infection related fulminant liver failure.

    PubMed

    Mouloudi, E; Vasiliadis, T; Aslanidis, T; Karapanagiotou, A; Papanikolaou, V; Gritsi-Gerogianni, N

    2012-11-01

    This case shows the development of fulminant hepatic failure due to acute hepatitis B virus infection in a multipara (32(nd) week of gestation) candidate for an emergency liver transplantation. Preterm labor began and she delivered a preterm healthy male baby. Postpartum, there were complications including a massive hemorrhage that was managed adequately. We also reviewed the literature regarding causes, complications, and management of acute liver failure during pregnancy and labor.

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

    PubMed

    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. PMID:27216884

  17. Radiographically occult intrasinusoidal liver metastases leading to hepatic failure in a case of breast cancer.

    PubMed

    Gulia, Seema; Khurana, Sachin; Shet, Tanuja; Gupta, Sudeep

    2016-02-15

    The liver is one of the commonest sites of metastatic involvement in breast cancer, usually evident as focal lesions on imaging tests. Rarely, the pattern of metastatic spread is so diffuse that it remains radiologically occult. Such patients usually present with signs of hepatic insufficiency without any focal lesions on liver imaging. In such cases, liver biopsy is required to make a definitive diagnosis. We report a case of a 56-year-old postmenopausal woman with metastatic breast cancer who presented with subacute progressive liver failure. Repeated imaging of the liver was normal or non-descript. Liver biopsy finally established the diagnosis of intrasinusoidal metastases from breast cancer.

  18. N-Acetylcysteine Use in Non-Acetaminophen-Induced Acute Liver Failure.

    PubMed

    McPheeters, Chelsey M; VanArsdale, Vanessa M; Weant, Kyle A

    2016-01-01

    This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease. PMID:27482990

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

    PubMed

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

    2014-11-01

    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 King's College criteria for acute liver failure. Two days after admission, he underwent liver transplantation and recovered. Careful investigation identified imported semi-dried tomatoes as the source of the hepatitis A infection. This patient was part of a foodborne hepatitis A outbreak in the Netherlands in 2010 affecting 13 patients. Virus sequence analysis of our patient's virus showed a strain commonly found in Turkey. Hepatitis A related acute liver failure is rare, but is associated with a poor prognosis. In developed countries, the incidence of hepatitis A is low, but foodborne outbreaks are emerging. Further, we review the literature on recent foodborne hepatitis A outbreaks in developed countries, hepatitis A related acute liver failure, and hepatitis A vaccine.

  20. Green tea extract: A potential cause of acute liver failure

    PubMed Central

    Patel, Shreena S; Beer, Stacey; Kearney, Debra L; Phillips, Garrett; Carter, Beth A

    2013-01-01

    The use of herbal products has increased significantly in recent years. Because these products are not subject to regulation by the Food and Drug Administration and are often used without supervision by a healthcare provider, the indication for and consumption of these supplements is quite variable. Moreover, their use is generally regarded as safe and natural by the lay-public. Unfortunately, there has been an increase in the number of reported adverse events occurring with the use of herbal products. We present a case of acute impending liver failure in an adolescent male using a weight-loss product containing green tea extract. Our case adds to the growing concern surrounding the ingestion of green tea extract and serves to heighten healthcare provider awareness of a potential green tea extract hepatotoxicity. Despite the generally touted benefits of green tea as a whole, clinical concern regarding its use is emerging and has been linked to its concentration in multiple herbal supplements. Interestingly, the suspected harmful compounds are those previously proposed to be advantageous for weight-loss, cancer remedy, and anti-inflammatory purposes. Yet, we emphasize the need to be aware of not just green tea extract, but the importance of monitoring patient use of all dietary supplements and herbal products. PMID:23964154

  1. Hepatitis e and acute liver failure in pregnancy.

    PubMed

    Shalimar; Acharya, Subrat K

    2013-09-01

    Hepatitis E virus is a positive strand RNA virus with three open reading frames which is transmitted predominantly through the fecal contamination of water and food. It is the most common cause of acute liver failure in endemic areas. Pregnant women especially from the Indian subcontinent and Africa are at increased risk of contracting acute HEV infection as well as developing severe complications including ALF. Transmission of HEV occurs from mother to unborn child. Both maternal and fetal complications may occur, including abortion, fetal demise, preterm labor and maternal or neonatal death. The precise reasons for increased susceptibility to HEV infection during pregnancy and associated severe disease are still an enigma. Management is supportive and termination of pregnancy is not recommended as a general rule. Prevention of infection is of vital importance, as availability of clean drinking water can reduce the burden of this disease in the community. There is a need for future research to focus on prevention of ALF in pregnancy and to study the disease pathogenesis, which is not explicitly understood at present. The availability of a vaccine may alter the natural course of the disease in this select population which is at risk. PMID:25755503

  2. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    PubMed Central

    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 cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

  3. Metastatic liver disease and fulminant hepatic failure: presentation of a case and review of the literature.

    PubMed

    Athanasakis, Elias; Mouloudi, Eleni; Prinianakis, George; Kostaki, Maria; Tzardi, Maria; Georgopoulos, Dimitrios

    2003-11-01

    Although liver metastases are commonly found in cancer patients, fulminant hepatic failure (FHF) secondary to diffuse liver infiltration is rare. Furthermore, clinical presentation and laboratory findings are obscure and far from being pathognomonic for the disease. We report a case of a patient who died in the intensive care unit of our hospital from multiple organ failure syndrome secondary to FHF, as a result of liver infiltration from poorly differentiated small cell lung carcinoma. We also present the current knowledge about the clinical picture, laboratory findings and physical history of neoplastic liver-metastasis-induced FHF.

  4. 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

    PubMed Central

    Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey

    2013-01-01

    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. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) 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 cells. In the +cell

  5. Review article: the molecular adsorbents recirculating system (MARS) in liver failure.

    PubMed

    Sen, S; Mookerjee, R P; Davies, N A; Williams, R; Jalan, R

    2002-12-01

    In recent years different artificial liver support systems are being developed for use in patients with acute decompensation of chronic liver disease or acute liver failure. The molecular adsorbents recirculating system (MARS), a device in which patient's blood is dialysed across an albumin-impregnated membrane against a recirculated albumin-containing solution, seems to be effective in removing albumin-bound toxins, such as fatty acids, bile acids and bilirubin. Although the clinical experience with MARS is scarce, some pilot studies have reported its effectiveness at improving liver function and hepatic encephalopathy in patients with acute decompensation of chronic liver disease, and renal function in patients with hepatorenal syndrome type I. Data regarding MARS experience in acute liver failure and in primary graft dysfunction are encouraging but limited. Its real usefulness in these settings is, at present, under evaluation in randomized controlled clinical trials.

  6. Alterations in expression of genes coding for key astrocytic proteins in acute liver failure.

    PubMed

    Desjardins, P; Bélanger, M; Butterworth, R F

    2001-12-01

    Cerebral edema and hepatic encephalopathy are major complications of acute liver failure. Brain herniation caused by increased intracranial pressure as a result of cell swelling is the major cause of death in this condition. Evidence available currently suggests that the rapid accumulation of ammonia by the brain is the major cause of the central nervous system complications of acute liver failure. Increased brain ammonia may cause cell swelling via the osmotic effects of an increase in astrocytic glutamine concentrations or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in brain, some of which code for important proteins involved in CNS function such as the glucose (GLUT-1) and glutamate (GLT-1) transporters, the astrocytic structural protein glial fibrillary acidic protein (GFAP) the "peripheral-type" benzodiazepine receptor (PTBR) and the water channel protein, aquaporin IV. Loss of expression of GLT-1 results in increased extracellular brain glutamate in acute liver failure. Experimental acute liver failure also results in post-translational modifications of the serotonin and noradrenaline transporters resulting in increased extracellular concentrations of these monoamines. Therapeutic measures currently used to prevent and treat brain edema and encephalopathy in patients with acute liver failure include mild hypothermia and the ammonia-lowering agent L-ornithine-L-aspartate. PMID:11746425

  7. Reversible retinal edema in an infant with neonatal hemochromatosis and liver failure.

    PubMed

    Maldonado, Ramiro S; Freedman, Sharon F; Cotten, C Michael; Ferranti, Jeffrey M; Toth, Cynthia A

    2011-02-01

    We present a case of bilateral severe retinal edema with subretinal fluid in an infant diagnosed with neonatal hemochromatosis and liver failure. A macular cherry-red spot in each eye mimicked the clinical appearance of many metabolic storage diseases. Both the clinical retinal appearance and the anatomic abnormalities observed on spectral domain optical coherence tomography resolved after successful liver transplant.

  8. Oxidative Stress and Liver Morphology in Experimental Cyclosporine A-Induced Hepatotoxicity

    PubMed Central

    Czechowska, Grażyna; Irla-Miduch, Joanna

    2016-01-01

    Cyclosporine A is an immunosuppressive drug used after organ's transplantation. The adverse effects on such organs as kidney or liver may limit its use. Oxidative stress is proposed as one of the mechanisms of organs injury. The study was designed to elucidate CsA-induced changes in liver function, morphology, oxidative stress parameters, and mitochondria in rat's hepatocytes. Male Wistar rats were used: group A (control) receiving physiological saline, group B cyclosporine A in a dose of 15 mg/kg/day subcutaneously, and group C the CsA-vehicle (olive oil). On the 28th day rats were anesthetized. The following biochemical changes were observed in CsA-treated animals: increased levels of ALT, AST, and bilirubin in the serum, statistically significant changes in oxidative stress parameters, and lipid peroxidation products in the liver supernatants: MDA+4HAE, GSH, GSSG, caspase 3 activity, and ADP/ATP, NAD+/NADH, and NADP+/NADPH ratios. Microscopy of the liver revealed congestion, sinusoidal dilatation, and focal hepatocytes necrosis with mononuclear cell infiltration. Electron microscope revealed marked mitochondrial damage. Biochemical studies indicated that CsA treatment impairs liver function and triggers oxidative stress and redox imbalance in rats hepatocytes. Changes of oxidative stress markers parallel with mitochondrial damage suggest that these mechanisms play a crucial role in the course of CsA hepatotoxicity. PMID:27298826

  9. Cardiac Failure after Liver Transplantation Requiring a Biventricular Assist Device

    PubMed Central

    Soe, Eiei; D'Alessandro, David; Shin, Julia; Jakobleff, William; Schwartz, Daniel; Kinkhabwala, Milan; Gaglio, Paul J.

    2014-01-01

    Increased hepatic iron load in extrahepatic organs of cirrhotic patients with and without hereditary hemochromatosis portends a poorer long term prognosis after liver transplant. Hepatic as well as nonhepatic iron overload is associated with increased infectious and postoperative complications, including cardiac dysfunction. In this case report, we describe a cirrhotic patient with alpha 1 antitrypsin deficiency and nonhereditary hemochromatosis (non-HFE) that developed cardiogenic shock requiring mechanical circulatory support for twenty days after liver transplant. Upon further investigation, she was found to have significant iron deposition in both the liver and heart biopsies. Her heart regained complete and sustained recovery following ten days of mechanical biventricular support. This case highlights the importance of preoperatively recognizing extrahepatic iron deposition in patients referred for liver transplantation irrespective of etiology of liver disease as this may prevent postoperative complications. PMID:25431733

  10. Survival Benefits With Artificial Liver Support System for Acute-on-Chronic Liver Failure

    PubMed Central

    Shen, Yi; Wang, Xu-Lin; Wang, Bin; Shao, Jian-Guo; Liu, Yan-Mei; Qin, Yan; Wang, Lu-Jun; Qin, Gang

    2016-01-01

    Abstract The artificial liver support system (ALSS) offers the potential to improve the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the literature has been inconsistent on its survival benefits. We aimed to conduct a time series-based meta-analysis of randomized clinical trials (RCTs) and observational studies which examined differences in mortality in ACLF patients treated with ALSS or not. MEDLINE, EMBASE, OVID, and COCHRANE library database were systemically searched up to December 2014. Quality of included studies was evaluated using the Jadad score. The outcome measure was mortality at different follow-up endpoints. Odds ratios (ORs) and survival curve data were pooled for analysis. Ten studies, 7 RCTs, and 3 controlled cohorts were enrolled, involving a total of 1682 ACLF patients, among whom 842 were treated with ALSS. ALSS was found to reduce the risk of short-term (1-month and 3-month) mortality for patients with ACLF by nearly 30%. Randomized trials and observational studies provided good internal and external validity respectively. The combined Kaplan–Meier curves showed a consistent pattern of findings. Meta-analysis also suggested that ALSS might reduce medium-term (6-month and 1-year) mortality risk by 30% and long-term (3-year) mortality risk by 50% in ACLF patients. ALSS therapy could reduce short-term mortality in patients with ACLF. Meanwhile, its impacts on medium- and long-term survival seem to be promising but remained inconclusive. Clinical utility of this system for survival benefit may be implied. PMID:26817889

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

    PubMed

    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. PMID:27222930

  12. [Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure].

    PubMed

    Bettinger, Dominik; Lutz, Lisa; Schultheiß, Michael; Werner, Martin; Thimme, Robert; Neumann-Haefelin, Christoph

    2016-09-01

    Primary systemic amyloidosis is a rare disorder resulting in extracellular deposition of insoluble fibrils in different organs. Liver involvement has been reported. Since hepatic amyloidosis often presents clinically asymptomatic without specific laboratory or imaging hallmarks, diagnosis is challenging. However, cases of progressive hepatic failure due to liver amyloidosis have been reported. A 63 year old man presented with newly diagnosed ascites to our department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy. Initially, alcoholic hepatitis was suspected. Due to the rapid deterioration of liver function, however, transjugular liver biopsy was performed showing light chain amyloidosis of kappa isotype. As diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality. PMID:27642740

  13. [Hepatic amyloidosis as a rare differential diagnosis of progressive liver failure].

    PubMed

    Bettinger, Dominik; Lutz, Lisa; Schultheiß, Michael; Werner, Martin; Thimme, Robert; Neumann-Haefelin, Christoph

    2016-09-01

    Primary systemic amyloidosis is a rare disorder resulting in extracellular deposition of insoluble fibrils in different organs. Liver involvement has been reported. Since hepatic amyloidosis often presents clinically asymptomatic without specific laboratory or imaging hallmarks, diagnosis is challenging. However, cases of progressive hepatic failure due to liver amyloidosis have been reported. A 63 year old man presented with newly diagnosed ascites to our department. The patient reported occasional alcohol consumption. Viral hepatitis, genetic-metabolic causes as well as hepatic vascular disorders were excluded and ultrasound did not show any signs of liver cirrhosis or intraabdominal malignancy. Initially, alcoholic hepatitis was suspected. Due to the rapid deterioration of liver function, however, transjugular liver biopsy was performed showing light chain amyloidosis of kappa isotype. As diagnosis of hepatic amyloidosis is challenging, early liver biopsy is mandatory in patients with unexplained acute or chronic liver disease to exclude rare diseases with high mortality.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27284486

  15. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents: A Case Report.

    PubMed

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians should rule

  16. Recurrent Acute Liver Failure Because of Acute Hepatitis Induced by Organic Solvents

    PubMed Central

    Ito, Daisuke; Tanaka, Tomohiro; Akamatsu, Nobuhisa; Ito, Kyoji; Hasegawa, Kiyoshi; Sakamoto, Yoshihiro; Nakagawa, Hayato; Fujinaga, Hidetaka; Kokudo, Norihiro

    2016-01-01

    Abstract The authors present a case of recurrent acute liver failure because of occupational exposure to organic solvents. A 35-year-old man with a 3-week history of worsening jaundice and flu-like symptoms was admitted to our hospital. Viral hepatitis serology and autoimmune factors were negative. The authors considered liver transplantation, but the patient's liver function spontaneously recovered. Liver biopsy revealed massive infiltration of neutrophils, but the cause of the acute hepatitis was not identified. Four months after discharge, the patient's liver function worsened again. The authors considered the possibility of antinuclear antibody-negative autoimmune hepatitis and initiated steroid treatment, which was effective. Four months after discharge, the patient was admitted for repeated liver injury. The authors started him on steroid pulse therapy, but this time it was not effective. Just before the first admission, he had started his own construction company where he was highly exposed to organic solvents, and thus the authors considered organic solvent-induced hepatitis. Although urine test results for organic solvents were negative, a second liver biopsy revealed severe infiltration of neutrophils, compatible with toxic hepatitis. Again, his liver function spontaneously improved. Based on the pathology and detailed clinical course, including the patient's high exposure to organic solvents since just before the first admission, and the spontaneous recovery of his liver damage in the absence of the exposure, he was diagnosed with toxic hepatitis. The authors strongly advised him to avoid organic solvents. Since then, he has been in good health without recurrence. This is the first report of recurrent acute liver failure because of exposure to organic solvents, which was eventually diagnosed through a meticulous medical history and successfully recovered by avoiding the causative agents. In acute liver failure with an undetermined etiology, clinicians

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

    PubMed Central

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

    2015-01-01

    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. PMID:26576097

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin. PMID:26136687

  20. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.

    PubMed

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-02-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system.

  1. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.

    PubMed

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-02-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

  2. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

    PubMed Central

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-01-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

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

    PubMed

    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. PMID:25891735

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

    PubMed Central

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

    2016-01-01

    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. PMID:27468190

  5. Platelet Dysfunction: Status of Thrombopoietin in Thrombocytopenia Associated with Chronic Liver Failure.

    PubMed

    Giannini, Edoardo G; Peck-Radosavljevic, Markus

    2015-07-01

    Thrombocytopenia is a common hematological abnormality in patients with chronic liver disease, and its prevalence is higher in patients with liver failure. Although the presence of thrombocytopenia has historically been associated with portal hypertension, the characterization of thrombopoietin has improved our understanding of the determinants of platelet count in patients with liver disease. In particular, the association between thrombopoietin levels and residual liver function helped disclose the multifaceted pathophysiology of thrombocytopenia in patients with chronic liver failure. In this regard, important results were provided by studies performed in patients with chronic viral hepatitis that assessed the complex interplay between thrombocytopenia induced by the myelosuppressive effect of interferon-based treatment and thrombopoietin pathophysiology. These studies showed that successful antiviral therapy is accompanied by improved hepatic thrombopoietin production. Moreover, studies that evaluated thrombopoietin and platelet count dynamics before and after liver transplantation were instrumental in describing how restoration of liver function determines a normalization of the thrombopoietin-platelet count feedback that is deranged in patients with end-stage liver disease. PMID:26049067

  6. Successful Management of Acute Liver Failure Patients Waiting for Liver Transplantation by On-Line Hemodiafiltration with an Arteriovenous Fistula.

    PubMed

    Haga, Yuki; Yasui, Shin; Kanda, Tatsuo; Hattori, Noriyuki; Wakamatsu, Toru; Nakamura, Masato; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Maruyama, Hitoshi; Ohtsuka, Masayuki; Oda, Shigeto; Miyazaki, Masaru; Yokosuka, Osamu

    2016-01-01

    On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middle-aged Japanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF. PMID:27403116

  7. Successful Management of Acute Liver Failure Patients Waiting for Liver Transplantation by On-Line Hemodiafiltration with an Arteriovenous Fistula

    PubMed Central

    Haga, Yuki; Yasui, Shin; Kanda, Tatsuo; Hattori, Noriyuki; Wakamatsu, Toru; Nakamura, Masato; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Maruyama, Hitoshi; Ohtsuka, Masayuki; Oda, Shigeto; Miyazaki, Masaru; Yokosuka, Osamu

    2016-01-01

    On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middle-aged Japanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF. PMID:27403116

  8. Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy

    PubMed Central

    Haack, Tobias B.; Staufner, Christian; 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; Kühr, Joachim; Himbert, Urban; Taylor, Robert W.; Distelmaier, Felix; Vockley, Jerry; Ghaloul-Gonzalez, Lina; Zschocke, Johannes; Kremer, Laura S.; Graf, Elisabeth; Schwarzmayr, Thomas; Bader, Daniel M.; Gagneur, Julien; Wieland, Thomas; Terrile, Caterina; Strom, Tim M.; Meitinger, Thomas; Hoffmann, Georg F.; Prokisch, Holger

    2015-01-01

    Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional six individuals from five families. Immunoblot analysis of mutant fibroblasts showed reduced protein levels of NBAS and its proposed interaction partner p31, both involved in retrograde transport between endoplasmic reticulum and Golgi. We recommend NBAS analysis in individuals with acute infantile liver failure, especially if triggered by fever. PMID:26073778

  9. Hepatic Copper Accumulation: A Novel Feature in Transient Infantile Liver Failure Due to TRMU Mutations?

    PubMed

    Grover, Z; Lewindon, P; Clousten, A; Shaag, A; Elpeleg, O; Coman, D

    2015-01-01

    Defects in the mitochondrial respiratory chain can induce a heterogeneous range of clinical and biochemical manifestations. Hepatic involvement includes acute fulminant hepatic failure, microvesicular steatosis, neonatal non-alloimmune haemochromatosis and cirrhosis. Recently pathogenic mutations in tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) gene (OMIM 610230) have been demonstrated to cause transient infantile liver failure (OMIM 613070). The human TRMU gene encodes a mitochondrial protein, 5-methylaminomethyl-2-thiouridylate methyltransferase, whose molecular function is that of mitochondrial tRNA modification.We report an infant who presented with acute liver failure, in whom we observed hepatic copper intoxication and cirrhosis on liver biopsy. We postulate that the hepatic copper intoxication observed in our patient is most likely a secondary event associated with cholangiopathy. Periportal copper accumulation has been implicated in causing secondary mitochondrial dysfunction; the impact of copper accumulation in patients with TRMU mutations is unclear and warrants long-term clinical follow-up.

  10. Texture feature analysis for prediction of postoperative liver failure prior to surgery

    NASA Astrophysics Data System (ADS)

    Simpson, Amber L.; Do, Richard K.; Parada, E. Patricia; Miga, Michael I.; Jarnagin, William R.

    2014-03-01

    Texture analysis of preoperative CT images of the liver is undertaken in this study. Standard texture features were extracted from portal-venous phase contrast-enhanced CT scans of 36 patients prior to major hepatic resection and correlated to postoperative liver failure. Differences between patients with and without postoperative liver failure were statistically significant for contrast (measure of local variation), correlation (linear dependency of gray levels on neighboring pixels), cluster prominence (asymmetry), and normalized inverse difference moment (local homogeneity). Though texture features have been used to diagnose and characterize lesions, to our knowledge, parenchymal statistical variation has not been quantified and studied. We demonstrate that texture analysis is a valuable tool for quantifying liver function prior to surgery, which may help to identify and change the preoperative management of patients at higher risk for overall morbidity.

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

    PubMed

    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.

  12. Potential Use of Biological Proteins for Liver Failure Therapy

    PubMed Central

    Taguchi, Kazuaki; Yamasaki, Keishi; Seo, Hakaru; Otagiri, Masaki

    2015-01-01

    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. PMID:26404356

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

    PubMed

    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.

  14. Meta-analysis of survival with the molecular adsorbent recirculating system for liver failure

    PubMed Central

    He, Guo-Lin; Feng, Lei; Duan, Chong-Yang; Hu, Xiang; Zhou, Chen-Jie; Cheng, Yuan; Pan, Ming-Xin; Gao, Yi

    2015-01-01

    This study aims to assess the treatment effects of the molecular adsorbent recirculating system (MARS) in patients with acute and acute-on-chronic liver failure. We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry database between January 1966 and January 2014. We included randomized controlled trials, which compared the treatment effects of MARS with standard medical treatment. Study quality assessed according to Consolidated Standards of Reporting Trials (CONSORT) criteria. The risk ratio was used as the effect-size measure according to a fixed-effects model. The search strategy revealed 72 clinical studies, 10 of which were randomized controlled trials that met the criteria and were included. Four addressed ALF (93 patients) and six addressed AOCLF (453 patients). The mean CONSORT score was 15 (range 10-20). By meta-analysis, MARS significantly improved survival in ALF (risk ratio 0.61; 95% CI 0.38, 0.97; P = 0.04). There was no significant survival benefit in AOCLF (risk ratio 0.88; 95% CI 0.74, 1.06; P = 0.16). MARS significantly improved survival in patients with acute liver failure, however, there is no evidence that it improved survival in patients with acute-on-chronic liver failure. In conclusion, the present meta-analysis indicates that MARS therapy can improve survival in patients with ALF. It is necessary to develop MARS treatment because of the increasing demand for liver transplantation and the risk of liver failure. PMID:26770295

  15. Tissue-Specific Regulation of p38α-Mediated Inflammation in Con A-Induced Acute Liver Damage.

    PubMed

    Kang, Young Jun; Bang, Bo-Ram; Otsuka, Motoyuki; Otsu, Kinya

    2015-05-15

    Because p38α plays a critical role in inflammation, it has been an attractive target for the development of anti-inflammation therapeutics. However, p38α inhibitors showed side effects, including severe liver toxicity, that often prevailed over the benefits in clinical studies, and the mechanism of toxicity is not clear. In this study, we demonstrate that p38α regulates the inflammatory responses in acute liver inflammation in a tissue-specific manner, and liver toxicity by p38α inhibitors may be a result of the inhibition of protective activity of p38α in the liver. Genetic ablation of p38α in T and NKT cells protected mice from liver injury in Con A-induced liver inflammation, whereas liver-specific deletion of p38α aggravated liver pathology. We found that p38α deficiency in the liver increased the expression of chemokines to recruit more inflammatory cells, indicating that p38α in the liver plays a protective anti-inflammatory role during acute liver inflammation. Therefore, our results suggest that p38α regulates the inflammatory responses in a tissue-specific manner, and that the tissue-specific p38α targeting strategies can be used for the development of an effective anti-inflammation treatment with an improved side-effect profile.

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

    PubMed Central

    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

    2015-01-01

    Background & Aims 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. Methods 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. Results 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. Conclusions The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients. PMID:25937432

  17. Plasmapheresis for hemolytic crisis and impending acute liver failure in Wilson disease.

    PubMed

    Asfaha, Samuel; Almansori, Mohammed; Qarni, Uwais; Gutfreund, Klaus S

    2007-01-01

    Wilsonian crisis is fatal unless copper removal is initiated early and liver transplantation is performed for patients that fulfill criteria for a poor outcome. We report a patient presenting with severe hemolysis and impending acute liver failure that made a rapid recovery with prompt initiation of plasmapheresis and chelation therapy. Rapid copper removal by plasmapheresis alleviated hemolysis and liver injury. A review of the literature was performed examining the use of plasmapheresis and albumin dialysis with continuous veno-venous hemodialysis or molecular adsorbents and recirculating system.

  18. Plasma exchange for hemolytic crisis and acute liver failure in Wilson disease.

    PubMed

    Verma, Nishant; Pai, Gautham; Hari, Pankaj; Lodha, Rakesh

    2014-05-01

    Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.

  19. Methanobactin reverses acute liver failure in a rat model of Wilson disease

    PubMed Central

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K.; Schirmacher, Peter; DiSpirito, Alan A.; Bandow, Nathan; Baral, Bipin S.; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P.; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A.; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H.J.; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz

    2016-01-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration– and European Medicines Agency–approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  20. Methanobactin reverses acute liver failure in a rat model of Wilson disease.

    PubMed

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Kabiri, Yaschar; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K; Schirmacher, Peter; DiSpirito, Alan A; Bandow, Nathan; Baral, Bipin S; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A; Adamski, Jerzy; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H J; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz; Zischka, Hans

    2016-07-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration- and European Medicines Agency-approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  1. Farnesyltransferase inhibitor, tipifarnib, prevents galactosamine/lipopolysaccharide-induced acute liver failure.

    PubMed

    Shirozu, Kazuhiro; Hirai, Shuichi; Tanaka, Tomokazu; Hisaka, Shinsuke; Kaneki, Masao; Ichinose, Fumito

    2014-12-01

    Acute liver failure (ALF) is a fatal syndrome associated with massive hepatocyte death. There is no cure for ALF except liver transplantation. Protein farnesylation is a lipid modification of cysteine residues that is catalyzed by farnesyltransferase (FTase) and has been proposed as an integral component of acute inflammation. Previously, we have demonstrated that FTase inhibitors improve survival in mouse models of endotoxemia and sepsis. Here we studied the effects of FTase inhibitor, tipifarnib, on galactosamine (GalN)/lipopolysaccharide (LPS)-induced ALF. The effects of tipifarnib (10 mg/kg, i.p.) were studied in GalN (400 mg/kg, i.p.)- and LPS (3 μg/kg)-challenged mice by histological and biochemical analyses. Galactosamine/LPS administration caused prominent liver injury characterized by the increased plasma alanine aminotransferase and aspartic aminotransferase levels, leading to significant mortality in mice. Tipifarnib inhibited GalN/LPS-induced caspase 3 activation, inflammatory cytokine production, and c-Jun N-terminal kinase phosphorylation in the liver. On the other hand, tipifarnib upregulated antiapoptotic protein, Bcl-xL, in the liver after GalN/LPS challenge. Tipifarnib also protected primary hepatocytes from GalN/tumor necrosis factor α-induced cell death by inhibiting caspase 3 activation and upregulating antiapoptotic proteins. Galactosamine/LPS-induced liver injury was associated with increased protein farnesylation in the liver. Tipifarnib prevented protein farnesylation in the liver and markedly attenuated liver injury and mortality in GalN/LPS-challenged mice. These results suggest that protein farnesylation is a novel potential molecular target to prevent hepatocyte death and acute inflammatory liver failure in fulminant hepatitis. PMID:25046541

  2. Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis.

    PubMed

    Santra, Saikat; Cameron, Jessie M; Shyr, Casper; Zhang, Linhua; Drögemöller, Britt; Ross, Colin J; Wasserman, Wyeth W; Wevers, Ron A; Rodenburg, Richard J; Gupte, Girish; Preece, Mary Anne; van Karnebeek, Clara D

    2016-05-01

    We report a patient from a consanguineous family who presented with transient acute liver failure and biochemical patterns suggestive of disturbed urea cycle and mitochondrial function, for whom conventional genetic and metabolic investigations for acute liver failure failed to yield a diagnosis. Whole exome sequencing revealed a homozygous 12-bp deletion in PCK1 (MIM 614168) encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK); enzymatic studies subsequently confirmed its pathogenic nature. We propose that PEPCK deficiency should be considered in the young child with unexplained liver failure, especially where there are marked, accumulations of TCA cycle metabolites on urine organic acid analysis and/or an amino acid profile with hyperammonaemia suggestive of a proximal urea cycle defect during the acute episode. If suspected, intravenous administration of dextrose should be initiated. Long-term management comprising avoidance of fasting with the provision of a glucose polymer emergency regimen for illness management may be sufficient to prevent future episodes of liver failure. This case report provides further insights into the (patho-)physiology of energy metabolism, confirming the power of genomic analysis of unexplained biochemical phenotypes.

  3. Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis.

    PubMed

    Santra, Saikat; Cameron, Jessie M; Shyr, Casper; Zhang, Linhua; Drögemöller, Britt; Ross, Colin J; Wasserman, Wyeth W; Wevers, Ron A; Rodenburg, Richard J; Gupte, Girish; Preece, Mary Anne; van Karnebeek, Clara D

    2016-05-01

    We report a patient from a consanguineous family who presented with transient acute liver failure and biochemical patterns suggestive of disturbed urea cycle and mitochondrial function, for whom conventional genetic and metabolic investigations for acute liver failure failed to yield a diagnosis. Whole exome sequencing revealed a homozygous 12-bp deletion in PCK1 (MIM 614168) encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK); enzymatic studies subsequently confirmed its pathogenic nature. We propose that PEPCK deficiency should be considered in the young child with unexplained liver failure, especially where there are marked, accumulations of TCA cycle metabolites on urine organic acid analysis and/or an amino acid profile with hyperammonaemia suggestive of a proximal urea cycle defect during the acute episode. If suspected, intravenous administration of dextrose should be initiated. Long-term management comprising avoidance of fasting with the provision of a glucose polymer emergency regimen for illness management may be sufficient to prevent future episodes of liver failure. This case report provides further insights into the (patho-)physiology of energy metabolism, confirming the power of genomic analysis of unexplained biochemical phenotypes. PMID:26971250

  4. Use of acetylcysteine for non-acetaminophen-induced acute liver failure.

    PubMed

    Sales, Ibrahim; Dzierba, Amy L; Smithburger, Pamela L; Rowe, Deanna; Kane-Gill, Sandra L

    2013-01-01

    The purpose of this review was to evaluate the effectiveness of acetylcysteine in the treatment of acute liver failure not related to acetaminophen. A search of MEDLINE April 2003 through May 2012 using the Pub Med database was conducted using the keywords acetylcysteine and non-acetaminophen-induced acute liver failure or acetylcysteine and liver failure. All human case reports, case series, and research articles that discussed the use of acetylcysteine for non-acetaminophen induced liver failure were evaluated. A total of 263 articles were identified during this broad search with 11 articles included for review in this article; eight case reports, two retrospective trials, and one prospective, randomized, double-blind multicenter study. In conclusion, the data suggest marginal benefit of IV acetylcysteine in NAI-ALF with coma grades I-II; however, the routine use of acetylcysteine cannot be recommended. It may be considered in non-transplant centers while awaiting referral or when transplantation is not an option. Further studies are necessary to determine optimal dosing, duration, and criteria for patient selection.

  5. Lifesaving liver transplantation for multi-organ failure caused by Bacillus cereus food poisoning.

    PubMed

    Tschiedel, Eva; Rath, Peter-Michael; Steinmann, Jörg; Becker, Heinz; Dietrich, Rudolf; Paul, Andreas; Felderhoff-Müser, Ursula; Dohna-Schwake, Christian

    2015-02-01

    Bacillus cereus is a spore-forming, gram-positive bacterium that causes food poisoning presenting with either emesis or diarrhea. Diarrhea is caused by proteinaceous enterotoxin complexes, mainly hemolysin BL, non-hemolytic enterotoxin (NHE), and cytotoxin K. In contrast, emesis is caused by the ingestion of the depsipeptide toxin cereulide, which is produced in B. cereus contaminated food, particularly in pasta or rice. In general, the illness is mild and self-limiting. However, due to cereulide intoxication, nine severe cases with rhabdomyolysis and/or liver failure, five of them lethal, are reported in literature. Here we report the first case of life-threatening liver failure and severe rhabdomyolysis in this context that could not be survived without emergency hepatectomy and consecutive liver transplantation.

  6. Ketone Body Therapy Protects From Lipotoxicity and Acute Liver Failure Upon Pparα Deficiency.

    PubMed

    Pawlak, Michal; Baugé, Eric; Lalloyer, Fanny; Lefebvre, Philippe; Staels, Bart

    2015-08-01

    Acute liver failure (ALF) is a severe and rapid liver injury, often occurring without any preexisting liver disease, which may precipitate multiorgan failure and death. ALF is often associated with impaired β-oxidation and increased oxidative stress (OS), characterized by elevated levels of hepatic reactive oxygen species (ROS) and lipid peroxidation (LPO) products. Peroxisome proliferator-activated receptor (PPAR)α has been shown to confer hepatoprotection in acute and chronic liver injury, at least in part, related to its ability to control peroxisomal and mitochondrial β-oxidation. To study the pathophysiological role of PPARα in hepatic response to high OS, we induced a pronounced LPO by treating wild-type and Pparα-deficient mice with high doses of fish oil (FO), containing n-3 polyunsaturated fatty acids. FO feeding of Pparα-deficient mice, in contrast to control sunflower oil, surprisingly induced coma and death due to ALF as indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, ammonia, and a liver-specific increase of ROS and LPO-derived malondialdehyde. Reconstitution of PPARα specifically in the liver using adeno-associated serotype 8 virus-PPARα in Pparα-deficient mice restored β-oxidation and ketogenesis and protected mice from FO-induced lipotoxicity and death. Interestingly, administration of the ketone body β-hydroxybutyrate prevented FO-induced ALF in Pparα-deficient mice, and normalized liver ROS and malondialdehyde levels. Therefore, PPARα protects the liver from FO-induced OS through its regulatory actions on ketone body levels. β-Hydroxybutyrate treatment could thus be an option to prevent LPO-induced liver damage. PMID:26087172

  7. Herpes Simplex Virus Hepatitis in an Immunocompetent Adult: A Fatal Outcome due to Liver Failure

    PubMed Central

    Poley, Rachel A.; Snowdon, Jaime F.; Howes, Daniel W.

    2011-01-01

    Objective. To present a case of a healthy 41-year-old female who developed fulminant hepatic failure leading to death. The cause of hepatic failure identified on postmortem exam was herpes simplex virus hepatitis. Design. Observation of a single patient. Setting. Intensive care unit of a tertiary care university teaching hospital in Canada. Patient. 41-year-old previously healthy female presenting with a nonspecific viral illness and systemic inflammatory response syndrome. Intervention. The patient was treated with intravenous fluids and broad-spectrum antibiotics. On the second day of admission, she was found to have elevated transaminases, and, over 48 hours, she progressed to fulminant liver failure with disseminated intravascular coagulopathy, refractory lactic acidosis, and shock. She progressed to respiratory failure requiring intubation and mechanical ventilation. She was started on N-acetylcysteine, a bicarbonate infusion, hemodialysis, and multiple vasopressors and inotropes. Measurements and Main Results. Despite treatment, the patient died roughly 70 hours after her initial presentation to hospital. Her postmortem liver biopsy revealed herpes simplex virus hepatitis as her cause of death. Conclusions. Herpes simplex virus must be considered in all patients presenting with liver failure of unknown cause. If suspected, prompt treatment with acyclovir should be initiated. PMID:24826316

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

    PubMed

    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

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

    PubMed Central

    Van Hootegem, Anneleen; Verslype, Chris; Van Steenbergen, Werner

    2011-01-01

    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. PMID:25954549

  10. Auxiliary liver transplantation in patients with fulminant hepatic failure: hepatobiliary scintigraphic follow-up.

    PubMed

    Buyck, D; Bonnin, F; Bernuau, J; Belghiti, J; Bok, B

    1997-02-01

    Auxiliary liver transplantation (ALT), retaining in place the liver of the recipient, has been proposed as an alternative to liver replacement in patients with fulminant hepatic failure (FHF). Hepatobiliary scintigraphy (HS) has proved a unique tool for the separate assessment of graft and native liver function. Forty-eight HS scans were performed, following the injection of technetium-99m trimethyl-bromo-imino-diacetic acid, in six patients who underwent ALT for FHF. Quantitative parameters were derived from the time-activity curves of both the graft and the native liver. The function of the graft remained normal as long as the patients remained under immunosuppressive therapy (IST). The function of the native liver was almost completely absent in the 1st month in five patients, but it improved gradually in four of them. IST was then decreased in four patients and finally withdrawn in three. Spontaneous graft atrophy occurred in two patients and the graft was removed in two. All of the patients in whom IST was reduced had a normal global hepatic function and selective uptake (RU) >30% at that time. In ALT patients with FHF, HS can distinguish non-invasively the functional performance of both the donor and the recipient liver and its evolution with time.

  11. Delta 4-3-oxosteroid 5 beta-reductase deficiency causing neonatal liver failure and hemochromatosis.

    PubMed

    Shneider, B L; Setchell, K D; Whitington, P F; Neilson, K A; Suchy, F J

    1994-02-01

    Neonatal liver failure was evaluated in two infants. Neither infant had evidence of congenital infection, galactosemia, alpha 1-antitrypsin deficiency, tyrosinemia, Zellweger syndrome, or hemophagocytic lymphohistiocytosis. Abnormal levels of iron were detected in the minor salivary glands of the first infant and in the explanted liver of the second. Analyses of urinary bile salts by fast-atom bombardment ionization mass spectrometry and gas chromatography-mass spectrometry revealed a paucity of primary bile acids and a predominance of 7 alpha-hydroxy-3-oxo-4-cholenoic and 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acids. These findings are consistent with delta 4-3-oxosteroid 5 beta-reductase deficiency, a primary genetic defect in bile acid synthesis. Postmortem evaluation of the first infant revealed significant iron deposition in the liver, pancreas, thyroid, adrenal glands, myocardium, stomach, and submucosal glands of the respiratory tract. In both infants examination of the liver revealed extensive loss of hepatic parenchyma. These cases expand the clinical spectrum of bile acid metabolism defects to include neonatal liver failure with associated hemochromatosis. PMID:8301429

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Mineralocorticoid receptor antagonists as diuretics: Can congestive heart failure learn from liver failure?

    PubMed

    Masoumi, Amirali; Ortiz, Fernando; Radhakrishnan, Jai; Schrier, Robert W; Colombo, Paolo C

    2015-05-01

    Despite significant improvements in diagnosis, understanding the pathophysiology and management of the patients with acute decompensated heart failure (ADHF), diuretic resistance, yet to be clearly defined, is a major hurdle. Secondary hyperaldosteronism is a pivotal factor in pathogenesis of sodium retention, refractory congestion in heart failure (HF) as well as diuretic resistance. In patients with decompensated cirrhosis who suffer from ascites, similar pathophysiological complications have been recognized. Administration of natriuretic doses of mineralocorticoid receptor antagonists (MRAs) has been well established in management of cirrhotic patients. However, this strategy in patients with ADHF has not been well studied. This article will discuss the potential use of natriuretic doses of MRAs to overcome the secondary hyperaldosteronism as an alternative diuretic regimen in patients with HF.

  15. Mineralocorticoid receptor antagonists as diuretics: Can congestive heart failure learn from liver failure?

    PubMed Central

    Ortiz, Fernando; Radhakrishnan, Jai; Schrier, Robert W.; Colombo, Paolo C.

    2014-01-01

    Despite significant improvements in diagnosis, understanding the pathophysiology and management of the patients with acute decompensated heart failure (ADHF), diuretic resistance, yet to be clearly defined, is a major hurdle. Secondary hyperaldosteronism is a pivotal factor in pathogenesis of sodium retention, refractory congestion in heart failure (HF) as well as diuretic resistance. In patients with decompensated cirrhosis who suffer from ascites, similar pathophysiological complications have been recognized. Administration of natriuretic doses of mineralocorticoid receptor antagonists (MRAs) has been well established in management of cirrhotic patients. However, this strategy in patients with ADHF has not been well studied. This article will discuss the potential use of natriuretic doses of MRAs to overcome the secondary hyperaldosteronism as an alternative diuretic regimen in patients with HF. PMID:25447845

  16. Functional renal failure (FRF) in cirrhosis of the liver and liver carcinoma

    PubMed Central

    Vesin, P.; Traverso, H.

    1975-01-01

    The term ‘functional renal failure’ has been used to describe the renal failure developing in advanced cirrhosis in which tubular function and structure remain intact. It may develop spontaneously, in which case prognosis is poor, but may be secondary to gastro-intestinal haemorrhage or excessive use of diuretics, in which case correction of the precipitating factor leads to improvement in renal function. It is suggested that the renal failure is due to a reduction in effective circulating plasma volume. PMID:1234327

  17. 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

    PubMed Central

    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. METHODS: 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). RESULTS: 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% (χ2 for trend, P = 0.002) and 90-d mortality was 16.7%, 27.3%, 78.6% and 100% (χ2 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

  18. [Intravascular hypothermia for the management of Intracranial hypertension in acute liver failure: case report].

    PubMed

    Castillo, Luis; Pérez, Cristian; Ruiz, Carolina; Bugedo, Guillermo; Hernández, Glenn; Martínez, Jorge; Jarufe, Nicolás; Pérez, Rosa; Mellado, Patricio; Domínguez, Pilar

    2009-06-01

    Acute liver failure has a mortality rate in excess of 80%. Most deaths are attributed to brain edema with intracranial hypertension and herniation of structures, where ammonium plays a major role in its generation. We report an 18 year-old female with a fulminant hepatic failure caused by virus A infection. The patient developed a profound sopor and required mechanical ventilation. A CT scan showed the presence of brain edema and intracranial hypertension. A Raudemic catheter was inserted to measure intracranial pressure and brain temperature. Intracranial hypertension became refractory and intravascular hypothermia was started, reducing brain temperature to 33 degrees C. Seventy two hours later, a liver transplantation was performed. After testing graft perfusion, rewarming was started, completing 122 hours of hypothermia at 33 degrees C. The patient was discharged in good conditions after 69 days of hospitalization.

  19. Molecular adsorbent recirculating system as artificial support therapy for liver failure: a meta-analysis.

    PubMed

    Vaid, Arjun; Chweich, Haval; Balk, Ethan M; Jaber, Bertrand L

    2012-01-01

    Molecular Adsorbent Recirculating System (MARS) is an artificial liver support system that has been developed for patients with liver failure until the liver regains function or as a bridge to transplantation. We conducted a meta-analysis to examine the efficacy of this promising therapy. We searched MEDLINE, EMBASE, and the Cochrane Registry of Controlled Trials databases, and abstracts from the proceedings of several scientific meetings. Patients with acute, acute on chronic, and hyperacute liver failure were included and we compared MARS with standard medical therapy. Randomized and nonrandomized controlled trials were included and Molecular Adsorbent Recirculating System was the intervention used. We evaluated net change in total bilirubin levels, improvement in hepatic encephalopathy and mortality. Nine randomized controlled trials and one nonrandomized controlled study met criteria and were included. By meta-analysis, MARS resulted in a significant decrease in total bilirubin levels (net change -7.0 mg/dl; 95% CI -10.4, -3.7; p < 0.001) and in an improvement in the West-Haven grade of hepatic encephalopathy (odds ratio [OR] 3.0; 95% CI 1.9, 5.0; p < 0.001). There was no beneficial effect on mortality (OR 0.91; 95% CI 0.64, 1.31; p = 0.62). The limitations of this study include a small sample size, an inability to blind with significant heterogeneity among studies, and variable definitions of liver failure. The Molecular Adsorbent Recirculating System is associated with a significant improvement in total bilirubin levels and hepatic encephalopathy but has no impact on survival. Large studies are required to assess the merit of this promising therapy on patient-centered outcomes. PMID:22210651

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

    PubMed

    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. PMID:24712173

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

    PubMed

    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.

  2. Heterotopic Auxiliary Rat Liver Transplantation With Flow-regulated Portal Vein Arterialization in Acute Hepatic Failure

    PubMed Central

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.1-3 The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.4 In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.5-6 We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor’s portal vein was carried out via the recipient’s right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient’s aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. 7 In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft’s weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  3. Heterotopic auxiliary rat liver transplantation with flow-regulated portal vein arterialization in acute hepatic failure.

    PubMed

    Schleimer, Karina; Kalder, Johannes; Grommes, Jochen; Jalaie, Houman; Tawadros, Samir; Greiner, Andreas; Jacobs, Michael; Kokozidou, Maria

    2014-01-01

    In acute hepatic failure auxiliary liver transplantation is an interesting alternative approach. The aim is to provide a temporary support until the failing native liver has regenerated.(1-3) The APOLT-method, the orthotopic implantation of auxiliary segments- averts most of the technical problems. However this method necessitates extensive resections of both the native liver and the graft.(4) In 1998, Erhard developed the heterotopic auxiliary liver transplantation (HALT) utilizing portal vein arterialization (PVA) (Figure 1). This technique showed promising initial clinical results.(5-6) We developed a HALT-technique with flow-regulated PVA in the rat to examine the influence of flow-regulated PVA on graft morphology and function (Figure 2). A liver graft reduced to 30 % of its original size, was heterotopically implanted in the right renal region of the recipient after explantation of the right kidney.  The infra-hepatic caval vein of the graft was anastomosed with the infrahepatic caval vein of the recipient. The arterialization of the donor's portal vein was carried out via the recipient's right renal artery with the stent technique. The blood-flow regulation of the arterialized portal vein was achieved with the use of a stent with an internal diameter of 0.3 mm. The celiac trunk of the graft was end-to-side anastomosed with the recipient's aorta and the bile duct was implanted into the duodenum. A subtotal resection of the native liver was performed to induce acute hepatic failure. (7) In this manner 112 transplantations were performed. The perioperative survival rate was 90% and the 6-week survival rate was 80%. Six weeks after operation, the native liver regenerated, showing an increase in weight from 2.3±0.8 g to 9.8±1 g. At this time, the graft's weight decreased from 3.3±0.8 g to 2.3±0.8 g. We were able to obtain promising long-term results in terms of graft morphology and function. HALT with flow-regulated PVA reliably bridges acute hepatic failure

  4. Preventing cerebral oedema in acute liver failure: the case for quadruple-H therapy.

    PubMed

    Warrillow, S J; Bellomo, R

    2014-01-01

    Severe cerebral oedema is a life-threatening complication of acute liver failure. Hyperammonaemia and cerebral hyperaemia are major contributing factors. A multimodal approach, which incorporates hyperventilation, haemodiafiltration, hypernatraemia and hypothermia (quadruple-H therapy), may prevent or attenuate severe cerebral oedema. This approach is readily administered by critical care clinicians and is likely to be more effective than the use of single therapies. Targeting of PaCO2 in the mild hyperventilation range, as seen in acute liver failure patients before intubation, aims to minimise hyperaemic cerebral oedema. Haemodiafiltration aims to achieve the rapid control of elevated blood ammonia concentrations by its removal and to reduce production via the lowering of core temperature. The administration of concentrated saline increases serum tonicity and further reduces cerebral swelling. In addition, the pathologically increased cerebral blood-flow is further attenuated by therapeutic hypothermia. The combination of all four treatments in a multimodal approach may be a safe and effective means of attenuating or treating the cerebral oedema of acute liver failure and preventing death from neurological complications. PMID:24471667

  5. Citrin deficiency presenting as acute liver failure in an eight-month-old infant.

    PubMed

    Zhang, Mei-Hong; Gong, Jing-Yu; Wang, Jian-She

    2015-06-21

    Citrin deficiency typically presents as neonatal intrahepatic cholestasis and resolves in late infancy. Here we report a case of citrin deficiency that presented as acute liver failure in late infancy in an apparently healthy child. The full-term male infant weighed 3400 g at birth, and exhibited normal development for eight months, at which time he contracted bronchial pneumonia. The infant developed jaundice and laboratory tests indicated elevated bilirubin and ammonia levels and an abnormal coagulation profile. Plasma amino acid analysis showed elevated levels of tyrosine, methionine, citrulline, and arginine. Citrin deficiency was suspected, and genomic DNA analysis revealed a mutation (IVS16ins3kb) in SLC25A13, which encodes a mitochondrial aspartate-glutamate carrier protein. The infant was immediately put on a lactose-free, medium-chain-triglyceride-enriched formula with ursodeoxycholic acid and lipid-soluble vitamins. However, cholestasis and abnormal laboratory indices persisted, and the infant died at the age of 11.5 mo, two days before a scheduled liver transplantation. This case demonstrates that citrin deficiency can present in late infancy as acute liver failure triggered by infection, and may require liver transplantation. PMID:26109823

  6. TIMP-1 attenuates blood–brain barrier permeability in mice with acute liver failure

    PubMed Central

    Chen, Feng; Radisky, Evette S; Das, Pritam; Batra, Jyotica; Hata, Toshiyuki; Hori, Tomohide; Baine, Ann-Marie T; Gardner, Lindsay; Yue, Mei Y; Bu, Guojun; del Zoppo, Gregory; Patel, Tushar C; Nguyen, Justin H

    2013-01-01

    Blood–brain barrier (BBB) dysfunction in acute liver failure (ALF) results in increased BBB permeability that often precludes the patients from obtaining a life-saving liver transplantation. It remains controversial whether matrix metalloproteinase-9 (MMP-9) from the injured liver contributes to the deregulation of BBB function in ALF. We selectively upregulated a physiologic inhibitor of MMP-9 (TIMP-1) with a single intracerebroventricular injection of TIMP-1 cDNA plasmids at 48 and 72 hours, or with pegylated-TIMP-1 protein. Acute liver failure was induced with tumor necrosis factor-α and 𝒟-(+)-galactosamine in mice. Permeability of BBB was assessed with sodium fluorescein (NaF) extravasation. We found a significant increase in TIMP-1 within the central nervous system (CNS) after the administration of TIMP-1 cDNA plasmids and that increased TIMP-1 within the CNS resulted in an attenuation of BBB permeability, a reduction in activation of epidermal growth factor receptor and p38 mitogen-activated protein kinase signals, and a restoration of the tight junction protein occludin in mice with experimental ALF. Pegylated TIMP-1 provided similar protection against BBB permeability in mice with ALF. Our results provided a proof of principle that MMP-9 contributes to the BBB dysfunction in ALF and suggests a potential therapeutic role of TIMP-1 in ALF. PMID:23532086

  7. Citrin deficiency presenting as acute liver failure in an eight-month-old infant

    PubMed Central

    Zhang, Mei-Hong; Gong, Jing-Yu; Wang, Jian-She

    2015-01-01

    Citrin deficiency typically presents as neonatal intrahepatic cholestasis and resolves in late infancy. Here we report a case of citrin deficiency that presented as acute liver failure in late infancy in an apparently healthy child. The full-term male infant weighed 3400 g at birth, and exhibited normal development for eight months, at which time he contracted bronchial pneumonia. The infant developed jaundice and laboratory tests indicated elevated bilirubin and ammonia levels and an abnormal coagulation profile. Plasma amino acid analysis showed elevated levels of tyrosine, methionine, citrulline, and arginine. Citrin deficiency was suspected, and genomic DNA analysis revealed a mutation (IVS16ins3kb) in SLC25A13, which encodes a mitochondrial aspartate-glutamate carrier protein. The infant was immediately put on a lactose-free, medium-chain-triglyceride-enriched formula with ursodeoxycholic acid and lipid-soluble vitamins. However, cholestasis and abnormal laboratory indices persisted, and the infant died at the age of 11.5 mo, two days before a scheduled liver transplantation. This case demonstrates that citrin deficiency can present in late infancy as acute liver failure triggered by infection, and may require liver transplantation. PMID:26109823

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

    PubMed

    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. PMID:25471806

  9. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: update. Consensus SEMICYUC-SENPE: liver failure and liver transplantation.

    PubMed

    Montejo González, J C; Mesejo, A; Bonet Saris, A

    2011-11-01

    Patients with liver failure have a high prevalence of malnutrition, which is related to metabolic abnormalities due to the liver disease, reduced nutrient intake and alterations in digestive function, among other factors. In general, in patients with liver failure, metabolic and nutritional support should aim to provide adequate nutrient intake and, at the same time, to contribute to patients' recovery through control or reversal of metabolic alterations. In critically-ill patients with liver failure, current knowledge indicates that the organ failure is not the main factor to be considered when choosing the nutritional regimen. As in other critically-ill patients, the enteral route should be used whenever possible. The composition of the nutritional formula should be adapted to the patient's metabolic stress. Despite the physiopathological basis classically described by some authors who consider amino acid imbalance to be a triggering factor and key element in maintaining encephalopathy, there are insufficient data to recommend "specific" solutions (branched-chain amino acid-enriched with low aromatic amino acids) as part of nutritional support in patients with acute liver failure. In patients undergoing liver transplantation, nutrient intake should be started early in the postoperative period through transpyloric access. Prevention of the hepatic alterations associated with nutritional support should also be considered in distinct clinical scenarios. PMID:22411515

  10. Renal failure and abdominal hypertension after liver transplantation: determination of critical intra-abdominal pressure.

    PubMed

    Biancofiore, Gianni; Bindi, Lucia; Romanelli, Anna Maria; Bisà, Massimo; Boldrini, Antonella; Consani, Giovanni; Danella, Augusta; Urbani, Lucio; Filipponi, Franco; Mosca, Franco

    2002-12-01

    There is growing interest in measuring intra-abdominal pressure (IAP) in postsurgical and critically ill patients because increased pressure can impair various organs and functions. The aim of this study was to evaluate the effect of different IAP levels on the postoperative renal function of subjects undergoing orthotopic liver transplantation. IAP was measured every 8 hours with the urinary bladder pressure method for at least 72 hours after surgery. At the end of the study, the patients were classified on the basis of their IAP values: < or = 18 mm Hg (group A), 19 to 24 mm Hg (group B), > or = 25 mm Hg (group C). The three groups were compared in terms of the incidence of acute renal failure (defined as blood creatinine > 1.5 mg/dL or an increase in the same of > 1.1 mg/dL within 72 hours of surgery), hourly diuresis, blood creatinine, the filtration gradient, hemodynamic variations, and outcome. The incidence of renal failure was higher among the subjects in group C (P < .05 versus group A and < .01 versus group B), who also had higher creatinine levels (P < .01), a greater need for diuretics (P < .01) and a worse outcome (P < .05). Receiver Operator Characteristic curve analysis showed that an abdominal pressure of 25 mm Hg had the best sensitivity/specificity ratio for renal failure. An intra-abdominal pressure of > or = 25 mm Hg is an important risk factor for renal failure in subjects undergoing liver transplant.

  11. Anti-4-1BB monoclonal antibodies attenuate concanavalin A-induced immune-mediated liver injury in mice

    PubMed Central

    Xia, Guangtao; Wu, Sensen; Zhang, Yuanchao

    2016-01-01

    Effective therapies for the treatment of immune-mediated liver disease are currently lacking. As a member of the tumor necrosis factor receptor superfamily, 4-1BB has a key role in T-cell activation and has been implicated in the development of autoimmune disorders. The purpose of the present study was to evaluate the potential therapeutic or preventive function of an anti-4-1BB monoclonal antibody (mAb) in a mouse model of concanavalin (Con) A-induced immune-mediated liver injury. A mouse model of immune-mediated liver injury was established by tail vein injection of Con A (20 mg/kg). 4-1BB mAb (100 µg), with or without methylprednisolone (MEP; 3 mg/kg), was intraperitoneally injected into the tail vein 2 h prior to or 2 h following Con A injection. Con A induced marked hepatocyte necrosis, significantly reduced CD 4+/CD25+ T-cell levels, and increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), in addition to the percentage of 4-1BB+ T-cells, compared with the control (all P<0.05). The administration of 4-1BB mAb prior to or following Con A injection was able to attenuate Con A-induced liver tissue damage and significantly reduce serum AST and ALT levels (P<0.05). A combination of MEP and 4-1BB mAb further reduced serum AST and ALT levels, compared with either treatment alone. In addition, administration of 4-1BB mAb and MEP alone or in combination significantly increased CD4+/CD25+ T-cell levels, compared with the control (P<0.05). These results suggested that 4-1BB mAb was able to attenuate liver injury and preserve liver function in a mouse model of Con A-induced immune-mediated liver injury by promoting the expansion of CD4+/CD25+ T-cells. Furthermore, a combination of 4-1BB mAb with MEP was associated with greater beneficial effects than either treatment alone. The clinical significance of 4-1BB mAb in immune-mediated liver disease remains to be elucidated in future studies. PMID:27588047

  12. Hepatic Hemodynamics and Elevation of Liver Stiffness as Possible Predictive Markers of Late-onset Hepatic Failure.

    PubMed

    Kakisaka, Keisuke; Kuroda, Hidekatsu; Abe, Tamami; Suzuki, Yuji; Yoshida, Yuichi; Kataoka, Kojiro; Miyamoto, Yasuhiro; Ishida, Kazuyuki; Takikawa, Yasuhiro

    2016-01-01

    A 52-year-old Japanese woman admitted to our hospital for the treatment of liver dysfunction due to an undetermined cause developed disorientation on the 58th hospital day and was diagnosed with late-onset liver failure. Abdominal ultrasound examinations were performed several times from the admission. Before the disorientation appeared, the results of the examinations revealed that the portal flow decreased, after which the hepatic arterial flow increased and the degree of liver stiffness became elevated. Although the pathophysiology of these changes remains unclear, hemodynamic changes and elevation of liver stiffness might be predictive markers of severe liver tissue damage.

  13. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure

    PubMed Central

    Chen, En-Qiang; Zeng, Fan; Zhou, Ling-Yun; Tang, Hong

    2015-01-01

    Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field. PMID:26576085

  14. Acute Liver Failure in an Adult, a Rare Complication of Alagille Syndrome: Case Report and Brief Review.

    PubMed

    Frongillo, F; Bianco, G; Silvestrini, N; Lirosi, M C; Sanchez, A M; Nure, E; Gaspari, R; Avolio, A W; Sganga, G; Agnes, S

    2015-09-01

    Alagille syndrome (AS) is an autosomal-dominant, multisystem disorder affecting the liver, heart, eyes, skeleton, and face. The manifestations are predominantly pediatric. Diagnosis is based on findings of a paucity of bile ducts on liver biopsy combined with ≥3 of 5 major clinical criteria. Orthotopic liver transplantation (OLT) is the only option for treating patients who developed liver failure, portal hypertension, severe itching, and xanthomatosis. It is difficult to establish clear criteria for OLT; indications are controversial because of the wide variety of clinical symptoms and the multisystem involvement. Generally, AS-associated liver disease is never an acute illness. We report the case of a 28-year-old woman with AS who underwent urgent OLT for acute liver failure. At 24 months posttransplant, the patient is in good clinical condition and with normal hepatic and renal function. PMID:26361673

  15. Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure.

    PubMed

    Kobashi-Margáin, Ramón A; Gavilanes-Espinar, Juan G; Gutiérrez-Grobe, Ylse; Gutiérrez-Jiménez, Angel A; Chávez-Tapia, Norberto; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez Sánchez, Nahum

    2011-06-01

    Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.

  16. Bench-to-bedside review: Current evidence for extracorporeal albumin dialysis systems in liver failure

    PubMed Central

    Karvellas, Constantine J; Gibney, Noel; Kutsogiannis, Demetrios; Wendon, Julia; Bain, Vincent G

    2007-01-01

    Acute liver failure (ALF) and acute on chronic liver failure (AoCLF) carry a high mortality. The rationale for extracorporeal systems is to provide an environment facilitating recovery or a window of opportunity for liver transplantation. Recent technologies have used albumin as a scavenging molecule. Two different albumin dialysis systems have been developed using this principle: MARS (Molecular Adsorbent Recirculation System) and SPAD (Single-Pass Albumin Dialysis). A third system, Prometheus (Fractionated Plasma Separation and Adsorption), differs from the others in that the patient's albumin is separated across a membrane and then is run over adsorptive columns. Although several trials have been published (particularly with MARS), currently there is a lack of controlled studies with homogenous patient populations. Many studies have combined patients with ALF and AoCLF. Others have included patients with different etiologies. Although MARS and Prometheus have shown biochemical improvements in AoCLF and ALF, additional studies are required to show conclusive benefit in short- and long-term survival. The appropriate comparator is standard medical therapy rather than head-to-head comparisons of different forms of albumin dialysis. PMID:17567927

  17. The effect of black raspberry extracts on MnSOD activity in protection against concanavalin A induced liver injury

    PubMed Central

    Li, Xuanyi; Li, Yan; States, Vanessa A.; Li, Suping; Zhang, Xiang; Martin, Robert C.G.

    2015-01-01

    Inflammation and oxidative stress are the key events in carcinogenetic transformation. Black raspberries (BRB) have been demonstrated to have antioxidant, anti-inflammatory and anti-cancer bioactivities. In this study, a concanavalin A induced hepatitis mouse model is used to examine the effect of BRB extract on hepatic injury. Three BRB extracts, including ethanol/H2O extracts (both anthocyanin-contained fraction and non-anthocyanin-contained fraction) and hexane extract were used. The alterations in hepatic histology, apoptosis and oxidative stress were observed in the animals pretreated with BRB extracts and then challenged by concanavalin A. Results indicate that ethanol/H2O extracts can inhibit Con A induced liver injury. The hepatic protection by the ethanol/H2O BRB extracts is associated with decreases of lipid peroxidation and NDA oxidative damage. Importantly, the BRB extracts increase manganese superoxide dismutase (MnSOD) activity but not the CuZnSOD. The preservation of MnSOD by BRB extracts is associated with the protective action in the liver challenged by Con A. Ethanol/H2O BRB extracts function as antioxidants, thus demonstrating the critical role of oxidative stress in the Con A induced liver injury, and providing evidence that the protective effects of ethanol/H2O BRB extracts result, at least in part, from their antioxidant action. PMID:24911141

  18. Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children.

    PubMed

    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 <15 years attending our institution during 1989-2011 were reviewed. Of the 41 ALF patients, 2, 6 and 33 patients had dengue hemorrhagic fever grade II, III and IV, respectively. Multiorgan 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.

  19. Novel lipid-based approaches to pediatric intestinal failure-associated liver disease.

    PubMed

    Diamond, Ivan R; Pencharz, Paul B; Feldman, Brian M; Ling, Simon C; Moore, Aideen M; Wales, Paul W

    2012-05-01

    Historically, intestinal failure-associated liver disease (IFALD) has been the greatest contributor to the morbidity experienced by children with intestinal failure. Although the cause of IFALD is multifactorial, recently much attention has been devoted to the critical role that intravenous lipid emulsions play in the development of IFALD. This attention has prompted an interest in alternate approaches to the provision of intravenous lipid in children with IFALD. The 2 approaches that have been advanced are that of lipid minimization and alternate intravenous lipid emulsions, including those containing ω-3 fatty acids. This article examines the rationale and current evidence for these approaches in children with intestinal failure. Our overall finding is that although these alternate approaches show significant promise, they have primarily been studied in uncontrolled settings, mainly in children with advanced IFALD. As such, we believe that there remains a lack of definitive evidence for their efficacy. Furthermore, important safety parameters remain to be evaluated, including the effect of these therapies on growth and development. Therefore, there is currently insufficient evidence to support the use of these novel therapies as standard of care in children with no or early IFALD with the goal of preventing the progression of liver disease.

  20. Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study.

    PubMed

    Zhou, Pengcheng; Shao, Li; Zhao, Lifu; Lv, Guoliang; Pan, Xiaoping; Zhang, Anye; Li, Jianzhou; Zhou, Ning; Chen, Deying; Li, Lanjuan

    2016-01-01

    Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 ± 7.9 h vs. 49.3 ± 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 ± 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate-chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL. PMID:27194381

  1. Efficacy of Fluidized Bed Bioartificial Liver in Treating Fulminant Hepatic Failure in Pigs: A Metabolomics Study

    PubMed Central

    Zhou, Pengcheng; Shao, Li; Zhao, Lifu; Lv, Guoliang; Pan, Xiaoping; Zhang, Anye; Li, Jianzhou; Zhou, Ning; Chen, Deying; Li, Lanjuan

    2016-01-01

    Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h. Serum samples were assayed using ultra-performance liquid chromatography-mass spectrometry. The difference in survival time (51.6 ± 7.9 h vs. 49.3 ± 6.6 h) and serum metabolome was negligible between the S and C groups, whereas FBBAL treatment significantly prolonged survival time (70.4 ± 11.5h, P < 0.01) and perturbed the serum metabolome, resulting in a marked decrease in phosphatidylcholines, lysophosphatidylcholines, sphingomyelinase, and fatty acids and an increase in conjugated bile acids. The FBBAL exhibits some liver functions and may exert its therapeutic effect by altering the serum metabolome of FHF pigs. Moreover, alginate–chitosan capsules have less influence on serum metabolites. Nevertheless, the alterations were not universally beneficial, revealing that much should be done to improve the FBBAL. PMID:27194381

  2. Immunotherapy in the treatment and prevention of infection in acute-on-chronic liver failure.

    PubMed

    Bernsmeier, Christine; Singanayagam, Arjuna; Patel, Vishal C; Wendon, Julia; Antoniades, Charalambos G

    2015-01-01

    Chronic liver disease, depicted by gradual destruction and fibrosis of the liver, is a condition with high and probably increasing prevalence worldwide. Its deterioration, acute-on-chronic liver failure (ACLF), is characterized by an in-hospital mortality of up to 65%. Infectious complications are the main precipitants eliciting ACLF and concurrently the main cause of death from ACLF. Patients have a marked susceptibility to bacterial infections, which is thought to arise a consequence of an inadequate immune response to microbial challenge, termed immuneparesis. The pathophysiologic mechanisms remain poorly understood. Treatments aimed at restoring the patients' immune function may prevent onset of ACLF and death from secondary infections. A number of drugs approved for patients with liver disease bear immunomodulatory potential such as albumin, glucocorticoids, N-acetylcysteine. Specific targets have been defined that may lead to development of new immunotherapeutic agents. Here, we summarize the pathophysiology of immuneparesis in ACLF and drug candidates to restore immune function and improve survival in the future.

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

    PubMed Central

    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. PMID:27672457

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

    PubMed

    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. PMID:27672457

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

    PubMed Central

    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.

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

    PubMed

    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.

  7. Acute liver failure as a rare initial manifestation of peripheral T-cell lymphoma

    PubMed Central

    Davis, Michael L; Hashemi, Nikroo

    2010-01-01

    Acute liver failure (ALF) is an uncommon disease in the United States, affecting more than 2 000 people each year. Of all the various causes, malignant infiltration is one of the least well known and carries with it a high mortality. We describe a case of ALF as the presenting manifestation of peripheral T-cell lymphoma in an elderly woman. By reporting this case, we hope to increase early recognition of this disease process in order to potentially improve treatment outcomes. PMID:21160947

  8. Liver failure induces a systemic inflammatory response. Prevention by recombinant N-terminal bactericidal/permeability-increasing protein.

    PubMed

    Boermeester, M A; Houdijk, A P; Meyer, S; Cuesta, M A; Appelmelk, B J; Wesdorp, R I; Hack, C E; Van Leeuwen, P A

    1995-11-01

    The observed increased susceptibility of patients with fulminant hepatic failure for local and systemic infections has been hypothesized to be due to a failure for the hepatic clearance function and subsequent leaking of endogenous endotoxins into the systemic circulation. However, experimental evidence for such a systemic inflammation during liver failure due to endogenous endotoxemia is lacking. Therefore, we designed a study to clarify whether circulating endotoxins due to liver failure could lead to the development of systemic inflammations. In a rat model for liver failure induced by a two-thirds partial hepatectomy, we evaluated the course of circulating tumor necrosis factor and interleukin-6, changes in blood chemistry and hemodynamics, and histopathological changes in the lungs. Partially hepatectomized animals, but not sham-operated animals, demonstrated cardiac failure, increased levels of creatinin and urea, metabolic acidosis, high plasma levels of tumor necrosis factor and interleukin-6, and an influx of PMNs in the lungs-together indicating the development of a systemic inflammatory response. Continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23), a well described endotoxin-neutralizing protein, prevented these inflammatory reactions. Ex vivo experiments with rat plasma samples confirmed the presence of circulating endotoxins in partially hepatectomized rats as opposed to those treated with rBPI23. Thus, our results indicate that the early phase of liver failure induces a systemic inflammatory response triggered by circulating endotoxins, which can be prevented by perioperative infusion of rBPI23.

  9. Relevance of liver failure for anti-infective agents: from pharmacokinetic alterations to dosage adjustments

    PubMed Central

    Büdingen, Fiona V.; Gonzalez, Daniel; Tucker, Amelia N.

    2014-01-01

    The liver is a complex organ with great ability to influence drug pharmacokinetics (PK). Due to its wide array of function, its impairment has the potential to affect bioavailability, enterohepatic circulation, drug distribution, metabolism, clearance, and biliary elimination. These alterations differ widely depending on the cause of the liver failure, if it is acute or chronic in nature, the extent of impairment, and comorbid conditions. In addition, the effects on liver functions do not occur in a proportional or predictable manner for escalating degrees of liver impairment. The ability of hepatic alterations to influence PK is also dependent on drug characteristics, such as administration route, chemical properties, protein binding, and extraction ratio, among others. This complexity makes it difficult to predict what effects these changes will have on a particular drug. Unlike certain classes of agents, efficacy of anti-infectives is most often dependent on fulfilling PK/pharmacodynamic targets, such as maximum concentration/minimum inhibitory concentration (Cmax/MIC), area under the curve/minimum inhibitory concentration (AUC/MIC), time above MIC (T>MIC), half-maximal inhibitory concentration (IC50) or half-maximal effective concentration (EC50), or the time above the concentration which inhibits viral replication by 95% (T>EC95). Loss of efficacy and/or an increased risk of toxicity may occur in certain circumstances of liver injury. Although it is important to consider these potential alterations and their effects on specific anti-infectives, many lack data to constitute specific dosing adjustments, making it important to monitor patients for effectiveness and toxicities of therapy. PMID:24949199

  10. Occurrence of chronic renal failure in liver transplantation: monitoring of pre- and posttransplantation renal function.

    PubMed

    Umbro, I; Tinti, F; Piselli, P; Fiacco, F; Giannelli, V; Di Natale, V; Zavatto, A; Merli, M; Rossi, M; Ginanni Corradini, S; Poli, L; Berloco, P B; Mitterhofer, A P

    2012-09-01

    The aim of our study was to evaluate the occurrence of middle and long-term chronic renal failure (CRF) after orthotopic liver transplantation (OLT) in relation to acute renal failure (ARF). We prospectively monitored 75 patients, studying renal function on the basis of serum creatinine and glomerular filtration rate as estimated using the Modification of Diet in Renal Disease formula before as well as 1,6, and 12 months after OLT. The prevalence of ARF was 56% classified by the Acute Kidney injury Network criteria (52% stage 1, 29% stage 2, and 19% stage 3). The occurrences of CRF were 18.6% (11/59), 11.5% (6/52), and 14% (6/43) at 1, 6, and 12 months after OLT, respectively. The occurrence of CRF before OLT was 14.7%. We did not find any association between ARF and post-OLT CRF. The most relevant result of our study was the association between CRF at 6 and 12 months after transplantation with pre-OLT CRF on univariate and multivariate analysis. We suggest that evaluation of pre-OLT renal function should always be considered in the follow-up of liver transplant patients. Pre-OLT renal dysfunction must be recognized to be a risk factor for post-OLT CRF, representing important criterion to define specific therapeutic interventions to reduce patient morbidity and mortality.

  11. Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure.

    PubMed

    Tang, Yunxia; Li, Qiongshu; Meng, Fanwei; Huang, Xingyu; Li, Chan; Zhou, Xin; Zeng, Xiaoping; He, Yixin; Liu, Jia; Hu, Xiang; Hu, Ji-Fan; Li, Tao

    2016-01-01

    Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms. PMID:27057357

  12. Therapeutic Potential of HGF-Expressing Human Umbilical Cord Mesenchymal Stem Cells in Mice with Acute Liver Failure

    PubMed Central

    Tang, Yunxia; Li, Qiongshu; Meng, Fanwei; Huang, Xingyu; Li, Chan; Zhou, Xin; Zeng, Xiaoping; He, Yixin; Liu, Jia; Hu, Xiang; Hu, Ji-Fan; Li, Tao

    2016-01-01

    Human umbilical cord-derived mesenchymal stem cells (UCMSCs) are particularly attractive cells for cellular and gene therapy in acute liver failure (ALF). However, the efficacy of this cell therapy in animal studies needs to be significantly improved before it can be translated into clinics. In this study, we investigated the therapeutic potential of UCMSCs that overexpress hepatocyte growth factor (HGF) in an acetaminophen-induced acute liver failure mouse model. We found that the HGF-UCMSC cell therapy protected animals from acute liver failure by reducing liver damage and prolonging animal survival. The therapeutic effect of HGF-UCMSCs was associated with the increment in serum glutathione (GSH) and hepatic enzymes that maintain redox homeostasis, including γ-glutamylcysteine synthetase (γ-GCS), superoxide dismutase (SOD), and catalase (CAT). Immunohistochemical staining confirmed that HGF-UCMSCs were mobilized to the injured areas of the liver. Additionally, HGF-UCMSCs modulated apoptosis by upregulating the antiapoptotic Bcl2 and downregulating proapoptotic genes, including Bax and TNFα. Taken together, these data suggest that ectopic expression of HGF in UCMSCs protects animals from acetaminophen-induced acute liver failure through antiapoptosis and antioxidation mechanisms. PMID:27057357

  13. Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir

    PubMed Central

    Mutimer, D; Feraz-Neto, B; Harrison, R; O'Donnell, K; Shaw, J; Cane, P; Pillay, D

    2001-01-01

    BACKGROUND—Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure.
CASE REPORT—A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the devlopment of graft failure.
OUTCOME—A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved.
CONCLUSION—The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.


Keywords: hepatitis B virus; adefovir; liver graft; lamivudine PMID:11709523

  14. Clinical management of acute liver failure: Results of an international multi-center survey

    PubMed Central

    Rabinowich, Liane; Wendon, Julia; Bernal, William; Shibolet, Oren

    2016-01-01

    AIM To assess the practice of caring for acute liver failure (ALF) patients in varying geographic locations and medical centers. METHODS Members of the European Acute Liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed, treating between 300 and 500 ALF cases and performing over 100 liver transplants (LT) for ALF annually. The questions pertained to details of the institution and their clinical activity, standards of care, referral and admission, ward- based care versus intensive care unit (ICU) as well as questions regarding liver transplantation - including criteria, limitations, and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted, treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers, particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamol-related ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals, lactulose, nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure (ICP). ICP monitoring was employed in 12 centers, with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT, with a 90% post transplant

  15. Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

    PubMed Central

    Andraus, Wellington; de Martino, Rodrigo Bronze; Ortega, Neli Regina de Siqueira; Abe, Jair Minoro; D’Albuquerque, Luiz Augusto Carneiro

    2015-01-01

    Background Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied. Methods and Findings A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na+ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome

  16. D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure?

    PubMed Central

    Saracyn, Marek; Zdanowski, Robert; Brytan, Marek; Kade, Grzegorz; Nowak, Zbigniew; Patera, Janusz; Dyrla, Przemysław; Gil, Jerzy; Wańkowicz, Zofia

    2015-01-01

    Background Short-term administration of Galactosamine to experimental animals causes liver damage and acute liver failure (ALF), as well as acute renal failure in some cases. The aim of our study was to describe kidney disorders that developed in the course of galactosamine-induced liver failure. Material/Methods Sprague-Dawley rats were randomly divided into 2 groups: a study group administered galactosamine intraperitoneally and a control group administered saline. Results All the animals in the study group developed liver damage and failure within 48 h, with significant increase of alanine (p<0.001), aspartate aminotransferases (p<0.0001), bilirubin (p<0.004), and ammonia (p<0.005) and decrease of albumin (p<0.001) concentrations. Acute renal failure was observed in all test animals, with a significant increase in creatinine (p<0.001) and urea (p<0.001) concentrations and a decrease in creatinine clearance (p<0.0012). Moreover, osmotic clearance (p<0.001), daily natriuresis (p<0.003), and fractional sodium excretion (p<0.016) decreased significantly in this group of animals. The ratio of urine osmolality to serum osmolality did not change. Histopathology of the liver revealed massive necrosis of hepatocytes, whereas renal histopathology showed no changes. Conclusions Acute renal failure that developed in the course of galactosamine-induced ALF was of a functional nature, with the kidneys retaining the ability to concentrate urine and retain sodium, and there were no renal changes in the histopathological examination. It seems that the experimental model of ALF induced by galactosamine can be viewed as a model of hepatorenal syndrome that occurs in the course of acute damage and liver failure. PMID:26009004

  17. Etiologies and Outcomes of Acute Liver Failure in a Spanish Community

    PubMed Central

    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. PMID:24024035

  18. [Acute liver failure due to T cell lymphoma without hepatic infiltration].

    PubMed

    Ortega López Juan, J; López Espinosa, J; Roqueta Mas, J; Sabado Alvarez, C; Ruiz Marcellan, C; Iglesias Berengué, J

    2003-01-01

    Hepatomegaly and alterations in hepatic function are common to all patients with sickle-cell disease. In these patients, hepatic sickling is a manifestation of severe intrahepatic vaso-oclusive crises, even at levels of 25 % HbS and hematocrits of more than 45-50 %, which in 10 % of cases can lead to acute hepatic failure (AHF). AHF can be due to a variety of causes, including hematologic malignancies, but T cell lymphoma, which is usually secondary to diffuse hepatic infiltration and ischemia, is an exceptional cause, although other mechanisms can be involved. Cytokines released by lymphomas have recently been implicated as a cause of AHF.We describe a black girl with sickle cell disease, who developed AHF due to T cell lymphoma without lymphomatous infiltration of the liver. The only mechanism found to explain the clinical findings was release of cytokines by lymphoma. In patients with AHF of unknown etiology we propose early liver biopsy, because prognosis depends on the presence or absence of hepatic tumour infiltration. If AHF develops in a patient with diagnosed malignant disease, cytokine release may be the cause of AHF. Consequently, early diagnosis of the underlying disease and provision of liver support, as well as direct removal of inflammatory mediators from the circulation by exchange transfusion or other methods, should be the main priorities. PMID:12628121

  19. Management of Liver Failure: From Transplantation to Cell-Based Therapy

    PubMed Central

    Francipane, Maria Giovanna; Cervello, Melchiorre; Vizzini, Giovanni Battista; Pietrosi, Giada; Montalto, Giuseppe

    2011-01-01

    The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiological role of endogenous stem cells in liver regeneration and on the therapeutic benefits of exogenous stem cell administration with specific emphasis on the potential clinical uses of mesenchymal stem cells. Moreover, critical points that still need clarification, such as the exact identity of the stem-like cell population exerting the beneficial effects, as well as the limitations of stem cell-based therapies, are discussed. PMID:26998399

  20. MARS (Molecular Adsorbent Recirculating System): experience in 34 cases of acute liver failure.

    PubMed

    Novelli, Gilnardo; Rossi, Massimo; Pretagostini, Renzo; Poli, Luca; Novelli, Luigi; Berloco, Pasquale; Ferretti, Giancarlo; Iappelli, Massimo; Cortesini, Raffaello

    2002-01-01

    As reported in the literature, the mortality rates for patients with Acute Hepatic Failure (AHF) approaches 80% in cases in which liver transplantation is not possible. Post-transplant mortality mostly depends on the severity of the neurological condition at the time of the operation (20% in I-II degree coma patients and 44% in III degree coma patients). The primary indications for liver transplantation in AHF are Fulminant Hepatitis (FH)(93%), Subfulminant Hepatitis (5%) and other indications (2%). Other causes of AHF are Primary Non-Function (PNF) and Delayed Function (DF), which occur in 7-10%. Therefore it becomes necessary to monitor the patients with a Liver Support Device to be able to improve the clinical condition of the patients before liver transplantation (LT). In our experience we used the Molecular Adsorbent Recirculating System (MARS) (MARS Monitor; Teraklin AG, Rostock Germany), which enables the selective removal of albumin-bound substances accumulating in liver failure by the use of albumin-enriched dialysate. The system is used as a bridging device to orthotopic liver transplantation (OLT) of patients with FHF. We studied 34 patients, including 16 males and 18 females: 9 were affected by Primary-Non-Function (PNF), nine by Fulminant Hepatitis (FH), six by Delayed-Non-Function (DNF), and ten by Acute on Chronic Hepatic Failure (AOCHF). The average age of the patients was 41.8 years and the average number of applications was 6.4; the median length of application was about eight hours. The parameters that we monitored, before and after each treatment, were neurological status (EEG, cerebral CT, Glasgow Coma Score), haemodynamic parameters, acid base equilibrium, and blood gas analysis. We also monitored hepatic and renal function. In addition, the clinical conditions of the patients were monitored using kidney and liver ultrasound/ultrasonography (US). Inclusion criteria were bilirubin > 15 mg/dL, ammonia > 160 micro g/dL and a Glasgow Coma Score

  1. Critical role of c‐jun (NH2) terminal kinase in paracetamol‐ induced acute liver failure

    PubMed Central

    Henderson, Neil C; Pollock, Katharine J; Frew, John; Mackinnon, Alison C; Flavell, Richard A; Davis, Roger J; Sethi, Tariq; Simpson, Kenneth J

    2007-01-01

    Background Acute hepatic failure secondary to paracetamol poisoning is associated with high mortality. C‐jun (NH2) terminal kinase (JNK) is a member of the mitogen‐activated protein kinase family and is a key intracellular signalling molecule involved in controlling the fate of cells. Aim To examine the role of JNK in paracetamol‐induced acute liver failure (ALF). Methods A previously developed mouse model of paracetamol poisoning was used to examine the role of JNK in paracetamol‐induced ALF. Results Paracetamol‐induced hepatic JNK activation both in human and murine paracetamol hepatotoxicity and in our murine model preceded the onset of hepatocyte death. JNK inhibition in vivo (using two JNK inhibitors with different mechanisms of action) markedly reduced mortality in murine paracetamol hepatotoxicity, with a significant reduction in hepatic necrosis and apoptosis. In addition, delayed administration of the JNK inhibitor was more effective than N‐acetylcysteine after paracetamol poisoning in mice. JNK inhibition was not protective in acute carbon tetrachloride‐mediated or anti‐Fas antibody‐mediated hepatic injury, suggesting specificity for the role of JNK in paracetamol hepatotoxicity. Furthermore, disruption of the JNK1 or JNK2 genes did not protect against paracetamol‐induced hepatic damage. Pharmacological JNK inhibition had no effect on paracetamol metabolism, but markedly inhibited hepatic tumour necrosis foctor α (TNF α) production after paracetamol poisoning. Conclusions These data demonstrated a central role for JNK in the pathogenesis of paracetamol‐induced liver failure, thereby identifying JNK as an important therapeutic target in the treatment of paracetamol hepatotoxicity. PMID:17185352

  2. New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure.

    PubMed

    Carvalho, Nélson R; da Rosa, Edovando F; da Silva, Michele H; Tassi, Cintia C; Dalla Corte, Cristiane L; Carbajo-Pescador, Sara; Mauriz, Jose L; González-Gallego, Javier; Soares, Félix A

    2013-01-01

    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 [(PhSe)2], 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 (PhSe)2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe)2 to the N-acetylcysteine (NAC) during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg), (PhSe)2 (15.6 mg/kg), NAC (1200 mg/kg), APAP+(PhSe)2 or APAP+NAC, where the (PhSe)2 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 (PhSe)2. The effectiveness of (PhSe)2 was similar at a lower dose than NAC. In summary, (PhSe)2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced. PMID:24349162

  3. Frequency and Pathophysiology of Acute Liver Failure in Ornithine Transcarbamylase Deficiency (OTCD)

    PubMed Central

    Laemmle, Alexander; Gallagher, Renata C.; Keogh, Adrian; Stricker, Tamar; Gautschi, Matthias; Nuoffer, Jean-Marc; Baumgartner, Matthias R.; Häberle, Johannes

    2016-01-01

    Background 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. Aim 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. Results 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%. Conclusion 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. PMID:27070778

  4. Emerging role of liver X receptors in cardiac pathophysiology and heart failure.

    PubMed

    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.

  5. Living-related liver transplantation for fulminant hepatic failure in children.

    PubMed

    Tanaka, K; Uemoto, S; Inomata, Y; Tokunaga, Y; Ueda, M; Tokka, A; Sato, B; Yamaoka, Y

    1994-01-01

    Liver transplantation is increasingly accepted as a choice of treatment for fulminant hepatic failure (FHF) since it has been proved to significantly improve the survival rate in these patients compared with other therapeutic modalities. We have successfully performed a total of 76 living related liver transplantations (LRLT) three of which were for FHF. The first case was an 11-year-old boy with FHF due to an unidentified cause. He had required plasmapheresis a total of 24 times and haemofiltration to save his life before LRLT. He was transplanted with a left lobe (420 g) graft, calculated as 1.05% of his weight (40 kg). He recovered hepatic function uneventfully and was discharged from hospital after 7 weeks. The second case was a 13-year-old girl who developed FHF with grade III encephalopathy due to acute Wilson's disease, and was referred to us. She underwent LRLT with a left lobe graft (440 g), estimated as 0.95% of her weight (47 kg), which functioned well after surgery. The third case was a 13-year-old girl with grade II encephalopathy due to acute Wilson's disease. She was 27% obese with a body weight of 58 kg. She underwent LRLT with ABO blood group incompatibility with a left lobe (352 g), estimated as 0.80% of her weight (modified 44 kg). She was discharged with sensorimotor neuropathy due to vitamin B deficiency. The present results suggest that LRLT is feasible for FHF both clinically and ethically, and that a partial liver graft weighing around 1% of the recipient's weight can maintain the recipient's life. We limit the diagnostic indication for LRLT to chronic liver disease, since an urgent situation may affect a voluntary decision for the patient's parents to donate the partial liver. However, LRLT is thought to be an acceptable choice of treatment provided it is requested by the patient and family. Furthermore, it is a potential option for resolving the graft shortage in paediatric liver transplantation, being independent of cadaver donor

  6. Model for end-stage liver disease predicts right ventricular failure in patients with left ventricular assist devices.

    PubMed

    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. PMID:26187243

  7. Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria.

    PubMed

    Ichai, Philippe; Legeai, Camille; Francoz, Claire; Boudjema, Karim; Boillot, Olivier; Ducerf, Christian; Mathurin, Philippe; Pruvot, François-René; Suc, Bertrand; Wolf, Philippe; Soubrane, Olivier; Le Treut, Yves Patrice; Cherqui, Daniel; Hannoun, Laurent; Pageaux, Georges-Philippe; Gugenheim, Jean; Letoublon, Christian; Saric, Jean; Di Martino, Vincent; Abergel, Armand; Chiche, Laurence; Antonini, Teresa Maria; Jacquelinet, Christian; Castaing, Denis; Samuel, Didier

    2015-04-01

    In France, decisions regarding superurgent (SU) liver transplantation (LT) for patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for SU LT and the factors that were predictive of spontaneous improvement and to determine the usefulness of the CV criteria. All patients listed in France for SU LT between 1997 and 2010 who were 15 years old or older with ALF were included. In all, 808 patients were listed for SU transplantation: 22% with paracetamol-induced ALF and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT, and 109 died or left the waiting list because of a worsening condition. The 1-year survival rate according to an intention-to-treat analysis and the survival after LT were 66.3% [interquartile range (IQR), 62.7%-69.7%] and 74.2% (IQR, 70.5%-77.6%), respectively. The factors that were predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxicity were as follows: hepatic encephalopathy grade 0, 1, or 2 [odds ratio (OR), 4.8; 95% confidence interval (CI), 1.99-11.6]; creatinine clearance≥60 mL/minute/1.73 m2 (OR, 4.77; 95% CI, 1.96-11.63), a bilirubin level<200 µmol/L (OR, 21.64; 95% CI, 1.76-265.7); and a factor V level>20% (OR, 5.79; 95% CI, 1.66-20.29). For ALF-related nonparacetamol hepatotoxicity, the factor that was predictive of a spontaneous recovery was a bilirubin level<200 µmol/L (OR, 10.38; 95% CI, 4.71-22.86). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50%, and 79%, respectively, for ALF due to paracetamol and 69%, 50%, 64%, and 55%, respectively, for ALF not related to paracetamol. The performance of current criteria for SU transplantation could be improved if paracetamol-induced ALF and non-paracetamol-induced ALF were split and 2 other items were included in this model: the

  8. Ammonia Level and Mortality in Acute Liver Failure: A Single-Center Experience.

    PubMed

    Niranjan-Azadi, Ashwini M; Araz, Filiz; Patel, Yuval A; Alachkar, Nada; Alqahtani, Saleh; Cameron, Andrew M; Stevens, Robert D; Gurakar, Ahmet

    2016-01-01

    BACKGROUND Acute liver failure (ALF) is an emergent condition that requires intensive care and manifests in particular by significant elevation in serum ammonia level. Patients with ALF with concomitant renal failure experience a further rise in ammonia levels due to decreased kidney excretion. The aim of this study was to evaluate the relationship between elevated ammonia levels and mortality and to characterize the subgroup of ALF patients who develop acute kidney injury (AKI) and require renal replacement therapy. MATERIAL AND METHODS This was a retrospective study of 36 consecutive patients admitted to Johns Hopkins Hospital's intensive care units from December 2008 to May 2013 who presented with grade III and IV hepatic encephalopathy (HE). Patients who developed AKI and required hemodialysis (HD) were compared to those without AKI. Patients with chronic kidney disease were excluded. RESULTS Sixteen patients developed AKI and underwent HD (HD group). Median ammonia levels in the HD and non-HD groups were not significantly different (p=0.95). In the HD group, 4 patients underwent liver transplantation (LT) and 3 of them survived the hospitalization. Among the 12 HD patients who did not receive LT, 6 (50%) survived. Out of 20 non-HD patients, 3 were transplanted, all of whom survived the hospitalization. Among the 17 non-HD patients who did not receive LT, 14 (82%) survived. Admission ammonia level (>120 µmol/L) was associated with higher mortality rate (OR=7.188 [95% CI 1.3326-38.952], p=0.026) in all patients. CONCLUSIONS Admission ammonia level is predictive of mortality in ALF patients with grade 3-4 HE. PMID:27480786

  9. MicroRNA-125b-5p mimic inhibits acute liver failure.

    PubMed

    Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep

    2016-01-01

    The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF. PMID:27336362

  10. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure.

    PubMed

    Romero-Gómez, Manuel; Montagnese, Sara; Jalan, Rajiv

    2015-02-01

    Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization.

  11. Acute Liver Failure in Adults: An Evidence-Based Management Protocol for Clinicians

    PubMed Central

    Misel, Michael; Gish, Robert G.

    2012-01-01

    With the goal of providing guidance on the provision of optimal intensive care to adult patients with acute liver failure (ALF), this paper defines ALF and describes a protocol for appropriately diagnosing this relatively rare clinical entity and ascertaining its etiology, where possible. This paper also identifies the few known therapies that may be effective for specific causes of ALF and provides a comprehensive approach for anticipating, identifying, and managing complications. Finally, one of the more important aspects of care for patients with ALF is the determination of prognosis and, specifically, the need for liver transplantation. Prognostic tools are provided to help guide the clinician in this critical decision process. Management of patients with ALF is complex and challenging, even in centers where staff members have high levels of expertise and substantial experience. This evidence-based protocol may, therefore, assist in the delivery of optimal care to this critically ill patient population and may substantially increase the likelihood of positive outcomes. PMID:22675278

  12. MicroRNA-125b-5p mimic inhibits acute liver failure

    PubMed Central

    Yang, Dakai; Yuan, Qinggong; Balakrishnan, Asha; Bantel, Heike; Klusmann, Jan-Henning; Manns, Michael P.; Ott, Michael; Cantz, Tobias; Sharma, Amar Deep

    2016-01-01

    The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF. PMID:27336362

  13. Population-representative Incidence of Acute-On-Chronic Liver Failure

    PubMed Central

    Shao, Jian-Guo; Zhu, Yong-Chang; Xu, Ai-Dong; Yao, Jian-Hua; Wang, Xu-Lin; Qian, Yin-Kun; Wang, Hua-Yu; Shen, Yi; Lu, Peng; Wang, Lu-Jun

    2016-01-01

    Background: Acute-on-chronic liver failure (ACLF) is a major cause of hepatic death in the world, but no population-based studies have evaluated the incidence of ACLF. This study was conducted to determine the incidence and short-term outcomes of ACLF in a region of Eastern China. Methods: In this prospective cross-sectional study, we collected data from public hospitals in Nantong city between January 1, 2005, and December 31, 2014. All hospitals with admission potential for ACLF patients were included. The primary outcome was ACLF defined as severe jaundice and coagulopathy with underlying chronic liver disease, according to diagnostic and laboratory criteria suggested by Chinese Society for Hepatology (CSH). Results: During the 10-year period, a consecutive sample of 1934 ACLF patients was included in this study. The overall ACLF incidence rate over the 10-year period was 2.53 (95% confidence interval, 2.16-2.91) per 100,000 population per year, decreasing from 3.35 in 2005 to 2.06 in 2014. Chronic hepatitis B virus (HBV) infection was the leading cause of chronic liver disease and HBV reactivation was the most common cause of acute hepatic event. The 28-day mortality for the ACLF patients had a clear decline during the study period, form 50.39% in 2005 to 35.44% in 2014. Conclusions: In the Eastern China population, the incidence of ACLF is decreasing and the prognosis improving. Short-term mortality was associated with the presence of cirrhosis and growing age. While ACLF remains a life-threatening disorder, our findings suggest that nationwide and long-term cohorts should be conducted for the natural history of ACLF. PMID:27136963

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

    PubMed Central

    Hosseinnezhad, Alireza; Vijayakrishnan, Rajakrishnan; Farmer, Mary Jo S.

    2011-01-01

    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. PMID:24765297

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

    PubMed Central

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

    2016-01-01

    AIM: To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats. METHODS: 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. RESULTS: 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 < 0.05); TLR4 mRNA/β-actin (0.07 ± 0.02, 0.22 ± 0.08 vs 0.41 ± 0.22, P < 0.05); NF-κB mRNA/β-actin (0.74 ± 0.41, 1.78 ± 0.64 vs 2.68 ± 1.35, P < 0.05); and caspase-3 mRNA/β-actin levels were all significantly reduced (1.61 ± 0.45, 2.57 ± 1.04 vs 3.41 ± 0.85, P < 0.05). The gene expression levels were

  16. Attenuation of Inflammation and Apoptosis by Pre- and Posttreatment of Darbepoetin-α in Acute Liver Failure of Mice

    PubMed Central

    Le Minh, Khoi; Klemm, Katja; Abshagen, Kerstin; Eipel, Christian; Menger, Michael D.; Vollmar, Brigitte

    2007-01-01

    In many liver disorders inflammation and apoptosis are important pathogenic components, finally leading to acute liver failure. Erythropoietin and its analogues are known to affect the interaction between apoptosis and inflammation in brain, kidney, and myocardium. The present study aimed to determine whether these pleiotropic actions also exert hepatoprotection in a model of acute liver injury. C57BL/6J mice were challenged with d-galactosamine (Gal) and Escherichia coli lipopolysaccharide (LPS) and studied 6 hours thereafter. Animals were either pretreated (24 hours before Gal-LPS exposure) or posttreated (30 minutes after Gal-LPS exposure) with darbepoetin-α (DPO, 10 μg/kg i.v.). Control mice received physiological saline. Administration of Gal-LPS caused systemic cytokine release and provoked marked hepatic damage, characterized by leukocyte recruitment and microvascular perfusion failure, caspase-3 activation, and hepatocellular apoptosis as well as enzyme release and necrotic cell death. DPO-pretreated and -posttreated mice showed diminished systemic cytokine concentrations, intrahepatic leukocyte accumulation, and hepatic perfusion failure. Hepatocellular apoptosis was significantly reduced by 50 to 75% after DPO pretreatment as well as posttreatment. In addition, treatment with DPO also significantly abrogated necrotic cell death and liver enzyme release. In conclusion, these observations may stimulate the evaluation of DPO as hepatoprotective therapy in patients with acute liver injury. PMID:17525263

  17. Ochratoxin A induces oxidative DNA damage in liver and kidney after oral dosing to rats.

    PubMed

    Kamp, Hennicke G; Eisenbrand, Gerhard; Janzowski, Christine; Kiossev, Jetchko; Latendresse, John R; Schlatter, Josef; Turesky, Robert J

    2005-12-01

    The nephrotoxic/carcinogenic mycotoxin ochratoxin A (OTA) occurs as a contaminant in food and feed and may be linked to human endemic Balkan nephropathy. The mechanism of OTA-derived carcinogenicity is still under debate, since reactive metabolites of OTA and DNA adducts have not been unambiguously identified. Oxidative DNA damage, however, has been observed in vitro after incubation of mammalian cells with OTA. In this study, we investigated whether OTA induces oxidative DNA damage in vivo as well. Male F344 rats were dosed with 0, 0.03, 0.1, 0.3 mg/kg bw per day OTA for 4 wk (gavage, 7 days/wk, five animals per dose group). Subsequently, oxidative DNA damage was determined in liver and kidney by the comet assay (single cell gel electrophoresis) with/without use of the repair enzyme formamido-pyrimidine-DNA-glycosylase (FPG). The administration of OTA had no effect on basic DNA damage (determined without FPG); however, OTA-mediated oxidative damage was detected with FPG treatment in kidney and liver DNA of all dose groups. Since the doses were in a range that had caused kidney tumors in a 2-year carcinogenicity study with rats, the oxidative DNA damage induced by OTA may help to explain its mechanism of carcinogenicity. For the selective induction of tumors in the kidney, increased oxidative stress in connection with severe cytotoxicity and increased cell proliferation might represent driving factors.

  18. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure

    PubMed Central

    Stutchfield, Benjamin M.; Antoine, Daniel J.; Mackinnon, Alison C.; Gow, Deborah J.; Bain, Calum C.; Hawley, Catherine A.; Hughes, Michael J.; Francis, Benjamin; Wojtacha, Davina; Man, Tak Y.; Dear, James W.; Devey, Luke R.; Mowat, Alan M.; Pollard, Jeffrey W.; Park, B. Kevin; Jenkins, Stephen J.; Simpson, Kenneth J.; Hume, David A.; Wigmore, Stephen J.; Forbes, Stuart J.

    2015-01-01

    Background & Aims Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. Methods We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. Results Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. Conclusions Serum CSF1 appears to be a prognostic marker for patients

  19. Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis.

    PubMed

    Strand, S; Hofmann, W J; Grambihler, A; Hug, H; Volkmann, M; Otto, G; Wesch, H; Mariani, S M; Hack, V; Stremmel, W; Krammer, P H; Galle, P R

    1998-05-01

    Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demonstrated to be involved in liver disease. In this study CD95 mediated apoptosis was investigated in patients with fulminant hepatic failure in the course of Wilson's disease and in an in vitro model of copper treated human hepatoma cells. In patients, hepatic expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in vitro resulted in hepatocytic apoptosis which could be reduced with a neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in activation of the CD95 system and induction of apoptosis which is operative during the course of hepatic failure in acute Wilson's disease.

  20. Autophagy-Modulated Human Bone Marrow-Derived Mesenchymal Stem Cells Accelerate Liver Restoration in Mouse Models of Acute Liver Failure

    PubMed Central

    Amiri, Fatemeh; Molaei, Sedigheh; Bahadori, Marzie; Nasiri, Fatemeh; Deyhim, Mohammad Reza; Jalili, Mohammad Ali; Nourani, Mohammad Reza; Habibi Roudkenar, Mehryar

    2016-01-01

    Background: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:26899739

  1. Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review.

    PubMed

    Wu, Fa-Ling; Shi, Ke-Qing; Chen, Yong-Ping; Braddock, Martin; Zou, Hai; Zheng, Ming-Hua

    2014-08-01

    Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems. PMID:24762209

  2. Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats.

    PubMed

    Demirel, Ulvi; Yalniz, Mehmet; Aygün, Cem; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Kazim; Ozercan, Ibrahim Hanifi; Bahçecioğlu, Ibrahim Halil

    2012-08-01

    Oxidative stress plays important role in the development of acute liver failure. In this study, we investigated effects of allopurinol (AP) upon thioacetamide (TAA)-induced liver injury and the potential mechanisms leading to amelioration in inflammation with AP treatment. Acute liver failure was induced by intraperitoneal administration of TAA (300 mg/kg/day for 2 days). Thirty-five rats were divided into five groups as control (group 1), TAA (group 2), TAA + 25AP (group 3), TAA + 50 AP (group 4), and TAA + 100AP (group 5). The number of animals in each group was seven. At the end of the study, histopathological, biochemical, and western blot analysis were done. TAA treatment significantly increased serum levels of aminotransferases, liver malondialdehyde (MDA), nuclear factor-kappa B (NF-қB ), activator protein-1 (AP-1), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels, and the necro-inflammation scores. Nevertheless, nuclear factor E2-related factor-2 and heme oxygenase-1 (HO-1) expressions in the liver were decreased by TAA. AP treatment significantly lowered the serum levels of aminotransferases (P < 0.01) and liver MDA, NF-κB, AP-1, TNF-α, COX-2, and IL-6 expressions (P < 0.05). Moreover, AP restored the liver Nrf2 and HO-1 expressions and improved the necro-inflammation scores significantly. AP improves oxidative stress-induced liver damage by regulating cellular redox-sensitive transcriptor factors and expression of pro-inflammatory and antioxidant defense mechanisms. AP probably exerts these beneficiary features by its free radical scavenging ability in a dose-dependent manner.

  3. Endoplasmic reticulum stress-activated glycogen synthase kinase 3β aggravates liver inflammation and hepatotoxicity in mice with acute liver failure.

    PubMed

    Ren, Feng; Zhou, Li; Zhang, Xiangying; Wen, Tao; Shi, Hongbo; Xie, Bangxiang; Li, Zhuo; Chen, Dexi; Wang, Zheling; Duan, Zhongping

    2015-01-01

    Endoplasmic reticulum stress (ER stress) has been increasingly recognized as an important mechanism in various liver diseases. However, its intrinsic physiological role in acute liver failure (ALF) remains largely undetermined. This study aimed to examine how ER stress orchestrates glycogen synthase kinase 3β (GSK3β) and inflammation to affect ALF. In a murine ALF model induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS), 4-phenylbutyric acid (4-PBA) is to be administered to relieve ER stress. The lethality rate, liver damage, cytokine expression, and the activity of GSK3β were evaluated. How to regulate LPS-induced inflammation and TNF-α-induced hepatocyte apoptosis by ER stress was investigated in vitro. In vivo, ER stress was triggered in the liver with the progression of mice ALF model. ER stress was essential for the development of ALF because ER stress inhibition by 4-PBA ameliorated the liver damage through decreasing liver inflammation and hepatocyte apoptosis. 4-PBA also decreased GSK3β activity in the livers of ALF mice. In vitro, ER stress induced by tunicamycin synergistically increased LPS-triggered pro-inflammatory cytokine induction and promoted the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathway in bone marrow-derived macrophages; moreover, tunicamycin also cooperated with TNF-α to increase hepatocyte apoptosis. ER stress promoted LPS-triggered inflammation depending on GSK3β activation because inhibition of GSK3β by SB216763, the specific inhibitor of GSK3β, resulted in downregulation of pro-inflammatory genes. ER stress contributes to liver inflammation and hepatotoxicity in ALF, particularly by regulating GSK3β, and is therefore a potential therapeutic target for ALF.

  4. Candidate Gene Polymorphisms in Patients with Acetaminophen-Induced Acute Liver Failure

    PubMed Central

    Peter, Inga; Hazarika, Suwagmani; Vasiadi, Magdalini; Greenblatt, David J.; Lee, William M.

    2014-01-01

    Acetaminophen is a leading cause of acute liver failure (ALF). Genetic differences might predispose some individuals to develop ALF. In this exploratory study, we evaluated genotype frequency differences among patients enrolled by the ALF Study Group who had developed ALF either intentionally from a single-time-point overdose of acetaminophen (n = 78), unintentionally after chronic high doses of acetaminophen (n = 79), or from causes other than acetaminophen (n = 103). The polymorphisms evaluated included those in genes encoding putative acetaminophen-metabolizing enzymes (UGT1A1, UGT1A6, UGT1A9, UGT2B15, SULT1A1, CYP2E1, and CYP3A5) as well as CD44 and BHMT1. Individuals carrying the CYP3A5 rs776746 A allele were overrepresented among ALF patients who had intentionally overdosed with acetaminophen, with an odds ratio of 2.3 (95% confidence interval, 1.1–4.9; P = 0.034) compared with all other ALF patients. This finding is consistent with the enhanced bioactivation of acetaminophen by the CYP3A5 enzyme. Persons homozygous for the CD44 rs1467558 A allele were also overrepresented among patients who had unintentionally developed ALF from chronic acetaminophen use, with an odds ratio of 4.0 (1.0–17.2, P = 0.045) compared with all other ALF subjects. This finding confirms a prior study that found elevated serum liver enzyme levels in healthy volunteers with the CD44 rs1467558 AA genotype who had consumed high doses of acetaminophen for up to 2 weeks. However, both genetic associations were considered relatively weak, and they were not statistically significant after adjustment for multiple comparisons testing. Nevertheless, both CYP3A5 rs776746 and CD44 rs1467558 warrant further investigation as potential genomic markers of enhanced risk of acetaminophen-induced ALF. PMID:24104197

  5. Acute liver failure in a term neonate after repeated paracetamol administration

    PubMed Central

    Bucaretchi, Fábio; Fernandes, Carla Borrasca; Branco, Maíra Migliari; Capitani, Eduardo Mello De; Hyslop, Stephen; Caldas, Jamil Pedro S.; Moreno, Carolina Araújo; Porta, Gilda

    2014-01-01

    Objective: Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. Case description: A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1mEq/L), hypoglycemia (18mg/dL), increased serum aminotransferase activity (AST=4,039IU/L; ALT=1,087IU/L) and hyperbilirubinemia (total: 9.57mg/dL; direct: 6.18mg/dL) 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. PMID:24676202

  6. 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

    PubMed Central

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

    2016-01-01

    Introduction 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. Methods 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. Results 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 (P<0.001 and P = 0.009 respectively, n = 725). In a Cox proportional hazards model, renal 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 175μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy. Conclusion 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. PMID:26930637

  7. Metabonomic analysis of liver tissue from BALB/c mice with d-galactosamine/lipopolysaccharide-induced acute hepatic failure

    PubMed Central

    2013-01-01

    Background Compared with biofluids, target tissues and organs more directly reflect the pathophysiological state of a disease process. In this study, a D-galactosamine (GalN) / lipopolysaccharide (LPS)-induced mouse model was constructed to investigate metabonomics of liver tissue and directly characterize metabolic changes in acute liver failure (ALF). Methods After pretreatment of liver tissue, gas chromatography coupled to time-of-flight mass spectrometry (GC/TOFMS) was used to separate and identify the liver metabolites. Partial least squares – discriminant analysis models were constructed to separate the ALF and control groups and to find those compounds whose liver levels differed significantly between the two groups. Results Distinct clustering was observed between the ALF and control mice. Fifty-eight endogenous metabolites were identified. Compared with the control mice, many metabolites, including sugars, amino acids, fatty acids, and organic acids, underwent significant changes in the ALF group, some of which differed from changes observed in plasma. Significant reduction of some important intermediate metabolites indicates that production of ketone bodies, the tricarboxylic acid and urea cycles, gluconeogenesis, glycolysis and pentose phosphate pathways are inhibited after GalN/LPS administration. Conclusions GC/TOFMS can be a powerful technique to perform metabonomic studies of liver tissue. GalN/LPS treatment can severely disturb substance metabolism in the liver, with different effects on metabolites compared with those observed in the plasma. PMID:23627910

  8. Granulocyte-colony stimulating factor for acute-on-chronic liver failure: systematic review and meta-analysis.

    PubMed

    Chavez-Tapia, Norberto C; Mendiola-Pastrana, Indira; Ornelas-Arroyo, Victoria J; Noreña-Herrera, Camilo; Vidaña-Perez, Desiree; Delgado-Sanchez, Guadalupe; Uribe, Misael; Barrientos-Gutierrez, Tonatiuh

    2015-01-01

    Acute-on-chronic liver failure (ACLF) is associated with increased short and long-term mortality. Animal models of liver failure have demonstrated that granulocyte-colony stimulating factor (G-CSF) accelerates the liver regeneration process and improves survival. However, clinical evidence regarding the use of G-CSF in ACLF remains scarce. The aim of this study was to assess the benefits and harms of G-CSF in patients with acute-on-chronic liver failure. An electronic search was made in The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS up to November 2013. Randomized clinical trials comparing the use of any regimen of G-CSF against placebo or no intervention in patients with ACLF were included. Primary outcomes included overal mortality, mortality due multi-organ failure, and adverse events. Relative risk (RR) and mean difference (MD) were used. Two trials involving 102 patients were included. A significant reduction in short-term overall mortality was observed in patients receiving G-CSF compared to controls (RR 0.56; 95%CI 0.39,0.80). G-CSF failed to reduce mortality secondary to gastrointestinal bleeding (RR 1.45; 95%CI 0.50, 4.27). Adverse effects reported included: fever, rash, herpes zoster, headache and nausea. In conclusion, the use of G-CSF for the treatment of patients with ACLF significantly reduced short-term mortality. While the evidence is still limited, the apparent benefit observed on short-term mortality, mild adverse effects and lack of an alternative therapy make the use of G-CSF in ACLF patients a reasonable alternative when liver transplantation is contraindicated or unavailable.

  9. Is it right to promote living donor liver transplantation for fulminant hepatic failure in pediatric recipients?

    PubMed

    Reding, Raymond

    2005-07-01

    Good clinical results are currently achieved in elective pediatric liver transplantation (LT) with living-related donors. However, the question whether such therapeutic approach may also be promoted in case of fulminant hepatic failure (FHF) remains a matter of debate. This work briefly reviews the ethical background and overall medical results of living-related donation in pediatric LT. When considering FHF, success is essentially conditioned by the availability of a suitable organ donor before the onset of irreversible brain damage and death of the transplant candidate on the waiting list. Accordingly, living donor LT provides several advantages for patients with FHF, including the short waiting time and the access to a transplant with reduced ischemic injury and optimal graft quality; however, living donation is also characterized by several drawbacks to be carefully considered, particularly the possibility of coercion to the recipient's family as well as the operative risks of the emergency donor hepatectomy. The ethical soundness of living parental donor LT for FHF is discussed, with emphasis to the type of medical context, with or without access to an efficient emergency postmortem organ sharing system. PMID:15943615

  10. Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review.

    PubMed

    Yellapu, Radha K; Mittal, Vivek; Grewal, Priya; Fiel, Mariaisabel; Schiano, Thomas

    2011-03-01

    Globally, people are struggling with obesity. Many effective, nonconventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful.

  11. LPS pretreatment ameliorates D-galactosamine/lipopolysaccharide-induced acute liver failure in rat.

    PubMed

    Dong, Jin-Zhong; Wang, Li-Ping; Zhang, Sai-Nan; Shi, Ke-Qing; Chen, Shao-Long; Yang, Nai-Bin; Ni, Shun-Lan; Zhu, Jian-Hua; Lu, Ming-Qin

    2014-01-01

    Acute liver failure (ALF) remains an extremely poor prognosis and high mortality; with no effective treatments. The endotoxin tolerance (ET) phenotype has been reported to exhibit protective activities in several sepsis models. We now investigated the effects and underlying intraperitoneal injection of the same volume of pyrogen-free 0.9% sodium chloride instead of LPS for five consecutive days before D-GalN/LPS injection in rats. The serum levels of TNF-α, IL-6, ALT, AST and TBiL from ET + ALF group and ALF group were measured at different time points. Our results showed that ET + ALF group markedly reduced the serum levels of TNF-α, IL-6, ALT, AST and TBiL and histological features in the ET + ALF group were improved significantly. Furthermore, LPS pre-treatment inhibited D-GalN/LPS-induced NF-κB activation, Bax activation, signal transducer and activator of transcription-1 (STAT1) and signal transducer and activator of transcription-3 (STAT3) activities. LPS pre-treatment also significantly enhance the expression of suppressors of cytokine signaling 1 (SOCS1) and suppressors of cytokine signaling 3 (SOCS3). Our experimental data indicated that ET might alleviate D-GalN/LPS-induced ALF by inhibiting the inflammatory response, inactivation of STAT1 and STAT3 and up-regulation of SOCS1 and SOCS3.

  12. Role of sulphated polysaccharides from Sargassum Wightii in Cyclosporine A-induced oxidative liver injury in rats

    PubMed Central

    Josephine, Anthony; Nithya, Kalaiselvam; Amudha, Ganapathy; Veena, Coothan Kandaswamy; Preetha, Sreenivasan P; Varalakshmi, Palaninathan

    2008-01-01

    Background Seaweeds or marine algae have long been made up a key part of the Asian diet, and as an antioxidant, sulphated polysaccharides have piqued the interest of many researchers as one of the ocean's greatest treasures. The present investigation suggests the therapeutic potential of sulphated polysaccharides from marine brown algae "Sargassum wightii" in Cyclosporine A (CsA)- induced liver injury. CsA is a potent immunosuppressive agent used in the field of organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains to be one of the major clinical challenges. Methods The effect of sulphated polysaccharides on CsA-induced hepatotoxicity was studied in adult male albino rats of Wistar strain, and the animals were randomized into four groups with six rats in each. Group I served as vehicle control. Group II rats were given CsA at a dosage of 25 mg/kg body weight, orally for 21 days. Group III rats were given sulphated polysaccharides at a dosage of 5 mg/kg body weight, subcutaneously for 21 days. Group IV rats were given sulphated polysaccharides simultaneously along with CsA, as mentioned in Group II for 21 days. Results CsA provoked hepatotoxicity was evident from the decreased activities of hepatic marker enzymes. A significant rise in the level of oxidants, along with a striking decline in both the enzymic and non-enzymic antioxidants, marks the severity of oxidative stress in CsA-induced rats. This in turn led to enhanced levels of lipid peroxidation, 8-hydroxy-2-deoxy guanosine and protein carbonyls, along with a decrease in ATPase activities and alterations in lipid profile. Histopathological changes also strongly support the above aberrations. However, concomitant treatment with sulphated polysaccharides restored the above deformities to near control and prevented the morphological alterations significantly. Conclusion Thus, the present study highlights that sulphated polysaccharides can act therapeutically against

  13. Prognostic value of 13C-phenylalanine breath test on predicting survival in patients with chronic liver failure

    PubMed Central

    Gallardo-Wong, I; Morán, S; Rodríguez-Leal, G; Castañeda-Romero, B; Mera, R; Poo, J; Uribe, M; Dehesa, M

    2007-01-01

    AIM: To evaluate the prognostic value of percentage of 13C-phenylalanine oxidation (13C-PheOx) obtained by 13C-phenylalanine breath test (13C-PheBT) on the survival of patients with chronic liver failure. METHODS: The hepatic function was determined by standard liver blood tests and the percentage of 13C-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. RESULTS: 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 13C-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 13C-PheOx (HR 0.449, 95% CI: 0.206-0.979, P = 0.034) were found to be independent predictors of survival. CONCLUSION: Percentage of 13C-PheOx obtained by 13C-PheBT is a strong predictor of survival in patients with chronic liver disease. PMID:17729409

  14. The Use of Fish Oil Lipid Emulsion in the Treatment of Intestinal Failure Associated Liver Disease (IFALD)

    PubMed Central

    Chang, Melissa I.; Puder, Mark; Gura, Kathleen M.

    2012-01-01

    Since 2004, fish oil based lipid emulsions have been used in the treatment of intestinal failure associated liver disease, with a noticeable impact on decreasing the incidence of morbidity and mortality of this often fatal condition. With this new therapy, however, different approaches have emerged as well as concerns about potential risks with using fish oil as a monotherapy. This review will discuss the experience to date with this lipid emulsion along with the rational for its use, controversies and concerns. PMID:23363993

  15. The Impact of Hospital/Surgeon Volume on Acute Renal Failure and Mortality in Liver Transplantation: A Nationwide Cohort Study

    PubMed Central

    Cheng, Chih-Wen; Liu, Fu-Chao; Lin, Jr-Rung; Tsai, Yung-Fong; Chen, Hsiu-Pin; Yu, Huang-Ping

    2016-01-01

    The aim of this study was to assess whether the case volume of surgeons and hospitals affects the rates of postoperative complications and survival after liver transplantation. This population-based retrospective cohort study included 2938 recipients of liver transplantation performed between 1998 and 2012, enrolled from the Taiwan National Health Insurance Research Database. They were divided into two groups, according to the cumulative case volume of their operating surgeons and the case volume of their hospitals. The duration of intensive care unit stay and post-transplantation hospitalization, postoperative complications, and mortality were analyzed. The results showed that, in the low and high case volume surgeons groups, respectively, acute renal failure occurred at the rate of 14.11% and 5.86% (p<0.0001), and the overall mortality rates were 19.61% and 12.44% (p<0.0001). In the low and high case volume hospital groups, respectively, acute renal failure occurred in 11% and 7.11% of the recipients (p = 0.0004), and the overall mortality was 18.44% and 12.86% (p<0.0001). These findings suggest that liver transplantation recipients operated on higher case volume surgeons or in higher case volume hospitals have a lower rate of acute renal failure and mortality. PMID:27706183

  16. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis.

    PubMed

    Li, Jingjing; Chen, Kan; Li, Sainan; Liu, Tong; Wang, Fan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2016-01-01

    This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis.

  17. Motor activity is modulated via different neuronal circuits in rats with chronic liver failure than in normal rats.

    PubMed

    Cauli, Omar; Mlili, Nisrin; Llansola, Marta; Felipo, Vicente

    2007-04-01

    The mechanisms by which liver failure alters motor function remain unclear. It has been suggested that liver disease alters the neuronal circuit between basal ganglia and cortex that modulates motor function. Activation of group I metabotropic glutamate receptors in the nucleus accumbens (NAcc) by injecting (S)-3,5-dihydroxyphenylglycine (DHPG) activates this circuit and induces locomotion We analysed by in vivo brain microdialysis the function of the circuits that modulate motor function in rats with liver failure due to portacaval shunt (PCS). We inserted cannulae in the NAcc and microdialysis probes in the NAcc, ventral pallidum (VP), substantia nigra pars reticulata (SNr), medio-dorsal thalamus (MDT), ventro-medial thalamus (VMT) or prefrontal cortex (PFCx). We injected DHPG in the NAcc and analysed extracellular neurotransmitters concentration in these areas. The results indicate that in control rats DHPG induces locomotion by activating the 'normal' neuronal circuit: NAcc --> VP --> MDT --> PFCx. In PCS rats this circuit is not activated. In PCS rats, DHPG injection activates an 'alternative' circuit: NAcc --> SNr --> VMT --> PFCx. This circuit is not activated in control rats. DHPG injection increases dopamine in the NAcc of control but not of PCS rats, and glutamate in PCS but not in control rats. DHPG-induced increase in dopamine would activate the 'normal' neuronal circuit, while an increase in glutamate would activate the 'alternative' circuit. The identification of the mechanisms responsible for altered motor function and coordination in liver disease would allow designing treatments to improve motor function in patients with hepatic encephalopathy.

  18. Promotion of mitochondrial energy metabolism during hepatocyte apoptosis in a rat model of acute liver failure

    PubMed Central

    CHEN, LI-YAN; YANG, BAOSHAN; ZHOU, LI; REN, FENG; DUAN, ZHONG-PING; MA, YING-JI

    2015-01-01

    Hepatocyte apoptosis and energy metabolism in mitochondria have an important role in the mechanism of acute liver failure (ALF). However, data on the association between apoptosis and the energy metabolism of hepatocytes are lacking. The current study assessed the activity of several key enzymes in mitochondria during ALF, including citrate synthase (CS), carnitine palmitoyltransferase-1 (CPT-1) and cytochrome c oxidase (COX), which are involved in hepatocyte energy metabolism. A total of 40 male Sprague-Dawley rats were divided into five groups and administered D-galactosamine and lipopolysaccharide to induce ALF. Hepatic pathology and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling examinations indicated that hepatocyte apoptosis was observed at 4 h and increased 8 h after ALF. Hepatocyte necrosis appeared at 12 h and was significantly higher at 24 h with inflammatory cell invasion. The results measured by electron microscopy indicated that ultrastructural changes in mitochondria began at 4 h and the mitochondrial outer membrane was completely disrupted at 24 h resulting in mitochondrial collapse. The expression of CS, CPT-1 and COX was measured and analyzed using assay kits. The activity and protein expression of CS, CPT-1 and COX began to increase at 4 h, reached a peak at 8 h and decreased at 12 h during ALF. The activities of CS, CPT-1 and COX were enhanced during hepatocyte apoptosis suggesting that these enzymes are involved in the initiation and development of ALF. Therefore, these results demonstrated that energy metabolism is important in hepatocyte apoptosis during ALF and hepatocyte apoptosis is an active and energy-consuming procedure. The current study on how hepatocyte energy metabolism affects the transmission of death signals may provide a basis for the early diagnosis and development of an improved therapeutic strategy for ALF. PMID:26135512

  19. Aquaporin-4 Deletion in Mice Reduces Encephalopathy and Brain Edema in Experimental Acute Liver Failure

    PubMed Central

    Rama Rao, Kakulavarapu V.; Verkman, A. S.; Curtis, Kevin M.; Norenberg, Michael D.

    2014-01-01

    Brain edema and associated astrocyte swelling leading to increased intracranial pressure are hallmarks of acute liver failure (ALF). Elevated blood and brain levels of ammonia have been implicated in the development of brain edema in ALF. Cultured astrocytes treated with ammonia have been shown to undergo cell swelling and such swelling was associated with an increase in the plasma membrane expression of aquaporin-4 (AQP4) protein. Further, silencing the AQP4 gene in cultured astrocytes was shown to prevent the ammonia-induced cell swelling. Here, we examined the evolution of brain edema in AQP4-null mice and their wild type counterparts (WT-mice) in different models of ALF induced by thioacetamide (TAA) or acetaminophen (APAP). Induction of ALF with TAA or APAP significantly increased brain water content in WT mice (by 1.6 ± 0.3 and 2.3 ± 0.4 %, respectively). AQP4 protein was significantly increased in brain plasma membranes of WT mice with ALF induced by either TAA or APAP. In contrast to WT-mice, brain water content did not increase in AQP4-null mice. Additionally, AQP4-null mice treated with either TAA or APAP showed a remarkably lesser degree of neurological deficits as compared to WT mice; the latter displayed an inability to maintain proper gait, and demonstrated a markedly reduced exploratory behavior, with the mice remaining in one corner of the cage with its head tilted downwards. These results support a central role of AQP4 in the brain edema associated with ALF. PMID:24321433

  20. Sulfonylurea Receptor 1 Contributes to the Astrocyte Swelling and Brain Edema in Acute Liver Failure

    PubMed Central

    Jayakumar, A.R.; Valdes, V.; Tong, X.Y.; Shamaladevi, N.; Gonzalez, W.; Norenberg, M.D.

    2014-01-01

    Astrocyte swelling (cytotoxic brain edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/brain edema in other neurological disorders is the ATP-dependent, non-selective cation channel (NCCa-ATP channel). We therefore examined its potential role in the astrocyte swelling/brain edema associated with ALF. Cultured astrocytes treated with 5 mM ammonia showed a 3-fold increase in the sulfonylurea receptor type 1 (SUR1) protein expression, a marker of NCCa-ATP channel activity. Blocking SUR1 with glibenclamide significantly reduced the ammonia-induced cell swelling in cultured astrocytes. Additionally, overexpression of SUR1 in ammonia-treated cultured astrocytes was significantly reduced by co-treatment of cells with BAY 11-7082, an inhibitor of NF-κB, indicating the involvement of an NF-κB-mediated SUR1 upregulation in the mechanism of ammonia-induced astrocyte swelling. Brain SUR1 mRNA level was also found to be increased in the thioacetamide (TAA) rat model of ALF. Additionally, we found a significant increase in SUR1 protein expression in rat brain cortical astrocytes in TAA-treated rats. Treatment with glibenclamide significantly reduced the brain edema in this model of ALF. These findings strongly suggest the involvement of NCCa-ATP channel in the astrocyte swelling/brain edema in ALF, and that targeting this channel may represent a useful approach for the treatment of the brain edema associated with ALF. PMID:24443056

  1. Increased blood-brain transfer in a rabbit model of acute liver failure

    SciTech Connect

    Horowitz, M.E.; Schafer, D.F.; Molnar, P.; Jones, E.A.; Blasberg, R.G.; Patlak, C.S.; Waggoner, J.; Fenstermacher, J.D.

    1983-05-01

    The blood-to-brain transfer of (/sup 14/C)alpha-aminoisobutyric acid was investigated by quantitative autoradiography in normal rabbits and rabbits with acute liver failure induced by the selective hepatotoxin galactosamine. The blood-to-brain transfer of alpha-aminoisobutyric acid was similar in control animals and animals 2 and 7 h after galactosamine injections, but was increased five- to tenfold in certain gray-matter areas of the brain in animals 11 and 18 h after galactosamine treatment. No detectable differences in white-matter uptake of (/sup 14/C)alpha-aminoisobutyric acid were found between the control and treated groups. The increase in alpha-aminoisobutyric acid transfer within the gray-matter areas suggested that a general or nonspecific increase in brain capillary permeability occurred in these areas. No clinical signs of early hepatic encephalopathy were observed in the treated rabbits, except for 1 animal from the 18-h postgalactosamine group. Thus, enhanced blood-brain transfer of alpha-aminoisobutyric acid preceded the development of overt hepatic encephalopathy. The distribution of radioactivity after the intravenous administration of (/sup 14/C)galactosamine showed that virtually none of the hepatotoxin localized in the brain, suggesting that the drug itself does not have a direct effect upon the blood-brain barrier or the brain. The increased uptake of alpha-aminoisobutyric acid at 11 and 18 h implies that the transfer of other solutes would also be enhanced, that central nervous system homeostasis would be compromised, and that the resulting changes in brain fluid composition could contribute to or cause hepatic encephalopathy.

  2. Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure.

    PubMed

    Arkadopoulos, Nikolaos; Vlahakos, Demetrios; Kostopanagiotou, Georgia; Panagopoulos, Dimitrios; Karvouni, Eleni; Routsi, Christina; Kalimeris, Konstantinos; Andreadou, Ioanna; Kouskouni, Evangelia; Smyrniotis, Vassilios

    2008-08-01

    Oxidative mechanisms have been implicated in the pathogenesis of brain edema in acute liver failure (ALF). The aim of this study was to test the hypothesis that inhibition of iron-catalyzed oxidative reactions through iron chelation using deferoxamine could attenuate brain edema in a swine model of ischemic ALF. Following ALF induction (end-to-side portacaval anastomosis and ligation of the hepatoduodenal ligament), 14 animals were randomized to a study group that received an intravenous infusion of 150 mg/kg deferoxamine (group DF; n = 7) or a control group (group C; n = 7). Six sham-operated animals were also assigned to a deferoxamine-treated group (n = 3) or a control group (n = 3). Hemodynamic, neurological, and hematological parameters were monitored postoperatively. All sham animals maintained normal hemodynamics and intracranial pressure. At 18 hours, group DF animals had higher mean arterial pressure (mean +/- standard deviation: 98.0 +/- 15.9 versus 69.9 +/- 15.8 mmHg, P < 0.004), lower intracranial pressure (18.1 +/- 8.6 versus 32.7 +/- 13.4 mmHg, P < 0.032), and higher cerebral perfusion pressure (76.4 +/- 16.4 versus 37.1 +/- 25.6 mmHg, P < 0.006) in comparison with group C. Similar differences were recorded up to the 24th postoperative hour, leading to a significant difference in animal survival (88% in group DF versus 17% in group C, P < 0.001). Furthermore, group DF exhibited an attenuated increase of serum malondialdehyde from the baseline (16% versus 74%, P < 0.05) and lower brain malondialdehyde concentrations (3.7 +/- 1.3 versus 5.7 +/- 2.0 microM/mg of protein, P < 0.05) in comparison with controls. In conclusion, deferoxamine delayed the development of intracranial hypertension and improved survival in pigs with ischemic ALF.

  3. Porcine Adipose-Derived Mesenchymal Stem Cells Retain Their Stem Cell Characteristics and Cell Activities While Enhancing the Expression of Liver-Specific Genes after Acute Liver Failure.

    PubMed

    Hu, Chenxia; Zhou, Ning; Li, Jianzhou; Shi, Ding; Cao, Hongcui; Li, Jun; Li, Lanjuan

    2016-01-05

    Acute liver failure (ALF) is a kind of complicated syndrome. Furthermore, adipose-derived mesenchymal stem cells (ADMSCs) can serve as a useful cell resource for autotransplantation due to their abundance and micro-invasive accessability. However, it is unknown how ALF will influence the characteristics of ADMSCs and whether ADMSCs from patients suffering from end-stage liver diseases are potential candidates for autotransplantation. This study was designed to compare various properties of ALF-derived ADMSCs with normal ADMSCs in pig models, with regard to their cellular morphology, cell proliferative ability, cell apoptosis, expression of surface antigens, mitochondrial and lysosomal activities, multilineage potency, and expression of liver-specific genes. Our results showed that ALF does not influence the stem cell characteristics and cell activities of ADMSCs. Intriguingly, the expression levels of several liver-specific genes in ALF-derived ADMSCs are higher than in normal ADMSCs. In conclusion, our findings indicate that the stem cell characteristics and cell activities of ADMSCs were not altered by ALF and these cells can serve as a new source for regenerative medicine.

  4. Porcine Adipose-Derived Mesenchymal Stem Cells Retain Their Stem Cell Characteristics and Cell Activities While Enhancing the Expression of Liver-Specific Genes after Acute Liver Failure

    PubMed Central

    Hu, Chenxia; Zhou, Ning; Li, Jianzhou; Shi, Ding; Cao, Hongcui; Li, Jun; Li, Lanjuan

    2016-01-01

    Acute liver failure (ALF) is a kind of complicated syndrome. Furthermore, adipose-derived mesenchymal stem cells (ADMSCs) can serve as a useful cell resource for autotransplantation due to their abundance and micro-invasive accessability. However, it is unknown how ALF will influence the characteristics of ADMSCs and whether ADMSCs from patients suffering from end-stage liver diseases are potential candidates for autotransplantation. This study was designed to compare various properties of ALF-derived ADMSCs with normal ADMSCs in pig models, with regard to their cellular morphology, cell proliferative ability, cell apoptosis, expression of surface antigens, mitochondrial and lysosomal activities, multilineage potency, and expression of liver-specific genes. Our results showed that ALF does not influence the stem cell characteristics and cell activities of ADMSCs. Intriguingly, the expression levels of several liver-specific genes in ALF-derived ADMSCs are higher than in normal ADMSCs. In conclusion, our findings indicate that the stem cell characteristics and cell activities of ADMSCs were not altered by ALF and these cells can serve as a new source for regenerative medicine. PMID:26742034

  5. Small for Size and Flow (SFSF) syndrome: An alternative description for posthepatectomy liver failure.

    PubMed

    Golriz, Mohammad; Majlesara, Ali; El Sakka, Saroa; Ashrafi, Maryam; Arwin, Jalal; Fard, Nassim; Raisi, Hanna; Edalatpour, Arman; Mehrabi, Arianeb

    2016-06-01

    Small for Size Syndrome (SFSS) syndrome is a recognizable clinical syndrome occurring in the presence of a reduced mass of liver, which is insufficient to maintain normal liver function. A definition has yet to be fully clarified, but it is a common clinical syndrome following partial liver transplantation and extended hepatectomy, which is characterized by postoperative liver dysfunction with prolonged cholestasis and coagulopathy, portal hypertension, and ascites. So far, this syndrome has been discussed with focus on the remnant size of the liver after partial liver transplantation or extended hepatectomy. However, the current viewpoints believe that the excessive flow of portal vein for the volume of the liver parenchyma leads to over-pressure, sinusoidal endothelial damages and haemorrhage. The new hypothesis declares that in both extended hepatectomy and partial liver transplantation, progression of Small for Size Syndrome is not determined only by the "size" of the liver graft or remnant, but by the hemodynamic parameters of the hepatic circulation, especially portal vein flow. Therefore, we suggest the term "Small for Size and Flow (SFSF)" for this syndrome. We believe that it is important for liver surgeons to know the pathogenesis and manifestation of this syndrome to react early enough preventing non-reversible tissue damages. PMID:26516057

  6. Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors.

    PubMed

    Rodrigues, Robim M; Sachinidis, Agapios; De Boe, Veerle; Rogiers, Vera; Vanhaecke, Tamara; De Kock, Joery

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds.

  7. Full-length genome characterization and genetic relatedness analysis of hepatitis A virus outbreak strains associated with acute liver failure among children.

    PubMed

    Vaughan, Gilberto; Forbi, Joseph C; Xia, Guo-Liang; Fonseca-Ford, Maureen; Vazquez, Roberto; Khudyakov, Yury E; Montiel, Sonia; Waterman, Steve; Alpuche, Celia; Gonçalves Rossi, Livia Maria; Luna, Norma

    2014-02-01

    Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes.

  8. The 55-kD tumor necrosis factor receptor and CD95 independently signal murine hepatocyte apoptosis and subsequent liver failure.

    PubMed Central

    Leist, M.; Gantner, F.; Künstle, G.; Bohlinger, I.; Tiegs, G.; Bluethmann, H.; Wendel, A.

    1996-01-01

    BACKGROUND: Activation of either the 55-kD tumor necrosis factor receptor (TNF-R1) or CD95 (Fas/Apo-1) causes apoptosis of cells and liver failure in mice, and has been associated with human liver disorders. The aim of this study was first to clarify the association between CD95 activation, hepatocyte apoptosis, and fulminant liver failure. Next, we investigated whether TNF-R1 and CD95 operate independently of each other in the induction of hepatocyte apoptosis. MATERIALS AND METHODS: Using both mice and primary liver cell cultures deficient in either TNF-R1 or functional CD95, the induction of apoptosis and hepatocyte death following activation of TNF-R1 or CD95 were studied in vitro and in various in vivo models of acute liver failure. RESULTS: In vivo or in vitro stimulation of CD95 caused apoptosis of wild-type (wt) murine hepatocytes which had not been sensitized by blocking transcription. Time course studies showed that DNA fragmentation and chromatin condensation preceded, respectively, membrane lysis in vitro and necrosis in vivo. Similar results were obtained after CD95 activation in hepatocytes or livers lacking TNF-R1. Conversely, hepatocytotoxicity due to endogenous or exogenous TNF was not affected in animals or liver cell cultures lacking the expression of functional CD95. CONCLUSIONS: TNF-R1 and CD95 are independent and differentially regulated triggers of murine apoptotic liver failure. Images FIG. 3 FIG. 6 FIG. 7 FIG. 9 PMID:8900539

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

    PubMed Central

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

    2016-01-01

    Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production. d-galactosamine plus lipopolysaccharide (GalN/LPS), concanavalin A (ConA), and acetaminophen (APAP) were given to C57BL/6N mice to induce liver injury, respectively, and the pathogenic role of circulating histones was studied. Besides, the protective effect of nonanticoagulant heparin, which can bind histones, was evaluated with in vivo and ex vivo investigations. We observed that circulating histones were significantly increased in patients with ALF, and correlated with disease severity and mortality. Significant systemic inflammation was also pronounced in ALF patients, which were associated with histone levels. ALF patients' sera induced significant L02 cell death and stimulated U937 cells to produce cytokines, which were abrogated by nonanticoagulant heparin. Furthermore, circulating histones were all released remarkably in GalN/LPS, ConA, and APAP-treated mice, and associated with high levels of inflammatory cytokines. Heparin reduced systemic inflammation and liver damage in mice, suggesting that it could interfere with histone-associated liver injury. Collectively, these findings demonstrate that circulating histones are critical mediators of systemic inflammation and cellular damage in ALF, which may be potentially translatable for clinical use. PMID:27685635

  10. Epstein-Barr Virus-Associated Acute Liver Failure Present in a 67-Year-Old Immunocompetent Female

    PubMed Central

    Zhang, Wei; Chen, Betty; Chen, Yongxin; Chamberland, Robin; Fider-Whyte, Alexa; Craig, Julia; Varma, Chintalapati; Befeler, Alex S.; Bisceglie, Adrian M. Di; Horton, Peter; Lai, Jin-Ping

    2016-01-01

    Acute liver failure (ALF) is a rare illness with a high mortality rate. The only favorable management is emergent liver transplantation. About 13% of ALF cases have no clear etiology. Epstein-Barr virus (EBV)-associated ALF accounts for less than 1% of all ALF cases, and is seen mostly in adults younger than 40 years. There are only a few cases of EBV-associated ALF in elderly immunocompromised adults. We report a case of ALF in an immunocompetent 67-year-old woman caused by EBV infection that was treated by orthotopic liver transplantation (OLT). The diagnosis of EBV-associated ALF was established by EBV-DNA polymerase chain reaction (PCR) and EBV-encoded RNA (EBER-RNA) in situ hybridization (EBER-RISH). The patient is currently doing well 6 months after transplantation without any evidence of clinical EBV infection. This case illustrates the importance of early recognition and diagnosis of EBV-associated ALF by detection of EBV from liver biopsy, especially when patients are immunocompetent and other causes are excluded. To the best of our knowledge, this is the first case of EBV-associated ALF present in an immunocompetent elderly female. PMID:27785330

  11. Fumigaclavine C improves concanavalin A-induced liver injury in mice mainly via inhibiting TNF-alpha production and lymphocyte adhesion to extracellular matrices.

    PubMed

    Zhao, Ying; Liu, Junyan; Wang, Jun; Wang, Lei; Yin, Hao; Tan, Renxiang; Xu, Qiang

    2004-06-01

    Fumigaclavine C, an alkaloidal metabolite, was produced by Aspergillus fumigatus (strain No. CY018). This study examined the effect of this compound on concanavalin A (Con A)-induced liver injury in mice, a T cell-dependent model of liver damage. Con A administration resulted in severe liver injury, T lymphocyte activation and a strong increment in spleen cell adhesion, as well as in tumour necrosis factor-alpha (TNF-alpha) production. Against this liver injury, the intraperitoneal administration of fumigaclavine C dose-dependently inhibited the elevation in transaminase activity, TNF-alpha production in serum and the histological changes, including inflammatory infiltration, hepatocyte necrosis and degeneration and Kupffer cell hyperplasia. In addition, this compound in-vitro also inhibited the proliferation of spleen cells induced by Con A, and reduced their IL-2 and TNF-alpha production. Moreover, the intraperitoneal administration of fumigaclavine C inhibited the potential of spleen cells isolated from the liver-injured mice to adhere to fibronectin, laminin and type IV collagen. These results suggest that the improvement of this T cell-mediated liver injury by fumigaclavine C may be related to the inhibition of lymphocyte activation, proliferation and adhesion to extracellular matrices as well as the reduction in TNF-alpha production. PMID:15231043

  12. Part of plasmapheresis with plasma filtration adsorption combined with continuous hemodiafiltration in the treatment of severe acute liver failure

    PubMed Central

    Li, Maoqin; Wang, Zhidong; Wang, Yining; Du, Changhong; Li, Songhai; Shi, Zaixiang; Lu, Bo

    2016-01-01

    The present study is a retrospective analysis of 11 cases with severe acute liver failure combined with multiple organ dysfunction syndrome (MODS) performed during the period June, 2012 to December, 2014. After part of plasmapheresis with plasma filtration adsorption combined with continuous hemodiafiltration treatment, good curative effects were obtained and the main clinical symptoms and biochemical index were significantly improved. Following treatment, 8 of the 11 patients survived at a survival rate of 72.7%, and 3 patients succumbed with a mortality of 27.3%. The results suggested that part of plasmapheresis with plasma filtration adsorption combined with continuous venovenous hemodiafiltration (CVVHDF) treatment is beneficial in the removal of metabolites and toxins. Additonally, it can effectively improve liver function and clinical symptoms, improve hepatic encephalopathy, correct the disorder of internal environment, and improve the prognosis of patients.

  13. Part of plasmapheresis with plasma filtration adsorption combined with continuous hemodiafiltration in the treatment of severe acute liver failure

    PubMed Central

    Li, Maoqin; Wang, Zhidong; Wang, Yining; Du, Changhong; Li, Songhai; Shi, Zaixiang; Lu, Bo

    2016-01-01

    The present study is a retrospective analysis of 11 cases with severe acute liver failure combined with multiple organ dysfunction syndrome (MODS) performed during the period June, 2012 to December, 2014. After part of plasmapheresis with plasma filtration adsorption combined with continuous hemodiafiltration treatment, good curative effects were obtained and the main clinical symptoms and biochemical index were significantly improved. Following treatment, 8 of the 11 patients survived at a survival rate of 72.7%, and 3 patients succumbed with a mortality of 27.3%. The results suggested that part of plasmapheresis with plasma filtration adsorption combined with continuous venovenous hemodiafiltration (CVVHDF) treatment is beneficial in the removal of metabolites and toxins. Additonally, it can effectively improve liver function and clinical symptoms, improve hepatic encephalopathy, correct the disorder of internal environment, and improve the prognosis of patients. PMID:27698760

  14. Use of dialysis in the treatment of renal failure in liver disease

    PubMed Central

    Parsons, Victor; Wilkinson, S. P.; Weston, M. J.

    1975-01-01

    Early and thorough peritoneal and haemodialysis has a part to play in the management of selected patients with hepato-renal failure. Patients with advanced irreversible hepatic damage due to cirrhosis, however, may have their prognosis shortened by dialysis, but there are many problems in these techniques in patients with multiple organ failure which still require investigation and solution. PMID:1234334

  15. Peritoneal Albumin Dialysis as a Novel Approach for Liver Support: Study in a Porcine Model of Acute Hepatic Failure.

    PubMed

    Defterevos, Georgios; Nastos, Constantinos; Papalois, Apostolos; Kalimeris, Konstantinos; Margelos, Vassileios; Fragulidis, George; Pafiti, Agathi; Mikrovas, Aggeliki; Nomikos, Tzortzis; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

    2016-08-01

    Artificial liver support gained considerable interest in recent years due to the development of various albumin dialysis systems, which prolong survival of some patients with acute liver failure (ALF). Τhis study aims to examine the role of peritoneal albumin dialysis in a postoperative ALF model. ALF was induced in 14 female Landrace pigs by a combination of major liver resection (70-75% of total parenchyma) and ischemic-reperfusion injury on the liver remnant. Animals were randomly divided in two groups (n = 7 each). Both were monitored for 12 h of reperfusion and received peritoneal dialysis for 6 h, beginning 6 h after reperfusion. The albumin group received an albumin-rich solution and the control group received albumin-free solution. The control group gradually developed intracranial hypertension, whereas, in the albumin group, rise in the intracranial pressure was substantially attenuated (P < 0.01, t = 12 h). Albumin-treated animals had significantly lower levels of ammonia (P < 0.01), total bile acids (P < 0.01), free fatty acids (P < 0.05), lactate (P < 0.01), and total bilirubin (P < 0.05). Liver malondialdehyde and protein carbonyl were significantly reduced (P = 0.007 and P = 0.001 at t = 12 h) after albumin dialysis. Results suggest that this method may become a useful adjunct in the management of ALF, thus, justifying further study. PMID:27094211

  16. The Frequency and Determinants of Liver Stiffness Measurement Failure: A Retrospective Study of “Real-Life” 38,464 Examinations

    PubMed Central

    Han, Ping; Li, Fan; Li, Bing; Zang, Hong; Niu, Xiaoxia; Li, Zhongbin; Xin, Shaojie; Chen, Guofeng

    2014-01-01

    Objective To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in “real-life” Chinese patients. Methods 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). Results 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/m2, 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). Conclusions 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. PMID:25122123

  17. Aetiology and Outcome of Acute Liver Failure in Children: Experience at a Tertiary Care Hospital of Bangladesh.

    PubMed

    Mazumder, M W; Karim, A B; Rukunuzzaman, M; Rahman, M A

    2016-07-01

    Acute liver failure (ALF) is a rapidly progressive, potentially fatal syndrome resulting from rapid death or injury to a large proportion of hepatocytes, caused by a variety of insult, leaving insufficient hepatic paranchymal mass to sustain liver function. The aetiology of ALF varies according to the age of patient and development of the country. The outcome of ALF also varies according to aetiology: survival is better in paracetamol poisoning whereas it is poor in metabolic diseases. The present study was undertaken to observe the underlying aetiology and outcome of ALF in children under 18 years of age admitted at the department of Paediatric Gastroenterology & Nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. It was a retrospective review of medical records from November 2011 through October 2014. During this period a total of 35 patients were diagnosed to have ALF. Aetiology was established in 25(71.4%) cases, whereas in 10(28.6%) cases, no identifiable cause was found. Viral hepatitis was the underlying cause in 12(34.3%) cases. After treatment 15(43%) ALF patients survived, 8(23%) left hospital with risk bond (DORB), and 12(34%) patients died. The study showed that among the 12 death patients, 5(41.7%) had viral hepatitis, 3(25%) Wilson's disease, and in 4(33.3%) no cause could be identified. Viral hepatitis and Wilson disease were found to be two common causes of ALF in this study. Future studies with larger sample size are required to know the actual causes of acute liver failure in Bangladeshi children. PMID:27612896

  18. Natural Killer Cells-Produced IFN-γ Improves Bone Marrow-Derived Hepatocytes Regeneration in Murine Liver Failure Model

    PubMed Central

    Li, Lu; Zeng, Zhutian; Qi, Ziping; Wang, Xin; Gao, Xiang; Wei, Haiming; Sun, Rui; Tian, Zhigang

    2015-01-01

    Bone-marrow transplantation (BMT) can repopulate the liver through BM-derived hepatocyte (BMDH) generation, although the underlying mechanism remains unclear. Using fumarylacetoacetate hydrolase–deficient (Fah−/−) mice as a liver-failure model, we confirmed that BMDHs were generated by fusion of BM-derived CD11b+F4/80+myelomonocytes with resident Fah−/− hepatocytes. Hepatic NK cells became activated during BMDH generation and were the major IFN-γ producers. Indeed, both NK cells and IFN-γ were required for BMDH generation since WT, but not NK-, IFN-γ–, or IFN-γR1–deficient BM transplantation successfully generated BMDHs and rescued survival in Fah−/− hosts. BM-derived myelomonocytes were determined to be the IFN-γ–responding cells. The IFN-γ–IFN-γR interaction contributed to the myelomonocyte–hepatocyte fusion process, as most of the CD11b+ BMDHs in mixed BM chimeric Fah−/− hosts transplanted with a 1:1 ratio of CD45.1+ WT and CD45.2+ Ifngr1−/− BM cells were of CD45.1+ WT origin. Confirming these findings in vitro, IFN-γ dose-dependently promoted the fusion of GFP+ myelomonocytes with Fah−/− hepatocytes due to a direct effect on myelomonocytes; similar results were observed using activated NK cells. In conclusion, BMDH generation requires NK cells to facilitate myelomonocyte–hepatocyte fusion in an IFN-γ–dependent manner, providing new insights for treating severe liver failure. PMID:26345133

  19. Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

    PubMed

    Leshinsky-Silver, E; Levine, A; Nissenkorn, A; Barash, V; Perach, M; Buzhaker, E; Shahmurov, M; Polak-Charcon, S; Lev, D; Lerman-Sagie, T

    2003-08-01

    CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency. PMID:12948744

  20. The Reg3α (HIP/PAP) Lectin Suppresses Extracellular Oxidative Stress in a Murine Model of Acute Liver Failure

    PubMed Central

    Moniaux, Nicolas; Darnaud, Marion; Garbin, Kévin; Dos Santos, Alexandre; Guettier, Catherine; Samuel, Didier; Amouyal, Gilles; Amouyal, Paul; Bréchot, Christian; Faivre, Jamila

    2015-01-01

    Background and Aims Acute liver failure (ALF) is a rapidly progressive heterogeneous illness with high mortality rate and no widely accessible cure. A promising drug candidate according to previous preclinical studies is the Reg3α (or HIP/PAP) lectin, which alleviates ALF through its free-radical scavenging activity. Here we study the therapeutic targets of Reg3α in order to gain information on the nature of the oxidative stress associated with ALF. Methods Primary hepatocytes stressed with the reactive oxygen species (ROS) inducers TNFα and H2O2 were incubated with a recombinant Reg3α protein. ALF was induced in C57BL/6J mice by an anti-CD95 antibody. Livers and primary hepatocytes were harvested for deoxycholate separation of cellular and extracellular fractions, immunostaining, immunoprecipitation and malondialdehyde assays. Fibrin deposition was studied by immunofluorescence in frozen liver explants from patients with ALF. Results Fibrin deposition occurs during experimental and clinical acute liver injuries. Reg3α bound the resulting transient fibrin network, accumulated in the inflammatory extracellular matrix (ECM), greatly reduced extracellular ROS levels, and improved cell viability. Hepatocyte treatment with ligands of death receptors, e.g. TNFα and Fas, resulted in a twofold increase of malondialdehyde (MDA) level in the deoxycholate-insoluble fractions. Reg3α treatment maintained MDA at a level similar to control cells and thereby increased hepatocyte survival by 35%. No antioxidant effect of Reg3α was noted in the deoxycholate-soluble fractions. Preventing fibrin network formation with heparin suppressed the prosurvival effect of Reg3α. Conclusions Reg3α is an ECM-targeted ROS scavenger that binds the fibrin scaffold resulting from hepatocyte death during ALF. ECM alteration is an important pathogenic factor of ALF and a relevant target for pharmacotherapy. PMID:25938566

  1. Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver Failure and Tissue Evidence of Impaired Energy Metabolism

    PubMed Central

    Valencia, C. Alexander; Wang, Xinjian; Wang, Jin; Peters, Anna; Simmons, Julia R.; Moran, Molly C.; Mathur, Abhinav; Husami, Ammar; Qian, Yaping; Sheridan, Rachel; Bove, Kevin E.; Witte, David; Huang, Taosheng; Miethke, Alexander G.

    2016-01-01

    Background & Aims The etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism. Methods Twelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis. Results A customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content <30% of controls, and reduced respiratory chain complex activity; both patients had good post-transplant outcome. One infant with severe lactic acidosis was found to carry two heterozygous variants in ACAD9, which was associated with isolated complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with heterozygous variants of unknown clinical significance in POLG and DGUOK developed ALF following drug exposure. Their hepatocytes displayed abnormal mitochondria by electron microscopy. Conclusion Targeted next generation sequencing and correlation with histological, ultrastructural and functional studies on liver tissue in children with elevated lactate/pyruvate ratio expand the spectrum of genes associated with pediatric ALF. PMID:27483465

  2. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B.

    PubMed Central

    Li, Hai; Chen, Liu-Ying; Zhang, Nan-nan; Li, Shu-Ting; Zeng, Bo; Pavesi, Marco; Amorós, Àlex; Mookerjee, Rajeshwar P; Xia, Qian; Xue, Feng; Ma, Xiong; Hua, Jing; Sheng, Li; Qiu, De-kai; Xie, Qing; Foster, Graham R; Dusheiko, Geoffrey; Moreau, Richard; Gines, Pere; Arroyo, Vicente; Jalan, Rajiv

    2016-01-01

    The diagnostic and prognostic criteria of acute-on-chronic liver failure (ACLF) were developed in patients with no Hepatitis B virus (HBV) cirrhosis (CANONIC study). The aims of this study were to evaluate whether the diagnostic (CLIF-C organ failure score; CLIF-C OFs) criteria can be used to classify patients; and the prognostic score (CLIF-C ACLF score) could be used to provide prognostic information in HBV cirrhotic patients with ACLF. 890 HBV associated cirrhotic patients with acute decompensation (AD) were enrolled. Using the CLIF-C OFs, 33.7% (300 patients) were diagnosed as ACLF. ACLF was more common in the younger patients and in those with no previous history of decompensation. The most common organ failures were ‘hepatic’ and ‘coagulation’. As in the CANONIC study, 90-day mortality was extremely low in the non-ACLF patients compared with ACLF patients (4.6% vs 50%, p < 0.0001). ACLF grade and white cell count, were independent predictors of mortality. CLIF-C ACLFs accurately predicted short-term mortality, significantly better than the MELDs and a disease specific score generated for the HBV patients. Current study indicates that ACLF is a clinically and pathophysiology distinct even in HBV patients. Consequently, diagnostic criteria, prognostic scores and probably the management of ACLF should base on similar principles. PMID:27146801

  3. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis

    PubMed Central

    Li, Jingjing; Chen, Kan; Li, Sainan; Liu, Tong; Wang, Fan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2016-01-01

    This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis. PMID:27035150

  4. Protective effects of luteolin against acetaminophen-induced acute liver failure in mouse.

    PubMed

    Tai, Minghui; Zhang, Jingyao; Song, Sidong; Miao, RunChen; Liu, Sushun; Pang, Qing; Wu, Qifei; Liu, Chang

    2015-07-01

    Acetaminophen (APAP) is widely used as a safety analgesic and antipyretic agent. Although considered safe at therapeutic doses, overdose of APAP can cause acute liver injury that is sometimes fatal, requiring efficient pharmacological intervention. Luteolin is a naturally occurring flavonoid which is abundant in plants. The objective of this study was to investigate corresponding anti-oxidative and anti-inflammatory activities of luteolin, using acetaminophen-treated mice as a model system. Male C57BL/C mice were randomly divided into three groups (n=6 each). The control group was given phosphate buffered saline (PBS) orally. The APAP group was given APAP by intraperitoneal injection (i.p) at 300 mg/kg suspended in PBS. The luteolin-treated group was given APAP and luteolin (0-100 mg/kg/day, 1 or 3 days before APAP administration) suspended in PBS orally. 16 h after APAP administration, the liver and serum were collected to determine the liver injury. Luteolin administration significantly decreased acetaminophen-induced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) levels, as well as glutathione (GSH) depletion and decrease of superoxide dismutase (SOD). Luteolin restored SOD, GSH and GSH-px activities and depressed the expression of pro-inflammatory factors, such as inducible nitric oxide synthase (i-NOS), TNF-α, nuclear factor kappa B (NF-κB), and IL-6, respectively. Moreover, luteolin down-regulated acetaminophen-induced nitrotyrosine (NT) formation and endoplasmic reticulum (ER) stress. These results suggest the presence of anti-oxidative, anti-inflammatory and anti-ER stress properties of luteolin in response to acetaminophen-induced liver injury in mice.

  5. The value of serial Doppler ultrasound as a predictor of clinical outcome and the need for transplantation in fulminant and severe acute liver failure.

    PubMed

    Deasy, N P; Wendon, J; Meire, H B; Sidhu, P S

    1999-02-01

    The aim of this study was to document the changes in Doppler ultrasound variables of the hepatic artery and portal vein in fulminant and severe acute liver failure, and to assess their prognostic significance. 18 adult patients with fulminant and severe acute liver failure underwent serial Doppler sonography, in the early stages after presentation. 12 hourly measurements of hepatic artery resistance index (HARI), spleen length, portal vein cross-sectional area, time average velocity (TAV) and flow volume were performed. Mean HARI (p = 0.03) and mean maximum HARI (p = 0.03) were significantly higher in those who fulfilled criteria for liver transplantation. Increased portal vein flow was demonstrated, although the difference between the groups was not significant. A significant increase in portal vein cross-sectional area (p < 0.02) and spleen length (p < 0.02) was demonstrated. In summary, an increase in portal blood flow to the damaged liver has been demonstrated. The mean HARI is significantly higher in patients who fulfil transplant criteria and may possibly be used as an indicator of poorer prognosis and the need for liver transplantation in acute severe and fulminant liver failure.

  6. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  7. Carnosine Reduces Oxidative Stress and Reverses Attenuation of Righting and Postural Reflexes in Rats with Thioacetamide-Induced Liver Failure.

    PubMed

    Milewski, Krzysztof; Hilgier, Wojciech; Fręśko, Inez; Polowy, Rafał; Podsiadłowska, Anna; Zołocińska, Ewa; Grymanowska, Aneta W; Filipkowski, Robert K; Albrecht, Jan; Zielińska, Magdalena

    2016-02-01

    Cerebral oxidative stress (OS) contributes to the pathogenesis of hepatic encephalopathy (HE). Existing evidence suggests that systemic administration of L-histidine (His) attenuates OS in brain of HE animal models, but the underlying mechanism is complex and not sufficiently understood. Here we tested the hypothesis that dipeptide carnosine (β-alanyl-L-histidine, Car) may be neuroprotective in thioacetamide (TAA)-induced liver failure in rats and that, being His metabolite, may mediate the well documented anti-OS activity of His. Amino acids [His or Car (100 mg/kg)] were administrated 2 h before TAA (i.p., 300 mg/kg 3× in 24 h intervals) injection into Sprague-Dawley rats. The animals were thus tested for: (i) brain prefrontal cortex and blood contents of Car and His, (ii) amount of reactive oxygen species (ROS), total antioxidant capacity (TAC), GSSG/GSH ratio and thioredoxin reductase (TRx) activity, and (iii) behavioral changes (several models were used, i.e. tests for reflexes, open field, grip test, Rotarod). Brain level of Car was reduced in TAA rats, and His administration significantly elevated Car levels in control and TAA rats. Car partly attenuated TAA-induced ROS production and reduced GSH/GSSG ratio, whereas the increase of TRx activity in TAA brain was not significantly modulated by Car. Further, Car improved TAA-affected behavioral functions in rats, as was shown by the tests of righting and postural reflexes. Collectively, the results support the hypothesis that (i) Car may be added to the list of neuroprotective compounds of therapeutic potential on HE and that (ii) Car mediates at least a portion of the OS-attenuating activity of His in the setting of TAA-induced liver failure. PMID:26801175

  8. Dynamic tracking of stem cells in an acute liver failure model

    PubMed Central

    Ezzat, Tarek; Dhar, Dipok Kumar; Malago, Massimo; Damink, Steven WM Olde

    2012-01-01

    AIM: To investigate a dual labeling technique, which would enable real-time monitoring of transplanted embryonic stem cell (ESC) kinetics, as well as long-term tracking. METHODS: Liver damage was induced in C57/BL6 male mice (n = 40) by acetaminophen (APAP) 300 mg/kg administered intraperitoneally. Green fluorescence protein (GFP) positive C57/BL6 mouse ESCs were stained with the near-infrared fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) immediately before transplantation into the spleen. Each of the animals in the cell therapy group (n = 20) received 5 × 106 ESCs 4 h following treatment with APAP. The control group (n = 20) received the vehicle only. The distribution and dynamics of the cells were monitored in real-time with the IVIS Lumina-2 at 30 min post transplantation, then at 3, 12, 24, 48 and 72 h, and after one and 2 wk. Immunohistochemical examination of liver tissue was used to identify expression of GFP and albumin. Plasma alanine aminotransferase (ALT) was measured as an indication of liver damage. RESULTS: DiR-stained ESCs were easily tracked with the IVIS using the indocyanine green filter due to its high background passband with minimal background autofluorescence. The transplanted cells were confined inside the spleen at 30 min post-transplantation, gradually moved into the splenic vein, and were detectable in parts of the liver at the 3 h time-point. Within 24 h of transplantation, homing of almost 90% of cells was confirmed in the liver. On day three, however, the DiR signal started to fade out, and ex vivo IVIS imaging of different organs allowed signal detection at time-points when the signal could not be detected by in vivo imaging, and confirmed that the highest photon emission was in the liver (P < 0.0001). At 2 wk, the DiRsignal was no longer detectable in vivo; however, immunohistochemistry analysis of constitutively-expressed GFP was used to provide an insight into the distribution of

  9. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain.

    PubMed

    Cauli, Omar; González-Usano, Alba; Cabrera-Pastor, Andrea; Gimenez-Garzó, Carla; López-Larrubia, Pilar; Ruiz-Sauri, Amparo; Hernández-Rabaza, Vicente; Duszczyk, Malgorzata; Malek, Michal; Lazarewicz, Jerzy W; Carratalá, Arturo; Urios, Amparo; Miguel, Alfonso; Torregrosa, Isidro; Carda, Carmen; Montoliu, Carmina; Felipo, Vicente

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.

  10. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

    PubMed Central

    Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

    2015-01-01

    Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

  11. Orthotopic liver transplantation in critically ill cirrhotic patients with multi-organ failure: a single-center experience.

    PubMed

    Umgelter, A; Lange, K; Kornberg, A; Büchler, P; Friess, H; Schmid, R M

    2011-12-01

    Due to the lack of donor organs for orthotopic liver transplantation (OLT) in Germany, a larger proportion of patients advance to multi-organ failure (MOF) before OLT. Twenty-three patients on the waiting list for OLT were admitted to our intensive care unit (ICU) from January 2007 until September 2009. They consisted of 16 men and 7 women of median (25th-75th percentile) age of 60 years (54-65). Acute Physiology and Chronic Health Evaluation (APACHE II) score upon ICU admission was 26 (19-34); Model of End-Stage Liver Disease (MELD) score was 29 (22-41); Sequential Organ Failure Assessment (SOFA) score was 12 (8-16). The 90-day mortality rate was 39%. A decrease in MELD score during the first 48 hours (-2 [-5-0] vs 2 [-1-4]; P=.019) was associated with survival. Thirteen patients underwent transplantation from the ICU. By the time of the OLT, the MELD scores had deteriorated to 38 (33-39) and SOFA scores to 19 (18-19). All patients were mechanically ventilated and received hemodynamic support with catecholamines. Ten of 13 patients (77%) received renal replacement therapy and/or single pass albumin dialysis. Eight of 13 patients (62%) had a SOFA score of 3 or 4 (organ failure) in each of the respective subscores for the cardiovascular, renal, and respiratory systems at the time of OLT. The 90-day mortality rate after OLT was 38% and the 1-year-mortality rate was 54%. Patients who did not survive 90 days post OLT showed lower MELD scores on admission (33 [18-35] vs 44 [32-46]; P=.045), an increased MELD during the first 48 hours (3 [1-4] vs -2 [-8-1]; P=.002), and a longer ICU stay before OLT (32 [18-37] vs 8 [2-15]; P=.006). In conclusion, OLT may be successful treatment for cirrhotic patients with MOF. Outcomes of MOF in cirrhotic patients may improve after OLT but are generally worse than acceptable. A shorter ICU waiting time seemed to be beneficial.

  12. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

  13. Thiabendazole-induced acute liver failure requiring transplantation and subsequent diagnosis of polyarteritis nodosa.

    PubMed

    Groh, Matthieu; Blanche, Philippe; Calmus, Yvon; Guillevin, Loïc

    2012-01-01

    Polyarteritis nodosa (PAN), a systemic necrotising vasculitis that affects medium- and small-sized arteries, has visceral involvement in 40-60% of the patients. According to the Five-Factor Score (FFS), it is associated with poor outcome. We describe a patient who underwent orthotopic liver transplantation (OLT) for severe ductopenia induced by thiabendazole that was empirically prescribed for chronic hypereosinophilia. Eleven years later, despite immunosuppressive treatment to prevent graft rejection, he developed mononeuritis multiplex; PAN was diagnosed. He also had severe recurrent ischaemic cholangitides because of post-OLT hepatic artery ligation to treat a postoperative severe haematemesis. His outcome was favourable after second OLT, under steroids, cyclophosphamide pulses and tacrolimus. In retrospect, his initial symptoms and hypereosinophilia were probably attributable to PAN.

  14. The failure of selenium supplementation to prevent copper-induced liver damage in Fischer 344 rats.

    PubMed Central

    Aburto, E M; Cribb, A; Fuentealba, I C; Ikede, B O; Kibenge, F S; Markham, F

    2001-01-01

    This study evaluates the ability of selenium (Se) supplementation to prevent experimental copper (Cu)-induced hepatocellular damage. Weanling male Fischer 344 rats were randomly assigned to groups of 15, 3 groups (A,B,C) were fed Cu-loaded diets (containing 2000 microg/g copper, added as CuSO4) and different levels of Se (added as Na2SeO3 x 5H2O) as follows: A) Cu-loaded/Se adequate diet (0.4 microg/g Se, fed basis); B) Cu-loaded/Se-supplemented diet (2 microg/g Se); and C) Cu-loaded/Se-deficient diet (< 0.2 microg/g). Three additional groups (D,E,F) were fed diets containing adequate levels of Cu (14 microg/g Cu, fed basis) and different levels of Se as follows: D) Cu-adequate/Se-adequate diet; E) Cu-adequate/Se-supplemented diet (2 microg/g Se); and F) Cu-adequate/Se-deficient (< 0.2 microg/g) diet. After 4, 8, and 12 weeks on the experimental diets, liver samples were processed for histology, histochemistry, metal analysis, glutathione peroxidase (GSH-Px) measurement, and quantification of malondialdehyde (MDA). Morphologic changes characteristic of Cu-associated hepatitis, without an increase in hepatic MDA levels, were seen in all Cu-loaded rats in each sampling. Similar changes occurred in rats fed Se-adequate, Se-supplemented and Se-deficient diets. This study demonstrates that Fischer 344 rats fed 2000 microg/g Cu develop morphologic changes due to Cu toxicity without evidence of lipid peroxidation. Furthermore, Se supplementation does not result in protection against Cu-induced liver injury. Images Figure 3. Figure 4. Figure 5. Figure 6. PMID:11346254

  15. Sphingosine kinase 1 dependent protein kinase C-δ activation plays an important role in acute liver failure in mice

    PubMed Central

    Lei, Yan-Chang; Yang, Ling-Ling; Li, Wen; Luo, Pan

    2015-01-01

    AIM: To investigate the role of protein kinase C (PKC)-δ activation in the pathogenesis of acute liver failure (ALF) in a well-characterized mouse model of D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced ALF. METHODS: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-GaIN (600 mg/kg) and LPS (10 μg/kg). 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 multiparameteric analyzer. Serum levels of high-mobility group box 1 (HMGB1), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 as well as nuclear factor (NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells (PBMCs) was analyzed by Western blot. RESULTS: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-GalN/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group (P < 0.001). Rottlerin treatment also significantly decreased serum levels of HMGB1 at 6, 12, and 24 h, TNF-α, IL-6 and IL-1 β at 12 h compared with the control group (P < 0.01). The inflammatory cell infiltration and necrosis in liver tissue were also decreased in the rottlerin treatment group. Furthermore, sphingosine kinase 1 (SphK1) dependent PKC-δ activation played an important role in promoting NF-κB activation and inflammatory cytokine production in ALF. CONCLUSION: SphK1 dependent PKC-δ activation plays an important role in promoting NF-κB activation and inflammatory response in ALF, and inhibition of PKC-δ activation might be

  16. Interaction of isosafrole, beta-naphthoflavone and other CYP1A inducers in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus).

    PubMed

    Ronisz, D; Förlin, L

    1998-11-01

    The CYP1A enzyme in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus) was induced by intraperitoneal injections of isosafrole (ISF), beta-naphthoflavone (BNF), retene, 3,3',4,4'-tetrachlorobiphenyl (TCB), Clophen A50 and combinations of these compounds. The livers were sampled 5 days after injection and the microsomal fraction was used to measure the activity of CYP1A (as ethoxyresorufin-O-deethylase (EROD)) and the level of the enzyme (measured semiquantitatively as absorbance using enzyme-linked immunosorbant assay (ELISA)). Induction of CYP1A above the additive effect was observed when ISF was given together with BNF or retene. It was suggested that ISF may stabilize the enzyme or its mRNA or that ISF metabolites inhibit CYP1A processing of BNF and retene, thus increasing the effective doses of these compounds in fish liver. The results indicate a need for further studies of interactions between different CYP1A inducers in fish and a comparison of CYP1A response between different fish species. These results may have implications for the use of CYP1A induction in fish as a biomarker in aquatic systems, since a high EROD activity could be due not only to the presence of one potent inducer, but to synergistic effects of two or more inducers at low concentrations. PMID:9972470

  17. A new multiparameter integrated MELD model for prognosis of HBV-related acute-on-chronic liver failure.

    PubMed

    Luo, Yue; Xu, Yun; Li, Mingming; Xie, Ya; Gong, Guozhong

    2016-08-01

    Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is one of the most deadly diseases. Many models have been proposed to evaluate the prognosis of it. However, these models are still controversial. In this study, we aimed to incorporate some characters into model for end-stage liver disease (MELD) to establish a new reliable and feasible model for the prognosis of HBV-ACLF.A total of 530 HBV-ACLF patients who had received antiviral therapy were enrolled into a retrospective study and divided into the training cohort (300) and validation cohort (230). Logistic regression analysis was used to establish a model to predict the 3-month mortality from the patients in the training cohort, and then, the new model was evaluated in the validation cohort.Except for MELD score, 4 other independent factors, namely degree of hepatic encephalopathy (HE), alpha-fetoprotein (AFP), white blood cell (WBC) count, and age, were important for the new model called HBV-ACLF MELD (HAM) model: R = 0.174 × MELD + 1.106 × HE - (0.003 × AFP) + (0.237 × WBC) + (0.103 × Age) - 11.388. The areas under receiver-operating characteristic curve of HAM in the training and validation cohort were 0.894 and 0.868, respectively, which were significantly higher than those of other 7 models. With the best cut-off value of -1.191, HAM achieved higher sensitivity and negative predictive value.We developed a new model that has a great prognostic value of the 3-month mortality of patients with HBV-ACLF. PMID:27559979

  18. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. PMID:24365491

  19. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.

  20. Protective effects of protostemonine on LPS/GalN-induced acute liver failure: Roles of increased hepatic expression of heme oxygenase-1.

    PubMed

    Cheng, Zhuo; Yue, Ling; Zhao, Wenhao; Yang, Xinzhou; Shu, Guangwen

    2015-12-01

    Here, we explored protective effects of protostemonine (PSN), on mouse acute liver failure induced by lipopolysaccharide/d-galactosamine (LPS/GalN). PSN dose-dependently declined LPS/GalN-induced lethality of mice as well as increase of ALT/AST activities in their serum. Hepatoprotective effects of PSN were also supported by liver histopathological examinations. After LPS/GalN treatment, severe oxidative stresses in the liver could be detected by boosted MDA and ROS as well as decreased GSH. Moreover, hepatic expression of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6, were sharply elevated. These symptoms were dose-dependently ameliorated by PSN. Mechanistically, PSN promoted the transcription and translation of heme oxygenase-1 (HO-1) in hepatocytes and liver Kupffer cells. Nrf2 is a master transcription factor contributing to the expression of HO-1. PSN elevated Nrf2 nuclear accumulation and enhanced Nrf2/HO-1 promoter interaction. Suppressing enzyme activity of HO-1 by co-treating mice with HO-1 inhibitor ZnPP abolished protective effects of PSN. ZnPP also abrogated alleviative impacts of PSN on LPS/GalN-mediated hepatic oxidative stresses and inflammatory responses. Finally, we showed that PSN exhibited undetectable toxic effects on vital organs of mice. Our findings suggested that PSN is able to attenuate LPS/GalN-induced acute liver failure and upregulating HO-1 expression is implicated in its hepatoprotective activity.

  1. Acute liver failure caused by ‘fat burners’ and dietary supplements: A case report and literature review

    PubMed Central

    Radha Krishna, Y; Mittal, V; Grewal, P; Fiel, MI; Schiano, T

    2011-01-01

    Globally, people are struggling with obesity. Many effective, non-conventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful. PMID:21499580

  2. Disruptive SCYL1 Mutations Underlie a Syndrome Characterized by Recurrent Episodes of Liver Failure, Peripheral Neuropathy, Cerebellar Atrophy, and Ataxia

    PubMed Central

    Schmidt, Wolfgang M.; Rutledge, S. Lane; Schüle, Rebecca; Mayerhofer, Benjamin; Züchner, Stephan; Boltshauser, Eugen; Bittner, Reginald E.

    2015-01-01

    Hereditary ataxias comprise a group of genetically heterogeneous disorders characterized by clinically variable cerebellar dysfunction and accompanied by involvement of other organ systems. The molecular underpinnings for many of these diseases are widely unknown. Previously, we discovered the disruption of Scyl1 as the molecular basis of the mouse mutant mdf, which is affected by neurogenic muscular atrophy, progressive gait ataxia with tremor, cerebellar vermis atrophy, and optic-nerve thinning. Here, we report on three human individuals, from two unrelated families, who presented with recurrent episodes of acute liver failure in early infancy and are affected by cerebellar vermis atrophy, ataxia, and peripheral neuropathy. By whole-exome sequencing, compound-heterozygous mutations within SCYL1 were identified in all affected individuals. We further show that in SCYL1-deficient human fibroblasts, the Golgi apparatus is massively enlarged, which is in line with the concept that SCYL1 regulates Golgi integrity. Thus, our findings define SCYL1 mutations as the genetic cause of a human hepatocerebellar neuropathy syndrome. PMID:26581903

  3. Report of a novel C1483W mutation in the hepatitis E virus polymerase in patients with acute liver failure.

    PubMed

    Borkakoti, Jayanta; Ahmed, Giasuddin; Kar, Premashis

    2016-10-01

    Here, we report the molecular alterations in the HEV genome from patients with acute liver failure (ALF) and acute viral hepatitis (AVH) from North India, including pregnant women and its association with the poor outcome of the disease. We partially sequenced the RNA Dependent RNA polymerase (RdRp) region of the ORF 1 protein in the HEV genome from representative samples from patients with ALF and AVH and identified two novel mutations Cysteine 1483 Tryptophan and Asparagine 1530 Threonine in 100% (25/25) of the patients with ALF compared to none (0/30) of the patients with AVH (P<0.0001). Disease severity parameters along with viral load corresponding to the samples with C1483W and N1530T mutations were significantly higher compared to those lacking the mutation showing significant association with the outcome in ALF patients. The nucleotide substitutions in the RdRp region may play a crucial role in enhancing HEV replication thus leading to disease severity. PMID:27320795

  4. L-arginine and asymmetric dimethylarginine are early predictors for survival in septic patients with acute liver failure.

    PubMed

    Brenner, Thorsten; Fleming, Thomas H; Rosenhagen, Claudia; Krauser, Ute; Mieth, Markus; Bruckner, Thomas; Martin, Eike; Nawroth, Peter P; Weigand, Markus A; Bierhaus, Angelika; Hofer, Stefan

    2012-01-01

    Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24 h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.

  5. Revised criteria for classification of the etiologies of acute liver failure and late-onset hepatic failure in Japan: A report by the Intractable Hepato-biliary Diseases Study Group of Japan in 2015.

    PubMed

    Mochida, Satoshi; Nakayama, Nobuaki; Ido, Akio; Takikawa, Yasuhiro; Yokosuka, Osamu; Sakaida, Isao; Moriwaki, Hisataka; Genda, Takuya; Takikawa, Hajime

    2016-03-01

    In 2011, the Intractable Liver Diseases Study Group of Japan, established novel diagnostic criteria for "acute liver failure ", and published the classification criteria for the etiologies of acute liver failure and late-onset hepatic failure (LOHF) in 2013. According to this classification, HBV carriers showing acute hepatitis exacerbation were divided into 3 subgroups; asymptomatic or inactive HBV carriers without drug exposure, asymptomatic or inactive HBV carriers developing HBV reactivation during and after immunosuppressive therapies and/or antineoplastic chemotherapies and those with previously resolved HBV infection showing iatrogenic HBV reactivation. In an annual nationwide survey in 2013, however, a patient with previously resolved HBV infection was enrolled, in whom LOHF developed as a result of HBV reactivation despite in the absence of immunosuppressive therapies and/or antineoplastic chemotherapies. Thus, the study group revised the classification criteria in 2015; HBV carriers developing acute hepatitis exacerbation were classified into asymptomatic or inactive HBV carriers and patients with previously resolved HBV infection, and both groups were further sub-classified into those receiving immunosuppressive therapies and/or antineoplastic chemotherapies and those without such drugs exposure.

  6. Salvianolic acid A preconditioning confers protection against concanavalin A-induced liver injury through SIRT1-mediated repression of p66shc in mice

    SciTech Connect

    Xu, Xiaomei; Hu, Yan; Zhai, Xiaohan; Lin, Musen; Chen, Zhao; Tian, Xiaofeng; Zhang, Feng; Gao, Dongyan; Ma, Xiaochi; Lv, Li; Yao, Jihong

    2013-11-15

    Salvianolic acid A (SalA) is a phenolic carboxylic acid derivative extracted from Salvia miltiorrhiza. It has many biological and pharmaceutical activities. The purpose of this study was to investigate the effect of SalA on concanavalin A (ConA)-induced acute hepatic injury in Kunming mice and to explore the role of SIRT1 in such an effect. The results showed that in vivo pretreatment with SalA significantly reduced ConA-induced elevation in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and decreased levels of the hepatotoxic cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Moreover, the SalA pretreatment ameliorated the increases in NF-κB and in cleaved caspase-3 caused by ConA exposure. Whereas, the pretreatment completely reversed expression of the B-cell lymphoma-extra large (Bcl-xL). More importantly, the SalA pretreatment significantly increased the expression of SIRT1, a NAD{sup +}-dependent deacetylase, which was known to attenuate acute hypoxia damage and metabolic liver diseases. In our study, the increase in SIRT1 was closely associated with down-regulation of the p66 isoform (p66shc) of growth factor adapter Shc at both protein and mRNA levels. In HepG2 cell culture, SalA pretreatment increased SIRT1 expression in a time and dose-dependent manner and such an increase was abrogated by siRNA knockdown of SIRT1. Additionally, inhibition of SIRT1 significantly reversed the decreased expression of p66shc, and attenuated SalA-induced p66shc down-regulation. Collectively, the present study indicated that SalA may be a potent activator of SIRT and that SalA can alleviate ConA-induced hepatitis through SIRT1-mediated repression of the p66shc pathway. - Highlights: • We report for the first time that SalA protects against ConA-induced hepatitis. • We find that SalA is a potential activator of SIRT1. • SalA's protection against hepatitis involves SIRT1-mediated repression of p66shc.

  7. Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic cholangiopathy and graft failure in liver transplantation from donation after circulatory death.

    PubMed

    Halldorson, J B; Rayhill, S; Bakthavatsalam, R; Montenovo, M; Dick, A; Perkins, J; Reyes, J

    2015-03-01

    Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.

  8. Resolution of norfloxacin-induced acute liver failure after N-acetylcysteine therapy: further support for the use of NAC in drug-induced ALF?

    PubMed

    Elliott, Timothy Ross; Symes, Tiffany; Kannourakis, George; Angus, Peter

    2016-01-01

    Liver injury due to idiosyncratic drug reactions can be difficult to diagnose and may lead to acute liver failure (ALF), which has a high mortality rate. N-acetylcysteine (NAC) is effective treatment for paracetamol toxicity, but its role in non-paracetamol drug-induced ALF is controversial. We report on the use of a validated bedside tool to establish causality for drug-induced liver injury (DILI) and describe the first case of resolution of norfloxacin-induced ALF after NAC therapy. NAC is easy to administer and generally has a good safety profile. We discuss the evidence to support the use of NAC in ALF secondary to DILI and possibilities for further clinical research in this field. PMID:26740270

  9. Peroxisome proliferator-activated receptor alpha acts as a mediator of endoplasmic reticulum stress-induced hepatocyte apoptosis in acute liver failure

    PubMed Central

    Zhang, Li; Ren, Feng; Zhang, Xiangying; Wang, Xinxin; Shi, Hongbo; Zhou, Li; Zheng, Sujun; Chen, Yu; Chen, Dexi; Li, Liying; Duan, Zhongping

    2016-01-01

    ABSTRACT Peroxisome proliferator-activated receptor α (PPARα) is a key regulator to ameliorate liver injury in cases of acute liver failure (ALF). However, its regulatory mechanisms remain largely undetermined. Endoplasmic reticulum stress (ER stress) plays an important role in a number of liver diseases. This study aimed to investigate whether PPARα activation inhibits ER stress-induced hepatocyte apoptosis, thereby protecting against ALF. In a murine model of D-galactosamine (D-GalN)- and lipopolysaccharide (LPS)-induced ALF, Wy-14643 was administered to activate PPARα, and 4-phenylbutyric acid (4-PBA) was administered to attenuate ER stress. PPARα activation ameliorated liver injury, because pre-administration of its specific inducer, Wy-14643, reduced the serum aminotransferase levels and preserved liver architecture compared with that of controls. The protective effect of PPARα activation resulted from the suppression of ER stress-induced hepatocyte apoptosis. Indeed, (1) PPARα activation decreased the expression of glucose-regulated protein 78 (Grp78), Grp94 and C/EBP-homologous protein (CHOP) in vivo; (2) the liver protection by 4-PBA resulted from the induction of PPARα expression, as 4-PBA pre-treatment promoted upregulation of PPARα, and inhibition of PPARα by small interfering RNA (siRNA) treatment reversed liver protection and increased hepatocyte apoptosis; (3) in vitro PPARα activation by Wy-14643 decreased hepatocyte apoptosis induced by severe ER stress, and PPARα inhibition by siRNA treatment decreased the hepatocyte survival induced by mild ER stress. Here, we demonstrate that PPARα activation contributes to liver protection and decreases hepatocyte apoptosis in ALF, particularly through regulating ER stress. Therefore, targeting PPARα could be a potential therapeutic strategy to ameliorate ALF. PMID:27482818

  10. Peroxisome proliferator-activated receptor alpha acts as a mediator of endoplasmic reticulum stress-induced hepatocyte apoptosis in acute liver failure.

    PubMed

    Zhang, Li; Ren, Feng; Zhang, Xiangying; Wang, Xinxin; Shi, Hongbo; Zhou, Li; Zheng, Sujun; Chen, Yu; Chen, Dexi; Li, Liying; Zhao, Caiyan; Duan, Zhongping

    2016-07-01

    Peroxisome proliferator-activated receptor α (PPARα) is a key regulator to ameliorate liver injury in cases of acute liver failure (ALF). However, its regulatory mechanisms remain largely undetermined. Endoplasmic reticulum stress (ER stress) plays an important role in a number of liver diseases. This study aimed to investigate whether PPARα activation inhibits ER stress-induced hepatocyte apoptosis, thereby protecting against ALF. In a murine model of D-galactosamine (D-GalN)- and lipopolysaccharide (LPS)-induced ALF, Wy-14643 was administered to activate PPARα, and 4-phenylbutyric acid (4-PBA) was administered to attenuate ER stress. PPARα activation ameliorated liver injury, because pre-administration of its specific inducer, Wy-14643, reduced the serum aminotransferase levels and preserved liver architecture compared with that of controls. The protective effect of PPARα activation resulted from the suppression of ER stress-induced hepatocyte apoptosis. Indeed, (1) PPARα activation decreased the expression of glucose-regulated protein 78 (Grp78), Grp94 and C/EBP-homologous protein (CHOP) in vivo; (2) the liver protection by 4-PBA resulted from the induction of PPARα expression, as 4-PBA pre-treatment promoted upregulation of PPARα, and inhibition of PPARα by small interfering RNA (siRNA) treatment reversed liver protection and increased hepatocyte apoptosis; (3) in vitro PPARα activation by Wy-14643 decreased hepatocyte apoptosis induced by severe ER stress, and PPARα inhibition by siRNA treatment decreased the hepatocyte survival induced by mild ER stress. Here, we demonstrate that PPARα activation contributes to liver protection and decreases hepatocyte apoptosis in ALF, particularly through regulating ER stress. Therefore, targeting PPARα could be a potential therapeutic strategy to ameliorate ALF. PMID:27482818

  11. Successful orthotopic liver transplantation and delayed delivery of a healthy newborn in a woman with fulminant hepatic failure during the second trimester of pregnancy.

    PubMed

    Mendizabal, Manuel; Rowe, Carlos; Piñero, Federico; Gonzalez-Campaña, Ariel; Fauda, Martín; Tomás Arufe, Diego; Pía Raffa, María; Barreiro, Mariano; Keller, Rodolfo; Cacheiro, Fernando; Beruti, Ernesto; Andriani, Oscar; Oscar Silva, Marcelo; Podestá, Luis Gustavo

    2014-01-01

    Severe liver dysfunction during pregnancy implies a serious risk for both mother and fetus, and represents a technical and ethical challenge for treating physicians. We report a case of a previously healthy 32-year old woman who was admitted to our hospital with idiopathic fulminant hepatic failure and underwent successful orthotopic liver transplantation (OLT) at gestation week 21. Patient's and fetus' immediate postoperative course were relatively uneventful until week six after OLT, when the mother developed oligohydramnios and preeclampsia. At pregnancy week 27, after inducing baby's lung maturation, a cesarean section was performed with the delivery of an otherwise healthy girl. After 3 years of follow-up, mother and child are leading normal lives with no complications related either to pregnancy or to OLT. We describe the case of a successful emergency liver transplant in a woman during the second trimester of pregnancy, demonstrating that OLT can be a viable option to preserve the life of the mother and an otherwise unviable fetus. Intrauterine baby's growths until the attainment of a viable gestational age was feasible despite the mother's fulminant hepatic failure and liver transplant surgery.

  12. An Analysis of Viral Testing in non-Acetaminophen (non-APAP) Pediatric Acute Liver Failure (PALF)

    PubMed Central

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

    2014-01-01

    Objective Viral infections are often suspected to cause pediatric acute liver failure (PALF) but large-scale studies have not been performed. We analyzed results of viral testing among non-acetaminophen (non APAP) PALF study participants. Methods 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 (CV) or Associated Viruses (AV). Supplemental testing for CV was performed if not done clinically and serum was available. Final diagnoses included “Viral”, “Indeterminate” and “Other”. Results Of 860 participants, 820 had at least one 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. CV 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 - 6 months and over 6 months, respectively. HSV was not tested in 61.0% and 53% of the over-all cohort and those 0 - 6 months, respectively. Supplemental testing yielded 17 positive, including 5 HSV. Conclusions Viral testing in PALF occurs frequently but is often incomplete. 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. PMID:25079486

  13. Recent Advances in the Diagnosis and Management of Cirrhosis-Associated Cardiomyopathy in Liver Transplant Candidates: Advanced Echo Imaging, Cardiac Biomarkers, and Advanced Heart Failure Therapies

    PubMed Central

    Farr, Maryjane; Schulze, Paul Christian

    2014-01-01

    Patients with end-stage liver disease in need of liver transplantation increasingly are older with a greater burden of cardiac disease and other co-morbidities, which may increase perioperative risk and adversely affect long-term prognosis. Cirrhosis of any etiology manifests hemodynamically as a state of low systemic vascular resistance, with high peripheral, but low central blood volume, leading to a state of neurohormonal activation and high cardiac output, which may adversely affect cardiac reserve under extreme perioperative stress, aptly termed cirrhosis-associated or cirrhotic cardiomyopathy. Evidence of asymptomatic cirrhotic cardiomyopathy may be found in subtle electrocardiographic and echocardiographic changes, but may progress to severe heart failure under the demands of bleeding and transfusions, vasopressors, rebounding peripheral vascular resistance, withdrawal of cardioprotective beta-blockers and mineralocorticoid antagonists, exacerbated by sepsis or systemic inflammatory response syndrome. This review will add to the current body of literature on cirrhotic cardiomyopathy by focusing on the role of advanced echocardiographic imaging techniques, cardiac biomarkers, and advanced heart failure therapies available to manage patients with cirrhotic cardiomyopathy while waiting for liver transplant and during the perioperative period. PMID:25657603

  14. Liver regeneration.

    PubMed

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-04-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

  15. Liver Regeneration

    PubMed Central

    Mao, Shennen A; Glorioso, Jaime M; Nyberg, Scott L

    2014-01-01

    The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review will provide an overview of the models of study currently utilized in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus will be placed on clinical applications of current knowledge in liver regeneration including small for size liver transplant. Furthermore, cutting edge topics in liver regeneration including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a three dimensional scaffold for liver repopulation will be proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration. PMID:24495569

  16. Peroxisome proliferator-activated receptor α activation attenuates the inflammatory response to protect the liver from acute failure by promoting the autophagy pathway.

    PubMed

    Jiao, M; Ren, F; Zhou, L; Zhang, X; Zhang, L; Wen, T; Wei, L; Wang, X; Shi, H; Bai, L; Zhang, X; Zheng, S; Zhang, J; Chen, Y; Han, Y; Zhao, C; Duan, Z

    2014-08-28

    Peroxisome proliferator-activated receptor α (PPARα) has been reported to induce a potent anti-inflammatory response. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that PPARα activation mediates autophagy to inhibit liver inflammation and protect against acute liver failure (ALF). PPARα expression during ALF and the impact of PPARα activation by Wy-14 643 on the hepatic immune response were studied in a D-galactosamine/lipopolysaccharide-induced mouse model. Autophagy was inhibited by 3-methyladenine or small interfering RNA (siRNA) against Atg7. In both the mouse model and human ALF subjects, PPARα was significantly downregulated in the injured liver. PPARα activation by pretreatment with Wy-14 643 protected against liver injury in mice. The protective effect of PPARα activation relied on the suppression of inflammatory mechanisms through the induction of autophagy. This hypothesis is supported by the following evidence: first, PPARα activation suppressed proinflammatory responses and inhibited phosphorylated NF-κBp65, phosphorylated JNK and phosphorylated ERK pathways in vivo. Second, protection by PPARα activation was due to the induction of autophagy because inhibition of autophagy by 3-methyladenine or Atg7 siRNA reversed liver protection and inflammation. Third, PPARα activation directly induced autophagy in primary macrophages in vitro, which protected cells from a lipopolysaccharide-induced proinflammatory response. Here, for the first time, we have demonstrated that PPARα-mediated induction of autophagy ameliorated liver injury in cases of ALF by attenuating inflammatory responses, indicating a potential therapeutic application for ALF treatment.

  17. Splenic CD11c(low)CD45RB(high) dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure.

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. [Neonatal hemochromatosis: Another entity that is no longer orphan. Advances in the diagnosis and management of the main cause of neonatal acute liver failure].

    PubMed

    Molera Busoms, C; Quintero Bernabeu, J; Martín de Carpi, J

    2015-09-01

    Neonatal hemochromatosis is the most common cause of acute liver failure in the neonatal period. It is associated with high morbidity and mortality due to iron overload in hepatic and extra-hepatic tissues. New evidence has emerged during the last few years as regards its alloimmune etiology, which have had an important repercussion on the diagnosis, treatment and prognosis of these patients. Treatment with immunoglobulins and exchange transfusions has radically changed the prognosis without liver transplant. Another great success has been the preventive use of immunoglobulin in pregnant women with a past history of neonatal hemochromatosis, thus decreasing the rate of disease recurrence up to 70%. This new paradigm has led to an entity with a poor prognosis becoming a curable disease if diagnosed and treated early. Nevertheless, a large widespread ignorance of the disease persists, with medical implications that result in significant health problems, due to the delayed referral of these patients to specialized centers.

  20. Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

    PubMed

    Chen, Hui; Zhang, Ji; Cao, Guang; Liu, Peng; Xu, Haifeng; Wang, Xiaodong; Zhu, Xu; Gao, Song; Guo, Jianhai; Zhu, Linzhong; Zhang, Pengjun

    2016-02-01

    Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials.

  1. Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure: A Prospective Study.

    PubMed

    Zheng, Qing-Fen; Zhang, Jing-Yun; Wu, Ju-Shan; Zhang, Ying; Liu, Mei; Bai, Li; Zhang, Jin-Yan; Zhao, Jing; Chen, Yu; Duan, Zhong-Ping; Zheng, Su-Jun

    2016-02-01

    Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, -21, -143, and -200a; downregulated: miRNA-486-5p, -192, -148a, -122, and -194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486-5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV

  2. Reductions in post-hepatectomy liver failure and related mortality after implementation of the LiMAx algorithm in preoperative work-up: a single-centre analysis of 1170 hepatectomies of one or more segments

    PubMed Central

    Jara, Maximilian; Reese, Tim; Malinowski, Maciej; Valle, Erika; Seehofer, Daniel; Puhl, Gero; Neuhaus, Peter; Pratschke, Johann; Stockmann, Martin

    2015-01-01

    Objectives Post-hepatectomy liver failure has a major impact on patient outcome. This study aims to explore the impact of the integration of a novel patient-centred evaluation, the LiMAx algorithm, on perioperative patient outcome after hepatectomy. Methods Trends in perioperative variables and morbidity and mortality rates in 1170 consecutive patients undergoing elective hepatectomy between January 2006 and December 2011 were analysed retrospectively. Propensity score matching was used to compare the effects on morbidity and mortality of the integration of the LiMAx algorithm into clinical practice. Results Over the study period, the proportion of complex hepatectomies increased from 29.1% in 2006 to 37.7% in 2011 (P = 0.034). Similarly, the proportion of patients with liver cirrhosis selected for hepatic surgery rose from 6.9% in 2006 to 11.3% in 2011 (P = 0.039). Despite these increases, rates of post-hepatectomy liver failure fell from 24.7% in 2006 to 9.0% in 2011 (P < 0.001) and liver failure-related postoperative mortality decreased from 4.0% in 2006 to 0.9% in 2011 (P = 0.014). Propensity score matching was associated with reduced rates of post-hepatectomy liver failure [24.7% (n = 77) versus 11.2% (n = 35); P < 0.001] and related mortality [3.8% (n = 12) versus 1.0% (n = 3); P = 0.035]. Conclusions Postoperative liver failure and postoperative liver failure-related mortality decreased in patients undergoing hepatectomy following the implementation of the LiMAx algorithm. PMID:26058324

  3. A comprehensive validation of HBV-related acute-on-chronic liver failure models to assist decision-making in targeted therapeutics

    PubMed Central

    Shen, Yi; Wang, Xulin; Zhang, Sheng; Qin, Gang; Liu, Yanmei; Lu, Yihua; Liang, Feng; Zhuang, Xun

    2016-01-01

    This research utilized an external longitudinal dataset of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) to compare and validate various predictive models that support the current recommendations to select the most effective predictive risk models to estimate short- and long-term mortality and facilitate decision-making about preferable therapeutics for HBV-ACLF patients. Twelve ACLF prognostic models were developed after a systematic literature search using the longitudinal data of 232 HBV-ACLF patients on the waiting list for liver transplantation (LT). Four statistical measures, the constant (A) and slope (B) of the fitted line, the area under the curve (C) and the net benefit (D), were calculated to assess and compare the calibration, discrimination and clinical usefulness of the 12 predictive models. According to the model calibration and discrimination, the logistic regression models (LRM2) and the United Kingdom model of end-stage liver disease(UKELD) were selected as the best predictive models for both 3-month and 5-year outcomes. The decision curve summarizes the benefits of intervention relative to the costs of unnecessary treatment. After the comprehensive validation and comparison of the currently used models, LRM2 was confirmed as a markedly effective prognostic model for LT-free HBV-ACLF patients for assisting targeted and standardized therapeutic decisions. PMID:27633520

  4. A comprehensive validation of HBV-related acute-on-chronic liver failure models to assist decision-making in targeted therapeutics.

    PubMed

    Shen, Yi; Wang, Xulin; Zhang, Sheng; Qin, Gang; Liu, Yanmei; Lu, Yihua; Liang, Feng; Zhuang, Xun

    2016-01-01

    This research utilized an external longitudinal dataset of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) to compare and validate various predictive models that support the current recommendations to select the most effective predictive risk models to estimate short- and long-term mortality and facilitate decision-making about preferable therapeutics for HBV-ACLF patients. Twelve ACLF prognostic models were developed after a systematic literature search using the longitudinal data of 232 HBV-ACLF patients on the waiting list for liver transplantation (LT). Four statistical measures, the constant (A) and slope (B) of the fitted line, the area under the curve (C) and the net benefit (D), were calculated to assess and compare the calibration, discrimination and clinical usefulness of the 12 predictive models. According to the model calibration and discrimination, the logistic regression models (LRM2) and the United Kingdom model of end-stage liver disease(UKELD) were selected as the best predictive models for both 3-month and 5-year outcomes. The decision curve summarizes the benefits of intervention relative to the costs of unnecessary treatment. After the comprehensive validation and comparison of the currently used models, LRM2 was confirmed as a markedly effective prognostic model for LT-free HBV-ACLF patients for assisting targeted and standardized therapeutic decisions. PMID:27633520

  5. Sphingosine kinase 1 inhibition improves lipopolysaccharide/D-galactosamine-induced acute liver failure by inhibiting mitogen-activated protein kinases pathway

    PubMed Central

    Tian, Tao; Tian, Weiliang; Yang, Fan; Zhao, Risheng; Huang, Qian

    2016-01-01

    Background Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptors (S1PRs) signaling plays a key role in inflammatory responses. Lei et al. showed that SphK1 inhibition presented a hepatoprotective effect on acute liver damage via decreasing hepatic high-mobility group box 1 (HMGB1) cytoplasmic translocation. Objective We aim to determine whether SphK1 or S1PRs inhibition improves lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced acute liver failure by inhibiting the mitogen-activated protein kinases (MAPKs) pathway. Methods A mouse model of acute liver failure was induced by LPS/GalN. Male C57BL/6J mice (6–8 weeks) were randomly distributed into five groups: control group, LPS/GalN group, SphK1 inhibition group (LPS/GalN+SKI-5c), S1PR1 inhibition group (LPS/GalN+W146), and S1PR3 inhibition group (LPS/GalN+CAY10444). Results We confirmed the findings of Lei et al. that hepatic SphK1 expression was upregulated; serum transaminase activity (AST, ALT), as well as serum TNF-α and IL-6, were decreased by SphK1 inhibition. We further showed that the expression of S1PR1 and S1PR3 was augmented in response to LPS/GalN. SphK1 inhibition improves hepatic hemorrhage, and the activities of hepatic caspase-3 and myeloperoxidase (MPO). Furthermore, the activation of the MAPKs family (JNK, ERK and p38) was suppressed by SphK1 inhibition. However, S1PR1 or S1PR3 inhibition did not protect the mouse against liver damage, though S1PR1 or S1PR3 inhibition reduced serum TNF-α and IL-6, and partially attenuated the phosphorylation of the MAPKs signaling. Conclusions SphK1 inhibition improves LPS/GalN-induced liver injury by inhibiting activation of MAPKs signaling. PMID:27733910

  6. Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure

    PubMed Central

    Węglewska-Jurkiewicz, Anna; Taybert, Joanna; Pronicki, Maciej; Szymańska-Dębińska, Tamara; Karkucińska-Więckowska, Agnieszka; Jakóbkiewicz-Banecka, Joanna; Kowalski, Paweł; Piekutowska-Abramczuk, Dorota; Pajdowska, Magdalena; Socha, Piotr; Sykut-Cegielska, Jolanta; Węgrzyn, Grzegorz

    2010-01-01

    Deoxyguanosine kinase deficiency (dGK) is a frequent cause of the hepatocerebral form of mitochondrial depletion syndrome (MDS). A group of 28 infants with severe progressive liver failure of unknown cause was recruited for post mortem search for deoxyguanosine kinase (DGUOK) gene mutations. Four affected patients (14% of the studied group), two homozygotes, one compound heterozygote, and one heterozygote, with DGUOK mutation found on only one allele, were identified. Three known pathogenic mutations in the DGUOK gene were detected, c.3G>A (p.Met1Ile), c.494A>T (p.Glu165Val), and c.766_767insGATT (p.Phe256X), and one novel molecular variant of unknown pathogeneity, c.813_814insTTT (p.Asn271_Thr272insPhe). Profound mitochondrial DNA depletion was confirmed in available specimens of the liver (4%, 15%, and 10% of the normal value) and in the muscle (4%, 23%, 45%, and 6%, respectively). The patients were born with low weights for gestational age and they presented adaptation trouble during the first days of life. Subsequently, liver failure developed, leading to death at the ages of 18, 6, 5.5, and 2.25 months, respectively. Mild neurological involvement was observed in all children (hypotonia, psychomotor retardation, and ptosis). Hypoglycemia (hypoketotic) and lactic acidosis were the constant laboratory findings. Elevated transferrin saturation, high ferritin, and alpha-fetoprotein levels resembled, in two cases, a neonatal hemochromatosis. Liver histopathology showed severe hepatic damage ranging from micronodular formation and cirrhosis to the total loss of liver architecture with diffuse fibrosis and neocholangiolar proliferation. Pancreatic islet cell hyperplasia with numerous confluent giant islets was found in both autopsied infants. Analysis of the natural history of the disease in our patients and the literature data led us to the following observations: (i) islet cell hyperplasia (and hyperinsulinism) may contribute to MDS-associated hypoglycemia; (ii

  7. Liver transplant - series (image)

    MedlinePlus

    Liver failure causes many problems, including malnutrition, problems with blood clotting, bleeding form the gastrointestinal tract, and jaundice. Frequently, patients who undergo liver transplantation are quite ill, and require ...

  8. High-volume plasma exchange in a patient with acute liver failure due to non-exertional heat stroke in a sauna.

    PubMed

    Chen, Kuan-Jung; Chen, Tso-Hsiao; Sue, Yuh-Mou; Chen, Tzay-Jinn; Cheng, Chung-Yi

    2014-10-01

    Heat stroke is a life-threatening condition characterized by an increased core body temperature (over 40°C) and a systemic inflammatory response, which may lead to a syndrome of multiple organ dysfunction. Heat stroke may be due to either strenuous exercise or non-exercise-induced exposure to a high environmental temperature. Current management of heat stroke is mostly supportive, with an emphasis on cooling the core body temperature and preventing the development of multiple organ dysfunction. Prognosis of heat stroke depends on the severity of organ involvement. Here, we report a rare case of non-exercise-induced heat stroke in a 73-year-old male patient who was suffering from acute liver failure after prolonged exposure in a hot sauna room. We successfully managed this patient by administering high-volume plasma exchange, and the patient recovered completely after treatment.

  9. Bone marrow-derived macrophages distinct from tissue-resident macrophages play a pivotal role in Concanavalin A-induced murine liver injury via CCR9 axis

    PubMed Central

    Amiya, Takeru; Nakamoto, Nobuhiro; Chu, Po-sung; Teratani, Toshiaki; Nakajima, Hideaki; Fukuchi, Yumi; Taniki, Nobuhito; Yamaguchi, Akihiro; Shiba, Shunsuke; Miyake, Rei; Katayama, Tadashi; Ebinuma, Hirotoshi; Kanai, Takanori

    2016-01-01

    The fundamental mechanism how heterogeneous hepatic macrophage (Mφ) subsets fulfill diverse functions in health and disease has not been elucidated. We recently reported that CCR9+ inflammatory Mφs play a critical role in the course of acute liver injury. To clarify the origin and differentiation of CCR9+Mφs, we used a unique partial bone marrow (BM) chimera model with liver shielding for maintaining hepatic resident Mφs. First, irradiated mice developed less liver injury with less Mφs accumulation by Concanavalin A (Con A) regardless of liver shielding. In mice receiving further BM transplantation, CD11blowF4/80high hepatic-resident Mφs were not replaced by transplanted donors under steady state, while under inflammatory state by Con A, CCR9+Mφs were firmly replaced by donors, indicating that CCR9+Mφs originate from BM, but not from hepatic-resident cells. Regarding the mechanism of differentiation and proliferation, EdU+CCR9+Mφs with a proliferative potential were detected specifically in the inflamed liver, and in vitro study revealed that BM-derived CD11b+ cells co-cultured with hepatic stellate cells (HSCs) or stimulated with retinoic acids could acquire CCR9 with antigen-presenting ability. Collectively, our study demonstrates that inflammatory Mφs originate from BM and became locally differentiated and proliferated by interaction with HSCs via CCR9 axis during acute liver injury. PMID:27725760

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

    PubMed Central

    Zhang, Geng-lin; Zhang, Ting; Ye, Yi-nong; Liu, Jing; Zhang, Xiao-hong; Xie, Chan; Peng, Liang; Gao, Zhi-liang

    2016-01-01

    The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Serum levels of the third and fourth complement components (C3, C4) and complement function (CH50) were examined in this prospective, observational study. Associations between their expression and disease activity were analyzed. Survival was analyzed by Kaplan-Meier curves. Predictors of clinical outcome were determined by Cox regression analysis. C3, C4, and CH50 levels were significantly lower in HBV-ACLF patients compared to controls. C3, C4, and CH50 levels were negatively correlated with Tbil levels but positively associated with PTA levels. C3 levels were negatively associated with MELD-Na. C3 levels were significantly lower in HBV-ACLF patients who died compared to patients who survived. In a median hospital stay of 39 days, mortality occurred in 41 patients with a progressive increase based on C3 grade (P = 0.008). The actuarial probability of developing mortality was significantly higher in patients with low C3 grade compared to those with high C3 grade (P < 0.001). Multivariate Cox regression analysis showed that C3 levels were an independent predictor of mortality. Complement played a pathogenic role in HBV-ACLF patients and C3 was an independent predictor of mortality. PMID:27144164

  11. Detection of Ophthalmic Acid in Serum from Acetaminophen-Induced Acute Liver Failure Patients Is More Frequent in Non-Survivors

    PubMed Central

    Kaur, Gurnit; Leslie, Elaine M.; Tillman, Holly; Lee, William M.; Swanlund, Diane P.; Karvellas, Constantine J.

    2015-01-01

    Background/Aim Acetaminophen (APAP) hepatotoxicity is related to the formation of N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified through conjugation with reduced glutathione (GSH). Ophthalmic acid (OA) is an analogue of GSH in which cysteine is replaced with 2-aminobutyrate. Metabolomics studies of mice with APAP-induced acute liver failure (APAP-ALF) identified OA as a marker of oxidative stress and hepatic GSH consumption. The aim of the current study was to determine whether OA is detectable in APAP-ALF human patients either early (day 2) or late (day 4) and whether OA levels were associated with in-hospital survival in the absence of liver transplant. Methods Serum samples from 130 APAP-ALF patients (82 survivors, 48 non-survivors) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and correlated with clinical data from the United States Acute Liver Failure Study Group (US ALFSG) Registry (2004–2011). Results Survivors had significantly lower admission bilirubin (4.2 vs. 5.7 mg/dl) and lactate levels (3.3 vs. 6.5 μmol/l, p<0.05 for all). During the first 7 days of the study, survivors were less likely to require mechanical ventilation (55% vs. 88%), vasopressor support (9.8% vs. 67%) or renal replacement therapy (26% vs. 63%, p< 0.001 for all). Non-survivors were more likely to have detectable OA levels early (31% vs. 15%, p = 0.034) and late (27% vs. 11%, p = 0.02). However there were no significant differences in mean OA levels between non-survivors and survivors (early 0.48 vs. 0.36, late 0.43 vs. 0.37, P > 0.5 for all). Conclusion OA was detectable more frequently in APAP-ALF non-survivors but mean OA levels were not associated with survival. The routine clinical administration of N-acetyl cysteine could replenish GSH levels and prevent OA production. PMID:26407170

  12. Protectin D1 reduces concanavalin A-induced liver injury by inhibiting NF-κB-mediated CX3CL1/CX3CR1 axis and NLR family, pyrin domain containing 3 inflammasome activation.

    PubMed

    Ren, Jun; Meng, Shanshan; Yan, Bingdi; Yu, Jinyan; Liu, Jing

    2016-04-01

    Protectin D1 (PD1) is a bioactive product generated from docosahexaenoic acid, which may exert anti-inflammatory effects in various inflammatory diseases. However, the underlying molecular mechanism of its anti‑inflammatory activity on concanavalin A (Con A)-induced hepatitis remains unknown. The aim of the present study was to investigate the protective effects of PD1 against Con A‑induced liver injury and the underlying mechanisms via intravenous injection of PD1 prior to Con A administration. C57BL/6 mice were randomly divided into four experimental groups as follows: Control group, Con A group (30 mg/kg), 20 µg/kg PD1 + Con A (30 mg/kg) group and 10 µg/kg PD1 + Con A (30 mg/kg) group. PD1 pretreatment was demonstrated to significantly inhibit elevated plasma aminotransferase levels, high mobility group box 1 and liver necrosis, which were observed in Con A‑induced hepatitis. Furthermore, compared with the Con A group, PD1 pretreatment prevented the production of pro‑inflammatory cytokines, including tumor necrosis factor‑α, interferon‑γ and interleukin‑2, ‑1β and ‑6. In addition, pretreatment with PD1 markedly downregulated cluster of differentiation (CD)4+, CD8+ and natural killer T (NKT) cell infiltration in the liver. PD1 pretreatment was observed to suppress the messenger RNA and protein expression levels of NLR family, pyrin domain containing 3 and Toll‑like receptor (TLR) 4 in liver tissue samples. Further data indicated that PD1 pretreatment inhibited the activation of the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) signaling pathway and chemokine (C‑X3‑C motif) ligand 1 (CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) axis by preventing phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α and NF‑κB in Con A‑induced liver injury. Therefore, these results suggest that PD1 administration protects mice against Con A‑induced liver injury via

  13. Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure

    PubMed Central

    Valbusa, Filippo; Bonapace, Stefano; Grillo, Cristina; Scala, Luca; Chiampan, Andrea; Rossi, Andrea; Zoppini, Giacomo; Lonardo, Amedeo; Arcaro, Guido; Byrne, Christopher D.; Targher, Giovanni

    2016-01-01

    Abstract Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46–12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF. PMID:26886619

  14. A model to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure using artificial neural network.

    PubMed

    Zheng, M-H; Shi, K-Q; Lin, X-F; Xiao, D-D; Chen, L-L; Liu, W-Y; Fan, Y-C; Chen, Y-P

    2013-04-01

    Model for end-stage liver disease (MELD) scoring was initiated using traditional statistical technique by assuming a linear relationship between clinical features, but most phenomena in a clinical situation are not linearly related. The aim of this study was to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure (ACHBLF) on an individual patient level using an artificial neural network (ANN) system. The ANN model was built using data from 402 consecutive patients with ACHBLF. It was trained to predict 3-month mortality by the data of 280 patients and validated by the remaining 122 patients. The area under the curve of receiver operating characteristic (AUROC) was calculated for ANN and MELD-based scoring systems. The following variables age (P < 0.001), prothrombin activity (P < 0.001), serum sodium (P < 0.001), total bilirubin (P = 0.015), hepatitis B e antigen positivity rate (P < 0.001) and haemoglobin (P < 0.001) were significantly related to the prognosis of ACHBLF and were selected to build the ANN. The ANN performed significantly better than MELD-based scoring systems both in the training cohort (AUROC = 0.869 vs 0.667, 0.591, 0.643, 0.571 and 0.577; P < 0.001, respectively) and in the validation cohort (AUROC = 0.765 vs 0.599, 0.563, 0.601, 0.521 and 0.540; P ≤ 0.006, respectively). Thus, the ANN model was shown to be more accurate in predicting 3-month mortality of ACHBLF than MELD-based scoring systems. PMID:23490369

  15. Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure.

    PubMed

    Chiang, Chih-Hung; Wu, Wai-Wah; Li, Hsin-Yang; Chien, Yueh; Sun, Cho-Chin; Peng, Chi-Hsien; Lin, Alex Tong-Long; Huang, Chi-Shuan; Lai, Ying-Hsiu; Chiou, Shih-Hwa; Hung, Shuen-Iu; Chang, Yuh-Lih; Lan, Yuan-Tzu; Liu, Dean-Mo; Chien, Chian-Shiu; Huo, Teh-Ia; Lee, Shou-Dong; Wang, Chien-Ying

    2015-01-01

    Acute hepatic failure (AHF) is a severe liver injury leading to sustained damage and complications. Induced pluripotent stem cells (iPSCs) may be an alternative option for the treatment of AHF. In this study, we reprogrammed human dental pulp-derived fibroblasts into iPSCs, which exhibited pluripotency and the capacity to differentiate into tridermal lineages, including hepatocyte-like cells (iPSC-Heps). These iPSC-Heps resembled human embryonic stem cell-derived hepatocyte-like cells in gene signature and hepatic markers/functions. To improve iPSC-Heps engraftment, we next developed an injectable carboxymethyl-hexanoyl chitosan hydrogel (CHC) with sustained hepatocyte growth factor (HGF) release (HGF-CHC) and investigated the hepatoprotective activity of HGF-CHC-delivered iPSC-Heps in vitro and in an immunocompromised AHF mouse model induced by thioacetamide (TAA). Intrahepatic delivery of HGF-CHC-iPSC-Heps reduced the TAA-induced hepatic necrotic area and rescued liver function and recipient viability. Compared with PBS-delivered iPSC-Heps, the HGF-CHC-delivered iPSC-Heps exhibited higher antioxidant and antiapoptotic activities that reduced hepatic necrotic area. Importantly, these HGF-CHC-mediated responses could be abolished by administering anti-HGF neutralizing antibodies. In conclusion, our findings demonstrated that HGF mediated the enhancement of iPSC-Hep antioxidant/antiapoptotic capacities and hepatoprotection and that HGF-CHC is as an excellent vehicle for iPSC-Hep engraftment in iPSC-based therapy against AHF.

  16. Molecular Adsorbent Recirculating System (MARS(®)) removal of piperacillin/tazobactam in a patient with acetaminophen-induced acute liver failure.

    PubMed

    Ruggero, M A; Argento, A C; Heavner, M S; Topal, J E

    2013-04-01

    The objective of this study was to illustrate the pharmacokinetic removal of piperacillin/tazobactam in an anuric patient on Molecular Adsorbent Recirculating System (MARS(®)). The patient was a 32-year-old woman who presented to a medical intensive care unit with acute liver failure secondary to an acetaminophen overdose. While awaiting transplant, she was started on MARS therapy as a bridge to liver transplant and empirically started on piperacillin/tazobactam therapy. MARS is an extracorporeal hemofiltration device, which incorporates a continuous venovenous hemofiltration (CVVHD) machine linked to an albumin-enriched dialysate filter to normalize excess electrolytes, metabolic waste, and protein-bound toxins. In addition to protein-bound waste, MARS removes water-soluble, low molecular-weight molecules. The patient received piperacillin/tazobactam 4.5 g infused intravenously over 3 h. A steep decline in serum levels occurred between hours 4 and 6 while MARS continued and no antibiotic was infused. The elimination rate constant (k(e)) for the removal of piperacillin in this patent was 0.453 h(-1) and the half-life (λ) was 1.53 h. The k(e) was 2.9-fold higher than with CVVHD alone and the λ was 3.7-fold shorter. Low levels of piperacillin are achieved during MARS therapy, but in the treatment of more resistant organisms, such as Pseudomonas aeruginosa, these low levels may not be adequate to achieve bactericidal activity. Drug levels following a standard infusion of 30 min would likely be even lower. Formalized pharmacokinetic studies of piperacillin/tazobactam removal in patients on MARS therapy are necessary to make clear dosing recommendations.

  17. Intrahepatic microcirculatory disorder, parenchymal hypoxia and NOX4 upregulation result in zonal differences in hepatocyte apoptosis following lipopolysaccharide- and D-galactosamine-induced acute liver failure in rats

    PubMed Central

    TANAKA, MASATAKE; TANAKA, KOSUKE; MASAKI, YUKO; MIYAZAKI, MASAYUKI; KATO, MASAKI; KOTOH, KAZUHIRO; ENJOJI, MUNECHIKA; NAKAMUTA, MAKOTO; TAKAYANAGI, RYOICHI

    2014-01-01

    Although the mechanisms responsible for acute liver failure (ALF) have not yet been fully elucidated, studies have indicated that intrahepatic macrophage activation plays an important role in the pathogenesis of ALF through intrahepatic microcirculatory disorder and consequent parenchymal cell death. Intrahepatic microcirculatory disorder has been demonstrated in animal models using intravital microscopy; however, the limitations of this method include simultaneously evaluating blood flow and the surrounding pathological changes. Therefore, in this study, we devised a novel method involving tetramethylrhodamine isothiocyanate (TRITC)-dextran administration for the pathological assessment of hepatic microcirculation. In addition, we aimed to elucidate the mechanisms through which intrahepatic microcirculatory disorder progresses with relation to activated macrophages. ALF was induced in Wistar rats by exposure to lipopolysaccharide and D-galactosamine. Intrahepatic microcirculation and microcirculatory disorder in zone 3 (pericentral zone) of the livers of rats with ALF was observed. Immunohistochemical examinations in conjunction with TRITC-dextran images revealed that the macrophages were mainly distributed in zone 2 (intermediate zone), while cleaved caspase-3-positive hepatocytes, pimonidazole and hypoxia-inducible factor 1-α were abundant in zone 3. We also found that 4-hydroxy-2-nonenal and nicotinamide adenine dinucleotide phosphate oxidase (NOX)4-positive cells were predominantly located in the zone 3 parenchyma. The majority of apoptotic hepatocytes in zone 3 were co-localized with NOX4. Our results revealed that the apoptotic cells in zone 3 were a result of hypoxic conditions induced by intrahepatic microcirculatory disorder, and were not induced by activated macrophages. The increased levels of oxidative stress in zone 3 may contribute to the progression of hepatocyte apoptosis. PMID:24317376

  18. Upregulated Expression of A20 on Monocytes is Associated With Increased Severity of Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Guo, Yonghong; He, Yu; Zhang, Ying; Zhou, Yun; Qin, Yuan; Fan, Chao; Ji, Guangxi; Zhang, Peixin; Jia, Zhansheng

    2015-01-01

    Abstract A20 expression is increased in various inflammatory diseases. However, the role of A20 in acute-on-chronic liver failure is unknown. This study was to evaluate A20 expression on monocytes and its associations with the severity of acute-on-chronic hepatitis B liver failure (ACHBLF). Thirty-seven patients with ACHBLF, 20 patients with chronic hepatitis B (CHB), and 15 healthy controls (HC) were enrolled in this case-control study. A20-positive monocytes were identified using flow cytometry. Serum levels of interleukin (IL)-10, IL-12p70, and TNF-α were determined using bead cytometry. A20 and IL-10 expressions were examined in THP-1 cells stimulated by lipopolysaccharide (LPS). The frequency of A20+ monocytes was significantly increased in patients with ACHBLF compared with HC (median [interquartile range, IQR]: 15.7 [22.8]% vs 2.5 [4.7]%, P < 0.001). Increased monocyte A20 expression was detected during the progression phase (including the mild/moderate and severe grades of ACHBLF) compared with patients in the recovery phase (both P < 0.05), and in the ACHBLF worsening group compared with patients in the improvement group (P < 0.001). LPS treatment upregulated A20 and IL-10 expressions in THP-1 cells. A20 expression on monocytes from patients with ACHBLF was positively correlated with total bilirubin (r = 0.60, P = 0.0001), direct bilirubin (r = 0.63, P < 0.0001), and MELD score (r = 0.43, P = 0.008), and inversely with prothrombin activity (r = −0.33, P = 0.046). IL-10 and TLR4 expression levels in monocytes, and serum levels of IL-10, IL-12p70, and TNF-α were increased in patients with ACHBLF compared with patients with CHB and HC. Increased A20 expression on monocytes was associated with the severity of ACHBLF. PMID:26426612

  19. New Point Mutations in Surface and Core Genes of Hepatitis B Virus Associated with Acute on Chronic Liver Failure Identified by Complete Genomic Sequencing

    PubMed Central

    Lou, Guohua; Zheng, Min; Cao, Qingyi; Chen, Zhi

    2015-01-01

    The objective of this study was to identify new viral biomarkers associated with acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV. Hepatitis B virus mutations associated with ACLF were screened by Illumina high-throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic hepatitis B patients, which were validated in 438 chronic hepatitis B patients (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The results of Illumina sequencing showed that the mutations at 7 sites (T216C, G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were significantly higher than those of 12 controls. In the validation cohorts, a significantly higher ratio of genotype B to C was found in patients with ACLF than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A, C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any combination, A/G1913 in any combination, and G/C2159 in any combination had high specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors independently associated with ACLF. Combined mutations in hepatitis B cases could play important roles in ACLF development. PMID:25849554

  20. The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis

    PubMed Central

    Yang, Jiao; Sun, Hang; Liu, Qi

    2016-01-01

    Background. Currently, both of entecavir and lamivudine are effective for patients with HBV-associated acute-on-chronic liver failure (ACLF). However, there is no consensus on the efficacy of entecavir versus lamivudine for patients with HBV-associated ACLF. The aim of the study was to compare the efficacy and safety of entecavir with that of lamivudine for HBV-associated ACLF patients. Methods. Publications on entecavir versus lamivudine in HBV-associated ACLF patients were comprehensively identified. Odds ratio and mean difference were used to measure the effect. Results. Ten studies, totaling 1254 patients, were eligible. No significant differences between the two drugs presented in the 1-, 2-, 3-, or 6-month survival rates. However, after 12 months of treatment, patients prescribed entecavir had a statistically higher survival rate (p = 0.008) and lower total bilirubin (p < 0.0001) and alanine aminotransferase (p = 0.04) levels compared to patients prescribed lamivudine. More patients achieved HBV negative levels when taking entecavir as measured at 1-, 3-, and 12-month time points and had a lower rate of HBV recurrence. Conclusion. While entecavir and lamivudine are both relatively safe and well tolerated, entecavir was more efficacious in terms of survival rate and clinical improvement in long-term treatment. Further prospective randomized controlled trials are needed to validate these results. PMID:27148364

  1. Successful Use of Higher-Dose Etanercept for Multirefractory Systemic Flare of Adult-Onset Still's Disease with Liver Failure with No Response to Tocilizumab Therapy

    PubMed Central

    Tamechika, Shinya; Iwagaitsu, Shiho; Maeda, Shinji; Togawa, Hiroyuki

    2013-01-01

    A 21-year-old woman with refractory systemic flare of adult-onset Still's disease with liver failure despite high-dose corticosteroids, cyclosporine, tacrolimus, and tocilizumab, was successfully treated with additional use of etanercept. Etanercept at a dose of 50 mg weekly was partially effective but could not reduce the dose of concomitant betamethasone from 5 mg/day. Etanercept at a dose of 75 mg weekly could lead her to clinical remission and enabled successful tapering off the corticosteroids and discontinuation of etanercept. Normalization of serum C-reactive protein and interleukin 6 and persistent elevation of serum tumor necrosis factor α under the treatment with high-dose corticosteroids and immunosuppressants suggest that tumor necrosis factor α was more deeply involved than at least interleukin 6 in the pathogenesis of refractoriness of the disease in this patient, and these findings might be indicative of potential efficacy for adjunctive use of a tumor necrosis factor inhibitor rather than an interleukin 6 inhibitor. PMID:24455384

  2. Bioartificial liver: current status.

    PubMed

    Pless, G; Sauer, I M

    2005-11-01

    Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

  3. Liver metastases

    MedlinePlus

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic; Colorectal cancer - liver metastases; Colon cancer - liver metastases; Esophageal cancer - liver metastases; Lung cancer - liver metastases; Melanoma - liver metastases

  4. [Organ replacement therapy - extracorporeal liver assist devices].

    PubMed

    Sinner, Barbara; Kirchner, Gabriele I

    2016-09-01

    Liver failure is a disease with a high mortality rate. Often liver transplantation is the sole therapeutic option. On the one hand, liver support systems probably support the liver to allow regeneration, on the other hand they are an option to bridge for transplantation. This article gives an overview on the clinically used liver assist devices (molecular adsorbent recirculating system [MARS], Prometheus system, single-pass albumin dialysis [SPAD], plasmapheresis) and discusses the applications in liver failure. PMID:27631450

  5. L-Ornithine phenylacetate reduces ammonia in pigs with acute liver failure through phenylacetylglycine formation: a novel ammonia-lowering pathway.

    PubMed

    Kristiansen, Rune Gangsøy; Rose, Christopher F; Fuskevåg, Ole-Martin; Mæhre, Hanne; Revhaug, Arthur; Jalan, Rajiv; Ytrebø, Lars Marius

    2014-11-15

    Glycine is an important ammoniagenic amino acid, which is increased in acute liver failure (ALF). We have previously shown that L-ornithine phenylacetate (OP) attenuates ammonia rise and intracranial pressure in pigs suffering from ALF but failed to demonstrate a stoichiometric relationship between change in plasma ammonia levels and excretion of phenylacetylglutamine in urine. The aim was to investigate the impact of OP treatment on the phenylacetylglycine pathway as an alternative and additional ammonia-lowering pathway. A well-validated and -characterized large porcine model of ALF (portacaval anastomosis, followed by hepatic artery ligation), which recapitulates the cardinal features of human ALF, was used. Twenty-four female pigs were randomized into three groups: (1) sham operated + vehicle, (2) ALF + vehicle, and (3) ALF + OP. There was a significant increase in arterial glycine concentration in ALF (P < 0.001 compared with sham), with a three-fold increase in glycine release into the systemic circulation from the kidney compared with the sham group. This increase was attenuated in both the blood and brain of the OP-treated animals (P < 0.001 and P < 0.05, respectively), and the attenuation was associated with renal removal of glycine through excretion of the conjugation product phenylacetylglycine in urine (ALF + vehicle: 1,060 ± 106 μmol/l; ALF + OP: 27,625 ± 2,670 μmol/l; P < 0.003). Data from this study provide solid evidence for the existence of a novel, additional pathway for ammonia removal in ALF, involving glycine production and removal, which is targeted by OP.

  6. Effects of N-Acetylcysteine on Cytokines in Non-Acetaminophen Acute Liver Failure: Potential Mechanism of Improvement in Transplant-Free Survival

    PubMed Central

    Stravitz, R. Todd; Sanyal, Arun J.; Reisch, Joan; Bajaj, Jasmohan S.; Mirshahi, Faridoddin; Cheng, Jianfeng; Lee, William M.

    2016-01-01

    Background N-Acetylcysteine (NAC) improves transplant-free survival in patients with non-acetaminophen acute liver failure (ALF) when administered in early stages of hepatic encephalopathy. The mechanisms of this benefit are unknown. Aim To determine whether NAC improves transplant-free survival in ALF by ameliorating the surge of pro-inflammatory cytokines. Methods Serum samples were obtained from 78 participants of the randomized, ALF Study Group NAC Trial with grade 1 or 2 hepatic encephalopathy on randomization. Concentrations of ten cytokines, chosen to represent a wide array of inflammatory responses, were determined by multiplex ELISA. Results In univariate analysis, predictors of transplant-free survival included NAC administration (P=0.012), admission bilirubin (P=0.003), INR (P=0.0002), grade 1 vs. grade 2 encephalopathy (P=0.006) and lower admission interleukin (IL)-17 concentrations (P=0.011). IL-17 levels were higher in patients with grade 2 vs. 1 encephalopathy on randomization (P=0.007) and in those who progressed to grade 3 or 4 encephalopathy over the following 7 days (P≤0.01). Stepwise multivariate logistic regression analysis identified only NAC administration and lower IL-17 concentrations as independent predictors of transplant-free survival. In patients with detectable IL-17 concentrations on admission, 78% of those who received NAC vs. 44% of those who received placebo had undetectable levels by day 3-5 (P=0.042), and the mean decrease in IL-17 concentrations between admission and late samples was significantly greater in patients who received NAC vs. placebo (P=0.045). Conclusions NAC may improve transplant-free survival in patients with non-acetaminophen ALF by ameliorating the production of IL-17, which is associated with progression of hepatic encephalopathy and poor outcome. PMID:23782487

  7. Association of Proton Pump Inhibitor Therapy with Hepatic Encephalopathy in Hepatitis B Virus-related Acute-on-Chronic Liver Failure

    PubMed Central

    Lin, Zhao-Ni; Zuo, Yong-Qing; Hu, Peng

    2014-01-01

    Background: Hepatic encephalopathy (HE) is an important neuropsychiatry complication of acute-on-chronic liver failure (ACLF). PPI therapy may increase the intestinal bacterial overgrowth and infections. Objectives: The aim of this study was to assess whether PPI use in ACLF is associated with HE. Patients and Methods: A retrospective case-control study was performed. Fifty five admitted patients with hepatitis B virus (HBV)-related ACLF complicated by Stage II-IV HE developed after admission between January 2008 and December 2012 were matched (by sex, age, and MELD score) with comparable HBV-related ACLF patients (n = 110) who did not develop this complication during hospitalization. We excluded combined HE upon admission and other neurological disorders in patients with ACLF. Univariate and multivariate analyses of 30 variables (laboratory examination, predisposition, treatment, etc.) before the occurrence of HE were carried out to identify the factors predictive of HE. Results: In univariate analysis, patients with HE in ACLF had a significantly higher rate of PPI use (89.1%) compared with non-HE (63.6%, P = 0.001). In addition, clinical and standard laboratory variables were significantly different between the two groups regarding the infection rate, hyponatremia, alpha-fetoprotein (AFP), Arginine Hydrochloride use and Lactulose use. Logistic regression analysis was used to examine the combined effects of the variables with HE as the outcome. HE in ACLF was associated with hyponatremia (odds ratio (OR) = 6. 318, 95% confidence interval (CI) = 2. 803-14.241; P = 0. 000), PPI use was independently associated with HE (OR = 4. 392, CI = 1. 604-12.031; P = 0. 004), and lactulose use was protective (OR = 0. 294, CI = 0. 136-0.675; P = 0. 003). Conclusions: The occurrence of HE is associated with hyponatremia and PPI use in patients with ACLF. PMID:24748895

  8. Cerebral microdialysis reflects the neuroprotective effect of fractionated plasma separation and adsorption in acute liver failure better and earlier than intracranial pressure: a controlled study in pigs

    PubMed Central

    2013-01-01

    Background Cerebral edema is a well-recognized and potentially fatal complication of acute liver failure (ALF). The effectiveness of treatments that address intracranial hypertension is generally assessed by measuring intracranial pressure (ICP). The aim of this study was to determine the role of cerebral microdialysis in monitoring the efficacy of fractionated plasma separation and adsorption (FPSA) treatment for ALF. We hypothesized that in ALF cerebral microdialysis reflects the benefits of FPSA treatment on cerebral edema before ICP. Methods A surgical resection model of ALF was used in 21 pigs. We measured plasma ammonia concentration, brain concentrations of glucose, lactate, pyruvate, glutamate and glutamine, and ICP. Animals were randomized into three groups: in one group eight animals received 6 hours of FPSA treatment 2 hours after induction of ALF; in another group 10 animals received supportive treatment for ALF only; and in the final group three underwent sham surgery. Results The ICP was significantly higher in the ALF group than in the FPSA group 9 hours after surgery. The lactate/pyruvate (L/P) ratio was significantly lower in the FPSA group than the ALF group 5 hours after surgery, before any significant difference in ICP was detected. Indeed, significant changes in the L/P ratio could be observed within 1 hour of treatment. Glutamine levels were significantly lower in the FPSA group than the ALF group between 6 hours and 10 hours after surgery. Conclusions Brain lactate/pyruvate ratio and concentration of glutamine measured by cerebral microdialysis reflected the beneficial effects of FPSA treatment on cerebral metabolism more precisely and rapidly than ICP in pigs with fulminant ALF. The role of glutamine as a marker of the efficacy of FPSA treatment for ALF appears promising, but needs further evaluation. PMID:23758689

  9. Genomewide Histone H3 Lysine 9 Acetylation Profiling in CD4+ T Cells Revealed Endoplasmic Reticulum Stress Deficiency in Patients with Acute-on-chronic Liver Failure.

    PubMed

    Jin, L; Wang, K; Liu, H; Chen, T; Yang, Y; Ma, X; Wang, J; Li, Y; Du, D; Zhao, Y; He, Y

    2015-11-01

    Acute-on-chronic liver failure (ACLF) displayed 'sepsis-like' immune paralysis. Little is known about the role of CD4+ T lymphocytes, the primary regulator of innate and adopted immune system, played in ACLF. Acetylation of histone H3 lysine 9 (H3K9ac), a key epigenetic modification, tightly controls gene transcription. Whether and how does H3K9ac modification regulate CD4+ T cells in ACLF remains unclear. PBMCs were isolated from patients with ACLF, immune tolerance of chronic hepatitis B (CHB-T) and immune active of chronic hepatitis B (CHB-A). Then, CD4+ T lymphocytes were purified by magnetic microbeads, and the purity was confirmed by flow cytometry. H3K9ac variations were analysed in CD4+ T cells using chromatin immunoprecipitation microarray and then confirmed by quantitative PCR. Whole-genome H3K9 acetylation analyses were conducted by bioinformatics. A total of 70 genes were differently modified in H3K9ac between CHB-A and ACLF groups, while 44 genes were differently modified in H3K9ac between CHB-T and ACLF groups. Clustering algorithm analysis showed patients with ACLF displayed 'sepsis-like' immune paralysis. Functional analysis showed endoplasmic reticulum (ER) stress, or downstream pathway-related genes, such as BIP, ATF4, PER1, CSNK1D, IRF3, BNIP1, AKT1 and UBC, were differentially modified in ACLF. We profiled H3K9 acetyl modification in CD4+ T lymphocytes from HBV-infected patients with three different immune states, that is ACLF, immune tolerance and immune active phases. ACLF displayed 'sepsis-like' immune paralysis. ER stress in CD4+ T lymphocytes attributed to ACLF. This study provides some useful clues for revealing the mechanisms underlying ACLF. PMID:26173605

  10. Interleukin-10 Contributes to Therapeutic Effect of Mesenchymal Stem Cells for Acute Liver Failure via Signal Transducer and Activator of Transcription 3 Signaling Pathway

    PubMed Central

    Ma, Hu-Cheng; Wang, Xin; Wu, Min-Na; Zhao, Xin; Yuan, Xian-Wen; Shi, Xiao-Lei

    2016-01-01

    Background: Mesenchymal stem cells (MSCs) transplantation has been proven to have therapeutic potential for acute liver failure (ALF). However, the mechanism remains controversial. Recently, modulation of inflammation by MSCs has been regarded as a crucial mechanism. The aim of the present study was to explore the soluble cytokines secreted by MSCs and their therapeutic effects in ALF. Methods: MSCs isolated from Sprague-Dawley rats were identified by fluorescence-activated cell sorting analysis. Conditioned medium derived from MSCs (MSCs-CM) was collected and analyzed by a cytokine microarray. MSCs and MSCs-CM were transplanted into rats with D-galactosamine-induced ALF. Liver function, survival rate, histology, and inflammatory factors were determined. Exogenous recombinant rat interleukin (IL)-10, anti-rat IL-10 antibody, and AG490 (signal transducer and activator of transcription 3 [STAT3] signaling pathway inhibitor) were administered to explore the therapeutic mechanism of MSCs-CM. Statistical analysis was performed with SPSS version 19.0, and all data were analyzed by the independent-sample t-test. Results: There are statistical differences of the survival curve between ALF+MSCs group and ALF+Dulbecco's modified Eagle's medium (DMEM) group, as well as ALF+MSCs-CM group and ALF+DMEM group (all P < 0.05). Serum alanine aminotransferase (ALT) level in the ALF+MSCs and ALF+MSCs-CM groups was lower than that in the ALF+DMEM group (865.53±52.80 vs. 1709.75±372.12 U/L and 964.72±414.59 vs. 1709.75±372.12 U/L, respectively, all P < 0.05); meanwhile, serum aspartate aminotransferase (AST) level in the ALF+MSCs and ALF+MSCs-CM groups was lower than that in the ALF+DMEM group (2440.83±511.94 vs. 4234.35±807.30 U/L and 2739.83±587.33 vs. 4234.35±807.30 U/L, respectively, all P < 0.05). Furthermore, MSCs or MSCs-CM treatment significantly reduced serum interferon-γ (IFN-γ), IL-1β, IL-6 levels and increased serum IL-10 level compared with DMEM (all P < 0

  11. Liver transplantatation- an overview.

    PubMed

    Rai, Rakesh

    2013-06-01

    Liver transplantation is a therapeutic option of choice for acute and chronic end-stage liver disease. Indications, contraindications, and surgical procedures for the liver transplantation have become well established. In most part of the world, the main source of liver for transplantation remains the donation after brain death (DBD), but in view of increasing death on the waiting list due to shortage of brain dead organs other options such as split liver transplantation, living donor liver transplantation (LDLT), and donation after cardiac death (DCD) have been used. In the pretransplantation era, liver failure was nearly universally fatal, with mortality from fulminant hepatic failure of 80-90 %, and 1-year mortality in decompensated cirrhosis of more than 50 %. In contrast, liver transplantation patient survival is presently more than 85 % at 1 year and more than 70 % at 5 years, emphasizing the clinical benefit of liver transplantation for either acute or chronic liver failure. PMID:24426424

  12. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  13. Importance of Kupffer Cells in the Development of Acute Liver Injuries in Mice

    PubMed Central

    Tsutsui, Hiroko; Nishiguchi, Shuhei

    2014-01-01

    Kupffer cells reside within the liver sinusoid and serve as gatekeepers. They produce pro- and anti-inflammatory cytokines and other biologically important molecules upon the engagement of pattern recognition receptors such as Toll-like receptors. Kupffer cell-ablated mice established by in vivo treatment with clodronate liposomes have revealed many important features of Kupffer cells. In this paper, we review the importance of Kupffer cells in murine acute liver injuries and focus on the following two models: lipopolysaccharide (LPS)-induced liver injury, which is induced by priming with Propionibacterium acnes and subsequent challenge with LPS, and hypercoagulability-mediated acute liver failure such as that in concanavalin A (Con A)-induced hepatitis. Kupffer cells are required for LPS sensitization induced by P. acnes and are a major cellular source of interleukin-18, which induces acute liver injury following LPS challenge. Kupffer cells contribute to Con A-induced acute liver failure by initiating pathogenic, intrasinusoidal thrombosis in collaboration with sinusoidal endothelial cells. The mechanisms underlying these models may shed light on human liver injuries induced by various etiologies such as viral infection and/or abnormal metabolism. PMID:24802875

  14. [Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): liver failure and transplantation].

    PubMed

    Montejo González, J C; Mesejo, A; Bonet Saris, A

    2011-11-01

    Patients with liver failure have a high prevalence of malnutrition, which is related to metabolic abnormalities due to the liver disease, reduced nutrient intake and alterations in digestive function, among other factors. In general, in patients with liver failure, metabolic and nutritional support should aim to provide adequate nutrient intake and, at the same time, to contribute to patients' recovery through control or reversal of metabolic alterations. In critically-ill patients with liver failure, current knowledge indicates that the organ failure is not the main factor to be considered when choosing the nutritional regimen. As in other critically-ill patients, the enteral route should be used whenever possible. The composition of the nutritional formula should be adapted to the patient's metabolic stress. Despite the physiopathological basis classically described by some authors who consider amino acid imbalance to be a triggering factor and key element in maintaining encephalopathy, there are insufficient data to recommend "specific" solutions (branched-chain amino acid-enriched with low aromatic amino acids) as part of nutritional support in patients with acute liver failure. In patients undergoing liver transplantation, nutrient intake should be started early in the postoperative period through transpyloric access. Prevention of the hepatic alterations associated with nutritional support should also be considered in distinct clinical scenarios. PMID:22309749

  15. [Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): liver failure and transplantation].

    PubMed

    Montejo González, J C; Mesejo, A; Bonet Saris, A

    2011-11-01

    Patients with liver failure have a high prevalence of malnutrition, which is related to metabolic abnormalities due to the liver disease, reduced nutrient intake and alterations in digestive function, among other factors. In general, in patients with liver failure, metabolic and nutritional support should aim to provide adequate nutrient intake and, at the same time, to contribute to patients' recovery through control or reversal of metabolic alterations. In critically-ill patients with liver failure, current knowledge indicates that the organ failure is not the main factor to be considered when choosing the nutritional regimen. As in other critically-ill patients, the enteral route should be used whenever possible. The composition of the nutritional formula should be adapted to the patient's metabolic stress. Despite the physiopathological basis classically described by some authors who consider amino acid imbalance to be a triggering factor and key element in maintaining encephalopathy, there are insufficient data to recommend "specific" solutions (branched-chain amino acid-enriched with low aromatic amino acids) as part of nutritional support in patients with acute liver failure. In patients undergoing liver transplantation, nutrient intake should be started early in the postoperative period through transpyloric access. Prevention of the hepatic alterations associated with nutritional support should also be considered in distinct clinical scenarios.

  16. Uptake of oleate from albumin solutions by rat liver. Failure to detect catalysis of the dissociation of oleate from albumin by an albumin receptor.

    PubMed Central

    Weisiger, R A; Ma, W L

    1987-01-01

    The hepatic removal of albumin-bound substances from plasma requires that they dissociate from albumin. Using indirect methods, we and others have proposed that dissociation may be catalyzed by interaction of albumin with the liver cell surface. This study looked for direct evidence of catalysis by comparing the rate of dissociation of oleate from albumin in vitro with the rate observed within the sinusoids of perfused rat liver. No evidence for catalysis was found. The rate of hepatic oleate removal from dilute albumin solutions did not exceed but instead closely paralleled the rate predicted from the in vitro dissociation rate constant (0.14s-1). These results suggest that under some conditions the liver can remove unbound material from the sinusoids faster than it can be replenished by dissociation from albumin, resulting in dissociation-limited removal. However, dissociation of oleate does not appear to be catalyzed by the liver. PMID:3031131

  17. Drug-induced fulminant hepatic failure in pregnancy.

    PubMed

    Firoz, Tabassum; Webber, Douglas; Rowe, Hilary

    2015-12-01

    Liver disease in pregnancy can be classified as predating, co-incidental or unique to pregnancy. Medications are often overlooked as a significant cause of liver disease. We present the case of a 39-year-old patient who presented at 20 weeks with jaundice, elevated liver enzymes, and abnormal liver function progressing eventually to fulminant hepatic failure. The patient was on methyldopa and labetalol from 12 weeks' gestational age. Liver biopsy was consistent with drug-induced liver injury. Both methyldopa and labetalol have been associated with hepatotoxicity including liver failure. This case highlights the importance of including medications as a cause of liver failure in pregnant patients.

  18. 3,3’-Diindolylmethane attenuates LPS-mediated acute liver failure by regulating miRNAs to target IRAK4 and suppress Toll-like receptor signalling

    PubMed Central

    Tomar, S; Nagarkatti, M; Nagarkatti, P S

    2015-01-01

    Background and Purpose Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. 3,3′-Diindolylmethane (DIM) is a natural plant-derived compound with anti-cancer activities. Recently, DIM has also been shown to have anti-inflammatory properties. Here, we tested the hypothesis that DIM would suppress endotoxin-induced ALF. Experimental Approach We investigated the therapeutic potential of DIM in a mouse model of D-galactosamine/Lipopolysaccharide (GalN/LPS)-induced ALF. The efficacy of DIM treatment was assessed by survival, liver histopathology, serum levels of alanine transaminase, pro-inflammatory cytokines and number of activated liver macrophages. Effects of DIM on the expression of two miRNAs, 106a and 20b, and their predicted target gene were measured by qRT-PCR and Western blotting. Effects of DIM on the release of TNF-α from RAW264.7 macrophages transfected with mimics of these miRNAs and activated by LPS was assessed by elisa. Key Results DIM treatment protected mice from ALF symptoms and reduced the number of activated liver macrophages. DIM increased expression of miR-106a and miR-20b in liver mononuclear cells and decreased expression of their predicted target gene IL-1 receptor-associated kinase 4 (IRAK4), involved in signalling from Toll-like receptor 4 (TLR4). In vitro transfection of RAW264.7 cells using miRNA mimics of miR-106a and 20b decreased expression of IRAK4 and of TNF-α secretion, following LPS stimulation. Conclusions and Implications DIM attenuated GalN/LPS-induced ALF by regulating the expression of unique miRNAs that target key molecules in the TLR4 inflammatory pathway. DIM may represent a potential novel hepatoprotective agent. PMID:25521277

  19. Use of Pediatric Health Information System database to study the trends in the incidence, management, etiology, and outcomes due to pediatric acute liver failure in the United States from 2008 to 2013.

    PubMed

    Kulkarni, Sakil; Perez, Carla; Pichardo, Caren; Castillo, Lina; Gagnon, Michael; Beck-Sague, Consuelo; Gereige, Rani; Hernandez, Erick

    2015-12-01

    Data were collected of children admitted with ALF to 16 US pediatric liver transplant centers from 2008 to 2013 using the PHIS for a retrospective analysis of PALF trends. Patient data linked to the principal diagnosis code for acute necrosis of the liver (570.00) were analyzed for the following: demographics, regional differences, changes over time, pharmaceutical trends, procedural trends, associated diagnoses, and patient outcomes. In 52.5% of 583 patients who met the selection criteria for PALF, the etiology remained undetermined. Acetaminophen toxicity (18.7%) was the most common identifiable etiology, and hepatic encephalopathy (38.6%) was the most common complication. Mortality was lower than previously reported; 95.4% survived and 73.2% survived without a liver transplant. Acute respiratory failure (OR = 3.4, p = 0.035), acute kidney injury (OR = 3.6, p = 0.003), and cerebral edema (OR = 3.6, p = 0.02) were independently associated with increased risk of mortality. The use of N-acetylcysteine in non-acetaminophen-related ALF, the use of intracranial pressure monitoring, and the proportion of sepsis decreased significantly during the study period. The PHIS database can be a useful tool to study the future trends of PALF patients. PMID:26388211

  20. Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

    PubMed Central

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; de Almeida, Adilson José; Pelajo-Machado, Marcelo; de Castro, Tatiana Xavier; do Nascimento, Jussara Pereira; Brown, Kevin E; Pinto, Marcelo Alves

    2016-01-01

    This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group. PMID:27074255

  1. Fulminant hepatic failure.

    PubMed

    Sass, David A; Shakil, A Obaid

    2003-12-01

    FHF is a devastating illness of varied causes, carrying considerable mortality and affecting patients with previously healthy livers. The clinical presentation varies widely but encephalopathy is the defining criterion. Management requires a multidisciplinary approach, including rapid triage, monitoring, and referral to a transplantation center for further evaluation. Early prognostication and timely availability of donor livers are essential for a successful outcome. A donor shortage, however, continues to pose problems for both hepatologists and surgeons. Effective liver support devices may greatly prolong the window of opportunity to provide a donor liver, or alternatively to allow the native liver to regenerate. Despite decades of great progress in the field of liver support systems, the ideal system is still a long-cherished goal in hepatology. Hybrid systems have garnered most of the recent attention, but the quest for improved synthetic function has not yet been realized. It is hoped that rapid conceptual and technologic developments with respect to hybrid systems, hepatocyte transplantation, and xenografting will yield a safe and accessible tool for managing these critically ill patients. Controlled, multicenter trials in well-defined patient groups and with standard outcome measures are essential to evaluate the clinical value of these devices. A better understanding of mechanisms responsible for liver cell death and multiorgan failure, and the development of strategies to enhance liver regeneration, may allow a more targeted approach to therapy.

  2. Nutrition and liver diseases.

    PubMed

    Teran, J C

    1999-08-01

    Malnutrition and micronutrient deficiencies are common in patients with liver diseases. The pathogenesis of protein-energy malnutrition in cirrhosis involves many factors, including poor oral intake, malabsorption, and metabolic abnormalities similar to stress. Encephalopathy may complicate cirrhosis but is usually not caused by diet. Protein restriction is only necessary in rare patients with refractory encephalopathy. The use of branched-chain amino-acid solutions is not supported by the literature. Chronic liver diseases without cirrhosis are not usually associated with protein-energy malnutrition, but vitamin and mineral deficiencies are common, especially with significant cholestasis. Fatty liver may result from excessive triglyceride uptake and production by the liver or by a secretory defect. Therapy for fatty liver depends on its cause. Chronic total parenteral nutrition may induce fatty liver and inflammation especially in patients with short-bowel syndrome. Deficiency of choline in parenteral nutrition has been proposed as the mechanism for liver disease. Acute liver diseases such as fulminant hepatic failure or alcoholic hepatitis are considered hypercatabolic diseases and thus require prompt nutritional intervention with a high-calorie enteral or parenteral formula. In fulminant hepatic failure, low-protein, fluid-restricted formulas are recommended. PMID:10980970

  3. Usefulness of Cardiac MetaIodobenzylguanidine Imaging to Improve Prognostic Power of the Model for End-Stage Liver Disease Scoring System in Patients With Mild-to-Moderate Chronic Heart Failure.

    PubMed

    Hakui, Hideyuki; Yamada, Takahisa; Tamaki, Shunsuke; Morita, Takashi; Furukawa, Yoshio; Iwasaki, Yusuke; Kawasaki, Masato; Kikuchi, Atsushi; Kondo, Takumi; Ishimi, Masashi; Sato, Yoshihiro; Seo, Masahiro; Ozaki, Tatsuhisa; Ikeda, Iyo; Fukuhara, Eiji; Sakata, Yasushi; Fukunami, Masatake

    2016-06-15

    Liver dysfunction has a prognostic impact on the outcomes of patients with advanced heart failure (HF). The model for end-stage liver disease (MELD) score is a robust system for rating liver dysfunction, and a high score has been shown to be associated with a poor prognosis in ambulatory patients with HF. In addition, cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with chronic HF (CHF). However, the long-term predictive value of combining the MELD score and cardiac MIBG imaging in patients with CHF has not been elucidated. To prospectively investigate whether cardiac MIBG imaging provides additional prognostic value to the MELD score in patients with mild-to-moderate CHF, we studied 109 CHF outpatients (New York Heart Association: 2.0 ± 0.6) with left ventricular ejection fraction <40%. At enrollment, an MELD score was obtained, and the heart-to-mediastinal ratio on delayed imaging and MIBG washout rate (WR) were measured using cardiac MIBG scintigraphy. During a follow-up period of 7.5 ± 4.2 years, 36 of 109 patients experienced cardiac death (CD). On multivariate Cox analysis, MELD score and WR were significantly independently associated with CD, although heart-to-mediastinal ratio showed an association with CD only on univariate Cox analysis. Patients with abnormal WR (>27%) had a significantly greater risk of CD than those with normal WR in both those with high MELD scores (≥10; hazard ratio 4.0 [1.2 to 13.6]) and with low MELD scores (<10; hazard ratio 6.4 [1.7 to 23.2]). In conclusion, cardiac MIBG imaging would provide additional prognostic information to the MELD score in patients with mild-to-moderate CHF. PMID:27237625

  4. Serum Interleukin (IL)-9 and IL-10, but not T-Helper 9 (Th9) Cells, are Associated With Survival of Patients With Acute-on-Chronic Hepatitis B Liver Failure

    PubMed Central

    Yu, Xueping; Zheng, Yijuan; Deng, Yong; Li, Julan; Guo, Ruyi; Su, Milong; Ming, Desong; Lin, Zhenzhong; Zhang, Jiming; Su, Zhijun

    2016-01-01

    Abstract CD4+ T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4+ Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4+ cells in peripheral blood. We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected. The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity. Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF. PMID:27100428

  5. Serum Interleukin (IL)-9 and IL-10, but not T-Helper 9 (Th9) Cells, are Associated With Survival of Patients With Acute-on-Chronic Hepatitis B Liver Failure.

    PubMed

    Yu, Xueping; Zheng, Yijuan; Deng, Yong; Li, Julan; Guo, Ruyi; Su, Milong; Ming, Desong; Lin, Zhenzhong; Zhang, Jiming; Su, Zhijun

    2016-04-01

    CD4 T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4 Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4 cells in peripheral blood. We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected. The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity.Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF.

  6. Liver Facts

    MedlinePlus

    ... Home / Before The Transplant / Organ Facts / Liver Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Facts How the Liver Works The liver is one ...

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

    PubMed Central

    Pan, Xingfei; Lu, Ying; Liao, Sihong; Wang, Xicheng; Wang, Guoying; Lin, Dongjun

    2015-01-01

    Background and Aims 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. Methods 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. Results 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. Conclusion Our results suggest that NKP30-B7-H6 interaction can aggravate hepatocyte damage, probably through up

  8. Kidney Failure

    MedlinePlus

    ... if You Have Kidney Disease Kidney Failure Expand Dialysis Kidney Transplant Preparing for Kidney Failure Treatment Choosing Not to Treat with Dialysis or Transplant Paying for Kidney Failure Treatment Contact ...

  9. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    PubMed

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.

  10. Apoptotic Response through a High Mobility Box 1 Protein-Dependent Mechanism in LPS/GalN-Induced Mouse Liver Failure and Glycyrrhizin-Mediated Inhibition

    PubMed Central

    Kuroda, Noriyuki; Inoue, Kouji; Ikeda, Tadayuki; Hara, Yaiko; Wake, Kenjiro; Sato, Tetsuji

    2014-01-01

    HMGB1 is a nuclear component involved in nucleosome stabilization and transcription regulation, but extracellularly it is able to serve as a potential late mediator of lethality. In the present study, we explored inflammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by glycyrrhizin (GL) in LPS/GalN-triggered mouse liver injury. At 1 to 10 h after LPS/GalN-treatment, mice were anesthetized to collect blood from heart puncture, and serum transaminase and HMGB1 were evaluated. Administration of LPS/GalN precipitated tissue injury associated with time-dependent alteration in HMGB1 serum levels. At 8 h nuclear immunoreactive products were remarkably reduced and extracellular HMGB1 expression was found exclusively in the pericentral foci. The treatment with GL significantly down-regulated the serum levels of ALT, AST, and HMGB1 in addition to the strong inhibition of tissue injury and extracellular immunoreactivity to HMGB1 and to acetylated-lysine. Furthermore, GL brought about a significant decrease in the number of apoptotic hepatocytes labeled with TUNEL-method. On the basis of these results, three apoptosis-associated genes were identified with microarray analysis and real-time PCR. The ChIP-assay revealed the binding of HMGB1 protein to Gsto1 promoter sequence in LPS/GalN-treated mice and the remarkable decrease in combined HMGB1 protein by GL. The current findings claim that a single injection of LPS/GalN might stimulate apoptosis of hepatocytes through the binding of HMGB1 protein to Gsto1 promoter region and that GL-treatment might prevent the apoptosis and inflammatory infiltrates caused with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence. PMID:24690901

  11. Liver Wellness

    MedlinePlus

    ... to liver wellness. • There are more than 100 liver diseases. • Liver disease is one of the top 10 causes of ... out of every 10 Americans is affected by liver disease. • Some liver diseases such as hepatitis A, hepatitis ...

  12. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction.

  13. Orlistat-induced fulminant hepatic failure.

    PubMed

    Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

    2014-12-01

    Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. PMID:25826164

  14. Hypoxia and fatty liver.

    PubMed

    Suzuki, Tomohiro; Shinjo, Satoko; Arai, Takatomo; Kanai, Mai; Goda, Nobuhito

    2014-11-01

    The liver is a central organ that metabolizes excessive nutrients for storage in the form of glycogen and lipids and supplies energy-producing substrates to the peripheral tissues to maintain their function, even under starved conditions. These processes require a considerable amount of oxygen, which causes a steep oxygen gradient throughout the hepatic lobules. Alcohol consumption and/or excessive food intake can alter the hepatic metabolic balance drastically, which can precipitate fatty liver disease, a major cause of chronic liver diseases worldwide, ranging from simple steatosis, through steatohepatitis and hepatic fibrosis, to liver cirrhosis. Altered hepatic metabolism and tissue remodeling in fatty liver disease further disrupt hepatic oxygen homeostasis, resulting in severe liver hypoxia. As master regulators of adaptive responses to hypoxic stress, hypoxia-inducible factors (HIFs) modulate various cellular and organ functions, including erythropoiesis, angiogenesis, metabolic demand, and cell survival, by activating their target genes during fetal development and also in many disease conditions such as cancer, heart failure, and diabetes. In the past decade, it has become clear that HIFs serve as key factors in the regulation of lipid metabolism and fatty liver formation. This review discusses the molecular mechanisms by which hypoxia and HIFs regulate lipid metabolism in the development and progression of fatty liver disease. PMID:25386057

  15. The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology.

    PubMed

    Yamada, Yohei; Hoshino, Ken; Irie, Rie; Tomita, Hirofumi; Kato, Mototoshi; Shimojima, Naoki; Fujino, Akihiro; Hibi, Taizo; Shinoda, Masahiro; Obara, Hideaki; Itano, Osamu; Kawachi, Shigeyuki; Tanabe, Minoru; Sakamoto, Michiie; Kitagawa, Yuko; Kuroda, Tatsuo

    2016-08-01

    The outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid-resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995-2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re-LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p < 0.00001). From 2008, three patients underwent LTx for cryptogenic FHF with PVI and conventional IS. PVI was well tolerated, and no relevant severe complications were observed. More strikingly, the patients who received PVI overcame biopsy-proven immunological events and are all currently doing well with excellent graft function after more than five yr. We conclude that PVI is technically safe and effective for preventing severe rejection in pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications.

  16. Development of a hybrid bioartificial liver.

    PubMed Central

    Rozga, J; Holzman, M D; Ro, M S; Griffin, D W; Neuzil, D F; Giorgio, T; Moscioni, A D; Demetriou, A A

    1993-01-01

    OBJECTIVE: The authors developed an extracorporeal liver support system and tested its efficacy in experimental animals with liver failure. The first clinical use of this system to treat a patient with liver failure is reported. SUMMARY BACKGROUND DATA: Multiple attempts have been made, ranging from plasma exchange to use of charcoal columns, to develop liver support systems for treating patients with acute severe liver failure. None of these systems has achieved wide clinical use. There is a need for providing liver support as a "bridge" to transplantation and for treating patients with potentially reversible liver dysfunction. METHODS: A hybrid liver support system has been developed consisting of plasma perfusion through a charcoal column and a porous hollow fiber module inoculated with 5 x 10(9) matrix-attached hepatocytes. The system was tested in dogs with ischemic liver failure (n = 7) who underwent plasmapheresis; a control group (n = 6) underwent charcoal perfusion alone. A patient with liver failure was treated with this hybrid system. RESULTS: After 6 hours of hybrid liver support treatment, animals had significantly decreased serum ammonia and lactate levels, increased glucose level, normal prothrombin time, and increased systolic blood pressure compared with controls treated with charcoal perfusion alone. Use of the system to treat a patient was well tolerated with evidence of clinical improvement. CONCLUSIONS: Plasma perfusion through a system consisting of a charcoal column and matrix-attached porcine hepatocytes had significant beneficial effects in animals with liver failure and was well tolerated by a patient with liver failure. Images Figure 2. PMID:8489313

  17. Liver biopsy

    MedlinePlus

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  18. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  19. Liver Transplant

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  20. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  1. Respiratory Failure

    MedlinePlus

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can' ...

  2. Cell and tissue engineering for liver disease.

    PubMed

    Bhatia, Sangeeta N; Underhill, Gregory H; Zaret, Kenneth S; Fox, Ira J

    2014-07-16

    Despite the tremendous hurdles presented by the complexity of the liver's structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near- and long-term prospects for such cell-based therapies and the unique challenges for clinical translation.

  3. Know HBV: What Every Asian and Pacific Islander Should Know About Hepatitis B and Liver Cancer

    MedlinePlus

    ... 2006 Asian Liver Center What every Asian and Pacific Islander should know about hepatitis B and liver ... or liver failure. » 1 in 10 Asian and Pacific Islanders is living with chronic (life-long) hepatitis ...

  4. Liver transplantation for Wilson's disease.

    PubMed

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  5. Liver xenotransplantation.

    PubMed

    Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

    1993-10-01

    During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure.

  6. Liver xenotransplantation.

    PubMed

    Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

    1993-10-01

    During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure. PMID:25951555

  7. Split liver transplantation.

    PubMed

    Yersiz, H; Cameron, A M; Carmody, I; Zimmerman, M A; Kelly, B S; Ghobrial, R M; Farmer, D G; Busuttil, R W

    2006-03-01

    Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

  8. American Liver Foundation

    MedlinePlus

    ... LALD) Intrahepatic Cholestasis of Pregnancy (ICP) Liver Biopsy Liver Cancer Liver Cysts Liver Function Tests Liver Transplant Newborn ... community. It's Liver Awareness Month- and it's also Liver Cancer Awareness Month, so we've teamed with Bayer ...

  9. [Liver damage caused by drugs].

    PubMed

    Strohmeyer, G; Weik, C

    1999-05-01

    The liver has a central role in the metabolism of many drugs, since this organ is the main site of biotransformation of endo- and xenobiotics. Water-soluble drugs have a small volume of distribution and can be eliminated unchanged in the urine. By contrast, lipid-soluble drugs have a larger volume of distribution and require conversion to water-soluble metabolites for their elimination in urine or bile. The liver with its specific receptors, transporters and enzymes is responsible for the uptake, transformation and excretion of the lipophilic drugs. While most of the drugs are transformed into stable metabolites, other drugs form reactive, potentially toxic, metabolites producing liver cell damage. Liver injury caused by drugs may mimic almost any kind of liver disease. Clinical findings are gastrointestinal symptoms with nausea, vomiting and abdominal pain, cholestatic liver injury with jaundice and pruritus of severe inflammatory and cirrhotic liver damage with signs of liver failure, encephalopathy and cerebral edema. The morphological changes vary from hepatitis, cholestasis, fatty liver, granulomatous hepatitis, peri-/portal inflammation, to fibrosis with cirrhotic alterations and vascular lesions and tumors. The most commonly used drugs causing severe liver injury are discussed in detail. These are anabolics, oral contraceptives, antituberculous and antifungal agents, nonsteroidal anti-inflammatory drugs, ring substituted amphetamins ("designer drugs"), antiarrhythmics and antibiotics.

  10. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure.

  11. Liver support systems.

    PubMed

    Santoro, Antonio; Mancini, Elena; Ferramosca, Emiliana; Faenza, Stefano

    2007-01-01

    Liver insufficiency is a dramatic syndrome with multiple organ involvement. A multiplicity of toxic substances (hydrophilic like ammonia and lipophilic like bilirubin or bile acids or mercaptans) are released into the systemic circulation, thus altering many enzymatic cellular processes. Patients frequently die while on the transplantation waiting list because of organ scarcity. Systems supporting liver function may be useful to avoid further complications due to the typical toxic state, 'bridging' the patients to the transplantation, or, in the event of an acute decompensation of a chronic liver disease, sustain liver function long enough to permit the organ's regeneration and functional recovery. An ideal liver support system should substitute the main functions of the liver (detoxification, synthesis and regulation). Extracorporeal systems now available may be totally artificial or bioartificial. While the first are only able to perform detoxification, the second may add the functions of synthesis (plasma proteins, coagulation factors) and regulation (neurotransmitters). Bioartificial liver working with isolated hepatocytes and a synthetic membrane in an extracorporeal system are however still far from being ready for clinical use. At present, liver insufficiency may be treated with an extracorporeal support technology aimed either at detoxification alone or at a real purification. Charcoal hemoperfusion or exchange/absorption resins may be used for blood detoxification. Blood or plasma exchange, from a theoretical point of view, could be suitable for a polyvalent intoxication, such as liver failure; however, the multicompartmental distribution of some solutes largely endangers the efficacy of these procedures. Selective plasmapheresis techniques are now available for some solutes (e.g. styrene for bilirubin) and may progressively reduce the plasma levels and presumably the deposits of the solute. Novel treatments introduced to improve detoxification, mainly of

  12. Liver Biopsy

    MedlinePlus

    ... PDF, 341 KB)​​​​. Alternate Language URL Español Liver Biopsy Page Content On this page: What is a ... to Remember Clinical Trials What is a liver biopsy? A liver biopsy is a procedure that involves ...

  13. Role of liver progenitors in acute liver injury

    PubMed Central

    Best, Jan; Dollé, Laurent; Manka, Paul; Coombes, Jason; van Grunsven, Leo A.; Syn, Wing-Kin

    2013-01-01

    Acute liver failure (ALF) results from the acute and rapid loss of hepatocyte function and frequently exhibits a fulminant course, characterized by high mortality in the absence of immediate state-of-the-art intensive care and/or emergency liver transplantation (ELT). The role of hepatocyte-mediated liver regeneration during acute and chronic liver injury has been extensively investigated, and recent studies suggest that hepatocytes are not exclusively responsible for the regeneration of the injured liver during fulminant liver injury. Liver progenitor cells (LPC) (or resident liver stem cells) are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. This review aims to provide an overview of the role of the LPC population during ALF, and the role of putative cytokines, growth factors, mitogens, and hormones in the LPC response. We will highlight the potential interaction among cellular compartments during ALF, and discuss the possible prognostic value of the LPC response on ALF outcomes. PMID:24133449

  14. Acute liver failure impairs function and expression of breast cancer-resistant protein (BCRP) at rat blood-brain barrier partly via ammonia-ROS-ERK1/2 activation.

    PubMed

    Li, Ying; Zhang, Ji; Xu, Ping; Sun, Binbin; Zhong, Zeyu; Liu, Can; Ling, Zhaoli; Chen, Yang; Shu, Nan; Zhao, Kaijing; Liu, Li; Liu, Xiaodong

    2016-07-01

    We once reported that P-glycoprotein (P-GP) and multidrug resistance-associated protein 2 (MRP2) were oppositely regulated at the blood-brain barrier (BBB) of thioacetamide-induced acute liver failure (ALF) rats. This study aimed to investigate whether ALF affected function and expression of breast cancer-resistant protein (BCRP) at the BBB of rats and the role of ammonia in the regulation. ALF rats were developed by intraperitoneal (i.p.) injection of thioacetamide (300 mg/kg) for 2 days. Hyperammonemic rats were developed by NH4 Ac (i.p. 4.5 mmol/kg). BCRP function and expression were measured by brain distribution of specific substrates (prazosin and methotrexate) and western blot, respectively. MDCK-BCRP cells and primarily cultured rat brain microvessel endothelial cells (rBMECs) were employed to investigate possible mechanisms through which ammonia regulated BCRP function and expression. The results showed that both ALF and hyperammonemia significantly weakened function and expression of BCRP in the brain of rats. The function and expression of BCRP in MDCK-BCRP cells and rBMECs were strikingly decreased after exposure to NH4 Cl and H2 O2 , accompanied by remarkable increases in the levels of phosphorylated ERK1/2 and reactive oxygen species (ROS). The altered BCRP expression and function by ammonia and H2 O2 were restored by ROS scavenger N-acetylcysteine and ERK1/2 inhibitor U0126. Markedly increased levels of ERK1/2 phosphorylation and ROS were found in the brains of ALF rats and hyperammonemic rats. All above results indicated ALF down-regulated expression and function of BCRP at BBB of rats partly via hyperammonemia. Activation of ROS-mediated ERK1/2 phosphorylation may be one of the reasons that ammonia impaired BCRP expression and function at the BBB. The present study showed that the expression and function of breast cancer resistant protein (BCRP) at blood-brain barrier (BBB) of thioacetamide-induced ALF rats were down-regulated which partly

  15. Acute liver failure impairs function and expression of breast cancer-resistant protein (BCRP) at rat blood-brain barrier partly via ammonia-ROS-ERK1/2 activation.

    PubMed

    Li, Ying; Zhang, Ji; Xu, Ping; Sun, Binbin; Zhong, Zeyu; Liu, Can; Ling, Zhaoli; Chen, Yang; Shu, Nan; Zhao, Kaijing; Liu, Li; Liu, Xiaodong

    2016-07-01

    We once reported that P-glycoprotein (P-GP) and multidrug resistance-associated protein 2 (MRP2) were oppositely regulated at the blood-brain barrier (BBB) of thioacetamide-induced acute liver failure (ALF) rats. This study aimed to investigate whether ALF affected function and expression of breast cancer-resistant protein (BCRP) at the BBB of rats and the role of ammonia in the regulation. ALF rats were developed by intraperitoneal (i.p.) injection of thioacetamide (300 mg/kg) for 2 days. Hyperammonemic rats were developed by NH4 Ac (i.p. 4.5 mmol/kg). BCRP function and expression were measured by brain distribution of specific substrates (prazosin and methotrexate) and western blot, respectively. MDCK-BCRP cells and primarily cultured rat brain microvessel endothelial cells (rBMECs) were employed to investigate possible mechanisms through which ammonia regulated BCRP function and expression. The results showed that both ALF and hyperammonemia significantly weakened function and expression of BCRP in the brain of rats. The function and expression of BCRP in MDCK-BCRP cells and rBMECs were strikingly decreased after exposure to NH4 Cl and H2 O2 , accompanied by remarkable increases in the levels of phosphorylated ERK1/2 and reactive oxygen species (ROS). The altered BCRP expression and function by ammonia and H2 O2 were restored by ROS scavenger N-acetylcysteine and ERK1/2 inhibitor U0126. Markedly increased levels of ERK1/2 phosphorylation and ROS were found in the brains of ALF rats and hyperammonemic rats. All above results indicated ALF down-regulated expression and function of BCRP at BBB of rats partly via hyperammonemia. Activation of ROS-mediated ERK1/2 phosphorylation may be one of the reasons that ammonia impaired BCRP expression and function at the BBB. The present study showed that the expression and function of breast cancer resistant protein (BCRP) at blood-brain barrier (BBB) of thioacetamide-induced ALF rats were down-regulated which partly

  16. Liver transplantation☆

    PubMed Central

    Rossi, M.; Mennini, G.; Lai, Q.; Ginanni Corradini, S.; Drudi, F.M.; Pugliese, F.; Berloco, P.B.

    2007-01-01

    Orthotopic liver transplantation (OLT) involves the substitution of a diseased native liver with a normal liver (or part of one) taken from a deceased or living donor. Considered an experimental procedure through the 1980s, OLT is now regarded as the treatment of choice for a number of otherwise irreversible forms of acute and chronic liver disease. The first human liver transplantation was performed in the United States in 1963 by Prof. T.E. Starzl of the University of Colorado. The first OLT to be performed in Italy was done in 1982 by Prof. R. Cortesini. The procedure was successfully performed at the Policlinico Umberto I of the University of Rome (La Sapienza). The paper reports the indications for liver transplantation, donor selection and organ allocation in our experience, surgical technique, immunosuppression, complications and results of liver transplantation in our center. PMID:23396075

  17. MARS therapy, the bridging to liver retransplantation – Three cases from the Hungarian liver transplant program

    PubMed Central

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

    2013-01-01

    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. PMID:24265893

  18. Artificial and Bioartificial Liver Support

    PubMed Central

    2007-01-01

    The fact that liver failure constitutes a life-threatening condition and can, in most cases, only be overcome by orthotopic liver transplantation, lead to the development of various artificial and bioartificial liver support devices. While artificial systems are based on the principles of adsorption and filtration, the more complex concept of bioartificial devices includes the provision of liver cells. Instead of solely focussing on detoxification, these concepts also support the failing organ concerning synthetic and regulative functions. The systems were evaluated in a variety of clinical studies, demonstrating their safety and investigating the impact on the patient's clinical condition. This review gives an overview over the most common artificial and bioartificial liver support devices and summarizes the results of the clinical studies. PMID:19279696

  19. Testicular failure

    MedlinePlus

    ... LH . Your doctor may also order a semen analysis to examine the number of healthy sperm you are producing. Sometimes, an ultrasound of the testes will be ordered. Testicular failure and low testosterone level may be hard to ...

  20. [Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

    PubMed

    Restellini, Sophie; Spahr, Laurent

    2012-06-27

    Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

  1. Liver transplantation for chronic liver disease: advances and controversies in an era of organ shortages

    PubMed Central

    Prince, M; Hudson, M

    2002-01-01

    Since liver transplantation was first performed in 1968 by Starzl et al, advances in case selection, liver surgery, anaesthetics, and immunotherapy have significantly increased the indications for and success of this operation. Liver transplantation is now a standard therapy for many end stage liver disorders as well as acute liver failure. However, while demand for cadaveric organ grafts has increased, in recent years the supply of organs has fallen. This review addresses current controversies resulting from this mismatch. In particular, methods for increasing graft availability and difficulties arising from transplantation in the context of alcohol related cirrhosis, primary liver tumours, and hepatitis C are reviewed. Together these three indications accounted for 42% of liver transplants performed for chronic liver disease in the UK in 2000. Ethical frameworks for making decisions on patients' suitability for liver transplantation have been developed in both the USA and the UK and these are also reviewed. PMID:11884694

  2. Cell and Tissue Engineering for Liver Disease

    PubMed Central

    Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

    2015-01-01

    Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

  3. Clinical implications of advances in liver regeneration.

    PubMed

    Kwon, Yong Jin; Lee, Kyeong Geun; Choi, Dongho

    2015-03-01

    Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

  4. Fulminant hepatic failure in autoimmune polyendocrine syndrome type-1.

    PubMed

    Sinha, R; Chapman, A R; Reid, G T; Hayes, P C

    2015-01-01

    Fulminant hepatic failure is liver disease that causes encephalopathy within 8 weeks of onset of symptoms or within 2 weeks of onset of jaundice in a patient without prior evidence of liver disease. Autoimmune polyendocrine syndrome type-1 is an autoimmune autosomal-recessive condition causing parathyroid and adrenal insufficiency, alopecia, chronic mucocutaneous candidiasis, ectodermal dystrophy and, rarely, hepatitis. Although the liver can be affected as a consequence of the autoimmune process, the spectrum of disease activity is varied. Autoimmune hepatitis develops in 10-20% of patients and successful liver transplantation has been reported in pediatric patients who failed immunosuppressive treatment. We report fulminant hepatic failure in an adult patient with autoimmune polyendocrine syndrome type-1 who responded to medical treatment and did not require liver transplantation. We highlight the diagnostic scoring system for autoimmune hepatitis and the referral criteria for liver transplantation in fulminant hepatic failure.

  5. New insights into the coagulopathy of liver disease and liver transplantation

    PubMed Central

    Senzolo, M; Burra, P; Cholongitas, E; Burroughs, AK

    2006-01-01

    The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis. Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore, these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery. PMID:17203512

  6. Heart failure.

    PubMed

    2014-12-15

    Essential facts Heart failure affects about 900,000 people in the UK. The condition can affect people of all ages, but it is more common in older people, with more than half of all patients over the age of 75. It is caused by the heart failing to pump enough blood around the body at the right pressure, usually because the heart muscle has become too weak or stiff to work properly. Acute heart failure, which occurs when symptoms develop quickly, is the leading cause of hospital admission in people over 65. PMID:25492766

  7. Liver spots

    MedlinePlus

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

  8. Heart Failure

    MedlinePlus

    ... of breath Common causes of heart failure are coronary artery disease, high blood pressure and diabetes. It is more common in people who are 65 years old or older, African Americans, people who are ... treatments fail. NIH: National Heart, Lung, and Blood Institute

  9. Rapid onset Chilaiditi's sign on top of fulminant hepatic failure.

    PubMed

    Chan, See-Ching; Liu, Chi-Leung; Lo, Chung-Mau; Fan, Sheung-Tat

    2004-08-01

    Fulminant hepatic failure is a medical emergency. When this condition declared itself irreversible, a timely liver transplantation is the only effective treatment. A 34-year-old Chinese with fulminant hepatic failure was evaluated as a potential liver transplantation candidate. On the erect chest radiograph, Chilaiditi's sign has developed over a very short period of a week due to rapid shrinkage of the liver. Awareness of Chilaiditi's sign facilitated distinguishing the condition of free gas under the diaphragm due to bowel perforation and subphrenic abscess by gas forming micro-organisms. Rapidity of onset of this sign parallels the deterioration of liver function and reflects the urgency of condition.

  10. Liver Regeneration

    PubMed Central

    Michalopoulos, George K.

    2009-01-01

    Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other. PMID:17559071

  11. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  12. Benign Liver Tumors

    MedlinePlus

    ... Search: Your Liver Liver Health and Wellness Recipes Liver Disease Information Patients & Families Caregiver's FAQ Become an Organ ... 2013 Liver Awareness Month Personal Story - David Roncori Liver Disease - The Big Picture 13 Ways to a Healthy ...

  13. Size mismatch in liver transplantation.

    PubMed

    Fukazawa, Kyota; Nishida, Seigo

    2016-08-01

    Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. PMID:27474079

  14. Liver Panel

    MedlinePlus

    ... liver; the best test for detecting hepatitis Alkaline phosphatase (ALP) – an enzyme related to the bile ducts ... only moderately elevated or close to normal. Alkaline phosphatase (ALP) ALP may be significantly increased with obstructed ...

  15. Liver transplant

    MedlinePlus

    ... toxins in the blood Storing sugars, fats, iron, copper, and vitamins The most common reason for a ... cirrhosis or primary sclerosing cholangitis Metabolic disorders of copper or iron ( Wilson's disease and hemochromatosis ) Liver transplant ...

  16. Liver cirrhosis.

    PubMed Central

    Williams, E. J.; Iredale, J. P.

    1998-01-01

    Liver fibrosis and its related complications continue to represent a significant worldwide healthcare burden. Over the past decade there has been considerable improvement in our understanding of the cellular mechanisms and pathophysiology underlying hepatic fibrosis. This greater insight into the relevant basic sciences may lead to the development of novel treatment strategies designed to block the fibrogenic cascade or even enhance matrix degradation. In addition, there have been significant advances in the management of the complications of cirrhosis, with specific treatments now available for some conditions. Perhaps most notably, liver transplantation is now a highly successful treatment for end-stage liver disease and should be considered in all patients with chronic liver disease. PMID:9683971

  17. Artificial liver support: a real step forward.

    PubMed

    Saliba, F; Samuel, D

    2015-02-01

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

  18. Artificial liver support: a real step forward.

    PubMed

    Saliba, F; Samuel, D

    2015-02-01

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

  19. Translational biomarkers of acetaminophen-induced acute liver injury.

    PubMed

    Beger, Richard D; Bhattacharyya, Sudeepa; Yang, Xi; Gill, Pritmohinder S; Schnackenberg, Laura K; Sun, Jinchun; James, Laura P

    2015-09-01

    Acetaminophen (APAP) is a commonly used analgesic drug that can cause liver injury, liver necrosis and liver failure. APAP-induced liver injury is associated with glutathione depletion, the formation of APAP protein adducts, the generation of reactive oxygen and nitrogen species and mitochondrial injury. The systems biology omics technologies (transcriptomics, proteomics and metabolomics) have been used to discover potential translational biomarkers of liver injury. The following review provides a summary of the systems biology discovery process, analytical validation of biomarkers and translation of omics biomarkers from the nonclinical to clinical setting in APAP-induced liver injury.

  20. Hepatitis C and liver transplantation

    NASA Astrophysics Data System (ADS)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  1. Vγ4 γδ T cell-derived IL-17A negatively regulates NKT cell function in Con A-induced fulminant hepatitis.

    PubMed

    Zhao, Na; Hao, Jianlei; Ni, Yuanyuan; Luo, Wei; Liang, Ruifang; Cao, Guangchao; Zhao, Yapu; Wang, Puyue; Zhao, Liqing; Tian, Zhigang; Flavell, Richard; Hong, Zhangyong; Han, Jihong; Yao, Zhi; Wu, Zhenzhou; Yin, Zhinan

    2011-11-15

    Con A-induced fulminant hepatitis is a well-known animal model for acute liver failure. However, the role of γδ T cells in this model is undefined. In this report, using TCR δ(-/-) mice, we demonstrated a protective role of γδ T cells in Con A-induced hepatitis model. TCR δ(-/-) mice showed significantly decreased levels of IL-17A and IL-17F in the Con A-treated liver tissue, and reconstitution of TCR δ(-/-) mice with wild-type (Wt), but not IL-17A(-/-), γδ T cells significantly reduced hepatitis, strongly suggesting a critical role of IL-17A in mediating the protective effect of γδ T cells. Interestingly, only Vγ4, but not Vγ1, γδ T cells exerted such a protective effect. Furthermore, depletion of NKT cells in TCR δ(-/-) mice completely abolished hepatitis, and NKT cells from Con A-challenged liver tissues of TCR δ(-/-) mice expressed significantly higher amounts of proinflammatory cytokine IFN-γ than those from Wt mice, indicating that γδ T cells protected hepatitis through targeting NKT cells. Finally, abnormal capacity of IFN-γ production by NKT cells of TCR δ(-/-) mice could only be downregulated by transferring Wt, but not IL-17(-/-), Vγ4 γδ T cells, confirming an essential role of Vγ4-derived IL-17A in regulating the function of NKT cells. In summary, our report thus demonstrated a novel function of Vγ4 γδ T cells in mediating a protective effect against Con A-induced fulminant hepatitis through negatively regulating function of NKT cells in an IL-17A-dependent manner, and transferring Vγ4 γδ T cells may provide a novel therapeutic approach for this devastating liver disease.

  2. Indications and Contraindications for Liver Transplantation

    PubMed Central

    Varma, Vibha; Mehta, Naimish; Kumaran, Vinay; Nundy, Samiran

    2011-01-01

    Patients with chronic liver disease and certain patients with acute liver failure require liver transplantation as a life-saving measure. Liver transplantation has undergone major improvements, with better selection of candidates for transplantation and allocation of scarce deceased donor organs (according to more objective criteria). Living donor liver transplantation came into existence to overcome the shortage of donor organs especially in countries where there was virtually no deceased donor programme. Advances in the technical aspects of the procedure, the intraoperative and postoperative care of both recipients and donors, coupled with the introduction of better immunosuppression protocols, have led to graft and patient survivals of over 90% in most high volume centres. Controversial areas like transplantation in alcoholic liver disease without abstinence, acute alcoholic hepatitis, and retransplantation for recurrent hepatitis C virus infection require continuing discussion. PMID:22007310

  3. Tulipalin A induced phytotoxicity.

    PubMed

    McCluskey, James; Bourgeois, Marie; Harbison, Raymond

    2014-04-01

    Tulipalin A induced phytotoxicity is a persistent allergic contact dermatitides documented in floral workers exposed to Alstroemeria and its cultivars.[1] The causative allergen is tulipalin A, a toxic glycoside named for the tulip bulbs from which it was first isolated.[2] The condition is characterized by fissured acropulpitis, often accompanied by hyperpigmentation, onychorrhexis, and paronychia. More of the volar surface may be affected in sensitized florists. Dermatitis and paronychia are extremely common conditions and diagnostic errors may occur. A thorough patient history, in conjunction with confirmatory patch testing with a bulb sliver and tuliposide A exposure, can prevent misdiagnosis. We report a case of Tulipalin A induced phytotoxicity misdiagnosed as an unresolved tinea manuum infection in a patient evaluated for occupational exposure. PMID:25024947

  4. Telomeres and marrow failure.

    PubMed

    Calado, Rodrigo T

    2009-01-01

    Telomeres, repeat sequences at the ends of chromosomes, are protective chromosomal structures highly conserved from primitive organisms to humans. Telomeres inevitably shorten with every cell cycle, and telomere attrition has been hypothesized to be fundamental to normal senescence of cells, tissues, and organisms. Molecular mechanisms have evolved to maintain their length and protective function; telomerase (TERT) is a reverse transcriptase enzyme that uses an RNA molecule (TERC) as the template to elongate the 3' ends of telomeres. Shelterin is a collection of DNA-binding proteins that cover and protect telomeres. The recent discovery of inherited mutations in genes that function to repair telomeres as etiologic in a range of human diseases, which have clinical manifestations in diverse tissues, including the hematopoietic tissue, suggests that defects in telomere repair and protection can cause organ failure. Dyskeratosis congenita is the prototype of telomere diseases; it is characterized by bone marrow failure, mucocutaneous abnormalities, pulmonary fibrosis, liver cirrhosis, and increased susceptibility to cancer, including acute myeloid leukemia. Aplastic anemia, acute myeloid leukemia, and idiopathic pulmonary fibrosis also are associated with inherited mutations in telomere repair or protection genes. Additionally, telomere defects associate with predisposition to hematologic malignancy and epithelial tumors. Telomere erosion is abnormally rapid in patients with mutations in telomerase genes but also after hematopoietic stem cell transplant, and telomeres are naturally shorter in older individuals-all conditions associated with higher rates of malignant diseases. In human tissue culture, short telomeres produce end-to-end chromosome fusion, nonreciprocal translocations, and aneuploidy.

  5. [(Bio)artificial liver support: ready for the patient?].

    PubMed

    Chamuleau, R A F M

    2016-05-01

    In 2016, an intensive-care physician has at his disposal a number of artificial organs for the support of patients with organ failure. Examples are the artificial kidney and the heart-lung machine. Artificial livers are being developed for patients with severe liver failure whose lives can only be saved at the present time by a transplant with a donor liver. These artificial livers are based either on a device that removes toxic materials from the patient's blood with, for example, albumin dialysis, or make use of bio-reactors filled with functioning liver cells, the so-called bio-artificial liver. In theory, the bio-artificial liver has the greatest potential to increase life expectancy. The results of clinical studies are also very promising. They are not yet sufficient, however, to permit general clinical use.

  6. [(Bio)artificial liver support: ready for the patient?].

    PubMed

    Chamuleau, R A F M

    2016-05-01

    In 2016, an intensive-care physician has at his disposal a number of artificial organs for the support of patients with organ failure. Examples are the artificial kidney and the heart-lung machine. Artificial livers are being developed for patients with severe liver failure whose lives can only be saved at the present time by a transplant with a donor liver. These artificial livers are based either on a device that removes toxic materials from the patient's blood with, for example, albumin dialysis, or make use of bio-reactors filled with functioning liver cells, the so-called bio-artificial liver. In theory, the bio-artificial liver has the greatest potential to increase life expectancy. The results of clinical studies are also very promising. They are not yet sufficient, however, to permit general clinical use. PMID:27166453

  7. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    PubMed Central

    Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

    2014-01-01

    Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration. PMID:24991941

  8. Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

    PubMed Central

    Derikx, Joep P. M.; Buurman, Wim A.; Peters, Wilbert H. M.; Roelofs, Hennie M. J.; Wigmore, Stephen J.; Dejong, Cornelis HC

    2007-01-01

    Background Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection. Methods Markers of hepatocyte injury (AST, GSTα, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with and without intermittent inflow occlusion. To study the separate involvement of the intestines and the liver in systemic L-FABP release, arteriovenous concentration differences for L-FABP were measured. Results During liver manipulation, liver injury markers increased significantly. Arterial plasma levels and transhepatic and transintestinal concentration gradients of L-FABP indicated that this increase was exclusively due to hepatic and not due to intestinal release. Intermittent hepatic inflow occlusion, anesthesia, and liver transection did not further enhance arterial L-FABP and GSTα levels. Hepatocyte injury was followed by an inflammatory response. Conclusions This study shows that liver manipulation is a leading cause of hepatocyte injury during liver surgery. A potential causal relation between liver manipulation and systemic inflammation remains to be established; but since the inflammatory response is apparently initiated early during major abdominal surgery, interventions aimed at reducing postoperative inflammation and related complications should be started early during surgery or beforehand. PMID:17668263

  9. [Fulminant hepatic failure due to tuberculostatic drugs: case report].

    PubMed

    Malla, Ivone; Fauda, Martín; Casanueva, Enrique; Fernández, María Isabel; Amante, Marcelo; Cheang, Yu; Giacove, Gisela; Pedreira, Alejandra; Petracca, Pablo; González Campaña, Ariel; Silva, Marcelo; Podestá, Gustavo

    2012-01-01

    Hepatoxicity of isoniazid, mainly in association with rifampin, is a rare secondary effect of tuberculostatic treatment. In the United States, it accounts for 0.2% of all pediatric orthotropic liver transplant, and 14% of transplants for drug hepatotoxicity. We report the case of a 10 year-old patient who presented with acute liver failure requiring orthotropic liver transplant after forty days of tuberculostatic treatment with isoniazid, rifampin and pyrazinamide.

  10. Transcriptomic studies on liver toxicity of acetaminophen.

    PubMed

    Toska, Endrit; Zagorsky, Robert; Figler, Bryan; Cheng, Feng

    2014-09-01

    Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen-induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen-induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen-induced acute liver failure. The following is a brief overview of some recent transcriptomic studies and gene-expression-based prediction models on liver toxicity induced by acetaminophen.

  11. Early postoperative complications following liver transplantation.

    PubMed

    Mueller, Andrea R; Platz, Klaus-Peter; Kremer, Bernd

    2004-10-01

    Liver transplantation is a highly successful treatment for patients with end-stage liver disease and acute liver failure. However, serious postoperative complications can significantly compromise patient survival. Complications can be technical, medical, or immunological in nature. The risk of developing early postoperative complications is associated with the patient's preoperative condition, the quality of the donor liver, the quality of the donor and recipient procedure, initial graft function, and perioperative anaesthesiological and intensive care management. The patient's preoperative condition can include gastrointestinal bleeding, acute renal failure, a requirement for cathecholamines or mechanical ventilation, and prolonged encephalopathy for the most detrimental risk factors for developing early postoperative complications. The necessity for prolonged mechanical ventilation or the requirement for reintubation after transplantation can significantly increase the risk of developing pneumonia, sepsis, and multiple organ dysfunction. A decrease in infectious and other complications can be achieved by early postoperative enteral nutition, including the application of probiotics. PMID:15494284

  12. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.

  13. Clinical Application of Bioartificial Liver Support Systems

    PubMed Central

    van de Kerkhove, Maarten Paul; Hoekstra, Ruurdtje; Chamuleau, Robert A. F. M.; van Gulik, Thomas M.

    2004-01-01

    Objective: To review the present status of bioartificial liver (BAL) devices and their obtained clinical results. Background: Acute liver failure (ALF) is a disease with a high mortality. Standard therapy at present is liver transplantation. Liver transplantation is hampered by the increasing shortage of organ donors, resulting in high incidence of patients with ALF dying on the transplantation waiting list. Among a variety of liver assist therapies, BAL therapy is marked as the most promising solution to bridge ALF patients to liver transplantation or to liver regeneration, because several BAL systems showed significant survival improvement in animal ALF studies. Until today, clinical application of 11 different BAL systems has been reported. Methods: A literature review was performed using MEDLINE and additional library searches. Only BAL systems that have been used in a clinical trial were included in this review. Results: Eleven BAL systems found clinical application. Three systems were studied in a controlled trial, showing no significant survival benefits, in part due to the insufficient number of patients included. The other systems were studied in a phase I trial or during treatment of a single patient and all showed to be safe. Most BAL therapies resulted in improvement of clinical and biochemical parameters. Conclusions: Bioartificial liver therapy for bridging patients with ALF to liver transplantation or liver regeneration is promising. Its clinical value awaits further improvement of BAL devices, replacement of hepatocytes of animal origin by human hepatocytes, and assessment in controlled clinical trials. PMID:15273544

  14. Corset liver

    SciTech Connect

    Philips, D.M.; LaBrecque, D.R.; Shirazi, S.S.

    1985-08-01

    The authors describe four patients with a benign hepatic malformation most consistent with the rarely described anomaly known as corset liver. Three of these patients were extensively evaluated to rule out a malignancy because of an abdominal mass. These patients illustrate several features which may help in making the diagnosis and avoiding unnecessary surgery.

  15. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  16. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  17. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  18. Liver transplantation for Wilson disease

    PubMed Central

    Catana, Andreea M; Medici, Valentina

    2012-01-01

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  19. Liver transplantation for Wilson disease.

    PubMed

    Catana, Andreea M; Medici, Valentina

    2012-01-27

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  20. Pig Liver Xenotransplantation: A Review of Progress Toward the Clinic.

    PubMed

    Cooper, David K C; Dou, Ke-Feng; Tao, Kai-Shan; Yang, Zhao-Xu; Tector, A Joseph; Ekser, Burcin

    2016-10-01

    Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained. Other topics discussed include the possible mechanisms for the development of the thrombocytopenis that rapidly occurs after pig liver xenotransplantation in a primate, the impact of pig complement on graft injury, the potential infectious risks, and potential physiologic incompatibilities between pig and human. There is cautious optimism that all of these problems can be overcome by judicious genetic manipulation of the pig. If liver graft survival could be achieved in the absence of thrombocytopenia or rejection for a period of even a few days, there may be a role for pig liver transplantation as a bridge to allotransplantation in carefully selected patients.

  1. Renal failure in fulminant hepatic failure and terminal cirrhosis: a comparison between incidence, types, and prognosis.

    PubMed Central

    Ring-Larsen, H; Palazzo, U

    1981-01-01

    Forty patients with terminal cirrhosis and 40 patients with fulminant hepatic failure-all consecutively admitted-were studied with regard to incidence, types, and prognosis of complicating renal insufficiency. Renal failure was considered present when the serum creatinine was greater than 0.20 mmol/l. Of the patients with cirrhosis 26 (65%) developed renal failure. In 15 the type was functional, in three due to acute tubular necrosis, and in eight indeterminable. Of the patients with fulminant hepatic failure 22 (55%) had renal insufficiency; of these 13 had functional renal failure, five acute tubular necrosis, and in four the type was indeterminable. In both categories of patients, renal failure was equally frequent among patients with or without gastrointestinal bleeding and with or without ascites or diuretic therapy. The biochemical tests of liver function were similar in patients with or without renal failure in both categories. The mean renal blood flow in seven unselected patients with fulminant hepatic failure was reduced in the same order as previously observed in patients with cirrhosis. In terminal cirrhosis the mortality rate was 88% in the presence of renal failure, 71% in its absence (p greater than 0.05), while the same figures in fulminant hepatic failure were 100% and 67% (p less than 0.05). The incidence, relative frequency, and prognosis of renal failure were not different in the two conditions, indicating identical pathophysiological circumstances. PMID:7262632

  2. Prevention and treatment of drug-induced liver disease.

    PubMed

    Speeg, K V; Bay, M K

    1995-12-01

    Many drugs may cause liver damage; some damage is predictable, but most is not. The most important preventive measure is judicious drug use by the prescribing physician. Early recognition of hepatotoxicity and cessation of the offending agent is essential for treatment. The best example of a specific treatment for drug-induced liver disease is N-acetylcysteine treatment for acetaminophen hepatotoxicity. Many examples are cited of other attempts at treatment in animal models of drug-induced liver disease. If drug-induced liver disease leads to fulminant hepatic failure, intensive management of the resulting complications is required. Liver transplantation may be the only treatment option.

  3. Hepatocyte cell therapy in liver disease.

    PubMed

    Bartlett, David Christopher; Newsome, Philip N

    2015-01-01

    Liver disease is a leading cause of morbidity and mortality. Liver transplantation remains the only proven treatment for end-stage liver failure but is limited by the availability of donor organs. Hepatocyte cell therapy, either with bioartificial liver devices or hepatocyte transplantation, may help address this by delaying or preventing liver transplantation. Early clinical studies have shown promising results, however in most cases, the benefit has been short lived and so further research into these therapies is required. Alternative sources of hepatocytes, including stem cell-derived hepatocytes, are being investigated as the isolation of primary human hepatocytes is limited by the same shortage of donor organs. This review summarises the current clinical experience of hepatocyte cell therapy together with an overview of possible alternative sources of hepatocytes. Current and future areas for research that might lead towards the realisation of the full potential of hepatocyte cell therapy are discussed. PMID:26212798

  4. [Wilson's disease: clinical spectrum of liver disease].

    PubMed

    Ochoa Palominos, Alejandra; Ibáñez Samaniego, Luis; Catalina Rodríguez, María-Vega; Pajares Díaz, José; Clemente Ricote, Gerardo

    2013-02-01

    Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism,characterized by copper accumulation in the liver and brain. This rare entity, which has a broad clinical spectrum, is often difficult to diagnose and should therefore always be suspected in patients with liver disease of unclear cause. We describe two types of manifestation of liver disease in two patients; the first developed fulminant hepatic failure requiring urgent liver transplantation and the second showed advanced chronic liver disease and received standard medical treatment. The objective of this clinical observation is to analyze the diagnosis of Wilson's disease in two patients with distinct onset, illustrating the broad clinical spectrum of the disease, and its treatment.

  5. Gut microbiota and probiotics in chronic liver diseases.

    PubMed

    Cesaro, Claudia; Tiso, Angelo; Del Prete, Anna; Cariello, Rita; Tuccillo, Concetta; Cotticelli, Gaetano; Del Vecchio Blanco, Camillo; Loguercio, Carmelina

    2011-06-01

    There is a strong relationship between liver and gut: the portal system receives blood from the gut, and intestinal blood content activates liver functions. The liver, in turn, affects intestinal functions through bile secretion into the intestinal lumen. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of complications of liver cirrhosis, such as infections, hepatic encephalopathy, spontaneous bacterial peritonitis, and renal failure. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation. This review summarizes the main literature findings about the relationships between gut microbiota and chronic liver disease, both in the pathogenesis and in the treatment by probiotics of the liver damage. PMID:21163715

  6. Liver repopulation and regeneration: new approaches to old questions

    PubMed Central

    Duncan, Andrew W.; Soto-Gutierrez, Alejandro

    2013-01-01

    Purpose of review Significant recent developments have occurred in the field of liver regeneration. Although the regenerative response to partial hepatectomy has been studied extensively, in recent years the use of new experimental approaches has incorporated a fresh look that may lead to a better understanding of hepatocyte dysfunction and regeneration. Recent findings Liver injury promotes the regenerative responses that are relatively rare in healthy livers. Current research efforts focus on the mechanisms of hepatocyte adaptation in response to liver injury. We will discuss how hepatic aneuploidy and polyploidy contributes to liver regeneration, as well as new modalities to study cellular interactions using the organ-specific microenvironment. Summary High mortality is generally limited to patients who develop terminal liver failure, which occurs when regenerative responses are unable to compensate for liver injury. Cellular adaptations and organ microenvironment changes are present during disease processes. This review aims to provide insights into the innovative approaches taken to investigate regeneration in liver diseases. PMID:23425785

  7. Liver transplantation at Mount Sinai.

    PubMed

    Kim-Schluger, L; Florman, S S; Gondolesi, G; Emre, S; Sheiner, P A; Fishbein, T M; Schwartz, M E; Miller, C M

    2000-01-01

    Nearly 2000 liver transplants have been performed over the past 12 years at Mount Sinai, with a recent exponential growth in living donor surgeries. Living-donor liver transplantation has emerged as an important option for our patients with end-stage liver disease. We are only beginning to recognize fully the advantages that 'scheduled' liver transplantation can offer. In this era of severe cadaver organ shortages, living donation offers patients the option of liver replacement in a timely fashion, before life-threatening complications of hepatic failure and/or carcinoma progression prohibit transplantation. The next era of transplantation at Mount Sinai will bring significant increases in the number of transplants performed with living donors, with projections of over 50% of the total transplants each year expected to involve living donations. We are committed to offering this option while recognizing that donor safety remains paramount and cannot be overemphasized. Proper donor and recipient selection, as well as surgical experience are imperative to success with this technically demanding procedure. Recurrent disease after transplantation, particularly with hepatitis C, remains a challenge clinically. Further investigations into the pathogenesis of the rapid progression of recurrent hepatitis C need to be addressed. Living donor transplantation could be an important option for these patients and would allow timely transplantation and the potential for improved survival in patients with hepatocellular carcinoma. PMID:11512318

  8. Liver transplantation in small babies.

    PubMed

    Vázquez, J; Gámez, M; Santamaría, M L; Murcia, J; Díaz, M C; Camarena, C; Jara, P; Tovar, J A

    1993-08-01

    Pediatric liver transplantation is an effective treatment for end-stage liver disease with 1- and 5-year survivals approaching 90% and 70%, respectively. Survival is influenced by the recipient's age, weight, primary disease, vascular malformations, and nutritional status. Younger patients weighing less than 13 kg are considered to be a high-risk group. The aim of this article is to evaluate the impact of this group of patients on the overall results of our pediatric liver transplant program. From January 1986 through January 1992 we performed 76 liver transplants in 59 pediatric patients. Sixteen received a second graft and a third was required in one. Fourteen patients weighed less than 13 kg (mean, 11 kg; range, 6 to 13 kg). Their mean age was 12 months, with a range of 8 to 36 months. Indications for transplantation were: biliary atresia (9), Byler's disease (1), tyrosinemia (3), and alpha 1-antitrypsin deficiency (1). The incidence of rejection in this group (52%) was not significantly different from that in other patients (61%). Ten episodes of acute rejection required only steroids: in one monoclonal antibodies were added. Five patients had a new graft implanted, four for hepatic artery thrombosis and one for primary liver nonfunction. Nine patients are alive (64%) with the follow-up time ranging from 2 to 56 months (mean, 31). Five patients died of multiorgan failure (3), portal vein thrombosis (1), and primary liver nonfunction (1). Four-year graft and patient survival rates were 47% and 64%, respectively. Small babies are a high-risk group in a pediatric liver transplant program.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. [Acute fatty liver during pregnancy: report of case].

    PubMed

    Ibargüen Burgos, Moira

    2003-01-01

    Acute fatty liver during pregnancy constitutes a rarely clinical entity with unknown pathogenesis and etiology. Its clinical picture is similar to preeclampsia including liver failure manifestations. Here in me expose a clinical case of a young woman 35 week first pregnancy with mild preeclampsia symptoms. We include a review of the literature.

  10. Multimodal brain monitoring in fulminant hepatic failure

    PubMed Central

    Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2016-01-01

    Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

  11. Multimodal brain monitoring in fulminant hepatic failure.

    PubMed

    Paschoal, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2016-08-01

    Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.

  12. Multimodal brain monitoring in fulminant hepatic failure.

    PubMed

    Paschoal, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

    2016-08-01

    Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

  13. Regenerative liver surgeries: the alphabet soup of emerging techniques.

    PubMed

    Parekh, Maansi; Kluger, Michael D; Griesemer, Adam; Bentley-Hibbert, Stuart

    2016-01-01

    New surgical procedures taking advantage of the regenerative abilities of the liver are being introduced as potential curative therapies to these patients either to provide auxiliary support while the native liver recovers or undergoes hypertrophy. For patients with hepatocellular carcinoma outside of the Milan criteria or bilobar colorectal metastases liver transplantation is not an option. Fulminant hepatic failure can be treated but requires life-long immunosuppression. These complex surgical procedures require high quality and directed imaging. PMID:26830622

  14. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  15. What Is Heart Failure?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Heart Failure? Heart failure is a condition in which the heart can' ... force. Some people have both problems. The term "heart failure" doesn't mean that your heart has stopped ...

  16. Human C1 inhibitor attenuates liver ischemia-reperfusion injury and promotes liver regeneration.

    PubMed

    Saidi, Reza F; Rajeshkumar, Barur; Shariftabrizi, Ahmad; Dresser, Karen; Walter, Otto

    2014-04-01

    Liver ischemia-reperfusion injury (IRI) is a well-known cause of morbidity and mortality after liver transplantation (LT). Activation of the complement system contributes to the pathogenesis of IRI. Effective treatment strategies aimed at reducing hepatic IRI and accelerating liver regeneration could offer major benefits in LT. Herein, we investigated the effect of C1-esterase inhibitor (human) [C1-INH] on IRI and liver regeneration. Mice were subjected to 60-min partial IRI, with or without 70% partial hepatectomy, or CCl4-induced acute liver failure. Before liver injury, the animals were pretreated with intravenous C1-INH or normal saline. Liver IRI was evaluated using serum levels of alanine aminotransferase, serum interleukin-6, and histopathology. Liver samples were stained for specific markers of regeneration (5-bromo-2'-deoxyuridine [BrdU] staining and proliferating cell nuclear antigen [PCNA]). Histology, serum interleukin-6, and alanine aminotransferase release revealed that C1-INH treatment attenuated liver injury compared with controls. Improved animal survival and increased number of BrdU- and PCNA-positive cells were observed in C1-INH-treated animals which underwent IRI + partial hepatectomy or CCl4 injection compared with control group. These data indicate that complement plays a key role in IRI and liver regeneration. C1-INH represents a potential therapeutic strategy to reduce IRI and promote regeneration in LT.

  17. Heart failure - medicines

    MedlinePlus

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  18. Liver regeneration - mechanisms and models to clinical application.

    PubMed

    Forbes, Stuart J; Newsome, Philip N

    2016-08-01

    Liver regeneration has been studied for many decades and the mechanisms underlying regeneration of the normal liver following resection or moderate damage are well described. A large number of factors extrinsic (such as bile acids and circulating growth factors) and intrinsic to the liver interact to initiate and regulate liver regeneration. Less well understood, and more clinically relevant, are the factors at play when the abnormal liver is required to regenerate. Fatty liver disease, chronic scarring, prior chemotherapy and massive liver injury can all inhibit the normal programme of regeneration and can lead to liver failure. Understanding these mechanisms could enable the rational targeting of specific therapies to either reduce the factors inhibiting regeneration or directly stimulate liver regeneration. Although animal models of liver regeneration have been highly instructive, the clinical relevance of some models could be improved to bridge the gap between our in vivo model systems and the clinical situation. Likewise, modern imaging techniques such as spectroscopy will probably improve our understanding of whole-organ metabolism and how this predicts the liver's regenerative capacity. This Review describes briefly the mechanisms underpinning liver regeneration, the models used to study this process, and discusses areas in which failed or compromised liver regeneration is clinically relevant. PMID:27353402

  19. Bioengineered transplantable porcine livers with re-endothelialized vasculature.

    PubMed

    Ko, In Kap; Peng, Li; Peloso, Andrea; Smith, Charesa J; Dhal, Abritee; Deegan, Daniel B; Zimmerman, Cindy; Clouse, Cara; Zhao, Weixin; Shupe, Thomas D; Soker, Shay; Yoo, James J; Atala, Anthony

    2015-02-01

    Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure.

  20. Bioengineered transplantable porcine livers with re-endothelialized vasculature.

    PubMed

    Ko, In Kap; Peng, Li; Peloso, Andrea; Smith, Charesa J; Dhal, Abritee; Deegan, Daniel B; Zimmerman, Cindy; Clouse, Cara; Zhao, Weixin; Shupe, Thomas D; Soker, Shay; Yoo, James J; Atala, Anthony

    2015-02-01

    Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure. PMID:25433603

  1. [Extracorporeal therapy of patients with liver disease in the intensive care unit].

    PubMed

    Fuhrmann, V; Horvatits, T; Drolz, A; Rutter, K

    2014-05-01

    Acute and acute-on-chronic liver failure are often associated with development of organ failure. Its occurrence is associated with high morbidity and mortality. Extracorporeal replacement therapies are frequently necessary in these patient populations. Replacement therapies can be divided into renal replacement therapies and liver support therapies. These therapies consist of artificial liver support systems (i.e., MARS(®) system, Prometheus(®)), which are able to remove water-soluble and albumin-bound toxins, and of bioartifical liver support systems. This manuscript provides a review of current practice in the extracorporeal support of patients with liver diseases in the intensive care unit. PMID:24770889

  2. Andrological status before and after liver transplantation.

    PubMed

    Madersbacher, S; Grünberger, T; Maier, U

    1994-05-01

    To determine the impact of liver transplantation on andrological status, we compared the endocrine profiles and spermiograms of 2 cohorts of patients before (9) and after (11) transplantation. Before liver transplantation testosterone (1.1 +/- 0.7 ng/ml) and free testosterone (2.0 +/- 1.6 pg/ml) were pathologically decreased in all 9 cases, and luteinizing hormone was lower (1.8 +/- 1.4 mIU/ml) in 5. Only 3 of 9 patients were able to produce ejaculates before liver transplantation, all of which were azoospermic. After a mean interval of 28 +/- 9 months (range 4 to 34 months) following liver transplantation testosterone (5.3 +/- 1.1 ng/ml), free testosterone (15.3 +/- 5.0 pg/ml) and luteinizing hormone (6.2 +/- 3.7 mIU/ml.) were consistently within the normal range, with a highly statistically significant difference (p < 0.025) from pre-liver transplantation values. Semen analyses after liver transplantation revealed normal density, motility and normal forms in 5 patients, 2 suffered from oligoasthenoteratospermia and 4 were unable to produce an ejaculate for semen analyses. These data demonstrate that the hypothalamic-pituitary-testicular hormone axis and gonadal tissue are capable of resuming normal function after liver transplantation in men with chronic liver failure who suffered from massive andrological dysfunction before transplantation.

  3. Liver Function Tests

    MedlinePlus

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  4. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  5. Progression of Liver Disease

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  6. Pyogenic liver abscess

    MedlinePlus

    Liver abscess; Bacterial liver abscess ... There are many potential causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

  7. Diet and Your Liver

    MedlinePlus

    ... scarring of your liver (cirrhosis). For people with liver disease, even a small amount of alcohol can make ... time. Eating an unhealthy diet can lead to liver disease. For example, a person who eats a lot ...

  8. LIVER MICROSOMES

    PubMed Central

    Palade, G. E.; Siekevitz, P.

    1956-01-01

    Rat liver, liver homogenates, and microsome fractions separated therefrom were examined systematically in the electron microscope in sections of OsO4-fixed, methacrylate-embedded tissue and pellets. It was found that most microsomes are morphologically identical with the rough surfaced elements of the endoplasmic reticula of hepatic cells. They appear as isolated, membrane-bound vesicles, tubules, and cisternae which contain an apparently homogeneous material of noticeable density, and bear small, dense particles (100 to 150 A) attached to their outer aspect. In solutions of various osmolar concentrations they behave like osmometers. The findings suggest that they derive from the endoplasmic reticulum by a generalized pinching-off process rather than by mechanical fragmentation. The microsome fractions contain in addition relatively few vesicles free of attached particles, probably derived from the smooth surfaced parts of the endoplasmic reticula. Dense, peribiliary bodies represent a minor component of the same fractions. The microsomes derived from 1 gm. wet weight liver pulp contained (averages of 10 experiments) 3.09 mg. protein N, 3.46 mg. RNA (RNA/protein N = 1.12), and 487 µg. phospholipide P. They displayed DPNH-cytochrome c reductase activity and contained an alcohol-soluble hemochromogen. The microsome preparations proved resistant to washing and "aging." Treatment with versene and incubation with ribonuclease (30 minutes at 37°C.) resulted in appreciable losses of RNA and in partial or total disappearance of attached particles. Treatment with deoxycholate (0.3 to 0.5 per cent, pH = 7.5) induced a partial clarification of the microsome suspensions which, upon centrifugation, yielded a small pellet of conglomerated small, dense particles (100 to 150 A) with only occasionally interspersed vesicles. The pellet contained ∼80 to 90 per cent of the RNA and ∼20 per cent of the protein N of the original microsomes. The supernatant accounted satisfactorily

  9. Liver immunology and its role in inflammation and homeostasis

    PubMed Central

    Robinson, Mark W; Harmon, Cathal; O'Farrelly, Cliona

    2016-01-01

    The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the non-diseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ‘dangerous' stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease. PMID:27063467

  10. Advanced Heart Failure

    MedlinePlus

    ... High Blood Pressure Tools & Resources Stroke More Advanced Heart Failure Updated:Oct 8,2015 When heart failure (HF) ... content was last reviewed on 04/06/2015. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  11. Amebic liver abscess

    MedlinePlus

    ... liver in response to an intestinal parasite called Entamoeba histolytica . ... Amebic liver abscess is caused by Entamoeba histolytica. This ... dysentery. After an infection has occurred, the parasite may ...

  12. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  13. Imaging of drug effects in perfused liver

    NASA Astrophysics Data System (ADS)

    Dammann, Marc; Mahlke, Christine; Kessler, Manfred D.

    2002-06-01

    Various medications affect the systemic circulation and organ oxygenation causing dilatation or constriction of blood vessels. Imminent liver failure can be generated by reduced perfusion of different origins. In this case hepatic vasodilatation would be a therapeutical approach for improving patient's condition. Our examinations have been performed in perfused rat liver using spectrometric methods. Two defined areas of the liver were measured punctually. We compared the influence of Tetramethylpyrazine and Glyceroltrinitrate on hemoglobin oxygenation (HbO2) and concentration (Hb-conc.) in rat liver after application of Norepinephrine, which caused a mid decrease in hemoglobin oxygenation of 47,9 %. Both increased the HbO2, but differed from each other in manner of time and extent. Tetramethylpyrazine indicated a longer effect than Glyceroltrinitrate. Furthermore, HbO2 and Hb-conc. showed a conversed relation. From the shape of the absorption spectra it is possible to derive the oxygenation of hemoglobin.

  14. New approaches to supporting the failing liver.

    PubMed

    Cao, S; Esquivel, C O; Keeffe, E B

    1998-01-01

    With the continued, growing disparity between the numbers of organ donations and patients waiting for liver transplantation, various efforts have been made to optimize the allocation of organs, as well as to devise means to support the failing liver. Over the years, the development of bioartificial liver-assist devices has aimed at replacing the three main functions of hepatocytes, which are synthetic, metabolic, and excretory. The application of porcine hepatocytes in humans to carry out biotransformation, as well as other metabolic functions and refinement of the membrane separator, have yielded some promising results in supporting patients with acute liver failure. Further advances will need to be made before these bioartificial devices can be considered for routine application in clinical settings.

  15. Dengue and its effects on liver

    PubMed Central

    Samanta, Jayanta; Sharma, Vishal

    2015-01-01

    Dengue has emerged as an important arboviral disease with significant impact on the disease burden in population residing in tropical countries. Dengue is spread by the bite of Aedes mosquito. The virus seems to have some hepatotoxic effects. Affliction of liver in form of derangements in the liver function tests is common and may include mild elevations in serum bilirubin, elevated transaminases and derangements in serum albumin. Although asymptomatic in most cases, clinical manifestations like jaundice, and acute liver failure (ALF) may occasionally complicate the clinical picture. Indeed, dengue has been implicated as an important cause of ALF in endemic countries. The present review focuses on the hepatic manifestations and the pathogenesis of the liver injury in dengue. PMID:25685758

  16. Application of Induced Pluripotent Stem Cells in Liver Diseases

    PubMed Central

    Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

    2014-01-01

    Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

  17. A facilitated technique for hepatectomy of porcine liver.

    PubMed

    Mizrahi, S S; Jones, J W; Bentley, F R

    1996-01-01

    The swine liver has been used for experimental transplantation and as an ex vivo support system for patients with fulminant hepatic failure. Preservation of liver function after the cold storage period can be accomplished by complying with several key steps during the procurement: Keep the procedure short, provide extensive exposure, allow only minimal dissection, irrigate the portal system through the splenic vein and thereby obtain regular blood flow through the organ up to the clamping point, and ice the liver abruptly in situ. This retrieval technique was used and evaluated in 10 pigs. The method allowed a short and successful organ procurement while preserving normal function of the liver ex vivo. PMID:8951663

  18. Biomechanical response of human liver in tensile loading.

    PubMed

    Kemper, Andrew R; Santago, Anthony C; Stitzel, Joel D; Sparks, Jessica L; Duma, Stefan M

    2010-01-01

    Motor vehicle collisions commonly result in serious life threatening liver injuries. Although finite element models are becoming an integral tool in the reduction of automotive related liver injuries, the establishment of accurate material models and tissue level tolerance values is critical for accurate injury risk assessment. This study presents a total of 51 tension tests performed on human liver parenchyma at various loading rates in order to characterize the viscoelastic and failure properties of human liver. Standard dog-bone coupons were obtained from fresh human livers and tested within 48 hours of death. Each coupon was tested once to failure at one of four loading rates (0.008 s(-1), 0.089 s(-1), 0.871 s(-1), and 9.477 s(-1)) to investigate the effects of rate dependence. Load and acceleration data were obtained from each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that liver parenchyma is rate dependent, with higher rate tests giving higher failure stresses and lower failure strains. The failure strains for all tests ranged from 11% to 54% and the failure stresses ranged from 7 kPa to 95 kPa. This study provides novel biomechanical data that can be used in the development of both rate dependent material models and tissue level tolerance values critical for the validation of finite element models used to assess injury risk in automobile collisions. PMID:21050588

  19. Biomechanical Response of Human Liver in Tensile Loading

    PubMed Central

    Kemper, Andrew R.; Santago, Anthony C.; Stitzel, Joel D.; Sparks, Jessica L.; Duma, Stefan M.

    2010-01-01

    Motor vehicle collisions commonly result in serious life threatening liver injuries. Although finite element models are becoming an integral tool in the reduction of automotive related liver injuries, the establishment of accurate material models and tissue level tolerance values is critical for accurate injury risk assessment. This study presents a total of 51 tension tests performed on human liver parenchyma at various loading rates in order to characterize the viscoelastic and failure properties of human liver. Standard dog-bone coupons were obtained from fresh human livers and tested within 48 hours of death. Each coupon was tested once to failure at one of four loading rates (0.008 s–1, 0.089 s–1, 0.871 s–1, and 9.477 s–1) to investigate the effects of rate dependence. Load and acceleration data were obtained from each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that liver parenchyma is rate dependent, with higher rate tests giving higher failure stresses and lower failure strains. The failure strains for all tests ranged from 11% to 54% and the failure stresses ranged from 7 kPa to 95 kPa. This study provides novel biomechanical data that can be used in the development of both rate dependent material models and tissue level tolerance values critical for the validation of finite element models used to assess injury risk in automobile collisions. PMID:21050588

  20. Factors predicting early postoperative liver cirrhosis-related complications after lung cancer surgery in patients with liver cirrhosis.

    PubMed

    Iwata, Takashi; Inoue, Kiyotoshi; Nishiyama, Noritoshi; Nagano, Koshi; Izumi, Nobuhiro; Tsukioka, Takuma; Hanada, Shoji; Suehiro, Shigefumi

    2007-12-01

    We aimed to determine the factors predicting liver cirrhosis-related complications in the early postoperative period after lung cancer surgery in patients with liver cirrhosis. We retrospectively reviewed the medical records of patients who underwent curative surgery for primary lung cancer in our institute from January 1990 to March 2007, finding 37 cases with comorbid liver cirrhosis. These patients were divided into two groups, according to whether liver failure, bleeding, and critical infection had occurred postoperatively. Various clinical parameters were analyzed statistically between the bigeminal groups. Liver cirrhosis-related complications occurred in seven of the 37 patients (18.9%). Transient liver failure occurred in two patients (5.4%) after pulmonary resection. Acute intrathoracic bleeding occurred in four cases (10.8%). Two patients died (5.4%) in both cases due to sepsis. Preoperative total bilirubin (P<0.05), and indocyanine green retention rate at 15 min (P<0.05) were significantly higher in patients with liver failure. Only serum value of total bilirubin was an independent risk factor (P<0.05) by multivariate analysis. In predicting death from infection, only preoperative nutritional status was a significant risk factor (P<0.05). To avoid postoperative cirrhosis-related complications, preoperative preparation to improve their liver function and nutrition status is essential. PMID:17766277

  1. Alcohol-Related Liver Disease

    MedlinePlus

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  2. [Liver and intestinal transplant in paediatric population].

    PubMed

    de la Rosa, G; Matesanz, R

    2015-12-01

    Our organizational model allows an annual 1,000 liver transplants. Pediatric liver transplantation constitutes 5% of such activity and provides, in children with severe, progressive and irreversible liver disease, a 1 year-survival of 90% and more than 80% after 15 years of follow-up. The main indication is biliary atresia followed by metabolic liver disease and acute liver failure. Around half of the procedures are performed in children under two years and 25-30% in the first year of life. The waiting list remains at around 35 patients, with an average of 100 patients enrolled annually and 60 of them finally transplanted after an average of 136.3 days on the waiting list. The prioritization of the candidates uses the PELD as an objective tool for decision-making. However, the progressive aging of donors, with a profile increasingly different from the requirements of the pediatric patients included in the waiting list, requires strategies such as living donor liver transplantation and the split liver transplantation, to increase the probability of transplant while reducing both time and mortality on the waiting list at the same time. Pediatric intestinal transplantation registers a low indication but involves strict requirements that outline a very uncommon donor in our country which, together with the absence of alternatives that outweigh the impact of these difficulties, penalizes the chances of transplant for these patients. PMID:26611879

  3. BIOCONJUGATION OF OLIGONUCLEOTIDES FOR TREATING LIVER FIBROSIS

    PubMed Central

    Ye, Zhaoyang; Hajj Houssein, Houssam S.; Mahato, Ram I.

    2009-01-01

    Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed. PMID:18154454

  4. Engineering Liver

    PubMed Central

    Griffith, Linda G.; Wells, Alan; Stolz, Donna Beer

    2014-01-01

    Interest in “engineering liver” arises from multiple communities: therapeutic replacement; mechanistic models of human processes; and drug safety and efficacy studies. An explosion of micro- and nano-fabrication, biomaterials, microfluidic, and other technologies potentially afford unprecedented opportunity to create microphysiological models of human liver, but engineering design principles for how to deploy these tools effectively towards specific applications, including how to define the essential constraints of any given application (including available sources of cells, acceptable cost, and user-friendliness) are still emerging. Arguably less appreciated is the parallel growth in computational systems biology approaches towards these same problems – particularly, in parsing complex disease processes from clinical material, building models of response networks, and in how to interpret the growing compendium of data on drug efficacy and toxicology in patient populations. Here, we provide insight into how the complementary paths of “engineering liver” – experimental and computational – are beginning to interplay towards greater illumination of human disease states and technologies for drug development. PMID:24668880

  5. Transport Advances in Disposable Bioreactors for Liver Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Catapano, Gerardo; Patzer, John F.; Gerlach, Jörg Christian

    Acute liver failure (ALF) is a devastating diagnosis with an overall survival of approximately 60%. Liver transplantation is the therapy of choice for ALF patients but is limited by the scarce availability of donor organs. The prognosis of ALF patients may improve if essential liver functions are restored during liver failure by means of auxiliary methods because liver tissue has the capability to regenerate and heal. Bioartificial liver (BAL) approaches use liver tissue or cells to provide ALF patients with liver-specific metabolism and synthesis products necessary to relieve some of the symptoms and to promote liver tissue regeneration. The most promising BAL treatments are based on the culture of tissue engineered (TE) liver constructs, with mature liver cells or cells that may differentiate into hepatocytes to perform liver-specific functions, in disposable continuous-flow bioreactors. In fact, adult hepatocytes perform all essential liver functions. Clinical evaluations of the proposed BALs show that they are safe but have not clearly proven the efficacy of treatment as compared to standard supportive treatments. Ambiguous clinical results, the time loss of cellular activity during treatment, and the presence of a necrotic core in the cell compartment of many bioreactors suggest that improvement of transport of nutrients, and metabolic wastes and products to or from the cells in the bioreactor is critical for the development of therapeutically effective BALs. In this chapter, advanced strategies that have been proposed over to improve mass transport in the bioreactors at the core of a BAL for the treatment of ALF patients are reviewed.

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

    PubMed

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

    2015-07-01

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

  7. Utilization of split liver grafts in orthotopic liver transplantation.

    PubMed

    Moreno-González, E; Gómez, S R; García, G I; Loinaz, S C; González-Pinto, I; Riaño, D; Ibáñez, J; Pérez-Cerdá, F; Bercedo, J; Dávila, P

    1993-02-01

    Among a total of 220 liver transplants, reduced-size liver was used in 21 cases due to discrepancies in size between recipient and donors in 19 patients. In the case of two adult patients suffering from fulminant hepatic failure and in a critical condition, only one donor organ became available, so that the graft was divided to give the two recipients an equal opportunity. The two patients with fulminant hepatic failure were admitted to the ICU requiring mechanical respiration almost at the same time. Hepatitis serologies were HBcAb+, HBsAb+, and VCA+ in one and negative in the second. They had different blood groups (A.Rh+, O.Rh-), and the only donor available was located in Milan, Italy. The graft perfused with UW. was divided into two (right side, segments IV, V, VI, VII, and VIII, and left side, segments I, II and III). The recipients were transplanted 50 and 48 hours after admission. The cold ischemia time was 7.10 and 16.50 hours. The first patient, who received the right lobe, was extubated at 48 hours and discharged on the 40th postransplant day. The second patient remained unconscious with progressive deterioration; an EEG on the 4th day revealed absence of higher cortical function.

  8. Contraceptive failure in China.

    PubMed

    Wang, Duolao

    2002-09-01

    This study examines patterns and differentials of contraceptive failure rates by method and characteristics of users, using the Chinese Two-per-Thousand Fertility Survey data. The results show that contraceptive failure rates for modern methods including sterilization are some of the highest in the world. The first year failure rates are 4.2% for male sterilization, 0.7% for female sterilization, 10.3% for IUD, 14.5% for pill, and 19.0% for condom. There are also some differentials in contraceptive failure rates by users' sociodemographic and fertility characteristics. Contraceptive failure rate declines with women's age for all reversible methods. Rural women have higher sterilization, IUD, and condom contraceptive failure rates than urban women. Women with two or more children have a higher failure rate for sterilization methods but have lower failure rates for other methods.

  9. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  10. Screening process failures for hepatocellular carcinoma.

    PubMed

    Singal, Amit G; Marrero, Jorge A; Yopp, Adam

    2014-03-01

    More than 60% of patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage, suggesting potential breakdowns in the HCC screening process. Understanding which steps in the screening process are not being performed is essential for designing effective interventions. To characterize HCC screening process failures, a retrospective cohort study of patients with cirrhosis diagnosed with HCC at a large urban safety-net hospital was conducted between 2005 and 2012. Screening process failures during the year before HCC diagnosis were characterized into 3 categories: absence of surveillance, failure of detection, and delayed follow-up. Univariate and multivariate analyses were performed to identify predictors of screening process failures. A total of 185 patients with cirrhosis and HCC were identified, of whom 91 (49%) were diagnosed at an early stage (Barcelona Clinic Liver Cancer system stage A). Only 16 (8.6%) patients successfully completed the screening process. Absence of surveillance was the most common screening process failure, found in 75.7% of all patients, and was associated with trends toward lower rates of early tumor detection (odds ratio, 0.51; 95% CI, 0.23-1.09) and worse overall survival (hazard ratio, 0.79; 95% CI, 0.49-1.25). Failure of detection and delayed follow-up were found in 11.4% and 2.7% of patients, respectively.

  11. Patterns of failure following curative resection of gastric carcinoma

    SciTech Connect

    Landry, J.; Tepper, J.E.; Wood, W.C.; Moulton, E.O.; Koerner, F.; Sullinger, J. )

    1990-12-01

    To identify patterns of failure following curative resection of gastric carcinoma, the records of 130 patients undergoing resection with curative intent at the Massachusetts General Hospital were reviewed. The total local-regional failure rate was 38% (49/130 patients), with 21 patients having local-regional failure alone and 28 patients having local-regional failure and distant metastases. The incidence of local failure rose with the more advanced stages of disease. Tumors staged B2, B3, C2, and C3 had local-regional failure rates in excess of 35%. This group of patients might benefit from adjuvant radiation therapy to the tumor bed and regional lymphatics. Local-regional failure rate was highest in the anastomosis or stump 33/130 (25%), followed by the stomach bed 27/130 (21%). The overall incidence of distant metastases was 52% (67/130 patients) and rose in the more advanced disease stages. Tumors staged B2, B3, C2, and C3 had rates of distant metastases greater than 50%. Sixty-one patients (77%) had failure in the abdomen (liver, peritoneal surface, adrenal, kidney, and spleen, but excluding tumor bed, anastomosis, or regional nodes). Patients with Stage B2, B3, C2, and C3 tumors had total abdominal failure rates greater than 40%. The highest failure rates in the liver were in Stages B3 and C3, in which the subsequent development of liver metastasis was 40% and 47%, respectively. Peritoneal seeding occurred in 30/130 (23%) of patients and was highest in Stages C2 and C3, with rates of 27% and 41%, respectively.

  12. Critical role of interleukin-17/interleukin-17 receptor axis in mediating Con A-induced hepatitis.

    PubMed

    Yan, Shu; Wang, Luman; Liu, Nan; Wang, Ying; Chu, Yiwei

    2012-04-01

    Concanavalin A (Con A)-induced hepatitis is thought to be a T-cell-mediated disease with active destruction of liver cells. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells. However, whether IL-17/IL-17 receptor (IL-17/IL-17R)-mediated responses are involved in T-cell-mediated Con A-induced liver injury remains unclear. In this study, we found that IL-17 expression was highly elevated in liver tissues during Con A-induced hepatitis. The increased levels of IL-17 were paralleled with the severity of liver injury reflected by Alanine aminotransaminase and histological assay as well as the secretion of tumor necrosis factor (TNF)-α and IL-6. Blockage of IL-17 significantly ameliorated Con A-induced hepatitis, while overexpression of IL-17 systemically resulted in massive hepatocyte necrosis in mice. Furthermore, overexpression of an IL-17R immunoglobulin G1 fusion protein significantly attenuated liver inflammation after acute Con A treatment. High expression of IL-17R on Kupffer cells was also observed along with the production of cytokines including TNF-α and IL-6. Inhibition of Kupffer cells by gadolinium chloride completely prevented Con A-induced liver injury and cytokine release. Finally, IL-17-expressing CD4(+) T and natural killer T cells were greatly increased in Con A-injected mice compared with that in controls. Overall, our results indicate that IL-17R signaling is critically involved in the pathogenesis in Con A-induced hepatitis, and blockade of IL-17/IL-17R signaling pathway may represent a novel therapeutic intervention in human autoimmune-related hepatitis.

  13. In Support of Failure

    ERIC Educational Resources Information Center

    Carr, Allison

    2013-01-01

    In this essay, I propose a concerted effort to begin devising a theory and pedagogy of failure. I review the discourse of failure in Western culture as well as in composition pedagogy, ultimately suggesting that failure is not simply a judgement or indication of rank but is a relational, affect-bearing concept with tremendous relevance to…

  14. Ammonia tank failure

    SciTech Connect

    Sweat, M.E.

    1983-04-01

    An ammonia tank failure at Hawkeye Chemical of Clinton, Iowa is discussed. The tank was a double-wall, 27,000 metric-ton tank built in 1968 and commissioned in December 1969. The paper presented covers the cause of the failure, repair, and procedural changes made to prevent recurrence of the failure. (JMT)

  15. Liver Transplant in a Patient under Methylphenidate Therapy: A Case Report and Review of the Literature

    PubMed Central

    Tong, Hoi Y.; Díaz, Carmen; Collantes, Elena; Medrano, Nicolás; Borobia, Alberto M.; Jara, Paloma; Ramírez, Elena

    2015-01-01

    Background. Methylphenidate (MPH) is widely used in treating children with attention-deficit-hyperactivity disorder. Hepatotoxicity is a rare phenomenon; only few cases are described with no liver failure. Case. We report on the case of a 12-year-old boy who received MPH for attention-deficit-hyperactivity disorder. Two months later the patient presented with signs and symptoms of hepatitis and MPH was discontinued, showing progressive worsening and developing liver failure and a liver transplantation was required. Other causes of liver failure were ruled out and the liver biopsy was suggestive of drug toxicity. Discussion. One rare adverse reaction of MPH is hepatotoxicity. The review of the literature shows few cases of liver injury attributed to MPH; all of them recovered after withdrawing the treatment. The probable mechanism of liver injury was MPH direct toxicity to hepatocytes. In order to establish the diagnosis of MPH-induced liver injury, we used CIOMS/RUCAM scale that led to an assessment of “possible” relationship. This report provides the first published case of acute MPH-induced liver failure with successful hepatic transplantation. Conclusions. It is important to know that hepatotoxicity can occur in patients with MPH treatment and monitoring the liver's function is highly recommended. PMID:25688317

  16. Autophagy in the liver: cell's cannibalism and beyond.

    PubMed

    Flores-Toro, Joseph A; Go, Kristina L; Leeuwenburgh, Christiaan; Kim, Jae-Sung

    2016-08-01

    Chronic liver disease and its progression to liver failure are induced by various etiologies including viral infection, alcoholic and nonalcoholic hepatosteatosis. It is anticipated that the prevalence of fatty liver disease will continue to rise due to the growing incidence of obesity and metabolic disorder. Evidence is accumulating to indicate that the onset of fatty liver disease is causatively linked to mitochondrial dysfunction and abnormal lipid accumulation. Current treatment options for this disease are limited. Autophagy is an integral catabolic pathway that maintains cellular homeostasis both selectively and nonselectively. As mitophagy and lipophagy selectively remove dysfunctional mitochondria and excess lipids, respectively, stimulation of autophagy could have therapeutic potential to ameliorate liver function in steatotic patients. This review highlights our up-to-date knowledge on mechanistic roles of autophagy in the pathogenesis of fatty liver disease and its vulnerability to surgical stress, with an emphasis on mitophagy and lipophagy. PMID:27515049

  17. New Developments on the Treatment of Liver Fibrosis.

    PubMed

    Koyama, Yukinori; Xu, Jun; Liu, Xiao; Brenner, David A

    2016-01-01

    Liver fibrosis results from many chronic injuries and often progresses to cirrhosis, liver failure, portal hypertension, and hepatocellular carcinoma. Liver transplantation is the only treatment available for patients with advanced stages of liver fibrosis. Therefore, new strategies for anti-fibrotic therapy are required. Various kinds of hepatocyte damage result in inflammation, which leads to the activation of hepatic stellate cells (HSCs), which are the major source of myofibroblasts in the liver. Myofibroblasts proliferate in response to various kinds of cytokines, chemokines, and growth factors and produce extracellular matrix proteins, which forms the fibrous scar. Myofibroblasts undergo apoptosis and inactivation when the underlying causative etiologies are cleared. Here we describe our current knowledge of targeting the steps in HSC activation as therapeutic target for liver fibrosis. PMID:27332862

  18. Living Related Liver Transplantation in an Infant with Neonatal Hemochromatosis

    PubMed Central

    Choi, Shin Jie; Choi, Jong Sub; Chun, Peter; Yoo, Jung Kyung; Moon, Jin Soo; Kim, Woo Sun; Kang, Gyeong Hoon; Yi, Nam-Joon

    2016-01-01

    Neonatal hemochromatosis (NH) is a severe neonatal liver injury that is confirmed by extra-hepatic iron accumulation. Although a recent study described treating NH with exchange transfusions and intravenous immunoglobulin, liver transplantation should be considered for patients with severe liver failure that does not respond to other medical treatment. Herein, we report the case of a two-month-old female infant who presented with persistent ascites and hyperbilirubinemia. Her laboratory findings demonstrated severe coagulopathy, high indirect and direct bilirubin levels, and high ferritin levels. Abdominal magnetic resonance imaging presented low signal intensity in the liver on T2-weighted images, suggesting iron deposition. The infant was diagnosed with NH as a result of the clinical findings and after congenital infection and metabolic diseases were excluded. The infant was successfully treated with a living-donor liver transplantation. Living related liver transplantation should be considered as a treatment option for NH in infants. PMID:27437193

  19. Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

    2010-02-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

  20. Living Related Liver Transplantation in an Infant with Neonatal Hemochromatosis.

    PubMed

    Choi, Shin Jie; Choi, Jong Sub; Chun, Peter; Yoo, Jung Kyung; Moon, Jin Soo; Ko, Jae Sung; Kim, Woo Sun; Kang, Gyeong Hoon; Yi, Nam-Joon

    2016-06-01

    Neonatal hemochromatosis (NH) is a severe neonatal liver injury that is confirmed by extra-hepatic iron accumulation. Although a recent study described treating NH with exchange transfusions and intravenous immunoglobulin, liver transplantation should be considered for patients with severe liver failure that does not respond to other medical treatment. Herein, we report the case of a two-month-old female infant who presented with persistent ascites and hyperbilirubinemia. Her laboratory findings demonstrated severe coagulopathy, high indirect and direct bilirubin levels, and high ferritin levels. Abdominal magnetic resonance imaging presented low signal intensity in the liver on T2-weighted images, suggesting iron deposition. The infant was diagnosed with NH as a result of the clinical findings and after congenital infection and metabolic diseases were excluded. The infant was successfully treated with a living-donor liver transplantation. Living related liver transplantation should be considered as a treatment option for NH in infants. PMID:27437193

  1. Overview of the Indications and Contraindications for Liver Transplantation

    PubMed Central

    Farkas, Stefan; Hackl, Christina; Schlitt, Hans Jürgen

    2014-01-01

    Liver transplantation is the only definitive treatment option for patients with irrevocable acute or chronic liver failure. In the last four decades, liver transplantation has developed from an experimental approach with a very high mortality to an almost routine procedure with good short- and long-term survival rates. Here, we present an up-to-date overview of the indications and contraindications for liver transplantation. It is shown how the evaluation of a candidate and finally listing for transplantation has to be performed in a multidisciplinary setting. Meticulous listing, timing, and organ allocation are the crucial factors to achieve an optimal outcome for the individual patient on the one hand, and reasonably using the limited deceased donor pool on the other hand. Living-donor liver transplantation is demanding but necessarily increasing. Because patients after liver transplantation need lifelong aftercare, it is important for primary care clinicians to understand the basic medical problems and risks. PMID:24789874

  2. In Vitro Platforms for Evaluating Liver Toxicity

    PubMed Central

    Senutovitch, Nina; Jindal, Rohit; Hegde, Manjunath; Gough, Albert; McCarty, William J; Bakan, Ahmet; Bhushan, Abhinav; Shun, Tong Ying; Golberg, Inna; DeBiasio, Richard; Usta, Berk Osman; Taylor, D. Lansing; Yarmush, Martin L.

    2014-01-01

    The liver is a heterogeneous organ with many vital functions, including metabolism of pharmaceutical drugs and is highly susceptible to injury from these substances. The etiology of drug induced liver disease is still debated although generally regarded as a continuum between an activated immune response and hepatocyte metabolic dysfunction, most often resulting from an intermediate reactive metabolite. This debate stems from the fact that current animal and in vitro models provide limited physiologically relevant information and their shortcomings have resulted in ‘silent’ hepatotoxic drugs being introduced into clinical trials, garnering huge financial losses for drug companies through withdrawals and late stage clinical failures. As we advance our understanding into the molecular processes leading to liver injury, it is increasingly clear that a) the pathologic lesion is not only due to liver parenchyma but is also due to the interactions between the hepatocytes and the resident liver immune cells, stellate cells and endothelial cells; and, b) animal models do not reflect the human cell interactions. Therefore, a predictive human, in vitro model must address the interactions between the major human liver cell types and measure key determinants of injury such as the dosage and metabolism of the drug, the stress response, cholestatic effect, and the immune and fibrotic response. In this mini-review, we first discuss the current state of macro-scale in vitro liver culture systems with examples that have been commercialized. We then introduce the paradigm of microfluidic culture systems that aim to mimic the liver with physiologically relevant dimensions, cellular structure, perfusion and mass transport by taking advantage of micro and nanofabrication technologies. We review the most prominent liver-on-a-chip platforms in terms of their physiological relevance and drug response. We conclude with a commentary on other critical advances such as the deployment of

  3. Diagnosis and Management of Alcoholic Liver Disease

    PubMed Central

    Dugum, Mohannad; McCullough, Arthur

    2015-01-01

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials. PMID:26356792

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

    PubMed

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

    2015-08-28

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

  5. The failure of earthquake failure models

    USGS Publications Warehouse

    Gomberg, J.

    2001-01-01

    In this study I show that simple heuristic models and numerical calculations suggest that an entire class of commonly invoked models of earthquake failure processes cannot explain triggering of seismicity by transient or "dynamic" stress changes, such as stress changes associated with passing seismic waves. The models of this class have the common feature that the physical property characterizing failure increases at an accelerating rate when a fault is loaded (stressed) at a constant rate. Examples include models that invoke rate state friction or subcritical crack growth, in which the properties characterizing failure are slip or crack length, respectively. Failure occurs when the rate at which these grow accelerates to values exceeding some critical threshold. These accelerating failure models do not predict the finite durations of dynamically triggered earthquake sequences (e.g., at aftershock or remote distances). Some of the failure models belonging to this class have been used to explain static stress triggering of aftershocks. This may imply that the physical processes underlying dynamic triggering differs or that currently applied models of static triggering require modification. If the former is the case, we might appeal to physical mechanisms relying on oscillatory deformations such as compaction of saturated fault gouge leading to pore pressure increase, or cyclic fatigue. However, if dynamic and static triggering mechanisms differ, one still needs to ask why static triggering models that neglect these dynamic mechanisms appear to explain many observations. If the static and dynamic triggering mechanisms are the same, perhaps assumptions about accelerating failure and/or that triggering advances the failure times of a population of inevitable earthquakes are incorrect.

  6. Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts.

    PubMed

    Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

    2015-01-01

    During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that's constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

  7. Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?

    PubMed

    Kim, Kyung-Hyun; Park, Kwan-Kyu

    2014-10-28

    Chronic liver diseases with different aetiologies rely on the chronic activation of liver injuries which result in a fibrogenesis progression to the end stage of cirrhosis and liver failure. Based on the underlying cellular and molecular mechanisms of a liver fibrosis, there has been proposed several kinds of approaches for the treatment of liver fibrosis. Recently, liver gene therapy has been developed as an alternative way to liver transplantation, which is the only effective therapy for chronic liver diseases. The activation of hepatic stellate cells, a subsequent release of inflammatory cytokines and an accumulation of extracellular matrix during the liver fibrogenesis are the major obstacles to the treatment of liver fibrosis. Several targeted strategies have been developed, such as antisense oligodeoxynucleotides, RNA interference and decoy oligodeoxynucleotides to overcome this barriers. With this report an overview will be provided of targeted strategies for the treatment of liver cirrhosis, and particularly, of the targeted gene therapy using short RNA and DNA segments.

  8. Biomarkers for liver fibrosis

    SciTech Connect

    Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

    2015-09-15

    Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

  9. Liver stiffness measurements by means of supersonic shear imaging in patients without known liver pathology.

    PubMed

    Sirli, Roxana; Bota, Simona; Sporea, Ioan; Jurchis, Ana; Popescu, Alina; Gradinaru-Tascău, Oana; Szilaski, Milana

    2013-08-01

    We used supersonic shear imaging to determine the liver stiffness (LS) values of 82 patients without known liver pathology and studied the factors that influence these measurements. Five LS measurements were made in each subject, and the median value, expressed in kilopascals, was calculated. Reliable LS measurements were obtained in 84.5% of patients. Higher body mass index and older age were associated with failure to obtain reliable measurements. The mean value of LS measurements determined by SSI in our cohort of patients without known liver pathology was 6 ± 1.4 kPa. The mean LS measurements determined by SSI for men were significantly higher than those for women; body mass index did not significantly influence SSI measurements. Thus, 6 kPa is the mean SSI value in patients without known liver pathology, with higher values being obtained in men.

  10. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia.

    PubMed

    Fukui, Hiroshi

    2015-03-27

    A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

  11. Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

    A “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

  12. Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

    PubMed Central

    ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

    2015-01-01

    Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

  13. Liver transplantation: Current status and challenges

    PubMed Central

    Jadlowiec, Caroline C; Taner, Timucin

    2016-01-01

    Great progress has been made in the field of liver transplantation over the past two decades. This progress, however, also brings up the next set of challenges: First, organ shortage remains a major limitation, and accounts for a large proportion of wait list mortality. While living donation has successfully increased the total number of liver transplants done in Asian countries, the total number of such transplants has been stagnant in the western hemisphere. As such, there has been a significant effort over the past decade to increase the existing deceased donor pool. This effort has resulted in a greater use of liver allografts following donation after cardiac death (DCD) along with marginal and extended criteria donors. Improved understanding of the pathophysiology of liver allografts procured after circulatory arrest has not only resulted in better selection and management of DCD donors, but has also helped in the development of mechanical perfusion strategies. Early outcomes demonstrating the clinical applicability of both hypothermic and normothermic perfusion and its potential to impact patient survival and allograft function have generated much interest. Second, long-term outcomes of liver transplant recipients have not improved significantly, as recipients continue to succumb to complications of long-term immunosuppression, such as infection, malignancy and renal failure. Furthermore, recent evidence suggests that chronic immune-mediated injury to the liver may also impact graft function. PMID:27182155

  14. Molecular mechanisms underlying chemical liver injury

    PubMed Central

    Gu, Xinsheng; Manautou, Jose E.

    2013-01-01

    The liver is necessary for survival. Its strategic localisation, blood flow and prominent role in the metabolism of xenobiotics render this organ particularly susceptible to injury by chemicals to which we are ubiquitously exposed. The pathogenesis of most chemical-induced liver injuries is initiated by the metabolic conversion of chemicals into reactive intermediate species, such as electrophilic compounds or free radicals, which can potentially alter the structure and function of cellular macromolecules. Many reactive intermediate species can produce oxidative stress, which can be equally detrimental to the cell. When protective defences are overwhelmed by excess toxicant insult, the effects of reactive intermediate species lead to deregulation of cell signalling pathways and dysfunction of biomolecules, leading to failure of target organelles and eventual cell death. A myriad of genetic factors determine the susceptibility of specific individuals to chemical-induced liver injury. Environmental factors, lifestyle choices and pre-existing pathological conditions also have roles in the pathogenesis of chemical liver injury. Research aimed at elucidating the molecular mechanism of the pathogenesis of chemical-induced liver diseases is fundamental for preventing or devising new modalities of treatment for liver injury by chemicals. PMID:22306029

  15. Perioperative monitoring in liver transplant patients.

    PubMed

    Singh, Shweta; Nasa, Vaibhav; Tandon, Manish

    2012-09-01

    Liver transplant (LT) is a major surgical undertaking involving major fluid shifts, hemodynamic instability and metabolic derangements in a patient with preexisting liver failure and multisystemic derangements. Monitoring and organ support initiated in the preoperative phase is continued intraoperatively and into the postoperative phase to ensure an optimal outcome. As cardiovascular events are the leading cause of non-graft related death among LT recipients, major emphasis is placed on cardiovascular monitoring. The other essential monitoring are the continuous assessment of coagulapathy, extent of metabolic derangements, dyselectrolytemis and intracranial pressure monitoring in patients with fulminant hepatic failure. The type and extent of monitoring differs with need according to preexisting child status of the patient and the extent of systemic derangements. It also varies among transplant centers and is mainly determined by individual or institutional practices.

  16. Perioperative monitoring in liver transplant patients.

    PubMed

    Singh, Shweta; Nasa, Vaibhav; Tandon, Manish

    2012-09-01

    Liver transplant (LT) is a major surgical undertaking involving major fluid shifts, hemodynamic instability and metabolic derangements in a patient with preexisting liver failure and multisystemic derangements. Monitoring and organ support initiated in the preoperative phase is continued intraoperatively and into the postoperative phase to ensure an optimal outcome. As cardiovascular events are the leading cause of non-graft related death among LT recipients, major emphasis is placed on cardiovascular monitoring. The other essential monitoring are the continuous assessment of coagulapathy, extent of metabolic derangements, dyselectrolytemis and intracranial pressure monitoring in patients with fulminant hepatic failure. The type and extent of monitoring differs with need according to preexisting child status of the patient and the extent of systemic derangements. It also varies among transplant centers and is mainly determined by individual or institutional practices. PMID:25755443

  17. Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model

    PubMed Central

    Abe, Hiroyuki; Kamimura, Kenya; Kobayashi, Yuji; Ohtsuka, Masato; Miura, Hiromi; Ohashi, Riuko; Yokoo, Takeshi; Kanefuji, Tsutomu; Suda, Takeshi; Tsuchida, Masanori; Aoyagi, Yutaka; Zhang, Guisheng; Liu, Dexi; Terai, Shuji

    2016-01-01

    Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of ~5 pg/ml (P < 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P < 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis. PMID:26730813

  18. Antioxidants in liver health

    PubMed Central

    Casas-Grajales, Sael; Muriel, Pablo

    2015-01-01

    Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

  19. Liver (Hepatocellular) Cancer Prevention

    MedlinePlus

    ... Liver cancer is not common in the United States. Liver cancer is the fourth most common cancer and the third leading cause of cancer death in the world. In the United States, men, especially Chinese American men, have an increased ...

  20. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  1. High liver glycogen in hereditary fructose intolerance

    PubMed Central

    Cain, A. R. R.; Ryman, Brenda E.

    1971-01-01

    A case of hereditary fructose intolerance is reported in a girl aged 2 years at the time of her death. She had apparently progressed normally until the age of 14 months. At 19 months she was admitted to hospital with failure to thrive, hepatomegaly, and superficial infections. Investigations revealed hypoglycaemia, persistent acidosis, aminoaciduria, and a high liver glycogen level which suggested that she had glycogen storage disease. There was also some evidence of malabsorption. At necropsy the liver enzyme estimations showed that fructose 1-phosphate aldolase activity was absent and that fructose 1,6-diphosphate aldolase activity was reduced. Hereditary fructose intolerance and glycogen storage disease have been confused in the past on clinical grounds, but a high liver glycogen level has not previously been reported in hereditary fructose intolerance. PMID:5289293

  2. Orthotropic liver transplantation for intractable neurological manifestations of Wilson's disease.

    PubMed

    Sutariya, Vaibhav K; Tank, Anad H; Modi, Pranjal R

    2015-01-01

    Wilson's disease (WD) is an inherited autosomal recessive disorder characterized by copper accumulation and toxicity, affecting mainly the liver and brain. Orthotopic liver transplantation (OLT) is the definitive therapy for patients with WD. Acute fulminant hepatic failure and decompensated cirrhosis are well-established indications for OLT. Patients with severe neurologic impairment can also be benefited by OLT. Here, we present a patient who underwent OLT for isolated neurological WD.

  3. Acute nontraumatic liver lesions.

    PubMed

    Caremani, Marcello; Tacconi, Danilo; Lapini, Laura

    2013-11-26

    The principal conditions requiring emergency/urgent intervention in patients with nontraumatic liver lesions are hemorrhage (with or without tumor rupture), rupture of hydatid cysts (with or without infection), complications arising from liver abscesses or congenital liver cysts, rupture related to peliosis hepatis, and in rare cases spontaneous hemorrhage. This article examines each of these conditions, its appearance on ultrasound (the first-line imaging method of choice for assessing any urgent nontraumatic liver lesion) and indications for additional imaging studies.

  4. Percutaneous liver biopsy.

    PubMed

    Rustagi, Tarun; Newton, Eric; Kar, Premashish

    2010-01-01

    Percutaneous liver biopsy has been performed for more than 120 years, and remains an important diagnostic procedure for the management of hepatobiliary disorders. Modern biochemical, immunologic, and radiographic techniques have facilitated the diagnosis and management of liver diseases but have not made liver biopsy obsolete. This comprehensive review article will discuss the history of development of percutaneous liver biopsy, its indications, contraindications, complications and the various aspects of the biopsy procedure in detail.

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

    PubMed

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

    2015-01-01

    Introdução: A falência hepática aguda é uma doença rara associada a elevada morbilidade e mortalidade apesar do aumento da sobrevida devido ao transplante hepático. Em 2008, decorreu em Portugal uma reunião sobre esta patologia em pediatria, resultando num consenso de atuação que salientou a importância da abordagem multidisciplinar e referenciação precoce para um centro de transplantação hepática. Objetivos: Caracterizar as admissões por falência hepática aguda no Serviço de Cuidados Intensivos Pediátricos do centro português com transplante hepático pediátrico. Comparar resultados antes (A) e depois de 2008 (B). Material e Métodos: Estudo observacional retrospetivo de 20 anos (1994-2014). Critérios de inclusão: idade < 18 anos e falência hepática aguda (INR ≥ 2 sem resposta à vitamina K e necrose hepatocelular). Excluíram-se as crianças com doença hepática crónica. Resultados: Incluíram-se 50 crianças com idade mediana de 24,5 meses. A causa mais comum de falência hepática aguda abaixo dos 2 anos foi metabólica (34,6%) e acima infeciosa (29,2%). Foram submetidos a transplante hepático 46%, tendo sobrevivido 78%. A mortalidade global foi 34%. A mediana do tempo de referenciação foi 7 dias no período A (n = 35) e 2 no B (n = 15; p = 0,006). A mediana do risco de mortalidade prevista pelo PRISM foi 14,7% no período A e 6,5% no B (p = 0,019). A mortalidade foi 37% vs 26% no período A e B respetivamente (p = 0,474).Discussão e Conclusões: A mortalidade global foi sobreponível à de outros centros europeus, sendo o transplante hepático a opção terapêutica mais eficaz. Após 2008 o tempo de referenciação e a gravidade dos casos na admissão reduziram, ainda sem tradução significativa na mortalidade.

  6. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

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

    2013-01-15

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

  7. Imaging in liver transplantation

    PubMed Central

    Caruso, Settimo; Miraglia, Roberto; Maruzzelli, Luigi; Gruttadauria, Salvatore; Luca, Angelo; Gridelli, Bruno

    2009-01-01

    The aim of this study was to illustrate the role of non-invasive imaging tools such as ultrasonography, multi-detector row computed tomography, and magnetic resonance imaging in the evaluation of pediatric and adult liver recipients and potential liver donors, and in the detection of potential complications arising from liver transplantation. PMID:19222090

  8. Duralumin - Defects and Failures

    NASA Technical Reports Server (NTRS)

    Nelson, WM

    1927-01-01

    It is proposed in this paper to identify some of the defects and failures in duralumin most frequently encountered by the aircraft industry with a view to indicate their importance. The defects and failures in duralumin may be classified into the following groups: 1) defects produced during manufacture; 2) defects produced during fabrication; 3) corrosion and erosion; and 4) fatigue failures. Only the first two will be covered in this report.

  9. Posttransplant Sarcopenia: An Underrecognized Early Consequence of Liver Transplantation

    PubMed Central

    Dasarathy, Srinivasan

    2014-01-01

    Liver transplantation is believed to reverse the clinical and metabolic abnormalities of cirrhosis. Reduced skeletal muscle mass or sarcopenia contributes to increased mortality and adverse consequences of cirrhosis. Failure of reversal of sarcopenia of cirrhosis after liver transplantation is not well recognized. Six temporally, geographically, and methodologically distinct follow-up studies in 304 cirrhotics reported conflicting data on changes in indirect measures of skeletal muscle mass after transplantation. Distinct measures of body composition but not skeletal muscle mass were used and did not focus on the clinical consequences of sarcopenia after transplantation. A number of studies reported an initial rapid postoperative loss of lean mass followed by incomplete recovery with a maximum follow-up of 2 years. Posttransplant sarcopenia may be responsible for metabolic syndrome and impaired quality of life after liver transplantation. Potential reasons for failure to reverse sarcopenia after liver transplantation include use of immunosuppressive agents [mammalian target of rapamycin (mTOR) and calcineurin inhibitors] that impair skeletal muscle growth and protein accretion. Repeated hospitalizations, posttransplant infections, and renal failure also contribute to posttransplant sarcopenia. Finally, recovery from muscle deconditioning is limited by lack of systematic nutritional and physical-activity-based interventions to improve muscle mass. Despite the compelling data on sarcopenia before liver transplantation, the impact of posttransplant sarcopenia on clinical outcomes is not known. There is a compelling need for studies to examine the mechanisms and consequences of sarcopenia post liver transplantation to permit development of therapies to prevent and reverse this disorder. PMID:23912247

  10. Fulminant Wilson's Disease Managed with Plasmapheresis as a Bridge to Liver Transplant.

    PubMed

    Hilal, Talal; Morehead, R Scott

    2014-01-01

    New-onset jaundice can be a manifestation of multiple pathologic processes including hemolysis, parenchymal liver disease, and cholestasis; the differential diagnosis is broad and requires a systematic approach. We report a case of a patient who presented with jaundice after starting minocycline for the treatment of acne vulgaris and rapidly developed fulminant liver failure found to be due to Wilson's disease. She also manifested severe Coomb's negative hemolytic anemia and renal failure secondary to hepatorenal syndrome. As a bridge to liver transplant, she was successfully treated with plasmapheresis to decrease serum copper in addition to hemodialysis for acidosis and hyperkalemia. She was able to receive a liver and made a full recovery. The case highlights the use of plasmapheresis as an adjunctive treatment modality in cases of fulminant liver failure due to Wilson's disease.

  11. Fulminant Wilson's Disease Managed with Plasmapheresis as a Bridge to Liver Transplant

    PubMed Central

    Morehead, R. Scott

    2014-01-01

    New-onset jaundice can be a manifestation of multiple pathologic processes including hemolysis, parenchymal liver disease, and cholestasis; the differential diagnosis is broad and requires a systematic approach. We report a case of a patient who presented with jaundice after starting minocycline for the treatment of acne vulgaris and rapidly developed fulminant liver failure found to be due to Wilson's disease. She also manifested severe Coomb's negative hemolytic anemia and renal failure secondary to hepatorenal syndrome. As a bridge to liver transplant, she was successfully treated with plasmapheresis to decrease serum copper in addition to hemodialysis for acidosis and hyperkalemia. She was able to receive a liver and made a full recovery. The case highlights the use of plasmapheresis as an adjunctive treatment modality in cases of fulminant liver failure due to Wilson's disease. PMID:25276143

  12. Fulminant Wilson's disease requiring liver transplantation in one monozygotic twin despite identical genetic mutation.

    PubMed

    Kegley, K M; Sellers, M A; Ferber, M J; Johnson, M W; Joelson, D W; Shrestha, R

    2010-05-01

    Acute decompensated Wilson's disease (WD) that presents as fulminant hepatic failure carries significant mortality without hepatic replacement. The abnormal gene implicated in WD, ATP7B, has been mapped to chromosome 13, and leads to decreased passage of copper from hepatocytes to bile. Excess copper accumulation exceeds hepatocyte storage capacity resulting in intracellular necrosis, apoptosis and cell death in various organs of the body. The hepatic injury induced by the abnormal accumulation of copper in WD has variable presentation such as acute hepatitis, rapid hepatic deterioration resembling fulminant hepatic failure, or as progressive chronic liver disease in the form of chronic active hepatitis or cirrhosis. There are reports in the literature describing monozygotic (identical) twins with similar hepatic progression requiring liver transplantation, however, with different neurological outcome after transplant. We report a case of one monozygotic twin presenting with acute liver failure requiring emergent liver transplantation while the other twin presented with mild liver disease, when both shared an identical genetic mutation.

  13. Resetting the transcription factor network reverses terminal chronic hepatic failure.

    PubMed

    Nishikawa, Taichiro; Bell, Aaron; Brooks, Jenna M; Setoyama, Kentaro; Melis, Marta; Han, Bing; Fukumitsu, Ken; Handa, Kan; Tian, Jianmin; Kaestner, Klaus H; Vodovotz, Yoram; Locker, Joseph; Soto-Gutierrez, Alejandro; Fox, Ira J

    2015-04-01

    The cause of organ failure is enigmatic for many degenerative diseases, including end-stage liver disease. Here, using a CCl4-induced rat model of irreversible and fatal hepatic failure, which also exhibits terminal changes in the extracellular matrix, we demonstrated that chronic injury stably reprograms the critical balance of transcription factors and that diseased and dedifferentiated cells can be returned to normal function by re-expression of critical transcription factors, a process similar to the type of reprogramming that induces somatic cells to become pluripotent or to change their cell lineage. Forced re-expression of the transcription factor HNF4α induced expression of the other hepatocyte-expressed transcription factors; restored functionality in terminally diseased hepatocytes isolated from CCl4-treated rats; and rapidly reversed fatal liver failure in CCl4-treated animals by restoring diseased hepatocytes rather than replacing them with new hepatocytes or stem cells. Together, the results of our study indicate that disruption of the transcription factor network and cellular dedi