WorldWideScience

Sample records for cholestatic liver failure

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  2. A case of cholestatic autoimmune hepatitis and acute liver failure: an unusual hepatic manifestation of mixed connective tissue disease and Sjögren's syndrome.

    OpenAIRE

    Min, J. K.; Han, N. I.; Kim, J. A; Lee, Y. S.; Cho, C.S.; Kim, H. Y.

    2001-01-01

    Although hepatomegaly is reported to occur occasionally in patients with mixed connective tissue disease (MCTD) or Sjögren's syndrome (SS), autoimmune liver diseases such as primary biliary cirrhosis, sclerosing cholangitis, and autoimmune hepatitis in association with MCTD or SS have rarely been described. We report a case of severe cholestatic autoimmune hepatitis presenting with acute liver failure in a 40-yr-old female patient suffering from MCTD and SS. The diagnosis of MCTD and SS was m...

  3. Nutrition for children with cholestatic liver disease

    NARCIS (Netherlands)

    Los, E. Leonie; Lukovac, Sabina; Werner, Anniek; Dijkstra, Tietie; Verkade, Henkjan J.; Rings, Edmond H. H. M.; Cooke, RJ; Vandenplas, Y; Wahn, U

    2007-01-01

    Cholestatic liver disease (CLD) in children negatively affects nutritional status, growth and development, which all lead to an increased risk of morbidity and mortality. This is illustrated by the fact that the clinical outcome of children with CLD awaiting a liver transplantation is in part predic

  4. Cholestatic liver disease masquerading as Wilson disease.

    Science.gov (United States)

    Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev; Alam, Seema

    2015-03-01

    Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.

  5. Utility of Noninvasive Markers of Fibrosis in Cholestatic Liver Diseases.

    Science.gov (United States)

    Corpechot, Christophe

    2016-02-01

    Methods of liver fibrosis assessment have changed considerably in the last 20 years, and noninvasive markers now have been recognized as major first-line tools in the management of patients with chronic viral hepatitis infection. But what about the efficiency and utility of these surrogate indices for the more uncommon chronic cholestatic liver diseases, namely primary biliary cirrhosis and primary sclerosing cholangitis? This article provides clinicians with a global overview of what is currently known in the field. Both diagnostic and prognostic aspects of noninvasive markers of fibrosis in cholestatic liver diseases are presented and discussed.

  6. Recurrence of cholestatic liver disease after living donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Sumihito Tamura; Masatoshi Hakuuchi; Yasuhiko Sugawara; Junichi Kaneko; Junichi Togashi; Yuichi Matsui; Noriyo Yamashiki; Norihiro Kokudo

    2008-01-01

    End-stage liver disease,due to cholestatic liver diseases with an autoimmune background such as primary biliary cirrhosis(PBC)and primary sclerosing cholangitis(PSC),is considered a good indication for liver transplantation.Excellent overall patient and graft outcomes,based mostly on the experience from deceased donor liver ransplantation(DDLT),have been reported.Due to the limited number of oraan donations from deceased donors in most Asian countries,living donor liver transplantation(LDLT)is the mainstream treatment for end-stage liver disease,including that resulting from PBC and PSC.Although the initial experiences with LDLT for PBC and PSC seem satisfactory or comparable to that with DLT,some aspects,including the timing of transplantation,the risk of recurrent disease,and its long-term clinical implications,require further evaluation.Whether or not the long-term outcomes of LDLT from a biologically related donor are equivalent to that of DDLT requires further observations.The clinical course following LDLT may be affected by he genetic background shared between the recipient and the living related donor.(C)2008 The WJG Press.All rights reserved.

  7. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications.

    Science.gov (United States)

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-08-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  8. Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver transplantation

    Science.gov (United States)

    Hori, Tomohide; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Ogura, Yasuhiro

    2016-01-01

    Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review.

  9. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus

    Institute of Scientific and Technical Information of China (English)

    Maud Lemoine; Aurélie Revaux; Claire Francoz; Guillaume Ducarme; Sabine Brechignac; Emmanuel Jacquemin; Michèle Uzan; Nathalie Ganne-Carrié

    2008-01-01

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of HARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.C 2008 The WJG Press. All rights reserved.

  10. Antioxidant enzyme activities in hepatic tissue from children with chronic cholestatic liver disease

    Directory of Open Access Journals (Sweden)

    Ismail Nagwa

    2010-01-01

    Full Text Available Background/Aim: To study the oxidative stress status in children with cholestatic chronic liver disease by determining activities of glutathione peroxidase (GPx, superoxide dismutase (SOD and catalase (CAT in liver tissue. Materials and Methods: A total of 34 children suffering from cholestatic chronic liver disease were studied. They were selected from the Hepatology Clinic, Cairo University, and compared with seven children who happened to have incidental normal liver biopsy. The patients were divided into three groups: extrahepatic biliary atresia (n=13, neonatal hepatitis (n=15 and paucity of intrahepatic bile ducts (n=6; GPx, SOD and CAT levels were measured in fresh liver tissue using ELISA . Results: In the cholestatic patients, a significant increase was found in mean levels of SOD, GPx and CAT in hepatic tissue compared to control children. The three enzymes significantly increased in the extrahepatic biliary atresia group, whereas in the groups of neonatal hepatitis and paucity of intrahepatic bile ducts, only GPx and CAT enzymes were significantly increased. Conclusion: Oxidative stress could play a role in the pathogenesis of cholestatic chronic liver diseases. These preliminary results are encouraging to conduct more extensive clinical studies using adjuvant antioxidant therapy.

  11. Xenobiotic-sensing nuclear receptors CAR and PXR as drug targets in cholestatic liver disease.

    Science.gov (United States)

    Kakizaki, Satoru; Takizawa, Daichi; Tojima, Hiroki; Yamazaki, Yuichi; Mori, Masatomo

    2009-11-01

    Cholestasis results in the intrahepatic retention of cytotoxic bile acid and it can thus lead to liver injury and/or liver fibrosis. Cholestatic liver damage is counteracted by a variety of intrinsic hepatoprotective mechanisms including a complex network of drug metabolizing enzymes and transporters. During the last decade, much progress has been made in dissecting the mechanisms which regulate the hepatic xeno- and endobiotic metabolism by nuclear receptors. The xenobiotic receptors CAR and PXR are two important members of the NR1I nuclear receptor family. They function as sensors of toxic byproducts derived from the endogenous metabolism and of exogenous chemicals, in order to enhance their elimination. Ligands for both receptors, including phenobarbital, have already been used to treat cholestatic liver diseases before the mechanisms of these receptors were revealed. Furthermore, Yin Zhi Huang, a traditional Chinese herbal medicine, which has been used to prevent and treat neonatal jaundice, was identified to be a CAR ligand which also accelerates bilirubin clearance. Therefore, CAR and PXR have a protective effect on cholestasis by activating both detoxification enzymes and transporters. As a result, novel compounds targeting CAR and PXR with specific effects and fewer side effects will therefore be useful for the treatment of cholestatic liver diseases. This article will review the current knowledge on xenobiotic-sensing nuclear receptors CAR and PXR, while also discussing their potential role in the treatment of cholestatic liver diseases. PMID:19925451

  12. Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

    Science.gov (United States)

    Zhang, Shuai; Li, Tao-Sheng; Soyama, Akihiko; Tanaka, Takayuki; Yan, Chen; Sakai, Yusuke; Hidaka, Masaaki; Kinoshita, Ayaka; Natsuda, Koji; Fujii, Mio; Kugiyama, Tota; Baimakhanov, Zhassulan; Kuroki, Tamotsu; Gu, Weili; Eguchi, Susumu

    2016-01-01

    Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the PH and sham groups 14 days after operation. However, compared with those in the sham group, the livers in mice in the PH+BDL group had a smaller size, a lower cell proliferative activity, and more fibrotic tissue 14 days after the operation, suggesting the insufficient regeneration of the cholestatic liver. Pathway-focused array analysis showed that many genes were up- or down-regulated over 1.5-fold in both PH+BDL and PH groups at 1, 3, 7, and 14 days after treatment. Interestingly, more genes that were functionally related to the extracellular matrix and inflammatory chemokines were found in the PH+BDL group than in the PH group at 7 and 14 days after treatment. Our data suggest that up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver.

  13. Up-regulated extracellular matrix components and inflammatory chemokines may impair the regeneration of cholestatic liver

    OpenAIRE

    Shuai Zhang; Tao-Sheng Li; Akihiko Soyama; Takayuki Tanaka; Chen Yan; Yusuke Sakai; Masaaki Hidaka; Ayaka Kinoshita; Koji Natsuda; Mio Fujii; Tota Kugiyama; Zhassulan Baimakhanov; Tamotsu Kuroki; Weili Gu; Susumu Eguchi

    2016-01-01

    Although the healthy liver is known to have high regenerative potential, poor liver regeneration under pathological conditions remains a substantial problem. We investigated the key molecules that impair the regeneration of cholestatic liver. C57BL/6 mice were randomly subjected to partial hepatectomy and bile duct ligation (PH+BDL group, n = 16), partial hepatectomy only (PH group, n = 16), or sham operation (Sham group, n = 16). The liver sizes and histological findings were similar in the ...

  14. The Role of Bile Salt Export Pump Gene Repression in Drug-Induced Cholestatic Liver Toxicity

    OpenAIRE

    Garzel, Brandy; Yang, Hui; Zhang, Lei; Huang, Shiew-Mei; Polli, James E.; Wang, Hongbing

    2014-01-01

    The bile salt export pump (BSEP, ABCB11) is predominantly responsible for the efflux of bile salts, and disruption of BSEP function is often associated with altered hepatic homeostasis of bile acids and cholestatic liver injury. Accumulating evidence suggests that many drugs can cause cholestasis through interaction with hepatic transporters. To date, a relatively strong association between drug-induced cholestasis and attenuated BSEP activity has been proposed. However, whether repression of...

  15. Fibrosing Cholestatic Hepatitis in a Complicated Case of an Adult Recipient After Liver Transplantation: Diagnostic Findings and Therapeutic Dilemma

    Science.gov (United States)

    Hori, Tomohide; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Ogura, Yasuhiro

    2016-01-01

    Patient: Male, 66 Final Diagnosis: Fibrosing cholestatic hepatitis Symptoms: Prolonged jaundice and intractable ascites Medication: Steroid pulse therapy and direct-acting antivirals Clinical Procedure: Liver transplantation Specialty: Transplantology Objective: Challenging differential diagnosis Background: Hepatitis C recurrence is a serious matter after liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV) positive recipients develop fibrosing cholestatic hepatitis (FCH). FCH rapidly results in graft loss. Currently, direct-acting antivirals (DAAs) are effective and safe for hepatitis C, even after LT. However, only a few cases of successfully treated FCH after LT have been reported. We present FCH in a complicated case with sepsis and portal flow obstruction after LT. Case Report: A 66-year-old man underwent cadaveric LT. Liver function disorders were observed from post-operative day (POD) 22. Sepsis repeated on POD 38, 74, and 101. Steroid pulse therapy was given from POD 40 to 54. The infectious focus was surgically removed on POD 89. Interventional radiology for portal venous obstruction was completed on POD 96. To make a real-time diagnosis and to investigate the graft condition, repeat liver needle biopsies (LNBs) were taken. Although there was a combined impact of sepsis, portal flow decrease, and recurrent hepatitis C on graft failure, it was interesting that recurrent hepatitis C was consistently detectable from the first LNB. HCV-ribonucleic acid increased on POD 68. Liver function disorders peaked on POD 71 and 72. Jaundice peaked on POD 82. DAA induction was regrettably delayed because of a reluctance to introduce DAAs under conditions of graft dysfunction. DAAs were administered after hospital discharge. Conclusions: A real-time and precise diagnosis based on histopathological examination and viral measurement is important for FCH treatment. Well-considered therapy with DAAs should be aggressively introduced for potentially fatal

  16. Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival in Patients with Cholestatic Liver Diseases

    Science.gov (United States)

    Wunsch, Ewa; Krawczyk, Marcin; Milkiewicz, Malgorzata; Trottier, Jocelyn; Barbier, Olivier; Neurath, Markus F.; Lammert, Frank; Kremer, Andreas E.; Milkiewicz, Piotr

    2016-01-01

    Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and liver injury. We aimed to investigate whether ATX is an indicator of cholestatic liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1–60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with liver biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as a predictor of survival. PMID:27506882

  17. Chinese Expert Consensus for the Diagnosis and Treatment of Cholestatic Liver Disease

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Cholestatic liver disease (CLD) is a common problem in clinical practice with the main manifestation being cholestasis.Recently,there has been a steady increase in knowledge associated with the diagnosis and treatment of CLD.Therefore,the experts in China were organized by the editorial board of Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition),Chinese Journal of Liver Diseases (Electronic Edition) and Infection International (Electronic Edition) to collect and analyze relevant research,ultimately resulting in the development of this work (Chinese Expert consensus for the diagnosis and treatment of CLDs,also abbreviated as consensus).

  18. Endotoxin detoxification by alkaline phosphatase in cholestatic livers

    NARCIS (Netherlands)

    Poelstra, K; Bakker, WW; Hardonk, MJ; Meijer, DKF; Wisse, E; Knook, DL; Balabaud, C

    1997-01-01

    Increased expression of alkaline phosphatase (AP) in the liver is a hallmark of cholestasis but the pathophysiological role of this is not clear. We argue that deprotonation of carboxyl groups at the active site of the enzyme may be a prerequisite for optimal AP activity. Such a creation of negative

  19. Acute liver failure

    DEFF Research Database (Denmark)

    Larsen, Fin Stolze; Bjerring, Peter Nissen

    2011-01-01

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

  20. Risk Factors for Development of Cholestatic Drug-Induced Liver Injury: Inhibition of Hepatic Basolateral Bile Acid Transporters Multidrug Resistance-Associated Proteins 3 and 4

    OpenAIRE

    Köck, Kathleen; Ferslew, Brian C.; Netterberg, Ida; Yang, Kyunghee; Urban, Thomas J.; Swaan, Peter W.; Stewart, Paul W.; Brouwer, Kim L.R.

    2014-01-01

    Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). The multidrug resistance-associated proteins (MRP) 3 and 4 are postulated to be compensatory hepatic basolateral bile acid efflux transporters when biliary excretion by the bile salt export pump (BSEP) is impaired. BSEP inhibition is a risk factor for cholestatic DILI. This study aimed to characterize the relationship between MRP3, MRP4, and BSEP inhibition and cholestatic potentia...

  1. Medical treatment of cholestatic liver diseases: From pathobiology to pharmacological targets

    Institute of Scientific and Technical Information of China (English)

    Gustav Paumgartner

    2006-01-01

    Bile secretion is dependent on the coordinated functions of a number of hepatobiliary transport systems.Cholestasis may be caused by an impairment of bile secretion, an obstruction of bile flow or a combination of the two. The common consequence of all forms of cholestasis is retention of bile acids and other potentially toxic compounds in the hepatocytes leading to apoptosis or necrosis of hepatocytes and eventually to chronic cholestatic liver disease. In certain cholestatic disorders there is also leakage of bile acids into the peribiliary space causing portal inflammation and fibrosis. The following pharmacological targets for treatment of intrahepatic cholestasis can be identified: stimulation of orthograde biliary secretion and retrograde secretion of bile acids and other toxic cholephils into the systemic circulation for excretion via the kidneys to reduce their retention in the hepatocytes; stimulation of the metabolism of hydrophobic bile acids and other toxic compounds to more hydrophilic, less toxic metabolites;protection of injured cholangiocytes against toxic effects of bile; inhibition of apoptosis caused by elevated levels of cytotoxic bile acids; inhibition of fibrosis caused by leakage of bile acids into the peribiliary space. The clinical results of ursodeoxcholic acid therapy of primary biliary cirrhosis may be regarded as the first success of this strategy.

  2. Tetrathiomolybdate protects against bile duct ligation-induced cholestatic liver injury and fibrosis.

    Science.gov (United States)

    Song, Ming; Song, Zhenyuan; Barve, Shirish; Zhang, Jingwen; Chen, Theresa; Liu, Marcia; Arteel, Gavin E; Brewer, George J; McClain, Craig J

    2008-05-01

    Tetrathiomolybdate (TM), a potent copper-chelating drug, was initially developed for the treatment of Wilson's disease. Our working hypothesis is that the fibrotic pathway is copper-dependent. Because biliary excretion is the major pathway for copper elimination, a bile duct ligation (BDL) mouse model was used to test the potential protective effects of TM. TM was given in a daily dose of 0.9 mg/mouse by means of intragastric gavage 5 days before BDL. All the animals were killed 5 days after surgery. Plasma liver enzymes and total bilirubin were markedly decreased in TM-treated BDL mice. TM also inhibited the increase in plasma levels of tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 seen in BDL mice. Cholestatic liver injury was markedly attenuated by TM treatment as shown by histology. Hepatic collagen deposition was significantly decreased, and it was paralleled by a significant suppression of hepatic smooth muscle alpha-actin and fibrogenic gene expression in TM-treated BDL mice. Although the endogenous antioxidant ability was enhanced, oxidative stress as shown by malondialdehyde and 4-hydroxyalkenals, hepatic glutathione/oxidized glutathione ratio, was not attenuated by TM treatment, suggesting the protective mechanism of TM may be independent of oxidative stress. In summary, TM attenuated BDL-induced cholestatic liver injury and fibrosis in mice, in part by inhibiting TNF-alpha and TGF-beta1 secretion. The protective mechanism seems to be independent of oxidative stress. Our data provide further evidence that TM might be a potential therapy for hepatic fibrosis.

  3. Acute liver failure

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  4. Successful treatment with sofosbuvir of fibrosing cholestatic hepatitis C after liver transplantation in an HIV-HCV-coinfected patient.

    Science.gov (United States)

    Borentain, Patrick; Colson, Philippe; Dhiver, Catherine; Gregoire, Emilie; Hardwigsen, Jean; Botta-Fridlund, Danielle; Garcia, Stéphane; Gerolami, René

    2015-01-01

    Fibrosing cholestatic hepatitis is a severe form of post-liver transplantation HCV recurrence. Fibrosing cholestatic hepatitis is characterized by its early onset and severe prognosis in HIV-infected patients. We report the case of an HIV-HCV genotype-4 coinfected patient successfully treated with a combination of sofosbuvir and ribavirin. After 4 weeks of treatment we observed a resolution of HCV recurrence related symptoms associated with a normalization of liver biochemistry and dramatic decrease of HCV viral load. This case illustrates the efficiency and tolerance of a sofosbuvir-based anti-HCV interferon-free regimen in post-liver HCV recurrence. Because of the absence of drug interactions between sofosbuvir and antiretroviral treatment or calcineurin inhibitors, its administration in HIV-HCV-coinfected liver transplanted patients is very promising.

  5. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: JLiu@kumc.edu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  6. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice.

    Science.gov (United States)

    Liu, Jie; Lu, Yuan-Fu; Zhang, Youcai; Wu, Kai Connie; Fan, Fang; Klaassen, Curtis D

    2013-11-01

    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential.

  7. [Nutrition and liver failure].

    Science.gov (United States)

    Plauth, M

    2013-06-01

    In the critically ill liver patient, nutrition support is not very different from that given for other illnesses. In hyperacute liver failure, nutrition support is of less importance than in the other subtypes of acute liver failure that take a more protracted course. Nasoenteral tube feeding using a polymeric standard formula should be the first-line approach, while parenteral nutrition giving glucose, fat, amino acids, vitamins, and trace elements is initiated when enteral nutrition is insufficient or impracticable. In chronic liver disease, notably cirrhosis, there is frequently protein malnutrition indicating a poor prognosis and requiring immediate initiation of nutrition support. Enteral nutrition ensuring an adequate provision of energy and protein should be preferred. Particular care should be taken to avoid refeeding syndrome and to treat vitamin and trace element deficiency.

  8. Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases

    Energy Technology Data Exchange (ETDEWEB)

    Kovač, Jelena Djokić, E-mail: jelenadjokic2003@yahoo.co.uk [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Daković, Marko [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Physical Chemistry, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Stanisavljević, Dejana [Institute for Statistics, Faculty of Medicine, University of Belgrade, Dr. Subotica 8, 11000 Belgrade (Serbia); Alempijević, Tamara; Ješić, Rada [Clinic for Gastroenterohepatology, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Seferović, Petar [Institute for Cardiovascular Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Pasterova 2, 11000 Belgrade (Serbia); Maksimović, Ružica [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade (Serbia)

    2012-10-15

    Purpose: To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. Materials and methods: Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b = 0, 50, 200, 400 and 800 s/mm{sup 2}. A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. Results: The mean ADCs (×10{sup −3} mm{sup 2}/s; b = 0–800 s/mm{sup 2}) were significantly different at stage F1 versus F ≥ 2 (p < 0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV = 9.54 ± 6.3%). Conclusion: DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution.

  9. S ciprofloksacinom povzročena holestatska okvara jeter: a case report: Ciprofloxacin-induced cholestatic liver injury: prikaz primera:

    OpenAIRE

    Ferlan-Marolt, Vera; Hafner, Matjaž; Kikec, Zdenko; Vujasinović, Miroslav

    2012-01-01

    Background: Drug-induced liver injury has been described for a large number ofdrugs. It is a common cause of drug withdrawal from the market. Ciprofloxacin is a commonly prescribed fluoroquinolone antibiotic and is a rare cause of hepatotoxicity. To our best knowledge this is the first case of ciprofloxacin-induced cholestatic liver injury in Slovenia. Case report: A 19year old man has been treated with ciprofloxacin at a daily dose of 500 mg twice a day due to a mild respiratory infection. A...

  10. Cephalexin Induced Cholestatic Jaundice

    OpenAIRE

    Abhinav Agrawal; Mana Rao; Sarfaraz Jasdanwala; Ajay Mathur; Margaret Eng

    2014-01-01

    Cephalexin is a very commonly prescribed orally administered antibiotic which has many potential side effects. Amongst these cholestatic jaundice has been infrequently reported as an adverse reaction. We present a case of a 57-year-old male who exhibited features of cholestatic jaundice including elevated liver function tests (LFTs) after taking cephalexin and showed improvement on removal of the offending agent. During this time he was symptomatically treated with cholestyramine. Complete re...

  11. Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

    International Nuclear Information System (INIS)

    Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility

  12. Pamidronate for the treatment of osteoporosis secondary to chronic cholestatic liver disease in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, F.A. [Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattar, R. [1Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Facincani, I. [Departamento de Pediatria e Neonatologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Ramalho, L.N.Z. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Jorgetti, V. [Departamento de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Volpon, J.B. [Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Paula, F.J.A. de [Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-09-14

    Osteoporosis is a major complication of chronic cholestatic liver disease (CCLD). We evaluated the efficacy of using disodium pamidronate (1.0 mg/kg body weight) for the prevention (Pr) or treatment (Tr) of cholestasis-induced osteoporosis in male Wistar rats: sham-operated (Sham = 12); bile duct-ligated (Bi = 15); bile duct-ligated animals previously treated with pamidronate before and 1 month after surgery (Pr = 9); bile duct-ligated animals treated with pamidronate 1 month after surgery (Tr = 9). Rats were sacrificed 8 weeks after surgery. Immunohistochemical expression of IGF-I and GH receptor was determined in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia and the right femur was used for biomechanical analysis. Bone material volume over tissue volume (BV/TV) was significantly affected by CCLD (Sham = 18.1 ± 3.2 vs Bi = 10.6 ± 2.2%) and pamidronate successfully increased bone volume. However, pamidronate administered in a preventive regimen presented no additional benefit on bone volume compared to secondary treatment (BV/TV: Pr = 39.4 ± 12.0; Tr = 41.2 ± 12.7%). Moreover, the force on the momentum of fracture was significantly reduced in Pr rats (Sham = 116.6 ± 23.0; Bi = 94.6 ± 33.8; Pr = 82.9 ± 22.8; Tr = 92.5 ± 29.5 N; P < 0.05, Sham vs Pr). Thus, CCLD had a significant impact on bone histomorphometric parameters and pamidronate was highly effective in increasing bone mass in CCLD; however, preventive therapy with pamidronate has no advantage regarding bone fragility.

  13. Acute liver failure and liver transplantation.

    Science.gov (United States)

    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

  14. Pyrazinamide Induced Rat Cholestatic Liver Injury through Inhibition of FXR Regulatory Effect on Bile Acid Synthesis and Transport.

    Science.gov (United States)

    Guo, Hong-Li; Hassan, Hozeifa M; Zhang, Yun; Dong, Si-Zhe; Ding, Ping-Ping; Wang, Tao; Sun, Li-Xin; Zhang, Lu-Yong; Jiang, Zhen-Zhou

    2016-08-01

    Pyrazinamide (PZA) is an indispensable first-line drug used for the treatment of tuberculosis which may cause serious hepatotoxicity; however, the mechanisms underlying these toxicities are poorly understood. Cholestasis plays an important role in drug-induced liver injury. Since there were no previous published works reported cholestasis and PZA hepatotoxicity relationship, this study aimed to identify whether PZA can induce liver injury with characterized evidences of cholestasis and to clarify expression changes of proteins related to both bile acid synthesis and transport in PZA-induced liver injury. PZA (2 g/kg) was administered for 7 consecutive days by oral gavage. Results showed there were 2-fold elevation in both ALT and AST serum levels in PZA-treated rats. In addition, a 10-fold increment in serum total bile acid was observed after PZA administration. The mRNA and protein expressions of bile acid synthesis and transport parameters were markedly altered, in which FXR, Bsep, Mrp2, Mdr2, Ostα/β, Oatp1a1, Oatp1b2, and Cyp8b1 were decreased (P < .05), while Mrp3, Ntcp, Oatp1a4, and Cyp7a1 were increased (P < .05). Moreover, treatment with the FXR agonist obeticholic acid (OCA) generated obvious reductions in serum ALT, AST, and TBA levels in PZA-treated rats. Those effects were due to transcriptional regulation of pre-mentioned target genes by OCA. Taken together, these results suggested that PZA-induced cholestatic liver injury was related to FXR inhibition, leading to the dysfunction in bile acid synthesis and transport. PMID:27255380

  15. Cross-activating invariant NKT cells and kupffer cells suppress cholestatic liver injury in a mouse model of biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Caroline C Duwaerts

    Full Text Available Both Kupffer cells and invariant natural killer T (iNKT cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry, mRNA expression (qtPCR, nitric oxide (NO (. production (Griess reaction, and protein secretion (cytometric bead-array or ELISAs were determined. To address the potential role of NO (. in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO (. , and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury.

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

    Directory of Open Access Journals (Sweden)

    Gabrielle B. Rocque

    2011-01-01

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

  17. Plasma Glutamine Concentrations in Liver Failure.

    Directory of Open Access Journals (Sweden)

    Gunnel Helling

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

  18. Nutritional support during liver failure.

    Science.gov (United States)

    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

  19. Repeated Oral Administration of Oleanolic Acid Produces Cholestatic Liver Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yasha Xu

    2013-03-01

    Full Text Available Oleanolic acid (OA is a triterpenoid and a fantastic molecule with many beneficial effects. However, high-doses and long-term use can produce adverse effects. This study aimed to characterize the hepatotoxic potential of OA. Mice were given OA at doses of 100–3,000 µmol/kg (45–1,350 mg/kg, po for 10 days, and the hepatotoxicity was determined by serum biochemistry, histopathology, and toxicity-related gene expression via real-time RT-PCR. Animal body weight loss was evident at OA doses of 1,000 µmol/kg and above. Serum alanine aminotransferase activities were increased in a dose-dependent manner, indicative of hepatotoxicity. Serum total bilirubin concentrations were increased, indicative of cholestasis. OA administration produced dose-dependent pathological lesions to the liver, including inflammation, hepatocellular apoptosis, necrosis, and feathery degeneration indicative of cholestasis. These lesions were evident at OA doses of 500 µmol/kg and above. Real-time RT-PCR revealed that OA produced dose-dependent increases in acute phase proteins (MT-1, Ho-1, Nrf2 and Nqo1, decreases in bile acid synthesis genes (Cyp7a1 and Cyp8b1, and decreases in liver bile acid transporters (Ntcp, Bsep, Oatp1a1, Oatp1b2, and Ostβ. Thus, the clinical use of OA and OA-type triterpenoids should balance the beneficial effects and toxicity potentials.

  20. Diagnostic and therapeutic approach to cholestatic liver disease Abordaje diagnóstico y terapéutico del síndrome colestásico

    Directory of Open Access Journals (Sweden)

    T. Pérez Fernández

    2004-01-01

    Full Text Available When cholestatic liver disease is present, liver ultrasound should be performed to ascertain if cholestasis is extrahepatic or intrahepatiic. If bile ducts appear dilated and the probability of interventional treatment is high, endoscopic retrograde cholagio-pancreatography (ERCP or trans-hepatic cholangiography (THC should be the next step. If the probability of interventional therapeutics is low, cholangio-MRI should be performed. Once bile duct dilation and space occupying lesions are excluded, a work up for intrahepatic cholestasis should be started. Some especific clinical situations may be helpful in the diagnostic strategy. If cholestasis occurs in the elderly, drug-induced cholestatic disease should be suspected, whereas if it occurs in young people with risk factors, cholestatic viral hepatitis is the most likely diagnosis. During the first trimester of pregnancy cholestasis may occur in hiperemesis gravidorum, and in the third trimester of gestation cholestasis of pregnancy should be suspected. A familial history of recurrent cholestasis points to benign recurrent intrahepatic cholestasis. The occurrence of intrahepatic cholestasis in a mid-dle-aged woman is a frequent presentation of primary biliary cirrhosis, whereas primary sclerosing cholangitis should be suspected in young males with inflammatory bowel disease. The presence of vascular spider nevi, ascites, and a history of alcohol abuse should point to alcoholic hepatitis. Neonatal cholestasis syndromes include CMV, toxoplasma and rubinfections or metabolic defects such as cystic fibrosis, α1-antitripsin deficiency, bile acid synthesis defects, or biliary atresia. The treatment of cholestasis should include a management of complications such as pruritus, osteopenia and correction of fat soluble vitamin deficiencies. When hepatocellular failure or portal hypertension-related complications occur, liver transplantation should be considered.Ante la presencia de colestasis, se debe

  1. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

    Full Text Available Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.HepG2.rNtcp cells were preconditioned (24 h with sub-apoptotic concentrations (0.1-50 μM of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h, menadione (50 μM, 6 h or cytokine mixture (CM; 6 h. Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11 and bile acid sensors, as well as intracellular GCDCA levels were analyzed.Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauroursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  2. The nutritional therapy of cholestatic liver disease in infants%婴儿胆汁淤积性肝病的营养治疗

    Institute of Scientific and Technical Information of China (English)

    黄志华; 李雪松

    2013-01-01

    There are various causes of cholestatic liver disease in infants that include extrahepatic biliary tract diseases, liver diseases, anatomical abnormality, metabolic or endocrine diseases, poisoning, infection, and so on. The causes leads to re-duction or interruption in bile lfow and thus results in nutrients malabsorption and comprehensive metabolic disorder. The aims of nutritional therapy for cholestatic liver disease are to reduce the risk of cholestasis related complications, to promote recov-ery of liver diseases, to restore bile flow, to promote growth and improve the comprehensive metabolic disorders, to improve quality of life and to prepare children for liver transplantation.%婴儿胆汁淤积性肝病的病因甚多,包括肝外胆道疾病、肝内疾病、解剖异常、代谢或内分泌疾病、中毒、感染等。由于胆流减少或中断,引起肠道营养物质吸收障碍及综合代谢紊乱。胆汁淤积性肝病的营养治疗,主要是减少胆汁淤积相关并发症;促进肝脏病变恢复,恢复胆流;促进生长发育和改善综合代谢紊乱;提高生存质量,为患儿后期肝移植奠定基础。

  3. Acute liver failure and self-medication

    OpenAIRE

    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 live...

  4. Inhibition of PAR-4 and P2Y12 receptor-mediated platelet activation produces distinct hepatic pathologies in experimental xenobiotic-induced cholestatic liver disease.

    Science.gov (United States)

    Joshi, Nikita; Kopec, Anna K; Ray, Jessica L; Luyendyk, James P

    2016-07-15

    Emerging evidence supports a protective effect of platelets in experimental cholestatic liver injury and cholangiofibrosis. Coagulation-mediated platelet activation has been shown to inhibit experimental chronic cholestatic liver necrosis and biliary fibrosis. This occurs through thrombin-mediated activation of protease activated receptor-4 (PAR-4) in mice. However, it is not known whether other pathways of platelet activation, such as adenosine diphosphate (ADP)-mediated receptor P2Y12 activation is also protective. We tested the hypothesis that inhibition of P2Y12-mediated platelet activation exacerbates hepatic injury and cholangiofibrosis, and examined the impact of P2Y12 inhibition in both the presence and absence of PAR-4. Treatment of wild-type mice with the P2Y12 receptor antagonist clopidogrel increased biliary hyperplasia and cholangiofibrosis in wild-type mice exposed to the xenobiotic alpha-naphthylisothiocyanate (ANIT) for 4 weeks compared to vehicle-treated mice exposed to ANIT. Interestingly, this effect of clopidogrel occurred without a corresponding increase in hepatocellular necrosis. Whereas biliary hyperplasia and cholangiofibrosis were increased in PAR-4(-/-) mice, clopidogrel treatment failed to further increase these pathologies in PAR-4(-/-) mice. The results indicate that inhibition of receptor P2Y12-mediated platelet activation exacerbates bile duct fibrosis in ANIT-exposed mice, independent of hepatocellular necrosis. Moreover, the lack of an added effect of clopidogrel administration on the exaggerated pathology in ANIT-exposed PAR-4(-/-) mice reinforces the prevailing importance of coagulation-mediated platelet activation in limiting this unique liver pathology. PMID:27475285

  5. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  6. Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Andres F. Carrion

    2010-01-01

    Full Text Available Propylthiouracil- (PTU- induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

  7. Therapeutic hypothermia for acute liver failure

    DEFF Research Database (Denmark)

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    Cerebral edema is a potentially life-threatening complication of acute liver failure, the syndrome of abrupt loss of liver function in a patient with a previously healthy liver. Although the prevalence of cerebral edema appears to be decreasing, patients with rapidly progressive (hyperacute) liver...... liver failure often can be temporarily controlled by manipulating body position, increasing the degree of sedation, and increasing blood osmolarity through pharmacologic means. However, these maneuvers often postpone, but do not eliminate, the risk of brainstem herniation unless orthotopic liver...... transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...

  8. Panhypopituitarism : a rare cause of neonatal cholestatic jaundice

    OpenAIRE

    Vella, Cecil; Gauci, Bettina; Torpiano, John

    2013-01-01

    Although not uncommon, neonatal cholestatic jaundice is usually caused by congenital anatomical defects of the biliary tree or intrinsic liver pathology. We describe a case of persistent cholestatic jaundice in a six week old female infant caused by panhypopituitarism. To our knowledge this is the first report of hypopituitarism presenting with cholestatic jaundice in Malta. Prolonged obstructive jaundice in the neonatal period should be urgently investigated until a cause is found.

  9. Cholestatic hepatitis with intravenous ceftriaxone

    Directory of Open Access Journals (Sweden)

    Inderpal Kaur

    2011-01-01

    Full Text Available Drug-induced liver injury is a major health problem. Its predominant forms include acute hepatitis, cholestasis, and a mixed pattern. Ceftriaxone is a third-generation cephalosporin and is widely used in the postoperative period due to its wider spectrum, longer half-life, and better tissue penetrability. Earlier cases of high aminotransferase levels and hepatitis have also been reported with the use of ceftriaxone. Here we report a case of cholestatic hepatitis with intravenous ceftriaxone.

  10. The Pathology of Acute Liver Failure.

    Science.gov (United States)

    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

  11. Clinical heterogeneity in autoimmune acute liver failure

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  12. Artificial and bioartificial support systems for liver failure

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  13. Steroid use in acute liver failure

    DEFF Research Database (Denmark)

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

    2014-01-01

    UNLABELLED: Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indete......UNLABELLED: Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug......-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS...

  14. Microarray Study of Pathway Analysis Expression Profile Associated with MicroRNA-29a with Regard to Murine Cholestatic Liver Injuries

    Directory of Open Access Journals (Sweden)

    Sung-Chou Li

    2016-03-01

    Full Text Available Accumulating evidence demonstrates that microRNA-29 (miR-29 expression is prominently decreased in patients with hepatic fibrosis, which consequently stimulates hepatic stellate cells’ (HSCs activation. We used a cDNA microarray study to gain a more comprehensive understanding of genome-wide gene expressions by adjusting miR-29a expression in a bile duct-ligation (BDL animal model. Methods: Using miR-29a transgenic mice and wild-type littermates and applying the BDL mouse model, we characterized the function of miR-29a with regard to cholestatic liver fibrosis. Pathway enrichment analysis and/or specific validation were performed for differentially expressed genes found within the comparisons. Results: Analysis of the microarray data identified a number of differentially expressed genes due to the miR-29a transgene, BDL, or both. Additional pathway enrichment analysis revealed that TGF-β signaling had a significantly differential activated pathway depending on the occurrence of miR-29a overexpression or the lack thereof. Furthermore, overexpression was found to elicit changes in Wnt/β-catenin after BDL. Conclusion: This study verified that an elevated miR-29a level could alleviate liver fibrosis caused by cholestasis. Furthermore, the protective effects of miR-29a correlate with the downregulation of TGF-β and associated with Wnt/β-catenin signal pathway following BDL.

  15. Portal hypertension in acute liver failure.

    OpenAIRE

    3.M. Navasa; Garcia-Pagán, J C; Bosch, J; Riera, J R; R. Bañares; 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 betw...

  16. Liver transplantation and artificial liver support in fulminant hepatic failure

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Zhu; Gui-Hua Chen; Xiao-Shun He; Min-Qiang Lu; Guo-Dong Wang; Chang-Jie Cai,; Yang Yang and; Jie-Fu Huang

    2001-01-01

    @@ INTRODUCTIONFulminant hepatic failure(FHF)is a severe disease with devastating consequences;the incidence is high in China.Before the availability of liver transplantation,the mortality rate was more than 80%[1,2].The advent of liver transplantation revolutionized the outcome of FHF[3,4].However,many patients were unwilling to accept liver transplantation until very late,hence most of them died because of donor shortage and urgency of the disease[5-7],To overcome he problems,we performed orthotopic liver transplantation(OLT)in combination with artificial liver support(ALS) in the treatment of FHF in the past 2 years with satisfactory results.Our experience was reported below.

  17. Acute Liver Failure Secondary to Niacin Toxicity

    Directory of Open Access Journals (Sweden)

    Marc A. Ellsworth

    2014-01-01

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

  18. Acute Renal Failure in Liver Transplant Patients: Indian Study

    OpenAIRE

    Naik, Pradeep; Premsagar, B.; Mallikarjuna, M.

    2013-01-01

    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 tac...

  19. Prognostic models for acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Wei-Bo Du; Xiao-Ping Pan; Lan-Juan Li

    2010-01-01

    BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES: Five English-language medical databases, MEDLINE, ScienceDirect, OVID, Springer Link and Wiley Interscience were searched for articles on"acute liver failure","prognosis", and related topics. RESULTS: Multi-variable prognostic models including the King's College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF, but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin, arterial blood lactate, serum phosphate, arterial blood ammonia, and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS: A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models.

  20. Imatinib-induced fatal acute liver failure

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Imatinib mesylate is a drug that has been approved for treatment of chronic myeloid leukemia (CML) in blast crisis, accelerated or chronic phase, and also for advanced gastrointestinal stromal tumors. Severe hepatic toxicity and three deaths from hepatic failure have been reported. We report the case of a 51-year-old woman who was admitted to our institution with severe acute hepatitis. She was diagnosed with CML and began treatment with imatinib mesylate at a dose of 400 mg/d.Five months after beginning treatment, she developed severe hepatitis associated with coagulopathy, and was admitted to our institution. She had been consuming acetaminophen 500-1000 mg/d after the onset of symptoms. She had a progressive increase in bilirubin level and a marked decrease of clotting factor Ⅴ. Five days after admission, grade Ⅱ encephalopathy developed and she was referred for liver transplantation. Her clinical condition progressively deteriorated, and 48 h after being referred for transplantation she suffered a cardiac arrest and died. This report adds concern about the possibility of imatinib-mesylate-induced hepatotoxicity and liver failure, particularly in the case of concomitant use with acetaminophen. Liver function tests should be carefully monitored during treatment and, with the appearance of any elevation of liver function tests, treatment should be discontinued.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  3. the Pathogenesis of acute on Chronic Hepatitis B liver Failure

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would beneift for the prognosis and raise the survival rate of patients.

  4. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    OpenAIRE

    Verhaag, Esther M.; Manon Buist-Homan; Martijn Koehorst; Groen, Albert K; Han Moshage; Klaas Nico Faber

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes agai...

  5. Plasma osteopontin in acute liver failure

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function...... in the setting of massive hepatocyte injury. METHODS: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1....../mL; range 2.6-86.4). RA and SF post op patients had elevated OPN levels (37ng/mL and 198ng/mL respectively), well below those of the ALF patients. Median OPN levels were highest in acetaminophen (3603ng/mL) and ischemia-related ALF (4102ng/mL) as opposed to viral hepatitis (706ng/mL), drug-induced liver...

  6. Effect of hepatic iron concentration reduction on hepatic fibrosis and damage in rats with cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Gil Peretz; Gabriela Link; Orit Pappo; Rafael Bruck; Zvi Ackerman

    2006-01-01

    AIM: To assess the effect of iron reduction after phlebotomy in rats with "normal" hepatic iron concentration (HIC) on the progression of hepatic fibrosis, as a result of bile duct ligation (BDL).METHODS: Rats underwent phlebotomy before or after sham operation or BDL. Animals undergone only BDL or sham operation served as controls. Two weeks after surgery, indices of hepatic damage and fibrosis were evaluated.RESULTS: Phlebotomy lowered HIC. Phlebotomy after BDL was associated with body weight increase, lower hepatic weight, less portal hypertension, less periportal necrosis, less portal inflammation, lower hepatic activity index score and higher albumin levels. On the other hand, phlebotomy before BDL was associated with body weight decrease and hepatic activity index score increase. Phlebotomy after sham operation was not associated with any hepatic or systemic adverse effects.CONCLUSION: Reduction of HIC after induction of liver damage may have beneficial effects in BDL rats.However, iron deficiency could induce impairment of liver function and may make the liver more susceptible to insults like BDL.

  7. Dengue fever with acute liver failure

    OpenAIRE

    Vinodh B; Bammigatti C; Kumar Ashok; Mittal V

    2005-01-01

    A virus belonging to the Flaviviridae group causes dengue haemorrhagic fever. Dengue presenting as acute liver failure is rare. Dengue is endemic in India. The last epidemic of dengue occurred in Delhi in 2003. During this epidemic, 2185 confirmed cases of dengue were reported. Dengue virus serotypes 2 and 3 were responsible for this epidemic. A 19-yr-old male presented to our hospital with the complaints of fever for 12 days, during this epidemic. He was diagnosed as having dengue shock synd...

  8. Ondansetron to Treat Pruritus Due to Cholestatic Jaundice

    OpenAIRE

    Dillon, Sarah; Tobias, Joseph D

    2013-01-01

    Intractable itching is a symptom of cholestatic liver disease of various causes that is bothersome and difficult to manage. Although treatment of the primary cause of cholestasis is paramount in resolving the issue, given the debilitating consequences of pruritus, symptomatic treatment is frequently necessary. Although many medications including cholestyramine, rifampin, opioid antagonists (i.e., naloxone, naltrexone), phenobarbital, and antihistamines have been used to treat cholestatic-indu...

  9. Gastrointestinal and Liver Issues in Heart Failure.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  12. Investigation of Homocystein Plasma Level in Cholestatic Rat and Its Effect on Nitric Oxide Secretion in Liver

    Directory of Open Access Journals (Sweden)

    N. Mirazi

    2005-04-01

    Full Text Available Homocystein (Hcy,one of the thio-amino acid is known as a risk factor in some cardiovascular diseases with releasing O2 radical . It has also been reported that; there is oxidative stress effects of Hcy in cholestasis. The aim of this study is to determine plasma Hcy alteration and nitric oxide (NO in liver and its effects on pathologic disfunction.In this study , 150 Spraque – Dawley male rats with 200 ± 20g body weight were used in the experiments and they were randomly divided in three control, SHAM and bile duct ligation (BDL groups (n= 10-12 . In 7th,14th,21st and 28th days cholestasis was observed in BDL group,the animal were anesthetized with ether and then blood samples were taken from heart directly and analysed for cystein , methionine by HPLC and HPLC-UV. Two hours before blood sampling , 40 and 100 mg/kg methionine were injected (I.P .All data are expressed as mean  SEM. Statistical evaluation of data performed by SPSS soft ware using analysis of variance (ANOVA followed by post hoc test. P-values less than 0.05 were considered statistically significant .The results suggest that billirubin and hepatic enzymes were significantly elevated in BDL rats compared with SHAM and controls (P<0.05. Homocystein concentration was significantly rised in 14th day in BDL group (P<0.05. The plasma cystein and methionine level were significantly elevated in BDL rats compared with SHAM and control groups ( p = 0.01 . Plasma nitrate / nitrite ratio were significantly increased in BDL rats compared with SHAM and control rats (P<0.05. With these data we suppose that some of the systemic oxidative stresses in BDL rat model of cholestasis contributes possibly through NO-dependent mechanisms disorders.

  13. Febrile cholestatic disease as an initial presentation of nodular lymphocyte-predominant Hodgkin lymphoma

    Institute of Scientific and Technical Information of China (English)

    Anna; Mrzljak; Slavko; Gasparov; Ika; Kardum-Skelin; Vesna; Colic-Cvrlje; Slobodanka; Ostojic; Kolonic

    2010-01-01

    Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL,a nodular lymphocyte-predominant HL(NLPHL).Liver involvement in the early stage of the usually indolent NLPHL's clinical course suggests an aggressiveness and unfavorable outcome.Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate tre...

  14. Flupirtine-induced hepatic failure requiring orthotopic liver transplant.

    Science.gov (United States)

    Klein, Fritz; Glanemann, Matthias; Rudolph, Birgit; Seehofer, Daniel; Neuhaus, Peter

    2011-08-01

    We present the case of a 48-year-old otherwise healthy man who required an urgent liver transplant owing to acute liver failure after flupirtine treatment. After 3 months of daily flupirtine intake as treatment for pseudoradicular pain syndrome, he presented at our institution with signs of jaundice and hepatic encephalopathy. Laboratory results showed elevated liver transaminases, and the liver histopathology supported the assumed drug-induced liver injury. After listing him for an urgent liver transplant, he was given a liver graft from a 21-year-old man. Despite a rejection episode on day 11 after the surgery (which was successfully treated by steroid pulse therapy), the postoperative course was uneventful and the patient recovered completely. To the best of our knowledge, this is the first report of a liver transplant for acute liver failure after taking flupirtine. PMID:21819373

  15. Heparin-induced thrombocytopenia associated with acute liver graft failure

    OpenAIRE

    Pannicke, Nadine; Pollok, Joerg-Matthias; Kluge, Stefan; Petzoldt, Martin

    2012-01-01

    An orthotopic liver transplantation (OLT) is of a proven benefit in an acute liver failure (ALF). Heparin-induced thrombocytopenia (HIT) is strongly associated with thromboembolic complications. We present the case of a 56-year-old patient who underwent an OLT owing to an ALF of unknown aetiology. HIT type II with consecutive hepatic and portal vein thrombosis caused progressive graft failure. Total hepatectomy and porto-caval shunt were performed to reduce the toxic effects of liver cell nec...

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

    OpenAIRE

    Tessier, Geneviève; Villeneuve, Edith; Villeneuve, Jean-Pierre

    2002-01-01

    BACKGROUND: Acute liver failure is a rare condition in which massive liver injury is associated with the rapid development of hepatic encephalopathy. Although viral hepatitis and drug-induced liver injury are the most common causes, no specific etiology is found in a substantial proportion of cases reported from Europe and the United States.AIM: To determine the etiology and outcome of patients with acute liver failure in the authors’ institution.PATIENTS AND METHODS: The charts of 81 consecu...

  17. Acute liver failure associated with Garcinia cambogia use.

    Science.gov (United States)

    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. PMID:26626648

  18. TNFR1 determines progression of chronic liver injury in the IKK gamma/Nemo genetic model

    NARCIS (Netherlands)

    Cubero, F.J.; Singh, A.; Borkham-Kamphorst, E.; Nevzorova, Y.A.; Masaoudi, Al M.; Haas, U.; Boekschoten, M.V.; Gassler, N.; Weiskirchen, R.; Muller, M.; Liedtke, C.; Trautwein, C.

    2013-01-01

    Death receptor-mediated hepatocyte apoptosis is implicated in a wide range of liver diseases including viral and alcoholic hepatitis, ischemia/reperfusion injury, fulminant hepatic failure, cholestatic liver injury, as well as cancer. Deletion of NF-kappa B essential modulator in hepatocytes (IKK ga

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

    Science.gov (United States)

    Naik, Pradeep; Premsagar, B; Mallikarjuna, M

    2015-01-01

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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Geneviève Tessier

    2002-01-01

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

  2. Severe acute cholestatic hepatitis of unknown etiology successfully treated with the Chinese herbal medicine Inchinko-to (TJ-135)

    Institute of Scientific and Technical Information of China (English)

    Susumu Ohwada; Isao Kobayashi; Nobuo Harasawa; Kyoichiro Tsuda; Yosikatsu Inui

    2009-01-01

    Severe acute hepatitis of unknown etiology is difficult to treat and often progresses to subacute fulminant hepatitis or late-onset hepatic failure. A 45-year-old wellnourished, healthy man had progressive fatigue and his liver function tests showed severe liver dysfunction. The etiology of sever acute cholestatic hepatitis was unknown. The liver function tests normalized gradually, which excluded high persistent total bilirubin after starting on predonine. A liver biopsy showed chronic active hepatitis with mild fibrosis (A2, F1). Oral Inchinko-to, a Chinese herbal medicine, at 7.5 g daily was prescribed. The treatment was effective with no adverse effects. We present a successfully treated case and discuss hepatoprotective and choleretic effects of Inchinko-to.

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

    Science.gov (United States)

    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

  4. SURVIVAL OF LIVER CELLS, IMMOBILIZED ON 3D-MATRIXES, IN LIVER FAILURE MODEL

    Directory of Open Access Journals (Sweden)

    M. Y. Shagidulin

    2011-01-01

    Full Text Available It was examined a new method for correction of hepatic failure by transplantation of liver support biounit (liver cells, immobilized on biocompatible and biodegradable 3D-matrixes ElastoPOB® into small intestine mesentery. It was determined that after modeling of acute hepatic failure on dogs by 65–70% liver resection and transplantation liver support biounit the restoration of disturbed biochemical indecies (such as total protein, lactate, cytolytic ensymes-ALT, AST, ALP, LDH, fibrinogen, protrombine index and others took place more rapidly on 9–14th day instead of 18th day in control. It was made a preposition about efficiency of the suggested method for correction both acute hepatic failure because even 90 days after transplantation of liver support biounit alive hepatocytes and neogenic plethoric vessels, growing through matrix were revealed. 

  5. Cell Therapy for Acute Liver Failure - Ideal source of cell

    Directory of Open Access Journals (Sweden)

    CM Habibullah

    2008-11-01

    Full Text Available Liver is the central metabolic organ that regulates body’s energy supply, secretes several essential compounds and clears substances by several methods, including recycling, inactivation andexcretion. Global loss of the liver function results in profound metabolic instability and disruption of essential functions such as acid-base balance and thermoregulation leading to acute liver failure (ALF.If this is not rapidly reversed, complications such as uncontrolled bleeding occur, and dependent organs such as brain and kidneys begin to fail, reducing the chance of recovery even further. Acute liver failure (ALF carries high morbidity and mortality (>80% even in the best centres. Presently, orthotopic liver transplantation (OLTx is the only treatment that improves the survival rate in patients with ALF. Advent of various immunosuppressive agents has improved the success rate of this procedure by preventing rejection. Non availability of donor organs however remained a major limitation. Two approaches viz., (i hepatocyte transplantation (ii extracorporeal liver support system, have been attempted to provide temporary liver support to failing liver till a suitable organ becomes available. These approaches have demonstrated their efficacy in the pre-clinical and clinical studies.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    Spósito A.C.

    1997-01-01

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

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

    DEFF Research Database (Denmark)

    Hvas, Christian; Kodjabashia, Kamelia; Nixon, Emma;

    2016-01-01

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

  10. Intestinal endotoxemia as a pathogenetic mechanism in liver failure

    Institute of Scientific and Technical Information of China (English)

    De-Wu Han

    2002-01-01

    Liver injury induced by various pathogenic factors (such as hepatitis virus, ethanol, drugs and hepatotoxicants, etc.)through their respective special pathogenesis is referred to as "primary liver injury" (PLI). Liver injury resultedfrom endotoxin (lipopolysaccharide, LPS) and the activation of Kupffer cells by LPS while intestinal endotoxemia (IETM) occurred during the occurrence and development of hepatitis is named the "secondary liver injury" (SLI).The latter which has lost their own specificities of primary pathogenic factors is ascribed to IETM. The "secondary liver injury" is of important action and impact on development and prognosis of hepatitis. More severe IETM commonly results in excessive inflammatory responses, with serious hepatic necrosis,further severe hepatitis and even induces acute liver failure.The milder IETM successively precipitates a cascade,including repeated and persistent hepatocytic impairment accompanied by infiltration of inflammatory cells, hepatic fibrosis, cirrhosis and hepatocarcinoma. Generally, the milder IETM ends with chronic hepatic failure. If PLI caused by various pathogenic factors through their independent specific mechanismis regarded as "the first hit" on liver, then SLI mediated by different chemical mediators from KCs activated by IETM in the course of hepatitis is "the second hit" on liver. Thus, fusing and overlapping of the primary and scondary liver injuries determine and influeuce the complexity of the illness and outcome of the patient with hepatitis. For this reason, the viewpoint of "SLI" induced by the "second hit" on liver inflicted by IFTM suggests that medical professionals should attach great importance to both "PLI"and "SLI" caused by IETM. That is, try to adjust the function of KSs and eliminate endotoxemia of the patient.

  11. Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

    Science.gov (United States)

    McCarthy, M; Ellis, A J; Wendon, J A; Heaton, N; Rela, M; Buxton-Thomas, M; Hughes, R D; Portmann, B C; Williams, R

    1997-04-01

    The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting. PMID:9160207

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

    Science.gov (United States)

    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.

  13. Intestinal endotoxemia as a pathogenetic mechanism in liver failure

    Institute of Scientific and Technical Information of China (English)

    De-WuHan

    2002-01-01

    Liver injury induced by various pathogenic factors(such as hepatitis virus,ethanol,drugs and hepatotoxicants,etc.)through their respective special pathogenesis is referred to as“primary liver injury”(LPS)and the activation of kupffer cells by LPS while intestinal endotoxemia(IETM)occurted during the occurrence and development of hepatitis is named the“secondary liver injury”(SLI).The latter which has lost their own specificities of primary pathogenic factors is ascribed to IETM.The“secondary liver injury”is of important action and impact on development and prognosis of hepatitis.More severe IETM commonly results in excessive inflammatory responses,with serious hepatic necrosis,further severe hepatitis and even induces acute liver failure.The milder IETM successively precipitates a cascade,including repeated and persistent hepatocytic impairment accompanied by infiltration of inflammatory cells,hepatic fibrosis,cirrhosis and hepatocarcinoma.Generally,the milder IETM ends with chronic hepatic failure.If PLI caused by various pathogenic factors through their independent specific mechanismis regarded as“the first hit”on liver,then SLI mediated by different chemical mediators from KC,activated by IETMin the course of hepatitis is “the second hit”on liver.Thus,fusing and overlapping of the primary and scorndary liver injunies determine and influeuce the complexity of the illness and outcome of the patient with hepatitis.For this reason,the viewpoint of “SLI”induced by the “second hit”on liver inflicted by IETM suggests that medical professionals should attach great importance to both“PLI”and“SLI”caused by IETM.That is,try to adjust the function of KS,and eliminate endotoxemia ofthe patient.

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

    Science.gov (United States)

    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.

  15. Outcome of acute liver failure in the elderly

    DEFF Research Database (Denmark)

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

    2009-01-01

    Older age is considered a poor prognostic factor in acute liver failure (ALF) and may still be considered a relative contraindication for liver transplantation for ALF. We aimed to evaluate the impact of older age, defined as age > or = 60 years, on outcomes in patients with ALF. One thousand one...... 48.2% in group 2 for non-acetaminophen patients (P < 0.001). The spontaneous survival rate (ie, survival without liver transplantation) was 64.9% in group 1 and 60.0% in group 2 (not significant) for acetaminophen patients and 30.8% in group 1 and 24.7% in group 2 for non-acetaminophen patients (P...... = 0.27). Age was not a significant predictor of spontaneous survival in multiple logistic regression analyses. Group 2 patients were listed for liver transplantation significantly less than group 1 patients. Age was listed as a contraindication for transplantation in 5 patients. In conclusion, in...

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

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    OpenAIRE

    Włodzimirow, K.A.

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    A. D. Kaprin

    2016-01-01

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

  20. Acute-on-chronic liver failure: a review

    Directory of Open Access Journals (Sweden)

    Zamora Nava LE

    2014-04-01

    Full Text Available Luis Eduardo Zamora Nava,1 Jonathan Aguirre Valadez,2 Norberto C Chávez-Tapia,3 Aldo Torre21Department of Endoscopy, 2Department of Gastroenterology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, 3Obesity and Digestive Diseases Unit, Medica Sur Clinic and Foundation, Mexico City, MexicoAbstract: There is no universally accepted definition of acute-on-chronic liver failure; however, it is recognized as an entity characterized by decompensation from an underlying chronic liver disease associated with organ failure that conveys high short-term mortality, with alcoholism and infection being the most frequent precipitating events. The pathophysiology involves inflammatory processes associated with a trigger factor in susceptible individuals (related to altered immunity in the cirrhotic population. This review addresses the different definitions developed by leading research groups, epidemiological and pathophysiological aspects, and the latest treatments for this entity.Keywords: acute-on-chronic liver failure, cirrhosis, organ failure, acute kidney injury, infection

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  3. Dengue fever presenting as acute liver failure- a case report

    Institute of Scientific and Technical Information of China (English)

    Rajat Jhamb; Bineeta Kashyap; Ranga GS; Kumar A

    2011-01-01

    Dengue fever(DF) and dengue haemorrhagic fever(DHF) are important mosquito-borne viral diseases of humans and recognized as important emerging infectious diseases in the tropics and subtropics. Compared to nine reporting countries in the 1950s, today the geographic distribution includes more than100 countries worldwide. Dengue viral infections are known to present a diverse clinical spectrum, ranging from asymptomatic illness to fatal dengue shock syndrome. Mild hepatic dysfunction in dengue haemorrhagic fever is usual. However, its presentation as acute liver failure(ALF)is unusual. We report a patient with dengue shock syndrome who presented with acute liver failure and hepatic encephalopathy in a recent outbreak of dengue fever in Delhi, India.

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

    Science.gov (United States)

    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

  5. Assessment of adult patients with chronic liver failure for liver transplantation in 2015: who and when?

    Science.gov (United States)

    McCaughan, G W; Crawford, M; Sandroussi, C; Koorey, D J; Bowen, D G; Shackel, N A; Strasser, S I

    2016-04-01

    In 2015, there are a few absolute contraindications to liver transplantation. In adult patients, survival post-liver transplant is excellent, with 1-year survival rate >90% and 5-year survival rates >80% and predicted median allograft survival beyond 20 years. Patients with a Child-Turcotte Pugh score ≥9 or a model for end-stage liver disease (MELD) score >15 should be referred for liver transplantation, with patients who have a MELD score >17 showing a 1-year survival benefit with liver transplantation. A careful selection of hepatocellular cancer patients results in excellent outcomes, while consideration of extra-hepatic disease (reversible vs irreversible) and social support structures are crucial to patient assessment. Alcoholic liver disease remains a challenge, and the potential to cure hepatitis C virus infection together with the emerging issue of non-alcoholic fatty liver disease-associated chronic liver failure will change the landscape of the who in the years ahead. The when will continue to be determined largely by the severity of liver disease based on the MELD score for the foreseeable future. PMID:27062203

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

    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.

  9. Diagnostic criteria for acute liver failure due to Wilson disease

    Institute of Scientific and Technical Information of China (English)

    Christoph Eisenbach; Olivia Sieg; Wolfgang Stremmel; Jens Encke; Uta Merle

    2007-01-01

    AIM: To describe the diagnostic criteria for acute liver failure due to Wilson disease (WD), which is an uncommon cause of acute liver failure (ALF).METHODS: We compared findings of patients presenting with ALF due to WD to those with ALF of other etiologies.RESULTS: Previously described criteria, such as low alkaline phosphatase activity, ratio of low alkaline phosphatase to total bilirubin or ratio of high aspartate aminotransferase (AST) to alanine aminotransferase (ALT), failed to identify patients with ALF due to WD. There were significant differences in low ALT and AST activities (53 ± 43 vs 1982 ± 938, P < 0.0001 and 87 ± 44 vs 2756 ± 2941, P = 0.037, respectively), low choline esterase activity (1.79 ± 1.2 vs 4.30 ± 1.2, P = 0.009), high urine copper concentrations (93.4 ± 144.0 vs 3.5 ± 1.8, P = 0.001) and low hemoglobin (7.0 ± 2.2 vs 12.6 ± 1.8, P < 0.0001) in patients with ALF caused by WD as compared with other etiologies. Interestingly, 4 of 7 patients with ALF due to WD survived without liver transplantation.CONCLUSION: In ALF, these criteria can help establish a diagnosis of WD. Where applicable, slit-lamp examination for presence of Kayser-Fleischer rings and liver biopsy for determination of hepatic copper concentration still remain important for the diagnosis of ALF due to WD. The need for liver transplantation should be evaluated carefully as the prognosis is not necessarily fatal.

  10. Clindamycin-induced acute cholestatic hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We report a case of acute hepatotoxicity in a 42-yearold woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase (ALT), 1795 IU/L (normal range 0-40); aspartate aminotransferase (AST), 1337 IU/L (normal range 5-34); alkaline phosphatase (ALP), 339 IU/L (normal range 40-150); γ-glutamyl transpeptidase (GGT), 148 IU/L (normal range 9-64 IU/L); total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time (PT), 13.5 s, with international normalized ratio (INR), 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixedtype liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.

  11. Ondansetron to Treat Pruritus Due to Cholestatic Jaundice

    Science.gov (United States)

    Dillon, Sarah; Tobias, Joseph D.

    2013-01-01

    Intractable itching is a symptom of cholestatic liver disease of various causes that is bothersome and difficult to manage. Although treatment of the primary cause of cholestasis is paramount in resolving the issue, given the debilitating consequences of pruritus, symptomatic treatment is frequently necessary. Although many medications including cholestyramine, rifampin, opioid antagonists (i.e., naloxone, naltrexone), phenobarbital, and antihistamines have been used to treat cholestatic-induced pruritus, none has resulted in uniform success. We report anecdotal success with the use of ondansetron to treat pruritus associated with cholestasis following prolonged intensive care unit course of a 16-year-old. The theories accounting for pruritus with cholestasis are presented, treatment options are reviewed, and the role of ondansetron in the treatment of pruritus is discussed. PMID:24052788

  12. Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in Mice.

    Science.gov (United States)

    Cheng, Yuanming; Luo, Chunling; Wu, Wenwu; Xie, Zhiqin; Fu, Xiangdong; Feng, Ying

    2016-06-01

    The liver performs a variety of unique functions critical for metabolic homeostasis. Here, we show that mice lacking the splicing factor SRSF2 but not SRSF1 in hepatocytes have severe liver pathology and biochemical abnormalities. Histological analyses revealed generalized hepatitis with the presence of ballooned hepatocytes and evidence of fibrosis. Molecular analysis demonstrated that SRSF2 governs splicing of multiple genes involved in the stress-induced cell death pathway in the liver. More importantly, SRSF2 also functions as a potent transcription activator, required for efficient expression of transcription factors mainly responsible for energy homeostasis and bile acid metabolism in the liver. Consistent with the effects of SRSF2 in gene regulation, accumulation of total cholesterol and bile acids was prominently observed in the mutant liver, followed by enhanced generation of reactive oxygen species and increased endoplasmic reticulum stress, as revealed by biochemical and ultrastructural analyses. Taking these observations together, inactivation of SRSF2 in liver caused dysregulated splicing events and hepatic metabolic disorders, which trigger endoplasmic reticulum stress, oxidative stress, and finally liver failure. PMID:27022105

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    Miguel Bispo; Ana Valente; Rosário Maldonado; Rui Palma; Helena Glória; Jo(a)o Nóbrega; Paula Alexandrino

    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.

  15. TECA hybrid artificial liver support system in treatment of acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Yi-Long Xue; Xin-Cui; Da-Guang Zhong; Zuo-Yun Zhang; Zhi-Qiang Huang; Shi-Feng Zhao; Yun-Luo; Xin-Jian Li; Zhong-Ping Duan; Xiao-Ping Chen; Wen-Ge Li; Xiao-Qiang Huang; Yan-Ling Li

    2001-01-01

    AIM: To assess the efficacy and safety of TECA type hybrid artificial liver support system (TECA-HALSS) in providing liver function of detoxification, metabolism and physiology by treating the patients with acute liver failure (ALF). METHODS: The porcine liver cells (1 - 2 ) x 1010 were separated from the Chinese small swine and cultured in the bioreactor of TECA-BALSS at 37.0°C and circulated through the outer space of the hollow fiber tubes in BALSS. The six liver failure patients with various degree of hepatic coma were treated by TECA-HALSS and with conventional medicines. The venous plasma of the patients was separated by a plasma separator and treated by charcoal adsorbent or plasma exchange. The plasma circulated through the inner space of the hollow fiber tubes of BALSS and mixed with the patients' blood cells and flew back to their blood circulation. Some small molecular weight substances were exchanged between theplasma and porcine liver cells. Each treatment lasted 6.0-7.0 h.Physiological and biochemical parameters were measured before, during and after the treatment. RESULTS: The average of porcine liver cells was (1.0- 3.0)x 1010 obtained from each swine liver using our modified enzymatic digestion method. The survival rate of the cells was 85% - 93% by tnypan blue stain and AO/PI fluorescent stain. After cultured in TECA-BALSS bioreactor for 6 h, the survival rate of cells still remained 70% - 85%. At the end of TECA-HALSS treatment, the levels of plasma NH3, ALT, TB and DB were significantly decreased. The patients who were in the state of drowsiness or coma before the treatment improved their appetite significantly and regained consciousness, some patients resumed light physical work on a short period after the treatment. One to two days after the treatment, the ratio of PTA increased warkedly. During the treatment, the heart rates, blood pressure, respiration condition and serum electrolytes (K+, Na+ and Cl) were stable without thrombosis and

  16. Pathological changes of the livers from 39 patients with hepatic failure

    Institute of Scientific and Technical Information of China (English)

    崇雨田

    2006-01-01

    Objective To explore the pathological changes of the livers from hepatic failure (HF) patients and its association with clinical disease stages. Methods Thirtynine patients with liver failure caused by HBV infections were investigated, and none accompanied with hepatocellular carcinoma. The sections of tissue were taken from the liver after liver transplantation and stained with hematoxylin -eosin (H&E) or RT (reticular fiber) staining. The pathological features were analyzed and compared between the clinical and pathological diagnosis.

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

    Directory of Open Access Journals (Sweden)

    Valentín Roales-Gómez

    2014-08-01

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

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

    Science.gov (United States)

    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

  19. 小儿胆汁淤积性肝病的病因学特征%Citrin deficiency is an important etiology for cholestatic liver disease in children

    Institute of Scientific and Technical Information of China (English)

    宋元宗; 牛飼美晴; 小林圭子; 佐伯武赖

    2009-01-01

    Objective To explore the major etiological features of cholestatie liver disease (CLD) in children, and to investigate the molecular epidemiological distribution of SLC25A13 mutations in CLD. Method A clinical cross-sectional invesitgation was performed on 63 CLD cases diagnosed from Oct. 2003 to Mar. 2009 in our department, including 36 males and 27 females. Their clinical data were collected, and etiology and prognosis were analyzed and summarized. Thirteen to 17 mutations in SLC25A13 gene were screened by means of procedures established previously by our group. Several SLC25A13 mutations were detected by direct sequencing of DNA fragments amplified by genomic DNA-PCR. Result No specific etiologies were identified in 24 of the 63 cases. Among the 39 cases with identified etiologies, inherited metabolic diseases were on top of the list, including 6 kinds and 27 cases in total, i.e. , neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD, 21 cases), transient galactosemia, tyrosinemia type Ⅰ, galactose kinase deficiency, omithine carbamoyl transferase deficiency and glycogen storage disease type Ⅰ, followed by acquired causes (7 cases in total ), such as total parenteral nutrition associated eholestasis (TPNAC), congenital syphilis and CMV hepatitis; and then biliary tract malformation (5 casesin total), including biliary atresia, Caroli's disease and gallbladder polyp, were the third. Ten of the 55 patients on follow-up have passed away, while the remaining 45 cases were improved or recovered clinically. SLC25A13 gene analysis were performed in 44 CLD subjects and 21 of them from 20 families (with 40 SLC25AI3 alleles in total) were found to have mutations, and the seven mutations detected were 851-854del (23/40), IVS6 +5G > A (6/40), IVS16ins3kb (3/40), 1638-1660dup (2/30), A541D (1/30), R319X (1/30) and G333D (1/30), respectively, and there were other 3 mutations (3/40) still needing identification in the remaining 3 alleles. Conclusion The

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

    Directory of Open Access Journals (Sweden)

    Ylse Gutiérrez-Grobe

    2013-01-01

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

  1. Idiopathic neonatal giant cell hepatitis presenting with acute hepatic failure on postnatal day one.

    Science.gov (United States)

    Correa, Kimberley K; Nanjundiah, Prathiba; Wirtschafter, David D; Alshak, Najeeb S

    2002-01-01

    We report a term male infant presenting on postnatal day 1 with fulminant hepatic failure. Described congenital infection, metabolic disorders, and cardiovascular etiologies of acute neonatal liver failure were assessed and eliminated. A liver biopsy on postnatal day 10 showed neonatal giant cell hepatitis (NGCH) with an unusual degree of fibrosis for this early postnatal age. NGCH is a clinical diagnosis of cholestatic disorders of unknown etiology in the newborn, and, to our knowledge, has not been previously associated with immediate neonatal hepatic failure. The giant cell transformation is a common response to a variety of insults and only rarely occurs beyond the neonatal period. Most cases present with cholestatic jaundice and varying degrees of coagulopathy, and, many, as in this case, show progressive resolution. PMID:11948391

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

    International Nuclear Information System (INIS)

    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

  3. Role of mitochondria in drug-induced cholestatic injury.

    Science.gov (United States)

    Kass, George E N; Price, Shirley C

    2008-02-01

    Mitochondria have multiple functions in eukaryotic cells and are organized into dynamic tubular networks that continuously undergo changes through coordinated fusion and fission and migration through the cytosol. Mitochondria integrate cell-signaling networks, especially those involving the intracellular messenger Ca(2+), into the regulation of metabolic pathways. Recently, it has become clear that mitochondria are central to the three main cell death pathways, namely necrosis, apoptosis, and autophagic cell death. This article discusses the role of mitochondria in drug-induced cholestatic injury to the liver. The role of mitochondria in the cellular adaptation against the toxic effects of bile acids is discussed also. PMID:18242496

  4. Unusual causes of intrahepatic cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    Elias E Mazokopakis; John A Papadakis; Diamantis P Kofteridis

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis,including consumption of Teucrium polium (family Lamiaceae) in the form of tea,Stauffer's syndrome,treatment with tamoxifen citrate for breast cancer,infection with Coxiella Burnetii (acute Q fever),and infection with Brucella melitensis (acute brucellosis).

  5. Aquaporins: Their role in cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This review focuses on currant knowledge on hepato-cyte aquaporins (AQPs) and their significance in bile formation and cholestasis. Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate wa-ter flow in response to the osmotic gradients created. During choleresis, hepatocytes rapidly increase their canalicular membrane water permeability by modulat-ing the abundance of AQP8. The question was raised as to whether the opposite process, i.e. a decreased canalicular AQP8 expression would contribute to the development of cholestasis. Studies in several experi-mental models of cholestasis, such as extrahepatic obstructive cholestasis, estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition, biophysical studies in canalicular plasma membranes revealed decreased water permeability as-sociated with AQP8 protein downregulation. The com-bined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow. Thus cholestasis may result from a mutual occurrence of impaired sol-ute transport and decreased water permeability.

  6. Unusual causes of intrahepatic cholestatic liver disease

    OpenAIRE

    Mazokopakis, Elias E.; Papadakis, John A; Kofteridis, Diamantis P.

    2007-01-01

    We report five cases with unusual causes of intrahepatic cholestasis, including consumption of Teucrium polium (family Lamiaceae) in the form of tea, Stauffer’s syndrome, treatment with tamoxifen citrate for breast cancer, infection with Coxiella Burnetii (acute Q fever), and infection with Brucella melitensis (acute brucellosis).

  7. Predictive factors for liver dysfunction and failure after hepatectomy: Analysis of 467 patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Guangjin Du; Liqun Wu; Chengzhan Zhu; Rong Ye; Xin Yi

    2012-01-01

    Objective: The aim of our study was to analyze hepatic dysfunction and failure after hepatocellular carcinoma (HCC) resection and relationship of clinical and pathological factors.Methods: Clinical and pathological data of 467 HCC patients was retrospectively reviewed, who underwent liver resection from January 2002 to December 2008 in the Affiliated Hospital of Medical College, Qingdao University, and the post-resectional liver dysfunction and failure risk factors were analyzed by univariate and multivariate analysis.Results: The morbidity of post-resectional liver dysfunction and failure was 1.7% and 2.1%.The post-resectional liver dysfunction and failure after HCC hepatectomy into the statistical analysis: univariate analysis revealed preoperative platelet level ( 64 U/L), Child-Pugh classification (B), MELD score (≥ 9), intraoperative bleeding (≥ 1000 mL), blood transfusion were positive factors, multivariate analysis (Logistic) revealed that preoperative platelet level (0.983, 95% CI = 0.971-0.995) and intraoperative blood transfusion (3.145, 95% CI = 1.027-12.028) were independent risk factors for post-resectional liver dysfunction and failure.Conclusion: Prevented liver failure and liver dysfunction occurring after liver resection, it is the key to accurate preoperative assessment of liver function and the patient's reserved liver functional, precise hepatectomy and reasonable blockage of hepatic inflow.

  8. Serum thymosin β4 levels in patients with hepatitis B virus-related liver failure

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate whether serum thymosinβ4 can provide diagnostic or prognostic information in liver failure patients caused by chronic hepatitis B virus(HBV) infection. METHODS:Serum thymosinβ4 levels were measured in 30 patients with acute-on-chronic liver failure(ACLF), 31 patients with chronic liver failure(CLF),30 patients with compensated liver cirrhosis(CR)and 32 patients with chronic hepatitis B and 30 healthy controls.Serum thymosinβ4 levels were measured by enzyme-linked immunosorbent assay and C...

  9. Risk factors of acute renal failure after liver transplantation.

    Science.gov (United States)

    Cabezuelo, J B; Ramírez, P; Ríos, A; Acosta, F; Torres, D; Sansano, T; Pons, J A; Bru, M; Montoya, M; Bueno, F S; Robles, R; Parrilla, P

    2006-03-01

    The objective of this study was to determine the risk factors of postoperative acute renal failure (ARF) in orthotopic liver transplantation (OLT). We reviewed 184 consecutive OLT. Postoperative ARF was defined as a persistent rise of 50% increase or more of the S-creatinine (S-Cr). The patients were classified as early postoperative ARF (E-ARF) (first week) and late postoperative ARF (L-ARF) (second to fourth week). Preoperative variables were age, sex, comorbidity, indication for OLT, Child-Pugh stage, united network for organ sharing status, analysis of the blood and urine, and donor's data. Intraoperative variables were systolic arterial pressure, mean arterial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance index. Surgical technique, number of blood products transfused, need for adrenergic agonist drugs, and intraoperative complications were also important. Postoperative variables were duration of stay in the intensive care unit, time on mechanic ventilation, liver graft dysfunction, need for adrenergic agonist drugs, units of blood products infused, episodes of acute rejection, re-operations, and bacterial infections. Firstly we carried out a univariate statistical analysis, and secondly a logistic regression analysis. The risk factors for E-ARF were: pretransplant ARF (odds ratio (OR)=10.2, P=0.025), S-albumin (OR=0.3, P=0.001), duration of treatment with dopamine (OR=1.6, P=0.001), and grade II-IV dysfunction of the liver graft (OR=5.6, P=0.002). The risk factors for L-ARF were: re-operation (OR=3.1, P=0.013) and bacterial infection (OR=2.9, P=0.017). The development of E-ARF is influenced by preoperative factors such as ARF and hypoalbuminemia, as well as postoperative factors such as liver dysfunction and prolonged treatment with dopamine. The predicting factors of L-ARF differ from E-ARF and correspond to postoperative causes such as bacterial infection and surgical re-operation.

  10. The clinical application of non-biotype artificial liver support system to acute liver failure of children

    Institute of Scientific and Technical Information of China (English)

    葛许华

    2014-01-01

    Objective To explore the therapeutic effect of non-biotype artificial liver support system(NBALSS)in acute liver failure(ALF)of children by analyzing the data of16 children with ALF treated with plasma exchange(PE)and continuous venovenous hemodiafiltration(CVVHDF)in the past 2 years.Methods A total of 16 children with ALF in PICU admitted

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

    OpenAIRE

    Jepsen, Peter; Schmidt, Lars E; Larsen, Fin Stolze; Vilstrup, Hendrik

    2010-01-01

    Abstract Background: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure is unknown. Aim: To examine whether paracetamol-induced acute liver failure increases long-term mortality. Methods: We followed all transplant-free survivors of paracetamol-induced acute liver injury hospitalized in a Danish national referral center during 1984-2004. We compared age-specific mortality rates from one year post-discharge through 2008 between those in wh...

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

    OpenAIRE

    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, Promethe...

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

    OpenAIRE

    Hessel Franz P

    2006-01-01

    Abstract Background Acute-on-chronic liver failure (ACLF) is a life threatening acute decompensation of a pre-existing chronic liver disease. The artificial liver support system MARS is a new emerging therapeutic option possible to be implemented in routine care of these patients. The medical efficacy of MARS has been demonstrated in first clinical studies, but economic aspects have so far not been investigated. Objective of this study was to estimate the cost-effectiveness of MARS. Methods I...

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

    Directory of Open Access Journals (Sweden)

    Jamshid Vafaeimanesh

    2013-01-01

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

  15. Intracranial Pressure Monitoring in Acute Liver Failure: Institutional Case Series.

    Science.gov (United States)

    Maloney, Patrick R; Mallory, Grant W; Atkinson, John L D; Wijdicks, Eelco F; Rabinstein, Alejandro A; Van Gompel, Jamie J

    2016-08-01

    Acute liver failure (ALF) has been associated with cerebral edema and elevated intracranial pressure (ICP), which may be managed utilizing an ICP monitor. The most feared complication of placement is catastrophic intracranial hemorrhage in the setting of severe coagulopathy. Previous studies reported hemorrhage rates between 3.8-22 % among various devices, with epidural catheters having lower hemorrhage rates and precision relative to subdural bolts and intraparenchymal catheters. We sought to identify institutional hemorrhagic rates of ICP monitoring in ALF and its associated factors in a modern series guided by protocol implantation. Patient records treated for ALF with ICP monitoring at Mayo Clinic in Rochester, MN from 1995 to 2014 were reviewed. Protocalized since 1995, epidural (EP) ICP monitors were first used followed by intraparenchymal (IP) for stage III-IV hepatic encephalopathy. The following variables and outcomes were collected: patient demographics, ICPs and treatment methods, laboratory data, imaging studies, number of days for ICP monitoring, radiographic and symptomatic hemorrhage rates, orthotopic liver transplantation rates, and death. A total of 20 ICP monitors were placed for ALF, 7 EP, and 13 IP. International normalized ratio (INR) at placement of an EP monitor was 2.4 (1.7-3.2) with maximum of 2.7 (2.0-3.6) over the following 2.3 (1-3) days. Mean EP ICP at placement was 36.3 (11-55) and maximum of 43.1 (20-70) mm Hg. INR at placement of an IP monitor was 1.3 (hepatic encephalopathy. Monitored patients in both groups experienced elevations of ICP in the setting of intermittent coagulopathy. Severity of coagulopathy did not influence hemorrhage rate. Yet, hemorrhages related to IP monitoring can be catastrophic and may add to the overall mortality. PMID:26966022

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

    Science.gov (United States)

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

    2016-09-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic disease, characterized by overwhelming stimulation of the immune system and categorized as primary or secondary types. Occasionally, acute liver failure (ALF) may dominate the clinical presentation. Given the systemic nature of HLH and risk of recurrence, HLH is considered by many a contraindication to liver transplantation (LT). The aim of this study is to review our single-center experience with LT in children with secondary HLH and ALF (HLH-ALF). This is a cross-sectional, retrospective study of children with secondary HLH-ALF that underwent LT in 2005-2014. Of 246 LTs, 9 patients (3 males; median age, 5 years; range, 0.7-15.4 years) underwent LT for secondary HLH-ALF. Disease progression was rapid with median 14 days (range, 6-27 days) between first symptoms and LT. Low fibrinogen/high triglycerides, elevated ferritin, hemophagocytosis on liver biopsy, and soluble interleukin 2 receptor levels were the most commonly fulfilled diagnostic criteria; HLH genetic studies were negative in all patients. Immunosuppressive therapy after LT included corticosteroids adjusted to HLH treatment protocol and tacrolimus. Thymoglobulin (n = 5), etoposide (n = 4), and alemtuzumab (n = 2) were used in cases of recurrence. Five (56%) patients experienced HLH recurrence, 1 requiring repeat LT, and 3 died. Overall graft and patient survival were 60% and 67%, respectively. Six patients are alive and well at a median of 24 months (range, 15-72 months) after transplantation. In conclusion, LT can be beneficial in selected patients with secondary HLH-ALF and can restore good health in an otherwise lethal condition. Liver Transplantation 22 1245-1253 2016 AASLD. PMID:27216884

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

    Science.gov (United States)

    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. Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Darin S Krygier; Urs P Steinbrecher; Martin Petric; Siegfried R Erb; Stephen W Chung; Charles H Scudamore; Andrzej K Buczkowski; Eric M Yoshida

    2009-01-01

    Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported,mainly in children.Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation.We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation.This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation.This case suggests that Parvovirus B19 induced liver disease can affect adults,can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation.

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

    Science.gov (United States)

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

    Directory of Open Access Journals (Sweden)

    G. Kneiseler

    2010-02-01

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

  1. 婴儿肠道菌群与分娩方式、喂养方式及胆汁淤积性肝病的关系%Relationship between Intestinal Flora of Infants, Delivery and Feeding Modes and Cholestatic Liver Disease

    Institute of Scientific and Technical Information of China (English)

    江玲; 单庆文; 王琳琳; 唐清; 陈秀奇; 杨少丽; 张智

    2012-01-01

    Objective To analyze the influence of delivery and feeding modes on intestinal flora of healthy infants and investigate the role and significance of the molecular microbial ecology related to intestinal canal in the cholestatic liver disease. Methods Thirty - seven cases of healthy infants (including 21 cases of vaginal delivery, 16 cases of caesarean birth; 15 cases of breast - feeding ,22 cases of bottle -feeding) and 84 cases of cholestatic liver disease were selected, and their stool were collected, the bacterial DNA in the stool between the both groups and A260 value was measured, and the numbers of the 3 kinds of representative bacteria of bifidobacterium, lactobacillus and escherichia coli were determined by applying real - time fluorescent PCR. Results In comparison of the delivery infants to caesarean infants and breast - feeding infants to bottle - feeding infants, the bacterial DNA A^,, value in stool specimen and the numbers of the 3 kinds of representative bacteria had no statistically significant difference (Pt >0.05). The bacterial DNA Ajg, value in the stool specimen in the healthy control group and cholestatic liver disease group were (1.94 ± 0. 47) g ? L"' and (0.40±0.09) g ? L"', respectively, there was statistically significant difference between both groups(t = 8.91 ,P=0. 00) ;log value of the numbers of 3 kinds of representative bacteria in healthy control group and cholestatic liver disease group were:bifidobacterium 9.49 ±0.59 is 7.68 ±0.57;lactobacillus 8.58 ±0.32 us 8. 16 ±0. 70;escherichia coli 6.87 ±0.67 vs 7.26 ±0. 86,respectively. In comparison of the 3 kinds of representative bacteria in both groups had statistically significant difference(? = 15.96,3.46, -2.41 ;P =0.00,0.00,0.02). Conclusions Different modes of delivery and feeding had no influence on intestinal flora of healthy infants; the intestinal flora of infants with cholestatic liver disease is different from that of healthy infants, total bacteria in the stool of the

  2. Vitamin A-induced cholestatic hepatitis: a case report

    DEFF Research Database (Denmark)

    Becker, P.; Maurer, B.; Schirrmacher, P.;

    2007-01-01

    We report a case of intrahepatic cholestasis due to chronic vitamin A supplementation. A 70-year-old woman was admitted to the hospital for jaundice and reduced nutritional and general status with a 2-month history of increasing cholestasis. Some years previously she had suffered from breast...... and ovarian cancer with subsequent surgery and chemotherapy. Chemotherapy was terminated one month before elevated serum transaminase activities and cholestatic serum markers were noted. Following the chemotherapy, supportive care included weekly vitamin A injections (100,000 IU per injection). Liver biopsy...... showed an acute toxic liver injury with focal parenchymal necrosis, sinusoidal lesions, inflammatory infiltrate (round cells, macrophages), and activation and proliferation of stellate cells. The hepatic vitamin A concentration was found to be significantly elevated. There were no signs of intrahepatic...

  3. Fulminant liver failure models with subsequent encephalopathy in the mouse

    Institute of Scientific and Technical Information of China (English)

    Ann-Marie T Baine; Tomohide Hori; Feng Chen; Lindsay B Gardner; Shinji Uemoto; Justin H Nguyen

    2011-01-01

    BACKGROUND:  A reliable model of fulminant liver failure (FLF) is urgently required in this research field. This study aimed to develop a murine FLF model. METHODS: We used three groups of male C57BL/6 mice:control, with azoxymethane treatment (AOM group), and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-α group). The effects of body temperature (BT) control on survival in all three groups were investigated. Using BT control, we compared the survival, histopathological findings and biochemical/coagulation profiles between the two experimental groups. The effects of hydration on international normalized ratios of prothrombin time (PT-INRs) were also checked. Dose-dependent survival curves were constructed for both experimental groups. Neurological behavior was assessed using a coma scale. RESULTS: No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNF-α group, showed a significant difference in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs, and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups. There were significant differences between FLF models in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study. CONCLUSIONS: AOM provides a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on the research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

  4. Adult-to-adult living donor liver transplantation for acute liver failure in China

    Institute of Scientific and Technical Information of China (English)

    Ding Yuan; Fei Liu; Yong-Gang Wei; Bo Li; Lv-Nan Yan; Tian-Fu Wen; Ji-Chun Zhao

    2012-01-01

    AIM:To investigate the long-term outcome of recipients and donors of adult-to-adult living-donor liver transplantation (AALDLT) for acute liver failure (ALF).METHODS:Between January 2005 and March 2010,170 living donor liver transplantations were performed at West China Hospital of Sichuan University.All living liver donor was voluntary and provided informed consent.Twenty ALF patients underwent AALDLT for rapid deterioration of liver function.ALF was defined based on the criteria of the American Association for the Study of Liver Diseases,including evidence of coagulation abnormality [international normalized ratio (INR) ≥ 1.5] and degree of mental alteration without pre-existing cirrhosis and with an illness of < 26 wk duration.We reviewed the clinical indications,operative procedure and prognosis of AALDTL performed on patients with ALF and corresponding living donors.The potential factors of recipient with ALF and corresponding donor outcome were respectively investigated using multivariate analysis.Survival rates after operation were analyzed using the Kaplan-Meier method.Receiver operator characteristic (ROC) curve analysis was undertaken to identify the threshold of potential risk factors.RESULTS:The causes of ALF were hepatitis B (n =18),drug-induced (n =1) and indeterminate (n =1).The score of the model for end-stage liver disease was 37.1 ± 8.6,and the waiting duration of recipients was 5 ± 4 d.The graft types included right lobe (n=17) and dual graft (n =3).The mean graft weight was 623.3 ± 111.3 g,which corresponded to graft-to-recipient weight ratio of 0.95% ± 0.14%.The segment Ⅴor Ⅷ hepatic vein was reconstructed in 11 right-lobe grafts.The 1-year and 3-year recipient's survival and graft survival rates were 65% (13 of 20).Postoperative results of total bilirubin,INR and creatinine showed obvious improvements in the survived patients.However,the creatinine level of the deaths was increased postoperatively and became more aggravated

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  6. Pre-Operative Risk Factors Predict Post-Operative Respiratory Failure after Liver Transplantation

    OpenAIRE

    Huang, Ching-Tzu; Lin, Horng-Chyuan; Chang, Shi-Chuan; Lee, Wei-Chen

    2011-01-01

    Objective Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF) after liver transplantation and the impact on short-term survival rates. Design The retrospective observational cohort study was conducted in a twelve-bed adult s...

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

    Directory of Open Access Journals (Sweden)

    D. V. Grizay

    2015-01-01

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

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

    Science.gov (United States)

    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.

  9. Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

    OpenAIRE

    Al-Chalabi, Ahmed; Matevossian, Edouard; v. Thaden, Anne-K.; Luppa, Peter; Neiss, Albrecht; Schuster, Tibor; Yang, Zejian; Schreiber, Catherine; Schimmel, Patrick; Nairz, Ewald; Perren, Aurel; Radermacher, Peter; Huber, Wolfgang; Schmid, Roland M.; Kreymann, Bernhard

    2013-01-01

    Background Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. Methods In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In...

  10. Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

    OpenAIRE

    Al-Chalabi, Ahmed; Matevossian, Edouard; v. Thaden, Anne-K.; Luppa, Peter; Neiss, Albrecht; Schuster, Tibor; Yang, Zejian; Schreiber, Catherine; Schimmel, Patrick; Nairz, Ewald; Radermacher, Peter; Huber, Wolfgang; Schmid, Roland M.; Kreymann, Bernhard; Perren, Aurel

    2013-01-01

    BACKGROUND Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6...

  11. Acute cholestatic hepatitis caused by amoxicillin/clavulanate

    Science.gov (United States)

    Beraldo, Daniel Oliveira; Melo, Joanderson Fernandes; Bonfim, Alexandre Vidal; Teixeira, Andrei Alkmim; Teixeira, Ricardo Alkmim; Duarte, André Loyola

    2013-01-01

    Amoxicillin/clavulanate is a synthetic penicillin that is currently commonly used, especially for the treatment of respiratory and cutaneous infections. In general, it is a well-tolerated oral antibiotic. However, amoxicillin/clavulanate can cause adverse effects, mainly cutaneous, gastrointestinal, hepatic and hematologic, in some cases. Presented here is a case report of a 63-year-old male patient who developed cholestatic hepatitis after recent use of amoxicillin/clavulanate. After 6 wk of prolonged use of the drug, he began to show signs of cholestatic icterus and developed severe hyperbilirubinemia (total bilirubin > 300 mg/L). Diagnostic investigation was conducted by ultrasonography of the upper abdomen, serum tests for infection history, laboratory screening of autoimmune diseases, nuclear magnetic resonance (NMR) of the abdomen with bile duct-NMR and transcutaneous liver biopsy guided by ultrasound. The duration of disease was approximately 4 mo, with complete resolution of symptoms and laboratory changes at the end of that time period. Specific treatment was not instituted, only a combination of anti-emetic (metoclopramide) and cholestyramine for pruritus. PMID:24379601

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

    Directory of Open Access Journals (Sweden)

    Rita Jermyn

    2014-01-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-08-01

    We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival. PMID:27222930

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  17. Artificial and bioartificial liver support: A review of perfusion treatment for hepatic failure patients

    Institute of Scientific and Technical Information of China (English)

    Katsutoshi Naruse; Wei Tang; Masatoshi Makuuchi

    2007-01-01

    Liver transplantation and blood purification therapy, including plasmapheresis, hemodiafiltration, and bioartificial liver support, are the available treatments for patients with severe hepatic failure. Bioartificial liver support, in which living liver tissue is used to support hepatic function, has been anticipated as an effective treatment for hepatic failure. The two mainstream systems developed for bioartificial liver support are extracorporeal whole liver perfusion (ECLP) and bioreactor systems. Comparing various types of bioartificial liver in view of function, safety, and operability, we concluded that the best efficacy can be provided by the ECLP system. Moreover, in our subsequent experiments comparing ECLP and apheresis therapy, ECLP offers more ammonia metabolism than HD and HF. In addition, ECLP can compensate amino acid imbalance and can secret bile. A controversial point with ECLP is the procedure is labor intensive, resulting in high costs. However, ECLP has the potential to reduce elevated serum ammonia levels of hepatic coma patients in a short duration. When these problems are solved, bioartificial liver support, especially ECLP, can be adopted as an option in ordinary clinical therapy to treat patients with hepatic failure.

  18. TREATMENT OF CANINE ACUTE LIVER FAILURE WITH MODIFIED EXTRACORPOREAL PIGLIVER PERFUSION

    Institute of Scientific and Technical Information of China (English)

    王博; 吕毅; 刘昌; 仵正; 潘承恩

    2003-01-01

    Objective To study the theraputic effect of extracorporeal liver perfusion on the treatment of acute liver failure. Methods Mongrel dogs weighing 12-14*!kg were selected. Hepatic failure was induced by an end-to-side portacaval shunt. The common hepatic and gastroduodenal arteries were occluded for 2 hours. To the control group (n=7), the dogs received standard medical therapy . To the treating group (n=10), the dogs received extracorporeal kidney and liver perfusion at the onset of the occlusion of the hepatic artery. During the liver support, the animals were frequently monitored regarding their clinical state, liver function, biochemical and hematological parameters. Results After the occlusion of the liver blood flow, all dogs died within 3-7.5 hours. The average survival time was (5.7±1.2) hours. Serum levels of ALT, AST, LDH and ammonia increased significantly. In the treating group, the dogs died within 7-10.5 hours. The average survival time was 8.6±1.1 hours. There were no significant diferences in serum levels of ALT, AST, LDH between the two groups(P>0.05). There were dramatic diferences in blood Ammonia level, PT, FIB between the two groups(P<0.05). The survival time was longer in treating group. The animals' blood pressure were more stable in the treating group than that in the control group. Conclusion The modified xenogenic liver perfusion can provide necessary hepatic function for the acute liver failure dogs.

  19. Amelioration of liver injury by continuously targeted intervention against TNFRp55 in rats with acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Yumin Xu

    Full Text Available BACKGROUND: Acute-on-chronic liver failure (ACLF is an acute deterioration of established liver disease. Blocking the TNF (tumor necrosis factor/TNFR (tumor necrosis factor receptor 1 pathway may reduce hepatocyte apoptosis/necrosis, and subsequently decrease mortality during development of ACLF. We demonstrated that a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc] prevented/reduced development of acute liver failure by blocking the TNF/TNFR1 (TNFRp55 pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease (liver fibrosis/cirrhosis was induced in Wistar rats by repeatedly challenging with human serum albumin (HSA, and confirmed by histopathology. ACLF was induced with D-galactosamine (D-GalN/lipopolysaccharide (LPS i.p. in the rats with chronic liver disease. Serum and liver were collected for biochemical, pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced interleukin (IL-6 levels in serum and liver, as well as reduced hepatic caspase-3 activity, compared to that of mock treated group. Reduced hepatic damage was confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased hepatocyte proliferation (PCNA. This is also supported by the findings that caspase-3 production was up-regulated significantly in ACLF group compared to the mock treated group. Moreover, up-regulated caspase-3 was inhibited following sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate during development of ACLF via ameliorating liver injury with a potential therapeutic value.

  20. Cost-utility of molecular adsorbent recirculating system treatment in acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Taru; Kantola; Suvi; Mklin; Anna-Maria; Koivusalo; Pirjo; Rsnen; Anne; Rissanen; Risto; Roine; Harri; Sintonen; Krister; Hckerstedt; Helena; Isoniemi

    2010-01-01

    AIM:To determine the short-term cost-utility of mo-lecular adsorbent recirculating system(MARS) treatment in acute liver failure(ALF).METHODS:A controlled retrospective study was conducted with 90 ALF patients treated with MARS from 2001 to 2005.Comparisons were made with a historical control group of 17 ALF patients treated from 2000 to 2001 in the same intensive care unit(ICU) specializing in liver diseases.The 3-year outcomes and number of liver transplantations were recorded.All direct liver disease-rel...

  1. Arterial steroid injection therapy can inhibit the progression of severe acute hepatic failure toward fulminant liver failure

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Kotoh; Tsuyoshi Tajima; Yoshiki Asayama; Kousei Ishigami; Masakazu Hirakawa; Munechika Enjoji; Makoto Nakamuta; Tsuyoshi Yoshimoto; Motoyuki Kohjima; Shusuke Morizono; Shinsaku Yamashita; Yuki Horikawa; Kengo Yoshimitsu

    2006-01-01

    AIM: To utilize transcatheter arterial steroid injection therapy (TASIT) via the hepatic artery to reduce hepatic macrophage activity in patients with severe acute hepatic failure.METHODS: Thirty-four patients with severe acute hepatic failure were admitted to our hospital between June 2002 to June 2006 providing for the possibility of liver transplantation (LT). Seventeen patients were treated using traditional liver supportive procedures, and the other 17 patients additionally underwent TASIT with 1000 mg methylprednisolone per day for 3 continuous days.RESULTS: Of the 17 patients who received TASIT, 13 were cured without any complications, 2 died, and 2 underwent LT. Of the 17 patients who did not receive TASIT, 4 were self-limiting, 7 died, and 6 underwent LT.Univariate logistic analysis revealed that ascites, serum albumin, prothrombin time, platelet count, and TASIT were significant variables for predicating the prognosis.Multivariate logistic regression analysis using stepwise variable selection showed that prothrombin time, platelet count, and TASIT were independent predictive factors.CONCLUSION: TASIT might effectively prevent the progression of severe acute hepatic failure to a fatal stage of fulminant liver failure.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  4. Epidemiological and clinical features of hepatitis B virus related liver failure in China

    Institute of Scientific and Technical Information of China (English)

    Chen Liu; Yu-Ming Wang; Ke Fan

    2011-01-01

    AIM: To examine the epidemiologic and clinical characteristics of hepatitis B virus (HBV) related liver failure in patients in China. METHODS: This study was conducted with a retrospective design to examine 1066 patients with HBVrelated liver failure in the southwest of China. RESULTS: There were more male than female patients. Young and middle-aged people comprised most of the patients. Farmers and laborers comprised the largest proportion (63.09%). Han Chinese accounted for 98.12%, while minority ethnic groups only accounted for 0.88% of patients. A total of 43.47% patients had a family history of HBV-related liver failure and 56.66% patients had a history of drinking alcohol. A total of 42.59% patients with HBV-related liver failure had definite causes. With regard to the clinical manifestation of HBV-related liver failure, the symptoms were: hypodynamia, anorexia and abdominal distension. Total bilirubin (TBIL) and alanine aminotransferase (ALT) levels were altered in 46.23% of patients with evident damage of the liver. Univariate logistic regression analysis showed that the patients' prognoses were correlated with ALT, aspartate aminotransferase, albumin, TBIL, prothrombin activity (PTA), and alpha-fetoprotein levels, and drinking alcohol, ascites, hepatorenal syndrome, infection and ≥ 2 complications. Multifactor logistic regression analysis showed that the activity of thrombinogen and the number of complications were related to the prognosis. CONCLUSION: Alcohol influences the patients' prognosis and condition. PTA and complications are independent factors that can be used for estimating the prognosis of HBV-related liver failure.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Progression of Liver Disease

    Science.gov (United States)

    ... Browse Related Terms Progression of Liver Disease , Family History of Liver Disease , Liver Wellness , Liver Failure , Liver Biopsy Home > Your Liver > Liver Disease Information > The Progression ...

  8. Effect of extracorporeal bioartificial liver support system on fulminant hepatic failure rabbits

    Institute of Scientific and Technical Information of China (English)

    Ying Jie Wang; Meng Dong Li; Yu Ming Wang; Guo Zheng Chen; Guo Dong Lu; Zao Xia Tan

    2000-01-01

    AIM To evaluate the possibility of using cultured human hepatocytes as a bridge between bioartificial liver and liver transplantation. METHODS In this experiment, the efficacy of extracorporeal bioartificial liver support system (EBLSS) consisting of spheriodal human liver cells and cultured hepatocytes supernatant was assessed in vivo using galactosamine induced rabbit model of fulminant hepatic failure. RiESULTS There was no difference of survival between the two groups of rabbits, but in the supported rabbits serum alanine aminotransferase, total bilirubin and creatinine were significantly lower and hepatocyte necrosis was markedly milder than those in control animals. In addition, a good viability of human liver cells was noted after the experiment. CONCLUSION EBLSS plays a biologic role in maintaining and compensating the function of the liver.

  9. [Liver damage caused by drugs].

    Science.gov (United States)

    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. Comparison between bioartificial and artificial liver for the treatment of acute liver failure in pigs

    Institute of Scientific and Technical Information of China (English)

    Yasushi Kawazoe; Susumu Eguchi; Nozomu Sugiyama; Yukio Kamohara; Hikaru Fujioka; Takashi Kanematsu

    2006-01-01

    AIM: To characterize and evaluate the therapeutic efficacy of bioartificial liver (BAL) as compared to that of continuous hemodiafiltration (CHDF) with plasma exchange (PE), which is the current standard therapy for fulminant hepatic failure (FHF) in Japan.METHODS: Pigs with hepatic devascularization were divided into three groups: (1) a non-treatment group (NT; n = 4); (2) a BAL treatment group (BAL; n = 4),(3) a PE + CHDF treatment group using 1.5 L of normal porcine plasma with CHDF (PE + CHDF, n = 4). Our BAL system consisted of a hollow fiber module with 0.2 μm pores and 1 × 1010 of microcarrier-attached hepatocytes inoculated into the extra-fiber space. Each treatment was initiated 4 h after hepatic devascularization.RESULTS: The pigs in the BAL and the PE + CHDF groups survived longer than those in the NT group. The elimination capacity of blood ammonia by both BAL and PE + CHDF was significantly higher than that in NT.Aromatic amino acids (AAA) were selectively eliminated by BAL, whereas both AAA and branched chain amino acids, which are beneficial for life, were eliminated by PE + CHDF.Electrolytes maintenance and acid-base balance were better in the CPE + CHDF group than that in the BAL group.CONCLUSION: Our results suggest that PE + CHDF eliminate all factors regardless of benefits, whereas BAL selectively metabolizes toxic factors such as AAA.However since PE + CHDF maintain electrolytes and acid-base balance, a combination therapy of BAL plus CPE + CHDF might be more effective for FHF.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ching-Tzu Huang

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

    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

  17. Optimizing management in autoimmune hepatitis with liver failure at initial presentation

    Institute of Scientific and Technical Information of China (English)

    Jonathan R Potts; Sumita Verma

    2011-01-01

    Autoimmune hepatitis (AIH) is a disease of unknown etiology, its hallmark being ongoing hepatic inflamma-tion. By its very nature, it is a chronic condition, al-though increasingly, we are becoming aware of patients with acute presentations, some of whom may have liver failure. There are very limited published data on patients with AIH with liver failure at initial diagnosis, which consist mostly of small retrospective studies. As a consequence, the clinical features and optimal management of this cohort remain poorly defined. A subset of patients with AIH who present with liver failure do respond to corticosteroids, but for the vast majority, an urgent liver transplantation may offer the only hope of long-term survival. At present, there is uncertainty on how best to stratify such a cohort into responders and non-responders to corticosteroids as soon as possible after hospitalization, thus optimizing their management. This editorial attempts to answer some of the unre-solved issues relating to management of patients with AIH with liver failure at initial presentation. However, it must be emphasized that, at present, this editorial is based mostly on small retrospective studies, and it is an understatement that multicenter prospective studies are urgently needed to address this important clinical issue.

  18. Treatment modalities in experimentally induced acute liver failure

    NARCIS (Netherlands)

    P.T. Ernst

    1988-01-01

    textabstractThe findings made in the presented study suggest that one or more still unknown factors inherent in the experimental models currently in use are of critical importance and that only a certain limited type of model of acute hepatic failure is suitable for the evaluation of the effectivene

  19. Emergency adult living donor right lobe liver transplantation for fulminant hepatic failure

    Institute of Scientific and Technical Information of China (English)

    ZHANG Feng; LU Sheng; PU Liyong; LU Ling; WANG Xuehao; LI Xiangcheng; KONG Lianbao; SUN Beicheng; LI Guoqiang; QIAN Xiaofen; CHEN Feng; WANG Ke

    2007-01-01

    Fulminant hepatitis is fatal in most cases and timely liver transplantation is the only effective treatment.This study evaluates the survival outcomes of patients who underwent living-donor liver transplantation (LDLT)using right lobe liver grafts for fulminant liver failure due to hepatitis B infection.Nine cases of adult right lobe LDLT were performed in our department from September 2002 to August 2005 and the clinical and following-up data were reviewed.According to the pre-transplant Child-Pugh-Turcotte classification,the nine patients were classified as grade C.The model for end-stage liver disease (MELD) score of these patients ranged from 16 to 42.The principal complications before transplantation included abnormal renal function,hepatic coma of different degrees and alimentary tract hemorrhage.The main complications after transplantation included pulmonary infection in two cases,acute renal failure in three cases and transplantation-related encephalopathy in one case.No primary failure of vascular or biliary complications occurred.The one-year survival rate was 55.6%.There were no serious complications or deaths in donors.In general,it is extremely difficult to treat fulminant hepatitis by conservative regimen,particularly,in cases with rapid progresslon.Emergency adult living-donor liver transplantation is an effective treatment for fulminant hepatitis patients and is relatively safe for donors.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-15

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

  1. HFRS with Severe Heart Liver and Renal Failure:a Case Report

    Institute of Scientific and Technical Information of China (English)

    Qing; Zhou; Meng-Hou; Lu; Lei; Fu; De-Ming; Tan

    2012-01-01

    Hemorrhagic fever with renal syndrome(HFRS) is caused by hantavirus infection,which was characterized by abrupt high fever,systemic hemorrhage,hypotension and renal damage.Although multiple system organ damage was not uncommon,but multiple organ system failure were rare.Hereafter we report one case with simultaneous renal,heart and liver failure.In this case,we received some experience and lessons.

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

    OpenAIRE

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

    2012-01-01

    We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvi...

  3. Role of monocytes and macrophages in experimental and human acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Lucia; A; Possamai; Charalambos; Gustav; Antoniades; Quentin; M; Anstee; Alberto; Quaglia; Diego; Vergani; Mark; Thursz; Julia; Wendon

    2010-01-01

    Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of AL...

  4. Chronic Liver Failure after Treatment with Infliximab for Ankylosing Spondylitis in a Patient with Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Yun-ru Li; Feng-xin Chen; Xue-fei Duan; Xue-song Gao; Xiao-ling Fan

    2013-01-01

    A 50-year-old man with ankylosing spondylitis was treated successfully with inlfiximab, who was also a HBV carrier for about twenty-ifve years. After injection with inlfiximab for four times, he developed jaundice and HBV DNA was detectable in serum. Serum aminotransferase and total bilirubin levels were higher than normal. Then he was hospitalized and treated with entacavir and Chinese herb medicine. But his liver damage aggravated and was diagnosed as acute on chronic liver failure. Finally, liver transplantation was carried out and he was cured successfully.

  5. Parvovirus B19 associated acute cholestatic hepatitis

    Directory of Open Access Journals (Sweden)

    S. Perrini

    2014-12-01

    Full Text Available There are few reports in the literature of hepatitis as a manifestation of Parvovirus B19 infection. We describe a case of Parvovirus B19 associated acute cholestatic hepatitis diagnosed based on a positive serologic test (IgM and molecular detection of parvovirus B19 DNA in peripheral blood. Parvovirus B19 infection should be considered in the differential diagnosis of patient presenting with acute hepatitis of unknown etiology.

  6. Parvovirus B19 associated acute cholestatic hepatitis

    OpenAIRE

    Perrini, S; B. Guidi; Torelli, P; A. Forte

    2014-01-01

    There are few reports in the literature of hepatitis as a manifestation of Parvovirus B19 infection. We describe a case of Parvovirus B19 associated acute cholestatic hepatitis diagnosed based on a positive serologic test (IgM) and molecular detection of parvovirus B19 DNA in peripheral blood. Parvovirus B19 infection should be considered in the differential diagnosis of patient presenting with acute hepatitis of unknown etiology.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  9. A Rare Cause of Neonatal Liver Failure: Neonatal Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Uluca Ü et al.

    2013-09-01

    Full Text Available Neonatal hemochromatosis (NH is a severe rare liver disease in neonatal period associated with ekstrahepatic siderosis. This disease is characterized by hepatocellular insufficiency that presented with jaundice, hypoglycemia, hypoalbuminemia, low fibrinogen levels, thrombocytopenia, anemia, direct and indirect hyperbilirubinemia from the first days of life. Herein we reported a case with Rh incompatibility whose jaundice was noted at the first day of life and referred to our hospital for exchange transfusion, but thereafter diagnosed as NH and reviewed the literature in the view point of the latest developments related to the topic.

  10. A cholestatic syndrome may be a surprising cause of medical error

    Directory of Open Access Journals (Sweden)

    M. Pătrășescu

    2015-04-01

    Full Text Available Autoimmune cholangitis defines a spectrum of cholestatic liver diseases that are characterized by inflammation of bile ducts and a reasonable response to immunosuppressive therapy. The two most common diseases associated with this term in the literature are: an overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis and a form of hyper IgG4 syndrome (currently associated with autoimmune pancreatitis. Liver biopsy is mandatory for the diagnosis. There are, whatsoever, in clinical practice, many cases that do not meet current diagnostic criteria but that have a good response to corticosteroid treatment.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    % of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. METHODS: In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus......BACKGROUND & AIMS: Acute liver failure (ALF) often results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15...

  12. An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats Um extrato aquoso de Bidens pilosa L. protege o fígado da doença colestática: estudo experimental em ratos jovens

    Directory of Open Access Journals (Sweden)

    Marta Izabel Suzigan

    2009-10-01

    Full Text Available PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa L. (BPE in cholestatic liver disease induced by ligature and resection of the common bile ducts (LRBD in young rats. METHODS: We studied four groups of ten 21 days old (P21 Wistar rats, Group SW: sham operation and water; Group SD: sham operation and BPE (160 mg of fresh leaves/100 g of body weight/day; Group LW: LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time (PST and serum activities of aspartate aminotransferase (AST and of alanine aminotransferase (ALT were determined after the sacrifice (P70. A Ruwart's score for hepatic fibrosis (RS was given to each animal. Were employed two way ANOVA and the test of Tukey or a non-parametric test for multiple comparisons. RESULTS: There were statistically significant differences between LW and LD in the measurements of the PST ((means LW=390; LD=173, AST (means LW=8, LD=5, ALT (medians LW=2; LD=1 e RS (medians LW=2; LD=1. CONCLUSION: BPE could be used in the phytotherapy of the hepatic damage induced by chronic obstructive cholestasis, because protects liver function, decreases the rate of necrosis and liver fibrosis in cholestatic liver disease.OBJETIVO: Testar o efeito hepatoprotetor do extrato aquoso de Bidens pilosa L. (EBP na doença hepática induzida pela ligadura e ressecção do ducto biliar comum (LRDBC em ratos jovens. MÉTODOS: Estudamos ratos Wistar com 21º. dia de vida (P21 divididos em quatro grupos de 10 animais, Grupo SA: operação simulada e água; Grupo SD: operação simulada e EBP (160mg de folhas frescas/100g de peso corporal/dia; Grupo LA: LRDBC e água e Grupo LD: LRDBC e EBP diariamente. O tempo de sono por pentobarbital (TSP, aspartato (AST e alanina (ALT aminotransferase foram determinadas após o sacrifício (P70. O Score de Ruwart (SR para fibrose hepática foi atribuído para cada animal. Foi realizada análise de variância com dois fatores e pelo teste de Tukey

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

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    1990-01-01

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

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-10-15

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

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

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    AIM: To propose an allocation system of patients with liver cirrhosis to intensive care unit (ICU), and developed a decision tool for clinical practice. METHODS: A systematic review of the literature was performed in PubMed, MEDLINE and EMBASE databases. The search includes studies on hospitalized...... patients with cirrhosis and organ failure, or acute on chronic liver failure and/or intensive care therapy. RESULTS: The initial search identified 660 potentially relevant articles. Ultimately, five articles were selected; two cohort studies and three reviews were found eligible. The literature...... on this topic is scarce and no studies specifically address allocation of patients with liver cirrhosis to ICU. Throughout the literature, there is consensus that selection criteria for ICU admission should be developed and validated for this group of patients and multidisciplinary approach is mandatory. Based...

  3. Acute liver failure due to primary amyloidosis in a nephrotic syndrome: a swiftly progressive course.

    Science.gov (United States)

    Cardoso, Brigite Aguiar; Leal, Rita; Sá, Helena; Campos, Mário

    2016-01-01

    AL amyloidosis is a clonal plasma cell proliferative disorder characterised by extracellular tissue deposits of insoluble fibrils derived from κ or λ immunoglobulin light chains. The most common organs affected by AL amyloidosis are the kidney, presenting with nephrotic syndrome and/or progressive renal dysfunction, and the heart, with restrictive cardiomyopathy. Hepatic deposition of fibrils occurs in half the cases but the liver is rarely the predominantly affected organ. The most common presentation of hepatic amyloidosis is hepatomegaly with elevated alkaline phosphatase. Acute liver failure with cholestasis and jaundice is a rare complication, with a prevalence of approximately 5%, and is usually associated with a worse prognosis. We report a case of a 39-year-old man admitted to our nephrology department with an unusual presentation of primary amyloidosis with nephrotic syndrome and acute liver failure, complicated by obstructive cholestasis resulting in death 2 months after diagnosis. PMID:26965175

  4.  Liver transplantation followed by autologous stem cell transplantation for acute liver failure caused by AL amyloidosis. Case report and review of the literature.

    Science.gov (United States)

    Elnegouly, Mayada; Specht, Katja; Zoller, Heinz; Matevossian, Edouard; Bassermann, Florian; Umgelter, Andreas

    2016-01-01

     Hepatic involvement in AL amyloidosis may present as acute liver failure. Historically, liver transplantation in these cases has achieved poor outcomes due to progress of amyloidosis and non-hepatic organ damage. In the era of bortezomib treatment, the prognosis of AL amyloidosis has been markedly improved and may also result in better post-transplant outcomes. We present a case of isolated acute liver failure caused by AL amyloidosis, bridged to transplantation with bortezomib and treated with sequential orthotopic liver transplantation (OLT) and autologous stem cell transplantation. The patient is in stable remission 3 years after OLT. PMID:27236160

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

    Directory of Open Access Journals (Sweden)

    Tae Yeob Kim

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

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

    Institute of Scientific and Technical Information of China (English)

    Hai-YingYu; Dai-RongXiang; Hai-JunHuang; JunLi; Ji-FangSheng

    2010-01-01

    BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance. METHODS: We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues. RESULTS: Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5±369.6 pmol/ml) than in 12 deteriorating patients (462.3±235.8 pmol/ml). Similar levels were found in 20 HCC patients (917.9±332. 7 pmol/ml), 24 chronic hepatitis B patients (969.2±332.5 pmol/ml) and 10 healthy persons (806.9±240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74×106) copies/μl] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82×103)copies/μl] or in healthy liver tissues [10E4.31 (2.04×104) copies/μl]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. CONCLUSION: Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.

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

    International Nuclear Information System (INIS)

    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. (orig.). With 3 figs., 1 tab

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

    Energy Technology Data Exchange (ETDEWEB)

    Buyck, D. [Department of Nuclear Medicine, Hopital Beaujon, Clichy (France); Bonnin, F. [Department of Nuclear Medicine, Hopital Beaujon, Clichy (France); Bernuau, J. [Department of Hepatology, Hopital Beaujon, Clichy (France); Belghiti, J. [Department of Surgery, Hopital Beaujon, Clichy (France); Bok, B. [Department of Nuclear Medicine, Hopital Beaujon, Clichy (France)

    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. (orig.). With 3 figs., 1 tab.

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

    Science.gov (United States)

    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. PMID:9021110

  10. Analyses of prognostic indices of chronic liver failure caused by hepatitis virus

    Institute of Scientific and Technical Information of China (English)

    Xiao-Mao Li; Lin Ma; Yue-Bo Yang; Zhong-Jie Shi; Shui-Sheng Zhou

    2005-01-01

    AIM: To analyze the related indices about the prognosesof chronic liver failure caused by hepatitis virus.METHODS: Retrospectively reviewed 320 cases of chronic liver failure caused by hepatitis viruses. An improved group and an ineffective group (IG) were made to compare and analyze their clinical manifestations, laboratory examination indices and complications. Logistic regression was also carried out. RESULTS: There were significant differences (P<0.05) between the improved group and the IG upon such indices as age, bilirubin, prothrombin time, albumin, alpha fetoprotein, the size of liver and complications (P<0.05). The regression formula was as follows: P = 1/(1+e-y)(y= 1.7262-0.0948X1+2.9846X2+0.6992X3+ 1.6019X4+2.0398X5). (Note: X1-Prothrombin activity; X2-digestive tract hemorrhage; X3-hepatic encephalopathy; X4-hepatorenal syndrome; X5-pulmonary infection.).CONCLUSION: Laboratory examination such as bilirubin, prothrombin time and alpha fetoprotein can be regarded as indices of the prognoses of chronic liver failure caused by hepatitis. Moreover, the regression equation can evaluate prognoses more comprehensively and direct our treatments.

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

    Directory of Open Access Journals (Sweden)

    G.M. Tronconi

    2012-10-01

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

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

    Science.gov (United States)

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

    2012-01-01

    We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus. PMID:23342747

  13. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Institute of Scientific and Technical Information of China (English)

    Masayuki Miyazaki; Masatake Tanaka; Akihiro Ueda; Tsuyoshi Yoshimoto; Masaki Kato; Makoto Nakamuta; Kazuhiro Kotoh; Ryoichi Takayanagi

    2011-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is a se-vere reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-10-01

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

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

    Science.gov (United States)

    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. High-output cardiac failure secondary to multiple vascular malformations in the liver: case report

    Energy Technology Data Exchange (ETDEWEB)

    Spaner, S.; Demeter, S. [Univ. of Alberta, Dept. of Radiology and Diagnostic Imaging, Edmonton, Alberta (Canada); Lien, D. [Univ. of Alberta, Dept. of Pulmonary Medicine, Edmonton, Alberta (Canada); Shapiro, J. [Univ. of Alberta, Dept. of Surgery, Edmonton, Alberta (Canada); McCarthy, M.; Raymond, G. [Univ. of Alberta, Dept. of Radiology and Diagnostic Imaging, Edmonton, Alberta (Canada)

    2001-08-01

    High-output cardiac failure is associated with several systemic illnesses, including hyperthyroidism, thiamine deficiency, severe anemia, multiple myeloma, Paget's disease of bone and Osler-Weber-Rendu syndrome. We present an unusual case of a woman with high-output cardiac failure as a result of multiple arteriovenous fistulas in the liver, most likely representing an unusual variant of Osler-Weber-Rendu syndrome (i.e., no other telangiectasias or a family history of vascular malformations was demonstrated). (author)

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  19. Acute liver failure due to Varicella zoster virus infection after lung transplantation: a case report.

    Science.gov (United States)

    Verleden, G M; Vos, R; Van Raemdonck, D E; Laleman, W; Vanaudenaerde, B M

    2012-06-01

    Most adults are Varicella zoster virus (VZV)-positive at the age of 20 years. Some, however, remain antibody-negative and may develop primary chicken pox during adulthood. We report a patient with Williams-Campbell syndrome who underwent double-lung transplantation while being VZV-negative. One year after the successful procedure, he was admitted with fulminant hepatic failure and some cutaneous vesicles in his face. Despite a rapid diagnosis of VZV infection and treatment with acyclovir, his situation deteriorated within 24 hours and while awaiting an urgent liver transplantation, he developed multiple organ failure and died. PMID:22664036

  20. Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report

    Institute of Scientific and Technical Information of China (English)

    Yuka Suzuki; Fumio Itoh; Hiroshi Yotsuyanagi; Chiaki Okuse; Yoshihiko Nagase; Hideaki Takahashi; Kyoji Moriya; Michihiro Suzuki; Kazuhiko Koike; Shiro lino

    2007-01-01

    We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of a-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

  1. Effects of chronic renal failure on protein synthesis and albumin messenger ribonucleic acid in rat liver.

    OpenAIRE

    Zern, M A; Yap, S.H.; Strair, R K; Kaysen, G A; Shafritz, D A

    1984-01-01

    Previously we reported that chronic renal failure in rats leads to preferential disaggregation of liver membrane-bound polysomes associated with a decrease in albumin synthesis. To determine whether reduced albumin synthesis results from reduced cellular levels of albumin messenger RNA (mRNA) or some other molecular mechanism, we have employed mRNA-DNA hybridization in conjunction with cell-free protein synthesis to determine albumin mRNA sequence content and biological activity in subcellula...

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

    OpenAIRE

    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) crite...

  3. Predictors of the outcomes of acute-on-chronic hepatitis B liver failure

    Institute of Scientific and Technical Information of China (English)

    Hsiu-Lung Fan; Po-Sheng Yang; Hui-Wei Chen; Teng-Wei Chen; De-Chuan Chan; Chi-Hong Chu; Jyh-Cherng Yu

    2012-01-01

    AIM:TO identify the risk factors in predicting the outcome of acute-on-chronic hepatitis B liver failure patients.METHODS:We retrospectively divided 113 patients with acute-on-chronic liver failure-hepatitis B virus (ACLF-HBV) and without concurrent hepatitis C or D virus infection and hepatocellular carcinoma into two groups according to their outcomes after anti-HBV therapy.Their demographic,clinical,and biochemical data on the day of diagnosis and after the first week of treatment were analyzed using the Mann-Whitney U test,Fisher's exact test,and a multiple logistic regression analysis.RESULTS:The study included 113 patients (87 men and 26 women) with a mean age of 49.84 years.Fiftytwo patients survived,and 61 patients died.Liver failure (85.2%),sepsis (34.4%),and multiple organ failure (39.3%) were the main causes of death.Multivariate analyses showed that Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ scores ≥ 12[odds ratio (OR) =7.160,95% CI:2.834-18.092,P <0.001] and positive blood culture (OR =13.520,95%CI:2.740-66.721,P =0.001) on the day of diagnosis and model for end-stage liver disease (MELD) scores ≥ 28 (OR =8.182,95% CI:1.884-35.527,P =0.005)after the first week of treatment were independent predictors of mortality.CONCLUSION:APACHE Ⅱ scores on the day of diagnosis and MELD scores after the first week of anti-HBV therapy are feasible predictors of outcome in ACLF-HBV patients.

  4. Subtle BBB alterations in brain edema associated with acute liver failure

    OpenAIRE

    Nguyen, Justin H

    2010-01-01

    Vasogenic mechanism of brain edema in acute liver failure (ALF) remains poorly understood. Recent work demonstrates that matrix metalloproteinase-9 (MMP-9) contributes to the development of brain edema in experimental ALF (J Hepatol 44:1105, 2006). Importantly, MMP-9 blockage with specific monoclonal antibodies and/or synthetic inhibitor, the edema is attenuated. Specifically, utrastructural evaluations demonstrate intact blood-brain barrier and its tight junction. These results suggest that ...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  7. Metabonomic analysis of hepatitis B virus-induced liver failure: identification of potential diagnostic biomarkers by fuzzy support vector machine

    Institute of Scientific and Technical Information of China (English)

    Yong MAO; Xin HUANG; Ke YU; Hai-bin QU; Chang-xiao LIU; Yi-yu CHENG

    2008-01-01

    Hepatitis B virus (HBV)-induced liver failure is an emergent liver disease leading to high mortality. The severity of liver failure may be reflected by the profile of some metabolites. This study assessed the potential of using metabolites as biomarkers for liver failure by identifying metabolites with good discriminative performance for its phenotype. The serum samples from 24 HBV-induced liver failure patients and 23 healthy volunteers were collected and analyzed by gas chromatography-mass spectrometry (GC-MS) to generate metabolite profiles. The 24 patients were further grouped into two classes according to the severity of liver failure. Twenty-five commensal peaks in all metabolite profiles were extracted, and the relative area values of these peaks were used as features for each sample. Three algorithms, F-test, k-nearest neighbor (KNN) and fuzzy support vector machine (FSVM) combined with exhaustive search (ES), were employed to identify a subset of metabolites (biomarkers) that best predict liver failure. Based on the achieved experimental dataset, 93.62% predictive accuracy by 6 features was selected with FSVM-ES and three key metabolites, glyceric acid, cis-aconitic acid and citric acid, are identified as potential diagnostic biomarkers.

  8. Relative biological effectiveness of carbon ions for causing fatal liver failure after partial hepatectomy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tomizawa, Minoru; Miyamoto, Tadaaki; Kato, Hirotoshi; Otsu, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan)

    2000-06-01

    To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD{sub 50/60}) was 42.2{+-}0.25 Gy (standard error) for X-rays, and 22.7{+-}0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD{sub 50/60}. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD{sub 50} of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure. (author)

  9. Relative biological effectiveness of carbon ions for causing fatal liver failure after partial hepatectomy in mice

    International Nuclear Information System (INIS)

    To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD50/60) was 42.2±0.25 Gy (standard error) for X-rays, and 22.7±0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD50/60. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure. (author)

  10. High neutrophil-lymphocyte ratio indicates poor prognosis for acute-on-chronic liver failure after liver transplantation

    Science.gov (United States)

    Lin, Bing-Yi; Zhou, Lin; Geng, Lei; Zheng, Zhi-Yun; Jia, Jun-Jun; Zhang, Jing; Yao, Jia; Zheng, Shu-Sen

    2015-01-01

    AIM: To investigate the significance of pre-transplant neutrophil-lymphocyte ratio (NLR) in determining the prognosis of liver transplant (LT) recipients with acute-on-chronic liver failure (ACLF). METHODS: Data were collected from the liver transplantation data bank. The NLR values and other conventional inflammatory markers were evaluated for their ability to predict the prognosis of 153 patients with ACLF after LT. The NLR cut-off value was based on a receiver operating characteristic curve analysis. A Kaplan-Meier curve analysis and univariate and multivariate Cox regression models were used to define the independent risk factors for poor outcomes. RESULTS: The optimal NLR cut-off value was 4.6. Out of 153 patients, 83 (54.2%) had an NLR ≥ 4.6. The 1-, 3-, and 5-year overall survival rates were 94.3%, 92.5% and 92.5%, respectively, in the normal NLR group and 74.7%, 71.8% and 69.8%, respectively, in patients with high NLRs (P < 0.001). Furthermore, there was a significant difference in infectious complications after LT between the high and normal NLR groups. There were no significant differences for other complications. In the multivariate Cox regression model, a high NLR was defined as a significant predictor of poor outcomes for LT. CONCLUSION: A high NLR is a convenient and available predictor for prognosis of LT patients and can potentially optimize the current criteria for LT in ACLF. PMID:25805939

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

    Science.gov (United States)

    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

  12. Clopidogrel-induced cholestatic liver injury in an old woman and literature review%氯吡格雷致胆汁淤积性肝损伤一例报道并文献回顾

    Institute of Scientific and Technical Information of China (English)

    刘芳勋; 吴静; 魏南; 王沧海

    2011-01-01

    @@ Introduction Clopidogrel is a thienopyridine derivative platelet aggrega-tion inhibitor that irreversibly and selectively binding to adenylate cyclase-coupled ADP receptors on the platelet surface,which has been shown to be effective in the secondary prevention of cardio-vascular events.Hepatotoxicity is a rare side-effect of clopi-dogrel, however, cases has been reported gradually since 2000,including one case of fatal liver injury[1] and two cases of system-ic inflammatory response syndrome ( SIRS)[2-3] associated with clopidogrel.

  13. Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system

    Institute of Scientific and Technical Information of China (English)

    Yi Gao; Ning Mu; Xiao-Ping Xu; Yan Wang

    2005-01-01

    AIM: To establish a highly reproducible animal model of acute liver failure (ALF), for assessing theeffect of bioartificial liver support system (BALSS).METHODS: A two-phase complete liver devascularization procedure was performed in eight loco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrieradhering hepatocytes, and a double pump, heparinized,thermostabilized, micro-capsulized activated carbonadsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into: control group (perfused without hepatocytes, n = 6) and treatment group (perfused with hepatocytes, n = 6). Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals.RESULTS: Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase Ⅱ surgery, ammonia (Amm) increased to (269±37) μmol/L.After 5 h of the surgery, fibrinogen (Fib) decreased to (1.5±0.2) g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were (7.6±1.8) nka/L, (40±5) nka/L, (55±8) μmol/L and (17.5±1.7) nka/L respectively. After 9 h of surgery, ALB and Cr were (27±4) g/L and (87±9) μmol/L. After 13 h of surgery, BUN was (3.5±0.9) μmol/L. All the above values were different from those determined before surgery.Survival time of pigs averaged 13.5±1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, Alb, BUN, Cr, Fib, and Amm (P<0.01), but there was no change of ALT and AST. The survival time was statistically different (P<0.01), and there was no significant difference in histological changes

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

    Science.gov (United States)

    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.

  15. Protective Role of α2HS-Glycoprotein in HBV-Associated Liver Failure

    Directory of Open Access Journals (Sweden)

    Xue-Gong Fan

    2011-06-01

    Full Text Available n this study, levels of plasma α2-Heremans-Schmid glycoprotein, serum tumor necrosis factor-α, serum liver function parameters and short-term mortality were measured in 100 hepatitis B patients. Release of interleukin-6 and tumor necrosis factor-α from the lipopolysaccharide-stimulated peripheral blood mononuclear cells in the presence/absence of spermine and α2-Heremans-Schmid glycoprotein were analyzed by enzyme-linked immunosorbent assay to determine the significance and potential mechanism of α2-Heremans-Schmid glycoprotein in hepatitis B virus-associated liver damage. Results showed that serum α2-Heremans-Schmid glycoprotein levels in acute-on-chronic liver failure patients were significantly lower than that in chronic hepatitis B patients or healthy controls (p < 0.05. A negative dependence between serum human α2-Heremans-Schmid glycoprotein and tumor necrosis factor-α levels was observed. Interleukin-6 and tumor necrosis factor-α levels in the lipopolysaccharide-induced peripheral blood mononuclear cell supernates were significantly reduced by spermine and/or α2-Heremans-Schmid glycoprotein. The latter two proteins jointly inhibited cytokine release. These observations suggest that plasma α2-Heremans-Schmid glycoprotein is an independent marker of liver damage and a prognostic indicator of hepatitis B virus chronicity. It may reduce liver inflammation by partially inhibiting release of inflammatory factors from activated peripheral blood mononuclear cells.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND & AIMS: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M......-, L-, and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome. METHODS: Serum samples from 75 patients enrolled by the US ALF Study Group were collected on days 1 and 3. We...

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

    Science.gov (United States)

    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

  18. Autologous bone marrow stem cell transplantation in patients with liver failure: a meta-analytic review.

    Science.gov (United States)

    Wang, Kewei; Chen, Xiaopan; Ren, Jinma

    2015-01-15

    Autologous bone marrow stem cell (ABMSC) transplantation has been utilized in clinical practice to treat patients with liver failure, but the therapeutic effect remains to be defined. A meta-analysis is essential to assess clinical advantages of ABMSC transplantation in patients with liver failure. A systematic search of published works [eg, PubMed, Medline, Embase, Chin J Clinicians (Electronic edition), and Science Citation Index] was conducted to compare clinical outcomes of ABMSC transplantation in patients with liver failure. Meta-analytic results were tested by fixed-effects model or random-effects model, dependent on the characteristics of variables. A total of 534 patients from seven studies were included in final meta-analysis. Subsequent to ABMSC transplantation, there was no significant improvement in general symptom and signs such as loss of appetite, fatigue, and ascites. Activities of serum ALT were not significantly decreased with weighted mean difference (WMD) of -19.36 and 95% confidence interval (CI) -57.53 to 18.80 (P=0.32). Postoperative level of albumin (ALB) was expectedly enhanced by stem cell transplantation (WMD 2.97, 95% CI 0.52 to 5.43, P<0.05, I(2)=84%). Coagulation function was improved as demonstrated by a short prothrombin time (PT) (WMD -1.18, 95% CI -2.32 to -0.03, P<0.05, I(2)=6%), but was not reflected by prothrombin activity (PTA) (P=0.39). Total bilirubin (TBIL) was drastically diminished after ABMSC therapy (WMD -14.85, 95% CI -20.39 to -9.32, P<0.01, I(2)=73%). Model for end-stage liver disease (MELD) scores were dramatically reduced (WMD -2.27, 95% CI -3.53 to -1.02, P<0.01, I(2)=0%). The advantage of ABMSC transplantation could be maintained more than 24 weeks as displayed by time-courses of ALB, TBIL, and MELD score. ABMSC transplantation does provide beneficial effects for patients with liver failure. Therapeutic effects can last for 6 months. However, long-term effects need to be determined. PMID:25356526

  19. Hyperlactatemia in patients with non-acetaminophen-related acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Pilar Taurá; Graciela Martinez-Palli; Julia Martinez-Ocon; Joan Beltran; Gerard Sanchez-Etayo; Jaume Balust; Teresa Anglada; Antoni Mas; Juan-Carlos Garcia-Valdecasas

    2006-01-01

    AIM: To characterize hyperlactatemia in patients with non-acetaminophen acute liver failure (ALF) in an attempt to clarify the mechanisms implicated and the role as a prognosis factor.METHODS: In the setting of liver transplantation, 63 consecutive patients with non-acetaminophen acute liver failure were studied in relation to tissue oxygenation,hemodynamic and metabolic parameters. Before and after transplantation, the number of infected patients and outcome were registered.RESULTS: Acute ALF showed higher levels of lactate than subacute ALF (5.4±1 mmol/L versus 2.2 ± 0.6 mmol/L, P=0.01). Oxygenation parameters were within the normal range. Lactate levels showed good correlation with respiratory quotient (r= 0.759, P< 0.005), mean glucose administration (r=0.664, P=0.01) and encephalopathy (r=0.698, P= 0.02), but not with splanchnic arteriovenous difference in PCO2, pH and the presence of infection (P=0.1). Portal vein lactate was higher (P< 0.05) than arterial and mixed venous lactate,suggesting its production of hyperlactatemia in the intestine and spleen. The presence of infection was an independent predictor of survival. CONCLUSION: Hyperlactatemia is not a prognosis factor due to byproduct of the overall acceleration in glycolysis.

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

    Science.gov (United States)

    Laoprasopwattana, Kamolwish; Jundee, Puthachat; Pruekprasert, Pornpimol; Geater, Alan

    2016-06-01

    To determine clinical course and outcomes of liver functions in children with dengue viral infection-caused acute liver failure (ALF), the records of patients aged 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. PMID:26851434

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

    Directory of Open Access Journals (Sweden)

    Hessel Franz P

    2006-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Lu Li

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-11-15

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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 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

  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.

    Science.gov (United States)

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

    2015-03-01

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

  7. Renal Failure in Patients with End Stage Liver Disease and its Impact on Clinical Outcome

    International Nuclear Information System (INIS)

    Objective: To evaluate the prevalence of renal failure (RF) in the patients of end stage liver disease (ESLD), to determine the causes of RF in these patients and its impact on patient's outcome. Study Design: Descriptive, analytical study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from May 2011 to March 2013. Methodology: A total of 523 patients with end stage liver disease (ESLD) were evaluated, renal failure (RF) and its causes were recognized in these patients according to established criteria. Outcome of these patients was assigned as reversal of RF or mortality. Data was analyzed using SPSS version 16. Chi-square test was used for comparing proportions and t-test was used for comparing mean values. P < 0.05 was considered significant. Results: Out of 523 patients, 261 (49.9%) had RF. Acute kidney injury (AKI) was the most common presentation seen in 160 (61%) patients. Hypovolemia and infections were the most frequent causes of RF. Mortality was significantly higher in the patients with RF, when compared to the patients without RF (31% vs. 4.5%, p < 0.001). Reversal of RF was seen in 98 (37%) of the affected patients. Reversal was more common in the patients with hypovolemia. The mortality was higher in the patients with hepatorenal syndrome (HRS) and infections. Conclusion: Renal failure in the end stage liver disease is an important prognostic factor. Etiology of RF is the key factor in patients' outcome. Patients of ESLD with RF had higher mortality. Majority of the cases of RF were reversible in patients of ESLD coming in the setup. (author)

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

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    Jody A Rule

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

  9. Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P.N.; Hauerberg, J.; Frederiksen, Hans-Jørgen;

    2008-01-01

    AIM: Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate-pyruvate ratio is associated...... with a rise in the glutamine concentration and ICP. PATIENTS AND METHODS: In 13 patients with ALF (8F/5M; median age 46 (range 18-66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion......-pyruvate ratio (r = 0.89, P rise in lactate...

  10. Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation.

    Science.gov (United States)

    Takeichi, Takayuki; Asonuma, Katsuhiro; Kim, Ildeok; Inomata, Yukihiro; Kasahara, Mureo; Ohwada, Susumu; Morishita, Yasuo; Tanaka, Koichi

    2002-08-01

    Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on-line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III-IV) who underwent living-related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE-72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Dong Ji

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

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

    Directory of Open Access Journals (Sweden)

    Emilio Fábrega

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nélson R Carvalho

    Full Text Available The acute liver failure (ALF induced by acetaminophen (APAP is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe2], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe2 to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe2 to the N-acetylcysteine (NAC during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg, (PhSe2 (15.6 mg/kg, NAC (1200 mg/kg, APAP+(PhSe2 or APAP+NAC, where the (PhSe2 or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe2. The effectiveness of (PhSe2 was similar at a lower dose than NAC. In summary, (PhSe2 provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.

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

    Science.gov (United States)

    Cannon, Megan V; van Gilst, Wiek H; de Boer, Rudolf A

    2016-01-01

    Liver X receptors (LXRs) are master regulators of metabolism and have been studied for their pharmacological potential in vascular and metabolic disease. Besides their established role in metabolic homeostasis and disease, there is mounting evidence to suggest that LXRs may exert direct beneficial effects in the heart. Here, we aim to provide a conceptual framework to explain the broad mode of action of LXRs and how LXR signaling may be an important local and systemic target for the treatment of heart failure. We discuss the potential role of LXRs in systemic conditions associated with heart failure, such as hypertension, diabetes, and renal and vascular disease. Further, we expound on recent data that implicate a direct role for LXR activation in the heart, for its impact on cardiomyocyte damage and loss due to ischemia, and effects on cardiac hypertrophy, fibrosis, and myocardial metabolism. Taken together, the accumulating evidence supports the notion that LXRs may represent a novel therapeutic target for the treatment of heart failure.

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

    Science.gov (United States)

    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

  17. Acute liver failure caused by concurrent autoimmune hepatitis and hepatitis B in a 16-year old girl

    OpenAIRE

    Pawłowska, Małgorzata; Halota, Waldemar

    2010-01-01

    A 16 year-old girl was admitted to hospital because of fatigue and somnolence, nausea, epistaxis and jaundice. Physical examination revealed jaundice, an enlarged liver and tenderness of upper right abdomen. Laboratory tests revealed an increased level of acute liver failure, bilirubin, bile acids, GGTP and a decreased prothrombin ratio, with elevated gamma-globulin and IgG levels, and the presence of anti-mitochondrial M2 antibodies and HBV infection markers. The patient was diagnosed with l...

  18. Renal Dysfunction Is an Independent Risk Factor for Mortality after Liver Resection and the Main Determinant of Outcome in Posthepatectomy Liver Failure

    Directory of Open Access Journals (Sweden)

    M. G. Wiggans

    2013-01-01

    Full Text Available Introduction. The aim of this study was to assess the interaction of liver and renal dysfunction as risk factors for mortality after liver resection. Materials and Methods. A retrospective analysis of 501 patients undergoing liver resection in a single unit was undertaken. Posthepatectomy liver failure (PHLF was defined according to the International Study Group of Liver Surgery (ISGLS definition (assessed on day 5 and renal dysfunction according to RIFLE criteria. 90-day mortality was recorded. Results. Twenty-three patients died within 90 days of surgery (4.6%. The lowest mortality occurred in patients without evidence of PHLF or renal dysfunction (2.7%. The mortality rate in patients with isolated PHLF or renal dysfunction was 20% compared to 45% in patients with both. Diabetes (, renal dysfunction (, and PHLF on day 5 ( were independent predictors of 90-day mortality. Discussion. PHLF and postoperative renal dysfunction are independent predictors of 90-day mortality following liver resection but the predictive value for mortality is significantly higher when failure of both organ systems occurs simultaneously.

  19. Combination of liver biopsy with MELD-XI scores for post-transplant outcome prediction in patients with advanced heart failure and suspected liver dysfunction

    Science.gov (United States)

    Farr, Maryjane; Mitchell, James; Lippel, Matthew; Kato, Tomoko S.; Jin, Zhezhen; Ippolito, Paul; Dove, Lorna; Jorde, Ulrich P.; Takayama, Hiroo; Emond, Jean; Naka, Yoshifumi; Mancini, Donna; Lefkowitch, Jay H.; Schulze, P. Christian

    2016-01-01

    BACKGROUND Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI improves prediction of adverse outcomes in patients evaluated for HTx. METHODS Sixty-eight patients suspected of advanced liver disease underwent liver biopsy as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) × MELD-XI was generated for each patient. RESULTS Fifty-two patients were listed, of whom 14 had mechanical circulatory support (MCS). Thirty-six patients underwent transplantation and 27 patients survived ≥1 year post-HTx (74%, as compared with 88% average 1-year survival in HTx patients without suspected liver disease; p ventilation times (55.6% vs 11.1%, p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk score at evaluation for HTx also predicted 1-year mortality after HTx listing (p < 0.001). CONCLUSIONS Patients with HF and advanced liver dysfunction are high-risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk stratification of patients with advanced HF and suspected irreversible liver dysfunction. PMID:25851466

  20. Ticlopidine-induced cholestatic hepatitis: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Luigi Anastasio

    2012-10-01

    Full Text Available Introduction Cholestatic hepatitis is frequently a drug-related syndrome. We describe the case of a 57-year-old man who developed cholestatic hepatitis two months after starting therapy with ticlopidine following a carotid endarterectomy.Materials and methods The patient presented with anorexia, nausea, and dark-colored urine. The work-up included laboratory tests and imaging studies of the liver (ultrasound and magnetic resonance imaging. The authors analyze the case using the scale developed by Maria and Victorino for the diagnosis of drug-induced hepatitis, the Naranjo algorithm for adverse drug reactions, and the RUCAM algorithm for causality assessment of hepatotoxicity. They also review data from the MedLine database on cases of ticlopidine-induced cholestatic hepatitis reported during the period 1982–2011.Results Bilirubin, aminotransferases, alkaline phosphatases, and gamma glutamyl transpeptidase levels were elevated at admission and progressively declined after ticlopidine was discontinued. The absence of biliary obstruction at ultrasonography and magnetic resonance cholangiography, the negative results of viral and immunologic tests, and the resolution of the syndrome after discontinuation of the drug all suggested ticlopidine-induced hepatotoxicity. The assessment of this case with toxicity algorithms confirmed that a causal link to ticlopidine was “probable” or “highly probable.” The patient was treated with ursodesoxycholic acid, clopidogrel (75 mg/day, and (after the laboratory parameters had normalized rosuvastatin (10 mg/day. No further clinical and laboratory abnormalities have been observed during two month follow-up.Discussion The toxicity of ticlopidine is well established: our review revealed reports of 57 cases of ticlopidine-induced cholestatic hepatitis during the period 1982–2011. The mechanisms underlying the toxic effects of this drug are not clear, but they are probably related to the chemical structure

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

    Directory of Open Access Journals (Sweden)

    Howie Forbes

    2010-03-01

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

  2. Wernicke encephalopathy in a patient with liver failure: Clinical case report.

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  6. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia.

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

    Directory of Open Access Journals (Sweden)

    Alireza Hosseinnezhad

    2011-05-01

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

  8. Experience of Treatments of Amanita phalloides-Induced Fulminant Liver Failure with Molecular Adsorbent Recirculating System and Therapeutic Plasma Exchange.

    Science.gov (United States)

    Zhang, Jicheng; Zhang, Ying; Peng, Zhiyong; Maberry, Donald; Feng, Xueqiang; Bian, Pengfei; Ma, Wenjuan; Wang, Chunting; Qin, Chengyong

    2014-01-01

    Ingestion of the mushroom containing Amanita phalloides can induce fulminant liver failure and death. There are no specific antidotes. Blood purifications, such as molecular adsorbent recirculating system (MARS) and therapeutic plasma exchange (TPE), are potential therapies. However, the extent to which these technologies avert the deleterious effects of amatoxins remains controversial; the optimal intensity, duration, and initiation criteria have not been determined yet. This study aimed to retrospectively observe the effects of MARS and TPE on nine patients with A. phalloides-induced fulminant liver failure. The survival rate for the nine patients was 66.7%. Both TPE and MARS might remove toxins and improve liver functions. However, a single session of TPE produced immediately greater improvements in alanine aminotransferase (-60% vs. -16.3%), aspartate aminotransferase (-47.6% vs. -15.4%), and total bilirubin (-37.3% vs. -17.1%) (compared with the values of pretreatment, all p MARS compared with MARS. Early intervention may be more effective than delayed therapy. Additionally, the presence of severe liver failure and renal failure indicated worse outcome. Although these findings are promising, additional case-controlled, randomized studies are required to confirm our results. PMID:24727538

  9. Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Hauerberg, John; Jørgensen, Linda;

    2010-01-01

    hypoxanthine, inosine, and lactate/pyruvate (LP) ratio are increased and correlated in patients with acute liver failure. Furthermore, we expect the purines and L/P ratio to correlate with intracranial pressure (ICP) (positively), and cerebral perfusion pressure (CPP) (negatively)....

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

    OpenAIRE

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

    2016-01-01

    AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).

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

    Science.gov (United States)

    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

  12. The soluble macrophage activation markers sCD163 and Mannose Receptor (sMR) predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF)

    DEFF Research Database (Denmark)

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

    2015-01-01

    INTRODUCTION: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose-receptor (sMR...

  13. Life Saving Plasmapheresis for the Management of Hemolytic Crisis and Acute Liver Failure in Wilson’s Disease

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Pashaei

    2009-06-01

    Full Text Available Wilson's disease, caused by a deficient cellular copper export system, is transmitted as an autosomal recessive inherited disorder and results in copper accumulation in liver and other organs, particularly in brain. Acute hepatic failure and severe Coombs' negative hemolysis may occur in the course of the disease which has a poor prognosis and most patients do not survive the crisis. Only liver transplantation has been recommended as an effective medical intervention. Herein, we presented a 25-year-old woman with impaired consciousness, acute hepatic failure and hemolysis who was treated with plasmapheresis and albumin replacement. Beside improvement in medical condition, serum copper and hemolysis decreased significantly and renal function was preserved. We concluded that plasmapheresis may be a life saving intervention during fulminant hepatic failure of Wilson's disease.

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

    Science.gov (United States)

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

    2016-01-01

    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

  15. Cholestatic jaundice by malignant lesions: pictorial essay;Ictericia colestatica por lesoes de natureza maligna: ensaio iconografico

    Energy Technology Data Exchange (ETDEWEB)

    Santa Anna, Tatiana Kelly Brasileiro de; Santana, Alex Menezes; Rizzuto, Mauricio Soares; Chagas, Alessandro Rosa Rodrigues; Zuppani, Aguinaldo Cunha, E-mail: tatianakelly@hotmail.co [Hospital Santa Marcelina, Sao Paulo, SP (Brazil). Setor de Radiologia e Diagnostico por Imagem; Rezende, Marcelo Bruno; Viveiros, Marcelo de Melo [Hospital Santa Marcelina, Sao Paulo, SP (Brazil). Servico de Cirurgia do Figado e Hipertensao Portal

    2009-12-15

    Malignant obstructive jaundice is most commonly caused by cancer of pancreatic head, papilla tumor, cholangiocarcinoma and biliary obstruction induced by secondary lesions of the liver or lymph nodes. Patients usually present with weight loss, abdominal pain, jaundice and progressive increase of direct bilirubin, being essential the evaluation by imaging methods for the proper diagnosis, staging and therapeutic planning. This essay illustrates the imaging aspects of ultrasound and computed tomography - and in specific situations magnetic resonance cholangiography - of the major malignancies that lead to cholestatic jaundice. (author)

  16. Fibrosing cholestatic hepatitis following cytotoxic chemotherapy for small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jaime Ceballos-Viro; José M López-Picazo; José L Pérez-Gracia; Jesús J Sola; Gregorio Aisa; Ignacio Gil-Bazo

    2009-01-01

    Fibrosing cholestatic hepatitis (FCH) is a variant of viral hepatitis reported in hepatitis B virus or hepatitis C virus infected liver, renal or bone transplantation recipients and in leukemia and lymphoma patients after conventional cytotoxic chemotherapy. FCH constitutes a well-described form of fulminant hepatitis having extensive fibrosis and severe cholestasis as its most characteristic pathological findings. Here, we report a case of a 49-year-old patient diagnosed with small-cell lung cancer who developed this condition following conventional chemotherapy-induced immunosuppression. This is the first reported case in the literature of FCH after conventional chemotherapy for a solid tumor. In addition to a detailed report of the case, a physiopathological examination of this potentially life-threatening condition and its treatment options are discussed.

  17. A new prognostic formula for adult acute liver failure using computer tomography-derived hepatic volumetric analysis

    International Nuclear Information System (INIS)

    King's College Hospital (KCH) criteria and the model for end-stage liver disease (MELD) score are useful and widely-employed prognostic markers for acute liver failure (ALF). We previously reported that liver atrophy is an important prognostic factor for ALF. The aim of the present study was to assess the value of liver volumetry and to generate a new prognostic formula. Computed tomography-derived liver volume (CTLV) and standardized liver volume (SLV) of 30 adult ALF patients were calculated at the time of diagnosis. Patients were assigned to one of two groups: group A consisted of 13 patients who recovered without surgical intervention, and group B consisted of 17 patients who died due to liver failure or who underwent living donor liver transplantation (LDLT). The median CTLV/SLV ratios of groups A and B were 1.019 and 0.757, respectively (P=0.0009). The difference was most significant (P=0.0002) at the probability cutoff point of 0.80 for CTLV/SLV ratio; the sensitivity and specificity were 76.5% and 92.3%, respectively. Serum total bilirubin (TB) levels and CTLV/SLV ratio were selected as independent prognostic factors by multivariate analysis. A prognostic formula including volumetric analysis was established: Z=-2.3813-[0.15234 x TB (mg/dl)]+[4.5734 x CTLV/SLV] (area under the ROC curve (AUC)=0.87783, P=0.0002). The CTLV/SLV ratio is a very useful marker for predicting the prognosis of adult ALF. Our prognostic formula including only the CTLV/SLV ratio and TB is simple and useful and awaits validation in a future larger-scale prospective study. (author)

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

    Directory of Open Access Journals (Sweden)

    Fabio Bucaretchi

    2014-03-01

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

  19. Primary hepatic lymphoma presenting as fulminant hepatic failure with hyperferritinemia: A case report

    Directory of Open Access Journals (Sweden)

    Haider Fyeza S

    2008-08-01

    Full Text Available Abstract Introduction Primary hepatic lymphoma is an unusual form of non-Hodgkin's lymphoma that usually presents with constitutional symptoms, hepatomegaly and signs of cholestatic jaundice. Diffuse hepatic infiltration is uncommon and presentation with acute hepatic failure even more rare. The presence of markedly elevated ferritin levels can complicate the evaluation process and suggest alternative diagnoses. We present the case of a middle-aged woman exhibiting pancytopenia, hyperferritinemia and rapidly deteriorating to develop acute hepatic failure. Her initial clinical picture led to a working diagnosis of adult onset Still's disease with probable hemophagocytic syndrome before her worsening liver function necessitated a percutaneous liver biopsy and establishment of the final diagnosis of primary hepatic lymphoma. Conclusion Primary hepatic lymphoma is an uncommon malignancy and its manifestation as progressive hepatitis or acute fulminant hepatic failure can be difficult to diagnose. The presence of constitutional symptoms, pancytopenia and high ferritin levels can complicate the evaluation process. A liver biopsy early in the course of liver dysfunction may establish the diagnosis without a higher risk of bleeding complications seen once liver failure sets in.

  20. 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.

    Directory of Open Access Journals (Sweden)

    Stephen R Knight

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

  1. Overlap syndromes among autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    Christian Rust; Ulrich Beuers

    2008-01-01

    The three major immune disorders of the liver are autoimmune hepatitis (AIH),primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC).Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.

  2. Changes of gut flora and endotoxin in rats with D-galactosamine-induced acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Lan-Juan Li; Zhong-Wen Wu; Dang-Sheng Xiao; Ji-Fang Sheng

    2004-01-01

    AIM: To investigate the changes of gut microflora and endotoxin levels in rats with acute liver failure (ALF) induced by D-galactosamine (GalN).METHODS: Flora and endotoxin levels in the jejunum, ileum and colon in normal rats (group A) and rats with GalNinduced ALF were determined at 24 h (group B) or 48 h (group C) after GalN injection, as well as the endotoxin level in portal venous blood (PVB) and right ventricle blood (RVB) were determined by chromogenic limulus amoebocyte assay.RESULTS: Intestinal (jejunum, ileum, colon)lactobacillus count was statistically reduced in group B compared with those in group A (3.4±0.3 vs4.9±0.3, 6.1±0.4 vs 8.0±0.3,8.1±0.2 vs 9.3±0.2, P<0.001, P<0.001 and P<0.001respectively) and recovered partially in the group C compared with those in the group B, whereas the count of Enterobacteriaceae in the jejunum, ileum and colon in group B was increased markedly compared with those in the group A (5.1±0.3 vs 3.6±0.2, 6.9±0.5 vs 5.3±0.3,8.7±0.2 vs7.6±0.1, P<0.001, P<0.05 and P<0.05 respectively)and restored partially in the group C compared with those in the group B. The endotoxin level in ileum was increased in the group B compared with those in the group A (111.3±22.8 vs 51.5±8.9, P<0.05). In addition, the endotoxin level in PVB was obviously increased in group B compared with that in the group A (76.8±9.1 vs40.6±7.3,P<0.01) and reduced to the baseline at 48 h (group C).CONCLUSIOM: Severely disturbed gut flora in rats with GalN-induced acute liver failure plays an important role in the elevation of endotoxin level in PVB.

  3. Hepatite aguda colestática pelo propiltiouracil: relato de caso Acute cholestatic hepatitis induced by propylthiouracil: case report

    Directory of Open Access Journals (Sweden)

    Mônica Beatriz PAROLIN

    2000-04-01

    Full Text Available Propiltiouracil é uma droga amplamente utilizada no tratamento do hipertiroidismo. A hepatotoxicidade é um dos efeitos colaterais mais raros e também mais graves associados a ela. Relata-se um caso de hepatite aguda colestática que acomete um jovem de 15 anos em uso de propiltiouracil para tratamento de hipertiroidismo. Causas virais, metabólicas e autoimunes foram excluídas e a biopsia hepática revelou achados histopatológicos sugestivos de hepatite colestática induzida por droga. Com a suspensão da droga, houve remissão dos sintomas e normalização progressiva das provas de função hepática. Raramente, os pacientes em uso de propiltiouracil podem desenvolver injúria hepática grave.Propylthiouracil is widely used to treat patients with hyperthyroidism. However, propylthiouracil-induced hepatitis is an uncommon entity. The case of a 15-year-old boy treated with propylthiouracil for hyperthyroidism who developed a cholestatic acute hepatitis is reported. Viral, metabolic and autoimmune liver diseases were excluded and liver biopsy showed a pattern suggestive of drug-induced cholestatic hepatitis. After discontinuating the drug, there was a progressive resolution of symptoms and normalization of liver biochemical tests. Despite its rarity, patients receiving propylthiouracil are exposed to develop severe hepatotoxicity.

  4. The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology.

    Science.gov (United States)

    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.

  5. Acute liver failure due to concomitant arterial, portal and biliary injury during laparoscopic cholecystectomy: is transplantation a valid life-saving strategy? A case report

    Directory of Open Access Journals (Sweden)

    Goldaracena Nicolas

    2009-09-01

    Full Text Available Abstract Background Combined iatrogenic vascular and biliary injury during cholecystectomy resulting in ischemic hepatic necrosis is a very rare cause of acute liver failure. We describe a patient who developed fulminant liver failure as a result of severe cholestasis and liver gangrene secondary to iatrogenic combine injury or the hepatic pedicle (i.e. hepatic artery, portal vein and bile duct during laparoscopic cholecystectomy. Case presentation A 40-years-old woman underwent laparoscopic cholecystectomy for acute cholecystitis. During laparoscopy, a severe bleeding at the liver hilum motivated the conversion to open surgery. Many sutures were placed across the parenchyma for bleeding control. After 48 hours, she rapidly deteriorated with encephalopathy, coagulopathy, persistent hypotension and progressive organ dysfunction including acute renal failure requiring hemodialysis and mechanical ventilation. An angiography documented an occlusion of right hepatic artery and right portal vein. In the clinical of acute liver failure secondary to liver gangrene, severe coagulopathy and progressive secondary multi-organ failure, the patient was included in the waiting list for liver transplantation. Two days later, the patient was successfully transplanted with initial adequate liver graft function. However, she developed bilateral pneumonia and severe gastrointestinal bleeding and finally died 24 days after transplantation due to bilateral necrotizing pneumonia. Conclusion The occurrence of acute liver failure due to portal triad injury during laparoscopic cholecystectomy is a catastrophic complication. Probably, the indication of liver transplantation as a life-saving strategy in patients with late diagnosis, acute liver failure, severe coagulopathy and progressive secondary multi-organ failure could be considered but only minimizing immunosuppressive regimen to avoid postoperative infections.

  6. Intra-abdominal hypertension is an independent cause of acute renal failure after orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    SHU Ming; PENG Chenghong; CHEN Hao; SHEN Boyong; ZHOU Guangwen; SHEN Chuan; LI Hongwei

    2007-01-01

    Abstract An independent association between acute renal failure(ARF)and intra-abdominal hypertension(IAH)after liver transplantation has not been established previously.The aim of this retrospective study was to understand the role of IAH as an independent risk factor for ARF in the early postoperative period.This study involved 62 subjects who underwent liver transplantation.Intra-abdominal pressure (IAP)was measured in the first three days after surgery by using the urinary bladder technique.An IAP of at least 20 mmHg per day was defined as IAH.Clinical parameters between group IAH and group NO-IAH were compared in terms of the incidence of ARF,blood creatinine levels,blood urea nitrogen (BUN)levels,urine volume per hour and glomerular filtration gradient(GFG).Hemodynamic variations were recorded in the first three postoperative days between group ARF and group NO-ARF.The perioperative suspected risk factors of ARF were determined for statistical evaluation using correlation coefficients and logistic regression analysiIn group IAH.45.8%patients developed ARF as against 7.9in group NO-IAH;GFG was significantly lower at 0-72 h after surgery;and blood creatinine levels,BUN levels,urine volume per hour were significantly different at 24-72 h after surgery compared with group NO-IAH.The patients with ARF were not significantly difierent from those without ARF in terms of central venous pressure,pulmonary artely pressure and mean arterial pressure(MAP) in the first three postoperative days despite a significant increase in heart rate at 24-72h after operation.Postoperative IAH,intraoperative MAP and intraoperative blood transfusion volume of more than 15 U were found to be independent risk factors for ARF.IAH impaired renal function and was an independent risk factor for ARF after liver transplantation.Routine measurement should be taken to monitor IAP every eight hours postoperatively.

  7. Liver support therapy with molecular adsorbents recirculating system in liver failure:a summary of 252 cases from 14 centers in China

    Institute of Scientific and Technical Information of China (English)

    WANG Min-min; HU Xiao-bin; LUO Hong-tao; LIU Yi-he; WANG Wen-ya; CHEN Shi-jun; YE Qi-fa; YANG Yi-jun; CHEN Shi-bin; ZHOU Xin-min; GUO Li-min; ZHANG Yue-xin; DING Xiao-qiang

    2008-01-01

    Background A liver support therapy,named molecular adsorbents recirculating system (MARS),has been used for more than 700 liver failure patients in China.We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure.Methods This report analyzed data of 252 patients (mean age (44.9±12.7) years) in three groups:acute severe hepatitis (ASH),subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH).The largest group was CSH (156 patients,61.9%),and 188 patients (74.6%,188/252) were infected with HBV.Results MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins.Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP).There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale.Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%.Survival within the ASH and SSH groups were 81.2% and 75.0%,respectively.In the CSH group,end stage patients were predominant (65/151,43%),whereas the early and middle stage patients had a better prognosis:early stage survival,including orthotopic liver transplantation (OLT) survival of 91.7%,middle stage survival of 75%,end stage survival of 33.8%.Conclusions MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions,including the majority of hepatitis B related liver failure conditions.The appropriate application of MARS for the right indications and stage of hepatic failure,as well as the fulfillment of prescribed treatments,will lead to the optimal therapeutic result.

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

    Science.gov (United States)

    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

  9. Does the standard vs piggyback surgical technique affect the development of early acute renal failure after orthotopic liver transplantation?

    Science.gov (United States)

    Cabezuelo, J B; Ramirez, P; Acosta, F; Torres, D; Sansano, T; Pons, J A; Bru, M; Montoya, M; Rios, A; Sánchez Bueno, F; Robles, R; Parrilla, P

    2003-08-01

    The objective of this study was to evaluate the effect of the surgical technique on postoperative renal function during the first week after liver transplantation (OLT). We performed a retrospective study of 184 consecutive OLT. Criteria for acute renal failure were: serum creatinine >1.5 mg/dL, an increase by 50% in the baseline serum creatinine, or oliguria requiring renal replacement therapy. The distribution of patients according to the surgical technique was: standard (n=84), venovenous bypass (n=20), and piggyback (n=80). Other variables analyzed were: intraoperative requirement for blood products, treatment with adrenergic agonists, intraoperative complications, and postreperfusion syndrome. Univariate analysis showed the following parameters to be significantly related to postoperative renal failure: intraoperative fresh frozen plasma and cryoprecipitate requirements, intraoperative complications, postreperfusion syndrome, need for noradrenaline or dobutamine, standard surgical technique versus piggyback (39% vs 18%, P20 U cryoprecipitate requirement (OR=1.04, P=.01). In conclusion, compared with the piggyback technique, the standard surgical technique appears to be an independent risk factor for postoperative acute renal failure. When venovenous bypass is used in patients who do not tolerate trial clamping of inferior vena cava, it does not reduce the incidence of postoperative renal failure. Finally, the piggyback technique significantly reduces the probability of acute renal failure after liver transplantation.

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

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    Cyntia Ferreira Gomes Viana

    2008-09-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  12. Comparison scoring model of severe viral hepatitis and model of end stage liver disease for the prognosis of patients with liver failure in China

    Institute of Scientific and Technical Information of China (English)

    Li Zhou; Pei-Ling Dong; Hui-Guo Ding

    2007-01-01

    AIM: To estimate the prognosis of patients with liver failure using a scoring model of severe viral hepatitis (SMSVH) and a model of end stage liver disease (MELD)to provide a scientific basis for clinical decision of treatment.METHODS: One hundred and twenty patients with liver failure due to severe viral hepatitis were investigated with SMSVH established. Patients with acute, subacute,and chronic liver failure were 40, 46 and 34, respectively.The follow-up time was 6 mo. The survival rates of patients with liver failure in 2 wk, 4 wk, 3 mo and 6 mo were estimated with Kaplan-Meier method. Comparison between SMSVH and MELD was made using ROC statistic analysis.RESULTS: The survival curves of group A (at low risk,SMSVH score ≤ 4) and group B (at high risk, SMSVH score ≥ 5) were significantly different (The 4-wk, 3-mo, 6-mo survival rates were 94.59%, 54.05%, 43.24% in group A,and 51.81%, 20.48%, 12.05% in group B, respectively,P < 0.001). The survival curves of group C (SMSVH scores unchanged or increased), group D (SMSVH scores decreased by 1) and group E (SMSVH scores decreased by 2 or more) were significantly different .The survival rates of groups C, D and E were 66.15%, 100%, 100% in 2-wk; 40.0%, 91.18%, 100% in 4-wk; 0%, 58.82%,80.95% in 3-mo and 0%, 38.24%, 61.90% in 6-mo,respectively, P < 0.001). The area under the ROC curve (AUC) of SMSVH scores at baseline and after 2 wk of therapy was significantly higher than that under the ROC curve of MELD scores (0.804 and 0.934 vs 0.689, P <0.001).CONCLUSION: SMSVH is superior to MELD in the estimation of the prognosis of patients with severe viral hepatitis within 6 mo. SMSVH may be regarded as a criterion for estimation of the efficacy of medical treatment and the decision of clinical treatment.

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

    Institute of Scientific and Technical Information of China (English)

    I Gallardo-Wong; S Morán; G Rodríguez-Leal; B Casta(n)eda-Romero; R Mera; J Poo; M Uribe; M Dehesa

    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.

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

    OpenAIRE

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

    2016-01-01

    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 w...

  15. Effect of oral naltrexone on pruritus in cholestatic patients

    Institute of Scientific and Technical Information of China (English)

    Fariborz Mansour-Ghanaei; Elham Farhangi; Zahra Pourrasouli; Amir Taheri; Hossein Froutan; Hadi Ghofrani; Mohsen Nasiri-Toosi; Amir-Hossein Bagherzadeh; Mohammad-Jafar Farahvash; Shahram Mirmomen; Naser Ebrahimi-Dariani

    2006-01-01

    AIM: To determine the efficacy and potential complications of oral naltrexone used in the treatment of pruritus in cholestatic patients and to compare them with other studies.METHODS: Thirty-four enrolled cholestatic patients complaining of pruritus were studied, In the initial phase,pruritus scores during day and night were evaluated. Subsequently, patients were given a placebo for one week followed by naltrexone for one week. In each therapeutic course (placebo or naltrexone) day and night pruritus scores were distinguished by a visual analogue scale (VAS) system and recorded in patients' questionnaires.RESULTS: Both naltrexone and placebo decreased VAS scores significantly. Naltrexone was more effective than placebo in decreasing VAS scores. Both day and night scores of pruritus decreased by half of the value prior to therapy in thirteen patients (38%). Daytime pruritus improved completely in two patients (5.9%), but no improvement in the nighttime values was observed in any patient.Sixteen patients (47%) suffered from naltrexone complications, eleven (32%) of them were related to its withdrawal. Complications were often mild. In the case of withdrawal, the complication was transient (within the first 24-28 h of therapy) and self-limited. We had to cease the drug in two cases (5.9%) because of severe withdrawal symptoms. CONCLUSION: Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.

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

    International Nuclear Information System (INIS)

    The blood-to-brain transfer of [14C]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 [14C]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 [14C]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

  17. 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

    Directory of Open Access Journals (Sweden)

    Chenxia Hu

    2016-01-01

    Full Text Available 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.

  18. Liver dysfunction assessed by model for end-stage liver disease excluding INR (MELD-XI scoring system predicts adverse prognosis in heart failure.

    Directory of Open Access Journals (Sweden)

    Satoshi Abe

    Full Text Available AIMS: Liver dysfunction due to heart failure (HF is often referred to as cardiac or congestive hepatopathy. The composite Model for End-Stage Liver Disease excluding INR (MELD-XI is a robust scoring system of liver function, and a high score is associated with poor prognosis in advanced HF patients with a heart transplantation and/or ventricular assist device. However, the impact of MELD-XI on the prognosis of HF patients in general remains unclear. METHODS AND RESULTS: We retrospectively analyzed 562 patients who were admitted to our hospital for the treatment of decompensated HF. A MELD-XI score was graded, and patients were divided into two groups based on the median value of MELD-XI score: Group L (MELD-XI <10, n = 289 and Group H (MELD-XI ≥10, n = 273. We compared all-cause mortality and echocardiographic findings between the two groups. In the follow-up period (mean 471 days, 104 deaths (62 cardiac deaths and 42 non-cardiac deaths were observed. The event (cardiac death, non-cardiac death, all-cause death-free rate was significantly higher in group L than in group H (logrank P<0.05, respectively. In the Cox proportional hazard analysis, a high MELD-XI score was found to be an independent predictor of cardiac deaths and all-cause mortality in HF patients. Regarding echocardiographic parameters, right atrial and ventricular areas, inferior vena cava diameter, and systolic pulmonary artery pressure were higher in group H than in group L (P<0.05, respectively. CONCLUSIONS: The MELD-XI scoring system, a marker of liver function, can identify high-risk patients with right heart volume overload, higher pulmonary arterial pressure and multiple organ failure associated with HF.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  1. ANCA Associated Vasculitis and Renal Failure Related to Propylthiouracil and Hyperthyroidism Induced Cholestasis in the Same Case

    Directory of Open Access Journals (Sweden)

    Mehmet Tuncay

    2014-01-01

    Full Text Available Introduction. Liver involvement due to hyperthyroidism and also ANCA positive vasculitis related renal failure cases were reported separately several times before. However, to our knowledge, these two complications together in the same case had never been observed before. Case Presentation. The case of an ANCA positive 71-year-old Caucasian male with renal failure and lung involvement, subclinical hyperthyroidism, and intrahepatic cholestatic jaundice was presented in this paper. After exclusion of all of the other possibilities, cholestatic hepatitis was explained by subclinical hyperthyroidism; renal failure and lung involvement were interpreted as ANCA related vasculitis which might be a side effect of propylthiouracil use. Conclusion. The coexistence of these rare conditions in the same patient deserves emphasis and it is worth reporting. This case demonstrates that following the clinical course of the patient is essential after prescribing any medications to see whether any complication occurs or not. If the complications of this case were noticed earlier, it would be possible to treat and to prevent the permanent damages.

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

    Directory of Open Access Journals (Sweden)

    Roland Amathieu

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

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

    Science.gov (United States)

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  5. Transplantation of human thioredoxin gene-modified hepatocytes for treatment of acute liver failure in rat model

    Institute of Scientific and Technical Information of China (English)

    LI Hua; JIANG Nan; ZHANG Jian; WANG Gen-shu; YANG Yang; CHEN Gui-hua

    2009-01-01

    Background Mostly because of the limited number and proliferative ability of the transplanted hepatocytes,hepatocyte transplantation offers only temporary support to the hepatic function with rather poor functional replacement of the damaged liver parenchyma.This study aimed to observe the therapeutic effect of human thioredoxin(hTrx)gene-modified hepatocytes on experimental acute liver failure in rats.Methods hTrx cDNA was obtained by reverse transcription-polymerase chain reaction(RT-PCR)from human osteosercoma 143(TK-)cells to construct the recombinant retrovirus vector pLEGFP/hTrx,which was packaged into PA317 cells to collect the recombinant retrovirus containing hTrx gene.After titration and characterization,the recombinant retrovirus was applied to primary cultured rat hepatocyte for infection to generate hTrx gene-modified rat hepatocytes,whose viability and antioxidative capacity were examined by immunohistochemistry and MIF assay,respectively.In a Sprague-Dawley(SD)rat model of acute liver failure,the modified hepatocytes were injected into the spleen,and the hepatic function and survival rate of the recipient rats were evaluated at different time points after the transplantation.Results NIH3T3 cells infected by the recombinant retrovirus were capable of expressing bioactive hTrx in the form of fusion proteins.Immunohistochemistry demonstrated normal function of the hTrx gene-modified hepatocytes,which possessed strong antioxidative capacity as shown by MTT assay.Transplantation of the modified hepatocytes in rats with acute liver failure resulted in significantly lowered serum alanine aminotransferase(ALT)and total bilirubin(TBIL)levels(P<0.05).The hepatocytes exhibited long-term survival and efficient proliferation after transplantation.Fourteen days after the operation,the rat models receiving hTrx gene-modified hepatocytes had significantly higher survival rate than those without the transplantation.Conclusion hTrx gene-modifled hepatocyte

  6. The Use of Induced Pluripotent Stem Cells for the Study and Treatment of Liver Diseases.

    Science.gov (United States)

    Hansel, Marc C; Davila, Julio C; Vosough, Massoud; Gramignoli, Roberto; Skvorak, Kristen J; Dorko, Kenneth; Marongiu, Fabio; Blake, William; Strom, Stephen C

    2016-01-01

    Liver disease is a major global health concern. Liver cirrhosis is one of the leading causes of death in the world and currently the only therapeutic option for end-stage liver disease (e.g., acute liver failure, cirrhosis, chronic hepatitis, cholestatic diseases, metabolic diseases, and malignant neoplasms) is orthotropic liver transplantation. Transplantation of hepatocytes has been proposed and used as an alternative to whole organ transplant to stabilize and prolong the lives of patients in some clinical cases. Although these experimental therapies have demonstrated promising and beneficial results, their routine use remains a challenge due to the shortage of donor livers available for cell isolation, variable quality of those tissues, the potential need for lifelong immunosuppression in the transplant recipient, and high costs. Therefore, new therapeutic strategies and more reliable clinical treatments are urgently needed. Recent and continuous technological advances in the development of stem cells suggest they may be beneficial in this respect. In this review, we summarize the history of stem cell and induced pluripotent stem cell (iPSC) technology in the context of hepatic differentiation and discuss the potential applications the technology may offer for human liver disease modeling and treatment. This includes developing safer drugs and cell-based therapies to improve the outcomes of patients with currently incurable health illnesses. We also review promising advances in other disease areas to highlight how the stem cell technology could be applied to liver diseases in the future. © 2016 by John Wiley & Sons, Inc. PMID:26828329

  7. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases

    OpenAIRE

    Lyberopoulou, Aggeliki; Chachami, Georgia; Gatselis, Nikolaos K.; Kyratzopoulou, Eleni; Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K.; Mamalaki, Avgi; Dalekos, George N; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimm...

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

    Science.gov (United States)

    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 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

  9. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats.

    Science.gov (United States)

    Verbeke, Len; Farre, Ricard; Verbinnen, Bert; Covens, Kris; Vanuytsel, Tim; Verhaegen, Jan; Komuta, Mina; Roskams, Tania; Chatterjee, Sagnik; Annaert, Pieter; Vander Elst, Ingrid; Windmolders, Petra; Trebicka, Jonel; Nevens, Frederik; Laleman, Wim

    2015-02-01

    Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis. PMID:25592258

  10. Excessive portal flow causes graft failure in extremely small-for-size liver transplantation in pigs

    Institute of Scientific and Technical Information of China (English)

    Hong-Sheng Wang; Tomohiro Narita; Hideyuki Yamaya; Atsushi Nakamura; Satoshi Sekiguchi; Naoki Kawagishi; Akira Sato; Susumu Satomi; Nobuhiro Ohkohchi; Yoshitaka Enomoto; Masahiro Usuda; Shigehito Miyagi; Takeshi Asakura; Hiroo Masuoka; Takashi Aiso; Keisuke Fukushima

    2005-01-01

    AIM: To evaluate the effects of a portocaval shunt on the decrease of excessive portal flow for the prevention of sinusoidal microcirculatory injury in extremely smallfor-size liver transplantation in pigs.METHODS: The right lateral lobe of pigs, i.e. the 25%of the liver, was transplanted orthotopically. The pigs were divided into two groups: graft without portocaval shunt (n = 11) and graft with portocaval shunt (n=11).Survival rate, portal flow, hepatic arterial flow, and histological findings were investigated.RESULTS: In the group without portocaval shunt, all pigs except one died of liver dysfunction within 24 h after transplantation. In the group with portocaval shunt,eight pigs survived for more than 4 d. The portal flow volumes before and after transplantation in the group without portocaval shunt were 118.2±26.9 mL/min/100 g liver tissue and 270.5±72.9 mL/min/100 g liver tissue,respectively. On the other hand, in the group with portocaval shunt, those volumes were 124.2±27.8 mL/min/100 g liver tissue and 42.7±32.3 mL/min/100 g liver tissue, respectively (P<0.01). As for histological findings in the group without portocaval shunt, destruction of the sinusoidal lining and bleeding in the peri-portal areas were observed after reperfusion, but these findings were not recognized in the group with portocaval shunt.CONCLUSION: These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

  11. Vitamin D status, liver enzymes, and incident liver disease and mortality

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Borglykke, Anders;

    2014-01-01

    Vitamin D deficiency is common among patients with liver diseases. Both cholestatic and non-cholestatic liver diseases can cause vitamin D deficiency. Whether vitamin D status can also affect liver function is poorly understood. To investigate the association between vitamin D status, liver enzymes......, and incident liver disease, we included a total of 2,649 individuals from the Monica10 study conducted in 1993-1994. Vitamin D status as assessed by serum 25-hydroxyvitamin, serum alanine transaminase (ALT), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) were measured at baseline....... Information on fatal and non-fatal liver disease was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death, respectively. Median follow-up time was 16.5 years, and there were 62 incident cases of fatal and non-fatal liver disease. Multivariable Cox regression analyses...

  12. Transgenic overexpression of Tcfap2c/AP-2gamma results in liver failure and intestinal dysplasia.

    Directory of Open Access Journals (Sweden)

    Daniel Holl

    Full Text Available BACKGROUND: The transcription factor Tcfap2c has been demonstrated to be essential for various processes during mammalian development. It has been found to be upregulated in various undifferentiated tumors and is implicated with poor prognosis. Tcfap2c is reported to impinge on cellular proliferation, differentiation and apoptosis. However, the physiological consequences of Tcfap2c-expression remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Therefore we established a gain of function model to analyze the role of Tcfap2c in development and disease. Induction of the transgene led to robust expression in all tissues (except brain and testis and lead to rapid mortality within 3-7 days. In the liver cellular proliferation and apoptosis was detected. Accumulation of microvesicular lipid droplets and breakdown of major hepatic metabolism pathways resulted in steatosis. Serum analysis showed a dramatic increase of enzymes indicative for hepatic failure. After induction of Tcfap2c we identified a set of 447 common genes, which are deregulated in both liver and primary hepatocyte culture. Further analysis showed a prominent repression of the cytochrome p450 system, PPARA, Lipin1 and Lipin2. These data indicate that in the liver Tcfap2c represses pathways, which are responsible for fatty acid metabolism. In the intestine, Tcfap2c expression resulted in expansion of Sox9 positive and proliferative active epithelial progenitor cells resulting in dysplastic growth of mucosal crypt cells and loss of differentiated mucosa. CONCLUSIONS: The transgenic mice show that ectopic expression of Tcfap2c is not tolerated. Due to the phenotype observed, iTcfap2c-mice represent a model system to study liver failure. In intestine, Tcfap2c induced cellular hyperplasia and suppressed terminal differentiation indicating that Tcfap2c serves as a repressor of differentiation and inducer of proliferation. This might be achieved by the Tcfap2c mediated activation of Sox9

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

    Directory of Open Access Journals (Sweden)

    Kenji Takemoto

    2014-01-01

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

  14. Thrombocytopenia-associated multiple organ failure or severe haemolysis, elevated liver enzymes, low platelet count in a postpartum case

    Directory of Open Access Journals (Sweden)

    Manish Jagia

    2013-01-01

    Full Text Available Thrombocytopenia-associated multiple organ failure (TAMOF is a thrombotic microangiopathic syndrome that includes thrombotic thrombocytopenic purpura, secondary thrombotic microangiopathy, and disseminated intravascular coagulation. We report a case of postpartum female who presented with TAMOF or severe Haemolysis, elevated liver enzymes, low platelet count (HELLP which was managed with plasma exchange. This case report is to make clinicians aware that TAMOF, severe HELLP, and other differential diagnosis in a postpartum case have a thin differentiating line and plasma exchange can be considered as one of the management options.

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

    Directory of Open Access Journals (Sweden)

    Melissa I. Chang

    2012-11-01

    Full Text Available 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.

  16. Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice

    OpenAIRE

    Wolf, A.M.; Wolf, D; M.A. Avila; Moschen, A R; Berasain, C; Enrich, B. (Barbara); Rumpold, H. (Holger); Tilg, H

    2006-01-01

    BACKGROUND/AIMS: Recent reports suggest that the adipose tissue and adipokines are potent modulators of inflammation. However, there is only scarce knowledge on the functional role and regulation of endogenous adiponectin in non-fat tissues such as the liver under conditions of acute inflammation. METHODS: In the present study, we investigated adiponectin expression in healthy murine liver tissue and under inflammatory conditions in vivo. RESULTS: Adiponectin mRNA was readily detectable...

  17. Development of fatal acute liver failure in HIV-HBV coinfected patients

    Institute of Scientific and Technical Information of China (English)

    Albert; M; Anderson; Marina; B; Mosunjac; Melody; P; Palmore; Melissa; K; Osborn; Andrew; J; Muir

    2010-01-01

    Coinfection with hepatitis B virus(HBV) is not uncommon in human immunodeficiency virus(HIV)-infected individuals and patients with HIV-HBV coinfection are at high risk for progression of liver disease.Current guidelines regarding the treatment of HIV infection recommend that patients who are coinfected with HIV and HBV receive highly active antiretroviral therapy(HAART) with activity against hepatitis B.While HIVHBV coinfected patients often experience liver enzyme elevations after starting antiretroviral ...

  18. Development and Pilot of a Checklist for Management of Acute Liver Failure in the Intensive Care Unit.

    Directory of Open Access Journals (Sweden)

    Oren K Fix

    Full Text Available Acute liver failure (ALF is an ideal condition for use of a checklist. Our aims were to develop a checklist for the management of ALF in the intensive care unit (ICU and assess the usability of the checklist among multiple providers.The initial checklist was developed from published guidelines and expert opinion. The checklist underwent pilot testing at 11 academic liver transplant centers in the US and Canada. An anonymous, written survey was used to assess the usability and quality of the checklist. Written comments were used to improve the checklist following the pilot testing period.We received 81 surveys involving the management of 116 patients during the pilot testing period. The overall quality of the checklist was judged to be above average to excellent by 94% of users. On a 5-point Likert scale, the majority of survey respondents agreed or agreed strongly with the following checklist characteristics: the checklist was easy to read (99% agreed/agreed strongly, easy to use (97%, items are categorized logically (98%, time to complete the checklist did not interfere with delivery of appropriate and safe patient care (94% and was not excessively burdensome (92%, the checklist allowed the user the freedom to use his or her clinical judgment (80%, it is a useful tool in the management of acute liver failure (98%. Web-based and mobile apps were developed for use of the checklist at the point of care.The checklist for the management of ALF in the ICU was shown in this pilot study to be easy to use, helpful and accepted by a wide variety of practitioners at multiple sites in the US and Canada.

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

    Science.gov (United States)

    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

  20. Role of ammonia, inflammation, and cerebral oxygenation in brain dysfunction of acute-on-chronic liver failure patients.

    Science.gov (United States)

    Sawhney, Rohit; Holland-Fischer, Peter; Rosselli, Matteo; Mookerjee, Rajeshwar P; Agarwal, Banwari; Jalan, Rajiv

    2016-06-01

    Hepatic encephalopathy (HE) is a common feature of acute-on-chronic liver failure (ACLF). Although ammonia, inflammation, and cerebral oxygenation are associated with HE in acute liver failure, their roles in ACLF are unknown. The aim of this prospective, longitudinal study was to determine the role of these pathophysiological variables in ACLF patients with and without HE. We studied 101 patients with ACLF admitted to the intensive care unit. Severity of ACLF and HE, arterial ammonia, jugular venous oxygen saturation (JVO2 ), white blood cell count (WCC), and C-reactive protein were measured at days 0, 1, 3, and 7. Patients were followed until death or hospital discharge. Mortality was high (51 patients, 50.5%), especially in patients with HE of whom 35 of 53 (66.0%) died regardless of ACLF severity. At baseline, increased WCC and abnormal JVO2 (high or low) were independent predictors of death. Further deterioration in inflammation, JVO2 , and ammonia were also predictive of mortality. JVO2 deviation and hyperammonemia were associated with the presence and severity of HE; improvement in these parameters was associated with a reduction in HE grade. No direct interaction was observed between these variables in regards to mortality or HE. In conclusion, this study describes potential mechanisms of HE in ACLF indicating that ammonia and abnormal cerebral oxygenation are important. The results suggest that ammonia, JVO2 , and WCC are important prognostic biomarkers and therapeutic targets. The relative roles of these pathophysiological factors in the pathogenesis of HE in ACLF or guiding therapy to improve survival requires future study. Liver Transplantation 22 732-742 2016 AASLD. PMID:27028317

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  2. Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist

    OpenAIRE

    Kiat-Hon Lim; Jason Pik-Eu Chang; Chee-Kiat Tan; Lynette Lin-Ean Oon; Boon-Huan Tan; Hoe-Nam Leong; Hui-Hui Tan

    2011-01-01

    Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  5. The therapeutic effect of CORM-3 on acute liver failure induced by lipopolysaccharide/D-galactosamine in mice

    Institute of Scientific and Technical Information of China (English)

    Bing-Zhu Yan; Bao-Shan Yang; Hui Li; Yan-Fen Zhang; Feng-Hua Pei; An-Chao Zhu; Xiao-Ren Wang; Bing-Rong Liu

    2016-01-01

    BACKGROUND: Acute liver failure (ALF) is a severe and life-threatening clinical syndrome resulting in a high mortality and extremely poor prognosis. Recently, a water-soluble CO-releas-ing molecule (CORM-3) has been shown to have anti-inflam-matory effect. The present study was to investigate the effect of CORM-3 on ALF and elucidate its underlying mechanism. METHODS: ALF was induced by a combination of LPS/D-GalN in mice which were treated with CORM-3 or inactive CORM-3 (iCORM-3). The efficacy of CORM-3 was evaluated based on survival, liver histopathology, serum aminotransferase activi-ties (ALT and AST) and total bilirubin (TBiL). Serum levels of inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10) and liver immunohistochemistry of NF-κB-p65 were determined;the expression of inflammatory mediators such as iNOS, COX-2 and TLR4 was measured using Western blotting. RESULTS: The pretreatment with CORM-3 significantly im-proved the liver histology and the survival rate of mice com-pared with the controls; CORM-3 also decreased the levels of ALT, AST and TBiL. Furthermore, CORM-3 significantly inhibited the increased concentration of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and increased the anti-in-flammatory cytokine (IL-10) productions in ALF mice. More-over, CORM-3 significantly reduced the increased expression of iNOS and TLR4 in liver tissues and inhibited the nuclear ex-pression of NF-κB-p65. CORM-3 had no effect on the increased expression of COX-2 in the ALF mice. An iCORM-3 failed to prevent acute liver damage induced by LPS/D-GalN. CONCLUSION: These findings provided evidence that CORM-3 may offer a novel alternative approach for the management of ALF through anti-inflammatory functions.

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

    Directory of Open Access Journals (Sweden)

    Dan Xu

    2014-04-01

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

  7. Inhibition of glycogen synthase kinase 3β promotes autophagy to protect mice from acute liver failure mediated by peroxisome proliferator-activated receptor α

    OpenAIRE

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

    2016-01-01

    Our previous studies have demonstrated that inhibition of glycogen synthase kinase 3β (GSK3β) activity protects mice from acute liver failure (ALF), whereas its protective and regulatory mechanism remains elusive. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that inhibition of GSK3β mediates autophagy to inhibit liver inflammation and protect against ALF. In ALF mice model induced by d-gala...

  8. Assessment of liver fibrosis: Noninvasive means

    Directory of Open Access Journals (Sweden)

    Poynard Thierry

    2008-01-01

    Full Text Available Liver biopsy, owing to its limitations and risks, is an imperfect gold standard for assessing the severity of the most frequent chronic liver diseases chronic hepatitis C (HCV, B (HBV non alcoholic (NAFLD and alcoholic (ALD fatty liver diseases. This review summarizes the advantages and the limits of the available biomarkers of liver fibrosis. Among a total of 2,237 references, a total of 14 validated serum biomarkers have been identified between 1991 and 2008. Nine were not patented and five were patented. Two alternatives to liver biopsy were the most evaluated FibroTest and Fibroscan. For FibroTest, there was a total of 38 different populations including 7,985 subjects with both FibroTest and biopsy (4,600 HCV, 1,580 HBV, 267 NAFLD, 524 ALD, and 1014 mixed. For Fibroscan, there was a total of 11 published studies including 2,260 subjects (1,466 HCV, 95 cholestatic liver disease, and 699 mixed. For FibroTest, the mean diagnostic value for the diagnosis of advanced fibrosis assessed using standardized area under the ROC curves was 0.84 (95% confidence interval 0.83-0.86, without a significant difference between the causes of liver disease, hepatitis C, hepatitis B, and alcoholic or non alcoholic fatty liver disease. High-risk profiles of false negative/false positive of FibroTest, mainly Gilbert syndrome, hemolysis and acute inflammation, are present in 3% of the populations. In case of discordance between biopsy and FibroTest, half of the failures can be due to biopsy; the prognostic value of FibroTest is at least similar to that of biopsy in HCV, HBV and ALD. In conclusion this overview of evidence-based data suggests that biomarkers could be used as an alternative to liver biopsy for the first line assessment of fibrosis stage in the four most common chronic liver diseases, namely HCV, HBV, NAFLD and ALD. Neither biomarkers nor biopsy alone is sufficient for taking a definite decision in a given patient; all the clinical and biological data

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

    Science.gov (United States)

    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 spleen length (p 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.

  10. Liver transplant

    Science.gov (United States)

    ... transplant - series References Keefe EB. Hepatic failure and liver transplantation. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Elsevier; 2011:chap 157. Martin P, Rosen HR. Liver transplantation. In: Feldman M, Friedman LS, Brandt LJ, eds. ...

  11. Safety and efficacy of N-acetylcysteine in children with non-acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Kortsalioudaki, Christine; Taylor, Rachel M; Cheeseman, Paul; Bansal, Sanjay; Mieli-Vergani, Giorgina; Dhawan, Anil

    2008-01-01

    Acute liver failure (ALF) carries a high mortality in children. N-acetylcysteine (NAC), an antioxidant agent that replenishes mitochondrial and cytosolic glutathione stores, has been used in the treatment of late acetaminophen-induced ALF and non-acetaminophen-induced ALF. In our unit, NAC was introduced as additional treatment for non-acetaminophen-induced ALF in 1995. The aim of this study was to evaluate the safety and efficacy of NAC in children with ALF not caused by acetaminophen poisoning. A retrospective review of medical records of 170 children presenting with nonacetaminophen-induced ALF between 1989 and 2004 was undertaken. ALF was defined as either international normalized ratio of prothrombin time (INR) > 2 and abnormal liver function or INR >1.5 with encephalopathy and abnormal liver function. Children were divided into the following groups: Group 1 (1989-1994), standard care (n = 59; 34 [58%] male; median age 2.03 yr, range 0.003-15.8 yr); and Group 2 (1995-2004), standard care and NAC administration (n = 111; 57 [51%] male; median age 3.51 yr, range 0.005-17.4 yr). NAC was administered as a continuous infusion (100 mg/kg/24 hours) until INR dizziness and peripheral edema in 1. One child had an allergic reaction (bronchospasm) and NAC was stopped. A total of 41 (71%) children in Group 1 vs. 85 (77%) in Group 2 required admission to intensive care, P = not significant (ns). The length of intensive care stay was 6 (range, 1-58) days in Group 1 vs. 5 (range, 1-68) days in Group 2, P = ns and length of hospital stay was 25 (range, 1-264) days vs. 19 (range, 1-201) days, P = 0.05. The 10-yr actuarial survival was 50% in Group 1 compared to 75% in Group 2, P = 0.009. Survival with native liver occurred in 13 (22%) in Group 1 vs. 48 (43%) in Group 2, P = 0.005; 15 (25%) in Group 1 died without transplant vs. 21 (19%) in Group 2, P = ns; and LT was performed in 32 (54%) vs. 42 (38%), P = ns. Death after transplantation occurred in 15 (39%) in Group 1 vs. 8

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    AIM: To investigate a dual labeling technique, which would enable real-time monitoring of transplanted em- bryonic 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

  14. Protection against Fas-induced fulminant hepatic failure in liver specific integrin linked kinase knockout mice

    OpenAIRE

    Donthamsetty, Shashikiran; Mars, Wendy M.; Orr, Anne; Wu, Chuanyue; Michalopoulos, George K

    2011-01-01

    Background Programmed cell death or apoptosis is an essential process for tissue homeostasis. Hepatocyte apoptosis is a common mechanism to many forms of liver disease. This study was undertaken to test the role of ILK in hepatocyte survival and response to injury using a Jo-2-induced apoptosis model. Methods For survival experiments, ILK KO and WT mice received a single intraperitoneal injection of the agonistic anti-Fas monoclonal antibody Jo-2 at the lethal dose (0.4 μg/g body weight) or s...

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

    Directory of Open Access Journals (Sweden)

    Olympia Anastasiou

    Full Text Available 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.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.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.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.

  16. Effectiveness of xenotransplantation of human fetal hepatocytes in spleen of rats with acute liver failure induced by CCL4

    Directory of Open Access Journals (Sweden)

    Abdukhakim Khadjibaev

    2013-04-01

    Full Text Available Human’s fetal hepatocytes (HFH were intrasplenic transplanted white non-pedigree rats with acute liver failure (ALF challenged by single per oral administration of hepatotropic toxin diluted in oil ССl4 at a dose 10 ml/kg (volumetric correlation 1:1 (10 mL/kg body weight as a 1:1 mixture of CCl4 and mineral oil. Transplantation had positive effect on all biochemical blood parameters of the studying animals. Morphologic study showed that reparative-restorative processes were arising in hepatic parenchyma after administration of HFH into splenic pulp of rats with model of ALF on days 14-21. Substantial and main factor in restoration of parenchyma was restoration of micro topographic interrelations in acinus as well as polyploidy of hepatic cells expressed in increase of hepatocytes’ nuclei sizes and hypertrophy of cells themselves. It is an indirect confirmation of engraftment of HFH in liver of rats with model of ALF.

  17. Liver disease in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Noel M Lee; Carla W Brady

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy.

  18. A patient with acute liver failure and extreme hypoglycaemia with lactic acidosis who was not in coma : causes and consequences of lactate-protected hypoglycaemia

    NARCIS (Netherlands)

    Oldenbeuving, G.; McDonald, J. R.; Goodwin, M. L.; Sayilir, R.; Reijngoud, D. J.; Gladden, L. B.; Nijsten, M. W. N.

    2014-01-01

    Lactate can substitute for glucose as a metabolic substrate. We report a patient with acute liver failure who was awake despite a glucose level of 0.7 mmol/l with very high lactate level of 25 mmol/l. The hypoglycaemia+hyperlactataemia combination may be considered paradoxical since glucose is the m

  19. Acute liver failure in a patient with sickle cell/β+ thalassaemia

    International Nuclear Information System (INIS)

    We describe a rare, severe, vaso-occlusive presentation of sickle cell disease, named sickle cell intrahepatic cholestasis (SCIC). Patients with sickle cell/β+ thalassaemia frequently have mild vaso-occlusive symptoms and only one case of SCIC developing in a patient with sickle cell/β+ thalassaemia has been previously described in the world literature. The present report represents only the second described case of SCIC in a patient with sickle cell/β+ thalassaemia. An abdominal computed tomography scan and Doppler ultrasound studies demonstrated massive hepatomegaly (25 cm span). Liver biopsy was performed and demonstrated dilatation and congestion of erythrocytes, severe cholestasis and fibrosis. The case demonstrates the importance of early recognition and institution of adequate therapy. Initial and correct diagnosis does not require biopsy or surgery which carry substantial risks of bleeding and mortality

  20. High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Lu-WenWang; Hui Chen; Zuo-Jiong Gong

    2010-01-01

    BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4+CD25+CD127low Treg cells among CD4+cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4+CD25+CD127low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4+ cells were found in liver failure patients than in CHB patients (82.6±20.1 μg/L vs. 34.2±13.7 μg/L; 4.55±1.34% vs. 9.52± 3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection

  1. Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure

    Institute of Scientific and Technical Information of China (English)

    Kun Huang; Jin-Hua Hu; Hui-Fen Wang; Wei-Ping He; Jing Chen; Xue-Zhang Duan; Ai-Min Zhang; Xiao-Yan Liu

    2011-01-01

    AIM: To investigate the survival rates and prognostic ffactors in patients with hepatitis B virus-related acute-on-chronic liver ffailure (HBV-ACLF).METHODS: Clinical data in hospitalized patients with HBV-ACLF admitted ffrom 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis.RESULTS: A total off 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014].The highest risk off death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001).CONCLUSION: Antiviral therapy has a strong effffect on the prognosis off the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances,and HE also affffect patient survival.

  2. Progress of Targeting Transforming Growth Factor-β1 Small Interfering RNA in Liver Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Xuan Zhou; Xue-feng Yang

    2014-01-01

    Liver fibrosis is a common pathological consequence of a variety of chronic stimuli, including viral, autoimmune, drug-induced, cholestatic and metabolic diseases. Fibrosis is driven by a dynamic process involving increased synthesis of matrix components and a failure of physiological mechanisms of matrix turnover. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis. HSCs are the main source of extracellular matrix (ECM). Transforming growth factor-beta (TGF-β), which is the fibrogenic master cytokine, can induce the activation of HSCs to produce a large amount of ECM, and is capable of inducing apoptosis of liver cells. RNA interference (RNAi) is a novel gene disruption technology. Studies have shown that small interfering RNA (siRNA) targeting TGF-β1 may inhibit the activation and proliferation of HSCs, suppress ECM synthesis and block liver fibrosis. TGF-β1 siRNA-mediated gene silencing therapy provides a new avenue for liver fibrosis. This review summarizes recent progresses in research on HSCs, TGF-β1 and TGF-β1 siRNA in liver fibrosis.

  3. Analysis of Liver Failure After Major Hepatectomy for Hepatocellular Carcinoma%大肝癌术后肝衰竭的防治

    Institute of Scientific and Technical Information of China (English)

    江勇; 汤建军; 远博

    2011-01-01

    Objective To identify risk factors for poatoperative liver failure after hepatectomy and explore its diagnosis and treatment. Methods Perioperative risk factors for liver failure after hepatectomy were analyzed in 53 patients with large hepatic carcinoma.The causes of liver failure were analyzed baaed on hoth the perioperative data and the intraoperative findings. A volumetric analysis by CT was then done to evaluate the remnant liver volume. Stepwise multivariate logistic regression was performed to investigate significant independent factors among the variables. Results Significant risk factors of postoperative liver failure were severe cirrhosis, operative blood loss and remnant liver volume(P <0.01) . Conclusion Sufficient preoperative evaluation of liver function and level of cirrosis, careful patient selection based on volumetric analysis, and control of intraoperative bleeding in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.%目的 探讨大肝癌切除术后肝衰竭的相关危险因素及其防治.方法 回顾性分析笔者医院近2年收治的53例大肝癌.对肝衰竭原因的分析基于围手术期的相关数据及手术情况,CT评估肝脏体积.多元Logistic回归法分析肝衰竭发生的相关危险因素.结果 53例大肝癌术后发生肝衰竭8例(15.1%),其中死亡3例.术前肝硬化程度、手术失血、肝切除量是术后肝衰竭发生的独立危险因素(P<0.01).结论 对于大肝癌需行肝切除的患者,术前做好肝硬化程度和肝切除量的评估,术中控制出血量及缩短肝门阻断时间是减少术后肝衰竭发生的重要因素.

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

    Science.gov (United States)

    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

  5. 人工肝治疗对重型病毒性肝病患者生存期的影响%Survival Analysis on Virus Liver Failure Patients Treated with Artificial Liver Support System

    Institute of Scientific and Technical Information of China (English)

    武文芳; 杜菁; 张晶

    2011-01-01

    Objective To evaluate the efficacy of artificial liver support system (ALSS ) in the treatment of virus liver failure patients in a large controlled clinic trial. Methods Nine hundred and two patients with virus liver failure enrolled were divided into an ALSS treatment group of 507 and a control group of 395 without ALSS treatment. The analysis of survival time was computed by the Kaplain-Maier method, and comparison among groups was done by Log-Rank and Breslow test. Results ALSS affected the survival time of acute and subacute virus liver failure patients and prolonged their survival time significantly. ALSS also prolonged the survival time of B liver failure patients and affected the short-term survival time of E liver failure patients. The number of times of ALSS effected on the survival time of liver patients obviously. ConclusionsMulti-ALSS treatment prolongs the survival time of acute and subacute virus liver failure patients and is more effective than the standard medicinal liver care treatment. The treatment with ALSS for the liver failure patients is important and necessary.%目的 通过大样本对照分析研究,探讨人工肝支持系统(artificial liver support system,ALSS)治疗对重型病毒性肝病患者生存期的影响.方法 选择重型病毒性肝病患者902例,将患者分为人工肝治疗组507例和常规内科治疗对照组395例,记录其诊断、分期等原始资料并进行随访,采用Kaplan-Meier方法和Log rank以及Breslow检验进行生存情况分析.结果 人工肝治疗对急性和亚急性重型病毒性肝炎患者的生存时间有明显影响,能够延长其生存时间;人工肝治疗可以延长乙型肝炎患者的生存时间,对戊型肝炎患者的短期生存率有影响;人工肝治疗次数对患者生存时间也有明显影响.结论 人工肝治疗能够延长急性和亚急性重型病毒性肝炎患者的生存时间,多次治疗效果显著优于单次治疗和内科治疗.

  6. Glutathione-S-transferase subtypes α and π as a tool to predict and monitor graft failure or regeneration in a pilot study of living donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Jochum C

    2011-01-01

    Full Text Available Abstract Objective Glutathione-S-Transferase (GST subtype α and π are differentially expressed in adult liver tissue. Objective of the study was if GST α and p may serve as predictive markers for liver surgery, especially transplantations. Methods 13 patients receiving living donor liver transplantation (LDLT and their corresponding donors were analyzed for standard serum parameters (ALT, AST, gGT, bilirubin as well as GST-α and -π before LDLT and daily for 10 days after LDLT. Patients (R and donors (D were grouped according to graft loss (R1/D1 or positive outcome (R2/D2 and above named serum parameters were compared between the groups. Results R1 showed significantly increased GST-α and significantly lower GST-π levels than R2 patients or the donors. There was a positive correlation between GST-α and ALT, AST as well as bilirubin and a negative correlation to γGT. However, γGT correlated positively with GST-π. Graft failure was associated with combined low GST-π levels in donors and their recipients before living donor liver transplantation. Conclusion Our data suggest that high GST-α serum levels reflect ongoing liver damage while GST-P indicates the capacity and process of liver regeneration. Additionally, GST-π may be useful as marker for optimizing donor and recipient pairs in living donor liver transplantation.

  7. A Molecular Adsorbent Recycling System in Treating Posthepatectomy Acute Hepatic Failure Patients with Hepatocellular Carcinoma: a Bridge to Liver Transplantation

    Institute of Scientific and Technical Information of China (English)

    Yu Wang; Yihe Liu; Weiping Zheng; Yu Ming; Zhongyang Shen

    2006-01-01

    OBJECTIVE To evaluate the effect and safety of a Molecular Adsorbent Recycling System (MARS) in treating posthepatoectomy hepatic failure (AHF) patients surgically treated for primary hepatocellular carcinoma (HCC).METHODS 12 AHF patients induced by resection of HCC were treated with MARS before orthotopic liver transplantation (OLT). Their vital signs, urine volume, APACHE Ⅲ and Glasgow scores were monitored. Routine laboratory blood tests, measurements of coagulatory function, liver and kidney function, serum ammonia, lactic acid and blood gas were conducted before and after treatment with MARS. All of the patients were followed up for a period of 6 months after OLT for prognosis and complication assessment.RESULTS Each patient was treated with MARS for 2~5 times (average of 3.6) with a length of 8~24 h each time. Their mean arterial blood pressure and urine volume were improved, APACHE Ⅲ and Glasgow scores were better. Liver function was improved with the following alterations before and after treatment with MARS: serum ammonia (127.1±21.4 umol/L vs. 77.4±19.7 umol/L, P<0.05), lactic acid (6.53±0.45 mmol/L vs. 3.75± 0.40 mmol/L, P<0.05) and total bilirubin (452.3±153.7 umol/L vs. 230.9± 115.2 umol/L, P<0.05). However, there was no significant change in platelet count (44.25±3.60×109/L vs. 43.19±8.26×109/L, P>0.05) on international normalized ratio (INR) (2.74±0.50 vs. 2.82±0.60, P>0.05), which showed the safety of MARS. For all patients no serious adverse effects occurred during the treatment with MARS.CONCLUSION MARS is effective and safe for treatment of AHF patients with HCC, especially as a bridge to OLT when a donor organ is not available.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  10. Prognostic Value of Gc-Globulin in Chinese Patients with Acute-On-Chronic Hepatitis B Liver Failure

    International Nuclear Information System (INIS)

    Objective: To determine dynamic Gc-globulin level change in Acute-on-Chronic Hepatitis B Liver Failure (ACHBLF) patients, and evaluate the prognostic value of Gc-globulin. Study Design: An analytical study. Place and Duration of Study: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from January 2010 to December 2012. Methodology: A total of 54 consecutive Chinese ACHBLF patients and 30 healthy volunteers as controls were recruited from 2010 to 2012. The patients were divided into improved group and aggravated group. Gc-globulin levels were determined in both groups and mean values compared with significance at p < 0.05. Cut-off value was also determined. Results: The Gc-globulin level was significantly decreased in ACHBLF patients (p < 0.001). Gc-globulin levels were significantly higher in improved patients than in aggravated patients, and a 215 mg/L cut-off value carried the best prognostic information. On longitudinal observations, Gc-globulin gradually elevated in improved groups. However, in aggravated groups, the Gc-globulin levels were always below normal levels and no significant change was observed before or after the treatment (p > 0.05). Conclusion: Gc-globulin monitoring offers a rapid and accurate method to estimate treatment outcomes on admission and an effective temporal indicator of curative effects in ACHBLF patients at an optimal cut-off value of 215 mg/L. (author)

  11. Evaluation of prognostic markers in severe drug-induced liver disease

    Institute of Scientific and Technical Information of China (English)

    Bo Li; Zhi Wang; Jian-Jiang Fang; Ci-Yi Xu; Wei-Xing Chen

    2007-01-01

    AIM: To analyze the outcome of patients with severe drug-induced liver disease (DILD) associated with jaundice classified as hepatocellular, cholestatic or mixed liver injury and to evaluate the validity of Hy's rule and the most important predictors for outcome.METHODS: The Adverse Drug Reaction Advisory Committee was set up in 1997 in our hospital to identify all suspicions of DILD following a structured prospective report form. Liver damage was divided into hepatocellular, cholestatic, and mixed types according to laboratory and histologic criteria when available. Further evaluation of causality assessment was performed.RESULTS: From January 1997 to December 2004, 265 patients were diagnosed with DILD, and 140 (52.8%) of them were female. Hepatocellular damage was the most common (72.1%), the incidence of death was 9.9% in patients with hepatocellular damage and 9.5% in patients with cholestatic/mixed damage (P < 0.05). There was no difference in age of dead and recovered patients. The proportion of females and males was similar in recovered and dead patients, no difference was observed in duration of treatment between the two groups. The serum total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and aspartate transaminase (AST) (P = 0.013) values were higher in dead patients than in recovered patients. Chinese herbal medicine was the most frequently prescribed, accounting for 24.2% of the whole series. However, antitubercular drugs (3.4%) were found to be the primary etiological factor for fetal DILD. Factors associated with the development of fulminant hepatic failure were hepatic encephalopathy (OR = 43.66, 95% CI = 8.47-224.95, P < 0.0001), ascite (OR = 28.48, 95% CI = 9.26-87.58, P < 0.0001), jaundice (OR = 11.43, 95% CI = 1.52-85.96, P = 0.003), alcohol abuse (OR = 3.83, 95% CI = 1.26-11.67, P = 0.035) and direct bilirubin (OR = 1.93, 95% CI = 1.25-2.58, P = 0.012).CONCLUSION: Death occurs in 9.8% of patients with DILD. Chinese herbal

  12. Invasive intracranial pressure monitoring is a useful adjunct in the management of severe hepatic encephalopathy associated with pediatric acute liver failure

    Science.gov (United States)

    Kamat, Pradip; Kunde, Sachin; Vos, Miriam; Vats, Atul; Heffron, Thomas; Romero, Rene; Fortenberry, James D.

    2011-01-01

    Introduction Pediatric acute liver failure (ALF) is often accompanied by hepatic encephalopathy, cerebral edema and raised intracranial pressure (ICP). Elevated ICP can be managed more effectively with intracranial monitoring, but ALF-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early ICP monitoring in ALF in children listed for liver transplantation. Methods Retrospective review of all intubated pediatric ALF patients with Grade 3 and Grade 4 encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant were identified from an institutional liver transplant patient database from 1999 to 2009. Result 14 patients were identified that met inclusion criteria. Age ranged from 7 months to 20 yrs. Diagnoses of ALF were infectious (3), drug induced (7), autoimmune hepatitis (2) and indeterminate (2). Grade 3 and 4 encephalopathy was seen in 10 (71%) and 4 (29%) patients respectively. CT scans prior to ICP monitor placement showed cerebral edema in 5 (35.7%) patients. Prior to ICP monitor placement, fresh frozen plasma, Vitamin K and activated recombinant factor VIIa were given to all 14 patients with significant improvement in coagulopathy (pliver transplant with 100% surviving neurologically intact. 4/14 (28%) patients had spontaneous recovery without liver transplant. 2 of 14 (14%) patients died due to multiple organ failure prior to transplant. One patient had a small 9mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection. Conclusion In our series of patients, ICP monitoring had a low complication rate and was associated with a high survival rate despite severe hepatic encephalopathy and cerebral edema in the setting of pediatric ALF. In our experience, monitoring of ICP allowed interventions to treat increased ICP and provided additional

  13. Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications.

    Directory of Open Access Journals (Sweden)

    Anne Chastre

    Full Text Available BACKGROUND/AIMS: Acute liver failure (ALF due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE, a serious neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM hepatotoxicity. METHODS/PRINCIPAL FINDINGS: Mice were administered saline or etanercept (10 mg/kg; i.p. 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001 and CD40L levels (3.7-fold; p<0.001 compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05, attenuated microglial activation (assessed by OX-42 immunoreactivity, and increased brain glutathione concentrations. CONCLUSIONS: These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting

  14. Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver

    Institute of Scientific and Technical Information of China (English)

    Samuel Wyllie; Neal R Barshes; Feng-Qin Gao; Saul J Karpen; John A Goss

    2008-01-01

    AIM: To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS: The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution.RESULTS: In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 min of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-κB was found between control and P-selectin antibody-treated livers.CONCLUSION: In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.

  15. 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.

    Science.gov (United States)

    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.

  16. Toward Predicting Drug-Induced Liver Injury: Parallel Computational Approaches to Identify Multidrug Resistance Protein 4 and Bile Salt Export Pump Inhibitors

    OpenAIRE

    Welch, Matthew A.; Köck, Kathleen; Urban, Thomas J.; Brouwer, Kim L.R.; Swaan, Peter W.

    2015-01-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were ...

  17. Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway

    OpenAIRE

    Furrer, Katarzyna; Rickenbacher, Andreas; Tian, Yinghua; Jochum, Wolfram; Bittermann, Anne Greet; Käch, Andres; Humar, Bostjan; Graf, Rolf; MORITZ, WOLFGANG; Clavien, Pierre-Alain

    2011-01-01

    The function of the liver is well-preserved during the aging process, although some evidence suggests that liver regeneration might be impaired with advanced age. We observed a decreased ability of the liver to restore normal volume after partial hepatectomy in elderly mice, and we identified a pathway that rescued regeneration and was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin receptor agonist, reversed the age-related pseudocapillarization of old liver and im...

  18. Reduction of elevated cytokine levels in acute/acute-on-chronic liver failure using super-large pore albumin dialysis treatment: an in vitro study.

    Science.gov (United States)

    Dominik, Adrian; Stange, Jan; Pfensig, Claudia; Borufka, Luise; Weiss-Reining, Helga; Eggert, Martin

    2014-08-01

    The removal of small water soluble toxins and albumin-bound toxins in acute liver failure patients (ALF) or acute-on-chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut-offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super-large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin-bound toxins were removed more efficiently using novel large (Emic2) to super-large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL-6 and tumor necrosis factor-α was drastically improved using super-large pore membranes. The Emic2 membrane predominantly removed IL-6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super-large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified. PMID:24215331

  19. Selective enrichment of hepatoeytes from mouse embryonic stem cells with a culture system containing cholestatic serum

    Institute of Scientific and Technical Information of China (English)

    Jun MIN; Er-wei SONG; Ji-sheng CHEN; Chang-zhen SHANG; Ya-jin CHEN; Lei ZHANG; Lu LIU; Xiao-geng DENG; Mei YANG; Dong-ping CHEN; Jun CAO

    2007-01-01

    Aim: There is increasing evidence indicating that embryonic stem (ES) cells are capable of differentiating into hepatocyte-like cells in vitro. However, it is neces- sary to improve the differentiation efficiency so as to promote the clinical application. Here, we report an efficient culture system to support hepatocyte differentiation from ES cells by utilizing cholestatic serum. Methods: One week after the induction of El4 mouse ES cells into hepatocytes with sodium butyrate, cholestatic serum was added into the culture system at various concentrations and hepatocyte-like cells were induced to proliferate. The morphological and phenotypic markers of hepatocytes were characterized using light microscopy, immunocytochemistry, and RT-PCR, respectively. The function of glycogen stor- age of the differentiated cells was detected by Periodic acid-Schiff (PAS) reaction, and the ratio of hepatic differentiation was determined by counting the albumin and PAS-positive cells. Results: In the presence of conditional selective medium containing cholestatic serum, numerous epithelial cells resembling hepatocytes were observed. The RT-PCR analysis showed that undifferentiated ES cells did not express any hepatic-specific markers; however, in the presence of sodium butyrate and conditional selective medium containing cholestatic serum, hepatic differentiation markers were detected. Immunofluorescence staining showed that those ES-derived hepatocytes were α-fetoprotein, albumin, and cytokeratin 18 positive, with the ability of storing glycogen. Further determination of the hepatic differentiation ratio showed that the application of cholestatic serum efficiently enriched ES-derived hepatocyte-like cells by inducing lineage differentiation and enhancing lineage proliferation. Conclusion: The conditional selective medium containing cholestatic serum is optimal to selectively enrich hepatocyte-like cells from mixed differentiated ES cells, which may provide a novel method to

  20. Severe sustained cholestatic hepatitis following temozolomide in a patient with glioblastoma multiforme: case study and review of data from the FDA adverse event reporting system.

    Science.gov (United States)

    Sarganas, Giselle; Orzechowski, Hans D; Klimpel, Andreas; Thomae, Michael; Kauffmann, Wolfgang; Herbst, Hermann; Bronder, Elisabeth; Garbe, Edeltraut

    2012-05-01

    Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults. Its established first-line adjuvant treatment is radiotherapy in combination with temozolomide (TZM). Hematotoxicity is listed as a frequent adverse drug reaction in the US prescribing information and hepatotoxicity has been reported infrequently in the postmarketing period. We here present the case of a patient diagnosed with GBM who developed severe sustained cholestatic hepatitis following treatment with TZM. The cholestasis was not reversible after withdrawal of TZM during 6 months before the patient's death. Another 2 published case reports of sustained cholestasis following TZM treatment were identified; however, the sustained nature of cholestasis was not emphasized in these reports. Sixteen cases of cholestatic hepatitis/cholestasis associated with TZM were identified in the FDA spontaneous reporting system between 2007 and 2010. Information on the course of the cholestasis in these cases could not be retrieved. In the literature there are other published reports of hepatotoxicity associated with TZM that have reported reversibility upon withdrawal of the drug. Thus, TZM appears to cause different types of hepatotoxicity. Particular attention should be paid to sustained cholestasis as a very serious type of TZM-associated liver toxicity. PMID:22394496

  1. Pegvisomant-Induced Cholestatic Hepatitis in an Acromegalic Patient with UGT1A1 ​⁎ 28 Mutation

    Directory of Open Access Journals (Sweden)

    Maria Susana Mallea-Gil

    2016-01-01

    Full Text Available Pegvisomant (PEGv is a growth hormone receptor antagonist approved for the treatment of acromegaly; one of its documented adverse effects is reversible elevation of hepatic enzymes. We report a 39-year-old male acromegalic patient with a pituitary macroadenoma who underwent transsphenoidal surgery. The patient’s condition improved but GH and IGF-I levels did not normalize; as a consequence, we first administered dopamine agonists and then somatostatin receptor ligands (SRLs with poor response. PEGv 15 mg every other day was added to lanreotide 120 mg monthly. The patient developed a severe hepatitis five months after starting the combination therapy. Elevated ferritin, iron, and transferrin saturation suggested probable hepatitis due to haemochromatosis. We performed a liver biopsy which showed an acute cholestatic hepatitis consistent with toxic etiology. A heterozygous genotype UGT1A1​⁎28 polymorphism associated with Gilbert’s syndrome was also found in this Argentine patient. The predominant clinical presentation resembled an acute cholestatic hepatitis associated with severe hemosiderosis, a different and new pattern of PEGv hepatotoxicity.

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

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2016-07-01

    Full Text Available 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.

  3. In vivo identification, survival, and functional efficacy of transplanted hepatocytes in acute liver failure mice model by FISH using Y-chromosome probe.

    Science.gov (United States)

    Krishna Vanaja, D; Sivakumar, B; Jesudasan, R A; Singh, L; Janardanasarma, M K; Habibullah, C M

    1998-01-01

    Hepatocyte transplantation has excited much interest in lending temporary metabolic support to a failing liver following acute liver injury. The exact site from which they act and the clinical, biochemical, and histological changes in the recipient body following hepatocyte transplantation is yet to be worked out. The present study is an attempt to delineate location and function of transplanted hepatocytes and also the overall survival of these cells with a fluorescent in situ hybridization (FISH) technique using a Y-chromosome-specific probe in a carbon tetrachloride (CCl4)-induced mice model of fulminant hepatic failure. Fifty-five syngenic adult Swiss female mice of approximately the same age and body weight were divided into three groups. Group-1 (n = 15), which received mineral oil, served as a negative control. Group-II (n = 15) received CCl4 (3 mL/kg) 40% vol/vol in mineral oil, by gavage served as positive control for hepatic failure. Group-III (n = 25) received intrasplenic transplantation of syngenic single cell suspension of hepatocytes in Hanks medium, after 30 h of CCl4 administration. Male Swiss adult mice (n = 15) served as donors of hepatocytes. The overall survival of animals in groups I to III was 100, 0, and 70%, respectively, by 2 wk of the study period. Transplanted hepatocytes were identified by Periodic Acid Schiff (PAS) staining and confirmed with a FISH technique using the Y-chromosome probe. The majority of exogenously transplanted hepatocytes were found in the liver and spleen sections even after 1 wk of hepatocyte transplantation. Transplanted cells were mostly found to be translocated into the sinusoids of the liver. Transplanted hepatocytes were found to be beneficial as a temporary liver support in a failing liver, significantly improving the survival of the animals. In the present study, the FISH technique was used to unequivocally distinguish the transplanted cells from the host, and thus describes a model for studying the

  4. An Update on Drug-induced Liver Injury.

    Science.gov (United States)

    Devarbhavi, Harshad

    2012-09-01

    Idiosyncratic drug-induced liver injury (DILI) is an important cause of morbidity and mortality following drugs taken in therapeutic doses. Hepatotoxicity is a leading cause of attrition in drug development, or withdrawal or restricted use after marketing. No age is exempt although adults and the elderly are at increased risk. DILI spans the entire spectrum ranging from asymptomatic elevation in transaminases to severe disease such as acute hepatitis leading to acute liver failure. The liver specific Roussel Uclaf Causality Assessment Method is the most validated and extensively used for determining the likelihood that an implicated drug caused DILI. Asymptomatic elevation in liver tests must be differentiated from adaptation. Drugs producing DILI have a signature pattern although no single pattern is characteristic. Antimicrobial and central nervous system agents including antiepileptic drugs are the leading causes of DILI worldwide. In the absence of a diagnostic test or a biomarker, the diagnosis rests on the evidence of absence of competing causes such as acute viral hepatitis, autoimmune hepatitis and others. Recent studies show that antituberculosis drugs given for active or latent disease are still a major cause of drug-induced liver injury in India and the West respectively. Presence of jaundice signifies a severe disease and entails a worse outcome. The pathogenesis is unclear and is due to a mix of host, drug metabolite and environmental factors. Research has evolved from incriminating candidate genes to genome wide analysis studies. Immediate cessation of the drug is key to prevent or minimize progressive damage. Treatment is largely supportive. N-acetylcysteine is the antidote for paracetamol toxicity. Carnitine has been tried in valproate injury whereas steroids and ursodeoxycholic acid may be used in DILI associated with hypersensitivity or cholestatic features respectively. This article provides an overview of the epidemiology, the patterns of

  5. [Clinic-epidemiological significance of drug hepatotoxicity in liver disease consultation].

    Science.gov (United States)

    Jmelnitzky, A C; Guidi, M; Bologna, A; Viola, M; Soccini, C; Barbero, R; Belloni, P; Apraiz, M

    2000-01-01

    To assess epidemiological and clinical significance of drug hepatotoxicity in the setting of liver diseases consultation, ten thousand and three hundred forty two prospectively designed clinical records from patient cared for in our Liver Unit in the period 1988-1998 were incorporated into the study; 58 out of 10,342 (prevalence = 5.6%) fulfilled at least the first three of the following causality requirements: 1.--Liver injury associated in time to drug exposition; 2.--Negative evaluation of more common other etiologies; (alcohol, viruses, immunologic, metabolic, etc) 3.--Favourable response to drug withdrawal (ALT 75%), moderate (presence of clinical complications, bilirubin > 5 mg/dl and prothrombin concentration between 50-75%), and severe (major clinical complications with bilirubin > 5 mg/dl and prothrombin concentration hypersensibility (fever, adenomegalies, rush, mononucleosis like syndrome, eosinophilia) in 29.3%. Acute injury represented 91.4% of the cases: 41.4% acute hepatitis, 15.5% "pure" cholestasis, 24.1% cholestatic hepatitis, and 10.3% indeterminate type. Four patients (4.5% of acute injury cases) were presented as severe acute liver failure, leading to liver transplant in one of them, drug association (INH-rifampicin and carbamazepine-phenobarbital) and inadverted challenge (sulphonamides and pemoline) were associated to clinical severity. Chronic injury were found in five patient (8.6%), four of them associated to chronic hepatitis and the other one to a ductopenic syndrome. Six drugs represented 53.4% of our cases; oral contraceptives (7 cases), INH alone or combined with rifampicin (6 cases), sulfonamides and clorpropamida (5 cases each), carbamazepine and amiodarone (4 cases each). Normalization of liver enzymes after drug suppression took 2 to 8 weeks in acute hepatitis type (X = 4 weeks), 4 to 20 in "pure" cholestasis (X = 12 weeks) and 8 to 24 weeks in cholestatic hepatitis or mixed type (X = 16 weeks). Two cases of chronic hepatitis

  6. Disseminated Langerhans Cell Histiocytosis Presenting as Cholestatic Jaundice

    OpenAIRE

    Kapoor, Rohit; Loizides, Anthony M; Sachdeva, Soumya; Paul, Premila

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely describe...

  7. Death from Liver Failure despite Lamivudine Prophylaxis during R-CHOP Chemotherapy due to Rapid Emergence M204 Mutations

    Directory of Open Access Journals (Sweden)

    Lay Lay Win

    2013-01-01

    hepatitis B with detectable HBV DNA undergoing chemotherapy with rituximab containing cytotoxic chemotherapy even if they have never had exposure to lamivudine in the past. In this setting, lamivudine failure due to resistance can develop quickly leading to liver failure that cannot be salvaged with tenofovir. Whether LAM is safe for prophylaxis with rituximab-based cytotoxic chemotherapy for patients with undetectable HBV DNA is unknown, but agents with a high barrier to resistance may be preferable.

  8. Liver regeneration.

    Science.gov (United States)

    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.

  9. 肝衰竭预后的危险因素分析%Causes of liver failure and impact analysis of prognostic risk factors

    Institute of Scientific and Technical Information of China (English)

    吴晓庆; 万红

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2014-01-01

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

  11. A Single Case of Rosai-Dorfman Disease Marked by Pathologic Fractures, Kidney Failure, and Liver Cirrhosis Treated with Single-Agent Cladribine

    Directory of Open Access Journals (Sweden)

    Koji eSasaki

    2014-10-01

    Full Text Available Rosai-Dorfman disease (RDD is a proliferative histiocytic disorder of unknown etiology which is characterized by sinus histiocytosis with massive lymphadenopathy. In most cases, RDD has a benign course and treatment is not necessary. However, severe cases of RDD require treatment, and the treatment strategy is determined on the basis of the severity of the disease or the extranodal involvement of vital organs. We report a single case of RDD with atypical presentation of persistent constitutional symptoms, progressing pathologic fractures, and end-organ dysfunction, including acute kidney failure and liver cirrhosis with esophageal varices.

  12. Quality of life is significantly Impaired in long-term survivors of Acute Liver Failure and particularly in Acetaminophen Overdose patients

    OpenAIRE

    Rangnekar, Amol S.; Ellerbe, Caitlyn; Durkalski, Valerie; McGuire, Brendan; Lee, William M.; Fontana, Robert J.

    2013-01-01

    Functional outcomes in long-term survivors of acute liver failure (ALF) are not well-characterized. The aim of this prospective study was to determine health related quality of life (HRQOL) in long-term adult ALF survivors. ALFSG registry participants completed the CDC HRQOL-14 and SF-36 questionnaires at a 1 and/or 2 year follow-up study visit. Responses were compared among ALF subgroups and to available U.S. general population controls. Among the 282 adult ALF patients, 125 had undergone li...

  13. Effect of Conditioned Medium and Bone Marrow Stem Cell Lysate on the Course of Acetaminophen-Induced Liver Failure.

    Science.gov (United States)

    Khubutiya, M Sh; Temnov, A A; Vagabov, V A; Sklifas, A N; Rogov, K A; Zhgutov, Yu A

    2015-05-01

    A composition containing culture medium conditioned by mesenchymal stem cells and mesenchymal stem cell lysate improves biochemical parameters, reduces inflammation, and stimulates regenerative processes in the liver. PMID:26033600

  14. Cell Therapies for Liver Diseases

    Science.gov (United States)

    Yu, Yue; Fisher, James E.; Lillegard, Joseph B.; Rodysill, Brian; Amiot, Bruce; Nyberg, Scott L.

    2011-01-01

    Cell therapies, which include bioartificial liver support and hepatocyte transplantation, have emerged as potential treatments for a variety of liver diseases. Acute liver failure (ALF), acute-on-chronic liver failure, and inherited metabolic liver diseases are examples of liver diseases that have been successfully treated with cell therapies at centers around the world. Cell therapies also have the potential for wide application in other liver diseases, including non-inherited liver diseases and liver cancer, and in improving the success of liver transplantation. Here we briefly summarize current concepts of cell therapy for liver diseases. PMID:22140063

  15. Evaluation of mannitol effect in patients with acute hepatic failure and acute-on-chronic liver failure using conventional MRI, diffusion tensor imaging and in-vivo proton MR spectroscopy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To evaluate the effect of an intravenous bolus of mannitol in altering brain metabolites, brain water content, brain parenchyma volume, cerebrospinal fluid (CSF) volume and clinical signs in controls and in patients with acute liver failure (ALF) and acute- on-chronic liver failure (ACLF), by comparing changes in conventional magnetic resonance imaging (MRI), in vivo proton magnetic resonance spectroscopy (PMRS) and diffusion tensor imaging (DTI) before and after its infusion. METHODS: Five patients each with ALF and ACLF in grade 3 or 4 hepatic encephalopathy and with clinical signs of raised intracranial pressure were studied along with five healthy volunteers. After baseline MRI, an intravenous bolus of 20% mannitol solution was given over 10 min in controls as well as in patients with ALF and ACLF. Repeat MRI for the same position was acquired 30 rain after completing the mannitol injection. RESULTS: No statistically significant difference was observed between controls and patients with ALF and ACLF in metabolite ratios, DTI metrics and brain volume or CSF volume following 45 min of mannitol infusion. There was no change in clinical status at the end of post-mannitol imaging. CONCLUSION: The osmotic effect of mannitol did not result in significant reduction of brain water content, alteration in metabolite ratios or any change in the clinical status of these patients during or within 45 min of mannitol infusion.

  16. Clinical analysis of urgent liver transplantation for acute liver failure (22 cases reports)%急诊肝移植治疗急性肝功能衰竭22例的临床分析

    Institute of Scientific and Technical Information of China (English)

    王营; 曲明; 杜英东; 尹惠生; 史彦芬; 刘延军; 张成钧

    2011-01-01

    目的 探讨急诊肝移植治疗急性肝功能衰竭的效果.方法 回顾分析2003年1月至2009年1月间22例急性肝功能衰竭患者急诊行肝移植的临床资料,对患者预后、存活率及并发症等情况进行总结.结果 22例患者中,与乙型病毒性肝炎相关肝功能衰竭14例,与药物相关性肝功能衰竭8例.术前等待供肝的平均时间为2.3d.围手术期死亡3例(13.6%),1例于术后5个月时死于严重肺部感染,1例于术后6个月时接受再次肝移植治疗,其他受者术后移植肝功能恢复良好.手术并发症主要为腹腔出血2例,胆道并发症2例,无血管并发症.非手术并发症主要包括不同程度的肾功能障碍22例,肺部感染11例,排斥反应3例,神经与精神症状17例,癫痫1例.术后1、2、3年受者存活率分别为81.8 %(18/22)、81.8 %(18/22)和81.8 %(18/22),移植物存活率分别为81.8%(18/22)、77.3 %(17/22)和77.3%(17/22).结论 急诊肝移植治疗急性肝功能衰竭的效果良好,术前应合理评估供肝和受者情况,减少等待供肝时间,术后有效地处理各种并发症是提高受者预后的关键.%Objective To approach the efficacy of urgent liver transplantation for acute liver failure.Methods The clinical data of 22 patients with acute liver failure undergoing urgent liver transplantation in our hospital from January 2003 to January 2009 were retrospectively analyzed.The prognosis,survival rate and complication were summarized.Results Among 22 patients,there were 14 cases of hepatitis B-induced acute liver failure,and 8 cases of drug-induced acute liver failure.The mean waiting time was 2.3 days.Three patients died perioperatively.Retransplantation was done in 1 patient.Complications after urgent liver transplantation included:abdominal cavity hemorrhage (2 cases),biliary complications (2 cases).There were no vascular complications.Renal dysfunction of different degrees occurred in all patients.Psychiatric symptom

  17. Transplantation of Porcine Hepatocytes Cultured with Polylactic Acid-O-Carboxymethylated Chitosan Nanoparticles Promotes Liver Regeneration in Acute Liver Failure Rats

    Directory of Open Access Journals (Sweden)

    Zhong Chen

    2011-01-01

    Full Text Available In this study, free porcine hepatocytes suspension (Group A, porcine hepatocytes embedded in collagen gel (Group B, porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel (Group C, and PLA-O-CMC nanoparticles alone (Group D were transplanted into peritoneal cavity of ALF rats, respectively. The result showed that plasma HGF levels were elevated post-transplantation with a peak at 12 hr. The rats in Group C showed highest plasma HGF levels at 2, 6, 12, 24 and 36 hr post-transplantation and lowest HGF level at 48 hr. Plasma VEGF levels were elevated at 48 hr post-transplantation with a peak at 72 hr. The rats in Group C showed highest plasma HGF levels at 48, 72, and 96 hr post-transplantation. The liver functions in Group C were recovered most rapidly. Compared with Group B, Group C had significant high liver Kiel 67 antigen labeling index (Ki-67 LI at day 1 post-HTx (P<.05. Ki-67 LI in groups B and C was higher than that in groups A and D at days 5 and 7 post-HTx. In conclusion, intraperitoneal transplantation of porcine hepatocytes cultured with PLA-O-CMC nanoparticles and embedded in collagen gel can promote significantly liver regeneration in ALF rats.

  18. Intestinal expressions of eNOSmRNA and iNOSmRNA in rats with acute liver failure

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Qin; Yang-De Zhang

    2001-01-01

    AIM To observe the gene expression change of eNOSmRNA and iNOSmRNA in the small and large intestines with acute liver failure (ALF), and to reveal the biological function of NO on the pathogenesis of ALF and multiple organs dysfunction at the molecular level.``METHODS Sixty male Wistar rats were selected,weighing from 250 g to 350 g, and divided into 5 groupsrandomly: SO, AUF (6 h, 12 h), L-Arg, L-NAME, L-Arg and L-NAIVE, each group with 10 rats. The dose of L-Arg was 300 mg. kg-1, and L-NAME was 30 mg-kg-1, the reagents diluted by normal saline were injected through tail vein 30minutes pre- and post-operation. The rats in the ALF group were respectively sacrificed postoperatively at 6 h,]2 h, and the rats in the other groups were sacrificed postoperatively at 6 h. The tissues of small and large intestines were harvested in 4% paraforaldehyde containing the reagent of DEPC and fixed at 6 h, embedded in paraffin, and 4 μm section was cut. The expression of eNOSmRNA and iNOSmRNA in these tissues was determined with in situ hybridization, and analyzed with the imaging analysis system of CMM-3 and SPSS statistical software.``RESULTS The expression of eNOSmRNA in the large intestine and iNOSmRNA in the small and large intestines increased significantly at 6 h after ALF, but the expression of iNOSmRNA in the small and large intestines reduced notably at 12h after ALF (P<0.05); the expression of eNOSmRNA in the large intestine and iNOSmRNA in the small and large intestines decreased significantly with the reagents of L-Arg at 6 h ALF, but the expression of eNOSmRNA and iNOSmRNA in the small and large intestines decreased totally with the reagents of L-NAME or association with L-Arg 6 h ALF.``CONCLUSION The expression of eNOSrnRNA in the large intestine increased notably at the early stage of ALF, NO induced by the enzyme of eNOS from the transplantation of eNOSmRNA can protect the function of the large intestine, the high expression of iNOSmRNA is involved in the

  19. Definitive exclusion of biliary atresia in infants with cholestatic jaundice: the role of percutaneous cholecysto-cholangiography.

    Science.gov (United States)

    Nwomeh, Benedict C; Caniano, Donna A; Hogan, Mark

    2007-09-01

    Definitive exclusion of biliary atresia in the infant with cholestatic jaundice usually requires operative cholangiography. This approach suffers from the disadvantage that sick infants are subjected to a time-consuming and potentially negative surgical exploration. The purpose of this study was to determine if percutaneous cholecystocholangiography (PCC) prevents unnecessary laparotomy in infants whose cholestasis is caused by diseases other than biliary atresia. This study is a 10 year retrospective review of all infants with persistent direct hyperbilirubinemia and inconclusive biliary nuclear scans who underwent further evaluation for suspected biliary atresia. A gallbladder ultrasound (US) was obtained in all patients. When the gallbladder was visualized, further imaging by PCC was done under intravenous sedation; otherwise, the standard operative cholangiogram (OCG) was performed, with liver biopsy as indicated. The primary outcome was the diagnostic accuracy of PCC, especially with respect to preventing a laparotomy. There were 35 infants with suspected biliary atresia, with a mean age of 8 weeks (range 1-14 weeks). Nine infants whose gallbladder was visualized by ultrasound underwent PCC that definitively excluded biliary atresia. Of this group, the most frequent diagnosis (five patients) was total parenteral nutrition-associated cholestasis. The other 26 infants with absent or decompressed gallbladder had laparotomy and OCG, which identified biliary atresia in 16 patients (61%). Laparotomy was avoided in all 9 patients who underwent PCC, thus reducing the negative laparotomy rate by 47%. There were no complications associated with PCC. Several alternative techniques to operative cholangiogram have been described for the definitive exclusion of biliary atresia, but many of these have distinct drawbacks. Advances in interventional radiology techniques have permitted safe percutaneous contrast evaluation of the biliary tree. Identification of a normal gall

  20. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

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

    Science.gov (United States)

    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.

  2. Disseminated Langerhans Cell Histiocytosis Presenting as Cholestatic Jaundice

    Science.gov (United States)

    Loizides, Anthony M.; Sachdeva, Soumya; Paul, Premila

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely described. Cholestasis may result from lymph nodes obstructing the porta hepatis. In this report, we describe a case of type II histiocytosis X with obstructive cholestasis and pulmonary involvement in the form of cysts without significant lymphadenopathy at the porta. PMID:25859497

  3. Disseminated langerhans cell histiocytosis presenting as cholestatic jaundice.

    Science.gov (United States)

    Kapoor, Rohit; Loizides, Anthony M; Sachdeva, Soumya; Paul, Premila

    2015-02-01

    Langerhans cell histiocytosis (LCH) is a disorder associated with proliferation of Langerhans cells in various organs. LCH secondary to multisystem involvement can present in a variety of ways. Because of its infiltrative nature, LCH can involve the skin, lymph nodes, the lung or the liver. Jaundice in LCH is a manifestation of liver disease; biliary dilatation secondary to lithiasis or may be due to coexistent Niemann-Pick disease. However, a case of cholestasis has been very rarely described. Cholestasis may result from lymph nodes obstructing the porta hepatis. In this report, we describe a case of type II histiocytosis X with obstructive cholestasis and pulmonary involvement in the form of cysts without significant lymphadenopathy at the porta. PMID:25859497

  4. Single injection of naked plasmid encoding α-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice

    International Nuclear Information System (INIS)

    Oxidative stress has been implicated in the propagation of acute liver injury. The aim of our study was to investigate whether gene transfer of α-melanocyte-stimulating hormone (α-MSH), a potent anti-inflammatory peptide, could prevent fulminant hepatic failure in mice. Acute liver damage was induced by intraperitoneal administration of thioacetamide. Hydrodynamics-based gene transfection with α-MSH expression plasmid via rapid tail vein injection was initiated 1 day prior to intoxication. The mortality in the α-MSH-treated mice was significantly lower compared to the vehicle group 3 days after injury. Liver histology significantly improved and TUNEL-positive hepatocytes decreased in the treated mice. The degradation of IκBα, endogenous inhibitor of nuclear factor κB, and upregulation of inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels were prevented in the α-MSH-treated group, indicating decreased oxidative stress and inflammation. These results suggest α-MSH gene therapy might protect against acute hepatic necroinflammatory damage with further potential applications

  5. Epstein-Barr Virus Infection with Acute Pancreatitis Associated with Cholestatic Hepatitis

    OpenAIRE

    Kang, Seok-Jin; Yoon, Ka-Hyun; Hwang, Jin-Bok

    2013-01-01

    Infection-induced acute hepatitis complicated with acute pancreatitis is associated with hepatitis A virus, hepatitis B virus or hepatitis E virus. Although rare, Epstein-Barr virus (EBV) infection should be considered also in the differential diagnosis if the patient has acute hepatitis combined with pancreatitis. We report a case of EBV infection with cholestatic hepatitis and pancreatitis with review of literature. An 11-year-old female was admitted due to 1-day history of abdominal pain a...

  6. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease

    OpenAIRE

    Lam, Ping; Soroka, Carol J.; Boyer, James L.

    2010-01-01

    The primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, BSEP deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasi...

  7. The value of gadoxetate disodium-enhanced MR imaging for predicting posthepatectomy liver failure after major hepatic resection: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Seung Hyun, E-mail: shcho2405@gmail.com [Department of Radiology, Daegu Fatima Hospital, 576-31 Sinam-dong, Dong-gu, Daegu 701-600 (Korea, Republic of); Kang, Ung Rae, E-mail: tadtail@hanmail.net [Department of Radiology, Catholic University of Daegu, School of Medicine, 3056-6 Daemyung-4-dong, Nam-gu, Daegu 705-718 (Korea, Republic of); Kim, Joo Dong, E-mail: milledr@naver.com [Department of Surgery, Catholic University of Daegu, School of Medicine, 3056-6 Daemyung-4-dong, Nam-gu, Daegu 705-718 (Korea, Republic of); Han, Young Seok, E-mail: gshyskhk@hanmail.net [Department of Surgery, Catholic University of Daegu, School of Medicine, 3056-6 Daemyung-4-dong, Nam-gu, Daegu 705-718 (Korea, Republic of); Choi, Dong Lak, E-mail: dnchoi@cu.ac.kr [Department of Surgery, Catholic University of Daegu, School of Medicine, 3056-6 Daemyung-4-dong, Nam-gu, Daegu 705-718 (Korea, Republic of)

    2011-11-15

    Purpose: To investigate whether preoperative gadoxetate-disodium-enhanced MR imaging predicts posthepatectomy liver failure (PHLF) in patients who underwent major hepatic resection. Materials and methods: Twenty nine patients who underwent preoperative gadoxetate-disodium-enhanced MR imaging and following major hepatic resection were enrolled. Hepatic parenchymal signal intensity (SI) on pre-contrast T1-weighted imaging and 20 min hepatocyte phase was measured at each of the four liver segments by two observers using region of interest measurements. The mean value was calculated and used at each phase. The relative contrast enhancement index (RCEI) was calculated: (20 min hepatocyte phase SI - pre-contrast SI)/pre-contrast SI. PHLF was determined by the International Study Group of Liver Surgery 2011 guidelines. Correlation analysis was performed between preoperative liver function test and RCEI. Diagnostic accuracy of RCEI for predicting PHLF was calculated with receiver operating characteristic curve analysis. The reproducibility of the RCEI measurement was evaluated. Results: There was a significant correlation between preoperative albumin (r = 0.496, P = 0.006), T-bilirubin (r = -0.383, P = 0.041), and RCEI. Seven patients (24%) experienced PHLF, and one of these patients (3%) died. The diagnostic accuracy of RCEI was 0.838 (sensitivity 85.7%, specificity 77.3%, cut-off value: 0.7508, 95% confidence interval: 0.654, 0.947). The 95% limits of agreement and ICC between repeated RCEI measurements were 18.4% of the mean and 0.94, respectively, and between RCEI measurements by the two observers were 21.7% and 0.929, respectively. Conclusion: Our results show that preoperative gadoxetate-disodium-enhanced MR imaging can predict PHLF in patients who underwent major hepatic resection.

  8. Liver in systemic disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

  9. Disruption of BSEP Function in HepaRG Cells Alters Bile Acid Disposition and Is a Susceptive Factor to Drug-Induced Cholestatic Injury.

    Science.gov (United States)

    Qiu, Xi; Zhang, Yueping; Liu, Tongtong; Shen, Hong; Xiao, Yongling; Bourner, Maureen J; Pratt, Jennifer R; Thompson, David C; Marathe, Punit; Humphreys, W Griffith; Lai, Yurong

    2016-04-01

    In the present study, we characterized in vitro biosynthesis and disposition of bile acids (BAs) as well as hepatic transporter expression followed by ABCB11 (BSEP) gene knockout in HepaRG cells (HepaRG-KO cells). BSEP KO in HepaRG cells led to time-dependent BA accumulation, resulting in reduced biosynthesis of BAs and altered BA disposition. In HepaRG-KO cells, the expression of NTCP, OATP1B1, OATP2B1, BCRP, P-gp, and MRP2 were reduced, whereas MRP3 and OCT1 were up-regulated. As a result, BSEP KO altered the disposition of BAs and subsequently underwent adaptive regulations of BA synthesis and homeostasis to enable healthy growth of the cells. Although BSEP inhibitors caused no or slight increase of BAs in HepaRG wild type cells (HepaRG-WT cells), excessive intracellular accumulation of BAs was observed in HepaRG-KO cells exposed to bosentan and troglitazone, but not dipyridamole. LDH release in the medium was remarkably increased in HepaRG-KO cultures exposed to troglitazone (50 μM), suggesting drug-induced cellular injury. The results revealed that functional impairment of BSEP predisposes the cells to altered BA disposition and is a susceptive factor to drug-induced cholestatic injury. In total, BSEP inhibition might trigger the processes but is not a sole determinant of cholestatic cellular injury. As intracellular BA accumulation is determined by BSEP function and the subsequent adaptive gene regulation, assessment of intracellular BA accumulation in HepaRG-KO cells could be a useful approach to evaluate drug-induced liver injury (DILI) potentials of drugs that could disrupt other BA homeostasis pathways beyond BSEP inhibition. PMID:26910619

  10. Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

    Institute of Scientific and Technical Information of China (English)

    Li-Mei Zhang; Dian-Wu Liu; Jian-Bo Liu; Xiao-Lin Zhang; Xiao-Bo Wang; Long-Mei Tang; Li-Qin Wang

    2005-01-01

    AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intravenously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals.RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the

  11. Evaluation Of Gonadotropin And Testosterone Hormons In Adult Male Cholestatic Rats

    Directory of Open Access Journals (Sweden)

    Nasiri E

    2003-11-01

    Full Text Available Obstructive cholestasis is associated with overproduction of endogenous opioids (EOP, nitric oxide (NO, and cytokins in the blood streams. Therefore we investigated the relationship between obstructive cholestasis and function of germ cells in adult male rats."nMaterial and Methods: To study this, we used three groups of animals: No-surgery, Sham-surgery, and surgical ligation of the bile duct. After 3 weeks all animal were killed by ether, serum concentrations of FSH, LH and testosterone were determined by Radioimmunoassay, apoptosis was evaluated by DNA fragmentation detected by in situ terminal deoxynucloetidyl Transfrase-mediated dUTP nike end labeling (TUNEL."nResults: The mean of FSH level in cholestatic, control and sham groups were 13.22+ 1.038, 18.14+ 1.276, and 16.92+ 1.072 ng/ml, respectively. The mean of LH level in cholestatic, control and sham groups were 0.83 + 0.21, 2.058 ± 0.26, and 1.84 + 0.17 ng/ml, respectively. In addition, the mean of testosterone level in cholestatic, control and sham groups were 1.52 ± 0.16, 2.41 ± 0.18, and 2.31 + 0.14 ng/ml, respectively. The results of this study were indicated that serum FSH, LH and testosterone were significantly lower in cholestatic than control and sham groups (p=0.0195, P= 0.0029, and P=0.0023, respectively. However there was no significant difference in apoptotic index between all of groups (P=0.195. The apoptotic index in cholestatic, control and sham rats were 9.897± 1.374, 7.086 + 0.91, and 7.729 + 1.101, respectively. "nConclusion: These findings have been shown which as obstructive cholestasis was decreased the levels of serum gonadotropins and testosterone but it has no significant effector testicular germinal cells apoptosis."n"n"n"n 

  12. Liver metastases

    Science.gov (United States)

    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 ...

  13. Predicting outcome on admission and post-admission for acetaminophen-induced acute liver failure using classification and regression tree models.

    Directory of Open Access Journals (Sweden)

    Jaime Lynn Speiser

    Full Text Available Assessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF patients often presents significant challenges. King's College (KCC has been validated on hospital admission, but little has been published on later phases of illness. We aimed to improve determinations of prognosis both at the time of and following admission for APAP-ALF using Classification and Regression Tree (CART models.CART models were applied to US ALFSG registry data to predict 21-day death or liver transplant early (on admission and post-admission (days 3-7 for 803 APAP-ALF patients enrolled 01/1998-09/2013. Accuracy in prediction of outcome (AC, sensitivity (SN, specificity (SP, and area under receiver-operating curve (AUROC were compared between 3 models: KCC (INR, creatinine, coma grade, pH, CART analysis using only KCC variables (KCC-CART and a CART model using new variables (NEW-CART.Traditional KCC yielded 69% AC, 90% SP, 27% SN, and 0.58 AUROC on admission, with similar performance post-admission. KCC-CART at admission offered predictive 66% AC, 65% SP, 67% SN, and 0.74 AUROC. Post-admission, KCC-CART had predictive 82% AC, 86% SP, 46% SN and 0.81 AUROC. NEW-CART models using MELD (Model for end stage liver disease, lactate and mechanical ventilation on admission yielded predictive 72% AC, 71% SP, 77% SN and AUROC 0.79. For later stages, NEW-CART (MELD, lactate, coma grade offered predictive AC 86%, SP 91%, SN 46%, AUROC 0.73.CARTs offer simple prognostic models for APAP-ALF patients, which have higher AUROC and SN than KCC, with similar AC and negligibly worse SP. Admission and post-admission predictions were developed.• Prognostication in acetaminophen-induced acute liver failure (APAP-ALF is challenging beyond admission • Little has been published regarding the use of King's College Criteria (KCC beyond admission and KCC has shown limited sensitivity in subsequent studies • Classification and Regression Tree (CART methodology allows the

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND AND AIMS: Non-selective beta-blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute on chronic liver failure (ACLF......) is characterized by systemic inflammation and high mortality. As NSBBs may have beneficial effects on gut motility and permeability and, systemic inflammation, the aims of this prospective, observational study were to determine whether on-going use of NSBBs reduced 28-day mortality in ACLF patients. METHODS......: The study was performed in 349 patients with ACLF included in the CANONIC study, which is a prospective observational investigation in hospitalized cirrhotic patients with acute deterioration. The data about the use of NSBBs, its type and dosage was specifically recorded. Patient characteristics...

  16. Extracorporeal Liver Support with Less Fresh Frozen Plasma for Treatment of Acute-on-chronic Liver Failure%少量血浆进行人工肝治疗慢加急性肝衰竭的探讨

    Institute of Scientific and Technical Information of China (English)

    章莉莎; 赵满芝; 许东

    2015-01-01

    目的:观察应用少量血浆进行人工肝治疗慢加急性肝衰竭的疗效。方法回顾性分析45例住院治疗的慢加急性肝衰竭患者,分为观察组(少量血浆PP+ PE组)、对照组1(PE组)、对照组2(PP+PE组)(PP为血浆吸附,PE为血浆置换),共接受人工肝治疗62次。结果3组患者治疗后与治疗前比较,临床症状均有所改善。3组间相比较,在降低谷丙转氨酶(ALT)、谷草转氨酶(AST)、直接胆红素(DBil)这3个指标上差异有统计学意义,对于总胆红素(TBil)的改善和降低血氨等方面无明显差异。在其余肝、肾功能各项指标上3组间差异无统计学意义。与对照组1和对照组2相比,观察组在改善凝血功能方面效果较差,差异有统计学意义。结论在目前血浆紧张的情况下,可以应用血浆吸附联合少量新鲜冰冻血浆进行人工肝治疗,能有效降低胆红素,缓解临床症状,减少并发症的发生。%Objective To observe the efficacy of extracorporeal liver support by using less fresh frozen plasma in the treat‐ment of acute‐on‐chronic liver failure.Methods A total of 45 patients with acute‐on‐chronic liver failure were divided into ob‐servation group[plasma perfusion(PP) with a small amount of plasma+ plasma exchange(PE)] ,control group 1(PE) ,control group 2(PP+PE)in terms of the amount of plasma used on the day of treatment. All the patients received artificial liver treatnts 62 times totally.Results The clinical symptoms were improved in the three groups after treatments.There were significant differences in the decrease of alanine transaminase (ALT) ,aspartate transaminase(AST) and direct bilirubin(DBil)rather than the decrease of total bilirubin(TBil)and blood ammonia among the groups.No significant difference was noted in the liver and kidney function among the three groups. The improvement of the coagulation function was poor in the

  17. 活体肝移植治疗HBV相关性急性亚急性肝功能衰竭%Living donor liver transplantation for hepatitis B virus related acute or subacute liver failure

    Institute of Scientific and Technical Information of China (English)

    杨占宇; 董家鸿; 王曙光; 别平; 刘祥德; 卢倩

    2008-01-01

    目的 探讨活体肝移植(living donor liver transplantation,LDLT)HBV感染导致的急性肝功能衰竭(acute liver failure,ALF)和亚急性肝功能衰竭(subacute liver failure,SALF)患者的可行性,并评价其疗效.方法 回顾性分析2000年11月至2007年10月完成的10例LDLT治疗ALF、SALF患者的临床资料.10例LDLT的供、受者均为成人,切取右半肝为移植物,8例含肝中静脉(middle hepatic vein,MHV).10例供者的评估均在确定实施LDLT的24 h内完成,供、受者手术均在确定供者后的12 h内完成.移植物质量与受者体质量比为(1.03±0.17)%(0.86%~1.22%),移植物体积与受者标准肝体积比为(52.2±11.8)%(47.6%~70.1%).结果 10例受者中,2例分别于术后7、28 d时因肺部感染、十二指肠球部溃疡穿孔腹腔感染死亡.1例胆管吻合口胆漏,经十二指肠镜下置入鼻胆管引流治愈.2例术后1周出现轻度急性排斥反应,增强免疫抑制强度后肝功能恢复正常.8例中位随访期9.6个月(2~84个月),生存质量优良.10例供者中,1例出现急性门静脉高压症导致脾脏破裂,行脾脏切除术,其后出现胆管断端胆漏,经鼻胆管引流结合经皮穿刺腹腔引流治愈.其余9例无并发症发生.结论 LDLT适宜治疗HBV感染导致的ALF、SALF,而且能获得较好的中、远期疗效.%Objective To investigate the feasibility and evaluate the outcome of living donor.liver transplantation(LDLT) for hepatitis B virus(HBV)related acute liver failure(ALF)or subacute liver failure (SALF).Methods A retrospective analysis was done based on the clinical data of 10 patients with ALF or SALF who underwent LDLT from November 2000 to October 2007. All the liver grafts,including right lobe with middle hepatic vein(MHV)(n=8)and right lobe without MHV(n=2),were obtained from adult donors.The Drocess of donor evaluation was accomplished within 12 hours after making the decision of LDLT, and the donor and recipient operation was performed

  18. Serum sphingolipids reflect the severity of chronic HBV infection and predict the mortality of HBV-acute-on-chronic liver failure.

    Directory of Open Access Journals (Sweden)

    Feng Qu

    Full Text Available Patients with HBV-acute-on-chronic liver failure (HBV-ACLF have high mortality and frequently require liver transplantation; few reliable prognostic markers are available. As a class of functional lipids, sphingolipids are extensively involved in the process of HBV infection. However, their role in chronic HBV infection remains unknown. The aim of this study was to determine the serum sphingolipid profile in a population of patients with chronic HBV infection, paying special attention to exploring novel prognostic markers in HBV-ACLF. High performance liquid chromatography tandem mass spectrometry was used to examine the levels of 41 sphingolipids in 156 serum samples prospectively collected from two independent cohorts. The training and validation cohorts comprised 20 and 28 healthy controls (CTRL, 29 and 23 patients with chronic hepatitis B (CHB, and 30 and 26 patients with HBV-ACLF, respectively. Biometric analysis was used to evaluate the association between sphingolipid levels and disease stages. Multivariate analysis revealed difference of sphingolipid profiles between CHB and HBV-ACLF was more drastic than that between CTRL and CHB, which indicated that serum sphingolipid levels were more likely to associate with the progression HBV-ACLF rather than CHB. Furthermore, a 3-month mortality evaluation of HBV-ACLF patients showed that dhCer(d18 : 0/24 : 0 was significantly higher in survivors than in non-survivors (including deceased patients and those undergoing liver transplantation, p < 0.05, and showed a prognostic performance similar to that of the MELD score. The serum sphingolipid composition varies between CTRL and chronic HBV infection patients. In addition, dhCer(d18 : 0/24 : 0 may be a useful prognostic indicator for the early prediction of HBV-ACLF.

  19. Efficacy and safety of integrative medical program based on blood cooling and detoxification recipe in treating patients with hepatitis B virus related acute-on-chronic liver failure:a randomized controlled clinical study

    Institute of Scientific and Technical Information of China (English)

    刘慧敏

    2014-01-01

    Objective To evaluate the clinical efficacy and safety of integrative medical program based on blood cooling and detoxification recipe(BCDR)in treating patients with hepatitis B virus related acute-on-chronic liver failure(HBV-ACLF)of heat-toxicity accumulation syndrome(HTAS).Methods Adopting randomized controlled

  20. Application of glucocorticoids in treatment of liver failure induced by hepatitis B%糖皮质激素在乙型肝炎肝功能衰竭治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    甄秀梅; 罗光汉

    2010-01-01

    @@ 肝功能衰竭(肝衰竭)是由多种因素引起的严重肝脏损害,导致其合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,出现以凝血机制障碍和黄疸、肝性脑病、腹水等为主要表现的一组临床症候群.根据病理组织学特点和病情进展速度,肝衰竭可分为4类:急性肝衰竭(acute liver failure, ALF)、亚急性肝衰竭(subacute liver failure, SALF)、慢加急性(亚急性)肝衰竭(acute-on-chronic liver failure, ACLF)和慢性肝衰竭(chronic liver failure, CLF).

  1. Efficacy Comparison between Artificial Liver PDF and PE + CHDF in the Treatment of Late Liver Failure%人工肝 PDF 与 PE + CHDF在晚期肝衰竭治疗中的疗效对比

    Institute of Scientific and Technical Information of China (English)

    周观林; 张伦理; 刘春文; 杨沛华; 张琼; 谢志军

    2014-01-01

    目的:评价人工肝血浆滤过透析(PDF)模式及人工肝血浆置换(PE)+血液滤过透析(CHDF)模式在晚期肝衰竭患者中的疗效对比。方法:选取肝衰竭晚期患者40例,随机均分为观察组和对照组;观察组在内科综合治疗基础上给予 PDF 治疗,对照组在内科综合治疗基础上给予 PE + CHDF 治疗,比较两组在治疗前、后临床肝功能生化的改善情况及对临床治疗3个月病死率的影响。结果:两组治疗前生化治疗比较无差别(P ﹥0.05),两组治疗后比较,对照组较观察组改善明显(P ﹤0.05),两组3个月死亡率相同,无统计学意义。结论:晚期肝衰竭患者在内科综合治疗基础上配合 PE + CHDF 治疗与配合 PDF 治疗相比,能获得更好的肾功能改善及脱水效果,相近的肝功能指标改善明显,但在节约治疗时间及治疗成本的控制方面 PDF 更有优势。两组患者3个月病死率相同。%Objective:To evaluate and compare the efficacy of the artificial liver Plasma filtration dialysis(PDF)mode and plasma exchange(PE)plus continuous hemofiltration dialysis(CHDF)mode in the treatment of the end-stage liver failure. Methods:40 patients with the end-stage liver failure were selected and randomly divided into observation group and control group;on the basis of comprehensive treatment the observation group was given PDF medical treatment where-as the control group was given PE plus CHDF therapy. The biochemical improvement of liver function and the three-month mortality before and after the treatment were observed and compared. Results:The control group had the better biochemi-cal improvement than observation group(P ﹥ 0. 05),but the two groups had the same three-month mortality. Conclusion:PE plus CHDF therapy on the basis of comprehensive treatment can get a better improvement in renal function and dehy-dration effects than PDF therapy mode,while there is no difference

  2. Nursing Problems in Care of a Patient with Very Early HCV Infection Recurrence After Liver Transplantation: A Case Report.

    Science.gov (United States)

    Hreńczuk, Marta; Sowińska, Renata; Tronina, Olga; Małkowski, Piotr; Durlik, Magdalena; Pacholczyk, Marek; Kosieradzki, Maciej

    2016-01-01

    BACKGROUND Recurrent HCV infection following liver transplantation is a common problem, and usually has a more aggressive course than primary infection. The aim of the paper was to present nursing problems in the care of a 22-year-old female patient after liver transplantation (Ltx) with a rapid recurrence of HCV infection shortly after Ltx. CASE REPORT Ltx was performed 22 July 2012 due to chronic cirrhosis secondary to HCV infection with viremia (HCV PCR 3.5×107 IU/mL). Graft function worsened 14 days following transplantation. Acute cholestatic hepatitis related to HCV reinfection was diagnosed based on biopsy. During a period of 20 months the patient received 3 different antiviral treatment regimens, beginning with a dual therapy (Interferon and Ribavirin), followed by the inclusion of Telaprevir, then Daclatasvir; however, these treatments were not successful. The fourth-line regimen with sofosbuvir (EU medical experiment) led to viremia elimination (HCV PCR) after 5 weeks of treatment. However, hepatic failure stabilization was unsuccessful, there was an increase in encephalopathy, and the MELD score was 25. Therefore, the patient underwent liver retransplantation. In the post-transplantation period, the patient was in good condition, with no viremia. CONCLUSIONS The most common nursing problems in the care of the patient were associated with the diagnostic process, therapies used (including experimental treatment), and progressive liver failure. The therapeutic success should be attributed to the intensive supervision and monitoring of viremia, immediate inclusion of adequate treatment methods, adequate patient preparation for diagnostic tests, and careful care after diagnostics, as well as psychological support and education. PMID:27357745

  3. Antiviral therapy effects upon hepatitis C cholestatic syndrome.

    Science.gov (United States)

    Vere, C C; Gofiţă, Eliza; Forţofoiu, C; Streba, Letiţia Adela Maria; Genunche, Amelia

    2007-01-01

    Cholestasis includes, as a syndrome, all clinical and biological manifestations caused by the deficient or simply absent biliar secretion or caused by the obstruction of the biliary ducts. The hepatic cholestasis from the chronic hepatitis C (HC VHC) is a result of the altered interlobular biliary canalicules, caused by the modified cellular transport mechanisms and it is associated with a medium to severe degree of fibrosis. The aim of this study was to evaluate the efficiency of antiviral therapy in HC VHC patients. The study included a number of 37 HC VHC patients admitted at the Medical Department no. 1 of the Emergency County Hospital of Craiova; they were treated with Pegasys, 180 microg/week and Copegus, 1000 or 1200 mg/day, taking in consideration their weight, for 48 weeks and they were monitored for 24 weeks after the treatment. The following parameters were analyzed: direct bilirubine, total cholesterol, alkaline phosphatase, gamma-glutamiltranspeptidase and leucin-aminopeptidase. Under treatment, the clinical status caused by the cholestasis (pruritus, icteric syndrome, hemoragipary syndrome) was improved in six of the given cases (16.22%). Before therapy, the hepatic cholestasis was present in 20 patients (54.05%), and after treatment in 14 patients (37.83%). During therapy, the average values for all the monitored parameters decreased: direct bilirubine (0.38 +/- 0.18 mg/dl vs. 0.34 +/- 0.24 mg/dl, p = 0.0867), total cholesterol (198.53 md/dl vs. 183.16 mg/dl, p = 0.0808), alkaline phosphatase (236.99 +/- 79.09 iu/l vs. 227.82 +/- 87.59 iu/l, p = 0.0845), gamma-glutamiltranspeptidase (47 +/- 32.89 iu/l vs. 43.91 +/- 29.66 iu/l, p = 0.1509), and leucin-aminopeptidase (32.33 +/- 13.22 iu/l vs. 28.95 +/- 14.22 iu/l, p = 0.0038). Under antiviral treatment there was noticed an improvement of the cholestasis clinical status in a small number of cases. Antiviral therapy favorably influenced the liver cholestasis associated in patients with chronic hepatitis

  4. Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Mukaddes Esrefoglu; Mehmet Gül; Memet Hanifi Emre; Alaattin Polat; Mukadder Ayse Selimoglu

    2005-01-01

    AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second,to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury.METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin,and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 μg/(kg.d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA),and reduced GSH. Total nitrite (NOx) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system.RESULTS: The histopathological changes including portal inflammation, necrosis, apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-infiammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOx, and a significant decrease in GSH levels. Mean±SE values of MDA, GSH and NOx levels of SO group were 147.47±6.69, 0.88±0.33 μmol/g and 180.70±6.58 nm/g, respectively. The values of BDL group were 200.14±21.30, 0.65±0.02 μmol/g, and 400.46±48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93±6.8, 0.74±0.02 μmol/g,and 290.38±32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOx levels.CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  7. Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum.

    Directory of Open Access Journals (Sweden)

    Santosh Singh

    Full Text Available BACKGROUND AND PURPOSE: Liver dysfunction led hyperammonemia (HA causes a nervous system disorder; hepatic encephalopathy (HE. In the brain, ammonia induced glutamate-excitotoxicity and oxidative stress are considered to play important roles in the pathogenesis of HE. The brain ammonia metabolism and antioxidant enzymes constitute the main components of this mechanism; however, need to be defined in a suitable animal model. This study was aimed to examine this aspect in the rats with acute liver failure (ALF. METHODS: ALF in the rats was induced by intraperitoneal administration of 300 mg thioacetamide/Kg. b.w up to 2 days. Glutamine synthetase (GS and glutaminase (GA, the two brain ammonia metabolizing enzymes vis a vis ammonia and glutamate levels and profiles of all the antioxidant enzymes vis a vis oxidative stress markers were measured in the cerebral cortex and cerebellum of the control and the ALF rats. RESULTS: The ALF rats showed significantly increased levels of ammonia in the blood (HA but little changes in the cortex and cerebellum. This was consistent with the activation of the GS-GA cycle and static levels of glutamate in these brain regions. However, significantly increased levels of lipid peroxidation and protein carbonyl contents were consistent with the reduced levels of all the antioxidant enzymes in both the brain regions of these ALF rats. CONCLUSION: ALF activates the GS-GA cycle to metabolize excess ammonia and thereby, maintains static levels of ammonia and glutamate in the cerebral cortex and cerebellum. Moreover, ALF induces oxidative stress by reducing the levels of all the antioxidant enzymes which is likely to play important role, independent of glutamate levels, in the pathogenesis of acute HE.

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

    Directory of Open Access Journals (Sweden)

    Zhihong Wan

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

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

    Science.gov (United States)

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

    2016-02-01

    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

  10. Serum testosterone levels and androgen receptor CAG polymorphism correlate with hepatitis B virus (HBV-related acute liver failure in male HBV carriers.

    Directory of Open Access Journals (Sweden)

    Bao-Yan Xu

    Full Text Available BACKGROUND: Augmentation of androgen/androgen receptor (AR pathway may influence chronic hepatitis B (CHB more likely in males. AR activity is modulated by a polymorphic CAG repeat sequence in AR exon 1. This study aimed to investigate the relationship between serum testosterone levels, CAG repeat numbers and hepatitis B virus (HBV-related acute liver failure (ALF. METHODS: Three hundred and seventy eight male CHB patients with ALF and 441 asymptomatic HBV carriers (AsCs were recruited. AR CAG repeats numbers were analyzed. The serum testosterone levels of AsCs, ALFs and patients with hepatitis B flare groups, and sequential serum samples, were assessed quantitatively. RESULTS: The median CAG repeat (M-CAG frequency was significantly higher in ALF patients than AsCs (P<0.001. Patients with M-CAG alleles (P<0.001, OR 3.0, 95% CI 2.1-4.2 had the highest risk for ALF. Serum testosterone levels were significantly higher (P<0.001 at hepatitis flare point (8.2 ± 3.0 ng/mL than inactive phase (6.4 ± 2.0 ng/mL. CHB (8.30 ± 2.71 ng/mL, P = 7.6 × 10(-6 and ALF group (2.61 ± 1.83 ng/mL, P = 1.7 × 10(-17 had significantly different levels of testosterone in comparison with AsCs group (6.56 ± 2.36 ng/mL. The serum testosterone levels sharply decreased from hepatitis flare phase to liver failure phase, and tended to be normal at the recovery phase. Male AsCs with M-CAG alleles had significantly lower serum testosterone levels (P<0.05. CONCLUSIONS: There was a serum testosterone fluctuation during hepatitis B flare and HBV-related ALF, and the median CAG repeats in AR gene exon 1 were associated with lower serum testosterone levels in asymptomatic HBV carriers and an increased susceptibility to HBV-related ALF.

  11. Intraparenchymal intracranial pressure monitoring in patients with acute liver failure Monitoreo intraparenquimatoso de presión intracraneana en pacientes con falla hepática aguda

    Directory of Open Access Journals (Sweden)

    Alejandra T. Rabadán

    2008-06-01

    Full Text Available BACKGROUND: Elevated intracranial pressure (ICP is a common cause of death in acute liver failure (ALF and is determinant for decision-making regarding the timing of liver transplantation. The recommended type ICP monitoring device is controversial in ALF patients. Epidural devices had less risk of hemorrhagic complications, but they are less reliable than intraparenchymal ones. METHOD: Twenty-three patients with ALF were treated, and 19 of them received a liver transplant. Seventeen patients had ICP monitoring because of grade III-IV encephalopathy. All patients received fresh plasma (2-3 units before and during placing the intraparenchymal device. RESULTS: Eleven cases (64.7% had elevated ICP, and 6 patients (35.2% had normal values. One patient (5.9% had an asymptomatic small intraparenchymal haemorrhage ANTECEDENTES: La presión intracraneana elevada (PIC es una causa frecuente de muerte en la falla hepática aguda (FHA y es determinante para la toma de decisiones respecto del momento del transplante hepático. El tipo de dispositivo para el monitoreo de OIC es controversial em los pacientes em FHA. Los dispositivos epidurales tienen menos riesgo de complicaciones hemorrágicas, pero son menos confiables que los intraparenquimatosos. MÉTODO: Veintitrés pacientes con FHA fueron tratados, y 19 de ellos recibieron un transplante hepático. diecisiete pacientes tuvieron monitoreo de PIC debido a encefalopatía grado III-IV. Todos los pacientes recibieron plasma fresco (2-3 unidades antes y durante la colocación de la fibra intraparenquimatosa. RESULTADOS: Once casos (64.7% tuvieron PIC elevada, y 6 pacientes (35.2% tuvieron valores normales. Un paciente (5.9% tuvo una pequeña hemorragia intraparenquimatosa asintomática <1cm³ en TAC, la cual no impidió el transplante hepático. CONCLUSIÓN: En nuestra experiencia, el monitoreo intraparenquimatoso de presión intracraneana en pacientes con FHA parece ser un método preciso y con bajo riesgo

  12. Stem cells in liver disease

    NARCIS (Netherlands)

    Poll, D. van

    2008-01-01

    Failure of the liver, the largest vital organ in the body, unequivocally results in death. Hepatic failure most commonly evolves over a period of several years as a result of chronic liver disease, most often viral hepatitis or alcoholic liver damage. In rarer cases, the organ shuts down within week

  13. Successful rescue of disseminated varicella infection with multiple organ failure in a pediatric living donor liver transplant recipient: a case report and literature review.

    Science.gov (United States)

    Yamada, Naoya; Sanada, Yukihiro; Okada, Noriki; Wakiya, Taiichi; Ihara, Yoshiyuki; Urahashi, Taizen; Mizuta, Koichi

    2015-01-01

    A 12-year-old female patient with biliary atresia underwent living donor liver transplantation (LDLT). Twelve months after the LDLT, she developed acute hepatitis (alanine aminotransferase 584 IU/L) and was diagnosed with disseminated varicella-zoster virus (VZV) infection with high level of serum VZV-DNA (1.5 × 10(5) copies/mL) and generalized vesicular rash. She had received the VZV vaccination when she was 5-years-old and had not been exposed to chicken pox before the LDLT, and her serum was positive for VZV immunoglobulin G at the time of the LDLT. Although she underwent treatment with intravenous acyclovir, intravenous immunoglobulin, and withdrawal of immunosuppressants, her symptoms worsened and were accompanied by disseminated intravascular coagulation, pneumonia, and encephalitis. These complications required treatment in the intensive care unit for 16 days. Five weeks later, her clinical findings improved, although her VZV-DNA levels remained high (8.5 × 10(3)copies/mL). Oral acyclovir was added for 2 weeks, and she was eventually discharged from our hospital on day 86 after admission; she has not experienced a recurrence. In conclusion, although disseminated VZV infection with multiple organ failure after pediatric LDLT is a life-threatening disease, it can be cured via an early diagnosis and intensive treatment. PMID:26081644

  14. Bioartificial liver: current status.

    Science.gov (United States)

    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.

  15. Prognostic risk factors and prognosis model for liver failure%肝衰竭预后危险因素及预后模型建立的研究

    Institute of Scientific and Technical Information of China (English)

    汤伟亮; 谢青; 赵钢德; 董志霞; 项晓刚; 王晖; 周惠娟; 桂红莲; 郭斯敏; 庄焱

    2011-01-01

    Objective To investigate the independent risk factors of the prognosis for liver failure and to establish a prognosis model. Methods The clinical data of 252 patients with liver failure treated in Ruijin hospital from Jun. 2006 to Dec. 2008 were retrospectively analyzed. Logistic regression analysis was used for selecting the independent risk factors for the prognosis of liver failure. Based on logistic regression analysis, the prognosis model for liver failure was established. Results Logistic regression analysis showed that age, hepatic eneephalopathy, upper gastrointestinal bleeding, infection, TBIL and PT were the independent risk factors for the prognosis of liver failure. Then the prognosis model was established. By calculating prognostic index and drawing receiver operating characteristic (ROC) curve, the area under the ROC curve was known to be 0.924 (95%CI 0.892, 0.957). Conclusions Age,hepatic encephalopathy, upper gastrointestinal bleeding, infection, TBIL and PT are the independent risk factors for the prognosis of liver failure. The prognosis model established in this study can predict short-term survival rate of patients with liver failure. It is of significant value in assessing the prognosis of liver failure.%目的 探讨影响肝衰竭预后的危险因素,并建立其预后模型.方法 回顾性调查2006年6月-2008年12月我科收治的252例肝衰竭患者的临床资料.采用多因素Logistic回归分析,得出相应的独立危险因素,并建立预后模型.结果 多因素Logistic回归分析显示,患者年龄、肝性脑病、上消化道出血、感染、TBIL、PT是影响肝衰竭患者预后的独立危险因素.对所得出的独立危险因素建立肝衰竭患者的预后判断模型,计算预后指数并绘制受试者工作特征曲线,其曲线下面积为0.924(95%CI0.892,0.957).结论 年龄、肝性脑病、上消化道出血、感染、TBIL、PT是影响肝衰竭患者预后的独立危险因素.本研究初步建立预

  16. Alcohol and liver, 2010

    Institute of Scientific and Technical Information of China (English)

    Natalia; A; Osna

    2010-01-01

    Liver is known as an organ that is primarily affected by alcohol. Alcoholic liver disease (ALD) is the cause of an increased morbidity and mortality worldwide. Progression of ALD is driven by "second hits". These second hits include the complex of nutritional, pharmacological, genetic and viral factors, which aggravate liver pathology. However, in addition to liver failure, ethanol causes damage to other organs and systems. These extrahepatic manifestations are regulated via the similar hepatitis mechanisms...

  17. Comparison of four prognostic models and a new Logistic regression model to predict short-term prognosis of acute-on-chronic hepatitis B liver failure

    Institute of Scientific and Technical Information of China (English)

    HE Wei-ping; HU Jin-hua; ZHAO Jun; TONG Jing-jing; DING Jin-biao; LIN Fang; WANG Hui-fen

    2012-01-01

    Background Acute-on-chronic hepatitis B liver failure (ACLF-HBV) is a clinically severe disease associated with major life-threatening complications including hepatic encephalopathy and hepatorenal syndrome.The aim of this study was to evaluate the short-term prognostic predictability of the model for end-stage liver disease (MELD),MELD-based indices,and their dynamic changes in patients with ACLF-HBV,and to establish a new model for predicting the prognosis of ACLF-HBV.Methods A total of 172 patients with ACLF-HBV who stayed in the hospital for more than 2 weeks were retrospectively recruited.The predictive accuracy of MELD,MELD-based indices,and their dynamic change (△) were compared using the area under the receiver operating characteristic curve method.The associations between mortality and patient characteristics were studied by univariate and multivariate analyses.Results The 3-month mortality was 43.6%.The largest concordance (c) statistic predicting 3-month mortality was the MELD score at the end of 2 weeks of admission (0.8),followed by the MELD:sodium ratio (MESO) (0.796) and integrated MELD (iMELD) (0.758) scores,△MELD (0.752),△MESO (0.729),and MELD plus sodium (MELD-Na) (0.728) scores.In multivariate Logistic regression analysis,the independent factors predicting prognosis were hepatic encephalopathy (OR=-3.466),serum creatinine,international normalized ratio (INR),and total bilirubin at the end of 2 weeks of admission (OR=10.302,6.063,5.208,respectively),and cholinesterase on admission (OR=0.255).This regression model had a greater prognostic value (c=0.85,95% Cl 0.791-0.909) compared to the MELD score at the end of 2 weeks of admission (Z=4.9851,P=-0.0256).Conclusions MELD score at the end of 2 weeks of admission is a useful predictor for 3-month mortality in ACLF-HBV patients.Hepatic encephalopathy,serum creatinine,international normalized ratio,and total bilirubin at the end of 2 weeks of admission and cholinesterase on admission are

  18. THE ROLE OF NITRIC OXIDE IN STRESS-INDUCED GASTRIC DAMAGE IN CHOLESTATIC RATS

    Directory of Open Access Journals (Sweden)

    Sh. Sadr

    1999-07-01

    Full Text Available In this study the effect of nitric oxide synthesis inhibition on stress-induced gastric damage was evaluated in bile duel ligated, sham operated and unoperated rats. Animals were injected intraperitoneally with NG-nitro-L-arginine methylester (L-NAME, 40 mglkg, L-argininc, 200 mg/kg or saline, 30 min before water-immersion stress. One hour after water immersion, the animals were killed and their stomachs were removed for measurement of gastric mucosal damage. Tfie results showed that L-NAME significantly enhances the development of gastric mucosal lesion in sham operated and unoperated rats, while in bile duct ligated animals, L-NAME decreases and L-arginine enhances the potentiation of stress-induced gastric mucosal damage. The results suggest that inhibition of nitric oxide synthase with L-NAME has different effects on stress-induced gastric damage in cholestatic rats compared with normal animals.

  19. Detection of Autoantibodies to Vascular Endothelial Growth Factor Receptor-3 in Bile Duct Ligated Rats and Correlations with a Panel of Traditional Markers of Liver Diseases

    Science.gov (United States)

    Duval, Florent; Cruz-Vega, Delia Elva; González-Gamboa, Ivonne; González-Garza, María Teresa; Ponz, Fernando; Sánchez, Flora; Alarcón-Galván, Gabriela; Moreno-Cuevas, Jorge E.

    2016-01-01

    There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bile duct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin (R2 = 0.8450, P = 3.04e − 12). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD. PMID:27212785

  20. Reversal of Intestinal Failure-Associated Liver Disease by Switching From a Combination Lipid Emulsion Containing Fish Oil to Fish Oil Monotherapy.

    Science.gov (United States)

    Lee, Sanghoon; Park, Hyo Jung; Yoon, Jihye; Hong, Seul Hee; Oh, Chae-Youn; Lee, Suk-Koo; Seo, Jeong-Meen

    2016-03-01

    Intestinal failure-associated liver disease (IFALD) is a serious complication of parenteral nutrition (PN). Studies have shown that the amount and content of intravenous lipid emulsions (LEs) used is closely related to the development of IFALD. We report 2 cases of IFALD reversed by switching from a combination lipid emulsion containing fish oil to fish oil monotherapy (Omegaven; Fresenius Kabi Austria Gmbh, Graz, Austria). Patients initially received PN containing SMOFlipid 20% (SMOF; Fresenius Kabi Austria Gmbh, Graz, Austria), 2.0-3.0 g/kg/d, over 24 hours. When IFALD developed, LE was switched from SMOF to Omegaven starting at 1.0 g/kg/d over 12 hours. Case 1 was an 11-month-old girl with a diagnosis of extensive Hirschsprung disease up to the proximal jejunum. She developed direct bilirubinemia at 3 months, and the patient's LE was switched to Omegaven. A decrease in direct bilirubin was observed after 60 days on Omegaven, and IFALD was completely resolved after 90 days. Case 2 was a 1-month-old boy with a history of gastroschisis diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome. He could not tolerate any oral feeds and was kept on full PN. He had elevated direct bilirubin and developed IFALD since 5 weeks. Omegaven treatment was initiated at 5 months. Direct bilirubin rose to 8 mg/dL during the first month on Omegaven. Then a gradual decrease in direct bilirubin was observed, and after 5 months on Omegaven, IFALD was completely resolved. In conclusion, 2 infants with advanced IFALD showed reversal of cholestasis by switching from SMOF to Omegaven monotherapy. PMID:25560679

  1. 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.

    Science.gov (United States)

    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.

  2. The roles of tumor necrosis factor-alpha in colon tight junction protein expression and intestinal mucosa structure in a mouse model of acute liver failure

    Directory of Open Access Journals (Sweden)

    Lv Sa

    2009-09-01

    Full Text Available Abstract Background Spontaneous bacterial peritonitis (SBP is a common clinical disease and one of the most severe complications of acute liver failure (ALF. Although the mechanism responsible for SBP is unclear, cytokines play an important role. The aim of this study was to investigate the effects of tumor necrosis factor-alpha (TNF-α on the structure of the intestinal mucosa and the expression of tight junction (Zona Occludens 1; ZO-1 protein in a mouse model of ALF. Methods We induced ALF using D-galactosamine/lipopolysaccharide (GalN/LPS or GalN/TNF-α and assessed the results using transmission electron microscopy, immunohistochemistry, Western blotting, ELISA and real-time quantitative PCR. The effects of administration of anti-TNF-α IgG antibody or anti-TNF-α R1 antibody before administration of GalN/LPS or GalN/TNF-α, respectively, on TNF-α were also assessed. Results Morphological abnormalities in the intestinal mucosa of ALF mice were positively correlated with serum TNF-α level. Electron microscopic analysis revealed tight junction (TJ disruptions, epithelial cell swelling, and atrophy of intestinal villi. Gut bacteria invaded the body at sites where TJ disruptions occurred. Expression of ZO-1 mRNA was significantly decreased in both ALF models, as was the level of ZO-1 protein. Prophylactic treatment with either anti-TNF-α IgG antibody or anti-tumor necrosis factor-a receptor1 (anti-TNF-α R1 antibody prevented changes in intestinal tissue ultrastructure and ZO-1 expression. Conclusion TNF-α affects the structure of the intestinal mucosa, decreases expression of ZO-1, and affects the morphology of the colon in a mouse model of ALF. It also may participate in the pathophysiological mechanism of SBP complicated to ALF.

  3. Extracorporeal liver support devices for listed patients.

    Science.gov (United States)

    Lee, Karla C L; Stadlbauer, Vanessa; Jalan, Rajiv

    2016-06-01

    An alternative to liver transplantation for patients with liver failure remains an unmet need. In acute liver failure, the ideal extracorporeal liver support device (ELSD) would replace the functions of the failing liver in order to permit spontaneous recovery, given the incredible regenerative potential of the liver, negating the need for transplantation. In acute-on-chronic liver failure, an ELSD would ideally support hepatic function until a recovery to liver function before acute decompensation or until liver transplantation. In decompensated cirrhosis, an ELSD could again be used to support hepatic function until transplant. In addition, ELSDs may have the potential to treat the multiorgan failure that accompanies liver failure including hepatic encephalopathy, renal failure, and immune dysfunction or indeed potential to promote liver regeneration. Creation of an extracorporeal bioartificial liver able to completely replace liver function remains an unmet need. This review will describe a number of technologies suitable for clinical trials in humans, which have resulted from decades of engineering and biological research to develop a bioreactor able to adequately sustain functional hepatocytes. In addition, this review will describe artificial liver support devices that are primarily designed to replace the detoxifying functions of the liver and will consider the current data available or studies required to support their use in liver failure patients on the transplant waiting list. Liver Transplantation 22 839-848 2016 AASLD. PMID:26785141

  4. The heart and the liver

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  5. Endovascular management in liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Kyu-Bo Sung

    2006-01-01

    @@ Liver transplantation was developed for the treatment of hepatic failure, and the first human liver transplantation was done in 1963. From the 1990 s,liver transplantation was generally accepted as a treatment modality for both end-stage liver disease and selected liver malignancies. Initially, liver transplantation was started with deceased donor whole-size liver transplantation (whole-size LT) as in other organ transplantation, but there is now a shortage of deceased liver donors has occurred. As a solution, deceased donor split liver transplantation (split LT) began in 1989 and living donor liver transplantation (LDLT) in the early 1990 s. Current liver transplantation techniques include whole-size LT, reduced-size liver transplantation (reduced-size LT), split LT and single or dual LDLT. Two donors give a part of their livers to one adult recipient simultaneously in dual LDLT.

  6. 27例肝衰竭患者合并侵袭性真菌感染的临床研究%Analysis on Liver Failure Complicated With Invasive Fungal Infections in 27 Patients

    Institute of Scientific and Technical Information of China (English)

    于飞

    2012-01-01

    Objective:To investigate the clinical characteristics of liver failure compared with invasive fungal infections and study the risk factors of infections.Mehtods:27 patients with liver failure compared with invasive fungal infections was observed. A cohort of 54 patients with liver failure but without fungal infections served as the control group.Then the clinical characteristics of liver failure compared with invasive fungal infections was identified and the risk factors in fungal infections with liver failure was identified by logic analysis. Results:Of the 27 patients, 37.0%developde fungal infections in lungs,22.2% in the digestive tract,14.8%in the urinary tract,14.8% in the blood and 11.1% in the peritoneal cavity respectively.Candida albicans was the most common bacteria,accounting for 51.9% and aspergillus for 18.5%.Logic regression multivariate analysis identified the following independent risk factors in the fungal infections:invasive medical manuipulation(OR=18.7,P<0.001),use multiple broad-spectrum antibiotics (OR=8.49,P<0.001),prolonged administration of corticosteroids (OR=6.31,P<0.001),declination of leukocyte (OR=2.01,P=0.015) and score of MELD (OR=1.21,P<0.001). Conclusion: Candida albicans remains the leading pathogen in pulmonary in patients with liver failure.The invasive medical manipulation,use of multiple broad-spectrum antibiotics,prolonged use of corticosteroids,declination of leukocyte and severity of original disease are the independent risk factors of invasive fungal infections in patients with liver failure.%目的 探讨肝衰竭合并侵袭性真菌感染的临床特点,分析感染发生的危险因素.方法 选择我院收治的肝衰竭合并侵袭性真菌感染患者27 例作为研究组,以同时期54 例无真菌感染的肝衰竭患者作为对照组.分析研究组患者的临床特点,并对感染相关的可疑因素行Logic 回归分析.结果 研究组患者感染部位依次为:肺部(37.0%) 、消化道(22.2%)

  7. Successful Treatment of Recurrent Primary Sclerosing Cholangitis after Orthotopic Liver Transplantation with Oral Vancomycin

    Directory of Open Access Journals (Sweden)

    Yinka K. Davies

    2013-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60–70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT; however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.

  8. Glucocorticosteroids for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Prince, M; Christensen, E; Gluud, C

    2005-01-01

    Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of presumed autoimmune etiology, characterised by the destruction of small intrahepatic bile ducts and the eventual development of cirrhosis and liver failure. Its progression may be influenced by immunosuppression...

  9. Glutathione-S-transferase subtypes α and π as a tool to predict and monitor graft failure or regeneration in a pilot study of living donor liver transplantation

    OpenAIRE

    Jochum C; Beste M; Sowa J-P; Farahani MS; Penndorf V; Nadalin S; Saner F; Canbay A; Gerken G

    2011-01-01

    Abstract Objective Glutathione-S-Transferase (GST) subtype α and π are differentially expressed in adult liver tissue. Objective of the study was if GST α and p may serve as predictive markers for liver surgery, especially transplantations. Methods 13 patients receiving living donor liver transplantation (LDLT) and their corresponding donors were analyzed for standard serum parameters (ALT, AST, gGT, bilirubin) as well as GST-α and -π before LDLT and daily for 10 days after LDLT. Patients (R)...

  10. Liver Transplant

    Science.gov (United States)

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about liver ... harmful substances from your blood. What is a liver transplant? A liver transplant is the process of replacing ...

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

    Directory of Open Access Journals (Sweden)

    Marcelo Perosa

    2001-04-01

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

  12. Liver disease associated with intestinal failure in the small bowel syndrome Doença hepática associada à falência intestinal na síndrome do intestino curto

    Directory of Open Access Journals (Sweden)

    Rafael Kemp

    2006-01-01

    Full Text Available The introduction of the Total Parenteral Nutrition (TPN has given rise to a new hope in the treatment of intestinal failure (LF associated with the Short Bowel Syndrome (SBS. However, together with the TPN and the increase of survival of these patients, new problems and questions have emerged, as well as new therapeutical procedures. Taking into consideration this emerging reality, this paper has the purpose to undertake a review of current concepts and available treatments for patients with IF associated-liver disease. Although TPN provides an increase of survival of patients with intestinal failure, it is a potential source of complication such as: septicemia, hyperglycemia, venous thrombosis and liver disease. There are several hypothesis conceived to explain the liver disease associated to intestinal failure, however the only definite treatment as a potential to reverse the non-cirrhotic liver disease is the small intestine transplantation. Despite indications for intestine transplantation are not entirely defined in literature, the trend is its early indication in high-risk patients, preserving the liver integrity and preventing the eventual need of both liver and intestine transplantations altogether.A introdução da Nutrição Parenteral Total (NPT despertou uma nova esperança para o tratamento da falência intestina (FI associada a Síndrome do Intestino Curto (SIC. No entanto, junto com a NPT e o aumento da sobrevida destes pacientes, novos problemas e perguntas emergiram, assim como novas terapêuticas. Tendo em vista esta realidade emergente, o intuito deste artigo é realizar uma revisão dos conceitos atuais e dos tratamentos disponíveis para pacientes com doença hepática associada a FI. A NPT apesar de proporcionar aumento da sobrevida nos pacientes com falência intestinal é fonte potencial de complicações, como: septicemia, hiperglicemia, trombose venosa e doença hepática. Diversas são as hipóteses aventadas para

  13. Establishment and evaluation of cholestatic mice model%胆汁淤积小鼠模型的探讨

    Institute of Scientific and Technical Information of China (English)

    张慧; 卞兆连; 王绮夏; 廉哲雄; 马雄

    2015-01-01

    目的:探讨建立胆汁淤积小鼠模型的可行性。方法胆管结扎(bile duct ligation,BDL)模型:手术结扎C57BL/6小鼠胆总管后关腹并设立假手术对照组,10 d 后处死小鼠,留取肝脏观察其病理变化。3,5-二乙氧基羰基-1,4-二氢-2,4,6-三甲基吡啶(3,5-diethoxycarbonyl-1,4-dihydrocollidine,DDC)模型:喂养含0.1%DDC 饲料的 C57BL/6小鼠。两周后处死,留取肝脏观察其病理变化。2-辛炔酸-牛血清白蛋白(2-octynoic acid-bovine serum albumin,2OA-BSA)模型:分别于0、3周时对 C57BL/6小鼠腹腔内注射100μg 的2OA-BSA,第8周时处死小鼠,留取肝脏观察其病理变化。显性阴性转移生长因子β受体 II (dominant-negative form of the human transforming growth factor-beta receptor II,dnTGF-βR II)转基因小鼠:取16周龄 dnTGF-βR II 转基因小鼠,留取肝脏观察其病理变化。结果四种造模小鼠病理切片均可见肝细胞损伤以及汇管区大量炎症细胞浸润,汇管区炎症分级统计如下:BDL 模型小鼠2.7±0.5;DDC 模型小鼠2.9±0.6;2OA-BSA 模型小鼠1.5±0.5;dnTGF-βR II 转基因小鼠1.2±0.6,与各自对照组相比均有显著统计学差异(P <0.01)。其中,BDL 和 DDC 模型以大胆管损伤为主;而2OA-BSA 模型和 dnTGF-βR II 转基因小鼠模型以小胆管损伤为主。结论上述4种小鼠胆汁淤积造模方法的可行,且形成周期短,稳定可靠。%Objective To establish and evaluate the cholestatic mice models induced by bile duct ligation (BDL)in C57BL/6 mice,3,5-diethoxycarbonyl-1 ,4-dihydrocollidine (DDC)-fed C57BL/6 mice,2-octynoic acid (2OA)coupled to bovine serum albumin (BSA)-immunized C57BL/6 mice,and dominant-negative form of the human transforming growth factor,beta receptor II (dnTGF-βR II)transgenic mice.Methods BDL mice:the bile ducts of mice were occluded by 1igation.A sham operation group was

  14. Etiology, clinical characteristics and prognosis of 175 infants with cholestatic jaundice%婴儿胆汁淤积性黄疸的病因、临床特点及转归分析

    Institute of Scientific and Technical Information of China (English)

    周建利; 周少明; 程勇卫; 朱忠生; 蔡华波; 代东伶

    2016-01-01

    目的:了解婴儿胆汁淤积性黄疸的病因、临床特点及转归情况。方法:回顾性分析175例胆汁淤积患儿的临床资料,电话随访转归情况。结果:175例胆汁淤积患儿病因分析示胆道闭锁为42例,死亡19例,肝移植恢复良好4例,肝硬化等待肝移植8例,葛西手术后恢复良好 5例,失访6例;胆管发育不良2例均恢复良好;先天性胆管扩张2例均恢复良好。CMV感染29例均恢复良好。遗传代谢性疾病16例,其中Citrin 蛋白缺陷病13例,恢复良好10例,失访2例,死亡1例;酪氨酸血症3例,恢复良好1例,失访 1例,肝硬化等待肝移植1例。TPN相关性胆汁淤积4例均恢复良好。病因未明80例,恢复良好79例,失访1例。临床特点提示胆汁淤积性黄疸患儿常伴有粪便颜色改变、肝脾肿大等,常合并肺炎、低蛋白血症、凝血功能障碍等。结论:胆汁淤积性黄疸患儿病因较多,早期诊治,预后更好。%Objective To learn about the etiology , clinical characteristics and prognosis of infants with cholestasis jaundice. Methods The clinical data of 175 cholestatic patients were retrospectively analyzed , then the prognosis was followed-up with telephone. Results After analyzing the etiology , we found that among 175 patients , there were 42 with biliary atresia , of which 19 infants died , 4 recovered well after liver transplanta-tion , 8 had liver cirrhosis waiting for transplantation , 5 recovered well after Kasai Portoenterostomy and 6 lost contact. There were 2 patients with Bile duct dysplasia and 2 with congenital cholangiectasis and they had posi-tive outcomes. And 29 patients with Cytomegalovirus infection also had positive outcome. There were 16 patients with Heredity metabolic diseases , among which 13 patients were with Citrin protein deficiency; 10 had positive outcomes; 2 lost contact and 1 died. There were 3 patients with tyrosinemia , of which one had

  15. Early diagnosis of bacterial and fungal infection in chronic cholestatic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Xiong-Zhi Wu; Dan Chen; Lian-San Zhao; Xiao-Hui Yu; Mei Wei; Yan Zhao; Qing Fang; Qian Xu

    2004-01-01

    AIM: To investigate the early diagnostic methods of bacterial and fungal infection in patients with chronic cholestatic hepatitis B.METHODS: One hundred and one adult in-patients with chronic hepatitis B were studied and divided into 3 groups:direct bilirubin (DBil)/total bilirubin (TBil)≥0.5, without bacterial and fungal infection (group A, n=38); DBil/TBil <0.5, without bacterial and fungal infection (group B, n=23);DBil/TBil≥0.5, with bacterial or fungal infection (group C,n=40). The serum biochemical index and pulse rate were analyzed.RESULTS: Level of TBil, DBil, alkaline phosphatase (ALP)and DBil/ALP in group A increased compared with that in group B. The level of ALP in group C decreased compared with that in group A, whereas the level of TBil, DBil and DBil/ALP increased (ALP: 156±43, 199±68, respectively,P<0.05; TBil: 370±227, 220±206, respectively, P<0.01;DBil: 214±143, 146±136, respectively, P<0.01; DBil/ALP:1.65±1.05, 0.78±0.70, respectively, P<0.001). The level of DBil and infection affected DBil/ALP. Independent of the effect of DBil, infection caused DBil/ALP to rise (P<0.05).The pulse rate in group A decreased compared with that in group B (63.7±6.4, 77.7±11.4, respectively, P<0.001),and the pulse rate in group C increased compared with that in group A (81.2±12.2, 63.7±6.4, respectively, P<0.001).The equation (infection=0.218 pusle rate +1.064 DBil/ALP -16.361), with total accuracy of 85.5%, was obtained from stepwise logistic regression. Pulse rate (≥80/min) and DBil/ALP (≥1.0) were used to screen infection. The sensitivity was 62.5% and 64.7% respectively, and the specificity was 100% and 82.8% respectively.CONCLUSION: Bacterial and fungal infection deteriorate jaundice and increase pulse rate, decrease serum ALP and increase DBil/ALP. Pulse rate, DBil/ALP and the equation (infection=0.218 pusle rate+1.064 DBil/ALP-16.361) are helpful to early diagnosis of bacterial and fungal infection in patients with chronic

  16. [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].

    Science.gov (United States)

    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

  17. [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].

    Science.gov (United States)

    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.

  18. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  19. 骨髓干细胞治疗慢性肝衰竭的研究进展%Research development of bone marrow stem cells for chronic liver failure treatment

    Institute of Scientific and Technical Information of China (English)

    杨帆; 秦波

    2010-01-01

    @@ 肝移植是治疗慢性肝衰竭(chronic liver failure,CLF)的有效手段,但因各种原因,其临床应用逐渐受到限制,探索新的治疗手段迫在眉睫.1996年Alison等诱导人骨髓干细胞(bone marrow stem cells,BMSCs)分化肝细胞获得成功,推动了BMSCs治疗CLF研究的快速发展.

  20. Drug-induced fulminant hepatic failure in pregnancy.

    Science.gov (United States)

    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.

  1. Single-center experience of perioperative treatment of liver transplantation for acute hepatic failure%急性肝功能衰竭急诊肝移植围术期治疗的单中心经验探讨

    Institute of Scientific and Technical Information of China (English)

    裴利娟; 徐鸿滨; 金鑫; 史宪杰

    2014-01-01

    BACKGROUND:Perioperative treatment of emergency liver transplantation for acute hepatic failure is extremely different from common liver transplantation, due to complex conditions, high risk, several complications, and high mortality. OBJECTIVE:To summarize the experience of emergency liver transplantation for acute hepatic failure during the perioperative period, and to increase the success rate in treatment of acute hepatic failure. METHODS:A retrospective analysis was undertaken on the clinical data of 38 cases undergone emergency liver transplantation for acute hepatic failure. There were 21 male and 17 female, who aged 15-69 years. Among them, 23 cases had hepatitis B virus (including 2 cases with hepatitis B and C virus), 7 cases had Wilsons disease, 3 cases had mushroom poisoning, 2 cases had unknown liver damage, 1 case had Tripterygium wilfordi poisoning, 1 case had decompensation after partial liver resection due to trauma, and 1 case had liver transplantation from corpse. RESULTS AND CONCLUSION:The survival time of the involve patients was 13-1 740 days, and the median survival time was 634 days. Perioperative survival rate was 76%, 1-year survival rate was 63%, and 2-year survival rate was 58%. During the perioperation nine cases died of brain edema and intracranial hypertension, renal failure, severe pulmonary infection, multiple organ failure, coagulation disorders (intracranial hemorrhage, upper digestive tract hemorrhage), acute respiratory distress syndrome and primary graft non-function. At present, emergency liver transplantation is stil the most effective way for acute liver failure. Hemorrhage, infection and rejection are the leading causes of the death. Each perioperative treatment is of great significance for the success of liver transplantation and long-term survival.%背景:急性肝衰竭行急诊肝移植患者围手术期治疗的病情复杂,风险大,并发症多,死亡率高,与普通肝脏移植有着明显不同。目的

  2. Drug-induced liver injury due to “natural products” used for weight loss: A case report

    OpenAIRE

    Tarantino, Giovanni; Pezzullo, Martina Gilda; Dario di Minno, Matteo Nicola; Milone, Francesco; Pezzullo, Luigi Sossio; Milone, Marco; Capone, Domenico

    2009-01-01

    Taking herbal-extracts to lose weight is an underestimated health hazard. Often, these products contain active agents that can cause acute liver damage. In this case report, a 22-year-old female patient, who presented with a feature of cholestatic syndrome, was so sure that the “natural products” were not dangerous that she did not inform her physicians that she had taken them, making their task that much more challenging. Clinical presentation mimicked acute cholecystitis and the patient und...

  3. Pediatric obesity and the liver

    NARCIS (Netherlands)

    B.G.P. Koot

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of obesity. In some of those with NAFLD, the fat accumulation in the liver will cause inflammation and fibrosis and can ultimately cause liver failure. In addition, in adults it has been established that NAFLD increases the risk of

  4. 润燥止痒胶囊致急性肝衰竭%Acute liver failure induced by Runzaozhiyang capsules(润燥止痒胶囊)

    Institute of Scientific and Technical Information of China (English)

    林芳; 李克

    2014-01-01

    A 25-year-old female patient with eczema and nettle-rash received 4 Runzaozhiyang capsules(润燥止痒胶囊)thrice daily followed the doctor's advice. She developed fatigue,jaundiced skin and sclera,poor appetite,and dark urine about one month after drug administration. Laboratory tests revealed the following results:alanine aminotransferase 2 211 U/L,aspartate aminotransferase 3 977 U/L, total bilirubin 299. 0 μmol/L and direct bilirubin 157. 2 μmol/L. The diagnosis on admission was drug-induced acute liver failure. The patient was given liver protecting agents and jaundice relieving therapy. On day 6 of admission,the patient developed fever,vomiting,and abdominal distension. The testing of ascites revealed the following results:total cell count 2 110 × 106/L,leucocyte count 1 200 × 106/L,neutrophilic granulocyte 0. 80. She was diagnosed as primary peritonitis and treated with anti-bacterial therapy. On day 7 of admission,the patient developed dysphoria and slow in response. The blood ammonia was 107 μmol/L. She was diagnosed as hepatic encephalopathy and treated with blood ammonia-reducing medicine. On day 9 of admission,the patient developed lethargy and dyspnea and treated with tracheal intubation. On day 10 of admission,the patient lost consciousness,had no response to orbital pressing,bilateral mydriasis,and dullness of light reflex. On day 11 of admission,she developed high fever and declined blood pressure. The blood ammonia was 306 μmol/L. She was diagnosed as hepatic encephalopathy( stage IV)and treated with drugs,enema,and continuous hemofiltration. On day 12 of admission,the patient died due to septic shock caused by abdominal infection.%1例25岁女性患者因湿疹、荨麻疹遵医嘱服用润燥止痒胶囊(4粒,3次/d),1个月余后出现乏力、皮肤及巩膜黄染,食欲差,尿液变黄。实验室检查示丙氨酸转氨酶2211 U/L,天冬氨酸转氨酶3977 U/L,总胆红素299.0μmol/L,直接胆红素157.2μmol/L。

  5. Management of Pruritus in Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Angeline Bhalerao

    2015-01-01

    Full Text Available Background. There continues to be uncertainty on the ideal treatment of pruritus in chronic liver disease. The aim of this study was to gather the latest information on the evidence-based management of pruritus in chronic liver disease. Methodology. A literature search for pruritus in chronic liver disease was conducted using Pubmed and Embase database systems using the MeSH terms “pruritus,” “chronic liver disease,” “cholestatic liver disease,” and “treatment.” Results. The current understanding of the pathophysiology of pruritus is described in addition to detailing research into contemporary treatment options of the condition. These medical treatments range from bile salts, rifampicin, and opioid receptor antagonists to antihistamines. Conclusion. The burden of pruritus in liver disease patients persists and, although it is a common symptom, it can be difficult to manage. In recent years there has been greater study into the etiology and treatment of the condition. Nonetheless, pruritus remains poorly understood and many patients continue to suffer, reiterating the need for further research to improve our understanding of the etiology and treatment for the condition.

  6. Liver transplantation in polycystic liver disease

    DEFF Research Database (Denmark)

    Krohn, Paul S; Hillingsø, Jens; Kirkegaard, Preben

    2008-01-01

    OBJECTIVE: Polycystic liver disease (PLD) is a rare, hereditary, benign disorder. Hepatic failure is uncommon and symptoms are caused by mass effects leading to abdominal distension and pain. Liver transplantation (LTX) offers fully curative treatment, but there is still some controversy about...... whether it is a relevant modality considering the absence of liver failure, relative organ shortage, perioperative risks and lifelong immunosuppression. The purpose of this study was to review our experience of LTX for PLD and to compare the survival with the overall survival of patients who underwent LTX....../kidney transplantation. One patient had undergone kidney transplantation 10 years earlier. RESULTS: Median follow-up was 55 months. One patient who underwent combined transplantation died after 5.4 months because of multiorgan failure after re-LTX, and one patient, with well-functioning grafts, died of lymphoma after 7...

  7. Effect of inositol requiring enzyme 1-mediated endoplasmic reticulum stress in liver cell apoptosis of experimental fulminant hepatic failure and its significance

    Institute of Scientific and Technical Information of China (English)

    甄真

    2013-01-01

    Objective To study the role of inositol requiring enzyme 1(IRE1)-mediated endoplasmic reticulum stress on hepatocyte apoptosis of experimental fulminant hepatic failure(FHF). Methods Thirty male depuratory Wistar

  8. 肝衰竭病原学分析及预后影响因素的Logistic回归分析%Liver failure:Etiology and Logistic regression analysis for the factors affecting its prognosis

    Institute of Scientific and Technical Information of China (English)

    汪佳月; 李家斌

    2016-01-01

    Objective:To understand the etiology for different liver failure and the factors affecting the prognosis .Methods:Retrospective Logistic regres-sion analysis was performed in 425 cases of liver failure pertaining to the etiology,gender,age,laboratory indexes and complications.Results:Univariate Lo-gistic regression analysis showed that the risks affecting the prognosis of different liver failure were involved in patient′s age,level of total bilirubin(TBIL) and direct bilirubin(DBIL),ratio of glutamic oxalacetic transaminase to glutamic-pyruvic transaminase(AST/ALT),content of albumin,blood ammonia and prealbumin,prothrombin(PT),prothrombin activity(PTA),count of white blood cell (WBC) and hemoglobin(HGB),level of creatinine,urea nitro-gen and serum sodium as well as concomitant hepatic encephalopathy,upper gastrointestinal hemorrhage,hepatorenal syndrome,spontaneous peritonitis and fluid and electrolyte imbalance.Conclusion:Man are susceptible to liver failure,particularly,it may progress as a result of chronic HBV infection.The prognosis of liver failure may be involved in various clinical indicators that can be used to estimate the patient′s conditions and outcomes.%目的:了解各型肝衰竭患者的病原学及影响肝衰竭患者预后的危险因素。方法:采用回顾性分析方法,对肝衰竭患者的病原学、性别、年龄、各项实验室指标及并发症情况等进行统计分析。结果:单因素Logistic回归分析结果显示,年龄、总胆红素( total bilirubin,TBIL)、直接胆红素( direct bilirubin,DBIL)、谷草转氨酶/谷丙转氨酶比值( the ratio of glutamic oxalacetic transaminase to glutamic-pyruvic transaminase,AST/ALT)、白蛋白、血氨、前白蛋白、凝血酶原时间( prothrombin time,PT)、凝血酶原活动度( prothrombin activityprothrombin time activity,PTA)、白细胞( white blood cell,WBC)计数、血红蛋白( hemoglobin,HGB)计数、肌

  9. 儿童急性肝功能衰竭短期预后的影响因素%Short-term prognostic factors in children with acute liver failure

    Institute of Scientific and Technical Information of China (English)

    裴亮; 文广富; 郭张妍; 宋文良; 王丽杰; 刘春峰

    2014-01-01

    ObjectiveTo investigate the factors that inlfuence the short-term (6 months) prognosis in children with acute liver failure.MethodsThe clinical information of 53 children with acute liver failure treated between June 2008 and September 2013 was retrospectively analyzed. The patients were divided into survival group (n=21) and death group (n=32) according to their outcomes. The liver function parameters and incidence of complications were compared between the two groups, and multivariate logistic regression analysis was used to identify major factors affecting the short-term prognosis in these patients.ResultsThere were significant differences between the death and survival groups in the indices of international normalized ratio (INR), blood ammonia and serum albumin (Alb), and complications such as hepatic encephalopathy, gastrointestinal hemorrhage, and multiple organ failure (P<0.05). Multivariate logistic regression analysis demonstrated that serum Alb, INR, and hepatic encephalopathy were the major factors affecting the short-term prognosis of acute liver failure (OR=0.616, 75.493 and 1210.727 respectively;P<0.05). ConclusionsINR, hepatic encephalopathy and serum Alb are the major factors that inlfuence the short-term prognosis in children with acute liver failure.%目的:探讨影响急性肝功能衰竭患儿短期(6个月)预后的影响因素。方法回顾性分析2008年6月至2013年9月间53例急性肝功能衰竭患儿的临床资料。53例患儿根据预后分为存活组(21例)和死亡组(32例),比较两组间肝功能指标及相关并发症等情况的不同,并进行logistic多因素回归分析筛选影响短期预后的主要影响因素。结果死亡组和存活组患儿国际标准化比值、血氨、血清白蛋白及并发症肝性脑病、消化道出血、多器官功能衰竭等指标比较差异有统计学意义(P<0.05)。多因素logistic回归分析显示血清白蛋白、INR及并发肝性脑病是急性

  10. 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.

    Science.gov (United States)

    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 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

  11. Altered expression and function of canalicular transporters during early development of cholestatic liver injury in Abcb4-deficient mice

    OpenAIRE

    Cai, Shi-Ying; Mennone, Albert; Soroka, Carol J.; Boyer, James L.

    2014-01-01

    Deficiency of ABCB4 is associated with several forms of cholestasis in humans. Abcb4−/− mice also develop cholestasis, but it remains uncertain what role other canalicular transporters play in the development of this disease. We examined the expression of these transporters in Abcb4−/− mice compared with their wild-type littermate controls at ages of 10 days and 3, 6, and 12 wk. Elevated plasma bile acid levels were already detected at 10 days and at all ages thereafter in Abcb4−/− mice. The ...

  12. Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience for diagnosis and management.

    Science.gov (United States)

    Sawlani, Kamal Kumar; Chaudhary, Shyam Chand; Singh, Jitendra; Raja, Deep Chandh; Mishra, Sanjay; Goel, Madhu Mati

    2016-01-01

    Dapsone (4,4'- diaminodiphenylsulfone) is the parent compound of the sulfones, and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects. It is used in the treatment of leprosy, dermatitis herpetiformis, and prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in a suspected case of dermatitis herpetiformis. Patient had an excellent response to corticosteroids after withdrawal of dapsone. PMID:27512715

  13. Clinical implications of advances in liver regeneration

    OpenAIRE

    Kwon, Yong Jin; Lee, Kyeong Geun; Choi, Dongho

    2015-01-01

    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....

  14. 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

    Science.gov (United States)

    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

  15. 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.

    Science.gov (United States)

    Leon, Luciane Almeida Amado; Marchevsky, Renato Sergio; Gaspar, Ana Maria Coimbra; Garcia, Rita de Cassia Nasser Cubel; Almeida, Adilson José de; Pelajo-Machado, Marcelo; Castro, Tatiana Xavier de; Nascimento, Jussara Pereira do; Brown, Kevin E; Pinto, Marcelo Alves

    2016-04-01

    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

  16. 肝外合成凝血相关蛋白在肝衰竭和肝硬化中的变化特点%Changes of extra-hepatic tissues synthetical protein in liver failure and cirrhosis

    Institute of Scientific and Technical Information of China (English)

    陈静; 丛玉隆

    2015-01-01

    Objective To study the changes of anti‐coagulation proteins synthesized from Beijing Aviation General Hospital by extra‐hepatic tissues in the developing trends of liver diseases and the relation between these proteins and bleeding‐clotting ,and to explore early sensitive indicator of liver diseases .Methods Coagulation Ⅷ(FⅧ) activity was measured by one clotting stage way ;tissue factor pathway inhibitor (TFPI) ,blood clots regulato‐ry proteins (TM ) ,von willebrand factor (vWF) and tissue factor (TF) concentration were measured by ELISA method .Results (1)TFPI:Ag detected values CHB patients 239 .3 ± 206 .4 ,liver cirrhosis patients 315 .0 ± 258 .6 , liver failure patients 319 .5 ± 298 .1 ,all higher than normal control 104 .0 ± 87 .1(F=5 .453 ,P<0 .05);(2)vWF :Ag detected values CHB patients 70 .3 ± 29 .5 ,liver cirrhosis patients 105 .5 ± 57 .9 ,liver failure patients 179 .3 ± 61 .7 ,all higher than normal control 21 .9 ± 7 .2(F=20 .104 ,P<0 .05);(3)TF detected values CHB patients 86 .0 ± 85 .7 ,liver cirrhosis patients 234 .2 ± 202 .9 ,liver failure patients 344 .7 ± 214 .6 ,all higher than normal control 12 .9 ± 8 .1(F=8 .619 ,P<0 .05);(4)FⅧ :C detected values CHB patients 157 .2 ± 53 .4 ,liver cirrhosis patients 206 .9 ± 86 .9 ,liver failure patients 335 .7 ± 117 .7 ,all higher than normal control 105 .5 ± 46 .2(F=13 .418 ,P<0 .05) .Conclusion Ex‐tra‐hepatic synthesis of coagulation proteins and disease development are negatively correlated ,that is ,these proteins rise with the aggravation of the disease ,suggesting that vessel wall damage is consistent with the severity of the dis‐ease and can be used as a comparatively sensitive indicator of monitoring vascular injury ;five detector increased in blood perhaps have relate to coagulation disorder in end‐stage liver disease patients .%目的:研究北京航空总医院肝外组织合成的凝血相关蛋白在肝病发展趋势中的变化及其与出凝血的关系

  17. 慢性心力衰竭患者肝、肾功能不全发生率及其与心衰严重程度的关系%The incidence rate of liver and renal insufficiency in the patients with chronic cardiac failure and its relationship with heart failure severity

    Institute of Scientific and Technical Information of China (English)

    戴希友

    2014-01-01

    Objective:To explore the incidence rate of liver and renal insufficiency in the patients with chronic cardiac failure(CHF) and its relationship with heart failure severity.Methods:96 cases with CHF were selected.According to the NYHA heart function classification,they were randomly divided into cardiac function Ⅰ,Ⅱ,Ⅲ,Ⅳ group.The incidence rates of liver and renal insufficiency of each groups were respectively calculated.The changs of alanine aminotransferase(ALT)、 glomerular filtration rate(eGFR) level and the relationship with heart failure severity.Results:The incidence rates of liver and renal insufficiency in the patients with chronic cardiac failure were respectively 42.0% and 38.5% .With the rise of heart function classification,the incidence rate of liver and renal insufficiency was rised.With the continuous deterioration of heart function, serum ALT and eGFR concentration were gradually increased,and there was significant difference in 4 groups(P<0.05). Conclusion:The phenomenon of liver and renal insufficiency in the patients with chronic cardiac failure is quite common.The cardiac functional grading of patients is more higher.The liver and kidney function damage will be more serious.%目的:探讨慢性心力衰竭(CHF)患者肝、肾功能不全发生率及其与心衰严重程度的关系。方法:收治CHF患者96例,按照NYHA心功能分级随机分为心功能Ⅰ、Ⅱ、Ⅲ、Ⅳ级组,分别计算各组肝、肾功能不全发生率,探讨丙氨酸氨基转移酶(ALT)、肾小球滤过率(eGFR)水平的变化与心衰严重程度的关系。结果:慢性心衰患者肝、肾功能不全的发生率分别为42.0%、38.5%,并且随心功能分级的升高,肝、肾功能不全发生率也在升高;随着心功能的不断恶化,血清ALT、eGFR浓度也逐渐升高,且4组组间差异有统计学意义(P<0.05)。结论:慢性心衰患者中肝、肾功能不全的现象相当普遍,且患者心功能分级越

  18. Metabolic Disturbances in Children with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    A Rezaeian

    2014-04-01

    . In various liver diseases, there may be reduced bile production by inadequately functioning hepatocytes, reduced hepatocyte excretion into the bile canaliculus (as in PFIC, or obstruction to biliary flow. The circulating bile salt pool may be depleted secondary to treatment with binding agents, such as cholestyramine, which is often prescribed for pruritus in cholestatic patients. Pancreatic insufficiency may further exacerbate fat malabsorption in certain cholestatic liver diseases. Vitamins: Fat malabsorption occurs in cholestatic disorders, and one must also consider any accompanying fat-soluble vitamin and essential fatty acid deficiencies.Breastfed infants with CLD are at high risk for vitamin D and K deficiencies.   Conclusion: The clinician should proactively evaluate, treat, and re-evaluate response to treatment of nutritional deficiencies. Because a better nutritional state is associated with better survival before and after LT, aggressive nutritional management is an important part of the care of these children.

  19. Chronic liver injury induced by drugs: a systematic review.

    Science.gov (United States)

    Stine, Jonathan G; Chalasani, Naga

    2015-11-01

    To examine the available literature and summarize what is known about chronic drug-induced liver injury. We reviewed PubMed/MEDLINE through March 2015. We developed a MEDLINE search strategy using PubMed medical subject heading terms chronic liver injury, hepatotoxicity, drug-induced liver injury, cirrhosis and chronic liver disease. We reviewed the reference list of included articles to identify articles missed in the database search. Chronic liver injury from drugs is more common than once thought with prevalence as high as 18% based on large national registries. Patients with cholestatic injury, age ≤65 years, and a long latency period (>365 days) are at increased risk. Of the most common drugs associated with drug-induced liver injury, antibiotics (amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin) are most likely to cause chronic injury. The presence of autoantibodies is common with chronic DILI, however, it is not diagnostic nor is it specific to autoimmune-like drug-induced liver injury. Immunosuppressive therapy may be necessary for individual cases of autoimmune-like drug-induced liver injury where cessation of the drug alone does not result in resolution of injury, however, the lowest dose should be used for the shortest duration with careful attention to the development of side effects. The effectiveness of treament of cholestatic liver injury with corticosteroids or ursodiol remains unclear. Cases of drug-induced fatty liver, nodular regenerative hyperplasia and peliosis hepatitis are less common subtypes of chronic drug-induced liver injury that deserve special consideration. A high degree of clinical suspicion is required for the diagnosis of chronic drug-induced liver injury and should be suspected in any patient with liver associated enzyme abnormalities that persist out past 6 months of initial presentation. Treatment with drug removal and/or immunosuppressive therapy appears to be effective for the majority of cases

  20. Bioartificial liver: Its pros and cons

    NARCIS (Netherlands)

    R.A.F.M. Chamuleau; P.P.C. Poyck; M.P. van de Kerkhove

    2006-01-01

    Both the large variety of liver functions for maintaining body homeostasis and the proven effectivity of whole liver transplantation in the therapy of acute liver failure (ALF), are important reasons to presume that cell-free liver support systems will not be able to adequately support the failing l

  1. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: Update. Consensus SEMICYUC-SENPE: Liver failure and liver transplantation Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico: Actualización. Consenso SEMICYUC-SENPE: Insuficiencia hepática y trasplante hepático

    Directory of Open Access Journals (Sweden)

    J. C. Montejo González

    2011-11-01

    Full Text Available 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 altera tions 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 regi men. 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.Los pacientes con insuficiencia hepática presentan una elevada prevalencia de malnutrición. Ésta se encuentra relacionada, entre otros factores, con las alteraciones del metabolismo derivadas de la enfermedad hepática, la disminución en la ingesta de nutrientes y las alteraciones en la función digestiva. De modo general, en los pacientes con insuficiencia hepática, el soporte metabólico-nutricional debe tener como objetivo el aporte adecuado de los requerimientos contribuyendo, al mismo

  2. 酒精性肝炎患者肝功能衰竭的护理管理对策研究%Study on Nursing Management of Patients with Alcoholic Hepatitis with Liver Function Failure

    Institute of Scientific and Technical Information of China (English)

    张月娜

    2016-01-01

    Objective To explore the nursing management methods and results of patients with alcoholic liver failure. Methods 65 cases of patients with alcoholic liver failure in our hospital from January 2010 to January 2015 were studied, and the effect of treatment and nursing were observed. Results After treatment and nursing,21 Cases were improved,10 cas-es were ineffective,2 cases were dischanged automa tically,and 2 Cases were improvved after dischange case fatality in 30 cases. Conclusion Shortens the uniting the course of alcoholic liver failure, prognosis is poor, difficult to care for the char-acteristics, establish the model of nurse patient management strategies, nurses should be active and doctors to communicate feedback, close observation of disease conditions, the correct evaluation formulated corresponding nursing management plan, a comprehensive understanding of the patient's condition and psychological changes, timely detection and nursing care of patients with alcohol withdrawal syndrome, the treatment program is accurate and effective implementation of, strengthen the safety nursing and care, nursing theory and practice and the humanistic care of a powerful combination.%目的:初步探讨酒精性肝功能衰竭患者的护理管理方法及效果。方法以2010年1月—2015年1月该院收治的65例酒精性肝功能衰竭患者为研究对象,观察治疗和护理效果。结果经过治疗和护理好转21例,无效10例,自动出院2例。出院后继续饮酒2例。病死30例。结论结合酒精性肝功能衰竭病程短,预后差,护理难的特点,需建立新型的护患管理对策,护士应主动与医生沟通反馈,严密观察病情,正确评估,制定相应护理管理计划,全面了解患者病情及心理变化,及时发现和护理酒精戒断综合征,使治疗方案准确有效的实施,加强安全护理和关怀,将护理理论与实践及人文关怀进行有力的结合。

  3. Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Takemura, Takayo; Yoshida, Yuichi [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Osaka (Japan); Kiso, Shinichi, E-mail: kiso@gh.med.osaka-u.ac.jp [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Osaka (Japan); Kizu, Takashi; Furuta, Kunimaro; Ezaki, Hisao; Hamano, Mina; Egawa, Mayumi; Chatani, Norihiro; Kamada, Yoshihiro [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Osaka (Japan); Imai, Yasuharu [Department of Gastroenterology, Ikeda Municipal Hospital, Ikeda, Osaka (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University, Graduate School of Medicine and Department of Cell Growth and Tumor Regulation, Proteo-Medicine Research Center (ProMRes), Ehime University, Shitsukawa, Toon, Ehime (Japan); Iwamoto, Ryo; Mekada, Eisuke [Department of Cell Biology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka (Japan); Takehara, Tetsuo [Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Osaka (Japan)

    2013-07-26

    Highlights: •HB-EGF expression was increased during the development of liver fibrosis. •Conditional HB-EGF knockout mouse showed enhanced experimental liver fibrosis. •HB-EGF antagonized TGF-β-induced activation of hepatic stellate cells. •We report a possible protective role of HB-EGF in cholestatic liver fibrosis. -- Abstract: Our aims were to evaluate the involvement of heparin-binding EGF-like growth factor (HB-EGF) in liver fibrogenesis of humans and mice and to elucidate the effect of HB-EGF deficiency on cholestatic liver fibrosis using conditional HB-EGF knockout (KO) mice. We first demonstrated that gene expression of HB-EGF had a positive significant correlation with that of collagen in human fibrotic livers, and was increased in bile duct ligation (BDL)-induced fibrotic livers in mouse. We then generated conditional HB-EGF knockout (KO) mice using the interferon inducible Mx-1 promoter driven Cre recombinase transgene and wild type (WT) and KO mice were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen, compared with WT mice. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. Interestingly, HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis.

  4. Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice

    International Nuclear Information System (INIS)

    Highlights: •HB-EGF expression was increased during the development of liver fibrosis. •Conditional HB-EGF knockout mouse showed enhanced experimental liver fibrosis. •HB-EGF antagonized TGF-β-induced activation of hepatic stellate cells. •We report a possible protective role of HB-EGF in cholestatic liver fibrosis. -- Abstract: Our aims were to evaluate the involvement of heparin-binding EGF-like growth factor (HB-EGF) in liver fibrogenesis of humans and mice and to elucidate the effect of HB-EGF deficiency on cholestatic liver fibrosis using conditional HB-EGF knockout (KO) mice. We first demonstrated that gene expression of HB-EGF had a positive significant correlation with that of collagen in human fibrotic livers, and was increased in bile duct ligation (BDL)-induced fibrotic livers in mouse. We then generated conditional HB-EGF knockout (KO) mice using the interferon inducible Mx-1 promoter driven Cre recombinase transgene and wild type (WT) and KO mice were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen, compared with WT mice. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. Interestingly, HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis

  5. Extracorporal hemodialysis with acute or decompensated chronical hepatic failure

    OpenAIRE

    Wasem, Jürgen; Caspary, Wolfgang; Siebert, Uwe; Schnell-Inderst, Petra; Grabein, Kristin; Hessel, Franz

    2006-01-01

    Background: Conventional diagnostic procedures and therapy of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can onl...

  6. The Potent Bile Acid Sequestrant Colesevelam Is Not Effective in Cholestatic Pruritus: Results of a Double-Blind, Randomized, Placebo-Controlled Trial

    NARCIS (Netherlands)

    E.M.M. Kuiper; K.J. van Erpecum; U. Beuers; B.E. Hansen; H.B. Thio; R.A. de Man; H.L.A. Janssen; H.R. van Buuren

    2010-01-01

    Colesevelam is an anion-exchange resin with a 7-fold higher bile acid binding capacity and fewer side effects than cholestyramine, the current first-line treatment option for cholestatic pruritus. The aim of this trial was to compare the effects of colesevelam and a placebo in patients with cholesta

  7. Effective analysis on treatment of rat acute liver failure by human fetal hepatocyte transplantation%人胚胎肝细胞移植治疗大鼠急性肝衰竭的效果分析

    Institute of Scientific and Technical Information of China (English)

    刘凯歌; 尚红利; 赵慧; 牛春燕; 汪雯

    2011-01-01

    目的 探讨人胚胎肝细胞移植治疗急性肝衰竭(ALF)的疗效及能否成为移植细胞源.方法 采用四甲基偶氮唑盐法检测人胚胎肝细胞增殖情况;免疫细胞化学检测其ALB、细胞角蛋白-18(CK-18)的表达; D-氨基半乳糖(D-gal)药物诱导ALF的实验动物模型;人胚胎肝细胞移植治疗ALF的动物模型,包括移植组与对照组在肝功能指标[ALT、AST、碱性磷酸酶(ALP)、总胆红素(TBIL)]的差异性比较.免疫组织化学法检测植入脾脏中的人胚胎肝细胞ALB及CK-18的表达.结果 培养第5天左右细胞数量达到最高峰,每天完成4~5次分裂,胚胎肝细胞的生长曲线呈抛物线型.免疫细胞化学检测提示其具有表达ALB、CK-18的功能; D-gal 1.6 g/kg腹腔注射72 h后大鼠ALF模型制备成功;移植第3~5天后,移植组与对照组比较,肝功能(ALT、AST、ALP、TBIL)指标差异有统计学意义(P<0.01).植入脾内的肝细胞具有分泌并表达CK-18、ALB的功能.结论 人胚胎肝细胞脾内移植能有效治疗ALF,并可能成为肝细胞移植的靶细胞源.%Objective To investigate the effect of treating rat acute liver failure and alternative sources of cells for transplantation by human fetal hepatocyte transplantation Methods The proliferation,expression of albumin and cytokeratin-18 of human fetal hepatocyte were detected by MTT and immunocytochemistry.The animal models of rat acute liver failure were made by D-galactosamine.Hepatic functions.such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin were measured between the treated and the control groups.The expression of albumin and cytokeratin-18 of human fetal hepatocyte transplanted in spleen were detected by immunohistochemistry.Results The cell population reached a peak, when human fetal hepatocyte were cultivated for 5 d.The cell division had 4 - 5 times per day,its growth curve present parabola.Immunocytochemistry revealed the

  8. Characteristics of energy metabolism in patients with acute liver failure and subacute liver failure%急性肝功能衰竭与亚急性肝功能衰竭患者能量代谢特点比较

    Institute of Scientific and Technical Information of China (English)

    赵娟; 王金环; 李胜利; 刘璐璐; 时淑云; 李娟; 于红卫; 孟庆华

    2016-01-01

    Objective To study the characteristics of energy metabolism in patients with acute liver failure (ALF) and subacute liver failure (SALF).Methods Thirteen ALF patients,23 SALF patients,20 cases of liver cirrhosis (LC) caused by hepatitis B virus admitted to Beijing Youan Hospital affiliated to Capital Medical University from March 2008 to December 2014,as well as 30 healthy controls (HC) were included in this study.Energy metabolism indexes were measured,including resting energy expenditure (REE),predict resting energy expenditure (pREE),respiratory quotient (RQ),carbohydrate oxidation rate (CHO),fat oxidation rate (FAT) and protein oxidation rate (PRO).Comparison between two groups were conducted by t test.Comparisons among groups were conducted by univariate variance analysis.The qualitative data were analyzed by)x2 test.Results REE in HC group,LC group,ALF group and SALF group were (6 180.05±1 434.68),(5 584.38±1 180.14),(7 107.01 ±1 641.22) and (6 530.31±1 306.92) kJ/d,respectively(F=3.557,P=0.018).REE/pREE(%) in four groups were (96.77±18.77)%,(88.80±17.71)%,(114.69±29.19)% and (112.48±17.33)%,respectively (F=7.389,P=0.000).RQin four groups were 0.87±0.04,0.83±0.06,0.84±0.06 and 0.79±0.04,respectively (F=10.499,P=0.000).CHO in four groups were (51.53± 13.00)%,(39.30±19.09)%,(41.15±20.35)% and (25.04±13.45)%,respectively (F=1.234,P=0.303).FAT in four groups were (37.00±13.99)%,(45.60±19.12)%,(43.85±21.01) %,and (59.39± 15.94) %,respectively(F=2.125,P=0.103).PRO in four groups were (11.47±3.47)%,(15.10±4.83)%,(15.00±4.55)% and (15.57±6.88)%,respectively (F=2.338,P=0.080).The onset time of SALF group was (38.17 ± 11.16) days,which was significantly longerthan the ALF group of (8.85 ± 3.21)days (t=-11.768,P=0.000).Conclusions REE and REE/pREE both increase in ALF and SALF patients,showing a hypermetabolic status.Nutrient metabolic disorder in SALF patients is more severe compared to ALF patients

  9. Successful rescue of disseminated varicella infection with multiple organ failure in a pediatric living donor liver transplant recipient: a case report and literature review

    OpenAIRE

    Yamada, Naoya; Sanada, Yukihiro; Okada, Noriki; Wakiya, Taiichi; Ihara, Yoshiyuki; Urahashi, Taizen; Mizuta, Koichi

    2015-01-01

    A 12-year-old female patient with biliary atresia underwent living donor liver transplantation (LDLT). Twelve months after the LDLT, she developed acute hepatitis (alanine aminotransferase 584 IU/L) and was diagnosed with disseminated varicella-zoster virus (VZV) infection with high level of serum VZV-DNA (1.5 × 105 copies/mL) and generalized vesicular rash. She had received the VZV vaccination when she was 5-years-old and had not been exposed to chicken pox before the LDLT, and her serum was...

  10. Hepatitis B related liver failure treated with hepatocyte transplantation: A two-year follow-up%肝细胞移植治疗慢性乙型重型肝炎:2年随访

    Institute of Scientific and Technical Information of China (English)

    周霖; 安林静; 齐冬颖; 陆荫英; 陈艳; 贾红军; 杨永平; 王春平; 马威; 王华明; 马雪梅; 冯永毅; 苏淑惠; 王福生

    2007-01-01

    BACKGROUND:Hepatocyte transplantation has attracted more and more attention as a therapeutic measure for liver failure and genetic metabolic liver diseases.OBJECTIVE:TO evaluate the efficacy and safety of human hepatocyte transplantation in treating hepatitis B related liver failure in one case by a 2-year follow-up.DESIGN:A case-report of 2-year follow-up.SETTING:No.9 Department of Infectious Diseases,Bioengineering Research Room,the 302 Hospital of Chinese PLA.PARTICI PANT:One inpatient with hepatitis B related liver failure was selected from the 302 Hospital of Chinese PLA.and she was diagnosed according the laboratory tests.The transplanted hepatocytes were originated frOm the healthy liver of a 24-year-old man,who had signed the protocol for liver donation before death.METHODS:The hepatocyte transplantation was completed in the Department of Radiology,the 302 Hospital of Chinese PLA in December 2004.Liver was isolated to obtain human primary hepatocytes, and then cryopreserved.The hepatocytes were transplanted into recipient spleen via femoral vein after resuscitation.The clinical symptoms,changes of blood biochemical indexes,and changes of spleen MRI signals were observed before and after operation.The patient was reexamined every half a year after operation, including liver function, blood coagulation function,B-mode ultrasonography,gastroscopy and MRI,and she was followed up for 2 years. MAIN OUTCOME MEASURES:Liver function,blood coagulation function, imaging indexes, immunological indexes,complication and rejection.RESULTS:①Totally(1-2)×1010 hepatocytes were harvested,and the viability of rewarmed hepatocytes was 60%,and finally 2×109 hepatocytes were transplanted.②Two months later,the clinical symptoms of the recipient were obviously ameliorated,and serum bilirubin and aspartate aminotransferase(AST)were obviously decreased,while prothrombin activity was markedly increased.20 months later,the MRI results showed that there was hepatocyte image in

  11. Dermatose perfurante adquirida associada à insuficiência hepática em paciente transplantado de fígado Acquired perforating dermatosis associated with hepatic failure in a liver-transplanted patient

    Directory of Open Access Journals (Sweden)

    Daniela Badziak

    2007-02-01

    Full Text Available A dermatose perfurante adquirida é entidade clinicopatológica caracterizada por eliminação transepitelial de material dérmico degenerado, ocorrendo em muitas condições, entre elas diabetes mellitus, insuficiência renal crônica e colangite esclerosante. Relata-se o caso de paciente de 17 anos, com dermatose perfurante adquirida associada à insuficiência hepática crônica, conseqüente à complicação hepática de transplante de fígado para tratamento de sua doença de base, a glicogenose tipo I.Acquired perforating dermatosis is characterized by transepithelial elimination of degenerated dermal substances. It occurs in many conditions, such as: diabetes mellitus, chronic renal failure and sclerosing cholangitis. This article describes a 17-year-old Caucasian female with type I glucogenosis and acquired perforating dermatosis due to chronic hepatic failure caused by hepatic complication of liver transplant.

  12. Adult liver stem cells in hepatic regeneration and cancer

    NARCIS (Netherlands)

    Nantasanti, Sathidpak

    2015-01-01

    An alternative source of livers for transplantation in patients with (genetic) liver diseases and liver failure is needed because liver donors are scarce. HPC-derived hepatocyte-like cells could be one of the options. Because dogs and humans share liver-pathologies and disease-pathways, the dog is c

  13. 乙型肝炎肝衰竭短期预后的影响因素%Analysis of short-term prognostic factors in patients with hepatitis B virus-related liver failure

    Institute of Scientific and Technical Information of China (English)

    彭蕾; 周学士; 甘建和; 黄小平; 潘林林; 赵卫峰

    2012-01-01

    AIM: To investigate the risk factors that influence short-term (3 mo) prognosis in patients with hepatitis B virus (HBV)-related liver failure and to establish a prognostic model. METHODS: A retrospective analysis of 137 patients with HBV-related liver failure treated at the First Affiliated Hospital of Soochow University from June 2005 to September 2008 was performed to observe their 3-month survival. The t-test, chi-square test and logistic regression analysis were used to identify independent risk factors affecting 3-month prognosis in these patients. RESULTS: Of the 137 patients with HBV-related liver failure, 86 (63.8%) were alive and 51 (36.2%) died. Univariate analyses indicated that age, liver cirrhosis, total bilirubin (Tbil), albumin (ALB), platelet international normalized ratio (INR), MELD, Child-Pugh, complicating hepatic encephalopathy, hepatorenal syndrome, pulmonary fungal infection, variceal bleeding, ascites, and spontaneous bacterial peritonitis were significant risk factors affecting 3-month prognosis in patients with HBV-related liver failure (P = 0.035, 0.001, 0.001, 0.001, 0.001, 0.001, 0.001, 0.001,0.001, 0.001,0.001,0.001,0.001,0.001, respectively). Multivariate Logistic regression analyses demonstrated that age, INR, hepatic encephalopathy, and pulmonary fungal infection were independent risk factors affecting 3-month prognosis in these patients. CONCLUSION: Age, INR, hepatic encephalopathy, and pulmonary fungal infection are independent risk factors affecting short-term prognosis in patients with HBV-related liver failure.%目的:探讨影响乙型肝炎肝衰竭患者短期(3 mo)预后的危险因素并构建预测模型.方法:回顾性分析2005-06/2008-09在苏州大学附属第一医院就治的乙型肝炎肝衰竭患者137例,观察其3 mo的生存情况,应用t检验、x2检验及Logistic回归分析筛选影响短期预后的独立危险因子.结果:137例患者短期生存率63.8%(86/137)、死亡率为36.2%(51/137).存活

  14. Metabolite profiles reveal energy failure and impaired beta-oxidation in liver of mice with complex III deficiency due to a BCS1L mutation.

    Directory of Open Access Journals (Sweden)

    Heike Kotarsky

    Full Text Available BACKGROUND & AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2O(2 production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.

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

    OpenAIRE

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

    2013-01-01

    Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accur...

  16. Ultrasonography and computed tomography in diffuse liver disease with cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Partanen, K.; Pikkarainen, P.; Pasanen, P.; Alhava, E.; Soimakallio, S. (Kuopio Univ. Central Hospital (Finland). Dept. of Clinical Radiology Kuopio Univ. Central Hospital (Finland). Dept. of Gastroenterology Kuopio Univ. Central Hospital (Finland). Dept. of Surgery)

    1990-09-01

    Ultrasonography (US) and computed tomography (CT) were performed on respectively 67 and 42 (altogether 72) patients, for the assessment of intrahepatic cholestasis. The diagnostic ability to differentiate between malignant (17 patients) and benign (55 patients) liver disease was analyzed. Coarse echogenicity of the liver led to inconclusive results in differentiating between cirrhosis (2 out of 29 patients) and malignant infiltration (4 out of 15 patients) by US. Other benign liver diseases in 23 patients, including acute hepatitis, chronic active hepatitis, fatty liver, and liver congestion, were correctly interpreted as benign. CT correctly disclosed malignant liver disease in all cases. A false positive diagnosis of malignancy was encountered in 4 (out of 17) patients with decompensated hepatic cirrhosis because of non-homogeneous expansive areas on CT in 3 cases. The true cause was in 2 patients non-uniform fatty infiltration, and in one patient with acute hepatitis A, small hypodense lesions. Among cholestatic patients, decompensated cirrhosis and malignant liver infiltration could not always be differentiated on US or CT. (orig.).

  17. Respiratory failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930118 Facial or nasal mask pressure supportventilation in managing acute exacerbation ofchronic respiratory failure in COPD patients.CHEN Rongchang(陈荣昌),et al.GuangzhouInstit Respir Dis,Guangzhou 510120.Chin Tu-berc & Respir Dis 1992;15(5)285-287.Eleven COPD patients(age:65±9 yrs)withacute exacerbation of chronic respiratory failure(PaCO2 11.3±1.1kPa)were treated with maskpressure support ventilation,another 10 similarpatients(age:68±12yrs)served as controls.Bi-PAP ventilator was used with the followingmodifications:(1)Non-rehreathing valve set-in proximal to mask;(2)5 LPM oxygen flow de-livered into mask to reduce the dead space ef-fect.Mask ventilation was given 2-3 hours ev-ery time and 1-2 times daily for 7 days.Syn-

  18. Role of farnesoid X receptor in rats with acute cholestatic hepatitis%法尼醇X受体在大鼠急性淤胆型肝炎中的作用

    Institute of Scientific and Technical Information of China (English)

    丁艳; 熊小丽; 赵雷; 李华蓉

    2016-01-01

    to measure the mRNA expression of FXR,UGT2B4,and BSEP in liver tissue at 48 hours after gavage.An automatic biochemical analyzer was used to measure the serum levels of total bilirubin,direct bilirubin,alanine aminotransferase,total bile acid,aspartate aminotransferase,alkaline phosphatase,and γ-glutamyl transferase.The independent samples t-test was used for comparison of means between groups.Results The model group had significantly lower mRNA expression of FXR,SHP,UGT2B4,and BSEP in liver tissue than the normal control group (0.152 ± 0.088/0.559 ±0.194/0.177 ± 0.039/0.561 ± 0.123 vs 1.137 ± 0.215/1.512 ± 0.309/2.394 ± 0.462/1.631 ± 0.376,t =13.408,8.260,15.121,and 8.553,all P < 0.05).The model group had significantly higher liver fumction parameters than the normal control group (all P < 0.01).Conclusion FXR,SHP,UGT2B4,and BSEP are involved in the development of acute cholestatic hepatitis.Reduced expression of FXR may cause reduced expression of downstream SHP,UGT2B4,and BSEP,increase the synthesis of bile acid,weaken detoxicating and transporting functions,and thus mediate the development of cholestatic hepatitis.

  19. 肝衰竭患者胃气定量评估及其与预后的关系%Gastric qi quantitative assessment and its influence on prognosis in liver failure patients

    Institute of Scientific and Technical Information of China (English)

    茹清静; 叶卫江; 杨丹红; 郑临; 崔景; 章亮; 施维群; 徐珊

    2012-01-01

    Objective: Establishing a quantitative evaluation model of gastric qi damage, examining the reliability and validity of the model, exploring the relativity between gastric qi damage and prognosis in liver failure patients. Methods; ① Studying 136 cases of liver failure with a prospective multicenter cases queue follow-up study. While observing the indexes including gastric qi injurydamage scores, indexes of serum biochemistry, MELD scores and living condition for 1, 3, 6 months from admission. ②The damaged degree of gastric qi is graded according to the 8 indexes including 'degree of the appetite fails' , 'degree of abdominal distension' , 'adverse rising of gastric qi degrees' , 'degree of diarrhoea' . 'degree of weakness ' , 'inspection of spirit, color and skin' , 'nutritional status' , 'observation of tongue fur' , and analysised the reliability; To work out the judgment model of prognosis of liver failure with TCM characteristics, and compare it with MELD model. Results: ①The ' gastric qi' scale has the sablility and concordance. ②The scores of gastric qi damages are positive correlated with the scores of MELD. R=0.323, p<0.01. At the same time, there is remarkable difference of the scores of gastric qi damages and MELD scores between the death group and survive group. ③The area under curve(AUC) of gastric qi model is 0.663, P=0.001. When the score of gastric qi damage is 11, it predicts the sensitivity of the death risk is 62%, the specificity is 60%. Conclusion: The scale of gastric qi injury on liver failure patients is simple and practica, and has stability and consistency by inherent reliability analysis. The score of gastric qi damages has positive correlation with MELD scores; The gastric qi injury score and TCM predictive model could predict the death risk of of liver failure patients in the near future.%目的:建立胃气损伤的量化评分表,进行信度和效度的检验;探讨肝衰竭患者胃气损伤与预后的关系.方法:①

  20. Clinical characteristics and treatment of invasive pulmonary aspergillosis in patients with liver failure%肝功能衰竭合并侵袭性肺曲霉病的临床特征与治疗

    Institute of Scientific and Technical Information of China (English)

    邹颖; 钱志平; 张宇一; 王介非; 黄金伟; 李光辉

    2012-01-01

    OBJECTIVE To analyze the clinical features of invasive pulmonary aspergillosis (IPA) in patients with liver failure and to improve the identification of aspergillosis at an early stage. METHODS Medical records of 39 liver failure patients with IPA admitted in Shanghai public health center from Jan 2006 to May 2011were reviewed. T test or non-parametric test was performed for inter-group comparison of means, and chi-square test was performed for enumeration data. RESULTS The clinical features of IPA with liver failure were atypical. The most common initial symptom was fever, accounting for 66. 7%. Early imaging showed multiple nodules or masses shadow with negative results in 1,3-β-D glucan test. The patients condition rapidly deteriorated after infection accompanied by significantly increased TB, Scr, INR, WBC and MELD score and significantly decreased Alb, Gib, PTA, HB, and PLT. Among the 39 cases, anti-fungal therapy was only effective in 8 patients who were discharged after improvement of hepatic function, while the other 31 patients were dead within 2 months of onset. The mortality rate was 79. 5%. 17 patients died during hospitalization with an average time of (5. 3±4. 7) days from the first symptom to death. There was no statistical significance between the survivors and the dead patients in respect of demographic characteristics, stage of liver failure and constitution of cause before IPA. However, the survivors had better MELD scores and received definite diagnosis and effective anti-fungal therapy earlier than dead patients. All the 8 survivors received a long-term treatment with echinocandin including two cases received combination of viriconazole. The mean therapeutic course lasted for (70. 9 + 26. 4) days. No serious adverse drug reactions such as hepatic function relapse were observed. The drugs were well tolerated. CONCLUSION Disease condition is rapidly deteriorated after liver failure complicated with IP A, with extremely high mortality. However

  1. A case of cholestatic hepatitis associated with histologic features of acute cholangitis

    Directory of Open Access Journals (Sweden)

    Takeuchi H

    2011-11-01

    Full Text Available Hajime Takeuchi1, Toru Kaneko1, Toshikazu Otsuka1, Kumiko Tahara1, Tadashi Motoori2, Makoto Ohbu3, Masaya Oda4, Hiroaki Yokomori11Department of Internal Medicine; 2Division of Pathology, Kitasato Medical Center Hospital, Kitasato University, Saitama; 3Department of Pathology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa; 4Department of Internal Medicine, Saitama Social Insurance Hospital, Saitama; 5Organized Center of Clinical Medicine, International University of Health and Welfare, Sanno Hospital, Tokyo, JapanAbstract: This report describes a case showing histologic features of acute cholangitis with an over-the-counter drug. A 48-year-old woman was diagnosed with general malaise and progressive jaundice. A thorough review of her medical history revealed that the patient had taken an over-the-counter drug, Pabron Gold®, which she had used previously, that may have caused liver injury. Laboratory investigations revealed jaundice and liver dysfunction. Endoscopic retrograde cholangiography detected no extrahepatic biliary duct dilatation or stones. Liver biopsy indicated acute cholangitis involving neutrophils and eosinophils. Electron microscopy revealed fragmented nuclei, indicating that the degenerative bile duct-related epithelial cells were in an apoptotic process.Keywords: liver injury, over-the-counter drug, histologic features, acute cholangitis, electron microscopy, Pabron Gold

  2. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    Science.gov (United States)

    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.

  3. Human adipese-derived sterm cells treatment of actute liver failure in rats%人脂肪干细胞治疗急性肝功能衰竭大鼠疗效的探索

    Institute of Scientific and Technical Information of China (English)

    金银鹏; 李莉; 周桁; 陈光风; 傅青春; 刘小青; 程明亮; 王晓今; 陈成伟; 吴银霞; 江甫柱

    2013-01-01

    Objective Isolate human adipose-derived stem cells (hADSC ) and explore its efficacy for acute liver failure rats in liver function reconstruction .Methods hADSC were isolated from fat tissue .30 SD rats induced by D-gal were randomly divided into hADSC transplantation group and PBS control group ,treatment group received 5 × 106 hADSC through spleen route and the control group received the same volume of PBS .Moreover ,20 SD rats were randomly divided into spleen transplantation group and femoral vein transplantation group ,5 × 106 hADSC were injected via the spleen and femoral vein respectively ,immunohistochemical method were applied to detect the migration of hADSC infected with lenti-virus expressed ZsGreen .Results hADSC which obtained from vitro cultured human adipose tissue express mesenchymal stem cell-associated surface antigens and differentiate into adipocytes ,cartilage cells and osteocytes .The hADSC transplan-tation group showed lower mortality (13 .3% ) significantly compared with the PBS control group (40% ) .Serum ALT and AST were significantly lower than the PBS control group after hADSC transplantation indicating the liver functional improvement .HE staining also showed significant improvement in liver tissue morphology .Moreover ,Tunnel assay and Ki-67 assay showed that hADSC transplantation could reduce cell apoptosis and promote cell proliferation .We further tracked the distribution of hADSC transplantation through spleen and femoral vein .Most hADSC migrated to the liver ,spleen and lung in both routes ,however ,more hADSC migrated to the liver via femoral vein transplantation route .Conclusion hADSC can be obtained through the adherent culture of isolated adipose tissue in vitro ;hADSC transplant through spleen and femoral vein promotes regneration and inhibits apoptosis ,improves liver function and survival rate of liver failure rat .%目的探讨人脂肪干细胞(adipose-derived stem cells ,hADSC )对急性肝衰竭大鼠生存

  4. Hepatitis E virus detection in liver tissue from patients with suspected drug-induced liver injury

    Directory of Open Access Journals (Sweden)

    Obinna eChijioke

    2015-03-01

    Full Text Available Hepatitis E virus (HEV infection is increasingly recognized as a cause of acute hepatitis in the industrialized world. We aimed to determine the frequency of acute Hepatitis E virus (HEV infection in cases of suspected drug-induced liver injury (DILI, mainly a diagnosis of exclusion. To this aim, formalin-fixed, paraffin-embedded (FFPE liver tissues of all cases routinely processed in our institute during a 2 ½ years period in which DILI was amongst the differential diagnoses (157 liver biopsies, one liver explant were subjected to semi-nested RT-PCR for the detection of hepatitis E virus (HEV RNA. Histopathology was re-evaluated on all cases tested positive. HEV RNA was detectable in three of 158 cases (2% tested, comprising autochthonic as well as travel-related infections with genotypes 1, 3, and 4 each found once, respectively. Histopathologic findings comprised one case with subtotal hepatic necrosis and two cases of acute (cholestatic hepatitis not distinguishable from acute hepatitis of other etiology. Thus, the overall frequency of acute hepatitis E virus (HEV infection as determined by detection of hepatitis E virus (HEV RNA in liver tissue is substantially increased in patients with suspected drug-induced liver injury compared to the healthy population, emphasizing the need to actively look for hepatitis E virus (HEV infection in cases of suspected drug-induced liver injury (DILI. Molecular testing for hepatitis E virus (HEV RNA in routinely processed formalin-fixed, paraffin-embedded (FFPE liver tissues can be applied to cases with undetermined hepatitis E virus (HEV status.

  5. LIVER AND BILIARY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    12.1 Liver function2003091 Treatment of acute hepatic failure by transplantation of microencapsulated xenogenic hepatocyte.ZHANG Weijie(张伟杰), et al. Instit Organ Transplant, Tongji Hosp, Huazhong Univ Sci & Technol, Wuhan 430030. World Chin J Digestol 2002; 10 (12): 1396-1398.

  6. Liver transplantation in mitochondrial respiratory chain disorders

    NARCIS (Netherlands)

    Sokal, EM; Sokol, R; Cormier, [No Value; Lacaille, F; McKiernan, P; Van Spronsen, FJ; Bernard, O; Saudubray, JM

    1999-01-01

    Mitochondrial respiratory chain disease may lead to neonatal or late onset liver failure, requiring liver transplantation. In rare cases, the disease is restricted to the liver and the patient is cured after surgery. More frequently, other organs are simultaneously involved and neuromuscular or othe

  7. Orlistat-induced fulminant hepatic failure.

    Science.gov (United States)

    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.

  8. ATP8B1 deficiency; Pathophysiology and treatment of a cholestatic syndrome with extrahepatic symptoms

    OpenAIRE

    Stapelbroek, J.M.

    2009-01-01

    ATP8B1 deficiency is a severe and clinically highly variable hereditary disorder that is primarily characterized by intrahepatic cholestasis. It generally presents as a permanent disorder, progressive familial intrahepatic cholestasis type 1 (PFIC1), or with intermittent cholestasis (benign recurrent intrahepatic cholestasis type 1 (BRIC1)). Currently there is no effective medical therapy, and most patients need invasive surgery such as partial biliary drainage (PBD) or liver transplantation....

  9. Dengue haemorrhagic fever presenting with cholestatic hepatitis: two case reports and a review of literature

    OpenAIRE

    Yudhishdran, Jevon; Navinan, Rayno; Ratnatilaka, Asoka; Jeyalakshmy, Sivakumar

    2014-01-01

    Background Dengue fever is a common mosquito borne viral fever in South Asia, which causes significant morbidity and mortality. Dengue fever is well known to involve the liver, especially in dengue hemorrhagic fever. The hepatic involvement is usually that of a mild hepatitis with transaminase derangement without jaundice. In cases of dengue hemorrhagic fever where shock has ensued, a severe hepatitis with gross derangements of transaminases and bilirubin may occur. These are two rare cases o...

  10. Monogenic diseases that can be cured by liver transplantation.

    Science.gov (United States)

    Fagiuoli, Stefano; Daina, Erica; D'Antiga, Lorenzo; Colledan, Michele; Remuzzi, Giuseppe

    2013-09-01

    While the prevalence of most diseases caused by single-gene mutations is low and defines them as rare conditions, all together, monogenic diseases account for approximately 10 in every 1000 births according to the World Health Organisation. Orthotopic liver transplantation (LT) could offer a therapeutic option in monogenic diseases in two ways: by substituting for an injured liver or by supplying a tissue that can replace a mutant protein. In this respect, LT may be regarded as the correction of a disease at the level of the dysfunctional protein. Monogenic diseases that involve the liver represent a heterogeneous group of disorders. In conditions associated with predominant liver parenchymal damage (i.e., genetic cholestatic disorders, Wilson's disease, hereditary hemochromatosis, tyrosinemia, α1 antitrypsin deficiency), hepatic complications are the major source of morbidity and LT not only replaces a dysfunctional liver but also corrects the genetic defect and effectively cures the disease. A second group includes liver-based genetic disorders characterised by an architecturally near-normal liver (urea cycle disorders, Crigler-Najjar syndrome, familial amyloid polyneuropathy, primary hyperoxaluria type 1, atypical haemolytic uremic syndrome-1). In these defects, extrahepatic complications are the main source of morbidity and mortality while liver function is relatively preserved. Combined transplantation of other organs may be required, and other surgical techniques, such as domino and auxiliary liver transplantation, have been attempted. In a third group of monogenic diseases, the underlying genetic defect is expressed at a systemic level and liver involvement is just one of the clinical manifestations. In these conditions, LT might only be partially curative since the abnormal phenotype is maintained by extrahepatic synthesis of the toxic metabolites (i.e., methylmalonic acidemia, propionic acidemia). This review focuses on principles of diagnosis, management

  11. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    Directory of Open Access Journals (Sweden)

    Aggeliki Lyberopoulou

    Full Text Available Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21, HBV (n = 23, autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34, autoimmune hepatitis (AIH; n