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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. Fatigue in cholestatic liver disease—a perplexing symptom

    OpenAIRE

    Kumar, D.; Tandon, R.

    2002-01-01

    Fatigue is an important symptom and a quality of life determinant in patients with cholestatic liver disease. The pathogenesis of fatigue is obscure, although alterations in central neurotransmission and peripheral muscle dysfunction have been incriminated. No effective treatment is available at present. The available literature on fatigue in cholestatic liver disease is reviewed.

  4. 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.

  5. Osteodystrophy in Cholestatic Liver Diseases Is Attenuated by Anti-γ-Glutamyl Transpeptidase Antibody

    OpenAIRE

    Kawazoe, Yusuke; Miyauchi, Mutsumi; Nagasaki, Atsuhiro; Furusho, Hisako; Yanagisawa, Syunryo; Chanbora, Chea; Inubushi, Toshihiro; Hyogo, Hideyuki; Nakamoto, Takashi; Suzuki, Keiko; Moriwaki, Sawako; Tazuma, Susumu; Niida, Shumpei; Takata, Takashi

    2015-01-01

    Background Cholestatic liver diseases exhibit higher levels of serum γ-glutamyl transpeptidase (GGT) and incidence of secondary osteoporosis. GGT has been identified as a novel bone-resorbing factor that stimulates osteoclast formation. The aim of this study was to elucidate the interaction of elevated GGT levels and cholestatic liver disease-induced bone loss. Methods Wistar rats were divided into three groups: sham-operated control (SO) rats, bile duct ligation (BDL) rats, and anti-GGT anti...

  6. 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.

  7. 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

  8. Acute Cholestatic Hepatitis A Virus Infection Presenting with Hemolytic Anemia and Renal Failure: A Case Report

    OpenAIRE

    Lapp, Robert T.; Fedja Rochling

    2013-01-01

    Hepatitis A virus is the most common acute viral hepatitis worldwide with approximately 1.5 million cases annually. Hepatitis A virus infection in general is self-limited. In rare cases, hepatitis A virus infection may cause renal failure, hemolytic anemia, and/or cholestasis. We report the first case of acute cholestatic hepatitis A virus infection complicated by hemolytic anemia, and renal failure in one patient. A 42-year-old Caucasian male presented with cholestasis, hemolytic anemia and ...

  9. 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...

  10. 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

  11. Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease.

    Science.gov (United States)

    Neff, Guy W; O'Brien, Christopher B; Reddy, K Rajender; Bergasa, Nora V; Regev, Arie; Molina, Enrique; Amaro, Rafael; Rodriguez, Miguel J; Chase, VeEtta; Jeffers, Lennox; Schiff, Eugene

    2002-08-01

    Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus. PMID:12190187

  12. 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....

  13. 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...

  14. Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice.

    Science.gov (United States)

    Yu, Su Jong; Bae, Seyeon; Kang, Jae Seung; Yoon, Jung-Hwan; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Wang Jae; Kim, Chung Yong; Lee, Hyo-Suk

    2015-09-01

    Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. PMID:26057690

  15. 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.

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

    International Nuclear Information System (INIS)

    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

  17. Organic anion transporting polypeptide 1a1 null mice are sensitive to cholestatic liver injury.

    Science.gov (United States)

    Zhang, Youcai; Csanaky, Iván L; Cheng, Xingguo; Lehman-McKeeman, Lois D; Klaassen, Curtis D

    2012-06-01

    Organic anion transporting polypeptide 1a1 (Oatp1a1) is predominantly expressed in livers of mice and is thought to transport bile acids (BAs) from blood into liver. Because Oatp1a1 expression is markedly decreased in mice after bile duct ligation (BDL). We hypothesized that Oatp1a1-null mice would be protected against liver injury during BDL-induced cholestasis due largely to reduced hepatic uptake of BAs. To evaluate this hypothesis, BDL surgeries were performed in both male wild-type (WT) and Oatp1a1-null mice. At 24 h after BDL, Oatp1a1-null mice showed higher serum alanine aminotransferase levels and more severe liver injury than WT mice, and all Oatp1a1-null mice died within 4 days after BDL, whereas all WT mice survived. At 24 h after BDL, surprisingly Oatp1a1-null mice had higher total BA concentrations in livers than WT mice, suggesting that loss of Oatp1a1 did not prevent BA accumulation in the liver. In addition, secondary BAs dramatically increased in serum of Oatp1a1-null BDL mice but not in WT BDL mice. Oatp1a1-null BDL mice had similar basolateral BA uptake (Na(+)-taurocholate cotransporting polypeptide and Oatp1b2) and BA-efflux (multidrug resistance-associated protein [Mrp]-3, Mrp4, and organic solute transporter α/β) transporters, as well as BA-synthetic enzyme (Cyp7a1) in livers as WT BDL mice. Hepatic expression of small heterodimer partner Cyp3a11, Cyp4a14, and Nqo1, which are target genes of farnesoid X receptor, pregnane X receptor, peroxisome proliferator-activated receptor alpha, and NF-E2-related factor 2, respectively, were increased in WT BDL mice but not in Oatp1a1-null BDL mice. These results demonstrate that loss of Oatp1a1 function exacerbates cholestatic liver injury in mice and suggest that Oatp1a1 plays a unique role in liver adaptive responses to obstructive cholestasis. PMID:22461449

  18. 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...... transplantation (ELT) is an established treatment option. These improvements in care are such that the majority of patients may now be expected to survive (Fig. 1). Key features of the condition have changed dramatically over time, with a remarkable fall in the incidence of cerebral edema and intracranial...

  19. 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.

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

    International Nuclear Information System (INIS)

    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/mm2. 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 (×10−3 mm2/s; b = 0–800 s/mm2) 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

  1. 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...

  2. Changes in GM1 ganglioside content and localization in cholestatic rat liver.

    Science.gov (United States)

    Jirkovská, Marie; Majer, Filip; Smídová, Jaroslava; Stríteský, Jan; Shaik, Gouse Mohiddin; Dráber, Petr; Vítek, Libor; Marecek, Zdenek; Smíd, Frantisek

    2007-07-01

    (Glyco)sphingolipids (GSL) are believed to protect the cell against harmful environmental factors by increasing the rigidity of plasma membrane. Marked decrease of membrane fluidity in cholestatic hepatocytes was described but the role of GSL therein has not been investigated so far. In this study, localization in hepatocytes of a representative of GSL, the GM1 ganglioside, was compared between of rats with cholestasis induced by 17alpha-ethinylestradiol (EE) and vehicle propanediol treated or untreated animals. GM1 was monitored by histochemical reaction employing cholera toxin B-subunit. Our findings in normal rat liver tissue showed that GM1 was localized in sinusoidal and canalicular hepatocyte membranes in both peripheral and intermediate zones of the hepatic lobules, and was nearly absent in central zones. On the contrary, in EE-treated animals GM1 was also expressed in central lobular zones. Moreover, detailed densitometry analysis at high magnification showed greater difference of GM1 expression between sinusoidal surface areas and areas of adjacent cytoplasm, caused as well by increased sinusoidal staining in central lobular zone as by decreased staining in cytoplasm in peripheral zone. These differences correlated with serum bile acids as documented by linear regression analyses. Both GM1 content and mRNA corresponding to GM1-synthase remained unchanged in livers; the enhanced expression of GM1 at sinusoidal membrane thus seems to be due to re-distribution of cellular GM1 at limited biosynthesis and could be responsible for protection of hepatocytes against harmful effects of bile acids accumulated during cholestasis. PMID:17333356

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

    Directory of Open Access Journals (Sweden)

    F.A. Pereira

    2012-12-01

    Full Text Available 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.

  4. 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.

  5. 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

  6. Cephalexin induced cholestatic jaundice.

    Science.gov (United States)

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

    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 resolution of LFTs was seen in four weeks. Cephalexin induced cholestasis is rare and hence requires a high degree of clinical suspicion for prompt diagnosis and treatment. PMID:25180107

  7. 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

  8. Activation of a Novel c-Myc-miR27-Prohibitin 1 Circuitry in Cholestatic Liver Injury Inhibits Glutathione Synthesis in Mice

    OpenAIRE

    YANG, Heping; Li, Tony W. H.; Zhou, Yu; Peng, Hui; Liu, Ting; Zandi, Ebrahim; Martínez-Chantar, María Luz; Mato, José M.; Lu, Shelly C.

    2015-01-01

    Aims: We showed that chronic cholestatic liver injury induced the expression of c-Myc but suppressed that of glutamate-cysteine ligase (GCL, composed of catalytic and modifier subunits GCLC and GCLM, respectively). This was associated with reduced nuclear antioxidant response element (ARE) binding by nuclear factor-erythroid 2 related factor 2 (Nrf2). Here, we examined whether c-Myc is involved in this process. Results: Similar to bile duct ligation (BDL), lithocholic acid (LCA) treatment in ...

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Lipid emulsions containing fish oil protect against PN-induced cholestatic liver disease in preterm piglets

    Science.gov (United States)

    During their first weeks of life preterm infants are dependent on parenteral nutrition (PN). However, PN is associated with the development of cholestasis (PN Associated Liver Disease PNALD). Studies in children showed that fish oil-based lipid emulsions can reverse PNALD; whether they prevent PNALD...

  14. 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.

  15. 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

  16. 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

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

    Science.gov (United States)

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

    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 against experimental cholestatic conditions. Methods 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. Results Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauro)ursodeoxycholic 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

  18. 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...

  19. 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....

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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....

  5. Mitochondrial dysfunction in liver failure requiring transplantation.

    Science.gov (United States)

    Lane, Maria; Boczonadi, Veronika; Bachtari, Sahar; Gomez-Duran, Aurora; Langer, Thorsten; Griffiths, Alexandra; Kleinle, Stephanie; Dineiger, Christine; Abicht, Angela; Holinski-Feder, Elke; Schara, Ulrike; Gerner, Patrick; Horvath, Rita

    2016-05-01

    Liver failure is a heterogeneous condition which may be fatal and the primary cause is frequently unknown. We investigated mitochondrial oxidative phosphorylation in patients undergoing liver transplantation. We studied 45 patients who had liver transplantation due to a variety of clinical presentations. Blue native polyacrylamide gel electrophoresis with immunodetection of respiratory chain complexes I-V, biochemical activity of respiratory chain complexes II and IV and quantification of mitochondrial DNA (mtDNA) copy number were investigated in liver tissue collected from the explanted liver during transplantation. Abnormal mitochondrial function was frequently present in this cohort: ten of 40 patients (25 %) had a defect of one or more respiratory chain enzyme complexes on blue native gels, 20 patients (44 %) had low activity of complex II and/or IV and ten (22 %) had a reduced mtDNA copy number. Combined respiratory chain deficiency and reduced numbers of mitochondria were detected in all three patients with acute liver failure. Low complex IV activity in biliary atresia and complex II defects in cirrhosis were common findings. All six patients diagnosed with liver tumours showed variable alterations in mitochondrial function, probably due to the heterogeneity of the presenting tumour. In conclusion, mitochondrial dysfunction is common in severe liver failure in non-mitochondrial conditions. Therefore, in contrast to the common practice detection of respiratory chain abnormalities in liver should not restrict the inclusion of patients for liver transplantation. Furthermore, improving mitochondrial function may be targeted as part of a complex therapy approach in different forms of liver diseases. PMID:27053192

  6. Dengue fever with acute liver failure

    Directory of Open Access Journals (Sweden)

    Vinodh B

    2005-01-01

    Full Text Available 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 syndrome, stage IV with acute liver failure. He had primary dengue infection. He made complete recovery with supportive management.

  7. 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.

  8. 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...

  9. Therapeutic hypothermia for acute liver failure

    DEFF Research Database (Denmark)

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...... of liver injury. Hypothermia has not been adequately studied for its safety and theoretically may increase the risk of infection, cardiac dysrhythmias, and bleeding, all complications independently associated with acute liver failure. Therefore, although an ample body of experimental and human data...

  10. 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.

  11. Sphingosine 1-Phosphate Receptor 2 and 3 Mediate Bone Marrow-Derived Monocyte/Macrophage Motility in Cholestatic Liver Injury in Mice.

    Science.gov (United States)

    Yang, Le; Han, Zhen; Tian, Lei; Mai, Ping; Zhang, Yuanyuan; Wang, Lin; Li, Liying

    2015-01-01

    Sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) system has been implicated in the pathological process of liver injury. This study was designed to evaluate the effects of S1P/S1PR on bone marrow-derived monocyte/macrophage (BMM) migration in mouse models of cholestatic liver injury, and identify the signaling pathway underlying this process. S1PR1-3 expression in BMM was characterized by immunofluorescence, RT-PCR and Western blot. Cell migration was determined in Boyden chambers. In vivo, the chimera mice, which received BM transplants from EGFP-transgenic mice, received an operation of bile duct ligation (BDL) to induce liver injury with the administration of S1PR2/3 antagonists. The results showed that S1PR1-3 were all expressed in BMMs. S1P exerted a powerful migratory action on BMMs via S1PR2 and S1PR3. Furthermore, PTX and LY-294002 (PI3K inhibitor) prevented S1PR2/3-mediated BMM migration, and Rac1 activation by S1P was inhibited by JTE-013, CAY-10444 or LY294002. Administration of S1PR2/3 antagonists in vivo significantly reduced BMM recruitment in BDL-treated mice, and attenuated hepatic inflammation and fibrosis. In conclusion, S1P/S1PR2/3 system mediates BMM motility by PTX-PI3K-Rac1 signaling pathway, which provides new compelling information on the role of S1P/S1PR in liver injury and opens new perspectives for the pharmacological treatment of hepatic fibrosis. PMID:26324256

  12. Azathioprine induced cholestatic hepatitis

    OpenAIRE

    Viju Moses; Banumathi Ramakrishna; Kurien Thomas

    2011-01-01

    We report a case of cholestatic hepatitis developed one week after exposure to azathioprine. The subsequent prolonged cholestatic phase was followed by full clinical remission. Current knowledge on pathogenesis and epidemiology and the diagnostic challenges presented by this rare complication are discussed, followed by recommendations for monitoring and management.

  13. Azathioprine induced cholestatic hepatitis

    Directory of Open Access Journals (Sweden)

    Viju Moses

    2011-01-01

    Full Text Available We report a case of cholestatic hepatitis developed one week after exposure to azathioprine. The subsequent prolonged cholestatic phase was followed by full clinical remission. Current knowledge on pathogenesis and epidemiology and the diagnostic challenges presented by this rare complication are discussed, followed by recommendations for monitoring and management.

  14. 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...

  15. Plasma osteopontin in acute liver failure

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  16. Brain cholinergic impairment in liver failure

    OpenAIRE

    García Ayllón, María Salud; Cauli, Omar; Silveyra, María Ximena; Rodrigo, Regina; Candela, Asunción; Compañ, Antonio; Jover, Rodrigo; Pérez-Mateo, Miguel; Martínez, Salvador; Felipo, Vicente; Sáez-Valero, Javier

    2008-01-01

    The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (∼30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltra...

  17. 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.

  18. 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.

  19. 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...

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

    Institute of Scientific and Technical Information of China (English)

    Zhao-chun Chi; Quan-jiang Dong; Chang-xin Geng

    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.

  1. Montelukast-induced acute fulminant liver failure: A case report

    OpenAIRE

    ÇELİK, Mustafa; Arabul, Mahmut; Alper, Emrah; CANTÜRK, Fatih; KANDEMİR, Altay; Vatansever, Sezgin; Ünsal, Belkıs

    2012-01-01

    Drug-induced liver injury is commonly encountered in general practice and a potential complication of many medications. Hepatotoxicity associated with montelukast-induced liver injury including elevated liver tests, hepatitis and fulminant liver failure has been described with rare case reports. We present the case of a 42-year-old woman with montelukast-induced fulminant liver failure. A 42-year-old woman had been taking salbutamol inhaler and salmeterol + fluticasone inhaler for five y...

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

    Science.gov (United States)

    Guillen, S S; Meijer, M; de Jongh, F E

    2016-01-01

    Sunitinib is a tyrosine kinase inhibitor that is used as an anticancer drug in renal cell carcinoma (RCC), pancreatic neuroendocrine tumours (PNETs) and gastrointestinal stromal tumour. Elevated liver enzymes are frequently observed during treatment but acute liver failure is uncommon. We describe a case of fulminant acute liver failure and acute kidney injury during treatment with sunitinib for metastatic RCC. PMID:26933184

  3. 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...

  4. 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...

  5. 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

  6. 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...

  7. 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.

  8. Steroid use in Acute Liver Failure

    Science.gov (United States)

    Karkhanis, Jamuna; Verna, Elizabeth C.; Chang, Matthew S.; Stravitz, R. Todd; Schilsky, Michael; Lee, William M; Brown, Robert S

    2014-01-01

    Background/Aims 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. Methods 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, survival without transplant). Results 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% vs. 66%, p=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of MELD (MELD > 40, survival 30% vs. 57%, p=0.03). In multivariable analysis controlling for steroid use and diagnosis, age (OR 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07) and pHsteroid use was associated with a marginal benefit in SS overall (35% v. 23%, p=0.047), this benefit did not persistent in multivariable analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and ALT (1.02) were the only significant predictors of SS. Conclusions Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores. PMID:23929808

  9. Brain cholinergic impairment in liver failure.

    Science.gov (United States)

    García-Ayllón, María-Salud; Cauli, Omar; Silveyra, María-Ximena; Rodrigo, Regina; Candela, Asunción; Compañ, Antonio; Jover, Rodrigo; Pérez-Mateo, Miguel; Martínez, Salvador; Felipo, Vicente; Sáez-Valero, Javier

    2008-11-01

    The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected. In agreement with the human data, AChE activity in brain cortical extracts of bile duct ligated (BDL) rats was increased (~20%) compared to controls. A hyperammonemic diet did not result in any further increase of AChE levels in the BDL model, and no change was observed in hyperammonemic diet rats without liver disease. Portacaval shunted rats which display increased levels of cerebral ammonia did not show any brain cholinergic abnormalities, confirming that high ammonia levels do not play a role in brain AChE changes. A selective increase of tetrameric AChE, the major AChE species involved in hydrolysis of acetylcholine in the brain, was detected in both cirrhotic humans and BDL rats. Histological examination of BDL and non-ligated rat brains shows that the subcellular localization of both AChE and choline acetyltransferase, and thus the accessibility to their substrates, appears unaltered by the pathological condition. The BDL-induced increase in AChE activity was not parallelled by an increase in mRNA levels. Increased AChE in BDL cirrhotic rats leads to a pronounced decrease (~50-60%) in the levels of acetylcholine. Finally, we demonstrate that the AChE inhibitor rivastigmine is able to improve memory deficits in BDL rats. One week treatment with rivastigmine (0.6 mg/kg; once a day, orally, for a week) resulted in a 25% of inhibition in the enzymatic activity of AChE with no change in protein composition, as assessed by sucrose density gradient

  10. 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

  11. 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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Patients with intestinal failure (IF) and home parenteral nutrition commonly develop abnormal liver function tests. The presentations of IF-associated liver disease (IFALD) range from mild cholestasis or steatosis to cirrhosis and decompensated liver disease. We describe the reversal of IFALD in an...

  13. 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...

  14. 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

  15. Hepatic encephalopathy: effects of liver failure on brain function.

    Science.gov (United States)

    Felipo, Vicente

    2013-12-01

    Liver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects. PMID:24149188

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

    OpenAIRE

    Naruse, Katsutoshi; Tang, Wei; Makuuchi, Masatoshi

    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...

  17. 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

  18. [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

  19. 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

  20. 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

  1. Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency.

    Science.gov (United States)

    Morris, A A M; Olpin, S E; Bennett, M J; Santani, A; Stahlschmidt, J; McClean, P

    2013-01-01

    Liver dysfunction usually accompanies metabolic decompensation in fatty acid oxidation disorders, including carnitine palmitoyltransferase (CPT) Ia deficiency. Typically, the liver is enlarged with raised plasma transaminase activities and steatosis on histological examination. In contrast, cholestatic jaundice is rare, having only been reported in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. We report a 3-year-old boy with CPT Ia deficiency who developed hepatomegaly and cholestatic jaundice following a viral illness. No cause for the jaundice could be found, apart from the fatty acid oxidation disorder. Liver histology showed diffuse, predominately macrovesicular steatosis, hepatocellular and canalicular cholestasis but no bile duct paucity or evidence of large duct obstruction. The liver dysfunction resolved in 4-7 weeks. PMID:23430491

  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. Acute-on-chronic liver failure due to bacterial infection in liver cirrhosis: causes and management

    OpenAIRE

    Han, Tao

    2015-01-01

    Bacterial infection is a common complication in patients with liver cirrhosis, and acute-on-chronic liver failure due to bacterial infection has become a serious clinical problem. There are still many problems in the research on the pathogenesis and management of bacterial infection in liver cirrhosis, such as insidious onset, difficult early diagnosis, and increased multi-drug resistant bacteria. This article reviews the research progress in the causes and management of bacterial infection i...

  4. Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency

    OpenAIRE

    Morris, A A M; Olpin, S E; Bennett, M. J.; Santani, A; Stahlschmidt, J; McClean, P

    2012-01-01

    Liver dysfunction usually accompanies metabolic decompensation in fatty acid oxidation disorders, including carnitine palmitoyltransferase (CPT) Ia deficiency. Typically, the liver is enlarged with raised plasma transaminase activities and steatosis on histological examination. In contrast, cholestatic jaundice is rare, having only been reported in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. We report a 3-year-old boy with CPT Ia deficiency who developed hepatomegaly and ch...

  5. 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.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    Curry S

    2011-06-01

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

  8. Steroid use in acute liver failure

    DEFF Research Database (Denmark)

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

    2014-01-01

    , survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61......% versus 66%, P = 0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (>40, survival 30% versus 57%, P = 0.......03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH steroid use was associated with a marginal benefit...

  9. 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.

  10. 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...

  11. Methimazole Induced Cholestatic Hepatitis: Case Report

    OpenAIRE

    Bunyamin Aydin

    2014-01-01

    Hyperthyroidism is a very common endocrine disease. MMI-induced cholestatic hepatitis is a rare complication. Cholestatic hepatitis usually recovers completely with the discontinuation of MMI. In this case report, we report a cholestatic hepatitis case which was induced with methimazole in a patient who used methimazole with toxic multinodular goiter diagnosis and was completely recovered with discontinuation of the drug.

  12. 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

  13. 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....

  14. 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).

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Hepatitis E and Acute Liver Failure in Pregnancy

    OpenAIRE

    Shalimar; Acharya, Subrat K.

    2013-01-01

    Hepatitis E virus is a positive strand RNA virus with three open reading frames which is transmitted predominantly through the fecal contamination of water and food. It is the most common cause of acute liver failure in endemic areas. Pregnant women especially from the Indian subcontinent and Africa are at increased risk of contracting acute HEV infection as well as developing severe complications including ALF. Transmission of HEV occurs from mother to unborn child. Both maternal and fetal c...

  20. Prognosis and Biomarkers in Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Mookerjee, Rajeshwar P

    2016-05-01

    As formal definitions of acute-on-chronic liver failure (ACLF) have now been established, and given an increased recognition of the dynamic nature of this condition, there is a growing clinical need to assess prognosis and response to interventions. Conventional scoring systems such as Model for End-Stage Liver Disease (MELD) fail to capture the two key prognostic elements in ACLF-namely, extrahepatic organ failure and measures of systemic inflammation-and as such are limited in their prognostic accuracy. Even the best available scoring systems such as the recently described CLIF (Chronic Liver Failure) Consortium ACLF (CLIF-C ACLF) score, are at best 75% accurate and need to be applicable to all etiologies of liver disease. Thus, in the absence of "gold standard" markers of prognosis that render one scoring system superior to another, there is a need to explore other markers of pathophysiology that may better define outcome. This review addresses the evidence for markers of oxidative stress, including those reflecting the inflammasome; elements of cell death such as cytokeratins M30 and M65; and indicators of immune dysfunction, innate immune failure and gut dysbiosis. Finally, evidence for relevance of markers of organ dysfunction, including hemodynamic response, are explored along with associated mediators such as copeptin, dimethylarginines, and renin. It is anticipated that further critique and validation of emerging and relevant biomarkers will facilitate a composite score which, either alone or in combination with existing scoring systems such as CLIF-C, will enable improved prognostication and targeting of therapy in ACLF. PMID:27172354

  1. Congenital Cholestatic Syndromes: What Happens When Children Grow Up?

    OpenAIRE

    Ling, Simon C.

    2007-01-01

    Although advances in the management of children with congenital cholestasis have enabled many to survive into adulthood with their native livers, even the most common of these conditions remains rare in adult hepatology practice. Among four congenital cholestatic syndromes (biliary atresia, Alagille syndrome, Caroli disease and congenital hepatic fibrosis, and progressive familial intrahepatic cholestasis), the published data on outcomes of the syndromes into adulthood suggest that a spectrum...

  2. Cholestatic hepatitis due to Salmonella typhi

    Directory of Open Access Journals (Sweden)

    Ayse Albayrak

    2011-04-01

    Full Text Available Salmonella infection occurs worldwide and is still an important public health problem in many developing countries. The infection can affect almost all major organs including the liver. Severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. In this paper, a 39-year-old male with acute cholestatic typhoid hepatitis is presented. The case had a tender hepatomegaly and elevated serum alanine and aspartate transaminase, alkaline phosphatase, and gamma glutamyl transferase levels; these features cannot been distinguished from those of acute viral hepatitis. Serological and viral markers of acute viral hepatitis were negative. No pathology could be determined in abdomen Ultrasonography (USG or Magnetic Reso - nance (MR Cholangiography. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance. When patients from an endemic or outbreak area present acute febrile hepatitis, typhoid fever should be a consideration.

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

    Science.gov (United States)

    Aron, Jonathan; Agarwal, Banwari; Davenport, Andrew

    2016-04-01

    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. PMID:26894968

  4. 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.

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

    OpenAIRE

    Kim, Tae Yeob; Song, Do Seon; Kim, Hee Yeon; Sinn, Dong Hyun; Yoon, Eileen L.; Kim, Chang Wook; Jung, Young Kul; Suk, Ki Tae; Lee, Sang Soo; Lee, Chang Hyeong; Kim, Tae Hun; Kim, Jeong Han; Choe, Won Hyeok; Yim, Hyung Joon; Kim, Sung Eun

    2016-01-01

    Background & Aim To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and Decem...

  6. 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

  7. 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

  8. Ondansetron to treat pruritus due to cholestatic jaundice.

    Science.gov (United States)

    Dillon, Sarah; Tobias, Joseph D

    2013-07-01

    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

  9. 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.

  10. New Strategies for Acute Liver Failure: Focus on Xenotransplantation Therapy

    Science.gov (United States)

    Alves, Luiz Anastácio; Bonavita, André; Quaresma, Kátia; Torres, Elenilde; Pacheco, Paulo Anastácio Furtado; Cotta-de-Almeida, Vinícius; Saraiva, Roberto Magalhães

    2010-01-01

    Acute liver failure (ALF) has a poor prognosis and, despite intensive care support, reported average survival is only 10–40%. The most common causes responsible for ALF are viral hepatitis (mainly hepatitis A and B) and acetaminophen poisoning. Hepatic transplantation is the only appropriate treatment for patients with unlikely survival with supportive care alone. Survival rates after transplantation can be as high as 80–90% at the end of the first year. However, there is a shortage of donors and is not uncommon that no appropriate donor matches with the patient in time to avoid death. Therefore, new technologies are in constant development, including blood purification therapies as plasmapheresis, hemodiafiltration, and bioartificial liver support. However, they are still of limited efficacy or at an experimental level, and new strategies are welcome. Accordingly, cell transplantation has been developed to serve as a possible bridge to spontaneous recovery or liver transplantation. Xenotransplant of adult hepatocytes offers an interesting alternative. Moreover, the development of transgenic pigs with less immunogenic cells associated with new immunosuppressor strategies has allowed the development of this area. This article reviews some of the newly developed techniques, with focus on xenotransplant of adult hepatocytes, which might have clinical benefits as future treatment for ALF. PMID:26998396

  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 enzym...

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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...

  18. 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...

  19. 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).

  20. 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.

  1. 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).

  2. 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...

  3. 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...

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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...

  11. Biallelic mutations in NBAS cause recurrent acute liver failure with onset in infancy

    OpenAIRE

    Haack, Tobias B.; Staufner, Christian; Köpke, Marlies G.; Straub, Beate K; Kölker, Stefan; Thiel, Christian; Freisinger, Peter; Barić, Ivo; McKiernan, Patrick J; Dikow, Nicola; Harting, Inga; Beisse, Flemming; Burgard, Peter; Kotzaeridou, Urania; Kühr, Joachim

    2015-01-01

    Acute liver failure (ALF) in infancy and childhood is a life-threatening emergency. Few conditions are known to cause recurrent acute liver failure (RALF), and in about 50% of cases, the underlying molecular cause remains unresolved. Exome sequencing in five unrelated individuals with fever-dependent RALF revealed biallelic mutations in NBAS. Subsequent Sanger sequencing of NBAS in 15 additional unrelated individuals with RALF or ALF identified compound heterozygous mutations in an additional...

  12. 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.

  13. Acute liver failure secondary to khat (Catha edulis)-induced necrotic hepatitis requiring liver transplantation: case report.

    Science.gov (United States)

    Roelandt, P; George, C; d'Heygere, F; Aerts, R; Monbaliu, D; Laleman, W; Cassiman, D; Verslype, C; van Steenbergen, W; Pirenne, J; Wilmer, A; Nevens, F

    2011-11-01

    We describe the case of a 26-year-old man with acute liver failure secondary to ingestion of khat (Catha edulis) leaves. In fact, this is the first case of acute liver failure due to khat reported outside the United Kingdom. The combination of specific epidemiologic data (young man of East African origin) and clinical features (central nervous system stimulation, withdrawal reactions, toxic autoimmune-like hepatitis) led to the diagnosis. Mechanisms of action and potential side effects of khat are elaborated on. PMID:22099826

  14. 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...

  15. 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...

  16. Metformin-induced mixed hepatocellular and cholestatic hepatic injury: case report and literature review

    Directory of Open Access Journals (Sweden)

    Saadi T

    2013-08-01

    Full Text Available Tarek Saadi,1–3 Matti Waterman,1–4 Heba Yassin,3 Yaacov Baruch1,41Liver Unit, 2Department of Gastroenterology, 3Department of Internal Medicine A, Rambam Health Care Campus, Haifa, Israel; 4The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, IsraelIntroduction: Metformin is a first-line drug choice for the treatment of type 2 diabetes mellitus (DM-2. Metformin-induced hepatotoxicity has rarely been reported. We report on a case of metformin-induced mixed hepatocellular and cholestatic liver injury in an elderly patient with DM-2 as well as review and summarize case reports of metformin hepatotoxicity available in English on the PubMed database.Case: After receiving metformin 850 mg/day for 2 weeks, a 78-year-old male presented with a 10-day history of abdominal pain, vomiting, diarrhea, and jaundice. Laboratory analysis showed severe hepatocellular and cholestatic hepatic injury. Other causes for acute liver injury were ruled out. Discontinuation of metformin treatment led to significant subjective improvement after 1 week, and all hepatic abnormalities resolved by 2 months.Conclusion: Metformin is an important drug for the treatment of DM-2, which is also used for treatment of patients with fatty liver. It can, however, induce hepatocellular and cholestatic hepatic injury; both physicians and patients should be aware of this potential side effect.Keywords: metformin, hepatocellular liver injury, cholestasis, hepatotoxicity

  17. 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.

  18. 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...

  19. 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

    2013-12-14

    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

  20. 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.

  1. 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.

  2. Role of NMDA receptors in acute liver failure and ammonia toxicity: therapeutical implications.

    Science.gov (United States)

    Rodrigo, Regina; Cauli, Omar; Boix, Jordi; ElMlili, Nisrin; Agusti, Ana; Felipo, Vicente

    2009-01-01

    Acute liver failure (ALF) may lead to rapid death unless the patients receive a liver for transplantation. However, the number of livers available is not enough and a number of patients die before a suitable liver is available for transplantation. The liver has a high capacity for regeneration which may allow complete recovery even in patients with severe liver failure. It would be therefore very useful to have procedures to prevent or delay the mechanisms by which ALF leads to death. These mechanisms are no well understood. Progression of ALF leads to multi-organ failure, systemic inflammatory response, hepatic encephalopathy, cerebral oedema and increased intracranial pressure, which seem the most important immediate causes of mortality in patients with ALF. A main contributor to these events is hyperammonemia, due to impaired ammonia detoxification in the liver. Acute hyperammonemia per se leads to death, which is mediated by activation of the NMDA type of glutamate receptors in brain and may be prevented by antagonists blocking these receptors. Acute liver failure also leads to hyperammonemia and excessive activation of NMDA receptors in brain which contributes to ALF-induced death. Sustained blocking of NMDA receptors by continuous administration of the antagonists MK-801 or memantine increases about twice the survival time of rats with severe ALF due to injection of 2.5g/kg of galactosamine. In rats with milder ALF due to injection of 1.5g/kg of galactosamine, blocking NMDA receptors increases the percentage of surviving rats from 23% to 62% and increases about twice the survival time of the rats which die. These data strongly support that blocking NMDA receptors would improve survival of patients with ALF, either by allowing more time for liver regeneration or to get a liver suitable for transplantation. PMID:19428814

  3. 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

  4. 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

  5. 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.

  6. 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 ...

  7. 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.

  8. 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

  9. 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.

  10. Selective plasma exchange with dialysis in patients with acute liver failure.

    Science.gov (United States)

    Nakae, Hajime; Igarashi, Toshiko; Tajimi, Kimitaka

    2012-10-01

    Selective plasma exchange with dialysis is a blood purification therapy in which simple plasma exchange is performed using a selective membrane plasma separator while the dialysate flows out of the hollow fibers. To evaluate the effect of plasma exchange with dialysis, biochemical examination of the blood, for example, the oxidative stress regulation system and interleukin 18 levels, was performed in patients with acute liver failure. We studied four patients with acute liver failure in whom the therapy was performed (nine times in total). The degree of hepatic encephalopathy and interleukin 18 levels decreased significantly after treatment. However, total protein levels did not change significantly. The level of reactive oxygen species and total antioxidant capacity did not change significantly. Plasma exchange with dialysis may be a useful blood purification therapy in cases of acute liver failure in terms of the removal of water-soluble and albumin-bound toxins. PMID:23046372

  11. 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.

  12. 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.

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

    OpenAIRE

    Essam Mady; Gehane Wissa; Ali Khalifa; Mahmoud El-Sabbagh

    1999-01-01

    This study was carried out to investigate the relationship between lipoprotein (a) levels and the development of atherosclerosis in chronic renal failure (CRF) patients with the possible role of the liver. Serum Lp (a) levels were measured in samples from 20 CRF patients on hemodialysis (HD), 20 liver cirrhosis (LC) patients, 20 patients having both CRF and LC and undergoing HD, and 20 normal control subjects. Renal function (blood urea nitrogen (BUN) and creatinine), hepatic function (transa...

  14. Low Levels of Blood Lipids Are Associated with Etiology and Lethal Outcome in Acute Liver Failure

    OpenAIRE

    Manka, Paul; Olliges, Verena; Bechmann, Lars P.; Schlattjan, Martin; Jochum, Christoph; Treckmann, Jürgen W.; Saner, Fuat H; Gerken, Guido; Syn, Wing-Kin; Canbay, Ali

    2014-01-01

    Background/Aims Emerging data links different aspects of lipid metabolism to liver regeneration. In patients with acute liver failure (ALF), low levels of lipids may correlate with disease severity. Thus, we determined whether there is an etiology-specific link between lipid levels in patients suffering from ALF and aimed to investigate an effect of lipid levels on the prognosis of ALF. Methods In this retrospective single center study, we reviewed 89 consecutive ALF patients, who met the cri...

  15. 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

  16. 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.

  17. 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...

  18. 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) and an...... increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  20. 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.

  1. 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.)

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD (ALF-WD), data and serum were collected from 140 ALF...... patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp <20 mg/dL by the oxidase method provided a...

  3. 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)

    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.

  4. 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...

  5. 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.

  6. 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

  7. 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...

  8. 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

  9. 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.)

  10. 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.)

  11. 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

  12. 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.

  13. 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.

  14. 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

  15.  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

  16. 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.

  17. 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

    HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof......-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken. RESULTS: For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP vs. 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95...... organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (p<0.001). CONCLUSIONS: Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation...

  18. 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.

  19. TAFI deficiency promotes liver damage in murine models of liver failure through defective down-regulation of hepatic inflammation.

    Science.gov (United States)

    Hugenholtz, G C G; Meijers, J C M; Adelmeijer, J; Porte, R J; Lisman, T

    2013-05-01

    Emerging evidence indicates that various haemostatic components can regulate the progression of liver disease. Thrombin-activatable fibrinolysis inhibitor (TAFI) possesses anti-inflammatory properties besides its anti-fibrinolytic function. Here, we investigated the contribution of TAFI to the progression of disease in murine models of chronic and acute liver failure. Chronic carbon tetrachloride (CCL4) administration induced liver damage and fibrosis both in TAFI knockout (TAFI-/-) mice and wild-type controls. Smooth muscle actin-α (α-SMA) content of liver tissue was significantly increased after 1 and 3 weeks, and pro-collagen α1 expression was significantly increased after 3 and 6 weeks in TAFI-/- mice. TAFI-/- mice showed significantly elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after 3 weeks of CCL4. Neutrophil influx was significantly increased in TAFI-/- mice after 6 weeks of CCL4. No difference in hepatic fibrin deposition between TAFI-/- and wild-types was observed. After acetaminophen intoxication, necrosis was significantly increased in TAFI-/- mice at 24 hours (h) after injection. AST and ALT levels were decreased at 2 and 6 h after acetaminophen injection in TAFI-/- mice, but were significantly higher in the TAFI-/- mice at 24 h. Similarly, hepatic fibrin deposition was decreased at 6 h in TAFI-/- mice, but was comparable to wild-types at 24 h after injection. In conclusion, TAFI deficiency results in accelerated fibrogenesis and increased liver damage in murine models of chronic and acute liver disease, which may be related to increased inflammation. PMID:23467679

  20. 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.

  1. 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.

  2. 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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Masayuki Miyazaki

    2011-01-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is a severe 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.

  5. 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.

  6. 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.

  7. [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

  8. Epidemiology and Healthcare Burden of Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Allen, Alina M; Kim, W Ray

    2016-05-01

    Chronic liver disease and cirrhosis, a common end result of viral hepatitis, alcohol abuse, and the emerging epidemic of nonalcoholic fatty liver disease are a significant source of morbidity and premature mortality globally. Acute clinical deterioration of chronic liver disease exemplifies the pinnacle of healthcare burden due to the intensive medical needs and high mortality risk. Although a uniformly accepted definition for epidemiological studies is lacking, acute-on-chronic liver failure (ACLF) is increasingly recognized as an important source of disease burden. At least in the United States, hospitalizations for ACLF have increased several fold in the last decade and have a high fatality rate. Acute-on-chronic liver failure incurs extremely high costs, exceeding the yearly costs of inpatient management of other common medical conditions. Although further epidemiological data are needed to better understand the true impact and future trends of ACLF, these data point to the urgency in the clinical investigation for ACLF and the deployment of healthcare resources for timely and effective interventions in affected patients. PMID:27172353

  9. Determinants of outcome among patients with acute liver failure listed for liver transplantation in the United States.

    Science.gov (United States)

    Reddy, K Rajender; Ellerbe, Caitlyn; Schilsky, Michael; Stravitz, R Todd; Fontana, Robert J; Durkalski, Valerie; Lee, William M

    2016-04-01

    Analyses of outcomes after acute liver failure (ALF) have typically included all ALF patients regardless of whether they were listed for liver transplantation (LT). We hypothesized that limiting analysis to listed patients might provide novel insights into factors associated with outcome, focusing attention on disease evolution after listing. Listed adult ALF patients enrolled in the US Acute Liver Failure Study Group registry between 2000 and 2013 were analyzed to determine baseline factors associated with 21-day outcomes after listing. We classified 617 patients (36% of overall ALF group) by 3-week outcome after study admission: 117 were spontaneous survivors (SSs; survival without LT), 108 died without LT, and 392 underwent LT. Only 22% of N-acetyl-p-aminophenol (APAP) ALF patients were listed; however, this group of 173 patients demonstrated greater illness severity: higher coma grades and more patients requiring ventilator, vasopressor, or renal replacement therapy support. Only 62/173 (36%) of APAP patients received a graft versus 66% for drug-induced liver injury patients, 86% for autoimmune-related ALF, and 71% for hepatitis B-related ALF. APAP patients were more likely to die than non-APAP patients (24% versus 17%), and the median time to death was sooner (2 versus 4.5 days). Despite greater severity of illness, the listed APAP group still had a SS rate of 40% versus 11% for non-APAP causes (P < 0.001). APAP outcomes evolve rapidly, mainly to SS or death. Patients with APAP ALF listed for LT had the highest death rate of any etiology, whereas more slowly evolving etiologies yielded higher LT rates and, consequently, fewer deaths. Decisions to list and transplant must be made early in all ALF patients, particularly in those with APAP ALF. PMID:26421889

  10. Micro-RNA-122 Levels in Acute Liver Failure and Chronic Hepatitis C

    Science.gov (United States)

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

    2016-01-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV–HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P<0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P<0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. PMID:24895202

  11. Artificial liver support for postoperative hepatic failure with anion exchange resin (BR-601).

    OpenAIRE

    Sakagami,Kenichi; MIYAZAKI, MASASHI; Matsuoka, Junji; Shiozaki,Shigehiro; Saito, Shinya; Orita,Kunzo

    1986-01-01

    An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast...

  12. 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

  13. 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)

  14. 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...

  15. 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.

  16. Changes in cerebral oxidative metabolism in patients with acute liver failure

    DEFF Research Database (Denmark)

    Bjerring, P N; Larsen, F S

    2013-01-01

    Acute liver failure patients with a persistence of hyperammonemia are at an increased risk of intracranial hypertension due to development of brain oedema. In vitro studies of brain tissue and cell cultures that indicates that exposure to ammonium inhibits enzymatic activity in the tricarboxylic...... acid cycle, induces substrate depletion through marked glutamate utilization for glutamine synthesis and leads to mitochondrial dysfunction. In patients with acute liver failure cerebral microdialysis studies show a linear correlation between the lactate to pyruvate ratio and the glutamine...... concentration, as well as to some of the adenosine triphosphate degradation products. However, clinical observations of cerebral exchange rates of oxygen, glucose, lactate and amino acids challenge the interpretation of these findings. In this review the conflicting data of cerebral metabolism during acute...

  17. Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

    Directory of Open Access Journals (Sweden)

    Ho Vincent

    2008-05-01

    Full Text Available Abstract Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity.

  18. Hodgkin’s lymphoma coexisting with liver failure secondary to acute on chronic hepatitis B

    OpenAIRE

    Palta, Renee; McClune, Amy; Esrason, Karl

    2013-01-01

    Acute on chronic liver failure (ACLF) is rarely the initial manifestation of a malignant process or precipitated by the initiation of anti-viral treatment with a nucleoside or nucleotide agent. We report an unusual case of ACLF temporally associated with initiation of Entecavir for treatment of chronic hepatitis B. Early Hodgkin’s lymphoma (HL) was unmasked with initiation of the anti-viral treatment which may have exacerbated ACLF. To the best of our knowledge, this has not been described in...

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

    OpenAIRE

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

    2014-01-01

    Astrocyte swelling (cytotoxic brain edema) is the major neurological complication of acute liver failure (ALF), a condition in which ammonia has been strongly implicated in its etiology. Ion channels and transporters are known to be involved in cell volume regulation and a disturbance in these systems may result in cell swelling. One ion channel known to contribute to astrocyte swelling/brain edema in other neurological disorders is the ATP-dependent, non-selective cation channel (NCCa-ATP ch...

  20. 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.

  1. 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...

  2. 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 ...

  3. 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...

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

    Directory of Open Access Journals (Sweden)

    E.V. Schwan

    2000-07-01

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

  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. 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

  7. 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)

  8. 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)

  9. 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

  10. 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

  11. 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.

  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. 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

  14. 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.

  15. 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.

  16. 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

  17. 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

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

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    Lu Li

    2014-01-01

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

  19. 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.)

  20. 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.)

  1. Liver disease and the e antigen in HBsAg carriers with chronic renal failure.

    Science.gov (United States)

    Coughlin, G P; Van Deth, A G; Disney, A P; Hay, J; Wangel, A G

    1980-02-01

    This study was undertaken to assess the frequency of development and the stages of evolution of chronic liver disease in patients with renal failure who are chronic carriers of hepatitis B surface antigen. Cirrhosis or chronic active hepatitis developed in five of 21 patients and could not be predicted by the initial histological appearance or by HLA-A and B typing but was associated with the e antigen in four of the five patients. However, the antigen was not a consistent indicator of a poor prognosis, as the four other e antigen positive patients did not develop chronic liver disease during the period of the study. Transmission of hepatitis B to spouses occurred in four cases, was fatal in one instance, and was associated with e antigen in three of the four. Determination of e antigen status in renal unit patients who are carriers of hepatitis B surface antigen may be of value to the patient and his home environment. PMID:7380332

  2. 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)

  3. Liver disease and the e antigen in HBsAg carriers with chronic renal failure.

    OpenAIRE

    Coughlin, G P; Van Deth, A G; Disney, A P; Van Hay, J.; Wangel, A. G.

    1980-01-01

    This study was undertaken to assess the frequency of development and the stages of evolution of chronic liver disease in patients with renal failure who are chronic carriers of hepatitis B surface antigen. Cirrhosis or chronic active hepatitis developed in five of 21 patients and could not be predicted by the initial histological appearance or by HLA-A and B typing but was associated with the e antigen in four of the five patients. However, the antigen was not a consistent indicator of a poor...

  4. 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

  5. Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Ashfaq, Samir; de los Santos, Mario; Grant, Stephanie; DeMorrow, Sharon

    2016-02-01

    Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1(-/-)) mice were fed a control, cholestyramine-containing, or bile acid-containing diet before azoxymethane (AOM)-induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1(-/-) mice reduced bile acid levels and delayed AOM-induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure. PMID:26683664

  6. Artificial liver support for postoperative hepatic failure with anion exchange resin (BR-601.

    Directory of Open Access Journals (Sweden)

    Sakagami,Kenichi

    1986-10-01

    Full Text Available An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.

  7. An unusual presentation of precursor T cell lymphoblastic leukemia/lymphoma with cholestatic jaundice: case report

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    Latif Sahibzada U

    2009-03-01

    Full Text Available Abstract Background Cholestatic jaundice as a presenting symptom of Precursor T-lymphoblastic leukemia (T-ALL/lymphoma (T-LBL has never been reported in literature. Similarly, precursor T-ALL/T-LBL is characteristically negative for synaptophysin. We report the first case of a patient with precursor T-ALL/T-LBL who presented with cholestatic jaundice and aberrant tumor expression of synaptophysin. Case report 42 year old male presented with anorexia, nausea, jaundice, pale stools, dark urine and about 35 pound weight loss over the previous 3 weeks. The initial laboratory work was suggestive of cholestatic jaundice. Markedly elevated LDH (2025 U/L and CA 19-9 (1778 u/ML were also noticed. The CT scan of abdomen showed massive hepatomegaly with coarse echotexture with contracted gall bladder and normal sized common bile duct. Chest x-ray revealed a mediastinal mass with mediastinal widening. CT scan of the chest showed anterior mediastinal mass (16 cm × 10 cm. CT guided biopsy of the mass showed malignant lymphoma with diffuse proliferation of medium sized lymphoid cells. The neoplastic cells were positive for CD1a, CD3, CD4, CD5, CD8 and CD43 with aberrant expression of synaptophysin. PET CT scan again showed a large anterior mediastinal mass with diffuse liver involvement and abnormal activity in axial bones. CT guided liver biopsy and bone marrow biopsy revealed the same morphology and immunohistochemistry. Bone marrow aspirate showed 85% lymphoblasts. Thus, the diagnosis of precursor T-ALL/T-LBL was made and jaundice with elevated CA 19-9 were attributed to intrahepatic cholestasis. Conclusion Our case illustrates an unusual presentation of hematological malignancies as cholestatic jaundice. It also indicates the non-specific nature of CA 19-9 for pancreaticobiliary malignancies. It is the first case report of neoplastic precursor T cell lymphoblasts with unusual expression of synaptophysin. Tissue biopsy with thorough immunohistochemistry is

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

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    Nélson R Carvalho

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

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

    Science.gov (United States)

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

    2016-01-01

    Background Acute liver failure (ALF) has been reported in ornithine transcarbamylase deficiency (OTCD) and other urea cycle disorders (UCD). The frequency of ALF in OTCD is not well-defined and the pathogenesis is not known. Aim To evaluate the prevalence of ALF in OTCD, we analyzed the Swiss patient cohort. Laboratory data from 37 individuals, 27 females and 10 males, diagnosed between 12/1991 and 03/2015, were reviewed for evidence of ALF. In parallel, we performed cell culture studies using human primary hepatocytes from a single patient treated with ammonium chloride in order to investigate the inhibitory potential of ammonia on hepatic protein synthesis. Results More than 50% of Swiss patients with OTCD had liver involvement with ALF at least once in the course of disease. Elevated levels of ammonia often correlated with (laboratory) coagulopathy as reflected by increased values for international normalized ratio (INR) and low levels of hepatic coagulation factors which did not respond to vitamin K. In contrast, liver transaminases remained normal in several cases despite massive hyperammonemia and liver involvement as assessed by pathological INR values. In our in vitro studies, treatment of human primary hepatocytes with ammonium chloride for 48 hours resulted in a reduction of albumin synthesis and secretion by approximately 40%. Conclusion In conclusion, ALF is a common complication of OTCD, which may not always lead to severe symptoms and may therefore be underdiagnosed. Cell culture experiments suggest an ammonia-induced inhibition of hepatic protein synthesis, thus providing a possible pathophysiological explanation for hyperammonemia-associated ALF. PMID:27070778

  10. Plasma Adiponectin Levels in Acute Liver Failure Patients Treated with Plasma Filtration with Dialysis and Plasma Exchange.

    Science.gov (United States)

    Yamamoto, Hiroshi; Nakae, Hajime; Uji, Yoshitaka; Maeda, Kazuhisa; Tani, Tohru; Eguchi, Yutaka

    2015-08-01

    Plasma filtration with dialysis (PDF) is a blood purification therapy in which simple plasma exchange (PE) is performed using a selective membrane plasma separator while the dialysate flows outside of the hollow fibers. Improvement of hypoadiponectinemia is considered to be a useful therapeutic approach for ameliorating fatal conditions including cardio-metabolic and infectious disease. We investigated the effects of PDF in comparison to PE in terms of plasma adiponectin (APN) changes in patients with acute liver failure. Seventeen patients with liver failure were studied; PDF was performed 55 times and PE 14 times. Plasma APN levels increased significantly after PDF, while decreasing significantly after PE. PDF appears to be among the most useful blood purification therapies in acute liver failure cases in terms of increasing APN levels. PMID:26386223

  11. 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.

  12. 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

  13. 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...

  14. Rifaximin induced Stevens-Johnson syndrome in a patient of acute on chronic liver failure

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    Cyriac Abby Philips

    2015-02-01

    Full Text Available Stevens–Johnson Syndrome (SJS forms part of a spectrum of severe adverse cutaneous reactions that can eventually culminate into toxic epidermal necrolysis (TEN, a potentially fatal condition. Drugs, most commonly allopurinol, antivirals, antiepileptics, sulfonamides and other antibiotics are implicated in this disease, even though, many case reports and series describe a variety of associations with many other classes of drugs. Infectious and inflammatory conditions also predispose to this severe cutaneous disease. Here, we present a patient who was initially diagnosed as a case of acute on chronic liver failure in hepatic encephalopathy grade I, in whom the introduction of rifaximin therapy led to aggressive cutaneous reactions, leading to SJS, which was managed with intensive supportive treatment because of which the patient improved substantially and was discharged after 14 days of onset of a potentially fatal condition. Rifaximin therapy leading to SJS - TEN has been reported only once before

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

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    Howie Forbes

    2010-03-01

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

  16. 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

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

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    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

  18. Cordyceps sinensis prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure.

    Science.gov (United States)

    Cheng, Yu-Jung; Cheng, Shiu-Min; Teng, Yi-Hsien; Shyu, Woei-Cherng; Chen, Hsiu-Ling; Lee, Shin-Da

    2014-01-01

    Cordyceps sinensis (C. sinensis) has long been considered to be an herbal medicine and has been used in the treatment of various inflammatory diseases. The present study examined the cytoprotective properties of C. sinensis on D(+)-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were randomly assigned into control, GalN/LPS, CS 20 mg and CS 40 mg groups (C. sinensis, oral gavage, five days/week, four weeks). After receiving saline or C. sinensis, mice were intraperitoneally given GalN (800 mg/kg)/LPS (10 μg/kg). The effects of C. sinensis on TNF-α, IL-10, AST, NO, SOD, and apoptoticrelated proteins after the onset of endotoxin intoxication were determined. Data demonstrated that GalN/LPS increased hepatocyte degeneration, circulating AST, TNF-α, IL-10, and hepatic apoptosis and caspase activity. C. sinensis pre-treatment reduced AST, TNF-α, and NO and increased IL-10 and SOD in GalN/LPS induced fulminant hepatic failure. C. sinensis attenuated the apoptosis of hepatocytes, as evidenced by the TUNEL and capase-3, 6 activity analyses. In summary, C. sinensis alleviates GalN/LPS-induced liver injury by modulating the cytokine response and inhibiting apoptosis. PMID:24707872

  19. 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.

  20. 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)....

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

    Science.gov (United States)

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

    2014-01-01

    Ingestion of the mushroom containing Amanita phalloides can induce fulminant liver failure and death. There are no specific antidotes. Blood purifications, such as molecular adsorbent recirculating system (MARS) and therapeutic plasma exchange (TPE), are potential therapies. However, the extent to which these technologies avert the deleterious effects of amatoxins remains controversial; the optimal intensity, duration, and initiation criteria have not been determined yet. This study aimed to retrospectively observe the effects of MARS and TPE on nine patients with A. phalloides-induced fulminant liver failure. The survival rate for the nine patients was 66.7%. Both TPE and MARS might remove toxins and improve liver functions. However, a single session of TPE produced immediately greater improvements in alanine aminotransferase (-60% vs. -16.3%), aspartate aminotransferase (-47.6% vs. -15.4%), and total bilirubin (-37.3% vs. -17.1%) (compared with the values of pretreatment, all p 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

  2. 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).

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

    Science.gov (United States)

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

    2016-01-01

    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

  4. 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.

  5. 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)

  6. 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.

  7. 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.

  8. 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.

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

    OpenAIRE

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

    2014-01-01

    Objective To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in “real-life” Chinese patients. Methods A total of 38,464 “real-life” Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical a...

  10. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain.

    Science.gov (United States)

    Cauli, Omar; Rodrigo, Regina; Boix, Jordi; Piedrafita, Blanca; Agusti, Ana; Felipo, Vicente

    2008-09-01

    Developing procedures to delay the mechanisms of acute liver failure-induced death would increase patients' survival by allowing time for liver regeneration or to receive a liver for transplantation. Hyperammonemia is a main contributor to brain herniation and mortality in acute liver failure (ALF). Acute ammonia intoxication in rats leads to N-methyl-D-aspartate (NMDA) receptor activation in brain. Blocking these receptors prevents ammonia-induced death. Ammonia-induced activation of NMDA receptors could contribute to ALF-induced death. If this were the case, blocking NMDA receptors could prevent or delay ALF-induced death. The aim of this work was to assess 1) whether ALF leads to NMDA receptors activation in brain in vivo and 2) whether blocking NMDA receptors prevents or delays ALF-induced death of rats. It is shown, by in vivo brain microdialysis, that galactosamine-induced ALF leads to NMDA receptors activation in brain. Blocking NMDA receptors by continuous administration of MK-801 or memantine through miniosmotic pumps affords significant protection against ALF-induced death, increasing the survival time approximately twofold. Also, when liver injury is not 100% lethal (1.5 g/kg galactosamine), blocking NMDA receptors increases the survival rate from 23 to 62%. This supports that blocking NMDA receptors could have therapeutic utility to improve survival of patients with ALF. PMID:18599589

  11. 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.

  12. 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)

  13. 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

  14. Fatal liver failure following food supplements during chronic treatment with montelukast.

    Science.gov (United States)

    Actis, G C; Bugianesi, E; Ottobrelli, A; Rizzetto, M

    2007-10-01

    High aminotransferases and prolonged prothrombin time on entering our liver unit were revealing parenchymal collapse for this 45-year-old obese woman; treatment failure led her to death. Autoimmunity, paracetamol use, alcoholism, and Wilson's disease were all excluded as causes. Because of chronic asthma, she had been receiving a leukotriene receptor antagonist (montelukast) for 5 years before the current presentation; 1 week before onset she had had 1 week of treatment with two dietary supplements for weight control; one of these included Garcinia Cambogia, a possible cause of two recent cases of hepatitis in the USA; in addition, both formulas contained a citrus derivative that interferes cytochrome functions. We speculate on a causal relationship between the assumption of the additives and the fatal hepatitis and envisage a synergy between the additives and montelukast, which per se has well been studied as a hepatotoxic drug. Despite the speculative nature of this presentation, we believe the warning may serve to focus attention on the uncontrolled escalation of food additives going on in these days. PMID:17157086

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Cyntia Ferreira Gomes Viana

    2008-09-01

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

  17. 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....

  18. 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.

  19. Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

    Directory of Open Access Journals (Sweden)

    Cao Hongcui

    2012-06-01

    Full Text Available Abstract Background Stem cell-based therapy to treat liver diseases is a focus of current research worldwide. So far, most such studies depend on rodent hepatic failure models. The purpose of this study was to isolate mesenchymal stem cells from human placenta (hPMSCs and determine their therapeutic potential for treating Chinese experimental miniature pigs with acute liver failure (ALF. Methods hPMSCs were isolated and analyzed for their purity and differentiation potential before being employed as the donor cells for transplantation. ALF models of Chinese experimental miniature pigs were established and divided into four groups: no cell transplantation; hPMSCs transplantation via the jugular vein; X-ray-treated hPMSCs transplantation via the portal vein; and hPMSCs transplantation via the portal vein. The restoration of biological functions of the livers receiving transplantation was assessed via a variety of approaches such as mortality rate determination, serum biochemical analysis, and histological, immunohistochemical, and genetic analysis. Results hPMSCs expressed high levels of CD29, CD73, CD13, and CD90, had adipogenic, osteogenic, and hepatic differentiation potential. They improved liver functions in vivo after transplantation into the D-galactosamine-injured pig livers as evidenced by the fact that ALT, AST, ALP, CHE, TBIL, and TBA concentrations returned to normal levels in recipient ALF pigs. Meanwhile, histological data revealed that transplantation of hPMSCs via the portal vein reduced liver inflammation, decreased hepatic denaturation and necrosis, and promoted liver regeneration. These ameliorations were not found in the other three groups. The result of 7-day survival rates suggested that hPMSCs transplantation via the portal vein was able to significantly prolong the survival of ALF pigs compared with the other three groups. Histochemistry and RT-PCR results confirmed the presence of transplanted human cells in recipient pig

  20. 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.

  1. 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...

  2. Liver delivery of NO by NCX-1000 protects against acute liver failure and mitochondrial dysfunction induced by APAP in mice

    OpenAIRE

    Fiorucci, Stefano; Antonelli, Elisabetta; Distrutti, Eleonora; Mencarelli, Andrea; Farneti, Silvana; Soldato, Piero Del; Morelli, Antonio

    2004-01-01

    NCX-1000, (3α, 5β, 7β)-3,7-dihydroxycholan-24oic acid[2-methoxy-4-[3-[4-(nitroxy)butoxy]-3-oxo-1-propenyl]phenyl ester, is a nitric oxide (NO)-derivative of ursodeoxyxholic acid (UDCA) that selectively release NO in the liver.Here, we demonstrated that administering mice with 40 μmol kg−1 NCX-1000, but not UDCA, improves liver histopathology and reduces mortality caused by 330 μmol kg−1 APAP from 60 to 25% (P

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

    Directory of Open Access Journals (Sweden)

    Małgorzata Pawłowska, Waldemar Halota

    2010-10-01

    Full Text Available 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 liver failure resulting from chronic hepatitis B with an autoimmune component. The treatment consisted of steroids, azathioprine, vitamin K, low-protein diet and lactulose enemas. After undergoing a molecular test (HBV DNA 3.23 × 105 IU/mL and mutations I 204 and I 80, the treatment was modified by adding entecavir. After one month the patient was discharged in good clinical condition, with the recommendation of continued entecavir, prednisone and azathioprine. In subsequent months, no clinical deterioration or abnormal biochemical liver function test results were found, despite the discontinuation of immunosuppressive therapy after 10 mo. The patient continues entecavir therapy.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND & AIMS: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), 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...... day 3 [3.35(1.84)(P = 0.006)]. H- and L-ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 [0.96 μg/ml(1.15) vs. 0.60(0.60)(P = 0.02)] and lower levels of L-ficolin by day 3 compared with patients who died or were transplanted [1.61 μg/ml(1...

  5. 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

  6. 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.

  7. Rapid liver enlargement and hepatic failure secondary to radiographic occult tumor invasion: two case reports and review of the literature

    Directory of Open Access Journals (Sweden)

    Simone Christine

    2012-11-01

    Full Text Available Abstract Introduction Unfamiliarity with certain clinical presentations, as illustrated in these cases, can lead to delayed diagnoses that in turn cause increased morbidity, prolonged hospitalization, and the need for autopsy. Case presentation In Case 1, a 63-year-old Caucasian woman presented with hepatic enlargement and insufficiency which progressed and resulted in her death over a period of less than 2 weeks. The patient underwent a detailed workup included magnetic resonance imaging and computed tomography scan of her liver, which did not reveal the source of her liver enlargement. Due to her progressive liver enlargement and insufficiency, she developed a life-threatening esophageal variceal bleeding during her hospital stay which further delayed the attainment of her diagnosis. She finally underwent a videoscopic laparotomy and liver biopsy which revealed complete replacement and filling in of the liver sinuous with Indian filing lobular breast cancer. The patient died shortly after her diagnosis and before she could be discharged. In Case 2, a 68-year-old Caucasian woman with non-small-cell lung cancer was admitted to our Oncology in-patient service with a presentation of rapid hepatic insufficiency and severe liver enlargement. Like the patient in Case 1, during her hospitalization, this patient underwent a thorough radiographic evaluation, including computed tomography and magnetic resonance imaging, to identify the source of her symptoms. Radiographic imaging showed only hepatomegaly and no discrete focal lesions. As the multiple imaging studies over a period of a week did not reveal a clear cause for her symptoms, she finally underwent an interventional radiology core biopsy which showed complete replacement of her liver with non-small-cell lung cancer. Her condition rapidly progressed due to continued liver enlargement and she died due to frank liver failure before her diagnosis was affirmed and she could be discharged. Conclusion

  8. 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.

  9. 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.

  10. Feasibility of gadoxetate disodium-enhanced MR cholangiography in chronic cholestatic biliary disease

    International Nuclear Information System (INIS)

    Aim: To investigate the feasibility of gadoxetate disodium-enhanced magnetic resonance (MR) cholangiography in chronic obstructive cholestatic biliary disease in the clinical setting. Materials and methods: Twenty-three patients with dilated bile duct trees and ten volunteers underwent gadoxetate disodium-enhanced liver MR cholangiography and were enrolled in the present retrospective study. Gadoxetate disodium was given in a standardized manner as a bolus injection at a dose of 0.25 mmol/kg of body weight (0.1 ml/kg). Region of interest-based measurement of mean enhancement of the dilated bile ducts was performed in series before gadoxetate disodium administration and during hepatobiliary phases. Results: Direct comparison of mean bile duct enhancement during hepatobiliary phases in the clinical imaging window between healthy volunteers [4.7 ± 2.2 arbitrary units (au)] and patients with dilated bile ducts (0.1 ± 0.3 au) revealed significantly lower or absent enhancement in dilated bile ducts (p = 0.001). Conclusion: Standard clinical gadoxetate disodium-enhanced MR cholangiography is not a reliable technique for the evaluation of the biliary trees, because of altered biliary gadoxetate disodium elimination in patients with chronic obstructive biliary diseases. - Highlights: • Biliary excretion of gadoxetic disodium is impaired in subjects with chronic central or segmental bile duct obstruction. • MR cholangiography using gadoxetic disodium is not feasible in patients with chronic cholestatic bile duct disease. • Gadoxetic disodium enhanced MRI is a potential biomarker to measure hepatobiliary transporter function

  11. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  13. 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

  14. 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...

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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 ...

  1. 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...

  2. 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

  3. High dose of buprenorphine in terminally ill patient with liver failure: efficacy and tolerability.

    Science.gov (United States)

    Ciccozzi, Alessandra; Angeletti, Chiara; Baldascino, Giada; Petrucci, Emiliano; Bonetti, Cristina; De Santis, Stefania; Paladini, Antonella; Varrassi, Giustino; Marinangeli, Franco

    2012-01-01

    Pain in terminally ill patients with cancer can be often hard to manage, due to the unpredictable kinetics of drugs caused by progressive kidney and liver dysfunction. Plasma concentrations of active metabolites-also a cause of dangerous side effects--could be difficult to estimate. This case report holds the idea that buprenorphine, a partial agonist of m-receptors, even at high dosage, may be effective and safe to use in terminally ill patients with significant liver and kidney impairment. PMID:22941853

  4. 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

  5. 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.

  6. Liver fibrosis

    OpenAIRE

    Bataller, Ramón; Brenner, David A.

    2005-01-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major ...

  7. 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

  8. 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.

  9. Branched chain amino acid transaminase and branched chain alpha-ketoacid dehydrogenase activity in the brain, liver and skele­tal muscle of acute hepatic failure rats

    Directory of Open Access Journals (Sweden)

    Takei,Nobuyuki

    1985-02-01

    Full Text Available Branched chain amino acid (BCAA transaminase activity increased in both the mitochondrial and supernatant fractions of brain from hepatic failure rats, in which a partial hepatectomy was performed 24h following carbon tetrachloride (CCl4 administration, although the activity of liver and skeletal muscle was the same as in control rats. The elevation of mitochondrial BCAA transaminase activity in liver-injured rats was partly due to increased activity of brain specific Type III isozyme. Branched chain alpha-ketoacid (BCKA dehydrogenase in the brain homogenates was not significantly altered in acute hepatic failure rats, while the liver enzyme activity was markedly diminished. BCKA dehydrogenase activity in the brain homogenates was inhibited by adding ATP to the assay system, and was activated in vitro by preincubating the brain homogenate at 37 degrees C for 15 min. These findings suggest that brain BCAA catabolism is accelerated in acute hepatic failure rats.

  10. 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

  11. 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...

  12. The expression levels of prolyl oligopeptidase responds not only to neuroinflammation but also to systemic inflammation upon liver failure in rat models and cirrhotic patients

    OpenAIRE

    Tenorio-Laranga, Jofre; Montoliu, Carmina; Urios, Amparo; Hernandez-Rabaza, Vicente; Ahabrach, Hanan; García-Horsman, J. Arturo; Felipo, Vicente

    2015-01-01

    Background Liver failure in experimental animals or in human cirrhosis elicits neuroinflammation. Prolyl oligopeptidase (PREP) has been implicated in neuroinflammatory events in neurodegenerative diseases: PREP protein levels are increased in brain glial cells upon neuroinflammatory insults, but the circulating PREP activity levels are decreased in multiple sclerosis patients in a process probably mediated by bioactive peptides. In this work, we studied the variation of PREP levels upon liver...

  13. 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. ...

  14. 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

  15. Survival Benefits With Artificial Liver Support System for Acute-on-Chronic Liver Failure: A Time Series-Based Meta-Analysis.

    Science.gov (United States)

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

    2016-01-01

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

  16. 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

  17. 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...

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

    OpenAIRE

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

    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 partia...

  19. 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.

  20. 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.

  1. 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...

  2. Glutamate-induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure.

    Science.gov (United States)

    Rodrigo, Regina; Erceg, Slaven; Rodriguez-Diaz, Jesus; Saez-Valero, Javier; Piedrafita, Blanca; Suarez, Isabel; Felipo, Vicente

    2007-07-01

    It has been proposed that impairment of the glutamate-nitric oxide-cyclic guanosine monophosphate (cGMP) pathway in brain contributes to cognitive impairment in hepatic encephalopathy. The aims of this work were to assess whether the function of this pathway and of nitric oxide synthase (NOS) are altered in cerebral cortex in vivo in rats with chronic liver failure due to portacaval shunt (PCS) and whether these alterations are due to hyperammonemia. The glutamate-nitric oxide-cGMP pathway function and NOS activation by NMDA was analysed by in vivo microdialysis in cerebral cortex of PCS and control rats and in rats with hyperammonemia without liver failure. Similar studies were done in cortical slices from these rats and in cultured cortical neurons exposed to ammonia. Basal NOS activity, nitrites and cGMP are increased in cortex of rats with hyperammonemia or liver failure. These increases seem due to increased inducible nitric oxide synthase expression. NOS activation by NMDA is impaired in cerebral cortex in both animal models and in neurons exposed to ammonia. Chronic liver failure increases basal NOS activity, nitric oxide and cGMP but reduces activation of NOS induced by NMDA receptors activation. Hyperammonemia is responsible for both effects which will lead, independently, to alterations contributing to neurological alterations in hepatic encephalopathy. PMID:17286583

  3. 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

  4. 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

  5. Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

    Science.gov (United States)

    Mira, Valerie; Boles, Richard G

    2012-01-01

    A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 μg/g creatinine) and liver (103 μg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders. PMID:23430866

  6. 99Tcm-MIBI hepatobiliary scintigraphy in peadiatric patients with severe cholestatic infant hepatitis syndrome

    International Nuclear Information System (INIS)

    Objective: Because of the limited of 99Tcm-diethyl iminodiacetic acid (99Tcm-EHIDA) hepatobiliary scintigraphy in the diagnosis of severe cholestatic infant hepatitis syndrome, trial use 99Tcm-methoxy isobutyl isonitrile (99Tcm-MIBI) as a new hepatobiliary scintigraphy imaging agent to understand its applied basis and primary evaluate value in diagnosis of severe cholestatic infant hepatitis syndrome. Methods: constructed choledochal atresia animal model and investigated the application basis of 99Tcm-MIBI hepatobiliary scintigraphy. Twenty-seven children patients of severe cholestatic who finally confirmed infant hepatitis syndrome were underwent firstly 99Tcm-EHIDIA hepatobiliary scintigraphy. After 24 h delay imaging next day, 99Tcm-MIBI hepatobiliary scintigraphy was underwent after 1 h. Two imaging agents of value in the diagnosis of severe cholestatic infant hepatitis syndrome were compared. Results: It was proved that 99Tcm-MIBI was surely excreted by hepatobiliary and had no intestinal autocrine phenomenon in animal test. So 99Tcm-MIBI can be used to undergo hepatobiliary scintigraphy. The sensitivity of 99Tcm-MIBI hepatobiliary scintigraphy in the diagnosis of severe cholestatic infant hepatitis syndrome was 100% in our primary clinical study. Its sensitivity was higher than which of 99Tcm-EHIDA hepatobiliary scintigraphy (66.67%) by far. Conclusion: With regard to those children patients who suspected highly severe cholestatic infant hepatitis syndrome in clinical, the sensitivity of 99Tcm-MIBI hepatobiliary scintigraphy is obviously superior to conventional 99Tcm-EHIDA hepatobiliary scintigraphy. (authors)

  7. Phoenix critical care journal club: intracranial pressure monitoring for fulminant liver failure

    Directory of Open Access Journals (Sweden)

    Raschke RA

    2015-03-01

    Full Text Available No abstract available. Article truncated at 150 words. The fellows performed an excellent follow-up to our last journal club in which we reviewed the above article. This cohort consisted of 140 patients who underwent ICP monitoring for grade III/VI encephalopathy, and 489 non-monitored controls. Only 87/140 (62% of monitored patients had sufficient available data for analysis, 51% of whom had demonstrable intracranial hypertension (ICH that was associated with nearly a doubling of mortality (43 vs.23% p=0.05. Monitoring and control groups were dissimilar. Monitored patients were statistically more likely to require mechanical ventilation, vasopressors and dialysis, and ultimately more than twice as likely to undergo liver transplant. Reasonably, monitored patients also received more treatments aimed at reducing ICH including osmotic therapy and hypothermia, although no treatment protocol was stipulated. Fatal hemorrhagic complications of ICP monitoring occurred in 3 of 56 patients for whom this outcome could be determined. Overall, 21-day mortality was similar in monitored and control patients: 33% ...

  8. 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.

  9. 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.

  10. 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.

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

    Science.gov (United States)

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

    2014-06-01

    Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration. PMID:24338618

  12. 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

  13. The clinical features and outcomes of acute liver failure associated with dengue infection in adults: a case series

    Directory of Open Access Journals (Sweden)

    Soek-Siam Tan

    2013-04-01

    Full Text Available OBJECTIVE: To describe the clinical manifestations and outcome of acute liver failure (ALF associated with dengue viral infection, a rare but severe complication. METHODS: One hundred and fifty five consecutive patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described. RESULTS: All patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum age was 33.5 (17, 47 years with 50% female. The median (minimum, maximum duration from the onset of fever to development of ALF was 7.5 (5, 13 days and the maximum hepatic encephalopathy (HE grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase [median admission 1140.5 u/L (639, 4161; median peak 2487 u/L (998, 5181], serum bilirubin [median admission 29 µmol/L (23, 291; median peak 127 µmol/L (72, 592], and prothrombin time [median admission 16.8 s (15.3, 26.2; median peak 22 s (15.3, 40.7]. The survival rate with standard medical therapy alone was 100%. CONCLUSIONS: Dengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.

  14. 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.

  15. 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.

  16. 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.

  17. 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)

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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...

  3. 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

  4. Liver Failure with Coagulopathy, Hyperammonemia and Cyclic Vomiting in a Toddler Revealed to Have Combined Heterozygosity for Genes Involved with Ornithine Transcarbamylase Deficiency and Wilson Disease

    OpenAIRE

    Mira, Valerie; Boles, Richard G.

    2011-01-01

    A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2–3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four other...

  5. 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 ...

  6. Correlation of the intracranial pressure to the central venous pressure in the late phase of acute liver failure in a porcine model.

    Science.gov (United States)

    Scheuermann, Kathrin; Thiel, Christian; Thiel, Karolin; Klingert, Wilfried; Hawerkamp, Elmar; Scheppach, Johannes; Königsrainer, Alfred; Morgalla, Matthias H; Leckie, Pamela; Proven, Andrew; Jalan, Rajiv; Davies, Nathan; Schuhmann, Martin U; Schenk, Martin

    2012-01-01

    Volume loading is a common method used to ensure adequate circulation. However, in the late phase of acute liver failure complications that often lead to death are cerebral swelling and brainstem edema, which are considered to result from increasing intracranial pressure (ICP). In former studies cerebral venous pressure (CVP) and ICP were reported to be independent entities. Acute liver failure was induced in 25 German land race pigs by acetaminophen intoxication. CVP and ICP were measured continuously. Hydroxyethyl starch solution and noradrenalin were administered to stabilize the circulation at a mean arterial pressure above 60mmHg. There is an increasing correlation in quantity and quality between the CVP and ICP in the last 24 h before exitus. Beginning with a slope of 0.24 (ICP against CVP) and a low correlation coefficient of 0.08. 24h before exitus, this situation remained stable until 16 h to exitus (m = 0.22, r = 0.1). The correlation increased from 16 to 8 h prior to exitus to a slope of m = 0.5 and a correlation of r = 0.3 and remained until exitus. In late acute liver failure it seems therefore clinically reasonable to keep circulation within an adequate range by the use of noradrenalin and to avoid fluid overload. PMID:22327729

  7. 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

  8. 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.

  9. 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

  10. Cell Therapies for Liver Diseases

    OpenAIRE

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

    2012-01-01

    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...

  11. 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

  12. 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

  13. The increased gastroprotective effect of pioglitazone in cholestatic rats: role of nitric oxide and tumour necrosis factor alpha.

    Science.gov (United States)

    Moezi, Leila; Janahmadi, Zeinab; Amirghofran, Zahra; Nekooeian, Ali Akbar; Dehpour, Ahmad R

    2014-02-01

    The prevalence of gastric ulcers is high in cholestatic patients, but the exact mechanism of this increased frequency remains uncertain. It has been shown that pioglitazone accelerates the healing of pre-existing gastric ulcers. The present study was designed to investigate the effect of pioglitazone, on the gastric mucosal lesions in cholestatic rats. Cholestasis was induced by surgical ligation of common bile duct and sham-operated rats served as control. Different groups of sham and cholestatic animals received solvent or pioglitazone (5, 15, 30 mg/kg) for 7 days. On the day eight rats were killed after oral ethanol administration and the area of gastric lesions was measured. The serums of rats were also collected to determine serum levels of tumour necrosis factor alpha (TNF-α), IL-1β and bilirubin. The ethanol-induced gastric mucosal damage was significantly more severe in cholestatic rats than sham-operated ones. Pretreatment with pioglitazone dose-dependently attenuated gastric lesions induced by ethanol in both sham and cholestatic rats, but this effect was more prominent in cholestatic ones. The effect of pioglitazone was associated with a significant fall in serum levels of TNF-α in cholestatic rats. L-NAME, a non-selective nitric oxide synthase (NOS) inhibitor, and decreased pioglitazone-induced gastroprotective effect in cholestatic rats, while aminoguanidine, a selective inducible NOS inhibitor, potentiated pioglitazone-induced gastroprotective effect in the cholestatic rats. Chronic treatment with pioglitazone exerts an enhanced gastroprotective effect on the stomach ulcers of cholestatic rats compared to sham rats probably due to constitutive NOS induction and/or inducible NOS inhibition and attenuating release of TNF-α. PMID:24456333

  14. 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.

  15. 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; Arroyo, Vicente; Moestrup, Søren K; Garcia, Elisabet; Solà, Elsa; Domenicali, Marco; Piano, Salvatore; Vilstrup, Hendrik; Møller, Holger Jon

    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 (s......-C AD-scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy: In ACLF patients sCD163 improved prediction of short-term mortality (C-index:0.74(0.67-0.80)) and in patients without ACLF sMR improved prediction of long-term mortality [C-index:0.......80(0.76-0.85]. CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform of the clinical scores...

  16. 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

  17. 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...

  18. 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

  19. 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

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway.

    Science.gov (United States)

    Jiang, Xueqiang; Li, Zhihao; Jiang, Shengfang; Tong, Xuefei; Zou, Xiaojing; Wang, Wan; Zhang, Zhengang; Wu, Liang; Tian, Deying

    2016-03-01

    Although rare, acute liver failure (ALF) is associated with high levels of mortality, warranting the development of novel therapies. Nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) play roles in ALF. Lipoxin A4 (LXA4) has been shown to alleviate inflammation in non-hepatic tissues. In the present study, we explored whether LXA4 exerted hepatoprotective effects in a rat model of ALF. A rat model of ALF was generated by intraperitoneal injections of D-galactosamine (300 mg/kg) and lipopolysaccharide (50 µg/kg). Animals were randomly assigned to: control group (no ALF); model group (ALF); and the groups treated with a low dose (0.5 µg/kg), medium dose (1 µg/kg), and high dose (2 µg/kg) of LXA4 (all with ALF); and pyrrolidine dithiocarbamate (PDTC)-treated group (ALF and 100 mg/kg PDTC, an inhibitor of NF-κB). Liver histology was measured using H&E staining, serum levels by ELISA, and liver mRNA expression was measured by RT-PCR for the detection of the pro‑inflammatory cytokines TNF-α and IL-6. Liver cell apoptosis (as measured using the TUNEL method and examining caspase-3 activity), and Kupffer cell NF-κB activity [using an electrophoretic mobility shift assay (EMSA)] were examined. Serum levels of transaminases, TNF-α and interleukin-6 (IL-6) were substantially higher in the model group compared to controls. In the model group, significant increases in TNF-α and IL-6 mRNA expression, TUNEL‑positive cells, and caspase-3 activity in the liver tissue were noted. LXA4 improved liver pathology and significantly decreased the indicators of inflammatory response and apoptosis in a dose-dependent manner. High-dose LXA4 provided better protection than PDTC. LXA4 administration significantly decreased NF-κB expression in hepatocytes and Kupffer cells. These results indicated that LXA4 inhibited NF-κB activation, reduced the secretion of pro-inflammatory cytokines, and inhibited apoptosis of liver cells

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

    Science.gov (United States)

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

    2016-02-01

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

  7. 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

  8. 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

  9. Living related liver transplantation in an adult patient with hepatocellular adenoma and carcinoma 13 years after bone marrow transplantation for Fanconi anemia: a case report

    Science.gov (United States)

    Colle, Isabelle; Laureys, Geneviève; Raevens, Sarah; Libbrecht, Louis; Reyntjens, Koen; Geerts, Anja; Rogiers, Xavier; Troisi, Roberto; Hoehn, Holger; Schindler, Detlev; Hanenberg, Helmut; De Wilde, Vincent; Van Vlierberghe, Hans

    2013-01-01

    Fanconi anemia is an inherited bone marrow failure syndrome, characterised by failing DNA repair. Hematopoetic stem cell transplantation, known to be curative for the bone marrow failure, does neither prevent or cure other manifestations such as the development of malignancies. We describe a 26-year-old male patient with known Fanconi anemia and Marfan syndrome who in 1994 underwent a successful bone marrow transplantation of stem cells from his HLA-identical sister. In 2006, three hepatocellular carcinoma (HCC) lesions in the liver were detected and promptly resected. The resection specimen contained 3 lesions, all showing activation of the beta-catenin pathway: a well differentiated steatotic HCC with remnants of the underlying adenoma from which it arose, an adenoma with small foci of well differentiated HCC and a cholestatic adenoma. Known risk factors for developing HCC include Fanconi anemia itself and the use of androgens (oxymetholone) for a period of 3 years preceeding transplantation. Because of the increased risk of developing additional HCC’s, liver transplantation was proposed, taking into account that immunosuppression increases the risk of other malignancies. By using part of the liver of the HLA-identical sister, already acting as bone marrow donor 13 years before, immunosuppression could be avoided. A left lobe liver transplantation was performed without immediate complications for donor and acceptor on July 2, 2007. Nine months after liver transplantation the recipient developed an anastomotic biliary stricture that had to be dilated by percutaneous transhepatic cholangiography. Two months later however, the stenosis recurred, necessitating a surgical reanastomosis (hepaticojejunostomy). Five years after liver transplantation the patient is still doing well. This case report is twofold special being the first case reporting Fanconi anemia linked to Marfan syndrome and being the first reported case of Fanconi anemia who was treated for

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Changes in GM1 ganglioside content and localization in cholestatic rat liver

    Czech Academy of Sciences Publication Activity Database

    Jirkovská, M.; Majer, F.; Šmídová, J.; Stříteský, J.; Shaik, Gouse Mohiddin; Dráber, Petr; Vítek, L.; Mareček, Z.; Šmíd, F.

    2007-01-01

    Roč. 24, 4-5 (2007), s. 231-241. ISSN 0282-0080 R&D Projects: GA MZd NR8079 Institutional research plan: CEZ:AV0Z50520514 Keywords : gangliosides * hepatocytes * sinusoidal membrane Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.602, year: 2007

  15. 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...

  16. 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

  17. Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

    OpenAIRE

    Hyun-Seok Cho; Young Kwang Choo; Hong Jin Lee; hyeon-Soo Lee

    2012-01-01

    Carnitine (?#11112;ydroxy-?#15220;rimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramat...

  18. 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...

  19. 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

  20. The Intrahepatic Expression and Distribution of BTLA and its Ligand HVEM in patients with HBV-related acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    Xu Huan

    2012-10-01

    Full Text Available Abstract Objective It has been demonstrated that signals from the inhibitory receptor B and T lymphocyte attenuator (BTLA are involved in regulating the pathogenesis of infectious diseases. However, the expression and anatomical distribution of BTLA and its ligand, the herpes virus entry mediator (HVEM, have not yet been determined in cases of HBV-related acute-on-chronic liver failure (HBV-ACLF patients. Methods In this study, the expression of BTLA and HVEM in liver tissues from HBV-ACLF, chronic hepatitis B (CHB patients and healthy individuals was analyzed by immunohistochemistry. Results The results of this analysis demonstrated that both molecules were observed in the HBV-ACLF samples and that their expression was chiefly in the infiltrating inflammatory cells and the damaged bile ducts. However, they were absent in liver sections from CHB patients and healthy controls. Immunofluorescence double-staining indicated that BTLA was found on CK-18+ epithelial cells, CD31+ endothelial cells, CD68+ macrophages, CD56+ NK cells, CD16+ monocytes, CD3+ , CD8+ T cells, and Foxp3+ regulatory T cells (Treg. By contrast, HVEM expression was restricted to CK18+ epithelial cells and CD68+ macrophages. Moreover, the expression of several members of the B7 superfamily, including PD-L1, PD-L2, B7-H3 and B7-H4, was also detected in these liver tissues, and these proteins were co-expressed with HVEM. Interestingly, the expression of fibrinogen-like protein 2 (FGL2, a virus-induced procoagulant molecule, was also found in liver sections from HBV-ACLF, this molecule also co-expresses with BTLA and HVEM. Conclusions These results suggest that BTLA-HVEM signaling is likely to affect the pathogenesis of HBV-ACLF, a clear understanding of the functional roles of these proteins should further elucidate the disease process. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8080806838149123

  1. 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 

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

    Science.gov (United States)

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

    2016-01-01

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

  3. A case of amoxicillin-induced hepatocellular liver injury with bile-duct damage

    OpenAIRE

    Kim, Ju Seung; Jang, Young Rock; Lee, Ji Won; Kim, Jin Yong; Jung, Young Kul; Chung, Dong Hae; Kwon, Oh Sang; Kim, Yun Soo; Choi, Duck Joo; Kim, Ju Hyun

    2011-01-01

    Amoxicillin, an antibiotic that is widely prescribed for various infections, is associated with a very low rate of drug-induced liver injury; hepatitis and cholestasis are rare complications. Here we present a case of a 39-year-old woman who was diagnosed with abdominal actinomycosis and received amoxicillin treatment. The patient displayed hepatocellular and bile-duct injury, in addition to elevated levels of liver enzymes. The patient was diagnosed with amoxicillin-induced cholestatic hepat...

  4. Decline in HAV-associated fulminant hepatic failure and liver transplant in children in Argentina after the introduction of a universal hepatitis A vaccination program

    Directory of Open Access Journals (Sweden)

    Cervio G

    2011-09-01

    Full Text Available Guillermo Cervio1, Julio Trentadue2, Daniel D'Agostino3, Carlos Luque4, Mariano Giorgi5, Judith Armoni6, Roberto Debbag6 1Unidad de Transplante Hepatico, Hospital Prof Dr Juan P Garrahan, 2Unidad de Terapia Intensiva, Hospital Universitario Fundación Favaloro, 3Unidad de Gastroenterología, Hospital Italiano De Buenos Aires, 4Unidad de Transplante Hepatico, Hospital Universitario Austral, 5Departamento de Farmacologia, Escuela de Medicina de la Universidad Austral, 6Sanofi Pasteur, Buenos Aires, Argentina Introduction: Hepatitis A virus (HAV infection is a vaccine-preventable disease. The most severe complication in children is fulminant hepatic failure (FHF, estimated to occur in 0.4% of cases; patients with FHF often require a liver transplant (LT. Following another outbreak of HAV infection in Argentina during 2003–2004, a one-dose HAV universal immunization (UI program was started in 2005, resulting in a reduction in the incidence of HAV infection. We have investigated the impact of HAV UI on the trends in the occurrence of FHF and LT in children. Methods: All pediatric cases of FHF admitted to four pediatric centers in Buenos Aires during March 1993–July 2005 were retrospectively reviewed, and data of cases during August 2005–December 2008 were collected. Information about demography, HAV infections and vaccination status, diagnostic data for FHF using the Pediatric Acute Liver Failure criteria, clinical laboratory results, encephalopathy, the severity of liver disease using the Pediatric End Stage Liver Disease score, assessment of patients on the LT waiting list using King's College Criteria for LT, treatment given for FHF (pre- and post-transplant, and clinical outcome were collected using a case report form. The frequency and outcomes of HAV-associated FHF and LT cases before and after UI were analyzed. Results: During the pre-immunization period, March 1993–July 2005, 54.6% (N = 165 of FHF cases were caused by HAV; HAV

  5. 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).

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

    Directory of Open Access Journals (Sweden)

    Hyun-Seok Cho

    2012-02-01

    Full Text Available Carnitine (?#11112;ydroxy-?#15220;rimethylaminobutyric acid is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramatically to oral carnitine supplementation.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Histological changes and impairment of liver mitochondrial bioenergetics after long-term treatment with α-naphthyl-isothiocyanate (ANIT)

    International Nuclear Information System (INIS)

    This study was designed to evaluate the effects of long-term treatment with α-naphthyl-isothiocyanate (ANIT) on liver histology and at the mitochondrial bioenergetic level. Since, ANIT has been used as a cholestatic agent and it has been pointed out that an impairment of mitochondrial function is a cause of hepatocyte dysfunction leading to cholestatic liver injury, serum markers of liver injury were measured and liver sections were analyzed in ANIT-treated rats (i.p. 80 mg/kg/weekx16 weeks). Mitochondrial parameters such as transmembrane potential, respiration, calcium capacity, alterations in permeability transition susceptibility and ATPase activity were monitored. Histologically, the most important features were the marked ductular proliferation, proliferation of mast cells and the presence of iron deposits in ANIT-treated liver. Mitochondria isolated from ANIT-treated rats showed no alterations in state 4 respiration, respiratory control ratio and ADP/O ratio, while state 3 respiration was significantly decreased. No changes were observed on transmembrane potential, but the repolarization rate was decreased in treated rats. Consistently with these data, there was a significant decrease in the ATPase activity of treated mitochondria. Associated with these parameters, mitochondria from treated animals exhibited increased susceptibility to mitochondrial permeability transition pore opening (lower calcium capacity). Since, human cholestatic liver disease progress slowly overtime, these data provide further insight into the role of mitochondrial dysfunction in the process

  19. 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...

  20. 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

  1. 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

  2. Resveratrol and liver: A systematic review

    Directory of Open Access Journals (Sweden)

    Forouzan Faghihzadeh

    2015-01-01

    Full Text Available Background: Recent studies demonstrated that resveratrol has many therapeutic effects on liver disorders. Resveratrol significantly increased survival after liver transplantation, decreased fat deposition, necrosis, and apoptosis which induced by ischemia in Wistar rats. It provided liver protection against chemical, cholestatic, and alcohol injury. Resveratrol can improve glucose metabolism and lipid profile and decrease liver fibrosis and steatosis. Furthermore, it was able to alter hepatic cell fatty acid composition. According to extension of liver disease around the world and necessity of finding new threat, this review critically examines the current preclinical in vitro and in vivo studies on the preventive and therapeutic effects of resveratrol in liver disorders. Materials and Methods: A search in PubMed, Google Scholar, and Scopus was undertaken to identify relevant literature using search terms, including "liver," "hepatic," and "Resveratrol." Both in vivo and in vitro studies were included. No time limiting considered for this search. Results: A total of 76 articles were eligible for this review. In these articles, resveratrol shows antioxidative properties in different models of hepatitis resulting in reducing of hepatic fibrosis. Conclusion: Resveratrol could reduce hepatic steatosis through modulating the insulin resistance and lipid profile in animals. These high quality preclinical studies propose the potential therapeutic implication of resveratrol in liver disorders especially those with hepatic steatosis. Resveratrol can play a pivotal role in prevention and treatment of liver disorders by reducing hepatic fibrosis.

  3. Hemostatic abnormalities in liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Kendal YALÇIN

    2009-06-01

    Full Text Available In this study, 44 patients with liver cirrhosis were investigated for hemostatic parameters. Patients with spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatorenal syndrome and cholestatic liver diseases were excluded. Patients were classified by Child-Pugh criterion and according to this 4 patients were in Class A, 20 in Class B and 20 in C. Regarding to these results, it was aimed to investigate the haematological disturbances in liver cirrhotic patients.In the result there was a correlation between activated partial thromboplastin time, serum iron, ferritin, transferrin, haptoglobin and Child-Pugh classification. Besides there was no correlation between prothrombin time, factor 8 and 9, protein C and S, anti-thrombin 3, fibrinogen, fibrin degradation products, serum iron binding capacity, hemoglobin, leukocyte, mean corpuscular volume and Child-Pugh classification.There were significant difference, in terms of AST, ferritin, haptoglobulin, sex and presence of ascites between groups (p0.05. In the summary, we have found correlation between hemostatic abnormalities and disease activity and clinical prognosis in patients with liver cirrhosis which is important in the management of these patients. This is also important for identification of liver transplant candidiates earlier.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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 to...... 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 are...

  9. 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 ...

  10. 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.

  11. Biochemical Characterization of P4-ATPase Mutations Associated with Intrahepatic Cholestatic Disease

    DEFF Research Database (Denmark)

    Gantzel, Rasmus; Vestergaard, Anna Lindeløv; Mikkelsen, Stine; Molday, Robert S.; Andersen, Jens Peter

    The cholestatic disorders progressive familial intrahepatic cholestasis type 1 (PFIC1, also referred to as Byler’s disease) and benign recurrent intrahepatic cholestasis type 1 (BRIC1) are caused by mutation of the P4-ATPase ATP8B1. The substrate of ATP8B1 is very likely to be phosphatidylserine...... families have been investigated, and more than 50 distinct disease mutations have been identified, with roughly half being missense mutations. In this project we try to answer the question whether PFIC1 mutations are generally more disturbing than BRIC1 mutations with respect to expression, structural...... stability and function. We investigate the mutations in our well functioning system of ATP8A2, being expressed in mammalian HEK293T cells, affinity-purified, and reconstituted in lipid vesicles. Well-known mutations from both groups of patients have been selected for study. I91P in ATP8A2 (L127P in ATP8B1...

  12. 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%)

  13. 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)...

  14. Bile acids affect liver mitochondrial bioenergetics: possible relevance for cholestasis therapy

    OpenAIRE

    Rolo, Anabela P.; Oliveira, Paulo J.; Moreno, António J. M.; Palmeira, Carlos M.

    2000-01-01

    It has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed to test if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were analyzed by monitoring changes in membrane potential and mitochondrial respiration, as well as alterations in H+ membrane permeability and mitochondrial permeability transition pore induction. Increasi...

  15. 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...... from 1992 to 2005. MATERIAL AND METHODS: A retrospective study of the journals of 440 patients, who underwent 506 LTXs between 1992 and 2005, showed that 14 patients underwent LTX for PLD. All patients had normal liver function. Three were receiving haemodialysis and thus underwent combined liver...

  16. 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

  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. PMID:22309749

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. Biochemical Characterization of P4-ATPase Mutations Associated with Intrahepatic Cholestatic Disease

    DEFF Research Database (Denmark)

    Gantzel, Rasmus; Vestergaard, Anna Lindeløv; Mikkelsen, Stine; S. Molday, Robert; Andersen, Jens Peter

    . Mutations I91P in ATP8A2 (L127P in ATP8B1) and L308F (I344F) are located in TM1 and TM3, respectively, and E897K (E891K) is located in the exoplasmic loop between TM5 and TM6. Our experiments are focusing on the ATPase activity, rate of phosphorylation and dephosphorylation, and affinities for vanadate and......The cholestatic disorders progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis type 1 (BRIC1) are caused by mutation of the P4-ATPase ATP8B1 that flips phospholipid from the exoplasmic leaflet to the cytoplasmic leaflet of canalicular membranes....... It is hypothesized that PFIC1 mutations are generally more disturbing than BRIC1 mutations with respect to expression, structural stability and/or function. Although recent data have indicated that the specific phospholipid substrate of ATP8B1 is phosphatidylcholine (PC) [1] whereas ATP8A2 flips...

  3. 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

  4. 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

  5. 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

  6. 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....

  7. Transarterial Therapy for Colorectal Liver Metastases.

    Science.gov (United States)

    Bhutiani, Neal; Martin, Robert C G

    2016-04-01

    Until recently, hepatic arterial therapies (HAT) had been used for colorectal liver metastases after failure of first-, second-, and third-line chemotherapies. HAT has gained greater acceptance in patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The current data demonstrate that HAT is a safe and effective option for preoperative downsizing, optimizing the time to surgery, limiting non-tumor-bearing liver toxicity, and improving overall survival after surgery in patients with colorectal liver-only metastases. The aim of this review is to present the current data for HAT in liver-only and liver-dominant colorectal liver metastases. PMID:27017870

  8. 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

  9. 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

  10. 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

  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. 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.

  13. 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

  14. 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

  15. Successful treatment for sorafenib-induced liver dysfunction: a report of case with liver biopsy.

    Science.gov (United States)

    Kuroda, Daisuke; Hayashi, Hiromitsu; Nitta, Hidetoshi; Imai, Katsunori; Abe, Shinya; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Beppu, Toru; Baba, Hideo

    2016-12-01

    Sorafenib is an oral multikinase inhibitor with anti-proliferative and anti-angiogenic effects and is used worldwide for the treatment of advanced or metastatic hepatocellular carcinoma (HCC). While the significant survival benefit of sorafenib in patients with advanced HCC was demonstrated, various treatment-related adverse events might happen. Of them, the incidence of drug-related severe liver dysfunction rarely occurs (liver dysfunction (T-Bil 28.6 mg/dL, AST 1611 IU/L, ALT 1098 IU/L) 2 months later even without either intrahepatic viable HCC or hepatitis B virus (HBV) reactivation. Then, the liver dysfunction was improved following aggressive treatment using hyperbaric oxygen. A liver biopsy demonstrated cholestasis, degeneration, and necrosis in hepatocytes with lymphocyte infiltration. Thus, sorafenib rarely can induce liver dysfunction characterized by cholestatic and hepatocellular injury types, and it could be a fatal event. Clinicians should pay attention to any increase in the liver enzymes in these patients. PMID:26943680

  16. Ovarian stimulation and liver dysfunction: Is a clinical relationship possible? A case of hepatic failure after repeated cycles of ovarian stimulation

    OpenAIRE

    Giugliano, Emilio; Cagnazzo, Elisa; Pansini, Giancarlo; Vesce, Fortunato; Marci, Roberto

    2013-01-01

    Liver damage induced by ovarian stimulation has been demonstrated in some cases reported in the literature. However, there has never been a fruitful debate on this topic. The present manuscript tried to fill this gap. We reported a case of a 35-year-old nulliparous woman admitted to our obstetric emergency room for severe pre-eclampsia. She had been subjected to four cycles of controlled ovarian stimulation for intrauterine insemination. At 32 weeks of gestation, she developed severe pre-ecla...

  17. 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

  18. 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.

  19. 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...

  20. Liver metastases

    Science.gov (United States)

    Metastases to the liver; Metastatic liver cancer; Liver cancer - metastatic ... Almost any cancer can spread to the liver. Cancers that can ... Lung cancer Melanoma Pancreatic cancer Stomach cancer The risk ...

  1. 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...

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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...

  7. Liver Hemangioma Might Lead to overestimation of Liver Fibrosis by Fibroscan; A Missed Issue in Two Cases

    OpenAIRE

    Seyed Hossein Aalaei-Andabili; Leila Mehrnoush; Shima Salimi; Mustafa Shafiei; Seyed Moayed Alavian

    2012-01-01

    Background: The assessment of liver fibrosis is an important way for prediction of liver disease progression and patient’s prognosis. Liver stiffness measurement (LSM) is strongly associated with stage of liver diseases. Overestimation of liver fibrosis in heart failure has been reported. We would like to introduce a new leading cause of liver fibrosis overestimation by presentation of two cases.Case Presentation: One case with right lobe hemangioma has an overestimation of liver fibrosis. Th...

  8. 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.).

  9. Liver transplantion in a patient with rapid onset parkinsonism-dementia complex induced by manganism secondary to liver failure Transplante hepático em um paciente com complexo parkinsonismo-demência rapidamente progressivo induzido por manganismo devido a insuficiência hepática

    Directory of Open Access Journals (Sweden)

    Giorgio Fabiani

    2007-09-01

    Full Text Available Bilateral and symmetric globus-pallidus hyperintensities are observed on T1-weighted MRI in most of the patients with chronic liver failure, due to manganese accumulation. We report a 53-year-old man, with rapid onset parkinsonism-dementia complex associated with accumulation of manganese in the brain, secondary to liver failure. A brain MRI was performed and a high signal on T1-weighted images was seen on globus-pallidus, as well as on T2-weighted images on the hemispheric white-matter. He was referred to a liver-transplantation. The patient passed away on the seventh postoperative day. Our findings support the concept of the toxic effects of manganese on the globus-pallidus. The treatment of this form of parkinsonism is controversial and liver-transplantation should not be considered as first line treatment but as an alternative one.Hiperintesidades simétricas e bilaterais dos gânglios da base são observadas em imagens de ressonância magnética encefálica (RM ponderadas em T1 na maioria dos pacientes com insuficiência hepática crônica devidas ao acúmulo de manganês. Nós relatamos o caso de um homem, com 53 anos de idade, com um complexo parkinsonismo-demência rapidamente progressivo associado com o acúmulo de manganês no cérebro, secundariamente a insuficiência hepática. Uma RM encefálica foi realizada e foram observadas imagens hiperintensas/hipersinal nas imagens ponderadas em T1 no globo pálido e, também, na substância branca dos hemisférios cerebrais ponderadas em T2. Devido à falta de resposta ao tratamento clinico optamos pelo transplante hepático. O paciente faleceu no 7º dia de PO. Nossos achados corroboram o conceito dos efeitos tóxicos do manganês nos gânglios da base/globo pálido. O tratamento desta forma de parkinsonismo é controverso e o transplante hepático não deverá ser considerada uma opção terapêutica de primeira linha, porém como um tratamento alternativo considerando-se os riscos

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Liver Panel

    Science.gov (United States)

    ... liver damage. Alpha-feto protein (AFP) – associated with regeneration or proliferation of liver cell Autoimmune antibodies (e. ... the body – such as in the skeletal muscles, pancreas, or heart. It may also indicate early liver ...

  15. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... the biopsy needle to be inserted into the liver. This is often done by using ultrasound. The ... the chance of damage to the lung or liver. The needle is removed quickly. Pressure will be ...

  16. Liver Manipulation Causes Hepatocyte Injury and Precedes Systemic Inflammation in Patients Undergoing Liver Resection

    OpenAIRE

    van de Poll, Marcel C. G.; Derikx, Joep P. M.; Buurman, Wim A.; Peters, Wilbert H. M.; Hennie M J Roelofs; Stephen J Wigmore; Dejong, Cornelis H C

    2007-01-01

    BACKGROUND:Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injury in patients undergoing liver resection.METHODS:Markers of hepatocyte injury (AST, GSTalpha, and L-FABP) and inflammation (IL-6) were measured in plasma of patients undergoing liver resection with ...

  17. 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

  18. Nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

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

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage...... that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy...... the potential role of exercise in treating and preventing NAFLD. Regular exercise can reverse insulin resistance, suppress low-grade systemic inflammation, and attenuate inflammatory markers associated with NAFLD. Thus, exercise has the potential to become an effective treatment and prevention modality...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements...... of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively.......025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P = 0...

  20. 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...

  1. 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....

  2. 130例酒精性肝衰竭患者临床特点与预后分析%Clinical features and prognosis in 130 patients with alcoholic liver failure

    Institute of Scientific and Technical Information of China (English)

    郝书理; 李保森; 孙颖; 常彬霞; 滕光菊; 赵军; 张伟; 邹正升

    2014-01-01

    目的:分析酒精性肝衰竭患者临床特点及预后影响因素。方法回顾性分析2004年1月至2013年5月住解放军第302医院的资料完整的130例酒精性肝衰竭患者的临床特点及预后影响因素。结果酒精性肝衰竭患者的诱发因素为感染(52.3%)、短期过度饮酒(8.5%)、疲劳(3.8%)、情绪激动(0.8%),另有34.6%原因不明;酒精性肝衰竭患者治愈或好转率为41.5%,无效率为42.3%,死亡率为16.1%,其中死亡前4位的原因分别为肝性脑病和脑水肿或脑疝(33.3%)、感染性休克(28.6%)、失血性休克(23.8%)和肝肾综合征(9.5%);无效或死亡患者脑水肿、脑疝和肝肾综合征的发生率分别为14%、7%和36%,显著高于治愈或好转患者[分别为1%、1%和6%,P 均<0.01)];无效或死亡患者血红蛋白水平[(85.0±28.3) g/L]显著低于治愈或好转组[(95.2±27.6)g/L,P<0.05)];无效或死亡患者 Maddrey 判别函数、MELD 评分和 Glasgow 评分分别为(94.56±63.17)、(25.52±8.29)和(9.76±1.04),均显著高于治愈或好转患者[分别为(68.24±24.61)、(19.03±10.13)和(9.30±1.11),P 均<0.01)];凝血酶原时间(r=-0.19, P=0.03)、国际标准化比值(r=-0.21,P=0.02)、尿素氮(r=-0.28,P=0.01)和肌酐(r=-0.28,P=0.01)水平与预后均呈负相关关系(P<0.05或 P<0.01),患者出现脑水肿(r=-0.26,P=0.01)、脑疝(r=-0.26,P=0.01)和肝肾综合征(r=-0.38, P=0.01)均与预后呈负相关(P<0.01)。结论酒精性肝衰竭的常见诱发因素为感染和短期过量饮酒,凝血功能、肾功能和脑功能障碍是预后不良的重要预测因素。%Objective To investigate the clinical features and prognosis of patients with alcoholic liver fail-ure. Methods The clinical features and prognosis in 130 patients with alcoholic liver failure who had admitted to Beijing 302nd Hospital of PLA

  3. BIOCONJUGATION OF OLIGONUCLEOTIDES FOR TREATING LIVER FIBROSIS

    OpenAIRE

    Ye, Zhaoyang; Hajj Houssein, Houssam S.; Mahato, Ram I.

    2007-01-01

    Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductul...

  4. Multivariate analysis of hepatic encephalopathy occurrence in patients with liver failure%乙型肝炎肝衰竭患者发生肝性脑病的多因素分析

    Institute of Scientific and Technical Information of China (English)

    潘晨; 许利军; 周锐; 周文; 黄建荣

    2012-01-01

    Objective To investigate the risk factors of hepatic encephalopathy in patients with liver failure.Methods Nine-hundred-and-seventy-six hepatitis B virus (HBV) patients with liver failure were retrospectively analzyed.Clinical data (sex,age,family history,liver cirrhosis,diabetes,celiac infection,pulmonary infection,liver kidney syndrome,upper gastrointestinal hemorrhage) and laboratory findings (albumin,globulin,total bilirubin,direct bilirubin,alanine aminotransferase,aspartate aminotransferase (AST),gamma-glutamyl transferase,alkaline phosphatase,cholesterol,cholinesterase,K+,Na+,creatinine,international normalized ratio (INR),alpha-fetoprotein,HBV DNA,white blood cell,hemoglobin,platelet)were collected and used to screen the risk factors for hepatic encephalopathy by univariate and multiple regress analyses.Results Multiple logistic regression analysis indicated that upper gastrointestinal hemorrhage [risk (R) =0.993,relative hazard (RH) =2.699,95% confidence interval (CI):1.567-4.651],pulmonary infection [R=1.043,RH=2.839,95%CI:1.680-4.797],INR [R =0.257,RH=1.293,95%CI:1.220-1.370],AST level [R =0.001,RH=1.001,95%CI:1.000-1.001],and cirrhosis [R =0.569,RH=1.815,95%CI 1.112-2.965]were closely correlated with hepatic encephalopathy.Conclusion HBV-infected patients presenting with upper gastrointestinal haemorrhage,pulmonary infection,prolonged INR,elevated AST,or liver cirrhosis should be carefully monitored for indications of hepatic encephalopathy to initiate timely therapeutic interventions.%目的 探讨乙型肝炎肝衰竭患者发生肝性脑病的危险因素,以便于临床早期干预,减少肝性脑病的发生.方法 收集976例乙型肝炎肝衰竭患者的基础临床资料(性别、年龄、家族史、肝硬化、糖尿病、腹腔感染、肺部感染、肝肾综合征、上消化道出血)和临床检测指标[白蛋白、球蛋白、总胆红素、直接胆红素、ALT、AST、Y-谷氨酰转移酶、碱性磷酸酶、胆固醇、

  5. Liver manipulation causes hepatocyte injury and precedes systemic inflammation in patients undergoing liver resection.

    NARCIS (Netherlands)

    Poll, M.C. van de; Derikx, J.P.M.; Buurman, W.A.; Peters, W.H.M.; Roelofs, H.M.J.; Wigmore, S.J.; Dejong, C.H.

    2007-01-01

    BACKGROUND: Liver failure following liver surgery is caused by an insufficient functioning remnant cell mass. This can be due to insufficient liver volume and can be aggravated by additional cell death during or after surgery. The aim of this study was to elucidate the causes of hepatocellular injur

  6. Challenging hepatitis C-infected liver transplant patients

    Directory of Open Access Journals (Sweden)

    Oliver M

    2016-01-01

    Full Text Available Madeleine Oliver,1 Christopher Chiodo Ortiz,2 Jorge Ortiz31University of Toledo College of Medicine, Toledo, OH, 2Bucknell University, Lewisburg, PA, 3Department of Transplant Surgery, University of Toledo Medical Center, Toledo, OH, USA Abstract: Caring for liver transplant patients suffering from chronic hepatitis C virus (HCV infection is a challenging task for transplant surgeons and primary physicians alike. HCV is the leading cause of liver transplantation in the USA and comes with a myriad of complications that increase morbidity and mortality. This review focuses on patient follow-up, spanning from before the liver transplant occurs to the patient's long-term health. Pretransplant, both donor and recipient variables, must be carefully chosen to ensure optimal surgical success. Risk factors must be identified and HCV viral load must be reduced to a minimum. In addition to standard transplant complications, HCV patients suffer from additional problems, such as fibrosing cholestatic hepatitis and widespread viremia. Physicians must focus on the balance of immunosuppressive and antiviral medications, while considering possible side effects from these potent drugs. Over the years following surgery, physicians must identify any signs of failing liver health, as HCV-positive patients have an increased risk for cirrhosis and certain life-threatening malignancies. Keywords: liver transplant, hepatitis C virus, postoperative, cirrhosis, donor and recipient variables, viremia

  7. Respiratory Failure

    Science.gov (United States)

    Respiratory failure happens when not enough oxygen passes from your lungs into your blood. Your body's organs, such ... brain, need oxygen-rich blood to work well. Respiratory failure also can happen if your lungs can't ...

  8. Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis

    Directory of Open Access Journals (Sweden)

    Güldeniz Karadeniz

    2008-01-01

    Full Text Available OBJECTIVE: The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION: There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA and superoxide-dismutase (SOD in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n = 8 and sham-operated rats (n = 8. RESULTS: Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION: Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

  9. Efficacy of extracorporeal albumin dialysis for acute kidney injury due to cholestatic jaundice nephrotoxicity.

    Science.gov (United States)

    Sens, Florence; Bacchetta, Justine; Rabeyrin, Maud; Juillard, Laurent

    2016-01-01

    We report a case of a 37-year-old man with Maturity Onset Diabetes of the Youth (MODY) type 5, admitted for an episode of cholestasis and a simultaneous acute kidney injury (AKI). Chronic liver disease was due to a mutation in the transcription factor 2 (TCF2) gene, thus highlighting the need for a close liver follow-up in these patients. AKI was attributed to a cholemic nephropathy based on the following rationale: (1) alternative diagnoses were actively ruled out; (2) the onset of AKI coincided with the onset of severe hyperbilirubinaemia; (3) renal pathology showed large bile tubular casts and a marked tubular necrosis and (4) creatinine serum dramatically decreased when bilirubin levels improved after the first sessions of extracorporeal albumin dialysis (ECAD), thus suggesting its role in renal recovery. Even though cholestasis can precipitate renal injury, the diagnosis of cholemic nephropathy could require a renal biopsy at times. Future studies should confirm the benefits of ECAD in cholemic nephropathy. PMID:27389722

  10. 酒精性肝衰竭患者能量代谢与临床特点%Energy metabolism and clinical features of patients with sub-acute-on-chronic alcoholic liver failure

    Institute of Scientific and Technical Information of China (English)

    王金环; 李娟; 冯岩梅; 张汾燕; 于红卫; 孟庆华

    2011-01-01

    Objective To investigate the energy metabolism and clinical features in patients with sub-acute-on-chronic alcoholic liver failure. Methods 76 patients with sub-acute-on-chronic liver failure were selected and divided into 2 groups: study group with 28 alcoholic liver failure patients (ASCLF) and control group with 48 hepatitis B patients (HSCLF). Then they were further divided into early and middle stages by disease progression, and recovery and death subgroups by prognosis. Resting energy expenditure (REE), respiratory quotient (RQ) and oxidation rate of carbohydrate (CHO), fat (FAT), protein (PRO) were evaluated by indirect calori-metry (IC) and 24-hour urea nitrogen. Results RQ of ASCLF was significantly lower than that of HSCLF [(0.80±0.06) vs. (0.84±0.05), P = 0.007). In middle stage or death group, RQ value of ASCLF was still significantly lower than HSCLF [(0.78±0.05)vs. (0.83±0.05); (0.75±0.04) vs. (0.82±0.05); both P = 0.001)]. RQ value in middle stage of ASCLF was significantly lower than in early stage [(0.78± 0.05) vs.(0.83±0.05), P = 0.007] and in death group it was significantly lower than in recovery group[(0.75±0.04) vs. (0.83± 0.04), P= 0.000)]; FAT oxidation rate in death group was significantly higher than in recovery group [(54.55±11.44)% vs. (40.29±14.53)%, P = 0.011], while CHO oxidation rate was significantly lower than in recovery group [(25.82± 13.04)% vs. (38.41±14.69)%, P= 0.029]. Conclusion REE in patients with ASCLF and HSCLF are similar, where FAT is used as the primary energy supply and CHO metabolism is abnormal. The trends of dynamic REE changes along with the course ofdisease are also consistent in two groups. RQ value in patients with ASCLF is lower. RQ value decreases more sharply in the serious phase of disease or death group, indicating that RQ is tightly related with prognosis.%目的 探讨酒精性慢加亚急性肝衰竭患者(酒精肝衰竭组)的能量代谢与临床特点.方法 选择28例酒

  11. 硫化氢对急性肝衰竭转运蛋白Bsep和Mdr2的调节%Regulation of hydrogen sulfide on transporter protein Bsep and Mdr2 in acute liver failure

    Institute of Scientific and Technical Information of China (English)

    王新国; 王炳元; 黄谦; 张波; 华忠

    2015-01-01

    目的 观察硫化氢对肝衰竭胆管侧膜转运蛋白Bsep、Mdr2的影响.方法 雄性SD大鼠24只,随机分为硫代乙酰胺(TAA)组、正常对照组、TAA+硫氢化钠组和TAA+炔丙基甘氨酸组,每组6只.用6%的TAA对TAA组及TAA+硫氢化钠组和TAA+炔丙基甘氨酸组动物腹腔注射造成肝衰竭;用硫氢化钠0.15 mmol/kg和炔丙基甘氨酸30 mg/kg于TAA注射之前1h腹腔注射,48 h处死动物,测定血清中的硫化氢、肝功能以及肝病理变化.利用免疫印迹和SP免疫组化方法检测肝组织胆管侧膜蛋白Bsep、Mdr2表达情况.结果 TAA导致肝脏衰竭,血清转氨酶明显升高>10倍[ALT (524.0±32.0) U/L比(28.3±8.4)U/L],硫氢化钠使血清转氨酶升高加剧[ALT(861.9±55.1) U/L],而炔丙基甘氨酸使转氨酶下降[ALT(59.5 ±10.2)U/L].TAA引起胆红素和胆汁酸明显升高,硫氢酸钠可使胆汁酸水平进一步升高和胆红素水平下降;反之PPG导致胆汁酸胆红素均明显下降.TAA组血清硫化氢明显增加,硫氢化钠使之升高更为显著;炔丙基甘氨酸则使硫化氢含量明显下降.TAA引起肝细胞高度水肿,大片坏死,炎症细胞浸润;硫氢酸钠则使肝细胞坏死面积增大,细胞变形严重,炎症细胞浸润加重;而炔丙基甘氨酸则使肝细胞坏死减轻.肝衰竭时Bsep、Mdr2明显减少,硫氢酸钠使之进一步减少,而炔丙基甘氨酸则使减少程度缓解.结论 硫化氢促进肝衰竭时胆管侧膜蛋白转运体Bsep、Mdr2丢失并引起高胆汁酸血症.%Objective To observe the effect of hydrogen sulfide on Bsep and Mdr2 in acute liver failure induced by thioacetamide.Methods Twenty-four male SD rats were randomly divided into thioacetamide (TAA) induced model group (n =6), control group (n =6), TAA + sodium hydrosulfide group (n =6), and TAA + propargylglycine group (n =6).TAA was given to enterocoelia at the dose of 600 mg/kg for the model group, sodium hydrosulfide group and propargylglycine group rats

  12. Progress in bioreactors of bioartiifcial livers

    Institute of Scientific and Technical Information of China (English)

    Cheng-Bo Yu; Xiao-Ping Pan; Lan-Juan Li

    2009-01-01

    BACKGROUND: Bioartiifcial liver support systems are becoming an effective therapy for hepatic failure. Bioreactors, as key devices in these systems, can provide a favorable growth and metabolic environment, mass exchange, and immunological isolation as a platform. Currently, stagnancy in bioreactor research is the main factor restricting the development of bioartiifcial liver support systems. DATA SOURCES: A PubMed database search of English-language literature was performed to identify relevant articles using the keywords "bioreactor", "bioartiifcial liver", "hepatocyte", and "liver failure". More than 40 articles related to the bioreactors of bioartiifcial livers were reviewed. RESULTS: Some progress has been made in the improvement of structures, functions, and modiifed macromolecular materials related to bioreactors in recent years. The current data on the improvement of bioreactor conifgurations for bioartiifcial livers or on the potential of the use of certain scaffold materials in bioreactors, combined with the clinical efifcacy and safety evaluation of cultured hepatocytesin vitro, indicate that the AMC (Academic Medical Center) BAL bioreactor and MELS (modular extracorporeal liver support) BAL bioreactor system can partly replace the synthetic and metabolic functions of the liver in phaseⅠ clinical studies. In addition, it has been indicated that the microlfuidic PDMS (polydimethylsiloxane) bioreactor, or SlideBioreactor, and the microfabricated grooved bioreactor are appropriate for hepatocyte culture, which is also promising for bioartiifcial livers. Similarly, modiifed scaffolds can promote the adhesion, growth, and function of hepatocytes, and provide reliable materials for bioreactors.CONCLUSIONS: Bioreactors, as key devices in bioartiifcial livers, play an important role in the therapy for liver failure both now and in the future. Bioreactor conifgurations are indispensable for the development of bioartiifcial livers used for liver

  13. Liver biopsy

    Science.gov (United States)

    Biopsy - liver; Percutaneous biopsy ... prevent pain or to calm you (sedative). The biopsy may be done through the abdominal wall: You ... provider will find the correct spot for the biopsy needle to be inserted into the liver. This ...

  14. Liver Diseases

    Science.gov (United States)

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  15. Naproxen-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    Sharif Ali; Jason D Pimentel; Chan Ma

    2011-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury. METHODS: We treated a 30-year-old woman with jaundice and intractablepruritusthatdevelopedshortlyaftertakingnaproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature. RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal. CONCLUSIONS:  Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.

  16. Surgical complications accompanying liver transplantation in Estonia.

    Science.gov (United States)

    Väli, T; Tein, A; Tikk, T; Sillakivi, T

    2010-12-01

    The purpose of this study was to evaluate surgical complications accompanying the introduction of orthotopic liver transplantation (OLT) in Estonia. Between 1999 and 2009, we performed the first 12 liver transplantations. Eight patients were males and four were females of age range 12 to 67 years. Their diagnoses were cholestatic disease (n = 5); tumor (n = 3); hepatitis C virus cirrhosis (n = 2); Budd-Chiari syndrome (n = 1); and cystic fibrosis (n = 1). Technical complications occurred in 7/12 patients. The early vascular complications in two patients were a suprahepatic vena cava lesion occurring at liver extraction, which resulted in uncontrolled suprahepatic bleeding after liver perfusion; the recipient died during transplantation. The other case displayed a right intrahepatic portal venous thrombosis, which was treated successfully with thrombolysis and anticoagulant therapy. Early biliary complications of biliary leaks occurred in three patients: two had undergone duct-to-duct reconstructions, which were treated by endoscopic retrograde cholangiography that successfully managed the anastomotic and recipient cystic duct leaks with a papillotomy and stenting. In one patient with a duct-to-jejunum anastomosis, a bile leak stopped at 3 weeks but he needed surgical therapy 2 years later due to an anastomotic stricture. Severe decubitus occurred in the lumbosacral region of the subjects with operating times of 14 hours. They required necretectomy and plastic surgery. One of them with postoperative intra-abdominal hypertension also displayed wound eventration requiring reoperations. The rate of hepatic (5/12) and extrahepatic (3/12) surgical complications, as well as of 1-year survival (9/12), in our period of implementation of OLT were satisfactory to continue OLT development in Estonia. PMID:21168717

  17. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    OpenAIRE

    Stefano Gitto; Erica Villa

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent signifi...

  18. Celiac axis stenosis and lethal liver ischemia after pancreaticoduodenectomy.

    Science.gov (United States)

    Lipska, Ludmila; Visokai, Vladimir; Levy, Miroslav; Koznar, Boris; Zaruba, Pavel

    2009-01-01

    Celiac axis stenosis can lead to a fatal hepatic ischemia after pancreaticoduodenectomy unless a simultaneous revascularisation of the celiac circulation is performed. In the present study are reported three cases of celiac axis stenosis, all of which had histologically confirmed periampullary cancer. Case 1: a 50-year-old male with a history of myocardial infarction and liver steatosis; visceral arteriography prior to the surgery demonstrated a celiac axis stenosis. Whipple operation was performed. After removing the specimen, no signs of liver ischemia were found (liver was cholestatic) and pulsation of the hepatic artery was strong. The patient died on the second postoperative day after an abrupt irreversible cardiac arrest. Autopsy proved acute severe hepatic ischemia. Case 2: a 64-year-old female. Preoperative visceral angiography showed significant celiac axis stenosis. As a first step of surgery the root of the celiac trunk was exposed, a fibrotic ring around it was divided. Standard D1 pylorus preserving pancreaticoduodenectomy was performed. Case 3: a 58-year-old female without preoperative angiography, indicated for surgery. After an occlusion test of the gastroduodenal artery the liver became ischemic. Division of the fibrotic ring around celiac axis was performed together with a standard D1 pylorus preserving pancreaticoduodenectomy. No postoperative complications were reported in both case 2 and 3. PMID:19760970

  19. Kidney Failure

    Science.gov (United States)

    ... Health Information > Health Communication Programs > National Kidney Disease Education Program > Learn About Kidney Disease > Living With Kidney Disease > Kidney Failure | Share External Link Disclaimer Living With Kidney Disease ...

  20. Interleukin-6 Mediates Angiotensinogen Gene Expression during Liver Regeneration

    OpenAIRE

    Hong-Shiee Lai; Wen-Hsi Lin; Shuo-Lun Lai; Hao-Yu Lin; Wen-Ming Hsu; Chia-Hung Chou; Po-Huang Lee

    2013-01-01

    BACKGROUND: Angiotensinogen is the precursor of angiotensin II, which is associated with ischemia-reperfusion injury. Angiotensin II reduces liver regeneration after hepatectomy and causes dysfunction and failure of reduced-size liver transplants. However, the regulation of angiotensinogen during liver regeneration is still unclear. AIMS: To investigate the regulation of angiotensinogen during liver regeneration for preventing angiotensin II-related ischemia-reperfusion injury during liver re...

  1. Liver resections for liver transplantations

    OpenAIRE

    2010-01-01

    Split-Liver and living-related donor liver transplantation are the newest and both technically and ethically most challenging developments in liver transplantation and have contributed to a reduction in donor shortage. We report the technical aspects of surgical procedures performed to achieve a partial graft from a cadaveric and a live donor.

  2. Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory

    OpenAIRE

    Fiegel, Henning C; Kaufmann, Peter M; Bruns, Helge; Kluth, Dietrich; Horch, Raymund E.; Vacanti, Joseph P.; Kneser, Ulrich

    2008-01-01

    Abstract Today, liver transplantation is still the only curative treatment for liver failure due to end-stage liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, for example, liver tissue engineering, are under investigation with the aim that in future an artificial liver tissue could be created and be used for the r...

  3. Etiology and functional status of liver cirrhosis by 31P MR spectroscopy

    Institute of Scientific and Technical Information of China (English)

    Monika Dezortova; Pavel Taimr; Antonin Skoch; Julius Spicak; Milan Hajek

    2005-01-01

    AIM: To assess the functional status and etiology of liver cirrhosis by quantitative 31p magnetic resonance spectroscopy (MRS).METHODS: A total of 80 patients with liver cirrhosis of different etiology and functional status described by Child-Pugh score were examined and compared to 11 healthy volunteers. MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique.Absolute concentrations of phosphomonoesters (PME),phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured.RESULTS: MRS changes reflected the degree of liver dysfunction in all the patients as well as in individual etiological groups. The most important change was a decrease of PDE. It was possible to distinguish alcoholic,viral and cholestatic etiologies based on MR spectra.Alcoholic and viral etiology differed in PDE (alcoholic,viral, controls: 6.5±2.3, 6.5±3.1, 10.8±2.7 mmol/L,P<0.001) and ATP (alcoholic, viral, controls: 2.9±0.8, 2.8±0.9, 3.7±1.0 mmol/L, P<0.01) from the control group.Unlike viral etiology, patients with alcoholic etiology also differed in Pi (alcoholic, controls: 1.2±0.4, 1.6±0.6mmol/L, P<0.05) from controls. No significant changes were found in patients with cholestatic disease and controls; nevertheless, this group differed from both alcoholic and viral groups (cholestatic, alcoholic, viral: 9.4±2.7, 6.5±2.3, 6.5±3.1 mmol/L, P<0.005) in PDE.CONCLUSION: 31p MRS can significantly help in noninvasive separation of different etiological groups leading to liver cirrhosis. In addition, MRS changes reflect functional liver injury.

  4. Benign Liver Tumors

    Science.gov (United States)

    ... Handouts Education Resources Support Services Helpful Links For Liver Health Information Call 1-800-GO-LIVER (1- ... Liver > Liver Disease Information > Benign Liver Tumors Benign Liver Tumors Explore this section to learn more about ...

  5. Normothermic machine perfusion for donor liver preservation

    NARCIS (Netherlands)

    Tolboom, H.

    2012-01-01

    Currently, liver transplantation is the only treatment for end-stage liver failure. Unfortunately, a sever shortage of donor organs causes significant mortality amongst patients awaiting transplantation. The donor organ shortage could be alleviated by using organs that are normally not accepted for

  6. Liver scintigraphy of fulminant hepatitis

    International Nuclear Information System (INIS)

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

  7. Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes.

    Science.gov (United States)

    Terelius, Ylva; Figler, Robert A; Marukian, Svetlana; Collado, Maria S; Lawson, Mark J; Mackey, Aaron J; Manka, David; Qualls, Charles W; Blackman, Brett R; Wamhoff, Brian R; Dash, Ajit

    2016-08-01

    Drug induced liver injury (DILI), a major cause of pre- and post-approval failure, is challenging to predict pre-clinically due to varied underlying direct and indirect mechanisms. Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) and Ritonavir, a protease inhibitor, are antiviral drugs that cause clinical DILI with different phenotypes via different mechanisms. Assessing DILI in vitro in hepatocyte cultures typically requires drug exposures significantly higher than clinical plasma Cmax concentrations, making clinical interpretations of mechanistic pathway changes challenging. We previously described a system that uses liver-derived hemodynamic blood flow and transport parameters to restore primary human hepatocyte biology, and drug responses at concentrations relevant to in vivo or clinical exposure levels. Using this system, primary hepatocytes from 5 human donors were exposed to concentrations approximating clinical therapeutic and supra-therapeutic levels of Nevirapine (11.3 and 175.0 μM) and Ritonavir (3.5 and 62.4 μM) for 48 h. Whole genome transcriptomics was performed by RNAseq along with functional assays for metabolic activity and function. We observed effects at both doses, but a greater number of genes were differentially expressed with higher probability at the toxic concentrations. At the toxic doses, both drugs showed direct cholestatic potential with Nevirapine increasing bile synthesis and Ritonavir inhibiting bile acid transport. Clear differences in antigen presentation were noted, with marked activation of MHC Class I by Nevirapine and suppression by Ritonavir. This suggests CD8+ T cell involvement for Nevirapine and possibly NK Killer cells for Ritonavir. Both compounds induced several drug metabolizing genes (including CYP2B6, CYP3A4 and UGT1A1), mediated by CAR activation in Nevirapine and PXR in Ritonavir. Unlike Ritonavir, Nevirapine did not increase fatty acid synthesis or activate the respiratory electron chain

  8. Heart Failure

    Science.gov (United States)

    ... blood. In other cases, the heart can't pump blood to the rest of the body with enough ... failure affects the right side, the heart cannot pump enough blood to the lungs, where it picks up oxygen. ...

  9. Heart Failure

    Science.gov (United States)

    ... together. About Rise Above HF Rise Above Heart Failure seeks to increase the dialogue about HF and improve the lives of people affected by the condition through awareness, education and support. Through the initiative, AHA strives to ...

  10. Respiratory Failure

    OpenAIRE

    Özyılmaz, Ezgi

    2014-01-01

    The main function of the lungs is to maintain the exchange between the pulmonary capillary and the air in the alveoli. By this way, the arteriel oxygen and carbondioxide tension remains constant. Respiratory failure is a syndrome which is defined as the loss of the ability of respiratory system to exchange oxygen and carbondioxide elimination function. The main pathophysiological causes of respiratory failure include ventilation-perfusion mismatch, alveolar hypoventilation, impaired diffusion...

  11. New insights into the coagulopathy of liver disease and liver transplantation

    Institute of Scientific and Technical Information of China (English)

    M Senzolo; P Burra; E Cholongitas; AK Burroughs

    2006-01-01

    The liver is an essential player in the pathway of coagulation in both primary and secondary haemostasis.Only von Willebrand factor is not synthetised by the liver, thus liver failure is associated with impairment of coagulation. However, recently it has been shown that the delicate balance between pro and antithrombotic factors synthetised by the liver might be reset to a lower level in patients with chronic liver disease. Therefore,these patients might not be really anticoagulated in stable condition and bleeding may be caused only when additional factors, such as infections, supervene. Portal hypertension plays an important role in coagulopathy in liver disease, reducing the number of circulating platelets, but platelet function and secretion of thrombopoietin have been also shown to be impaired in patients with liver disease. Vitamin K deficiency may coexist, so that abnormal clotting factors are produced due to lack of gamma carboxylation. Moreover during liver failure, there is a reduced capacity to clear activated haemostatic proteins and protein inhibitor complexes from the circulation. Usually therapy for coagulation disorders in liver disease is needed only during bleeding or before invasive procedures. When end stage liver disease occurs, liver transplantation is the only treatment available, which can restore normal haemostasis, and correct genetic clotting defects, such as haemophilia or factor V Leiden mutation. During liver transplantation haemorrage may occur due to the pre-existing hypocoagulable state, the collateral circulation caused by portal hypertension and increased fibrinolysis which occurs during this surgery.

  12. Liver scintigraphy

    International Nuclear Information System (INIS)

    Liver scintigraphy can be classified into 3 major categories according to the properties of the radiopharmaceuticals used, i.e., methods using radiopharmaceuticals which are (1) incorporated by hepatocytes, (2) taken up by reticulo endothelial cells, and (3) distributed in the blood pool of the liver. Of these three categories, the liver scintigraphy of the present research falls into category 2. Radiopharmaceuticals which are taken up by endothelial cells include 198Au colloids and 99mTc-labelled colloids. Liver scintigraphy takes advantage of the property by which colloidal microparticles are phagocytosed by Kupffer cells, and reflect the distribution of endothelial cells and the intensity of their phagocytic capacity. This examination is indicated in the following situations: (i) when you suspect a localized intrahepatic lesion (tumour, abscess, cyst, etc.), (ii) when you want to follow the course of therapy of a localized lesion, (iii) when you suspect liver cirrhosis, (iv) when you want to know the severity of liver cirrhosis or hepatitis, (v) when there is hepatomegaly and you want to determine the morphology of the liver, (vi) differential diagnosis of upper abdominal masses, and (vii) when there are abnormalities of the right diaphragm and you want to know their relation to the liver

  13. Alcoholic liver disease and changes in bone mineral density

    Directory of Open Access Journals (Sweden)

    Germán López-Larramona

    2013-12-01

    Full Text Available Osteoporosis and osteopenia are alterations in bone mineral density (BMD that frequently occur in the context of chronic liver disease (CLD. These alterations have been studied predominantly in chronic cholestatic disease and cirrhosis of the liver. Alcohol consumption is an independent risk factor for the onset of osteoporosis, whose estimated prevalence in patients with alcoholic liver disease (ALD ranges between 5 % and 40 %. The loss of BMD in ALD is the result of an imbalance between bone formation and resorption. Its pathogenesis is multifactorial and includes the toxic effects of alcohol on bone and endocrine and nutritional disorders secondary to alcoholism and a deficiency of osteocalcin, vitamin D and insulin growth factor-1. The diagnosis of BMD alterations in ALD is based on its measurement using bone densitometry. Treatment includes smoking and alcohol cessation and general measures such as changes in nutrition and exercise. Calcium and vitamin D supplements are recommended in all patients with ALD and osteoporosis. Bisphosphonates are the most commonly prescribed drugs for the specific treatment of this condition. Alternatives include raloxifene, hormone replacement therapy and calcitonin. This review will address the most important aspects involved in the clinical management of abnormal BMD in the context of ALD, including its prevalence, pathogenesis and diagnosis. We will also review the treatment of osteoporosis in CLD in general, focusing on specific aspects related to bone loss in ALD.

  14. ADULT RESPIRATORY DISTRESS SYNDROME SECONDARY TO END-STAGE LIVER DISEASE—SUCCESSFUL OUTCOME FOLLOWING LIVER TRANSPLANTATION1

    OpenAIRE

    Doyle, Howard R.; Marino, Ignazio R.; Miro, Adelaida; Scott, Victor; Martin, Maureen; Fung, John; Kramer, David; Starzl, Thomas E.

    1993-01-01

    The adult respiratory distress syndrome (ARDS) complicating liver failure carries a 100% mortality. Two cases of ARDS that resolved following liver transplantation have been reported, one associated with acute allograft rejection, and the second due to sepsis. There is, however, a great reluctance to transplant these very-high-risk patients. We report the first series of patients with ARDS secondary to liver failure who successfully underwent OLTX. No patient had sepsis or pneumonia. Posttran...

  15. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  16. 慢加急性肝衰竭患者发生肝肾综合征的多因素分析%Risk factors of hepatorenal syndrome in patients with acute on chronic liver failure

    Institute of Scientific and Technical Information of China (English)

    张冬青; 陈立; 甘巧蓉; 林清锋; 潘晨

    2013-01-01

    Objective To identify the risk factors of hepatorenal syndrome in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure(ACLF).Methods A total of 726 hospitalized patients with HBV-ACLF were retrospectively analyzed.Data of demographic and clinical parameters (sex,age,family history,and presence of liver cirrhosis and diabetes),common complications (spontaneous bacterial peritonitis,pulmonary infection,hepatic encephalopathy,and upper gastrointestinal hemorrhage),and baseline biochemical parameters (albumin,globulin,total bilirubin,direct bilirubin,alanine aminotransferase,aspartate aminotransferase,gamma-glutamyl transferase,alkaline phosphatase,cholesterol,cholinesterase,K+,Na+,plasma thromboplastin antecedent,alpha-fetoprotein,HBV DNA,white blood cell count,hemoglobin,and platelet count) were collected from the medical records database.Univariate and multiple regression analyses were performed to determine the risk factors of hepatorenal syndrome.Results Multiple logistic regression analysis indicated that upper gastrointestinal hemorrhage [risk (R) =1.313,relative hazard (RH) =3.716,95% confidence interval (CI):2.156-6.404],hepatic encephalopathy (R =1.120,RH=3.065,95% CI:1.900-4.945),spontaneous bacterial peritonitis (R =1.005,RH =2.733,95% CI:1.379-5.417),pulmonary infection (R =1.051,RH=2.862,95% CI:1.783-4.592),and white blood cellcount (R =0.056,RH=1.058,95% CI:1.010-1.107) were independent risk factors for hepatorenal syndrome development in patients with HBV-ACLF.Conclusion Several risk factors were significantly associated with the development of hepatorenal syndrome in HBV-ACLF,including upper gastrointestinal hemorrhage,hepatic encephalopathy,spontaneous bacterial peritonitis,pulmonary infection,and elevated white blood cell count.%目的 探讨慢加急性乙型肝炎肝衰竭患者发生肝肾综合征的危险因素. 方法 收集726例慢加急性乙型肝炎肝衰竭患者的基础临床资料(性别、年龄、

  17. 大黄素对胆汁淤积大鼠肝细胞转运体基因表达的影响%Effect of emodin on transporter gene expression of hepatocytes in intrahepatic cholestatic rats

    Institute of Scientific and Technical Information of China (English)

    周方; 许红梅

    2009-01-01

    AIM: To investigate the effect and mechanism of emodin on acute intrahepatic choles-tasis in rats. METHODS: Acute cholestatic model in rats was induced by alpha-naphthyliso thiocya-nate( ANIT). Normal control group, emodin group without ANIT treatment, model group and emodin group with ANIT treat ment were set up. liver function and pathological changes of hepatic tissue were examined. Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transporter bile salt export pump( BSEP) ,multidrug resistance-asso ciated protein 2 ( MRP2 ) , Na ~+ /taurocholate cotransporting peptide (NTCP) , multidrug resistance protein 2( MDR2), multidrug resist ance-associated protein 3 ( MRP3 ) and the nuclear receptor farne soid X receptor (FXR). RESULTS: In the model group compared with the normal control group, the concentrations of serum total bil irubin ( TB ) , direct bilirubin ( DB ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , alkaline phosphatase (ALP) and total bile acid ( TBA ) were increased ( P < 0. 01 ) ; inflammatory cell infiltration, hepatic cellular change and necrosis could be observed by light microscop; the genes expression of NT CP and FXR were down-regulated ( P < 0. 01 ), the MDR2 and MRP3 were up-regulated ( P < 0. 01 or P < 0. 05 ). But the expression of BSEP and MRP2 could not be affected. However,by emod in treatment, the concentrations of TB, DB, ALT, AST, ALP and TBA were decreased ( P < 0. 01 or P < 0. 05 ) ; Only mild his topathological change in liver could be seen;the genes expression of NTCP,MDR2 and MRP3 were higher than those of the model group(P<0. 05) ,but the expression of BSEP, FXR and MRP2 could not be affected. In emodin group without ANIT treatment compared with the normal control group,the changes of liver function, histopathology and transporter genes were not significantly different. CONCLUSION: Emodin has a protective effect on hepatocytes and a restoring activity on

  18. Role of polymorphic bile salt export pump (BSEP, ABCB11) transporters in anti-tuberculosis drug-induced liver injury in a Chinese cohort.

    Science.gov (United States)

    Chen, Ru; Wang, Jing; Tang, Shaowen; Zhang, Yuan; Lv, Xiaozhen; Wu, Shanshan; Yang, Zhirong; Xia, Yinyin; Chen, Dafang; Zhan, Siyan

    2016-01-01

    Evidence indicates that the polymorphisms in bile salt export pump (BSEP, encoded by ABCB11) may play an important role in the development of anti-tuberculosis drug-induced liver injury (ATDILI) and we aim to investigate the association between genetic variants of ABCB11 and the risk of ATDILI in a Chinese cohort. A total of 89 tuberculosis patients with ATDILI and 356 matched ATDILI -free patients constituted cases and controls. Genetic polymorphisms of ABCB11 were determined by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model. There were no significant differences in genotype frequencies of ABCB11 between cases and controls. In the subgroup analysis, polymorphisms of rs2287616 were found to be associated with cholestatic/mixed pattern of liver injury under dominant and addictive model (OR = 3.84, 95% CI:1.16-12.75, P = 0.028 and OR = 2.51, 95% CI:1.12-5.62, P = 0.025, respectively), however the significance disappeared after Bonferroni correction. This study suggested that genetic variants of ABCB11 gene might contribute to anti-tuberculosis drug-induced cholestatic liver injury in Chinese patients. Studies in larger, varied populations are required to confirm these findings. PMID:27293027

  19. Stem cells and liver disease

    Directory of Open Access Journals (Sweden)

    Javed Akhter

    2011-07-01

    Full Text Available Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs, complications associated with rejection and immunosuppression. An increasingly unbridgeable gap exists between the supply and demand of transplantable organs. Hence stem cell research and regenerative medicine have the potential to revolutionize the future of medicine with the ability to regenerate damaged and diseased organs. Stem cells serving as a repair system for the body, can theoretically divide without limit to replenish other cells. These cells could relieve the symptoms of liver disease or the genetic error could potentially be corrected by gene therapy. In cases of acute liver failure in adults, stem cell therapies might be used to support the liver, allowing it time to recover.

  20. Paracetamol overdose: the liver unit perspective.

    LENUS (Irish Health Repository)

    Iqbal, M

    2012-09-01

    Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.

  1. What Is Liver Cancer?

    Science.gov (United States)

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  2. Risk factors of prognosis for patients with HBV related liver failure and the prognosis model%乙型肝炎相关肝功能衰竭患者预后危险因素及预后模型建立

    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

    目的 探讨影响乙型肝炎相关肝衰竭患者预后的危险因素并建立其预后模型.方法 回顾性收集2006年6月至2008年12月在我科收治的178例乙型肝炎相关肝衰竭患者的临床资料.采用x 2和t检验和非参数检验进行单因素分析,Logistic回归进行多因素分析.结果 年龄、腹水、感染、消化道出血、肝性脑病、肝肾综合征、甲胎蛋白、PT、WBC、TBil、DBil、Cr、BUN、血清钠在生存组与死亡组之间差异均有统计学意义(P<0.05).Logistic多因素分析进一步显示,肝性脑病、感染、PT、TBil是影响乙型肝炎相关肝衰竭患者预后的独立危险因素.同时对所得出的独立危险因素建立该人群的预后判断模型,通过计算预后指数并绘制ROC曲线,计算其曲线下面积(AUC)为0.931(95%CI:0.893~0.970).其评估价值优于CTP分级(0.862)、MELD评分(0.807)及MELD-Na评分(0.774).结论 肝性脑病、感染、PT、TBil是影响乙型肝炎相关肝衰竭患者预后的独立危险因素.建立的预后模型能够较为准确地预测乙型肝炎相关肝衰竭患者的短期预后,是一个较为理想的乙型肝炎相关肝衰竭预后评估系统.%Objective To investigate the risk factors of the prognosis for HBV related liver failure and thus to establish a prognosis model. Methods Retrospective analysis of the clinical data of 178 patients with HBV related liver failure in Ruijin hospital from June 2006 to December 2008. Quantitative data were analyzed by using t test and rank test, and qualitative data were analyzed by using Chi-square test. Then Logistic regression analysis was used for selecting the independent risk factors of the prognosis for HBV related liver failure. Based on independent risk factors from Logistic regression analysis, prognostic model for the patients with HBV related liver failure was established. Results The differences of age, ascites, infection, upper gastrointestinal bleeding, hepatic

  3. Liver Facts

    Science.gov (United States)

    ... idiopapathic) Liver tumors Biliary atresia Was this information helpful? E-mail us with feedback or questions. Reference ... or other discrepancies. Share this: Was this information helpful? Related topics Find transplant centers specializing in certain ...

  4. Liver spots

    Science.gov (United States)

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... your skin by using skin bleaching lotions or creams. Most bleaching lotions use hydroquinone. This medicine is ...

  5. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

    International Nuclear Information System (INIS)

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

  6. Plasma biomarkers of liver injury and inflammation demonstrate a lack of apoptosis during obstructive cholestasis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Jenkins, Rosalind E. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-12-15

    Cholestasis is a pathological common component of numerous liver diseases that results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis due to direct toxicity of hydrophobic bile acid exposure, recent work suggests that the injury occurs through inflammatory necrosis. In order to resolve this controversy, we used novel plasma biomarkers to assess the mechanisms of cell death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct ligation (BDL) for 6–72 h, or sham operation. Another group of mice were given D-galactosamine and endotoxin as a positive control for apoptosis and inflammatory necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR-122) and high mobility group box-1 protein (HMGB1) increased progressively after BDL with peak levels observed after 48 h. These results indicate extensive cell necrosis after BDL, which is supported by the time course of plasma alanine aminotransferase activities and histology. In contrast, plasma caspase-3 activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments (cK18) were not elevated at any time during BDL suggesting the absence of apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for macrophage and monocyte activation, was increased as early as 12 h but mainly at 48–72 h. However, progressive neutrophil accumulation in the area of necrosis started at 6 h after BDL. In conclusion, these data indicate that early cholestatic liver injury in mice is an inflammatory event, and occurs through necrosis with little evidence for apoptosis. - Highlights: • The mechanism of cell death during cholestasis remains a controversial topic. • Plasma biomarkers offer new insight into cell death after bile duct ligation. • Cytokeratin-18, microRNA-122 and HMGB

  7. Long-term care in orthotopic liver transplantation

    OpenAIRE

    Maria C. Morelli; Pinna, Antonio D

    2013-01-01

    Orthotopic liver transplantation is the treatment of choice for selected patients with end-stage liver disease or acute liver failure. Given the excellent long-term survival associated with this procedure, increasing emphasis is being placed on the recognition and prevention of post-transplant complications, detection of recurrent liver disease, and effective management of immunosuppressive drug therapy, which involves regular monitoring of blood levels and the identification of adverse effec...

  8. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Kerlijne; De; Groote; Hans; Prenen

    2015-01-01

    In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer.

  9. Heart failure

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009170 Curcumin attenuates left ventricular dysfunction and remodeling in rabbits with chronic heart failure. TANG Yanhong(唐艳红),et al.Dept Cardiol,Renmin Hosp,Wuhan Univ,Wuhan 430060.Chin J Cardiol,2009;37(3):262-267.

  10. Failure Modes

    DEFF Research Database (Denmark)

    Jakobsen, K. P.; Burcharth, H. F.; Ibsen, Lars Bo; Sørensen, John Dalsgaard

    1999-01-01

    The present appendix contains the derivation of ten different limit state equations divided on three different failure modes. Five of the limit state equations can be used independently of the characteristics of the subsoil, whereas the remaining five can be used for either drained or undrained s...

  11. Heart failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970284 Effects of enalapril on heart rate variabilityin patients with congestive heart failure. ZHANGYouhua(章友华), et a1. Dept Cardiol, Cardiovasc Instit& Fuwai Hosp, CAMS & PUMC, Beijing, 100037. ChinCir J 1996; 11(2): 729-732.

  12. Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Ezgi Ozyilmaz

    2014-06-01

    Full Text Available The main function of the lungs is to maintain the exchange between the pulmonary capillary and the air in the alveoli. By this way, the arteriel oxygen and carbondioxide tension remains constant. Respiratory failure is a syndrome which is defined as the loss of the ability of respiratory system to exchange oxygen and carbondioxide elimination function. The main pathophysiological causes of respiratory failure include ventilation-perfusion mismatch, alveolar hypoventilation, impaired diffusion capacity and increased shunt. A number of diseases may result in respiratory failure by different pathophysiological reasons. The most common causes are Type 1 (hypoxemic and Type 2 (hypercapnic respiratory failure. When suspected with clinical signs and symptoms, the diagnosis should be confirmed with arterial blood gases. At this step, other diagnostic interventions, which could be performed, may be used to enlighten the underlying pathophysiological cause. Although the main therapeutic approach is similar, specific treatment are also required based on the underlying cause. The basic pathophysiological points, diagnosis and basic treatment approach have been evaluated in this review article. [Cukurova Med J 2014; 39(3.000: 428-442

  13. Liver function

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008308 Study on transplantation of induced bone marrow mesenchymal stem cells via a series of the treatment of chronic liver injury. SUN Yan(孙艳), et al. Dept Gastroenterol, 1st Hosp, Jilin Univ, Changchun 130021. Chin J Dig 2008;28(3):171-174.Objective To investigate the efficacy of transplantation of induced bone marrow mesenchymal stem cells(MSCs)via a series of treatment of chronic liver injury.Methods MSCs were isolated and expanded by density

  14. Liver failure from R-CHOP chemotherapy for the treatment of non-Hodgkin′s lymphoma:one case report and literature review%利妥昔单抗联合化疗治疗非霍奇金淋巴瘤致肝功能衰竭报道并文献复习

    Institute of Scientific and Technical Information of China (English)

    李宁; 程琦; 郑建铭; 陈明泉

    2014-01-01

    目的:探讨利妥昔单抗联合 CHOP 方案(R-CHOP)治疗非霍奇金淋巴瘤合并非活动性 HBsAg 携带者的治疗方法。方法报道1例行 R-CHOP 方案治疗非霍奇金淋巴瘤合并非活动性 HBsAg 携带者患者,未行抗病毒治疗的疾病进程,并复习近年来国内外发表的相关文献。结果本例患者应用 R-CHOP 方案化疗前未行抗病毒治疗,引起HBV 再激活,致肝功能衰竭。结论应明确抗病毒治疗对防止非霍奇金淋巴瘤患者化疗过程中 HBV 再激活的重要性。%Objective To review the role of antiviral therapy among inactive HBsAg carriers with non-Hodgkin′s lymphoma (NHL)treated with rituximab in combination with CHOP chemotherapy (R-CHOP).Methods We reported an inactive HBsAg carrier with NHL who was treated with R-CHOP and developed liver failure,and the relevant literatures were reviewed.Results Lacking prnor-antiviral therapytreatment for hepatitis B virus infection before R-CHOP,which increased the risk of hepatitis flare-up in inactive HBsAg carriers with NHL,might cause damage to the liver and even eventually lead to full-blown liver failure.Conclusion Antiviral treatment for hepatitis B virus infection in inactive HBsAg carriers with NHL should be paid more attention.

  15. [Liver intervention].

    Science.gov (United States)

    Oi, H

    2000-12-01

    Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation. PMID:11197832

  16. Pediatric liver transplantation in 31 consecutive children

    Institute of Scientific and Technical Information of China (English)

    SHEN Zhong-yang; WANG Zi-fa; ZHU Zhi-jun; ZANG Yun-jin; ZHENG Hong; DENG Yong-lin; PAN Cheng; CHEN Xin-guo

    2008-01-01

    Background Although liver transplantation has become a standard therapy for end-stage liver diseases, the experience of pediatric liver transplantation is limited in China. In this article we report our experience in pediatric liver transplantation, and summarize its characters in their indications, surgical techniques, and postoperative managements. Methods Thirty-one children (≤18 years old) underwent liver transplantation in our centers. The mean age at transplantation was 12.4 years old (ranged from 5 months to 18 years) with 7 children being less than 4 years of age at transplantation. The most common diagnosis of patients who underwent liver transplantation were biliary atresia, Wilson's disease, primary biliary cirrhosis, glycogen storage disease, hepatoblastoma, urea cycle defects, fulminant hepatic failure, etc. The surgical procedures included 12 standard (without venovenous bypass), 6 pigyback, 6 reduced-size, 3 split, 3 living donor liver transplantation, and 1 Domino liver transplantation. The triple-drug (FK506, steroid, and mycophenolate mofetil) immunosuppressive regimen was used in most of patients. Patients were followed up for a mean of 21.8 months. Results Five of the 31 patients died during perioperative time; mortality rate was 16.1%. The reasons of death were infections, primary non-function, heart failure, and hypovolemic shock. Postoperative complications in 10 patients included biliary leakage, acute rejection, abdominal infection, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and pulmonary infection. Overall patient cumulative survival rate at 1-, 3-, and 5-year was 78.1%, 62.6%, 62.6%, respectively.Conclusions The most common indications of pediatric liver transplantation were congenital end-stage liver diseases. According to patients' age and body weight, standard, piggyback, reduced-size, split, or living donor liver transplantation should be performed. Pediatric liver transplantation especially requires higher

  17. Artificial liver support: a real step forward.

    Science.gov (United States)

    Saliba, F; Samuel, D

    2015-02-01

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

  18. IL-4 mediates dicloxacillin-induced liver injury in mice.

    Science.gov (United States)

    Higuchi, Satonori; Kobayashi, Masanori; Yoshikawa, Yukitaka; Tsuneyama, Koichi; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

    2011-02-01

    Drug-induced liver injury (DILI) is a major problem in drug development and clinical drug therapy. In most cases, the mechanisms are still unknown. It is difficult to predict DILI in humans due to the lack of experimental animal models. Dicloxacillin, penicillinase-sensitive penicillin, rarely causes cholestatic or mixed liver injury, and there is some evidence for immunoallergic idiosyncratic reaction in human. In this study, we investigated the mechanisms of dicloxacillin-induced liver injury. Plasma ALT and total-bilirubin (T-Bil) levels were significantly increased in dicloxacillin-administered (600 mg/kg, i.p.) mice. Dicloxacillin administration induced Th2 (helper T cells)-mediated factors and increased the plasma interleukin (IL)-4 level. Neutralization of IL-4 suppressed the hepatotoxicity of dicloxacillin, and recombinant mouse IL-4 administration (0.5 or 2.0 μg/mouse, i.p.) exacerbated it. Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2) is a cognate receptor for prostaglandin (PG) D(2), and is suggested to be involved in Th2-dependent allergic inflammation. We investigated the effect of 13,14-Dihydro-15-keto-PGD(2) (DK-PGD(2); 10 μg/mouse, i.p.) administration on dicloxacillin-induced liver injury. DK-PGD(2)/dicloxacillin coadministration resulted in a significant increase of alanine aminotransferases and a remarkable increase of macrophage inflammatory protein 2 expression. In conclusion, to the best of our knowledge, this is the first report to demonstrate that dicloxacillin-induced liver injury is mediated by a Th2-type immune reaction and exacerbated by DK-PGD(2). PMID:21094227

  19. Liver Biopsy in Liver Transplant Recipients

    OpenAIRE

    Van Ha, Thuong G.

    2004-01-01

    Liver biopsy has been used in the assessment of the nature and course of liver diseases and to monitor treatments. In nontransplanted patients, liver biopsies have been well described. Less has been written on the biopsies of transplanted livers. In the liver transplant population, liver biopsy remains the “gold standard” for the diagnosis of rejection. The transplanted liver has additional considerations that can make biopsy less routine and more challenging.

  20. Hepatitis C and liver transplantation

    Science.gov (United States)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.